ORCID Profile
0000-0002-0937-6165
Current Organisation
The University of Newcastle
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Publisher: Public Library of Science (PLoS)
Date: 28-11-2012
Publisher: Elsevier BV
Date: 07-2014
DOI: 10.1016/J.PREGHY.2014.04.003
Abstract: Hypertension in pregnancy and preecl sia have been linked to poor outcomes in cognitive, mental and psychomotor development however, few longitudinal studies have researched their effect on offspring motor development, particularly in late childhood and adolescence. The purpose of this study was to determine if maternal hypertensive diseases during pregnancy are a risk factor for compromised motor development at 10, 14, and 17years. Longitudinal cohort study using data from the Western Australian Pregnancy Cohort Study (Raine). Offspring (n=2868) were classified by their maternal blood pressure profiles during pregnancy: normotension (n=2133), hypertension (n=626) and preecl sia (n=109). Offspring motor development, at 10, 14, and 17years was measured by the Neuromuscular Developmental Index (NDI) of the McCarron Assessment of Motor Development (MAND). Linear mixed models were used to compare outcomes between pregnancy groups. Offspring from pregnancies complicated by preecl sia had poorer motor outcomes at all ages than offspring from either normotensive mothers (p⩽0.001) or those with hypertension (p=0.002). Hypertensive diseases during pregnancy, in particular preecl sia, have long term and possibly permanent consequences for motor development of offspring.
Publisher: Public Library of Science (PLoS)
Date: 11-11-2013
Publisher: Elsevier BV
Date: 04-1999
Publisher: Hindawi Limited
Date: 26-07-2012
DOI: 10.4081/MI.2012.E20
Abstract: Some patients with severe mental disorders are refractory to psychotherapeutic or psychopharmacological interventions. We describe a patient with severe symptoms from the age of 16 to 44. Her illness is best described as a schizo-affective disorder. Several series of electroconvulsive therapy (ECT) followed by maintenance once a week for more than six years has kept her out of hospital beds for three years. The patient demonstrates the feasibility of long term ECT and the absence of disturbing cognitive reductions.
Publisher: Public Library of Science (PLoS)
Date: 29-03-2012
Publisher: Hindawi Limited
Date: 26-07-2012
DOI: 10.4081/MI.2012.E21
Abstract: Genetic risk for depressive disorders is poorly understood despite consistent suggestions of a high heritable component. Most genetic studies have focused on risk associated with single variants, a strategy which has so far only yielded small (often non-replicable) risks for depressive disorders. In this paper we argue that more substantial risks are likely to emerge from genetic variants acting in synergy within and across larger neurobiological systems (polygenic risk factors). We show how knowledge of major integrated neurobiological systems provides a robust basis for defining and testing theoretically defensible polygenic risk factors. We do this by describing the architecture of the overall stress response . Maladaptation via impaired stress responsiveness is central to the aetiology of depression and anxiety and provides a framework for a systems biology approach to candidate gene selection. We propose principles for identifying genes and gene networks within the neurosystems involved in the stress response and for defining polygenic risk factors based on the neurobiology of stress-related behaviour. We conclude that knowledge of the neurobiology of the stress response system is likely to play a central role in future efforts to improve genetic prediction of depression and related disorders.
Publisher: Oxford University Press (OUP)
Date: 22-02-2012
Abstract: Periodontal disease (PD) is a common chronic infectious and inflammatory disease of the gums and its supporting tissues, associated with several adverse health outcomes including significant obstetric consequences. PD is treatable with good oral hygiene and dental care, and consequently is a modifiable variable that may lead to improvements in adult health. To date, there are no published studies describing the influence of PD on a woman's time to conceive (TTC). This study formed part of the Smile study, which was a multi-centre randomized controlled trial of treatment for PD in mid-pregnancy. PD was defined as the presence of pockets ≥4-mm deep at ≥12 probing sites in fully erupted teeth. At the time of recruitment, women were asked about their TTC and whether they had required fertility treatment. Of 3737 pregnant women recruited to the study, information was available from 3416 spontaneous conceptions, including 1014 cases with PD (29.7%). Planned pregnancies accounted for 1956 of the 3416 pregnancies available for study. For 146 women, the TTC was >12 months and PD was more prevalent in this group (34.9% versus 25.7%, P = 0.015). The mean TTC in women with PD was 7.1 months [confidence interval (CI): 5.7-8.6] compared with 5.0 months (CI: 4.4-5.5, P = 0.019) in those without PD. PD was present in 23.8% of Caucasian women and 41.4% of non-Caucasian women. Compared with Caucasian women without PD, non-Caucasian women with PD had an increased likelihood of TTC >12 months [13.9% versus 6.2%, odds ratio (OR): 2.88 (CI: 1.62-5.12), P 1 year included age, BMI >25 and smoking. In the non-Caucasian population, PD was associated with an increased TTC, but whether this is related to PD, or some other factor also present within this population, should be further investigated.
Publisher: Rockefeller University Press
Date: 24-08-1998
Abstract: The Ras target AF-6 has been shown to serve as one of the peripheral components of cell–cell adhesions, and is thought to participate in cell–cell adhesion regulation downstream of Ras. We here purified an AF-6-interacting protein with a molecular mass of ∼220 kD (p220) to investigate the function of AF-6 at cell–cell adhesions. The peptide sequences of p220 were identical to the amino acid sequences of mouse Fam. Fam is homologous to a deubiquitinating enzyme in Drosophila, the product of the fat facets gene. Recent genetic analyses indicate that the deubiquitinating activity of the fat facets product plays a critical role in controlling the cell fate. We found that Fam accumulated at the cell–cell contact sites of MDCKII cells, but not at free ends of plasma membranes. Fam was partially colocalized with AF-6 and interacted with AF-6 in vivo and in vitro. We also showed that AF-6 was ubiquitinated in intact cells, and that Fam prevented the ubiquitination of AF-6.
Publisher: Elsevier BV
Date: 11-1995
Publisher: Springer Science and Business Media LLC
Date: 17-12-2015
DOI: 10.1038/NCOMMS10257
Abstract: Nature Communications 6, Article number: 7756 (2015) Published 4 August 2015 Updated 17 December 2015 In the Results section and in the legend of Table 1 of this Article, the company deCODE genetics, Inc. is incorrectly referred to as ‘Diabetes Epidemiology: collaborative analysis of Diagnostic criteria in Europe’.
Publisher: The Endocrine Society
Date: 17-05-2021
Abstract: Human and animal studies suggest that hypothalamic-pituitary-adrenal axis (HPA-A) function may be programmed in utero however, these findings are inconsistent. Given the powerful metabolic actions of cortisol, it is important to clarify the influence of early life on adult HPA-A function. To determine the relationship between fetal growth and HPA-A stress response to a psychosocial stressor in young adults. Multigenerational, prospective cohort study (the Raine Study) conducted between 1989 and 1991. King Edward Memorial Hospital, Perth, Western Australia, Australia. A total of 917 participants aged 18 years from Gen2 of the Raine Study. Measures of hypothalamic-pituitary-adrenal axis function before and after exposure to the Trier Social Stress Test. In fully adjusted models, an inverse linear relationship was observed between birthweight and plasma measures of (1) baseline cortisol (β = -0.90%, 95% CI: -1.73 to -0.07 P = 0.03) (2) peak cortisol (β = -0.78%, 95% CI -1.51 to -0.06 P = 0.03) (3) area under the curve with respect to ground (β = -0.89%, 95% CI -1.60 to -0.18 P = 0.01) and (4) adrenal sensitivity (β = -1.02, 95% CI: -1.85 to -0.18 P = 0.02). Similar results were demonstrated for percent optimal birthweight. No consistent quadratic relationships were identified. No associations were found between measures of fetal adiposity and HPA-A function at age 18 years, or fetal growth and HPA-A response pattern. Removal of anticipatory responders from the models substantially attenuated the observed relationships. We observed an inverse linear relationship between fetal growth and HPA-A function at age 18 years. This differs from the inverse parabolic relationship (inverted U curve) reported in adults of advanced age. Altered adrenal sensitivity may underlie this relationship.
Publisher: The Endocrine Society
Date: 05-2011
DOI: 10.1210/JC.2010-2316
Abstract: A recent genome-wide association study identified variants near CCNL1/LEKR1 (rs900400) and in ADCY5 (rs9883204) to be associated with birth weight. We examined the associations of these variants with fetal growth characteristics in different trimesters, with a main interest in the timing of the associations and the affected body proportions. We used data from two prospective cohort studies from fetal life onward in The Netherlands and Australia. Repeated fetal ultrasound examinations were performed to measure head circumference (HC), abdominal circumference (AC), femur length (FL), and estimated fetal weight (EFW). Analyses were based on a total group of 3909 subjects. The C-allele of rs900400 was associated in second trimester with smaller fetal HC and FL, and in third trimester with smaller HC, AC, FL, and EFW. For each C-allele, the combined effect estimate for EFW in third trimester was -18.6 g (95% confidence interval, -27.5, -9.7 g P = 4.2 × 10(-5)). The C-allele of rs9883204 was not associated with fetal growth characteristics in second trimester but was associated with restriction of all growth characteristics, except HC, in third trimester and at birth. For each C-allele, the combined effect estimate was -16.9 g (95% confidence interval, -26.8, -7.0 g P = 8.4 × 10(-4)) for EFW in third trimester. Both genetic variants were associated with lower birth and placenta weight. Our results suggest that a genetic variant of rs900400 leads to symmetric growth restriction from early pregnancy onward, whereas a genetic variant of rs9883204 leads to asymmetric growth restriction, characterized by a relatively larger HC, from third trimester.
Publisher: Oxford University Press (OUP)
Date: 12-04-2018
DOI: 10.1093/HMG/DDY121
Publisher: Springer Science and Business Media LLC
Date: 20-03-2014
DOI: 10.1007/S00198-014-2665-X
Abstract: The relationships between fat mass and bone mass in young adults are unclear. In 1,183 young Australians, lean body mass had a strong positive relationship with total body bone mass in both genders. Fat mass was a positive predictor of total body bone mass in females, with weaker association in males. Body weight and lean body mass are established as major determinants of bone mass, but the relationships between fat mass (including visceral fat) and peak bone mass in young adults are unclear. The aim of this study was to evaluate the associations between bone mass in young adults and three body composition measurements: lean body mass, fat mass and trunk-to-limb fat mass ratio (a surrogate measure of visceral fat). Study participants were 574 women and 609 men aged 19-22 years from the Raine study. Body composition, total body bone mineral content (TBBMC), bone area and areal bone mineral density (TBBMD) were measured using DXA. In multivariate linear regression models with height, lean body mass, fat mass and trunk-to-limb fat mass ratio as predictor variables, lean mass was uniquely associated with the largest proportion of variance of TBBMC and TBBMD in males (semi-partial R(2) 0.275 and 0.345, respectively) and TBBMC in females (semi-partial R(2) 0.183). Fat mass was a more important predictor of TBBMC and TBBMD in females (semi-partial R(2) 0.126 and 0.039, respectively) than males (semi-partial R(2) 0.006 and 0.018, respectively). Trunk-to-limb fat mass ratio had a weak, negative association with TBBMC and bone area in both genders (semi-partial R(2) 0.004 to 0.034). Lean body mass has strong positive relationship with total body bone mass in both genders. Fat mass may play a positive role in peak bone mass attainment in women but the association was weaker in men different fat compartments may have different effects.
Publisher: Microbiology Society
Date: 10-1990
Publisher: Wiley
Date: 20-01-2012
DOI: 10.1111/J.1365-3016.2011.01257.X
Abstract: The current study sought to determine whether hypertensive diseases of pregnancy (gestational hypertension and pre-ecl sia) are associated with neurocognitive outcomes in middle childhood. Participants were members of the Western Australian Pregnancy Cohort (Raine) Study. Data were available for 1389 children (675 females mean age = 10.59 years SD = 0.19). Twenty-five per cent of these participants were offspring of pregnancies complicated by either gestational hypertension (n = 279), or pre-ecl sia (n = 34). Verbal ability at age 10 years was assessed with the Peabody Picture Vocabulary Test - Revised (PPVT-R), and non-verbal ability with Ravens Colored Progressive Matrices (RCPM). Separate multivariable regression analyses, incorporating sociodemographic, antenatal, obstetric and postnatal covariates, investigated the effect of a two- (normotensive pregnancy vs. hypertensive pregnancy) and three-level (normotensive pregnancy vs. gestational hypertension vs. pre-ecl sia) predictor variable on PPVT-R and RCPM scores. Offspring of pregnancies complicated by maternal hypertension (gestational hypertension or pre-ecl sia) had a mean PPVT-R score that was 1.83 ([95% confidence interval (CI) -3.48, -0.17], P = 0.03) points lower than children from normotensive pregnancies. Multivariable regression analysis also identified a significant inverse association between the three-level predictor variable and offspring PPVT-R scores (P = 0.02). Gestational hypertension (without pre-ecl sia) reduced offspring PPVT-R scores by 1.71 points [95% CI -3.39, -0.03] and pre-ecl sia led to a reduction of 3.53 points [95% CI -8.41, 1.35], although this latter association did not achieve statistical significance. There was no effect of the two- (P = 0.99) or three-level (P = 0.92) predictor variable on RCPM scores. Maternal hypertensive diseases of pregnancy are a risk factor for a small reduction in offspring verbal ability.
Publisher: Springer Science and Business Media LLC
Date: 11-08-2016
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 13-11-2018
DOI: 10.1002/HEP.29347
Abstract: Nonalcoholic fatty liver disease (NAFLD) is a complex chronic liver disorder. Examination of parental pregnancy‐related characteristics may provide insights into the origins of risk of NAFLD in offspring. We examined relationships between parental pregnancy‐related characteristics and NAFLD in 1,170 adolescent offspring aged 17 years participating in the Western Australian Pregnancy (Raine) Cohort Study. Fatty liver was diagnosed using liver ultrasound. NAFLD was diagnosed in 15.2% of adolescents at age 17 years. In univariate analysis, maternal factors associated with NAFLD in female offspring were younger maternal age ( P = 0.02), higher maternal prepregnancy BMI ( P 0.001), higher maternal weight gain by 18 weeks' gestation ( P 0.001), and maternal smoking during pregnancy ( P = 0.04). Paternal age or body mass index (BMI) were not associated with NAFLD in female offspring. In contrast, higher paternal BMI ( P 0.001), maternal prepregnancy BMI ( P 0.001), and lower family socioeconomic status (SES) at time of birth ( P = 0.001), but not parental age nor maternal gestational weight gain, were associated with NAFLD in male offspring. Using multivariate logistic regression, factors independently associated with NAFLD after adjusting for obesity in adolescent females included maternal obesity (odds ratio [OR], 3.46 95% confidence interval [CI], 1.49‐8.05 P = 0.004) and maternal weight gain ≥6.0 kg by the 18th week of gestation (OR, 1.10 95% CI, 1.04‐1.15 P 0.001). In adolescent males, family SES at the time of birth (OR, 9.07 95% CI, 1.54‐53.29 P = 0.02) remained significantly associated with NAFLD after multivariate modeling adjusted for adolescent obesity. Conclusion: Early‐life contributors to NAFLD show considerable sexual dimorphism. Maternal obesity and higher early‐mid gestational weight gain were associated with NAFLD in female offspring, whereas lower family SES at birth was associated with NAFLD in male offspring independent of adolescent obesity. (H epatology 2018 :108‐122).
Publisher: Springer Science and Business Media LLC
Date: 30-04-2015
DOI: 10.1038/GENE.2015.12
Abstract: Streptococcus pneumoniae causes invasive pneumococcal disease. Delayed development of antibodies to S. pneumoniae in infancy is associated with the development of atopy and asthma. Pneumococcal surface protein C (PspC) is a vaccine candidate and variation in its choline-binding region is associated with invasive disease. This study examined 523 060 single-nucleotide polymorphisms in The Western Australian Pregnancy Cohort (Raine) Study to find loci influencing immunoglobulin G1 (IgG1) responses to PspC measured at age 14 years (n=1152). Genome-wide significance (top SNP rs9275596 P=3.1 × 10(-14)) was only observed at human leucocyte antigen (HLA). Imputed HLA amino-acid polymorphisms showed the strongest associations at positions DRB1 47 (P=3.2 × 10(-11)), 13SRG (P=9.8 × 10(-10)) and 11SP (P=9.8 × 10(-10)), and at DQA1 34 (P=6.4 × 10(-10)), DQB1 167R (P=9.3 × 10(-6)) and HLA-B 95 W (P=1.2 × 10(-9)). Conditional analyses showed independent contributions from DRB1 47 and DQB1 167R to the signal at rs9275596, supported by an omnibus test showing a strong signal for the haplotype DRB1_47_DQB1_167 (P=9.02 × 10(-15)). In silico analysis showed that DRB1 four-digit allele groups defined by DRB1 47F bind to a greater complexity of core 9-mer epitopes compared with DRB1 47Y, especially across repeats in the C-term choline-binding region. Consequent differences in CD4 T-cell help for IgG1 to PspC could have implications for vaccine design. Further analysis in other cohorts is merited.
Publisher: Elsevier BV
Date: 12-1994
Publisher: F1000 Research Ltd
Date: 06-2020
DOI: 10.12688/WELLCOMEOPENRES.15846.1
Abstract: Background: Lung function is highly heritable and differs between the sexes throughout life. However, little is known about sex-differential genetic effects on lung function. We aimed to conduct the first genome-wide genotype-by-sex interaction study on lung function to identify genetic effects that differ between males and females. Methods: We tested for interactions between 7,745,864 variants and sex on spirometry-based measures of lung function in UK Biobank (N=303,612), and sought replication in 75,696 independent in iduals from the SpiroMeta consortium. Results: Five independent single-nucleotide polymorphisms (SNPs) showed genome-wide significant (P x10 -8 ) interactions with sex on lung function, and 21 showed suggestive interactions (P x10 -6 ). The strongest signal, from rs7697189 (chr4:145436894) on forced expiratory volume in 1 second (FEV 1 ) (P=3.15x10 -15 ), was replicated (P=0.016) in SpiroMeta. The C allele increased FEV 1 more in males (untransformed FEV 1 β=0.028 [SE 0.0022] litres) than females (β=0.009 [SE 0.0014] litres), and this effect was not accounted for by differential effects on height, smoking or pubertal age. rs7697189 resides upstream of the hedgehog-interacting protein ( HHIP ) gene and was previously associated with lung function and HHIP lung expression. We found HHIP expression was significantly different between the sexes (P=6.90x10 -6 ), but we could not detect sex differential effects of rs7697189 on expression. Conclusions: We identified a novel genotype-by-sex interaction at a putative enhancer region upstream of the HHIP gene. Establishing the mechanism by which HHIP SNPs have different effects on lung function in males and females will be important for our understanding of lung health and diseases in both sexes.
Publisher: Wiley
Date: 17-09-2003
DOI: 10.1002/BIES.10332
Publisher: Elsevier BV
Date: 02-1988
Publisher: F1000 Research Ltd
Date: 24-05-2021
DOI: 10.12688/WELLCOMEOPENRES.15846.2
Abstract: Background: Lung function is highly heritable and differs between the sexes throughout life. However, little is known about sex-differential genetic effects on lung function. We aimed to conduct the first genome-wide genotype-by-sex interaction study on lung function to identify genetic effects that differ between males and females. Methods: We tested for interactions between 7,745,864 variants and sex on spirometry-based measures of lung function in UK Biobank (N=303,612), and sought replication in 75,696 independent in iduals from the SpiroMeta consortium. Results: Five independent single-nucleotide polymorphisms (SNPs) showed genome-wide significant (P x10 -8 ) interactions with sex on lung function, and 21 showed suggestive interactions (P x10 -6 ). The strongest signal, from rs7697189 (chr4:145436894) on forced expiratory volume in 1 second (FEV 1 ) (P=3.15x10 -15 ), was replicated (P=0.016) in SpiroMeta. The C allele increased FEV 1 more in males (untransformed FEV 1 β=0.028 [SE 0.0022] litres) than females (β=0.009 [SE 0.0014] litres), and this effect was not accounted for by differential effects on height, smoking or pubertal age. rs7697189 resides upstream of the hedgehog-interacting protein ( HHIP ) gene and was previously associated with lung function and HHIP lung expression. We found HHIP expression was significantly different between the sexes (P=6.90x10 -6 ), but we could not detect sex differential effects of rs7697189 on expression. Conclusions: We identified a novel genotype-by-sex interaction at a putative enhancer region upstream of the HHIP gene. Establishing the mechanism by which HHIP SNPs have different effects on lung function in males and females will be important for our understanding of lung health and diseases in both sexes.
Publisher: Oxford University Press (OUP)
Date: 15-04-2005
DOI: 10.1093/HMG/DDI101
Publisher: Wiley
Date: 09-1994
Publisher: Springer Science and Business Media LLC
Date: 06-01-2013
DOI: 10.1038/NG.2506
Publisher: Cambridge University Press (CUP)
Date: 11-04-2017
DOI: 10.1017/S0954579417000372
Abstract: There is debate about the relative importance of timing of stressful events prenatally and over the life course and risk for subsequent depressive/anxious illness. The aim of this study was to examine the relative roles of prenatal stress and postnatal stress trajectories in predicting depression and anxiety in early adulthood in males and females. Exposure to life stress events was examined in the Western Australian Pregnancy Cohort (Raine) Study during pregnancy and ages 1, 2, 3, 5, 8, 10, 14, and 17 years. At age 20, offspring completed the Depression Anxiety Stress Scale. Prenatal stress and trajectories of stress events from age 1 to 17 were analyzed in linear regression analyses. Five postnatal stress trajectories were identified. In females, medium to high chronic stress exposure or exposure during puberty/adolescence predicted depression and anxiety symptoms while low or reduced stress exposure over the life course did not, after adjustment for relevant confounders. High stress early in pregnancy contributed to male depression/anxiety symptoms independent of postnatal stress trajectory. In females, postnatal stress trajectory was more important than prenatal stress in predicting depression/anxiety symptoms. Interventions focused on reducing and managing stress events around conception regnancy and exposure to chronic stress are likely to have beneficial outcomes on rates of depression and anxiety in adults.
Publisher: Informa UK Limited
Date: 21-11-2013
DOI: 10.3109/14767058.2012.712564
Abstract: To assess the accuracy and reliability of cervico-portio (CP) length estimated using the Cervilenz™ compared with transvaginal ultrasound (TVU) cervical-length in women at high and low risk of spontaneous preterm birth (SPTB). Cervical-length was assessed longitudinally across gestation utilizing CP-length measured with Cervilenz™ and TVU. Altman-Bland plots were used to compare Cervilenz™ and TVU cervical-length. Regression analysis was used to assess the effect of gestational age, previous SPTB and previous cervical surgery on Cervilenz™ accuracy. Receiver operator curves (ROC) were utilized to determine the CP-length measured by Cervilenz™ with the optimum sensitivity and specificity for predicting TVU cervical-length <25 mm. ROCs were utilised to compare the ability of Cervilenz™ with TVU to predict SPTB. Seventy-five women were recruited (low risk N = 57, high risk N = 18). A total of 259 TVU and 253 Cervilenz™ measurements were taken with up to six measures in each woman. The Cervilenz™ CP-length was on average 9 mm shorter than TVU measured cervical-length. The difference decreased with advancing gestational age (p < 0.001). Cervilenz™ CP-length <24 mm was a good predictor of TVU cervical-length <25 mm (area under the curve (AUC) = 0.867). After accounting for baseline Cervilenz™ measurements, the relationship between Cervilenz™ and TVU measures was not influenced by pregnancy risk status. There were no significant differences between Cervilenz™ (AUC = 0.716) and TVU (AUC = 0.706) in predicting SPTB. Cervilenz™ is an effective tool for screening cervical-length in comparison to TVU. Cervilenz™ may facilitate greater access to cervical-length measurement and assessment of risk of preterm birth.
Publisher: Springer Science and Business Media LLC
Date: 28-09-2016
DOI: 10.1038/NATURE19806
Publisher: Public Library of Science (PLoS)
Date: 13-09-2016
Publisher: American Society for Microbiology
Date: 07-2004
DOI: 10.1128/JB.186.13.4387-4389.2004
Abstract: Three mutants with Tn 5 -B21 insertion in tonB3 (PA0406) of Pseudomonas aeruginosa exhibited defective twitching motility and reduced assembly of extracellular pili. These defects could be complemented with wild-type tonB3 .
Publisher: Wiley
Date: 05-1995
Publisher: Springer Science and Business Media LLC
Date: 12-2015
Publisher: Elsevier BV
Date: 07-2022
DOI: 10.1016/J.JAAC.2021.11.035
Abstract: To investigate the genetic architecture of internalizing symptoms in childhood and adolescence. In 22 cohorts, multiple univariate genome-wide association studies (GWASs) were performed using repeated assessments of internalizing symptoms, in a total of 64,561 children and adolescents between 3 and 18 years of age. Results were aggregated in meta-analyses that accounted for s le overlap, first using all available data, and then using subsets of measurements grouped by rater, age, and instrument. The meta-analysis of overall internalizing symptoms (INT Genetic correlations indicate that childhood and adolescent internalizing symptoms share substantial genetic vulnerabilities with adult internalizing disorders and other childhood psychiatric traits, which could partially explain both the persistence of internalizing symptoms over time and the high comorbidity among childhood psychiatric traits. Reducing phenotypic heterogeneity in childhood s les will be key in paving the way to future GWAS success.
Publisher: Wiley
Date: 07-2007
DOI: 10.1111/J.1471-0528.2007.01307.X
Abstract: To describe trends in mode of delivery, to identify significant factors which affected mode of delivery, and to describe how these factors and their impact have changed over time. Total population birth cohort. Western Australia 1984-2003. The analysis was restricted to all singleton infants delivered at 37-42 weeks of gestation with a cephalic presentation (n = 432,327). Logistic regression analyses were undertaken to estimate significant independent risk factors separately for elective and emergency caesarean sections compared with vaginal delivery (spontaneous and instrumental), adjusting for potential confounding variables. Trends in mode of delivery, demographic factors, and pregnancy and delivery complications. Estimated likelihood of elective caesarean section compared with vaginal delivery and emergency caesarean section compared with vaginal delivery. Between 1984-88 and 1999-2003, the likelihood of women having an elective caesarean section increased by a factor of 2.35 times (95% CI 2.28-2.42) and the likelihood of an emergency caesarean section increased 1.89 times (95% CI 1.83-1.96). These caesarean section rate increases remained even after adjustment for their strong associations with many sociodemographic factors, obstetric risk factors, and obstetric complications. Rates of caesarean section were higher in older mothers, especially those older than 40 years of age (elective caesarean section, OR 5.42 [95% CI 4.88-6.01] emergency caesarean section, OR 2.67 [95% CI 2.39-2.97]), and in nulliparous women (elective caesarean section, OR 1.54 [95% CI 1.47-1.61] emergency caesarean section, OR 3.61 [95% CI 3.47-3.76]). Our data show significant changes in mode of delivery in Western Australia from 1984-2003, with an increasing trend in both elective and emergency caesarean section rates that do not appear to be explained by increased risk or indication.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2011
Publisher: Springer Science and Business Media LLC
Date: 03-2019
Publisher: Springer Science and Business Media LLC
Date: 03-06-2019
DOI: 10.1038/S41588-019-0447-2
Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Publisher: Public Library of Science (PLoS)
Date: 22-06-2016
Publisher: AMPCo
Date: 12-2012
DOI: 10.5694/MJA12.10698
Publisher: Springer Science and Business Media LLC
Date: 30-10-2012
Publisher: Elsevier BV
Date: 05-1991
Publisher: Springer Science and Business Media LLC
Date: 29-05-2012
DOI: 10.1038/NG0612-732C
Publisher: Wiley
Date: 19-02-2016
DOI: 10.1002/OSP4.28
Publisher: Wiley
Date: 05-1984
Publisher: Cambridge University Press (CUP)
Date: 06-09-2013
DOI: 10.1017/S2040174412000578
Abstract: Maternal pre-pregnancy obesity has been linked with an increased risk for negative emotionality and inattentiveness in offspring in early childhood. The aim of this study was to examine the association between maternal pre-pregnancy body mass index (BMI) and the development of affective problems (dysthymic disorder, major depressive disorder) throughout childhood and adolescence. In the Western Australian Pregnancy Cohort (Raine) Study, 2900 women provided data on their pre-pregnancy weight, and height measurements were taken at 18 weeks of gestation. BMI was calculated and categorized using standardized methods. Live-born children ( n = 2868) were followed up at ages 5, 8, 10, 14 and 17 years using the Diagnostic and Statistical Manual of Mental Disorders-oriented scales of the Child Behavior Checklist (CBCL/4–18). Longitudinal models were applied to assess the relationships between maternal pre-pregnancy BMI and affective problems from age 5 through 17. There was a higher risk of affective problems between the ages of 5 and 17 years among children of women who were overweight and obese compared with the offspring of women in the healthy pre-pregnancy weight range (BMI 18.5–24.99) after adjustment for confounders, including paternal BMI. Maternal pre-pregnancy overweight and obesity may be implicated in the development of affective problems, including depression, in their offspring later in life.
Publisher: Elsevier BV
Date: 08-2013
Publisher: Springer Science and Business Media LLC
Date: 16-11-2021
DOI: 10.1038/S41467-021-26783-X
Abstract: Previous genome-wide association studies revealed multiple common variants involved in eczema but the role of rare variants remains to be elucidated. Here, we investigate the role of rare variants in eczema susceptibility. We meta-analyze 21 study populations including 20,016 eczema cases and 380,433 controls. Rare variants are imputed with high accuracy using large population-based reference panels. We identify rare exonic variants in DUSP1 , NOTCH4 , and SLC9A4 to be associated with eczema. In DUSP1 and NOTCH4 missense variants are predicted to impact conserved functional domains. In addition, five novel common variants at SATB1-AS1 / KCNH8 , TRIB1 / LINC00861 , ZBTB1 , TBX21 / OSBPL7 , and CSF2RB are discovered. While genes prioritized based on rare variants are significantly up-regulated in the skin, common variants point to immune cell function. Over 20% of the single nucleotide variant-based heritability is attributable to rare and low-frequency variants. The identified rare/low-frequency variants located in functional protein domains point to promising targets for novel therapeutic approaches to eczema.
Publisher: Springer Science and Business Media LLC
Date: 18-02-2019
Publisher: Springer Science and Business Media LLC
Date: 12-1977
DOI: 10.1007/BF00808386
Publisher: Wiley
Date: 20-07-2010
Publisher: Oxford University Press (OUP)
Date: 1993
DOI: 10.1093/NAR/21.3.783
Publisher: Research Square Platform LLC
Date: 15-12-2020
DOI: 10.21203/RS.3.RS-124700/V1
Abstract: Background: It is well established that genetics, environment, and interplay between them play crucial roles in adult disease. We aimed to evaluate the role of genetics, early life nutrition, and interaction between them, on optimal adult health. Methods: As part of a large international consortium (n~154,000), we identified 60 SNPs associated with both birthweight and adult disease. Utilising the Raine Study, we developed a birthweight polygenic score (BW-PGS) based the 60 SNPs and examined relationships between BW-PGS and adulthood cardiovascular risk factors, specifically evaluating interactions with early life nutrition. Findings: Healthy nutrition was beneficial for all in iduals longer duration of any breastfeeding was associated with lower BMI and lower Systolic Blood Pressure in those with higher BW-PGS. Interpretation: Optimal breastfeeding offers the greatest benefit to reduce adult obesity and hypertension in those genetically predisposed to high birthweight. This provides an ex le of how precision medicine in early life can improve adult health.
Publisher: Cold Spring Harbor Laboratory
Date: 05-06-2020
DOI: 10.1101/2020.06.04.20121061
Abstract: Substantial genetic correlations have been reported across psychiatric disorders and numerous cross-disorder genetic variants have been detected. To identify the genetic variants underlying general psychopathology in childhood, we performed a genome-wide association study using a total psychiatric problem score. We analyzed 6,844,199 common SNPs in 38,418 school-aged children from 20 population-based cohorts participating in the EArly Genetics and Lifecourse Epidemiology (EAGLE) consortium. The SNP heritability of total psychiatric problems was 5.4% (SE=0.01) and two loci reached genome-wide significance: rs10767094 and rs202005905. We also observed an association of SBF2 , a gene associated with neuroticism in previous GWAS, with total psychiatric problems. The genetic effects underlying the total psychiatric problem score were shared with known genetic variants for common psychiatric disorders only (attention-deficit/hyperactivity disorder, anxiety, depression, insomnia) (r G 0.49), but not with autism or the less common adult disorders (schizophrenia, bipolar disorder, or eating disorders) (r G 0.01). Importantly, the total psychiatric problem score also showed at least a moderate genetic correlation of with intelligence, educational attainment, wellbeing, smoking, and body fat (r G 0.29).The results suggest that many common genetic variants are associated with childhood psychiatric symptoms and related phenotypes in general instead of with specific symptoms. Further research is needed to establish causality and pleiotropic mechanisms between psychiatric disorders and related traits.
Publisher: Public Library of Science (PLoS)
Date: 20-12-2016
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2010
Publisher: Springer Science and Business Media LLC
Date: 12-2010
Abstract: Preterm birth is the leading cause of perinatal morbidity and mortality. Risk factors for preterm birth include a personal or familial history of preterm delivery, ethnicity and low socioeconomic status yet the ability to predict preterm delivery before the onset of preterm labour evades clinical practice. Evidence suggests that genetics may play a role in the multi-factorial pathophysiology of preterm birth. The All Our Babies Study is an on-going community based longitudinal cohort study that was designed to establish a cohort of women to investigate how a women's genetics and environment contribute to the pathophysiology of preterm birth. Specifically this study will examine the predictive potential of maternal leukocytes for predicting preterm birth in non-labouring women through the examination of gene expression profiles and gene-environment interactions. Collaborations have been established between clinical lab services, the provincial health service provider and researchers to create an interdisciplinary study design for the All Our Babies Study. A birth cohort of 2000 women has been established to address this research question. Women provide informed consent for blood s le collection, linkage to medical records and complete questionnaires related to prenatal health, service utilization, social support, emotional and physical health, demographics, and breast and infant feeding. Maternal blood s les are collected in PAXgene™ RNA tubes between 18-22 and 28-32 weeks gestation for transcriptomic analyses. The All Our Babies Study is an ex le of how investment in clinical-academic-community partnerships can improve research efficiency and accelerate the recruitment and data collection phases of a study. Establishing these partnerships during the study design phase and maintaining these relationships through the duration of the study provides the unique opportunity to investigate the multi-causal factors of preterm birth. The overall All Our Babies Study results can potentially lead to healthier pregnancies, mothers, infants and children.
Publisher: Elsevier BV
Date: 06-2014
DOI: 10.1016/J.JAAC.2013.12.028
Abstract: Preschool internalizing problems (INT) are highly heritable and moderately genetically stable from childhood into adulthood. Gene-finding studies are scarce. In this study, the influence of genome-wide measured single nucleotide polymorphisms (SNPs) was investigated in 3 cohorts (total N = 4,596 children) in which INT was assessed with the same instrument, the Child Behavior Checklist (CBCL). First, genome-wide association (GWA) results were used for density estimation and genome-wide complex trait analysis (GCTA) to calculate the variance explained by all SNPs. Next, a fixed-effect inverse variance meta-analysis of the 3 GWA analyses was carried out. Finally, the overlap in results with prior GWA studies of childhood and adulthood psychiatric disorders and treatment responses was tested by examining whether SNPs associated with these traits jointly showed a significant signal for INT. Genome-wide SNPs explained 13% to 43% of the total variance. This indicates that the genetic architecture of INT mirrors the polygenic model underlying adult psychiatric traits. The meta-analysis did not yield a genome-wide significant signal but was suggestive for the PCSK2 gene located on chromosome 20p12.1. SNPs associated with other psychiatric disorders appeared to be enriched for signals with INT (λ = 1.26, p < .03). Our study provides evidence that INT is influenced by many common genetic variants, each with a very small effect, and that, even as early as age 3, genetic variants influencing INT overlap with variants that play a role in childhood and adulthood psychiatric disorders.
Publisher: American Society for Microbiology
Date: 1987
DOI: 10.1128/JB.169.1.33-41.1987
Abstract: Type 4 fimbriae are found in a range of pathogenic bacteria, including Bacteroides nodosus, Moraxella bovis, Neisseria gonorrhoeae, and Pseudomonas aeruginosa. The structural subunits of these fimbriae all contain a highly conserved hydrophobic amino-terminal sequence preceding a variable hydrophilic carboxy-terminal region. We show here that recombinant P. aeruginosa cells containing the B. nodosus fimbrial subunit gene under the control of a strong promoter (pL, from bacteriophage lambda) produced large amounts of fimbriae that were structurally and antigenically indistinguishable from those produced by B. nodosus. This was demonstrated by fimbrial isolation and purification, electrophoretic and Western transfer analyses, and immunogold labeling and electron microscopy. These results suggest that type 4 fimbriated bacteria use a common mechanism for fimbrial assembly and that the structural subunits are interchangeable, thereby providing a basis for the development of multivalent vaccines.
Publisher: Cambridge University Press (CUP)
Date: 18-04-2011
DOI: 10.1017/S0954579411000241
Abstract: The maternal experience of stressful events during pregnancy has been associated with a number of adverse consequences for behavioral development in offspring, but the measurement and interpretation of prenatal stress varies among reported studies. The Raine Study recruited 2900 pregnancies and recorded life stress events experienced by 18 and 34 weeks' gestation along with numerous sociodemographic data. The mother's exposure to life stress events was further documented when the children were followed-up in conjunction with behavioral assessments at ages 2, 5, 8, 10, and 14 years using the Child Behavior Checklist. The maternal experience of multiple stressful events during pregnancy was associated with subsequent behavioral problems for offspring. Independent (e.g., death of a relative, job loss) and dependent stress events (e.g., financial problems, marital problems) were both significantly associated with a greater incidence of mental health morbidity between age 2 and 14 years. Exposure to stressful events in the first 18 weeks of pregnancy showed similar associations with subsequent total and externalizing morbidity to events reported at 34 weeks of gestation. These results were independent of postnatal stress exposure. Improved support for women with chronic stress exposure during pregnancy may improve the mental health of their offspring in later life.
Publisher: Springer Science and Business Media LLC
Date: 05-2021
DOI: 10.1186/S13643-021-01679-5
Abstract: Preterm birth (PTB) is the leading cause of death in children under five years. Spontaneous preterm birth (SPTB) is the major cause of preterm delivery. The key risk factors for SPTB are women who have a short cervix and women who have had previous preterm birth. Cervical cerclage has been used for several decades and has shown to decrease rates of preterm birth. The most commonly used cerclage techniques were described by Shirodkar and McDonald, with no current consensus on the preferred technique. The objective of this review is to determine and compare the effectiveness of both techniques. Studies will be sourced from six electronic databases, as well as from experts in the field, reference lists, and grey literature. Eligible studies will include pregnant women, with a singleton or twin pregnancy, requiring a cervical cerclage, using either the Shirodkar or McDonald technique and run comparative analyses between the two techniques. Randomized control trials (RCT)s, non-randomized control trials, and cohort studies will be eligible. Two independent reviewers will conduct study screening at abstract and full-text level, data extraction and risk of bias assessment. Discrepancies will be resolved by a consensus third reviewer if required. Fixed-effects or random-effects models will be used where appropriate to synthesize results. Alternative synthesis methods will be investigated in instances where a meta-analysis is not appropriate, such as summarizing effect estimates, combining P values, vote counting based on direction of effect, or synthesis in narrative form. This review will synthesize the evidence on both the Shirodkar and McDonald cerclage method, and will help clinicians and health services to determine and deliver best practice antenatal care that has the potential to make an impact on preterm birth. PROSPERO on 25 of May, 2020 with registration number CRD42020177386
Publisher: Informa UK Limited
Date: 03-04-2012
DOI: 10.3109/14767058.2011.653421
Abstract: Hypoxic-ischaemic encephalopathy (HIE) is a major acute neurologic manifestation of perinatal asphyxia associated with significant mortality and morbidity. The study aimed to develop a simple, accurate method of predicting HIE at delivery. Between January 2003 and December 2009, all HIE cases were identified from the 38,404 deliveries at a single tertiary centre. Receiver operating curve (ROC) analysis and multivariate logistic regression assessed the ability of clinical and biochemical assessments to predict HIE. Sixty neonates met the HIE criteria: 39 were moderate-severe HIE. Univariate analyses identified clinical neonatal markers (Apgar scores and neonatal resuscitation level) to be better HIE predictors than biochemical markers (umbilical artery pH, base excess and lactate values). Multivariable models using two to four predictors had areas under ROC curves up to 0.98, sensitivities up to 93% and specificities up to 99%. For moderate-severe HIE, the most effective predictor was neonatal resuscitation level and arterial lactate (ROC 0.98, sensitivity 85%, specificity 99%). The combination of umbilical arterial lactate and neonatal resuscitation level provides a rapid and accurate method of predicting moderate-severe HIE that can identify neonates at birth that may benefit from tertiary care and neuroprotective therapies.
Publisher: Wiley
Date: 10-2013
DOI: 10.1111/AJO.12132
Abstract: There is growing support for umbilical cord blood gas analysis (UCBGA) to be conducted at delivery. A recent study in a tertiary level obstetric unit found that universal UCBGA was associated with improved perinatal outcomes, but there is less evidence of benefit in lower-risk environments. In such settings, lactate analysis may be a suitable alternative. This study evaluated the introduction of universal UCBGA into a secondary obstetric unit and universal umbilical cord lactate analysis program into primary and secondary units. After education, universal UCBGA or lactate analysis was introduced into one primary and two secondary level obstetric units. Univariate and adjusted analysis assessed changes in UCBGA values and Apgar scores over the study period. There were no significant changes in mean blood gas and lactate values at any centre following introduction of universal UCBGA or lactate analysis. However, there was at the primary level obstetric unit a significant reduction in the proportion of neonates with moderate to severe elevations in umbilical artery lactate values. There was a non-significant reduction in arterial pH values less than 7.10 at the secondary metropolitan centre. The data presented in this study suggest that the benefits of introducing UCBGA into a tertiary obstetric centre may be reproduced in a primary obstetric centre within 12 months of implementation. Larger studies are required in secondary units to assess infrequent adverse obstetric and neonatal outcomes.
Publisher: Wiley
Date: 22-11-2013
DOI: 10.1111/AJO.12012
Abstract: Advances in obstetric care have been accompanied by increasing rates of intervention which often involve elective delivery at 37 weeks, soon after term gestation has been achieved. The aim of this study was to examine the behavioural sequelae for children born at this early term gestational age compared with those born at later weeks. The Western Australian Pregnancy Cohort (Raine) Study provided comprehensive obstetric data from 2900 pregnancies. Offspring were followed up at ages two, five, eight, 10, 14 and 17 years using the parent report Child Behaviour Checklist (CBCL) with clinical cutoffs for overall, internalising (withdrawn, somatic complaints, anxious/depressed) and externalising (delinquent, aggressive) behaviour (T-score ≥ 60). We used longitudinal logistic regression models incorporating generalised estimating equations (GEE) with step-wise adjustment for ante-, peri- and postnatal confounding factors. Approximately 9% of our cohort was born within the range of 37(0/7) and 37(6/7) weeks. Those born at 37 weeks' gestation were at increased risk for overall (OR = 1.43, 95% CI = 1.02, 2.01) and externalising (OR = 1.42, 95% CI = 1.01, 2.01) behavioural problems in the fully adjusted model when compared with infants born from 39 weeks onwards. Infants born late preterm (34-36 weeks) and at 38 weeks did not show a significantly increased risk for behavioural problems. Infants born at 37 weeks' gestation are at increased risk for behavioural problems over childhood and adolescence compared with those born later in gestation. We suggest that 37 weeks' gestation may not be the optimal cutoff for defining perinatal risk as it applies to behavioural development.
Publisher: Springer Science and Business Media LLC
Date: 11-09-2014
DOI: 10.1038/GENE.2014.52
Abstract: This genome-wide association study (GWAS) utilises data from the Western Australian Pregnancy Cohort (Raine) Study for 25-hydroxyvitamin D (25(OH)D) levels measured in blood collected at age 6 years (n=673) and at age 14 years (n=1140). Replication of significantly associated genes from previous GWASs was found for both ages. Genome-wide significant associations were found both at age 6 and 14 with single nucleotide polymorphisms (SNPs) on chromosome 11p15 in PDE3B/CYP2R1 (age 6: rs1007392, P=3.9 × 10(-8) age14: rs11023332, P=2.2 × 10(-10)) and on chromosome 4q13 in GC (age 6: rs17467825, P=4.2 × 10(-9) age14: rs1155563 P=3.9 × 10(-9)). In addition, a novel association was observed at age 6 with SNPs on chromosome 7p15 near NPY (age 6: rs156299, P=1.3 × 10(-6)) that could be of functional interest in highlighting alternative pathways for vitamin D metabolism in this age group and merits further analysis in other cohort studies.
Publisher: Public Library of Science (PLoS)
Date: 05-12-2012
Publisher: Informa UK Limited
Date: 03-2011
Publisher: Springer Science and Business Media LLC
Date: 07-1987
DOI: 10.1007/BF02100020
Publisher: Frontiers Media SA
Date: 19-11-2014
Publisher: Elsevier BV
Date: 07-2017
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2011
DOI: 10.1002/HEP.24097
Abstract: Nonalcoholic fatty liver disease (NAFLD) is a predominantly adult-diagnosed disorder. Knowledge regarding the epidemiology, phenotype, and metabolic risk factors, during adolescence is limited. We sought to determine the prevalence, phenotype, and predictors of NAFLD in 1170 community-based adolescents in the Western Australian Pregnancy Cohort (Raine) Study (the Raine Cohort) who underwent a cross-sectional assessment that included questionnaires, anthropometry, cardiovascular examinations, blood tests, and abdominal ultrasound examinations. Among the 1170 adolescents assessed, the prevalence of NAFLD was 12.8%. Females compared with males had a significantly higher prevalence of NAFLD (16.3% versus 10.1%, P = 0.004) and central obesity (33.2% versus 9.9%, P < 0.05). The severity of hepatic steatosis was associated with the body mass index, waist circumference, subcutaneous adipose tissue thickness (SAT), serum leptin level, homeostasis model assessment for insulin resistance score (P < 0.001 for all), and serum alanine aminotransferase level (P < 0.005) in both genders, but it was associated with increasing visceral adipose tissue thickness (VAT P < 0.001) and decreasing serum adiponectin levels (P 0.05) however, in comparison with females with NAFLD, males with NAFLD had greater VAT, a more severe metabolic phenotype with higher glucose levels and systolic blood pressure and lower adiponectin and high-density lipoprotein cholesterol levels (P < 0.001 for all), and greater measures of liver injury (alanine aminotransferase and aspartate aminotransferase, P < 0.001 for all). Similarly, metabolic syndrome was more common in males than females with NAFLD (24% versus 8%, P = 0.01). Suprailiac skinfold thickness predicted NAFLD independently of the body mass index, insulin resistance, and VAT. Gender differences in adolescent NAFLD are related to differences in adipose distribution and adipocytokines. The male phenotype of NAFLD is associated with more adverse metabolic features and greater visceral adiposity than the female phenotype despite the lower prevalence of NAFLD.
Publisher: Oxford University Press (OUP)
Date: 04-04-2013
DOI: 10.1093/AJE/KWS473
Publisher: Wiley
Date: 02-05-2013
Abstract: To characterise changing risk factors of preterm birth in Western Australia between 1984 and 2006. Population-based study. Western Australia. All non-Aboriginal women giving birth to live singleton infants between 1984 and 2006. Multinomial, multivariable regression models were used to assess antecedent profiles by preterm status and labour onset types (spontaneous, medically indicated, prelabour rupture of membranes [PROM]). Population attributable fraction (PAF) estimates characterized the contribution of in idual antecedents as well as the overall contribution of two antecedent groups: pre-existing medical conditions (including previous obstetric history) and pregnancy complications. Antecedent relationships with preterm birth, stratified by labour onset type. Marked increases in maternal age and primiparous births were observed. A four-fold increase in the rates of pre-existing medical complications over time was observed. Rates of pregnancy complications remained stable. Multinomial regression showed differences in antecedent profiles across labour onset types. PAF estimates indicated that 50% of medically indicated preterm deliveries could be eliminated after removing six antecedents from the population estimates for PROM and spontaneous preterm reduction were between 10 and 20%. Variables pertaining to previous and current obstetric complications (previous preterm birth, previous caesarean section, pre-ecl sia and antepartum haemorrhage) were the most influential predictors of preterm birth and adverse labour onset (PROM and medically indicated). Preterm antecedent profiles have changed markedly over the 23 years studied. Some changes may be attributable to true change, others to advances in surveillance and detection. Still others may signify change in clinical practice.
Publisher: Oxford University Press (OUP)
Date: 07-01-2017
DOI: 10.1093/IJE/DYW308
Publisher: Cold Spring Harbor Laboratory
Date: 06-2003
DOI: 10.1101/GR.1015703
Abstract: The chromodomain is 40–50 amino acids in length and is conserved in a wide range of chromatic and regulatory proteins involved in chromatin remodeling. Chromodomain-containing proteins can be classified into families based on their broader characteristics, in particular the presence of other types of domains, and which correlate with different subclasses of the chromodomains themselves. Hidden Markov model (HMM)-generated profiles of different subclasses of chromodomains were used here to identify sequences encoding chromodomain-containing proteins in the mouse transcriptome and genome. A total of 36 different loci encoding proteins containing chromodomains, including 17 novel loci, were identified. Six of these loci (including three apparent pseudogenes, a novel HP1 ortholog, and two novel Msl-3 transcription factor-like proteins) are not present in the human genome, whereas the human genome contains four loci (two CDY orthologs and two apparent CDY pseudogenes) that are not present in mouse. A number of these loci exhibit alternative splicing to produce different isoforms, including 43 novel variants, some of which lack the chromodomain. The likely functions of these proteins are discussed in relation to the known functions of other chromodomain-containing proteins within the same family.
Publisher: Public Library of Science (PLoS)
Date: 14-05-2014
Publisher: Elsevier BV
Date: 02-1988
Publisher: American Society of Tropical Medicine and Hygiene
Date: 07-03-2018
Publisher: Wiley
Date: 03-1994
Publisher: Springer Science and Business Media LLC
Date: 04-2023
DOI: 10.1038/S41588-023-01343-9
Abstract: The timing of parturition is crucial for neonatal survival and infant health. Yet, its genetic basis remains largely unresolved. We present a maternal genome-wide meta-analysis of gestational duration ( n = 195,555), identifying 22 associated loci (24 independent variants) and an enrichment in genes differentially expressed during labor. A meta-analysis of preterm delivery (18,797 cases, 260,246 controls) revealed seven associated loci and large genetic similarities with gestational duration. Analysis of the parental transmitted and nontransmitted alleles ( n = 136,833) shows that 15 of the gestational duration genetic variants act through the maternal genome, whereas 7 act both through the maternal and fetal genomes and 2 act only via the fetal genome. Finally, the maternal effects on gestational duration show signs of antagonistic pleiotropy with the fetal effects on birth weight: maternal alleles that increase gestational duration have negative fetal effects on birth weight. The present study provides insights into the genetic effects on the timing of parturition and the complex maternal–fetal relationship between gestational duration and birth weight.
Publisher: Frontiers Media SA
Date: 2011
Publisher: Elsevier BV
Date: 03-1992
Publisher: Springer Science and Business Media LLC
Date: 08-2008
Publisher: Frontiers Media SA
Date: 04-06-2018
Publisher: Springer Science and Business Media LLC
Date: 04-2004
DOI: 10.1038/NRG1321
Publisher: Elsevier BV
Date: 04-2014
DOI: 10.1016/J.PREGHY.2014.03.005
Abstract: Four putative single nucleotide polymorphism (SNP) risk variants at the preecl sia susceptibility locus on chromosome 2q22 rs2322659 (LCT), rs35821928 (LRP1B), rs115015150 (RND3) and rs17783344 (GCA), were recently shown to associate with known cardiovascular risk factors in a Mexican American cohort. This study aimed to further evaluate the pleiotropic effects of these preecl sia risk variants in an independent Australian population-based cohort. The four SNPs were genotyped in the Western Australian Pregnancy Cohort (Raine) Study that included DNA, clinical and biochemical data from 1246 mothers and 1404 of their now adolescent offspring. Genotype association analyses were undertaken using the SOLAR software. Nominal associations (P<0.05) with cardiovascular risk factors were detected for all four SNPs. The LCT SNP was associated with decreased maternal height (P=0.005) and decreased blood glucose levels in adolescents (P=0.022). The LRP1B SNP was associated with increased maternal height (P=0.026) and decreased maternal weight (P=0.044). The RND3 SNP was associated with decreased triglycerides in adolescents (P=0.001). The GCA SNP was associated with lower risk in adolescents to be born of a preecl tic pregnancy (P=0.003) and having a mother with prior preecl tic pregnancy (P=0.033). Our collective findings support the hypothesis that genetic mechanisms for preecl sia and CVD are, at least in part, shared, but need to be interpreted with some caution as a Bonferroni correction for multiple testing adjusted the statistical significance threshold (adjusted P<0.001).
Publisher: Public Library of Science (PLoS)
Date: 17-02-2011
Publisher: Public Library of Science (PLoS)
Date: 04-2014
Publisher: American Society for Microbiology
Date: 09-1987
DOI: 10.1128/JB.169.9.4018-4023.1987
Abstract: The roles of the fimbrial subunit and the putative basal protein antigens in the serological classification of Bacteroides nodosus have been examined by Western blot (immunoblot)-antibody binding studies of fimbriae isolated from a wide range of strains representative of different serogroups and serotypes. Fimbrial subunits were recognized by antiserum against the homologous serogroup but not generally by heterologous antisera, whereas recognition of the basal antigen was independent of serological classification. Secondary cross-reaction patterns among fimbrial subunits indicated that some serogroups may be more closely related than others. Ex les include serogroups C and G and serogroups D and H. Similar analyses of isolates classified within serotypes A1 and A2, with serotype-specific antisera, showed that this sub ision is also determined by the fimbrial subunit and that significant variation does occur even at this level. These studies suggest that the various serogroups and serotypes of B. nodosus comprise a series of overlapping sets of antigenically related strains.
Publisher: Wiley
Date: 28-02-2013
Abstract: To evaluate the risk of placenta praevia accreta following primary (first) elective or primary emergency caesarean section in a pregnancy complicated by placenta praevia. Retrospective matched case-control study, employing variable matching. Tertiary referral centre between 1993 and 2008. Sixty-five cases and 102 controls were used for the analysis from a total of 82 667 births during the study period. Relevant data were abstracted from clinical records. Matching of cases with controls was based on co-existing placenta praevia, number of previous caesarean sections, and age, with one or two controls per case. Results are presented as odds ratios (ORs) with 95% confidence intervals (95% CIs). Placenta accreta in a pregnancy complicated by placenta praevia following a primary elective or emergency caesarean section, and morbidity associated with pregnancies complicated by placenta accreta. Significantly more cases than controls had an elective caesarean section for their primary caesarean delivery (46.2 versus 18.6% P < 0.001). There were no differences between groups for previous pregnancy loss, uterine surgery, and vaginal delivery, before or after the primary caesarean section. Compared with primary emergency caesarean section, primary elective caesarean section significantly increased the risk of placenta accreta in a subsequent pregnancy in the presence of placenta praevia (OR 3.00 95% CI 1.47-6.12 P = 0.025). Our results suggest that women with a primary elective caesarean section without labour are more likely, compared with those undergoing primary emergency caesarean section with labour, to develop an accreta in a subsequent pregnancy with placenta praevia.
Publisher: Oxford University Press (OUP)
Date: 05-06-2015
DOI: 10.1093/HMG/DDV211
Abstract: Keratoconus is a degenerative eye condition which results from thinning of the cornea and causes vision distortion. Treatments such as ultraviolet (UV) cross-linking have proved effective for management of keratoconus when performed in early stages of the disease. The central corneal thickness (CCT) is a highly heritable endophenotype of keratoconus, and it is estimated that up to 95% of its phenotypic variance is due to genetics. Genome-wide association efforts of CCT have identified common variants (i.e. minor allele frequency (MAF) >5%). However, these studies typically ignore the large set of exonic variants whose MAF is usually low. In this study, we performed a CCT exome-wide association analysis in a s le of 1029 in iduals from a population-based study in Western Australia. We identified a genome-wide significant exonic variant rs121908120 (P = 6.63 × 10(-10)) in WNT10A. This gene is 437 kb from a gene previously associated with CCT (USP37). We showed in a conditional analysis that the WNT10A variant completely accounts for the signal previously seen at USP37. We replicated our finding in independent s les from the Brisbane Adolescent Twin Study, Twin Eye Study in Tasmania and the Rotterdam Study. Further, we genotyped rs121908120 in 621 keratoconus cases and compared the frequency to a s le of 1680 unscreened controls from the Queensland Twin Registry. We found that rs121908120 increases the risk of keratoconus two times (odds ratio 2.03, P = 5.41 × 10(-5)).
Publisher: American Society for Microbiology
Date: 15-12-2003
DOI: 10.1128/JB.185.24.7068-7076.2003
Abstract: Twitching motility is a form of surface translocation mediated by the extension, tethering, and retraction of type IV pili. Three independent Tn 5 -B21 mutations of Pseudomonas aeruginosa with reduced twitching motility were identified in a new locus which encodes a predicted protein of unknown function annotated PA4959 in the P. aeruginosa genome sequence. Complementation of these mutants with the wild-type PA4959 gene, which we designated fimX , restored normal twitching motility. fimX mutants were found to express normal levels of pilin and remained sensitive to pilus-specific bacteriophages, but they exhibited very low levels of surface pili, suggesting that normal pilus function was impaired. The fimX gene product has a molecular weight of 76,000 and contains four predicted domains that are commonly found in signal transduction proteins: a putative response regulator (CheY-like) domain, a PAS-PAC domain (commonly involved in environmental sensing), and DUF1 (or GGDEF) and DUF2 (or EAL) domains, which are thought to be involved in cyclic di-GMP metabolism. Red fluorescent protein fusion experiments showed that FimX is located at one pole of the cell via sequences adjacent to its CheY-like domain. Twitching motility in fimX mutants was found to respond relatively normally to a range of environmental factors but could not be stimulated by tryptone and mucin. These data suggest that fimX is involved in the regulation of twitching motility in response to environmental cues.
Publisher: Elsevier BV
Date: 06-1997
Publisher: Walter de Gruyter GmbH
Date: 18-08-2012
Abstract: We determined a series of quality control (QC) analyses to assess the usability of DNA collected and processed from different countries utilizing different DNA extraction techniques prior to genome-wide association studies (GWAS). The quality of DNA collected utilizing four different DNA extraction techniques and the impact of shipping DNA at different temperatures on array performance were evaluated. Fifteen maternal-fetal pairs were used from four countries. DNA was extracted using four approaches: whole blood, blood spots with whole genome lification (WGA), saliva and buccal swab. S les were sent to a genotyping facility, either on dry ice or at room temperature and genotyped using Affymetrix SNP array 6.0. QC measured included extraction techniques, effect of shipping temperatures, accuracy and Mendelian concordance. Significantly fewer (50%) single nucleotide polymorphisms (SNPs) passed QC metrics for buccal swab DNA (P .0001) due to missing genotype data (P .0001). Whole blood or saliva DNA had the highest call rates (99.2 0.4% and 99.3 0.2%, respectively) and Mendelian concordance. Shipment temperature had no effect. DNA from blood or saliva had the highest call rate accuracy, and buccal swabs had the lowest. DNA extracted from blood, saliva and blood spots were found suitable for GWAS in our study.
Publisher: Springer Science and Business Media LLC
Date: 12-10-2011
Abstract: Preterm birth is the leading cause of neonatal mortality and perinatal morbidity. The etiology of preterm is multi-factorial and still unclear. As evidence increases for a genetic contribution to PTB, so does the need to explore genomics, transcriptomics, proteomics and metabolomics in its study. This review suggests research guidelines for the conduct of high throughput systems biology investigations into preterm birth with the expectation that this will facilitate the sharing of s les and data internationally through consortia, generating the power needed to study preterm birth using integrated "-omics" technologies. The issues to be addressed include: (1) integrated "-omics" approaches, (2) phenotyping, (3) s le collection, (4) data management-integrative databases, (5) international consortia and (6) translational feasibility. This manuscript is the product of discussions initiated by the "-Omics" Working Group at the Preterm Birth International Collaborative Meeting held at the World Health Organization, Geneva, Switzerland in April 2009.
Publisher: Springer Science and Business Media LLC
Date: 10-11-2017
DOI: 10.1038/S41598-017-11852-3
Abstract: Hair cortisol concentration (HCC) is a promising measure of long-term hypothalamus-pituitary-adrenal (HPA) axis activity. Previous research has suggested an association between HCC and psychological variables, and initial studies of inter-in idual variance in HCC have implicated genetic factors. However, whether HCC and psychological variables share genetic risk factors remains unclear. The aims of the present twin study were to: (i) assess the heritability of HCC (ii) estimate the phenotypic and genetic correlation between HPA axis activity and the psychological variables perceived stress, depressive symptoms, and neuroticism using formal genetic twin models and molecular genetic methods, i.e. polygenic risk scores (PRS). HCC was measured in 671 adolescents and young adults. These included 115 monozygotic and 183 dizygotic twin-pairs. For 432 subjects PRS scores for plasma cortisol, major depression, and neuroticism were calculated using data from large genome wide association studies. The twin model revealed a heritability for HCC of 72%. No significant phenotypic or genetic correlation was found between HCC and the three psychological variables of interest. PRS did not explain variance in HCC. The present data suggest that HCC is highly heritable. However, the data do not support a strong biological link between HCC and any of the investigated psychological variables.
Publisher: American Society for Microbiology
Date: 1996
DOI: 10.1128/JB.178.1.46-53.1996
Abstract: The opportunistic pathogen Pseudomonas aeruginosa produces type 4 fimbriae which promote adhesion to epithelial cells and are associated with a form of surface translocation called twitching motility. We have used transposon mutagenesis to identify loci required for fimbrial assembly or function by screening for mutants that lack the spreading colony morphology characteristic of twitching motility. A subset of these mutants is resistant to fimbria-specific phage. One of these mutants (R270) was found to contain a transposon insertion in a new gene, termed pilZ, which is located on chromosomal SpeI fragment I at about 40 min on the P. aeruginosa map, a position remote from other loci involved in fimbrial biogenesis. pilZ appears to be linked to and possibly forms an operon with a gene, holB*, which is homologous to the gene encoding the delta' subunit of Escherichia coli DNA polymerase III. The product of the pilZ gene is a protein of 118 amino acids (predicted molecular weight, 12,895) which probably has a cytoplasmic location. PilZ appears to be a new class of protein which has not hitherto been represented in the sequence databases, and its function is unknown. Complementation studies indicate that pilZ is able to restore the expression of fimbriae on the surface of P. aeruginosa, as well as twitching motility and sensitivity to fimbria-specific phage when provided in trans to the R270 mutant.
Publisher: American Society for Microbiology
Date: 07-1985
DOI: 10.1128/AAC.28.1.96
Abstract: A 7.7-kilobase BamHI fragment was cloned from the transconjugant of a clinical isolate of Escherichia coli containing a 120-kilobase multiresistance IncC plasmid. The recombinant plasmid conferred resistance to kanamycin, gentamicin, tobramycin, sulfamethoxazole, and trimethoprim. This clone was used to generate a series of subclones from which a 2.0-kilobase BamHI-HindIII probe containing a gentamicin 2''-O-adenylyltransferase [AAD(2'')] gene was obtained. This probe hybridized specifically in both colony and Southern hybridizations with the AAD(2'') gene but not with other resistance genes, including other aminoglycoside-modifying genes, or with a reference IncC plasmid lacking the AAD(2'') gene. The AAD(2'') gene may be part of a transposon, since hybridization occurred with both nonconjugative plasmids and the chromosome in some isolates.
Publisher: Wiley
Date: 03-1981
Publisher: Wiley
Date: 27-01-2006
Publisher: Oxford University Press (OUP)
Date: 1991
Publisher: Springer Science and Business Media LLC
Date: 03-1996
DOI: 10.1038/NG0396-329
Publisher: Elsevier BV
Date: 09-2000
DOI: 10.1016/S0006-8993(00)02692-5
Abstract: We isolated a mammalian homologue of the C. elegans gene unc-50 that we have named UNCL. The 777 kb rat UNCL cDNA encodes a 259 amino acid protein that is expressed in a wide variety of tissues with highest mRNA levels in brain, kidney and testis. Hydropathy plot analysis and in vitro translation experiments with microsomal membranes indicate that UNCL is a transmembrane protein. Hemagglutinin tagged UNCL was stably transfected into SaOS-2 osteosarcoma cells and exhibited a nuclear rim staining pattern which was retained following extraction with 1% Triton X-100, suggesting that UNCL localizes to the inner nuclear membrane. UNCL-HA was extractable in 350 mM NaCl, suggesting that UNCL is not associated with the nuclear matrix. Homopolymer RNA-binding assays performed on in vitro translated UNCL protein and 'structural modeling by homology' suggest that UNCL binds RNA via an amino-terminal RNA Recognition-like Motif. Since unc-50 is required for expression of assembled muscle-type nicotinic receptors in the nematode we investigated whether UNCL had a similar function for mammalian nicotinic receptors. When UNCL was co-expressed with neural nicotinic receptors in Xenopus oocytes or COS cells it increased expression of functional cell surface receptors up to 1. 6-fold. We conclude that UNCL is a novel inner nuclear membrane protein that associates with RNA and is involved in the cell-surface expression of neuronal nicotinic receptors. UNCL plays a broader role because UNCL homologues are present in two yeast and a plant species, none of which express nicotinic receptors and it is also found in tissues that lack nicotinic receptors.
Publisher: Wiley
Date: 22-04-2014
DOI: 10.1002/JBMR.2138
Abstract: It is uncertain whether the vitamin D status of pregnant women influences bone mass of their children. Cohort studies have yielded conflicting results none have examined offspring at skeletal maturity. This longitudinal, prospective study investigated the association between maternal vitamin D status and peak bone mass of offspring in 341 mother and offspring pairs in the Western Australian Pregnancy Cohort (Raine) Study. Maternal serum s les collected at 18 weeks gestation were assayed for 25-hydroxyvitamin D (25OHD). Outcomes were total body bone mineral content (BMC) and bone mineral density (BMD) measured by dual-energy X-ray absorptiometry in offspring at 20 years of age. The mean (± SD) maternal serum 25OHD concentration was 57.2 ± 19.2 nmol/L 132 women (38.7%) were vitamin D-deficient (25OHD <50 nmol/L). After adjustment for season of s le collection, maternal factors, and offspring factors (sex, birth weight, and age, height, lean mass, and fat mass at 20 years), maternal 25OHD concentration was positively associated with total body BMC and BMD in offspring, with a mean difference of 19.2 (95% confidence interval [CI], 5.6-32.7) g for BMC and 4.6 (95% CI, 0.1-9.1) mg/cm(2) for BMD per 10.0 nmol/L of maternal 25OHD. Maternal vitamin D deficiency was associated with 2.7% lower total body BMC (mean ± SE) (2846 ± 20 versus 2924 ± 16 g, p = 0.004) and 1.7% lower total body BMD (1053 ± 7 versus 1071 ± 5 mg/cm(2) , p = 0.043) in the offspring. We conclude that vitamin D deficiency in pregnant women is associated with lower peak bone mass in their children. This may increase fracture risk in the offspring in later life.
Publisher: The Endocrine Society
Date: 2007
DOI: 10.1210/JC.2006-1378
Abstract: The objective of this study was to determine the influence of birth weight and postnatal weight gain on age at menarche. This was a prospective cohort study where girls from the West Australian Pregnancy (Raine) Cohort Study were followed prospectively from fetal life (18 wk of pregnancy) to adolescence (12-14 yr). Age at menarche was the main outcome measure. Growth status at birth was judged by expected birth weight ratio (EBW a ratio of observed infant's birth weight over median birth weight appropriate for maternal age, weight, height, parity, infant sex, and gestational age). Postnatal growth status was judged by body mass index (BMI). Both EBW (P = 0.020) and BMI in childhood (8 yr of age) (P < 0.001) were associated with age at menarche. Menarche occurred earlier in girls with lower EBW and higher BMI. We have demonstrated for the first time that both birth weight and weight gain in childhood are associated with age at menarche. Weight gain before birth and subsequent weight gain up to the age of 8 yr were found to have opposing influences on the timing of menarche. Lower EBW combined with higher BMI during childhood predicted early age at menarche, and this relationship existed across normal birth weight and BMI ranges.
Publisher: Springer Science and Business Media LLC
Date: 29-09-2017
DOI: 10.1038/S41467-017-00556-X
Abstract: There are few ex les of robust associations between rare copy number variants (CNVs) and complex continuous human traits. Here we present a large-scale CNV association meta-analysis on anthropometric traits in up to 191,161 adult s les from 26 cohorts. The study reveals five CNV associations at 1q21.1, 3q29, 7q11.23, 11p14.2, and 18q21.32 and confirms two known loci at 16p11.2 and 22q11.21, implicating at least one anthropometric trait. The discovered CNVs are recurrent and rare (0.01–0.2%), with large effects on height ( .4 cm), weight ( kg), and body mass index (BMI) ( .5 kg/m 2 ). Burden analysis shows a 0.41 cm decrease in height, a 0.003 increase in waist-to-hip ratio and increase in BMI by 0.14 kg/m 2 for each Mb of total deletion burden ( P = 2.5 × 10 −10 , 6.0 × 10 −5 , and 2.9 × 10 −3 ). Our study provides evidence that the same genes (e.g., MC4R , FIBIN , and FMO5 ) harbor both common and rare variants affecting body size and that anthropometric traits share genetic loci with developmental and psychiatric disorders.
Publisher: Elsevier BV
Date: 06-1994
Publisher: Elsevier BV
Date: 07-2011
Publisher: Oxford University Press (OUP)
Date: 11-12-2018
DOI: 10.1093/IJE/DYY273
Publisher: Wiley
Date: 03-1991
Publisher: Oxford University Press (OUP)
Date: 15-11-2012
DOI: 10.1093/IJE/DYS171
Abstract: For years, body mass index (BMI) has been used by scientists to track weight problems and obesity in children and adults. Recent studies have implicated the fat mass and obesity gene (FTO) in the increase of BMI in young adults. A longer duration of breastfeeding is known to reduce the risk of being overweight later in life, but its ability to modify the effect because of FTO is not known. We studied 1096 children from the Western Australian Pregnancy (Raine) cohort who were followed up from birth to 14 years of age. Linear mixed-effects models were used to investigate BMI growth trajectories in boys and girls separately. An association was found between BMI growth and the duration of exclusive breastfeeding (EXBF) among carriers of the risk allele of the FTO SNP rs9939609. In girls, EXBF interacts with the SNP at baseline and can reverse the increase in BMI because of SNP risk allele by age 14 years after 3 months of EXBF. In boys, EXBF reduces BMI both in carriers and non-carriers of the risk allele with an association found after 10 years of age. Six months of EXBF will put the boys' BMI growth curves back to the normal range. Our study could have major health implications by providing new perspectives for the prevention of growth problems in children carrying risk alleles in the FTO gene.
Publisher: Springer Science and Business Media LLC
Date: 05-2019
Publisher: Springer Science and Business Media LLC
Date: 02-09-2200
DOI: 10.1038/S41467-019-11881-8
Abstract: The duration of pregnancy is influenced by fetal and maternal genetic and non-genetic factors. Here we report a fetal genome-wide association meta-analysis of gestational duration, and early preterm, preterm, and postterm birth in 84,689 infants. One locus on chromosome 2q13 is associated with gestational duration the association is replicated in 9,291 additional infants (combined P = 3.96 × 10 −14 ). Analysis of 15,588 mother-child pairs shows that the association is driven by fetal rather than maternal genotype. Functional experiments show that the lead SNP, rs7594852, alters the binding of the HIC1 transcriptional repressor. Genes at the locus include several interleukin 1 family members with roles in pro-inflammatory pathways that are central to the process of parturition. Further understanding of the underlying mechanisms will be of great public health importance, since giving birth either before or after the window of term gestation is associated with increased morbidity and mortality.
Publisher: Wiley
Date: 02-2002
Publisher: Elsevier BV
Date: 1996
Publisher: Elsevier BV
Date: 11-2015
DOI: 10.1016/J.JRI.2015.05.002
Abstract: Periodontal disease (PD) in pregnancy is associated with an increased risk of adverse pregnancy outcomes including miscarriage and preterm birth. Evidence exists that periodontal disease treatment may reduce inflammatory mediators in gingival crevicular fluid (GCF) and the risk of inflammation-associated pregnancy complications. The aim was to determine if periodontal disease treatment during mid-pregnancy alters local inflammation in GCF and has beneficial effects on clinical dental parameters. Eighty pregnant women with clinically diagnosed PD were recruited from a randomised controlled trial on the treatment of periodontal disease in pregnancy conducted in Perth, Australia. The treatment group underwent intensive PD treatment (20-28 weeks' GA), while the control group underwent the same treatment postnatally. GCF was collected at 20 and 28 weeks' gestation and concentrations of cytokines determined by multiplex assay: IL-1β, IL-6, IL-8, IL-10, IL-12p70, IL-17, TNF-α and MCP-1. Periodontal treatment significantly reduced the GCF levels of IL-1β, IL-10, IL-12p70 and IL-6 at 28 weeks' GA compared with controls, while levels of MCP-1, IL-8 and TNF-α exhibited a significant gestational age-dependent increase, but no treatment response. Post-treatment clinical parameters improved with significant reductions in bleeding on probing, clinical attachment loss, and probing depth. No changes in pregnancy-related outcomes were observed, although the severity of periodontal disease was significantly associated with an increased risk of infants born small for gestational age. PD treatment in pregnancy reduces the levels of some inflammatory mediators in the GCF and improves dental parameters, with no overt effects on pregnancy outcome.
Publisher: Informa UK Limited
Date: 08-08-2011
DOI: 10.3109/14767058.2011.596959
Abstract: Umbilical cord blood gas analysis has a significant and growing role in early neonatal assessment. Factors often delay analysis of cord blood allowing values to change. Consequently, this study evaluates the impact of time, temperature and method of storage on umbilical blood gas and lactate analyses. Umbilical cord segments from 80 singleton deliveries were randomized to: cords at room temperature (CR), cords stored on ice (CI), syringes at room temperature (SR) or syringes stored on ice (SI). Analysis occurred every 15 minutes for one-hour. Mixed model analysis of variance allowing for repeated measures was utilized. Cord arterial pH deteriorated in CR, CI, and SI within 15 minutes (p ≤ 0.001), with SR stable until 60 minutes (p = 0.002). Arterial pCO(2) remained stable in SR and CI, increased in SI (p = 0.002 45 minutes) and decreased in CR (p < 0.001 45 minutes). Arterial base excess deteriorated in CR and SI (p ≤ 0.009 15 minutes), SR (p < 0.001 30 minutes), and CI (p < 0.001 45 minutes). Arterial lactate levels increased within 15 minutes in all groups (p < 0.001). Cord blood gas values change rapidly after delivery. Smallest changes were seen in SR group. Data suggest that analyses should be conducted as soon as possible after delivery.
Publisher: Springer Science and Business Media LLC
Date: 2013
Publisher: American Association for the Advancement of Science (AAAS)
Date: 28-05-2004
Abstract: There are 481 segments longer than 200 base pairs (bp) that are absolutely conserved (100% identity with no insertions or deletions) between orthologous regions of the human, rat, and mouse genomes. Nearly all of these segments are also conserved in the chicken and dog genomes, with an average of 95 and 99% identity, respectively. Many are also significantly conserved in fish. These ultraconserved elements of the human genome are most often located either overlapping exons in genes involved in RNA processing or in introns or nearby genes involved in the regulation of transcription and development. Along with more than 5000 sequences of over 100 bp that are absolutely conserved among the three sequenced mammals, these represent a class of genetic elements whose functions and evolutionary origins are yet to be determined, but which are more highly conserved between these species than are proteins and appear to be essential for the ontogeny of mammals and other vertebrates.
Publisher: Springer Science and Business Media LLC
Date: 22-12-2017
Publisher: Cambridge University Press (CUP)
Date: 05-12-2012
Publisher: Springer Science and Business Media LLC
Date: 29-01-2014
DOI: 10.1038/MP.2012.184
Publisher: Springer Science and Business Media LLC
Date: 16-09-2014
DOI: 10.1038/NCOMMS5831
Abstract: Twin studies suggest that expressive vocabulary at ~24 months is modestly heritable. However, the genes influencing this early linguistic phenotype are unknown. Here we conduct a genome-wide screen and follow-up study of expressive vocabulary in toddlers of European descent from up to four studies of the EArly Genetics and Lifecourse Epidemiology consortium, analysing an early (15–18 months, ‘one-word stage’, N Total =8,889) and a later (24–30 months, ‘two-word stage’, N Total =10,819) phase of language acquisition. For the early phase, one single-nucleotide polymorphism (rs7642482) at 3p12.3 near ROBO2 , encoding a conserved axon-binding receptor, reaches the genome-wide significance level ( P =1.3 × 10 −8 ) in the combined s le. This association links language-related common genetic variation in the general population to a potential autism susceptibility locus and a linkage region for dyslexia, speech-sound disorder and reading. The contribution of common genetic influences is, although modest, supported by genome-wide complex trait analysis (meta-GCTA h 2 15–18-months =0.13, meta-GCTA h 2 24–30-months =0.14) and in concordance with additional twin analysis (5,733 pairs of European descent, h 2 24-months =0.20).
Publisher: Oxford University Press (OUP)
Date: 24-11-2015
DOI: 10.1093/HMG/DDV472
Publisher: Elsevier BV
Date: 04-1995
DOI: 10.1016/S0002-9149(99)80416-0
Abstract: Amyl nitrite may be used to provoke latent gradients in patients with hypertrophic cardiomyopathy (HC) without significant resting outflow tract gradients, but afterload reduction may not be comparable to a more physiologic stressor such as symptom-limited exercise testing. This study compared the ability of amyl nitrite and exercise testing to provoke outflow tract gradients in 57 patients (40 men and 17 women, mean age +/- SD 49 +/- 16 years) with HC (septal thickness 19 +/- 5 mm, average resting gradient 13 +/- 10 mm Hg) who underwent echocardiography at rest, after amyl nitrite inhalation, and after maximal exercise. No significant gradient (< 50 mm Hg) was induced after either provocation in 26 patients (46%) in 15 patients (26%), inducibility was achieved after both stressors, in 6 (11%) after exercise only, and in 10 (18%) after amyl only. Patients with amyl-induced gradients differed from those in whom gradients were noninducible on the basis of smaller outflow tract dimensions (p < 0.001), larger resting gradients (p < 0.001), and a greater prevalence of "septal bulge" morphology (p = 0.02). Those with exercise-induced gradients were able to attain a greater workload (p = 0.07), have larger resting gradients (p = 0.02), and also tended to have a septal bulge morphology (p < or = 0.01). Although outflow tract obstruction increased to similar levels after amyl nitrite (49 +/- 39 mm Hg) and symptom-limited exercise (47 +/- 39 mm Hg), gradients induced by exercise and amyl correlated poorly (r = 0.54).(ABSTRACT TRUNCATED AT 250 WORDS)
Publisher: American Chemical Society (ACS)
Date: 09-10-2014
DOI: 10.1021/PR500852P
Abstract: Threatened preterm labor (TPTL) accounts for ∼30% of pregnancy-related hospital admissions. Maternal peripheral leukocytes can be used to monitor a variety of physiological processes occurring in the body. Two high-throughput mass spectrometry methodologies, SWATH and iTRAQ, were used to study differentially expressed peripheral blood leukocyte lysate proteins in symptomatic women admitted for TPTL who had a preterm birth within 48 h (n = 16) and those who did not (n = 24). The SWATH spectral library consisted of 783 proteins. SWATH methodology quantified 258 proteins (using ≥2 peptides) and 5 proteins (ALBU, ANXA6, HNRPK, HSP90A, and PDIA1) were differentially expressed (p < 0.05, Mann-Whitney U). iTRAQ workflow identified 765 proteins 354 proteins were quantified and 14 proteins (MIF, UBIQ, HXK3, ALBU, HNRPD, ST1A2, RS15A, RAP1B, CAN1, IQGA2, ST1A1, COX5A, ADDA, and UBQL1) were significantly different between the two groups of women (p < 0.05, Mann-Whitney U). Albumin was the only common differentially expressed protein in both SWATH (28% decrease) and iTRAQ studies (45% decrease). This decrease in albumin was validated using ELISA (11% decrease, p < 0.05, Mann-Whitney U) in another 23 TPTL women. This work suggests that albumin is a broad indicator of leukocyte activation with impending preterm birth and provides new future work directions to understand the pathophysiology of TPTL.
Publisher: Wiley
Date: 18-06-2015
DOI: 10.1002/AJMG.B.32333
Abstract: In idual differences in aggressive behavior emerge in early childhood and predict persisting behavioral problems and disorders. Studies of antisocial and severe aggression in adulthood indicate substantial underlying biology. However, little attention has been given to genome-wide approaches of aggressive behavior in children. We analyzed data from nine population-based studies and assessed aggressive behavior using well-validated parent-reported questionnaires. This is the largest s le exploring children's aggressive behavior to date (N = 18,988), with measures in two developmental stages (N = 15,668 early childhood and N = 16,311 middle childhood/early adolescence). First, we estimated the additive genetic variance of children's aggressive behavior based on genome-wide SNP information, using genome-wide complex trait analysis (GCTA). Second, genetic associations within each study were assessed using a quasi-Poisson regression approach, capturing the highly right-skewed distribution of aggressive behavior. Third, we performed meta-analyses of genome-wide associations for both the total age-mixed s le and the two developmental stages. Finally, we performed a gene-based test using the summary statistics of the total s le. GCTA quantified variance tagged by common SNPs (10-54%). The meta-analysis of the total s le identified one region in chromosome 2 (2p12) at near genome-wide significance (top SNP rs11126630, P = 5.30 × 10(-8) ). The separate meta-analyses of the two developmental stages revealed suggestive evidence of association at the same locus. The gene-based analysis indicated association of variation within AVPR1A with aggressive behavior. We conclude that common variants at 2p12 show suggestive evidence for association with childhood aggression. Replication of these initial findings is needed, and further studies should clarify its biological meaning. © 2015 Wiley Periodicals, Inc.
Publisher: American Society for Microbiology
Date: 05-1990
DOI: 10.1128/JB.172.5.2601-2607.1990
Abstract: Type 4 fimbriae (pili) are found in a wide variety of gram-negative bacteria and are composed of small structural subunits which share significant sequence homology among different species, especially at their amino-terminal ends. Previous studies demonstrating morphogenetic expression of Bacteroides nodosus fimbriae from cloned subunit genes in Pseudomonas aeruginosa suggested that there is a common mechanism for type 4 fimbriae assembly and that the structural subunits are interchangeable (J. S. Mattick et al., J. Bacteriol. 169:33-41, 1987). Here we have examined the expression of Moraxella bovis fimbrial subunits in P. aeruginosa. M. bovis subunits were assembled into extracellular fimbriae in this host, in some cases as a homopolymer but in others as a mosaic with the indigenous subunit, indicating structural equivalence. This result contrasts with other studies in which recombinant P. aeruginosa expressing different subunits produced fimbriae composed almost exclusively of one subunit or the other (T. C. Elleman and J. E. Peterson, Mol. Microbiol. 1:377-380, 1987). Both observations can be explained by reversibility of subunit-subunit interactions at the site of assembly, with the forward equilibrium favoring chain extension between compatible subunits.
Publisher: Wiley
Date: 11-12-2017
Publisher: Oxford University Press (OUP)
Date: 25-04-2014
DOI: 10.1093/HMG/DDU150
Publisher: Elsevier BV
Date: 11-2016
DOI: 10.1016/J.EJOGRB.2016.07.509
Abstract: To compare women's views about blood pressure (BP) control in CHIPS (Control of Hypertension In Pregnancy Study) (NCT01192412). Quantitative and qualitative analysis of questionnaire responses. International randomised trial (94 sites, 15 countries). 911 (92.9%) women randomised to 'tight' (target diastolic blood pressure, 85mmHg) or 'less tight' (target diastolic blood pressure, 100mmHg) who completed questionnaires. A questionnaire was administered at ∼6-12 weeks postpartum regarding post-discharge morbidity and views about trial participation. Questionnaires were administered by the site co-ordinator, and contact was made by phone, home or clinic visit rarely, data was collected from medical records. Quantitative analyses were Chi-square or Fisher's exact test for categorical variables, mixed effects multinomial logistic regression to adjust for confounders, and p<0.001 for statistical significance. NVivo software was used for thematic analysis of women's views. Satisfaction, measured as willingness to have the same treatment in another pregnancy or recommend that treatment to a friend. Among the 533 women in 'tight' (N=265) vs. 'less tight' (N=268) control who provided comments for qualitative analysis, women in 'tight' (vs. 'less tight') control made fewer positive comments about the amount of medication taken (5 vs. 28 women, respectively) and intensity of BP monitoring (7 vs. 17, respectively). However, this did not translate into less willingness to either have the same treatment in another pregnancy (434, 95.8% vs. 423, 92.4%, respectively p=0.14) or recommend that treatment to a friend (435, 96.0% and 428, 93.4%, respectively p=0.17). Importantly, although satisfaction remained high among women with an adverse outcome, those in 'tight' control who suffered an adverse outcome (vs. those who did not) were not consistently less satisfied, whereas this was not the case among women in 'less tight' control among whom satisfaction was consistently lower for the CHIPS primary outcome (p<0.001), severe hypertension (p≤0.01), and pre-ecl sia (p<0.001). Women in 'tight' (vs. 'less tight') control were equally satisfied with their care, and more so in the face of adverse perinatal or maternal outcomes.
Publisher: Elsevier BV
Date: 04-2016
DOI: 10.1016/J.BONE.2016.01.016
Abstract: In older adults, high-normal circulating cortisol levels are associated with lower bone mass, but relationships between hypothalamic-pituitary-adrenal axis function and peak bone mass in young adults have not been examined. We studied 411 male and 390 female participants in the Western Australia Pregnancy Cohort (Raine) Study. At 18years of age, participants underwent a Trier Social Stress Test (TSST) with measurement of plasma and salivary cortisol at baseline and at multiple time points after stress. Cortisol responses were classified as anticipatory responder (significant fall in cortisol during the test), reactive responder (significant increase) or non-responder. At 20years, total body bone mineral content (BMC) and density (BMD) were measured by DXA. In males, after adjustment for weight, height (for BMC and bone area only), alcohol and smoking, there was a significant inverse relationship between both plasma and salivary cortisol measured at baseline in the TSST and each of BMC and BMD, such that each additional 10% of salivary cortisol was associated with reductions of 6.9g (95% CI -11.7, -2.2) in BMC, and 1.8mg/cm(2) (95% CI -3.3, -0.4) in BMD. Males classified as anticipatory responders in the TSST had 3.2% lower BMC (adjusted mean±SE: 3131±28 vs. 3233±18g, P=0.006) and 2.5% lower BMD (1108±9 vs. 1136±6mg/cm(2), P=0.022) than reactive responders. In females, there were no significant relationships between baseline cortisol or TSST responses and BMC or BMD in covariate-adjusted analyses. We conclude that in young males (but not females), higher circulating cortisol at the baseline of the stress test and an anticipatory responder pattern on the TSST are associated with lower total body bone mass.
Publisher: American Society for Microbiology
Date: 15-08-2002
DOI: 10.1128/JB.184.16.4544-4554.2002
Abstract: The response regulator AlgR is required for both alginate biosynthesis and type IV fimbria-mediated twitching motility in Pseudomonas aeruginosa . In this study, the roles of AlgR signal transduction and phosphorylation in twitching motility and biofilm formation were examined. The predicted phosphorylation site of AlgR (aspartate 54) and a second aspartate (aspartate 85) in the receiver domain of AlgR were mutated to asparagine, and mutant algR alleles were introduced into the chromosome of P. aeruginosa strains PAK and PAO1. Assays of these mutants demonstrated that aspartate 54 but not aspartate 85 of AlgR is required for twitching motility and biofilm initiation. However, strains expressing AlgR D85N were found to be hyperfimbriate, indicating that both aspartate 54 and aspartate 85 are involved in fimbrial biogenesis and function. algD mutants were observed to have wild-type twitching motility, indicating that AlgR control of twitching motility is not mediated via its role in the control of alginate biosynthesis. In vitro phosphorylation assays showed that AlgR D54N is not phosphorylated by the enteric histidine kinase CheA. These findings indicate that phosphorylation of AlgR most likely occurs at aspartate 54 and that aspartate 54 and aspartate 85 of AlgR are required for the control of the molecular events governing fimbrial biogenesis, twitching motility, and biofilm formation in P. aeruginosa .
Publisher: Wiley
Date: 03-1991
Publisher: Elsevier BV
Date: 11-2014
Publisher: Springer Science and Business Media LLC
Date: 21-11-2010
DOI: 10.1038/NG.714
Publisher: Elsevier BV
Date: 10-1996
Publisher: Public Library of Science (PLoS)
Date: 07-01-2013
Publisher: Wiley
Date: 28-05-2010
DOI: 10.1111/J.1471-0528.2010.02596.X
Abstract: To examine the association of fetal alcohol exposure during pregnancy with child and adolescent behavioural development. The Western Australian Pregnancy Cohort (Raine) Study recruited 2900 pregnancies (1989-91) and the 14-year follow up was conducted between 2003 and 2006. Tertiary obstetric hospital in Perth, Western Australia. The women in the study provided data at 18 and 34 weeks of gestation on weekly alcohol intake: no drinking, occasional drinking (up to one standard drink per week), light drinking (2-6 standard drinks per week), moderate drinking (7-10 standard drinks per week), and heavy drinking (11 or more standard drinks per week). Methods Longitudinal regression models were used to analyse the effect of prenatal alcohol exposure on Child Behaviour Checklist (CBCL) scores over 14 years, assessed by continuous z-scores and clinical cutoff points, after adjusting for confounders. Their children were followed up at ages 2, 5, 8, 10 and 14 years. The CBCL was used to measure child behaviour. Light drinking and moderate drinking in the first 3 months of pregnancy were associated with child CBCL z-scores indicative of positive behaviour over 14 years after adjusting for maternal and sociodemographic characteristics. These changes in z-score indicated a clinically meaningful reduction in total, internalising and externalising behavioural problems across the 14 years of follow up. Our findings do not implicate light-moderate consumption of alcohol in pregnancy as a risk factor in the epidemiology of child behavioural problems.
Publisher: Springer Science and Business Media LLC
Date: 06-2017
DOI: 10.1007/S10555-017-9671-3
Abstract: The significant role of platelets in the protection of tumour cells from immune attack and shear forces and the promotion of tumour cell extravasation from the bloodstream in the process of haematogenous metastasis have been extensively studied. The role of platelets, and in particular platelet membranes, in the promotion of a more metastatic phenotype in tumour cells is a more recent and, therefore, less well-recognised area of research. This review article summarises studies that have focused on the impact of tumour cell interactions with platelets and platelet membranes on tumour cell behaviour in vitro and in vivo. Furthermore, the gene expression changes that occur within tumour cells following contact with platelet membranes are also extensively reviewed. Overall, the interaction of platelet membranes with tumour cells results in a more invasive phenotype and the promotion of epithelial to mesenchymal transition with our own genetic studies revealing that matrix metalloproteinase-1, plasminogen activator inhibitor-1 and interleukin-8 are globally upregulated in a range of tumour cell lines.
Publisher: Elsevier BV
Date: 04-2011
Abstract: High birth weight is associated with adult body mass index (BMI). We hypothesized that birth weight and BMI may partly share a common genetic background. The objective was to examine the associations of 12 established BMI variants in or near the NEGR1, SEC16B, TMEM18, ETV5, GNPDA2, BDNF, MTCH2, BCDIN3D, SH2B1, FTO, MC4R, and KCTD15 genes and their additive score with birth weight. A meta-analysis was conducted with the use of 1) the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk, Hertfordshire, Fenland, and European Youth Heart Study cohorts (n(max) = 14,060) 2) data extracted from the Early Growth Genetics Consortium meta-analysis of 6 genome-wide association studies for birth weight (n(max) = 10,623) and 3) all published data (n(max) = 14,837). Only the MTCH2 and FTO loci showed a nominally significant association with birth weight. The BMI-increasing allele of the MTCH2 variant (rs10838738) was associated with a lower birth weight (β ± SE: -13 ± 5 g/allele P = 0.012 n = 23,680), and the BMI-increasing allele of the FTO variant (rs1121980) was associated with a higher birth weight (β ± SE: 11 ± 4 g/allele P = 0.013 n = 28,219). These results were not significant after correction for multiple testing. Obesity-susceptibility loci have a small or no effect on weight at birth. Some evidence of an association was found for the MTCH2 and FTO loci, ie, lower and higher birth weight, respectively. These findings may provide new insights into the underlying mechanisms by which these loci confer an increased risk of obesity.
Publisher: Wiley
Date: 21-08-2012
Publisher: Wiley
Date: 04-2015
DOI: 10.1111/GBB.12213
Publisher: Springer Science and Business Media LLC
Date: 03-02-2011
DOI: 10.1038/GENE.2011.2
Abstract: Otitis media (OM) is a common childhood disease characterised by middle ear inflammation following infection. Susceptibility to recurrent acute OM (rAOM) and chronic OM with effusion (COME) is highly heritable. Two murine mutants, Junbo and Jeff, spontaneously develop severe OM with similar phenotypes to human disease. Fine-mapping of these mutants identified two genes (Evi1 and Fbxo11) that interact with the transforming growth factor β (TGFβ) signalling pathway. We investigated these genes, as well as four Sma- and Mad-related (SMAD) genes of the TGFβ pathway, as candidate rAOM/COME susceptibility genes in two predominantly Caucasian populations. Single-nucleotide polymorphisms (SNPs) within FBXO11 (family-based association testing Z-Score=2.61 P(best)=0.009) were associated with severe OM in family-based analysis of 434 families (561 affected in iduals) from the Western Australian Family Study of OM. The FBXO11 association was replicated by directed analysis of Illumina 660W-Quad Beadchip data available for 253 cases and 866 controls (OR=1.55 (95% CI 1.28-1.89) P(best)=6.9 × 10(-6)) available within the Western Australian Pregnancy Cohort (Raine) Study. Combined primary and replication results show P(combined)=2.98 × 10(-6). Neither cohort showed an association with EVI1 variants. Family-based associations at SMAD2 (P=0.038) and SMAD4 (P=0.048) were not replicated. Together, these data provide strong evidence for FBXO11 as a susceptibility gene for severe OM.
Publisher: EMBO
Date: 11-2001
DOI: 10.1093/EMBO-REPORTS/KVE230
Abstract: Around 98% of all transcriptional output in humans is non‐coding RNA. RNA‐mediated gene regulation is widespread in higher eukaryotes and complex genetic phenomena like RNA interference, co‐suppression, transgene silencing, imprinting, methylation, and possibly position‐effect variegation and transvection, all involve intersecting pathways based on or connected to RNA signaling. I suggest that the central dogma is incomplete, and that intronic and other non‐coding RNAs have evolved to comprise a second tier of gene expression in eukaryotes, which enables the integration and networking of complex suites of gene activity. Although proteins are the fundamental effectors of cellular function, the basis of eukaryotic complexity and phenotypic variation may lie primarily in a control architecture composed of a highly parallel system of trans ‐acting RNAs that relay state information required for the coordination and modulation of gene expression, via chromatin remodeling, RNA–DNA, RNA–RNA and RNA–protein interactions. This system has interesting and perhaps informative analogies with small world networks and dataflow computing.
Publisher: Informa UK Limited
Date: 10-01-2013
DOI: 10.3109/13816810.2012.755632
Abstract: The Raine Eye Health Study (REHS) was conceived to determine the prevalence of and risk factors for eye disease in young adults, and to characterize ocular biometric parameters in a young adult cohort. This article summarizes the rationale and study design of REHS and outlines the baseline prevalence of ophthalmic disease in this population. The Western Australian Pregnancy Cohort (Raine) Study originated as a randomized-controlled trial of 2900 women recruited from the state's largest maternity hospital. Their offspring (N = 2868) have been followed at birth, ages 1, 2, 3, 5, 8, 10, 14, 17 and 20 years of age in a prospective cohort study. DNA has been collected from participants for genome-wide association studies. At the 20-year follow-up participants completed a comprehensive eye assessment that included visual acuity, orthoptic assessment and cycloplegic autorefraction, as well as several ocular biometric variables and multiple ophthalmic photographs of the anterior and posterior segments. A total of 1344 participants (51.3% male) were assessed over a 24-month period. For the majority of examined participants (85.5%) both parents were Caucasian, 63.3% had completed school year 12 or equivalent, 5.5% had myopia (spherical equivalent ≤-3 diopters) and 15 participants (1.2%) had unilateral or bilateral pterygia. Keratoconus, cataract, keratitis and uveitis were rare. The REHS design and methodology allow comparison with other population-based studies of eye disease. The study established the prevalence of eye disorders in a large s le of predominantly Caucasian young Australian adults.
Publisher: Microbiology Society
Date: 10-2000
Publisher: Wiley
Date: 28-07-2009
DOI: 10.1111/J.1471-0528.2009.02279.X
Abstract: To compare the efficacy and patient satisfaction of three methods of labour induction (double balloon catheters, single balloon catheters and prostaglandin gel) in term nulliparous women with unfavourable cervices. Randomised controlled trial. A total of 330 nulliparous women with unfavourable cervices induced at term. Three cervical ripening study arms were used: double balloon catheter (107 women) 16F Foley catheter (110 women) and PGE(2) gel (2 mg) (113 women). Caesarean section, induction to delivery interval, adverse reactions and patient satisfaction. There was no difference in caesarean delivery rates between groups (double balloon 43%, single balloon 36%, PGE(2) 37%, P = 0.567). The induction to delivery interval was longer in the double balloon group (median 24.5 95% CI 23.7, 30.6 hours) than the single balloon (23.2 20.8, 25.8 hours) or PGE(2) (23.8 21.7, 26.8 hours) (P = 0.043). Uterine hyperstimulation occurred in 14% of the PGE(2) group with none occurring with mechanical cervical ripening. Cord blood gases were worse in the PGE(2) group: median arterial pH double balloon 7.26 (range 7.03-7.40) single balloon 7.26 (7.05-7.44) PGE(2) 7.25 (6.91-7.41) (P = 0.050). Cervical ripening with the single balloon catheter was associated with significantly less pain (pain score > or =4: double balloon 55%, single balloon 36%, PGE(2) 63%, P < 0.001). Labour induction in nullipara with unfavourable cervices results in high caesarean delivery rates. Although all methods in this study had similar efficacy, the single balloon catheter offers the best combination of safety and patient comfort.
Publisher: KARGER
Date: 2009
DOI: 10.1159/000221166
Publisher: Microbiology Society
Date: 12-1991
Publisher: Oxford University Press (OUP)
Date: 27-07-2012
DOI: 10.1093/HMG/DDS304
Publisher: Elsevier BV
Date: 04-1997
Publisher: Springer Science and Business Media LLC
Date: 15-04-2012
DOI: 10.1038/NG.2245
Publisher: Springer Science and Business Media LLC
Date: 21-01-2019
DOI: 10.1038/S41467-018-07863-X
Abstract: Cranial growth and development is a complex process which affects the closely related traits of head circumference (HC) and intracranial volume (ICV). The underlying genetic influences shaping these traits during the transition from childhood to adulthood are little understood, but might include both age-specific genetic factors and low-frequency genetic variation. Here, we model the developmental genetic architecture of HC, showing this is genetically stable and correlated with genetic determinants of ICV. Investigating up to 46,000 children and adults of European descent, we identify association with final HC and/or final ICV + HC at 9 novel common and low-frequency loci, illustrating that genetic variation from a wide allele frequency spectrum contributes to cranial growth. The largest effects are reported for low-frequency variants within TP53 , with 0.5 cm wider heads in increaser-allele carriers versus non-carriers during mid-childhood, suggesting a previously unrecognized role of TP53 transcripts in human cranial development.
Publisher: Wiley
Date: 06-2012
Publisher: Springer Science and Business Media LLC
Date: 08-04-2012
DOI: 10.1038/NG.2247
Publisher: Springer Science and Business Media LLC
Date: 16-07-2018
Publisher: Elsevier BV
Date: 12-1994
Publisher: S. Karger AG
Date: 2014
DOI: 10.1159/000365031
Abstract: b i Introduction: /i /b Systematic reviews suggest that a longer duration of breast-feeding is associated with a reduction in the risk of later overweight and obesity. Most studies examining breast-feeding in relation to adiposity have not used longitudinal analysis. In our study, we aimed to examine early infant feeding and adiposity risk in a longitudinal cohort from birth to young adulthood using new as well as published data. b i Methods: /i /b Data from the Western Australian Pregnancy Cohort (Raine) Study in Perth, W.A., Australia, were used to examine associations between breast-feeding and measures of adiposity at 1, 2, 3, 6, 8, 10, 14, 17, and 20 years. b i Results: /i /b Breast-feeding was measured in a number of ways. Longer breast-feeding (in months) was associated with reductions in weight z-scores between birth and 1 year (β = -0.027 p 0.001) in the adjusted analysis. At 3 years, breast-feeding for months increased the odds of infants experiencing early rapid growth (OR 2.05 95% CI 1.43-2.94 p 0.001). From 1 to 8 years, children breast-fed for ≤4 months compared to ≥12 months had a significantly greater probability of exceeding the 95th percentile of weight. The age at which breast-feeding was stopped and a milk other than breast milk was introduced (introduction of formula milk) played a significant role in the trajectory of the BMI from birth to 14 years the 4-month cutoff point was consistently associated with a higher BMI trajectory. Introduction of a milk other than breast milk before 6 months compared to at 6 months or later was a risk factor for being overweight or obese at 20 years of age (OR 1.47 95% CI 1.12-1.93 p = 0.005). b i Discussion: /i /b Breast-feeding until 6 months of age and beyond should be encouraged and is recommended for protection against increased adiposity in childhood, adolescence, and young adulthood. Adverse long-term effects of early growth acceleration are fundamental in later overweight and obesity. Formula feeding stimulates a higher postnatal growth velocity, whereas breast-feeding promotes slower growth and a reduced likelihood of overweight and obesity. Biological mechanisms underlying the protective effect of breast-feeding against obesity are based on the unique composition and metabolic and physiological responses to human milk.
Publisher: Springer Science and Business Media LLC
Date: 12-1975
DOI: 10.1007/BF00331451
Publisher: Oxford University Press (OUP)
Date: 04-2015
DOI: 10.1093/IJE/DYV077
Publisher: Springer Science and Business Media LLC
Date: 23-07-2014
DOI: 10.1038/NATURE13545
Publisher: Springer Science and Business Media LLC
Date: 29-06-2017
Publisher: Elsevier BV
Date: 11-2011
Publisher: Cambridge University Press (CUP)
Date: 08-04-2013
DOI: 10.1017/THG.2013.13
Abstract: Twin–twin transfusion syndrome (TTTS) is an antenatal complication of monochorionic multiple gestations. There have been few studies exploring the role of laser photocoagulation or outcomes following treatment in monochorionic triplet pregnancies with TTTS. We present a case where TTTS and twin anemia–polycythemia sequence (TAPS) complicated a monochorionic triplet pregnancy. Following the laser photocoagulation to treat the TTTS between the triplets, an intra-uterine death occurred in one triplet and TAPS developed in the remaining two triplets. Intervention in this case resulted in a 2-week prolongation of pregnancy and a positive outcome for the remaining fetuses. This case and other published data reviewed in this article suggest that laser photocoagulation has a potential role for TTTS in monochorionic triplet pregnancies.
Publisher: Oxford University Press (OUP)
Date: 30-01-2015
DOI: 10.1093/HMG/DDV027
Abstract: Primary open-angle glaucoma (POAG) is a blinding disease. Two important risk factors for this disease are a positive family history and elevated intraocular pressure (IOP), which is also highly heritable. Genes found to date associated with IOP and POAG are ABCA1, CAV1/CAV2, GAS7 and TMCO1. However, these genes explain only a small part of the heritability of IOP and POAG. We performed a genome-wide association study of IOP in the population-based Rotterdam Study I and Rotterdam Study II using single nucleotide polymorphisms (SNPs) imputed to 1000 Genomes. In this discovery cohort (n = 8105), we identified a new locus associated with IOP. The most significantly associated SNP was rs58073046 (β = 0.44, P-value = 1.87 × 10(-8), minor allele frequency = 0.12), within the gene ARHGEF12. Independent replication in five population-based studies (n = 7471) resulted in an effect size in the same direction that was significantly associated (β = 0.16, P-value = 0.04). The SNP was also significantly associated with POAG in two independent case-control studies [n = 1225 cases and n = 4117 controls odds ratio (OR) = 1.53, P-value = 1.99 × 10(-8)], especially with high-tension glaucoma (OR = 1.66, P-value = 2.81 × 10(-9) for normal-tension glaucoma OR = 1.29, P-value = 4.23 × 10(-2)). ARHGEF12 plays an important role in the RhoA/RhoA kinase pathway, which has been implicated in IOP regulation. Furthermore, it binds to ABCA1 and links the ABCA1, CAV1/CAV2 and GAS7 pathway to Mendelian POAG genes (MYOC, OPTN, WDR36). In conclusion, this study identified a novel association between IOP and ARHGEF12.
Publisher: Proceedings of the National Academy of Sciences
Date: 03-09-1996
Abstract: Mucoid strains of Pseudomonas aeruginosa isolated from the lungs of cystic fibrosis patients produce large amounts of the exopolysaccharide alginate. AlgR has long been considered a key regulator of alginate production, but its cognate sensor has not been identified. Here we show that AlgR is required for twitching motility, which is a form of bacterial surface translocation mediated by type 4 fimbriae. Adjacent to algR we have identified a sensor gene (fimS), which is also required for twitching motility. However, FimS does not appear to be required for alginate production in mucoid strains. FimS and AlgR are representative of a new subclass of two-component transmitter-receiver regulatory systems. The alternative sigma factor AlgU also affects both alginate production and twitching motility. Therefore, these two virulence determinants appear to be closely associated and coordinately regulated.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2201
Publisher: Springer Science and Business Media LLC
Date: 02-2017
DOI: 10.1038/NATURE21039
Publisher: Springer Science and Business Media LLC
Date: 02-12-2012
DOI: 10.1038/NG.2477
Publisher: Cold Spring Harbor Laboratory
Date: 20-10-2023
Publisher: Wiley
Date: 22-06-2014
DOI: 10.1111/JPC.12672
Abstract: (i) To compare the Centers for Disease Control and Prevention (CDC) reference and World Health Organization (WHO) standard/reference for height, particularly with respect to short stature and eligibility for growth hormone (GH) treatment by applying them to contemporary Australian children (ii) To examine the implications for identifying short stature and eligibility for GH treatment. Children from the longitudinal Raine Study were serially measured for height from 1991 to 2005 (2-15-year-old girls (660) and boys (702) from Western Australia). In the cross-sectional Australian National Children's Nutrition and Physical Activity survey (2-16-year-old boys (2415) and girls (2379) from all states), height was measured in 2007. Heights were converted to standard deviation scores (SDSs) based on CDC and WHO. Means and standard deviations of height-SDS varied between CDC and WHO definitions and with age and gender within each definition. However, both identified similar frequencies of short stature (<1st centile for GH eligibility), although these were very significantly less than the anticipated 1% (0.1-0.7%) of the Australian cohorts. Mean heights in the Australian cohorts were greater than both the WHO and CDC means. Neither CDC nor WHO height standardisations accurately reflect the contemporary Australian child population. Australian children are taller than the CDC or WHO height means, and significantly less than 1% of Australian children are defined as being short using either CDC or WHO. This study suggests there may be a case for an Australian-specific standard/reference for height.
Publisher: Microbiology Society
Date: 10-1999
Publisher: Informa UK Limited
Date: 14-07-2016
DOI: 10.3109/14767058.2015.1070139
Abstract: To develop customized biometric charts to better define abnormal fetal growth. A total of 1056 singleton fetuses from the Raine Study underwent serial ultrasound biometry (abdominal circumference [AC], head circumference, and femur length) at 18, 24, 28, 34, and 38 weeks' gestation. Customized biometry trajectories were developed adjusting for epidemiological influences upon fetal biometry using covariates available at 18 weeks gestation. Prediction accuracy (areas under the receiver operating characteristic curve [AUC] and 95% confidence interval [95%CI]) was evaluated by repeated random sub-s ling cross-validation methodology. The model for derived estimated fetal weight (EFW) performed well for EFW less than 10th predicted percentile (AUC = 0.695, 95%CI, 0.692-0.699) and EFW greater than 90th predicted percentile (AUC = 0.705, 95%CI, 0.702-0.708). Fetal AC was also well predicted for growth restriction (AUC = 0.789, 95%CI, 0.784-0.794) and macrosomia (AUC = 0.796, 95%CI, 0.793-0.799). Population-derived, sex-specific charts misclassified 7.9% of small fetuses and 10.7% of large fetuses as normal. Conversely, 9.2% of those classified as abnormally grown by population-derived charts were considered normal by customized charts, potentially leading to complications of unnecessary intervention. Customized fetal biometric charts may offer improved ability for clinicians to detect deviations from optimal fetal growth and influence pregnancy management.
Publisher: Wiley
Date: 10-05-2010
Publisher: Springer Science and Business Media LLC
Date: 1983
DOI: 10.1007/BF00927420
Publisher: Wiley
Date: 08-1981
Publisher: Springer Science and Business Media LLC
Date: 09-07-2018
Publisher: Public Library of Science (PLoS)
Date: 17-01-2013
Publisher: Proceedings of the National Academy of Sciences
Date: 05-1983
Abstract: Cloned DNA copies of the double-stranded RNA genomic segments of simian 11 rotavirus have been used to determine the coding assignment for VP7, the type-specific antigen of this virus. Translation of hybrid-selected mRNAs in an in vitro system supplemented with canine pancreatic microsomes permitted VP7 to be assigned to segment 9 and the two nonstructural viral proteins NCVP4 and NCVP3, to segments 7 and 8, respectively. Hybridization of cloned DNA probes for segments 7-9 with the corresponding segments of human rotavirus Wa confirmed these assignments. The complete nucleotide sequence of gene 9 has been determined. The deduced amino acid sequence reveals VP7 to be 326 amino acids in length with two NH2-terminal hydrophobic regions and a single glycosylation site at residues 69-71.
Publisher: American Diabetes Association
Date: 21-05-2011
DOI: 10.2337/DB10-1575
Abstract: To investigate whether associations of common genetic variants recently identified for fasting glucose or insulin levels in nondiabetic adults are detectable in healthy children and adolescents. A total of 16 single nucleotide polymorphisms (SNPs) associated with fasting glucose were genotyped in six studies of children and adolescents of European origin, including over 6,000 boys and girls aged 9–16 years. We performed meta-analyses to test associations of in idual SNPs and a weighted risk score of the 16 loci with fasting glucose. Nine loci were associated with glucose levels in healthy children and adolescents, with four of these associations reported in previous studies and five reported here for the first time (GLIS3, PROX1, SLC2A2, ADCY5, and CRY2). Effect sizes were similar to those in adults, suggesting age-independent effects of these fasting glucose loci. Children and adolescents carrying glucose-raising alleles of G6PC2, MTNR1B, GCK, and GLIS3 also showed reduced β-cell function, as indicated by homeostasis model assessment of β-cell function. Analysis using a weighted risk score showed an increase [β (95% CI)] in fasting glucose level of 0.026 mmol/L (0.021–0.031) for each unit increase in the score. Novel fasting glucose loci identified in genome-wide association studies of adults are associated with altered fasting glucose levels in healthy children and adolescents with effect sizes comparable to adults. In nondiabetic adults, fasting glucose changes little over time, and our results suggest that age-independent effects of fasting glucose loci contribute to long-term interin idual differences in glucose levels from childhood onwards.
Publisher: Microbiology Society
Date: 05-2003
Abstract: The las and rhl quorum sensing (QS) systems regulate the expression of several genes in response to cell density changes in Pseudomonas aeruginosa . Many of these genes encode surface-associated or secreted virulence factors. Proteins from stationary phase culture supernatants were collected from wild-type and P. aeruginosa PAO1 mutants deficient in one or more of the lasRI , rhlRI and vfr genes and analysed using two-dimensional gel electrophoresis. All mutants released significantly lower amounts of protein than the wild-type. Protein spot patterns from each strain were compared using image analysis and visible spot differences were identified using mass spectrometry. Several previously unknown QS-regulated proteins were characterized, including an aminopeptidase (PA2939), an endoproteinase (PrpL) and a unique ‘hypothetical’ protein (PA0572), which could not be detected in the culture supernatants of Δ las mutants, although they were unaffected in Δ rhl mutants. Chitin-binding protein (CbpD) and a hypothetical protein (PA4944) with similarity to host factor I (HF-I) could not be detected when any of the lasRI or rhlRI genes were disrupted. Fourteen proteins were present at significantly greater levels in the culture supernatants of QS mutants, suggesting that QS may also negatively control the expression of some genes. Increased levels of two-partner secretion exoproteins (PA0041 and PA4625) were observed and may be linked to increased stability of their cognate transporters in a QS-defective background. Known QS-regulated extracellular proteins, including elastase ( lasB ), LasA protease ( lasA ) and alkaline metalloproteinase ( aprA ) were also detected.
Publisher: Elsevier BV
Date: 08-2008
Publisher: Cambridge University Press (CUP)
Date: 26-10-2011
Publisher: Wiley
Date: 13-03-2012
DOI: 10.1002/J.1532-2149.2012.00131.X
Abstract: There is significant evidence to suggest that psychological and stress-related factors are important predictors of the onset of chronic widespread pain (CWP) and fibromyalgia (FM). The hypothalamic-pituitary-adrenal axis, together with the efferent sympathetic/adrenomedullary system, influence all body organs (including muscles) during short- and long-term threatening stimuli. The aim of this study was to investigate the relationship between genetic variants in adrenergic candidate genes and chronic musculoskeletal complaints (MSCs) in adolescents. Adolescents from the Western Australian Pregnancy (Raine) Cohort attending the 17-year cohort review completed a questionnaire containing a broad range of psychosocial factors and pain assessment (n = 1004). Blood s les were collected for DNA extraction and genotyping. Genotype data was obtained for 14 single nucleotide polymorphisms (SNPs) in two candidate genes - beta-2 adrenergic receptor (ADRB2) and catecholamine-O-methyltransferase (COMT). Haplotypes were reconstructed for all in iduals with genotype data. Both female gender and poor mental health were associated with (1) an increased risk for chronic, disabling comorbid neck and low back pain (CDCP) and (2) an increase in the number of areas of pain. Of the 14 SNPs evaluated, only SNP rs2053044 (ADRB2, recessive model) displayed an association with CDCP [odds ratio (OR) = 2.49 95% confidence interval (CI) = 1.25, 4.98 p = 0.01] and pain in three to four pain areas in the last month (OR = 1.86 95% CI = 1.13, 3.06 p = 0.02). These data suggest that genetic variants in ADRB2 may be involved in chronic MSCs.
Publisher: Springer Science and Business Media LLC
Date: 10-2004
Publisher: Springer Science and Business Media LLC
Date: 29-05-2013
DOI: 10.1038/NG0613-713C
Publisher: Elsevier BV
Date: 2018
Publisher: Oxford University Press (OUP)
Date: 18-10-2012
DOI: 10.1093/HMG/DDR478
Publisher: Springer Science and Business Media LLC
Date: 2007
Abstract: The association between suboptimal intrauterine environment and developmental origins of adult health and disease is variable, suggesting that genotype may contribute to eventual outcome. The objective of this study was to characterize maternal and fetal responses to maternal dietary restriction during pregnancy in 2 phylogenetically distant strains of mice. Pregnant A/J (n=35) and C57BL/6J (B6) (n=36) mice underwent either a 30% dietary restriction (DR) from day 6.5 until day 17.5 of gestation or were fed ad libitum. Seven mothers from each strain and diet were randomly selected for dissection on day 18.5 to assess fetal body and organ weights and maternal endocrine status through the collection of serum to measure progesterone, corticosterone, cortisol, and estradiol levels. The remaining mice were allowed to deliver spontaneously to assess gestational effects. Both strains showed similar responses to maternal DR during pregnancy in terms of reductions in maternal weight gain during pregnancy, reductions in fetal body weight, increased pup death within 24 hours of birth, and decreased placental 11beta-HSD2 protein expression. The impact of maternal DR was greater in B6 mice than A/J when assessing reductions in fetal kidney weight, embryo-placenta ratio, increases in placental weight, fetal brain-liver ratio, and maternal corticosterone and cortisol levels. Moreover, preterm delivery was significantly increased in DR B6 mice compared to DR A/J mice. The observed strain variations in response to dietary restriction may offer a unique opportunity to investigate gene-environment interactions associated with developmental origins of adult health and disease.
Publisher: Springer Science and Business Media LLC
Date: 29-05-2013
DOI: 10.1038/NG0613-713A
Publisher: Wiley
Date: 26-05-2016
DOI: 10.1111/CEN.13092
Abstract: Maternal total and free cortisol concentrations are reduced in pre-ecl sia (PE) and gestational hypertension (GH). However, the effect of this on the hypothalamic-pituitary-adrenal (HPA) axis function in the offspring is unknown. We examined the basal HPA axis activity in adolescent offspring of mothers with pre-pregnancy hypertension/GH/PE. A total of 1182 participants (mean age 17·1 years) recruited from the Western Australian Pregnancy Cohort (Raine) Study provided fasting morning blood s les for basal HPA axis and concomitant clinical assessments, including blood pressure. Plasma ACTH, total cortisol, corticosteroid-binding globulin (CBG) and free cortisol calculated by Coolens' equation were measured from the blood s les collected at home before 10:00 am. Total plasma cortisol (689 ± 153 nmol/l vs 583 ± 172 nmol/l, P = 0·024), ACTH (15·5 ± 13 pmol/l vs 10·8 ± 5·1 pmol/l, P = 0·040) and calculated free cortisol (52 ± 21 nmol/l vs 42 ± 22 nmol/l, P = 0·052) were higher in the PE offspring than in controls. The pre-pregnancy hypertension group had evidence of a lower ACTH lasma free cortisol ratio (0·22 vs 0·33 P = 0·020) and lower CBG (713 nmol/l vs 821 nmol/l, P = 0·004) compared with controls. Systolic blood pressure was elevated in the GH/PE group compared with controls (120 mmHg vs 116 mmHg, P = 0·006). Hypothalamic-pituitary-adrenal axis activity is increased in the adolescent offspring of mothers with pre-ecl sia. This may be an adaptation resulting from the reduced maternal cortisol during foetal life. The resulting mild hypercortisolism may have implications for long-term health outcomes and warrants further investigation.
Publisher: Springer Science and Business Media LLC
Date: 04-2000
DOI: 10.1038/74153
Publisher: Springer Science and Business Media LLC
Date: 08-1990
DOI: 10.1038/346604C0
Publisher: Cambridge University Press (CUP)
Date: 31-01-2012
Publisher: Wiley
Date: 20-11-2018
DOI: 10.1111/AJI.12784
Abstract: Advances in reproductive medicine have significantly increased the success of fertility treatments. Nevertheless, some women experience recurrent implantation failure (RIF) after in-vitro fertilization (IVF) or recurrent pregnancy loss (RPL). Imbalances in the immune system and failure to achieve immune tolerance to the foetus have been implicated as potentially modifiable causes of idiopathic RIF and RPL. As such, women are increasingly being treated with immunomodulatory agents in an attempt to achieve a successful pregnancy. This systematic review examines the published evidence on immune changes in these patients, the use of immunomodulation therapies and diagnostic testing modalities to guide their use or to identify patient subsets most likely to benefit. The PubMed database was searched for the terms "recurrent implantation failure" and "recurrent pregnancy loss" in conjunction with T-helper (Th) cells and their subsets in particular Th1, Th2, Th17 and T-regulatory (Treg) cells, natural killer (NK) cells, cytokine imbalance as well as immune modulators and immune suppressants. The reference lists of articles were examined to identify additional articles. There remains limited data on the immunological changes in cytokine and cellular profiles during the hormonal cycle as well as prior to, during and after implantation in health as well as idiopathic RIF and RPL. There is a need to advance immunological diagnostics to match the clinical need in this emerging field and to guide clinicians to make optimal and safe therapeutic choices. It is also imperative that the well-being of the infants conceived after such intervention is monitored.
Publisher: Springer Science and Business Media LLC
Date: 18-09-2013
Abstract: Social communication difficulties represent an autistic trait that is highly heritable and persistent during the course of development. However, little is known about the underlying genetic architecture of this phenotype. We performed a genome-wide association study on parent-reported social communication problems using items of the children’s communication checklist (age 10 to 11 years) studying single and/or joint marker effects. Analyses were conducted in a large UK population-based birth cohort (Avon Longitudinal Study of Parents and their Children, ALSPAC, N = 5,584) and followed-up within a s le of children with comparable measures from Western Australia (RAINE, N = 1364). Two of our seven independent top signals ( P- discovery .0E-05) were replicated (0.009 P- replication ≤0.02) within RAINE and suggested evidence for association at 6p22.1 (rs9257616, meta- P = 2.5E-07) and 14q22.1 (rs2352908, meta- P = 1.1E-06). The signal at 6p22.1 was identified within the olfactory receptor gene cluster within the broader major histocompatibility complex (MHC) region. The strongest candidate locus within this genomic area was TRIM27 . This gene encodes an ubiquitin E3 ligase, which is an interaction partner of methyl-CpG-binding domain (MBD) proteins, such as MBD3 and MBD4, and rare protein-coding mutations within MBD3 and MBD4 have been linked to autism. The signal at 14q22.1 was found within a gene-poor region. Single-variant findings were complemented by estimations of the narrow-sense heritability in ALSPAC suggesting that approximately a fifth of the phenotypic variance in social communication traits is accounted for by joint additive effects of genotyped single nucleotide polymorphisms throughout the genome (h 2 (SE) = 0.18(0.066), P = 0.0027). Overall, our study provides both joint and single-SNP-based evidence for the contribution of common polymorphisms to variation in social communication phenotypes.
Publisher: Wiley
Date: 28-06-2010
Publisher: No publisher found
Date: 2012
Publisher: Wiley
Date: 07-12-2001
DOI: 10.1002/JCB.1277
Publisher: Wiley
Date: 03-2011
Publisher: Oxford University Press (OUP)
Date: 17-12-2004
DOI: 10.1093/NAR/GKI089
Publisher: Elsevier BV
Date: 12-2001
Publisher: Springer Science and Business Media LLC
Date: 04-08-2015
DOI: 10.1038/NCOMMS8756
Abstract: More than 100 loci have been identified for age at menarche by genome-wide association studies however, collectively these explain only ∼3% of the trait variance. Here we test two overlooked sources of variation in 192,974 European ancestry women: low-frequency protein-coding variants and X-chromosome variants. Five missense/nonsense variants (in ALMS1 / LAMB2 / TNRC6A/TACR3/PRKAG1 ) are associated with age at menarche (minor allele frequencies 0.08–4.6% effect sizes 0.08–1.25 years per allele P × 10 −8 ). In addition, we identify common X-chromosome loci at IGSF1 (rs762080, P =9.4 × 10 −13 ) and FAAH2 (rs5914101, P =4.9 × 10 −10 ). Highlighted genes implicate cellular energy homeostasis, post-transcriptional gene silencing and fatty-acid amide signalling. A frequently reported mutation in TACR3 for idiopathic hypogonatrophic hypogonadism (p.W275X) is associated with 1.25-year-later menarche ( P =2.8 × 10 −11 ), illustrating the utility of population studies to estimate the penetrance of reportedly pathogenic mutations. Collectively, these novel variants explain ∼0.5% variance, indicating that these overlooked sources of variation do not substantially explain the ‘missing heritability’ of this complex trait.
Publisher: Wiley
Date: 08-2014
DOI: 10.1002/UOG.13399
Abstract: Through comprehensive ophthalmic examination of adult offspring we sought to determine the impact of multiple prenatal ultrasound scans on ocular development. 2743 pregnant women recruited to the Western Australian Pregnancy (Raine) Cohort study during 1989-1991 were randomized to receive at King Edward Memorial Hospital, Western Australia either multiple prenatal ultrasound scans and Doppler flow studies (intensive group) or a single ultrasound scan at 18 weeks' gestation. Neonatal birth weight of the offspring and other physical measurements were collected prospectively. At age 20 years, participants underwent a comprehensive ophthalmic examination including measurement of ocular biometry and visual acuity. Complete data were available for 1134 adult offspring participants. The mothers of 563 of these had been randomized to receive multiple prenatal ultrasound scans. The mean age of participants at follow-up was 20.0 years. There was no statistically significant difference between the two groups with regard to ocular biometric or visual outcomes, except for slightly higher intraocular pressure identified in in iduals exposed to multiple ultrasound scans (P = 0.034). Although infants in the intensive-ultrasound arm were more likely to have birth weights in the lower quartiles, this was not reflected in adult eye development. Axial length, lens thickness, corneal curvature and thickness and optic cup to disc ratio (a risk factor for glaucomatous optic neuropathy) were not significantly influenced by the more frequent ultrasound protocol. Prior to this study, there was a paucity of safety data for ultrasound with regard to eye development. We found that frequent in-utero exposure to ultrasound, including B-mode imaging and the use of spectral Doppler mode from 18 weeks' gestation, had no significant impact on visual outcomes or ocular biometry.
Publisher: Elsevier BV
Date: 03-2000
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2012
Publisher: Public Library of Science (PLoS)
Date: 10-07-2014
Publisher: American Society for Microbiology
Date: 05-1986
DOI: 10.1128/JB.166.2.453-460.1986
Abstract: The fimbriae of Bacteroides nodosus play a major role in protective immunity against ovine footrot and are an important determinant in the serological classification system that ides field isolates into at least eight serogroups and 16 serotypes. Purified fimbriae contain two polypeptide antigens, the structural subunit of the fimbrial strand (molecular weight about 17,000) and a basal protein (molecular weight about 80,000), both of which exhibit structural variation. Fimbriae were prepared from all prototype strains, as well as from a number of other isolates representative of each of the B. nodosus serotypes, and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Substantial variation was observed in the electrophoretic mobility of the fimbrial subunits from the prototypes of each of the eight serogroups. With the exception of serogroup H, which is an unusual case, the apparent molecular weights of the fimbrial subunits ranged from about 16,500 in serogroup D to 19,000 in serogroup F (serotype 1) in serogroup A, B, C and E, the apparent molecular weights were clustered in the range of 17,000 to 17,500, whereas serogroup G was about 18,500. Serogroup H fimbriae appeared to consist of two smaller polypeptides, which in the prototype (H1) had apparent molecular weights of about 6,000 and 10,000 and which seem to have arisen as a consequence of an internal proteolytic nick in the original subunit. Electrophoretic variation in the fimbrial subunit was also observed between different serotypes, although with the exceptions of serogroups F and H, this was not as pronounced as between the serogroups. Examination of a number of isolates classified within the same serotypes showed that some variation, although minor, also occurred at this level. The basal antigen exhibited significant variation at all levels of the serotypic hierarchy in a manner apparently unrelated to the classification system. Among the range of isolates examined, the apparent molecular weight of this antigen varied from about 77,000 to 88,000.
Publisher: Springer Science and Business Media LLC
Date: 2002
Publisher: Elsevier BV
Date: 12-2001
Publisher: Cold Spring Harbor Laboratory
Date: 04-11-2021
DOI: 10.1101/2021.11.04.466897
Abstract: The use of spoken and written language is a capacity that is unique to humans. In idual differences in reading- and language-related skills are influenced by genetic variation, with twin-based heritability estimates of 30-80%, depending on the trait. The relevant genetic architecture is complex, heterogeneous, and multifactorial, and yet to be investigated with well-powered studies. Here, we present a multicohort genome-wide association study (GWAS) of five traits assessed in idually using psychometric measures: word reading, nonword reading, spelling, phoneme awareness, and nonword repetition, with total s le sizes ranging from 13,633 to 33,959 participants aged 5-26 years (12,411 to 27,180 for those with European ancestry, defined by principal component analyses). We identified a genome-wide significant association with word reading (rs11208009, p=1.098 × 10 −8 ) independent of known loci associated with intelligence or educational attainment. All five reading-/language-related traits had robust SNP-heritability estimates (0.13–0.26), and genetic correlations between them were modest to high. Using genomic structural equation modelling, we found evidence for a shared genetic factor explaining the majority of variation in word and nonword reading, spelling, and phoneme awareness, which only partially overlapped with genetic variation contributing to nonword repetition, intelligence and educational attainment. A multivariate GWAS was performed to jointly analyse word and nonword reading, spelling, and phoneme awareness, maximizing power for follow-up investigation. Genetic correlation analysis of multivariate GWAS results with neuroimaging traits identified association with cortical surface area of the banks of the left superior temporal sulcus, a brain region with known links to processing of spoken and written language. Analysis of evolutionary annotations on the lineage that led to modern humans showed enriched heritability in regions depleted of Neanderthal variants. Together, these results provide new avenues for deciphering the biological underpinnings of these uniquely human traits.
Publisher: Elsevier BV
Date: 08-2013
DOI: 10.1016/J.PSYNEUEN.2012.11.010
Abstract: Dysfunctional regulation of the hypothalamic-pituitary-adrenal (HPA) axis has been proposed as an important biological mechanism underlying stress-related diseases however, a better understanding of the interlinked neuroendocrine events driving the release of cortisol by this stress axis is essential for progress in preventing or halting irreversible development of adverse HPA-function. We aimed to investigate basal HPA-activity in a normal population in late adolescence, the time of life believed to overlap with HPA-axis maturation and establishment of a lasting set point level of HPA function. A total of 1258 participants (mean age 16.6 years) recruited from the Western Australian Pregnancy (Raine) Cohort provided fasting morning blood and saliva s les for basal HPA activity assessment. Irrespective of gender, linear regression modelling identified a positive correlation between the main components of the HPA-cascade of events, ACTH, total cortisol and free cortisol in saliva. Corticosteroid binding globulin (CBG) was inversely associated with free cortisol in saliva, an effect most clearly observed in boys. ACTH levels were lower, but cortisol levels were higher in girls than in boys. Girls may also be exposed to more bioactive cortisol, based on higher average free cortisol measured in saliva at awakening. These relatively higher female free cortisol levels were significantly reduced by oral contraceptive use, eliminating the gender specific difference in salivary cortisol. Free plasma cortisol, calculated from total circulating cortisol and CBG concentrations, was also significantly reduced in girls using oral contraceptives, possibly via an enhancing effect of oral contraceptives on blood CBG content. This study highlights a clear gender difference in HPA activity under non-stressful natural conditions. This finding may be relevant for research into sex-specific stress-related diseases with a typical onset in late adolescence.
Publisher: Elsevier BV
Date: 07-2019
Publisher: American Medical Association (AMA)
Date: 04-2015
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2021
DOI: 10.1161/CIRCGEN.120.003288
Abstract: ChREBP (carbohydrate responsive element binding protein) is a transcription factor that responds to sugar consumption. Sugar-sweetened beverage (SSB) consumption and genetic variants in the CHREBP locus have separately been linked to HDL-C (high-density lipoprotein cholesterol) and triglyceride concentrations. We hypothesized that SSB consumption would modify the association between genetic variants in the CHREBP locus and dyslipidemia. Data from 11 cohorts from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium (N=63 599) and the UK Biobank (N=59 220) were used to quantify associations of SSB consumption, genetic variants, and their interaction on HDL-C and triglyceride concentrations using linear regression models. A total of 1606 single nucleotide polymorphisms within or near CHREBP were considered. SSB consumption was estimated from validated questionnaires, and participants were grouped by their estimated intake. In a meta-analysis, rs71556729 was significantly associated with higher HDL-C concentrations only among the highest SSB consumers (β, 2.12 [95% CI, 1.16–3.07] mg/dL per allele P .0001), but not significantly among the lowest SSB consumers ( P =0.81 P Diff .0001). Similar results were observed for 2 additional variants (rs35709627 and rs71556736). For triglyceride, rs55673514 was positively associated with triglyceride concentrations only among the highest SSB consumers (β, 0.06 [95% CI, 0.02–0.09] ln-mg/dL per allele, P =0.001) but not the lowest SSB consumers ( P =0.84 P Diff =0.0005). Our results identified genetic variants in the CHREBP locus that may protect against SSB-associated reductions in HDL-C and other variants that may exacerbate SSB-associated increases in triglyceride concentrations. URL: www.clinicaltrials.gov Unique identifier: NCT00005133, NCT00005121, NCT00005487, and NCT00000479.
Publisher: Springer Science and Business Media LLC
Date: 06-02-2017
DOI: 10.1038/NG.3787
Publisher: Elsevier BV
Date: 09-1987
Publisher: American Physical Society (APS)
Date: 20-07-2005
Publisher: Wiley
Date: 04-02-2005
Publisher: Springer Science and Business Media LLC
Date: 05-10-2023
Publisher: American Society for Microbiology
Date: 07-2002
DOI: 10.1128/JB.184.13.3598-3604.2002
Abstract: It has been reported that mutations in the quorum-sensing genes lasI and rhlI in Pseudomonas aeruginosa result in, among many other things, loss of twitching motility (A. Glessner, R. S. Smith, B. H. Iglewski, and J. B. Robinson, J. Bacteriol. 181:1623-1629, 1999). We constructed knockouts of lasI and rhlI and the corresponding regulatory genes lasR and rhlR and found no effect on twitching motility. However, twitching-defective variants accumulated during culturing of lasI and rhlI mutants. Further analysis showed that the stable twitching-defective variants of lasI and rhlI mutants had arisen as a consequence of secondary mutations in vfr and algR , respectively, both of which encode key regulators affecting a variety of phenotypes, including twitching motility. In addition, when grown in shaking broth culture, lasI and rhlI mutants, but not the wild-type parent, also accumulated unstable variants that lacked both twitching motility and swimming motility and appeared to be identical in phenotype to the S1 and S2 variants that were recently reported to occur at high frequencies in P. aeruginosa strains grown as a biofilm or in static broth culture (E. Deziel, Y. Comeau, and R. Villemur, J. Bacteriol. 183:1195-1204, 2001). These results indicate that mutations in one regulatory system may create distortions that select during subsequent culturing for compensatory mutations in other regulatory genes within the cellular network. This problem may have compromised some past studies of regulatory hierarchies controlled by quorum sensing and of bacterial regulatory systems in general.
Publisher: EMBO
Date: 09-2000
Publisher: Public Library of Science (PLoS)
Date: 17-03-2020
Publisher: Cold Spring Harbor Laboratory
Date: 17-05-2005
DOI: 10.1101/GR.3545105
Abstract: Recently, we identified a large number of ultraconserved (uc) sequences in noncoding regions of human, mouse, and rat genomes that appear to be essential for vertebrate and amniote ontogeny. Here, we used similar methods to identify ultraconserved genomic regions between the insect species Drosophila melanogaster and Drosophila pseudoobscura , as well as the more distantly related Anopheles gambiae. As with vertebrates, ultraconserved sequences in insects appear to occur primarily in intergenic and intronic sequences, and at intron-exon junctions. The sequences are significantly associated with genes encoding developmental regulators and transcription factors, but are less frequent and are smaller in size than in vertebrates. The longest identical, nongapped orthologous match between the three genomes was found within the homothorax ( hth ) gene. This sequence spans an internal exon-intron junction, with the majority located within the intron, and is predicted to form a highly stable stem-loop RNA structure. Real-time quantitative PCR analysis of different hth splice isoforms and Northern blotting showed that the conserved element is associated with a high incidence of intron retention in hth pre-mRNA, suggesting that the conserved intronic element is critically important in the post-transcriptional regulation of hth expression in Diptera .
Publisher: Oxford University Press (OUP)
Date: 09-2001
Publisher: Springer Science and Business Media LLC
Date: 31-10-2019
DOI: 10.1038/S41467-019-12283-6
Abstract: In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients ( F ROH ) for .4 million in iduals, we show that F ROH is significantly associated ( p 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: F ROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44–66%] in the odds of having children. Finally, the effects of F ROH are confirmed within full-sibling pairs, where the variation in F ROH is independent of all environmental confounding.
Publisher: Hogrefe Publishing Group
Date: 30-06-2015
DOI: 10.1027/1016-9040/A000212
Abstract: Despite huge advances in obstetric management and technology in recent decades, there has not been an accompanying decrease in patients’ perception of risk during pregnancy. The aim of this paper is to examine the context of risk perception in pregnancy and what practitioners can do to manage it. The modern pregnancy may induce a heightened perception of risk due to increased prenatal testing and surveillance, medico-legal complexity, fertility treatment, and the increasing use of the internet and social media as a source of information. The consequences of an inflated perception of risk during pregnancy include stress, anxiety, and depression, and these issues may have long-lasting implications for patients, their babies, and their families. There are numerous resilience and vulnerability factors that can help care providers identify those who may be predisposed to increased risk perception in pregnancy, and there is a role for both obstetric care providers and psychologists engaged in obstetric settings to manage and reduce risk perception in patients where possible. Ultimately, the medical management of risk during pregnancy can be complex but a thorough understanding of the social and emotional context can assist providers to support their patients through both high- and low-risk pregnancy and birth.
Publisher: Elsevier BV
Date: 08-2010
DOI: 10.1016/J.EARLHUMDEV.2010.06.009
Abstract: There is accumulating evidence for a link between maternal stress during pregnancy and later behavioural and emotional problems in children. Little research has examined other developmental outcomes. To determine the effect of maternal stress during pregnancy on offspring language ability in middle childhood. Longitudinal pregnancy cohort-study. A total of 2900 mothers were recruited prior to the 18th week of pregnancy, delivering 2868 live births. The language ability of just under half of the offspring cohort (n=1309 45.6% of original s le) was assessed in middle childhood (Mean age=10 , Standard deviation=0 , range: 9 -11 ). Language ability was measured using the Peabody Picture Vocabulary Test-Revised (PPVT-R). The main predictor variable was the frequency of 10 typically 'stressful' life events experienced by mothers during early and/or late pregnancy. Children were allocated to four groups according to whether they were exposed to high maternal stress (>or=2 life events) during early pregnancy only, late pregnancy only, both, or neither. Mixed-effects regression analyses revealed no association between the maternal experience of two or more stressful life events at any time-point during pregnancy and PPVT-R scores. Repeating the regression analyses with more lenient (>or=1 life events) or strict (>or=3 life events) thresholds for defining high-levels of maternal stress did not alter the pattern of findings. Maternal experience of typically stressful life events during pregnancy has a negligible effect on vocabulary development to middle childhood.
Publisher: Wiley
Date: 11-10-2010
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2009
Publisher: Springer Science and Business Media LLC
Date: 24-11-2016
DOI: 10.1038/IJO.2016.214
Abstract: An association between depression and obesity is well recognised, but longitudinal studies of depressive symptoms in adolescents as a predictor of body composition are lacking. We examined depressive symptoms at age 14, 17 and 20 years as predictors of lean, fat and bone mass at age 20 years in a birth cohort. In 1161 participants (569 females) in the Western Australia Pregnancy Cohort (Raine) Study, depressive symptoms were assessed using the Beck Depression Inventory for Youth at age 14 and 17 years, and the Depression, Anxiety and Stress Scale 21 at age 20 years. Participants were further classified into two trajectories using latent class analysis: no/transient and persistent/recurrent depression. At age 20 years, lean body mass (LBM), fat body mass (FBM) and total body bone mass were measured by dual-energy X-ray absorptiometry. In females, accounting for age and lifestyle factors, depression scores at age 14 and 20 years were positively associated with body weight, body mass index (BMI), FBM and % FBM (r=0.110-0.184, P<0.05) but negatively correlated with % LBM (r=-0.120, P<0.05) at age 20 years. Females in the persistent/recurrent depression trajectory (n=99) had significantly higher body weight (+5.1 kg), BMI (+1.8 kg m Depressive symptoms and persistent/recurrent depression in adolescence are predictors of greater adiposity at age 20 years in females, but not males, but do not predict bone mass in either gender.
Publisher: Informa UK Limited
Date: 16-03-2012
DOI: 10.3109/14767058.2012.663824
Abstract: An observational study of a consecutive case series of pre-viable PPROM (16-24 gestational weeks) was performed between 2001 and 2007 in a single tertiary centre to identify factors that predict neonatal survival. Detailed obstetric, ultrasound and neonatal data were abstracted from clinical records. Univariate, multivariate and receiver operator curve (ROC) analyses were performed to identify predictors of neonatal survival to discharge. A total of 143 cases of PPROM were identified. Survival to discharge was less with PPROM at 16-20 weeks than 20-24 weeks (17% versus 39% p=0.042). GA at PPROM, latency, mode of delivery and electronic foetal monitoring (EFM) were all significant, independent, predictors of survival (p<0.05). Ultrasound assessed amniotic fluid index (AFI) was a poor predictor of survival (area under ROC=0.649, 95% CI=0.532-0.766). A multivariable predictive model, including GA at PPROM, latency, mode of delivery and EFM had an area under the ROC of 0.954 (95% CI=0.916-0.993, sensitivity 97%, specificity 89% and accuracy 92%). Pre-viable PPROM has a poor prognosis, though modern neonatal management techniques may improve survival in late pre-viable PPROM. The predictive model generated from this consecutive case series of this rare condition provides valuable data for counselling patients with this condition.
Publisher: Springer Science and Business Media LLC
Date: 15-04-2005
Publisher: American Association for the Advancement of Science (AAAS)
Date: 11-02-2005
Publisher: Brill
Date: 12-2004
Publisher: Bioscientifica
Date: 12-1992
Abstract: Residues within the first disulphide loop of the GH receptor are highly conserved, and the two cysteines forming this motif are conserved across many cytokine receptors. We have used site-directed mutagenesis and the polymerase chain reaction with splicing by overlap extension to show that these residues are essential for binding of bovine (b)GH and human (h)GH to the rabbit GH receptor. When all residues within this loop were replaced with an equivalent polyalanine sequence, hormone binding was abolished. Conversion of Arg 39 within the loop to aspartate (R39D) decreased affinity for bGH by up to 20-fold. Conversion of Glu 42 to lysine (E42K) also resulted in a fivefold loss of affinity for bGH. However, charge reversals at Lys 37, Glu 44 and the conversion of Leu 43 to an arginine (as in the human receptor) were without a major effect on bGH binding. The lack of effect of the L43R mutation on bGH affinity, despite a significant (threefold) decrease in hGH affinity, argues against a role for Arg 43 as a residue conferring primate GH-binding specificity on the human receptor. Examination of the affinities of poly Ala, R39D and E42K mutants for a variety of hormone-binding-site directed and other monoclonal antibodies (MAbs) to the GH receptor revealed that these mutations were without a major effect on tertiary structure. It is of interest that the epitopes for the hormone-binding inhibitory MAbs 263 and 7 are located within this first loop, since the poly Ala mutation abolished the binding of both MAbs, and the R39D mutation abolished binding of MAb 7. In conclusion, residues within the first disulphide loop of the GH receptor are critical for hormone binding, and are epitopes for the binding of inhibitory MAbs. These findings may be applicable to other cytokine receptors.
Publisher: Wiley
Date: 15-01-2004
DOI: 10.1002/JCC.10411
Abstract: A new method has been developed for prediction of transmembrane helices using support vector machines. Different coding schemes of protein sequences were explored, and their performances were assessed by crossvalidation tests. The best performance method can predict the transmembrane helices with sensitivity of 93.4% and precision of 92.0%. For each predicted transmembrane segment, a score is given to show the strength of transmembrane signal and the prediction reliability. In particular, this method can distinguish transmembrane proteins from soluble proteins with an accuracy of approximately 99%. This method can be used to complement current transmembrane helix prediction methods and can be used for consensus analysis of entire proteomes. The predictor is located at genet.imb.uq.edu.au redictors/SVMtm.
Publisher: Springer Science and Business Media LLC
Date: 11-08-2015
Publisher: Bioscientifica
Date: 04-2014
DOI: 10.1530/REP-13-0331
Abstract: We hypothesised that antenatal exposure to ubiquitous phthalates may lead to an earlier menarche and a lower prevalence of polycystic ovarian syndrome (PCOS) and polycystic ovarian morphology (PCO) in adolescence. The Western Australian Pregnancy Cohort (Raine) Study recruited 3000 women at 18 weeks of gestation in 1989–1991, 1377 had antenatal serum stored without thawing at −80 °C. An unselected subset was evaluated in the early follicular phase for PCO and PCOS by ultrasound and serum evaluation in adolescence. Serum was analysed for anti-Müllerian hormone (AMH), inhibin B, sex hormone binding globulin (SHBG), testosterone, androstenedione and DHEAS. Four hundred microlitres of the frozen maternal serum underwent isotope-diluted liquid chromatography–tandem mass spectrometry, with preceding enzymatic deconjugation followed by solid-phase extraction to determine phthalate exposure. Two hundred and forty four girls attended assessment and most common phthalate metabolites were detectable in the majority of the 123 s les available. Several phthalates were negatively associated with maternal SHBG, and associations with maternal androgens were less consistent. The sum of the metabolites of di-(2-ethylhexyl) phthalate was associated with a non-significant tendency towards an earlier age at menarche ( P =0.069). Uterine volume was positively associated with mono-(carboxy-iso-octyl) phthalate ( P =0.018). Exposure to monoethyl phthalate (MEP) and the sum of all phthalate metabolites (Σall phth.m) were protective against PCOS in adolescence ( P =0.001 and P =0.005 respectively). There were negative associations of MEP with PCO ( P =0.022) and of MEP with serum AMH ( P =0.031). Consequently, our data suggest that antenatal exposure to environmental phthalates may be associated with oestrogenic and/or anti-androgenic reproductive effects in adolescent girls.
Publisher: Springer Science and Business Media LLC
Date: 16-08-2018
DOI: 10.1038/S41588-018-0197-6
Abstract: In the version of this article initially published, in Fig. 3, the y-axis numbering did not match the log scale indicated in the axis label. The error has been corrected in the HTML and PDF version of the article.
Publisher: Wiley
Date: 1993
Publisher: Cambridge University Press (CUP)
Date: 21-04-2022
DOI: 10.1017/S2040174422000186
Abstract: Animal and human data demonstrate independent relationships between fetal growth, hypothalamic-pituitary-adrenal axis function (HPA-A) and adult cardiometabolic outcomes. While the association between fetal growth and adult cardiometabolic outcomes is well-established, the role of the HPA-A in these relationships is unclear. This study aims to determine whether HPA-A function mediates or moderates this relationship. Approximately 2900 pregnant women were recruited between 1989-1991 in the Raine Study. Detailed anthropometric data was collected at birth (per cent optimal birthweight [POBW]). The Trier Social Stress Test was administered to the offspring (Generation 2 Gen2) at 18 years HPA-A responses were determined (reactive responders [RR], anticipatory responders [AR] and non-responders [NR]). Cardiometabolic parameters (BMI, systolic BP [sBP] and LDL cholesterol) were measured at 20 years. Regression modelling demonstrated linear associations between POBW and BMI and sBP quadratic associations were observed for LDL cholesterol. For every 10% increase in POBW, there was a 0.54 unit increase in BMI (standard error [SE] 0.15) and a 0.65 unit decrease in sBP (SE 0.34). The interaction between participant’s fetal growth and HPA-A phenotype was strongest for sBP in young adulthood. Interactions for BMI and LDL-C were non-significant. Decomposition of the total effect revealed no causal evidence of mediation or moderation.
Publisher: Springer Science and Business Media LLC
Date: 1977
DOI: 10.1007/BF00693081
Publisher: Public Library of Science (PLoS)
Date: 25-10-2012
Publisher: Springer Science and Business Media LLC
Date: 1977
DOI: 10.1007/BF00693080
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 11-10-2012
Publisher: The Endocrine Society
Date: 20-02-2019
Abstract: “Accelerated aging,” assessed by adult DNA methylation, predicts cardiovascular disease (CVD). Adolescent accelerated aging might predict CVD earlier. We investigated whether epigenetic age acceleration (assessed age, 17 years) was associated with adiposity/CVD risk measured (ages 17, 20, and 22 years) and projected CVD by middle age. DNA methylation measured in peripheral blood provided two estimates of epigenetic age acceleration: intrinsic (IEAA preserved across cell types) and extrinsic (EEAA dependent on cell admixture and methylation levels within each cell type). Adiposity was assessed by anthropometry, ultrasound, and dual-energy x-ray absorptiometry (ages 17, 20, and 22 years). CVD risk factors [lipids, homeostatic model assessment of insulin resistance (HOMA-IR), blood pressure, inflammatory markers] were assessed at age 17 years. CVD development by age 47 years was calculated by Framingham algorithms. Results are presented as regression coefficients per 5-year epigenetic age acceleration (IEAA/EEAA) for adiposity, CVD risk factors, and CVD development. In 995 participants (49.6% female age, 17.3 ± 0.6 years), EEAA (per 5 years) was associated with increased body mass index (BMI) of 2.4% (95% CI, 1.2% to 3.6%) and 2.4% (0.8% to 3.9%) at 17 and 22 years, respectively. EEAA was associated with increases of 23% (3% to 33%) in high-sensitivity C-reactive protein, 10% (4% to 17%) in interferon-γ–inducible protein of 10 kDa, and 4% (2% to 6%) in soluble TNF receptor 2, adjusted for BMI and HOMA-IR. EEAA (per 5 years) results in a 4% increase in hard endpoints of CVD by 47 years of age and a 3% increase, after adjustment for conventional risk factors. Accelerated epigenetic age in adolescence was associated with inflammation, BMI measured 5 years later, and probability of middle age CVD. Irrespective of whether this is cause or effect, assessing epigenetic age might refine disease prediction.
Publisher: Elsevier BV
Date: 02-2012
Publisher: Wiley
Date: 04-07-2016
DOI: 10.1002/JBMR.2890
Abstract: Sedentary behaviors such as watching television (TV) are associated with increased risk of cardiometabolic disease. The effects of TV watching during key developmental stages on skeletal health are uncertain. Hours of TV watching/week were recorded by parental or self-report at 5, 8, 10, 14, 17, and 20 years of age in 1181 members (48% female) of a pregnancy cohort (the Raine Study). Participants were classified into one of three TV-watching trajectories (using latent class analysis): low (consistently <14 h/week 20.3%), high (consistently ≥14 h/week 44.4%), or increasing (increased from <14 to ≥14 h/week during adolescence 35.3%). General linear models tested associations between TV trajectory and bone mineral content (BMC) measured at age 20 years using dual-energy X-ray absorptiometry. After adjustment for height, body mass, physical activity, calcium intake, serum 25-hydroxyvitamin D levels, alcohol, and smoking (all at age 20 years), males in the low TV-watching trajectory had greater BMC for whole body (mean ± SEM, 3338 ± 59 g versus 3111 ± 31 g), legs (612 ± 12 g versus 569 ± 6 g), and arms (234 ± 5 g versus 214 ± 3 g) than those in the high TV-watching trajectory. Differences between low and high TV-watching trajectories were similar for females. BMC in the increasing TV-watching trajectory also differed for both sexes, for ex le males in the increasing TV-watching trajectory had greater whole-body BMC (3252 ± 38 g) than males in the high TV-watching trajectory (3111 ± 31 g) but less arm BMC (218 ± 3 g) than those in the low TV-watching trajectory (234 ± 5 g). In this community-based cohort, consistently high TV watching during childhood and adolescence independently predicted reduced peak bone mass at age 20 years. Because attainment of optimal peak bone mass is protective against osteoporosis in later life, reducing sedentary time in children may have long-term skeletal benefits. © 2016 American Society for Bone and Mineral Research.
Publisher: Wiley
Date: 24-04-2012
DOI: 10.1111/J.1471-0528.2012.03308.X
Abstract: To compare six validation criteria for umbilical cord blood gas (UCBG) values in vigorous and nonvigorous neonates. Retrospective cohort study. Single tertiary obstetric centre, King Edward Memorial Hospital (KEMH), Perth, Western Australia. A total of 37,763 consecutive deliveries at >23 weeks of gestation. Six validation criteria were compared to evaluate the proportion of deliveries with 'valid' UCBG data and the proportion of vigorous and nonvigorous neonates with metabolic acidaemia. Proportion of deliveries with 'valid' UCBG values proportions of vigorous and nonvigorous neonates with normal, borderline and abnormal UCBG values. The criteria based on KEMH 5th centile arteriovenous pH and Pco(2) differences resulted in a higher proportion of neonates with 'valid' UCBG values than the previously described Westgate and Kro criteria. The increase in 'valid' UCBG values occurred across the entire study population including vigorous and nonvigorous neonates. Among neonates with short-term neonatal complications there was an increase in nonvigorous neonates with umbilical artery metabolic acidaemia. There was no corresponding increase in vigorous neonates diagnosed with abnormal UCBG values. Use of the KEMH criteria results in an increase in the proportion of nonvigorous term neonates with UCBG data considered 'valid' to aid clinicians in the management of the neonate shortly after delivery. This change occurs without increasing the rate of false-positive diagnoses of acidaemia in vigorous neonates. The KEMH 'validation' criteria were developed from an entire presenting population and provide a simple algorithm that can be universally applied to identify neonates with nonphysiological UCBG values.
Publisher: Wiley
Date: 25-06-2002
DOI: 10.1002/PROT.10176
Publisher: Walter de Gruyter GmbH
Date: 2016
Abstract: There is an increasing body of literature supporting universal umbilical cord blood gas analysis (UCBGA) into all maternity units. A significant impediment to UCBGA’s introduction is the perceived expense of the introduction and associated ongoing costs. Consequently, this study set out to conduct the first cost-effectiveness analysis of introducing universal UCBGA. : Analysis was based on 42,100 consecutive deliveries ≥23 weeks of gestation at a single tertiary obstetric unit. Within 4 years of UCBGA’s introduction there was a 45% reduction in term special care nursery (SCN) admissions g. Incurred costs included initial and ongoing costs associated with universal UCBGA. Averted costs were based on local diagnosis-related grouping costs for reduction in term SCN admissions. Incremental cost-effectiveness ratio (ICER) and sensitivity analysis results were reported. : Under the base-case scenario, the adoption of universal UCBGA was less costly and more effective than selective UCBGA over 4 years and resulted in saving of AU$641,532 while adverting 376 SCN admissions. Sensitivity analysis showed that UCBGA was cost-effective in 51.8%, 83.3%, 99.6% and 100% of simulations in years 1, 2, 3 and 4. These conclusions were not sensitive to wide, clinically possible variations in parameter values for neonatal intensive care unit and SCN admissions, magnitude of averted SCN admissions, cumulative delivery numbers, and SCN admission costs. Universal UCBGA is associated with significant initial and ongoing costs however, potential averted costs (due to reduced SCN admissions) exceed incurred costs in most scenarios.
Publisher: Springer Science and Business Media LLC
Date: 13-11-2012
Publisher: The Endocrine Society
Date: 24-06-2016
DOI: 10.1210/JC.2016-1646
Abstract: The impact of early life events on testicular function in adulthood is not well understood. To study the early influences of fetal growth, exposures to cigarette smoke in utero and cord blood estrogens, and the influences of growth and adiposity in childhood through adolescence on testicular function in adulthood. Male members of the Western Australian Pregnancy Cohort (Raine) were contacted at 20-22 years of age. Of 913 contacted, 423 (56%) agreed to participate 404 underwent a testicular ultrasound, 365 provided a semen s le, and reproductive hormones were measured (384). Fetal growth measurements (n = 137), umbilical cord estrogen concentrations (n = 128), cord testosterone (T) (n = 125), and child-adulthood growth charts (n = 395) were available. Median sperm output for the 18.6% of men exposed in utero to smoking was lower than nonexposed (82.4 × 10(6) vs 123.1 × 10(6) P = .029). Sperm output in adulthood was inversely correlated with cord serum estradiol (P = .019) and estrone (P = .018). The sperm output of men whose cord blood estradiol and estrone were less than 50th percentile vs more than 50th percentile was 191.1 × 10(6) vs 100.5 × 10(6) (P = .002) and 190.0 × 10(6) vs 106.0 × 10(6) (P = .012), respectively. Men with favorable fetal growth patterns in utero were less likely to have total motile sperm counts within the lowest quartile (P = .011), and men born prematurely had reduced serum T levels in adulthood (13.4 vs 16.6nmol/L, P = .024). Consistent height above the 50th percentile for age through childhood was associated with larger adult mean testicular volume (P < .001). Optimal body mass index trajectory through childhood and adolescence was associated with larger testicular volume (P = .009) and higher serum inhibin B (P = .010) and T (P = .003) in adulthood. Exposures to maternal smoking and higher cord blood estrogens at delivery were associated with a reduced sperm output in adulthood. Optimal adult testicular function depends on being born at or above average weight, and maintaining optimal growth and adiposity into adulthood.
Publisher: Elsevier BV
Date: 08-1999
Publisher: Walter de Gruyter GmbH
Date: 2014
Abstract: Genome-wide association studies have been successful in uncovering novel genetic variants that are associated with disease status or cross-sectional phenotypic traits. Researchers are beginning to investigate how genes play a role in the development of a trait over time. Linear mixed effects models (LMM) are commonly used to model longitudinal data however, it is unclear if the failure to meet the models distributional assumptions will affect the conclusions when conducting a genome-wide association study. In an extensive simulation study, we compare coverage probabilities, bias, type 1 error rates and statistical power when the error of the LMM is either heteroscedastic or has a non-Gaussian distribution. We conclude that the model is robust to misspecification if the same function of age is included in the fixed and random effects. However, type 1 error of the genetic effect over time is inflated, regardless of the model misspecification, if the polynomial function for age in the fixed and random effects differs. In situations where the model will not converge with a high order polynomial function in the random effects, a reduced function can be used but a robust standard error needs to be calculated to avoid inflation of the type 1 error. As an illustration, a LMM was applied to longitudinal body mass index (BMI) data over childhood in the ALSPAC cohort the results emphasised the need for the robust standard error to ensure correct inference of associations of longitudinal BMI with chromosome 16 single nucleotide polymorphisms.
Publisher: Elsevier BV
Date: 06-2009
DOI: 10.1016/J.OGC.2009.03.004
Abstract: There is increasing evidence that obesity has its origins in early life. Predisposition is based on interactions between the genome and environmental influences acting through epigenetic modifications. In iduals most at risk are those whose ancestral line has made a rapid transition from a traditional to a Westernized style of life. The process involves not only metabolism, but also behavior. As a result, those people who are most at risk of obesity may be those least likely to respond to educational programs based on lifestyle modification. Understanding the mechanisms and pathways that underpin the early origins of obesity is vital if we are to make progress in addressing this major problem of modern life.
Publisher: Springer Science and Business Media LLC
Date: 31-08-2014
DOI: 10.1038/NG.3087
Publisher: Elsevier BV
Date: 03-2018
DOI: 10.1016/J.RBMO.2017.11.009
Abstract: Bisphenol A (BPA) is a ubiquitous chemical suspected to possess oestrogenic hormonal activities. Male population studies suggest a negative impact on testicular function. As Sertoli cell proliferation occurs during fetal or early postnatal life, it is speculated that oestrogenic environmental exposures may influence mature testicular function. Among 705 Western Australian Pregnancy Cohort (Raine) Study men aged 20-22 years, 404 underwent testicular ultrasound examination (149 had maternal serum available), and/or 365 provided semen (136 had maternal serum) and/or 609 serum s les for sex steroids, gonadotrophins and inhibin B analysis (244 had maternal serum). Maternal serum collected at 18 and 34 weeks' gestation was pooled and assayed for concentrations of total BPA (free plus conjugated) as an estimate of antenatal exposure. Testicular volume was calculated by ultrasonography, and semen analysis performed. Serum LH, FSH and inhibin B were measured by immunoassay testosterone, oestradiol, oestrone andBPA were measured by liquid chromatography-mass spectrometry. BPA levels were detectable in most (89%) maternal serum s les. After adjustment for maternal smoking, abstinence and varicocele, sperm concentration and motility were significantly correlated to maternal serum BPA (r = 0.18 P = 0.04 for both). No other associations of maternal serum BPA with testicular function were observed.
Publisher: Springer Science and Business Media LLC
Date: 09-1991
DOI: 10.1007/BF01310670
Publisher: Wiley
Date: 07-11-2015
DOI: 10.1111/CEO.12455
Abstract: Sun exposure is associated with several ophthalmic diseases, including pterygium which may develop in adolescence. This study reports the prevalence of pterygium and its associations in a large cohort of young Australian adults. Conjunctival ultraviolet autofluorescence, a biomarker of ocular sun exposure, has recently been characterized in some Australian populations. Cross-sectional population-based study. One thousand three hundred forty-four subjects aged 18-22 years in the Western Australian Pregnancy Cohort (Raine) Study. Standardized colour and ultraviolet autofluorescence photographs of the nasal and temporal conjunctiva were taken, and assessed for presence of pterygium and area of autofluorescence. Sun exposure and protective factors were assessed by structured questionnaire. Area of conjunctival ultraviolet autofluorescence in square millimetre (mm(2)) and presence of pterygium. Median total conjunctival autofluorescence was 44.2 mm(2) (interquartile range 20.2-69.8 mm(2)). Median conjunctival autofluorescence was higher in nasal than in temporal quadrants (23.8 mm(2) vs. 18.9 mm(2), P < 0.001), but did not differ according to age or gender. Higher body mass index was associated with lower levels of autofluorescence. Total autofluorescence increased with increasing time spent outdoors. Prevalence of pterygium was 1.2% (95% confidence interval 0.6-1.8%), and was associated with male gender (odds ratio 6.71, P = 0.012). Participants with pterygium had significantly more conjunctival autofluorescence than those without (median 73.4 mm(2) vs. 44.0 mm(2), P = 0.001). Conjunctival ultraviolet autofluorescence is associated with increased time spent outdoors, and increased prevalence of pterygium. The association of this biomarker with other ophthalmohelioses, including cataract, ocular surface squamous neoplasia and eyelid malignancy, has yet to be determined.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-2013
Publisher: American Society for Microbiology
Date: 07-1996
DOI: 10.1128/JB.178.13.3809-3817.1996
Abstract: Type 4 fimbriae are surface filaments produced by a range of bacterial pathogens for colonization of host epithelial surfaces. In Pseudomonas aeruginosa, they are involved in adhesion as well as in a form of surface translocation called twitching motility, and sensitivity to infection by fimbria-specific bacteriophage. Analysis of the 2.5-kb intergenic region between the previously defined pilR and pilV genes on P. aeruginosa genomic SpeI fragment E has identified three new genes, fimT, fimU, and dadA*. The predicted 18.5-kDa products of the fimT and fimU genes contain prepilin-like leader sequences, whereas the third gene, dadA*, encodes a protein similar to the D-amino acid dehydrogenase of Escherichia coli. Isogenic mutants constructed by allelic exchange demonstrated that the fimU gene was required for fimbrial biogenesis and twitching motility, whereas the fimT and dada* mutants retained wild-type phenotypes. However, overexpression of the fimT gene was found to be able to functionally replace the lack of a fimU gene product, suggesting a subtle role in fimbrial biogenesis. The identification of these proteins increases the similarity between type 4 fimbrial biogenesis and the supersystems involved in macromolecular traffic, such as extracellular protein secretion and DNA uptake, all of which now possess multiple protein species that possess prepilin-like leader sequences.
Publisher: Springer Science and Business Media LLC
Date: 10-02-2013
DOI: 10.1038/NG.2554
Publisher: Wiley
Date: 07-07-2016
DOI: 10.1002/AUR.1518
Abstract: Numerous studies have observed that a proportion of infants later diagnosed with autism spectrum disorder (ASD) experience accelerated head growth during the first years of life. An emerging methodology for examining the developmental trajectory prior to a diagnosis of ASD is to investigate siblings of affected in iduals. The current study is the first prospective investigation of fetal growth in siblings of children with ASD. Two groups of pregnant women were recruited as part of the PRegnancy Investigation of Siblings and Mothers of children with autism cohort in Perth, Western Australia. The "high risk" group (n = 23) comprised pregnant women who have an existing child with a diagnosis of ASD and the "low risk" group (n = 36) comprised pregnant mothers who have an existing child who has developed typically. Prenatal ultrasounds were procured at multiple time-points throughout the second- and third-trimesters, enabling an examination of growth trajectories. Growth measurements were then compared for the high- and low-risk fetuses. Mixed linear regression models identified no significant differences between the high- and low-risk fetuses in the rate of prenatal head and body growth throughout the second- and third-trimester (all P-values >0.05). Similarly, there were no significant differences observed when comparing high and low risk groups on a ratio of head circumference relative to body size (β = -0.019, P = 0.75). Future studies may consider looking beyond the macro architecture of the prenatal brain and examine the growth of brain subregions that have been implicated in the presentation of ASD symptoms.
Publisher: Wiley
Date: 10-1993
Publisher: Informa UK Limited
Date: 07-2021
Publisher: Springer Science and Business Media LLC
Date: 05-2012
Abstract: Preterm birth is a major societal and economic problem accounting for 80 to 90% of neonatal morbidity and mortality worldwide. It is recognized as a complex multifactorial condition comprising several distinct clinical phenotypes with different underlying etiologies. As animal models are expensive and fail to mimic the biology of spontaneous preterm birth in humans, understanding the pathophysiology requires detailed clinical studies. Meta-analyses and clinical translation of data, however, are limited by heterogeneity of study design and size, publication and reporting biases, definition of patient groups, and a lack of standard universal definitions. This article provides a harmonized open-source template for designing clinical studies addressing preterm birth. Recommendations are made for clinical definitions, choice and assignment to preterm birth phenotypes, selection of enriched populations and control pregnancies, and potential confounding factors. In addition, recommendations are made for study design, s le size and power calculations, the minimal data sets needed for any study of preterm birth, and the optimal data set of an ideal study. Recommended patient phenotypes are infection, uterine overdistension, hemorrhage, stress (either maternal or fetal), and idiopathic. Confounding factors include medical conditions, obesity, antenatal glucocorticoids, multifetal pregnancies, and fetal sex. Guidelines regarding study design, s le size, and clinical data acquisition are provided to serve as a universal template for preterm birth studies. Adoption of a harmonized template will allow generation of protocols and studies with a basic degree of compatibility and will allow data to be compared, and s les and data sets to be combined for meaningful meta-analyses.
Publisher: Informa UK Limited
Date: 11-04-2011
Publisher: American Society for Microbiology
Date: 07-2002
DOI: 10.1128/JB.184.13.3605-3613.2002
Abstract: Vfr, a homolog of Escherichia coli cyclic AMP (cAMP) receptor protein, has been shown to regulate quorum sensing, exotoxin A production, and regA transcription in Pseudomonas aeruginosa . We identified a twitching motility-defective mutant that carries a transposon insertion in vfr and confirmed that vfr is required for twitching motility by construction of an independent allelic deletion-replacement mutant of vfr that exhibited the same phenotype, as well as by the restoration of normal twitching motility by complementation of these mutants with wild-type vfr . Vfr-null mutants exhibited severely reduced twitching motility with barely detectable levels of type IV pili, as well as loss of elastase production and altered pyocyanin production. We also identified reduced-twitching variants of quorum-sensing mutants (PAK lasI ::Tc) with a spontaneous deletion in vfr (S. A. Beatson, C. B. Whitchurch, A. B. T. Semmler, and J. S. Mattick, J. Bacteriol., 184:3598-3604, 2002), the net result of which was the loss of five residues (EQERS) from the putative cAMP-binding pocket of Vfr. This allele (VfrΔEQERS) was capable of restoring elastase and pyocyanin production to wild-type levels in vfr -null mutants but not their defects in twitching motility. Furthermore, structural analysis of Vfr and VfrΔEQERS in relation to E. coli CRP suggests that Vfr is capable of binding both cAMP and cyclic GMP whereas VfrΔEQERS is only capable of responding to cAMP. We suggest that Vfr controls twitching motility and quorum sensing via independent pathways in response to these different signals, bound by the same cyclic nucleotide monophosphate-binding pocket.
Publisher: Informa UK Limited
Date: 03-03-2016
DOI: 10.3109/10253890.2016.1146672
Abstract: Dysregulation of the biological stress response system has been implicated in the development of psychological, metabolic, and cardiovascular disease. Whilst changes in stress response are often quantified as an increase or decrease in cortisol levels, three different patterns of stress response have been reported in the literature for the Trier Social Stress Test (TSST) (reactive-responders (RR), anticipatory-responders (AR) and non-responders (NR)). However, these have never been systematically analyzed in a large population-based cohort. The aims of this study were to examine factors that contribute to TSST variation (gender, oral contraceptive use, menstrual cycle phase, smoking, and BMI) using traditional methods and novel analyses of stress response patterns. We analyzed the acute stress response of 798, 18-year-old participants from a community-based cohort using the TSST. Plasma adrenocorticotrophic hormone, plasma cortisol, and salivary cortisol levels were quantified. RR, AR, and NR patterns comprised 56.6%, 26.2%, and 17.2% of the cohort, respectively. Smokers were more likely to be NR than (RR or AR adjusted, p < 0.05). Overweight and obese subjects were less likely to be NR than the other patterns (adjusted, p < 0.05). Males were more likely to be RR than NR (adjusted, p = 0.05). In addition, we present a novel AUC measure (AUCR), for use when the TSST baseline concentration is higher than later time points. These results show that in a young adult cohort, stress-response patterns, in addition to other parameters vary with gender, smoking, and BMI. The distribution of these patterns has the potential to vary with adult health and disease and may represent a biomarker for future investigation.
Publisher: Wiley
Date: 02-2012
Publisher: Springer Science and Business Media LLC
Date: 2003
Publisher: Springer Science and Business Media LLC
Date: 09-10-2017
DOI: 10.1038/IJO.2017.248
Publisher: Wiley
Date: 19-10-2010
Publisher: Elsevier BV
Date: 07-1991
Publisher: Elsevier BV
Date: 09-2017
DOI: 10.1016/J.JACI.2016.10.055
Abstract: The relationship between allergy and autoimmune disorders is complex and poorly understood. We sought to investigate commonalities in genetic loci and pathways between allergy and autoimmune diseases to elucidate shared disease mechanisms. We meta-analyzed 2 genome-wide association studies on self-reported allergy and sensitization comprising a total of 62,330 subjects. These results were used to calculate enrichment for single nucleotide polymorphisms (SNPs) previously associated with autoimmune diseases. Furthermore, we probed for enrichment within genetic pathways and of transcription factor binding sites and characterized commonalities in variant burden on tissue-specific regulatory sites by calculating the enrichment of allergy SNPs falling in gene regulatory regions in various cells using Encode Roadmap DNase-hypersensitive site data. Finally, we compared the allergy data with those of all known diseases. Among 290 loci previously associated with 16 autoimmune diseases, we found a significant enrichment of loci also associated with allergy (P = 1.4e-17) encompassing 29 loci at a false discovery rate of less than 0.05. Such enrichment seemed to be a general characteristic for autoimmune diseases. Among the common loci, 48% had the same direction of effect for allergy and autoimmune diseases. Additionally, we observed an enrichment of allergy SNPs falling within immune pathways and regions of chromatin accessible in immune cells that was also represented in patients with autoimmune diseases but not those with other diseases. We identified shared susceptibility loci and commonalities in pathways between allergy and autoimmune diseases, suggesting shared disease mechanisms. Further studies of these shared genetic mechanisms might help in understanding the complex relationship between these diseases, including the parallel increase in disease prevalence.
Publisher: Oxford University Press (OUP)
Date: 1989
Publisher: Wiley
Date: 10-1996
Publisher: Springer Science and Business Media LLC
Date: 23-04-2011
DOI: 10.1007/S10803-010-1019-6
Abstract: Fetal head circumference (HC) growth was examined prospectively in children with autism spectrum disorder (ASD). ASD participants (N = 14) were each matched with four control participants (N = 56) on a range of parameters known to influence fetal growth. HC was measured using ultrasonography at approximately 18 weeks gestation and again at birth using a paper tape-measure. Overall body size was indexed by fetal femur-length and birth length. There was no between-groups difference in head circumference at either time-point. While a small number of children with ASD had disproportionately large head circumference relative to body size at both time-points, the between-groups difference did not reach statistical significance in this small s le. These preliminary findings suggest that further investigation of fetal growth in ASD is warranted.
Publisher: Wiley
Date: 03-1993
Publisher: Wiley
Date: 08-1993
Publisher: Informa UK Limited
Date: 10-08-2011
DOI: 10.3109/14767058.2011.597899
Abstract: To (1) investigate the current distribution of PTB phenotypes (2) identify factors associated with spontaneous preterm labour (SPTL), PPROM, and indicated PTB (3) investigate the relationship of gestational age (ga) with each PTB phenotype. Retrospective review of all live, singleton births 23(+0) to 36(+6) weeks ga at an obstetric referral centre 2004-2008. A total of 4,522 PTBs were included (SPTL 31.7%, PPROM 27.4%, indicated 40.8%). PTB phenotype distribution differed between ga groups (<27 weeks: SPTL 45%, PPROM 32%, indicated 23% 27-33 weeks: SPTL 30%, PPROM 32%, indicated 39% 34-36 weeks: SPTL 32%, PPROM 24%, indicated 44%, p < 0.001). Between 34-36 weeks', demographic factors were significantly different between PTB phenotypes (age ≥35: SPTL 13.8%, PPROM 15.4%, indicated 21.6% Caucasian ethnicity: SPTL 61.6%, PPROM 69.0%, indicated 70.2% Assisted Reproductive Technology (ART): SPTL 2.8%, PPROM 1.9%, indicated 9.3% all p < 0.001). Between 27-33 weeks' PTB phenotype was associated with smoking (SPTL 24.9%, PPROM 29.3%, indicated 20.2% p = 0.002) and ART (SPTL 2.3%, PPROM 1.6%, indicated 5.0% p = 0.002). Demographic factors were not associated with PTB phenotype at 23-26 weeks. The increase in PTB rates may be explained by medical indications at late preterm gestations, primarily in older, Caucasian women requiring fertility assistance. Interventions to reduce the rate of PTB need to be targeted to this high-risk population.
Publisher: Proceedings of the National Academy of Sciences
Date: 05-1990
Abstract: Bacteria, tomatoes, and trypanosomes all contain genes for a large protein with extensive homology to the regulatory subunit, ClpA, of the ATP-dependent protease of Escherichia coli, Clp. All members of the family have between 756 and 926 amino acids and contain two large regions, of 233 and 192 amino acids, each containing consensus sequences for nucleotide binding. Within these regions there is at least 85% similarity between the most distant members of the family. The high degree of similarity among the ClpA-like proteins suggests that Clp-like proteases are likely to be important participants in energy-dependent proteolysis in prokaryotic and eukaryotic cells.
Publisher: Springer Science and Business Media LLC
Date: 02-11-2017
Publisher: Springer Science and Business Media LLC
Date: 06-04-2010
DOI: 10.1038/NG.567
Publisher: Springer Science and Business Media LLC
Date: 06-11-2015
DOI: 10.1038/NCOMMS9804
Abstract: Eczema often precedes the development of asthma in a disease course called the ‘atopic march’. To unravel the genes underlying this characteristic pattern of allergic disease, we conduct a multi-stage genome-wide association study on infantile eczema followed by childhood asthma in 12 populations including 2,428 cases and 17,034 controls. Here we report two novel loci specific for the combined eczema plus asthma phenotype, which are associated with allergic disease for the first time rs9357733 located in EFHC1 on chromosome 6p12.3 (OR 1.27 P= 2.1 × 10 −8 ) and rs993226 between TMTC2 and SLC6A15 on chromosome 12q21.3 (OR 1.58 P= 5.3 × 10 −9 ). Additional susceptibility loci identified at genome-wide significance are FLG (1q21.3), IL4/KIF3A (5q31.1), AP5B1/OVOL1 (11q13.1), C11orf30/LRRC32 (11q13.5) and IKZF3 (17q21). We show that predominantly eczema loci increase the risk for the atopic march. Our findings suggest that eczema may play an important role in the development of asthma after eczema.
Publisher: Springer Science and Business Media LLC
Date: 06-02-2014
Publisher: Elsevier BV
Date: 07-1994
Publisher: AMPCo
Date: 14-07-2019
DOI: 10.5694/MJA2.50266
Abstract: To compare rates of detectability of circulating Rh(D)-immunoglobulin (anti-D) at delivery with single and two-dose antenatal anti-D prophylaxis (RAADP) regimens to compare compliance with the two regimens. Open label, randomised controlled trial between May 2013 and November 2015. 277 women who attended a tertiary obstetric referral hospital in Perth for antenatal care and were at least 18 years of age, less than 30 weeks pregnant and yet to receive RAADP, Rh(D)-negative (negative antibody screen), and who intended to deliver their baby at the hospital. Exclusion criteria were prior anti-D sensitisation, any contraindication of anti-D administration, and a history of isolated IgA deficiency. One 1500 IU anti-D dose at 28 weeks of pregnancy (single dose regimen) two doses of 625 IU each at 28 and 34 weeks of pregnancy (two-dose regimen). The primary outcome was the proportion of women with detectable anti-D levels at delivery the secondary outcome was compliance with the allocated RAADP regimen. Circulating anti-D was detectable at delivery in a greater proportion of women in the two-dose group (111 of 129, 86%) than in the single dose group (70 of 125, 56% P < 0.001). Compliance was not significantly different between the single dose (86 of 138, 61%) and two-dose groups (70 of 139, 50% P = 0.06). The two-dose RAADP schedule currently recommended in Australia provides better protection against Rh(D) sensitisation than a one-dose regimen. Australian and New Zealand Clinical Trials Registry (ACTRN12613000661774).
Publisher: Wiley
Date: 04-03-2013
DOI: 10.1111/AJO.12058
Abstract: Despite a growing body of evidence demonstrating the value of universal umbilical cord blood gas analysis (UCBGA), there remains reluctance in some maternity units to adopt universal testing. Identify perceived barriers and benefits of universal UCBGA. Medical and midwifery staff involved in intrapartum care at four level two maternity units (one metropolitan and three regional) completed questionnaires evaluating attitudes to UCBGA. Questionnaires included 13 statements with responses ranging from strongly agree to strongly disagree and background demographic data. Most respondents considered UCBGA beneficial to perinatal care (n = 72 67.3%), with only nine in iduals (8.4%) believing UCBGA had no place in perinatal care. The majority of respondents considered benefits of UCBGA to include being an effective and objective marker of neonatal status (n = 64 59.8%), as well as playing a role in medicolegal issues (n = 74 69.2%) and audit and teaching (n = 64 59.8%). Respondents considered that barriers to universal UCBGA introduction included insufficient time following delivery, increased workload and encroachment of technology into birth. The majority of respondents indicated support for UCBGA. Information derived from this study may be useful in identifying and resolving concerns prior to the introduction of UCBGA. Further, it could be useful in the preparation of education and implementation packages necessary for introduction of UCBGA.
Publisher: Elsevier BV
Date: 04-2016
DOI: 10.1016/J.PSYNEUEN.2016.01.002
Abstract: Activation of the hypothalamic-pituitary-adrenal (HPA) axis has been associated with higher levels of cardiovascular (CVD) risk factors in adults. This study aimed to assess the relation between measures of HPA axis activity under resting conditions and CVD risk factors in a general population of adolescents at 17 years. A total of 1134 adolescents from the Western Australian Pregnancy Cohort (Raine) Study had phenotypic and socio-demographic data. The associations between HPA axis measures (plasma ACTH, total cortisol, calculated free cortisol, corticosteroid binding globulin (CBG), and salivary cortisol) and a range of cardiovascular risk factors were examined using multivariable linear regression models, with adjustment for gender, adiposity, birth weight, gestational age, and socio-behavioural factors. Plasma total cortisol was positively associated with systolic blood pressure (SBP) (p=0.011), total cholesterol, HDL-cholesterol, and triglycerides (all p<0.001), and hs-CRP (p=0.047). Salivary cortisol was associated positively with HDL-C (p=0.033) and negatively with LDL-cholesterol (p=0.016) plasma calculated free cortisol was positively associated with triglycerides (p=0.006) plasma CBG was positively associated with total cholesterol and HDL-cholesterol (both p<0.001), LDL-cholesterol (p=0.022), and hs-CRP (p=0.001). After correction for multiple comparisons, significant associations remained for total cortisol with total cholesterol, HDL-C, and triglycerides for calculated free cortisol with triglycerides and for CBG with HDL-C, total cholesterol, and hs-CRP. Plasma ACTH was not associated with any cardiovascular risk factor. There was no association between BMI and any measure of HPA axis activity. In an adolescent population, HPA axis measures under resting conditions are associated with a range of CVD risk factors. Clarification of the mechanisms underlying these associations in adolescence would be an important step in understanding the evolution of adult CVD.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2013
Publisher: Oxford University Press (OUP)
Date: 05-09-2012
DOI: 10.1093/HMG/DDS372
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2013
DOI: 10.1002/HEP.26184
Abstract: Genetic factors account for a significant proportion of the phenotypic variance of nonalcoholic fatty liver disease (NAFLD) however, very few predisposing genes have been identified. We aimed to (1) identify novel genetic associations with NAFLD by performing a genome-wide association study (GWAS), and (2) examine the biological expression of the strongest genetic associations in a separate cohort. We performed GWAS of a population-based cohort (Raine Study) of 928 adolescents assessed for NAFLD by ultrasound at age 17. Expression of genes with single nucleotide polymorphisms (SNPs) that were associated with NAFLD at a significance level of P < 10(-5) was examined in adults with NAFLD and controls by quantifying hepatic messenger RNA (mRNA) expression and serum levels of protein. After adjustment for sex and degree of adiposity, SNPs in two genes expressed in liver were associated with NAFLD adolescents: group-specific component (GC) (odds ratio [OR], 2.54 P = 1.20 × 10(-6)) and lymphocyte cytosolic protein-1 (LCP1) (OR, 3.29 P = 2.96 × 10(-6)). SNPs in two genes expressed in neurons were also associated with NAFLD: lipid phosphate phosphatase-related protein type 4 (LPPR4) (OR, 2.30 P = 4.82 × 10(-6)) and solute carrier family 38 member 8 (SLC38A8) (OR, 3.14 P = 1.86 × 10(-6) ). Hepatic GC mRNA was significantly reduced (by 83%) and LCP1 mRNA was increased (by 300%) in liver biopsy s les from patients with NAFLD compared to controls (P < 0.05). Mean serum levels of GC protein were significantly lower in patients with NAFLD than controls (250 ± 90 versus 298 ± 90, respectively P = 0.004) GC protein levels decreased with increasing severity of hepatic steatosis (P < 0.01). The association between GC and LCP1 SNPs and NAFLD as well as altered biological expression implicate these genes in the pathogenesis of NAFLD.
Publisher: Wiley
Date: 05-1995
Publisher: Elsevier BV
Date: 02-2007
DOI: 10.1016/J.AJOG.2006.03.109
Abstract: Over the last decade, it has become increasingly apparent that the cause of preterm birth is multifactorial, involving both genetic and environmental factors. With the development of new technologies capable of probing the genome, exciting possibilities now present themselves to gain new insight into the mechanisms leading to preterm birth. This review aims to develop research guidelines for the conduct of genetic epidemiology studies of preterm birth with the expectation that this will ultimately facilitate the comparison of data sets between study cohorts, both nationally and internationally. Specifically, the 4 areas addressed in this review includes: (1) phenotypic criteria, (2) study design, (3) considerations in the selection of control populations, and (4) candidate gene selection. This article is the product of discussions initiated by the authors at the 3rd International Workshop on Biomarkers and Preterm Birth held at the University of California, Los Angeles, Los Angeles, CA, in March 2005.
Publisher: Informa UK Limited
Date: 08-02-2021
Publisher: Springer Science and Business Media LLC
Date: 22-12-2017
Publisher: Oxford University Press (OUP)
Date: 27-02-2013
DOI: 10.1093/HMG/DDT104
Publisher: Elsevier BV
Date: 11-2015
Publisher: BMJ
Date: 07-2023
DOI: 10.1136/BMJOPEN-2023-072205
Abstract: Multiple cohort studies have been established to investigate the impact of early life factors on development and health outcomes. In Australia the majority of these studies were established more than 20 years ago and, although longitudinal in nature, are inherently susceptible to socioeconomic, environmental and cultural influences which change over time. Additionally, rapid leaps in technology have increased our understanding of the complex role of gene–environment interactions in life course health, highlighting the need for new cohort studies with repeated biological s ling and in-depth phenotype data across the first 1000 days of life from conception. The Newcastle 1000 (NEW1000) Study, based in the regional city of Newcastle, New South Wales, was developed after an extensive consultation process involving 3 years of discussion with key stakeholders and healthcare consumer organisations and seven healthcare consumer workshops. This prospective population-based pregnancy cohort study will recruit 500 families per year for 5 years, providing detailed, longitudinal, multisystem phenotyping, repeated ultrasound measures and serial s le collection to investigate healthcare consumer identified health outcomes of priority. Stage 1 will involve recruitment of pregnant participants and their partners at 14 weeks gestation, with dense phenotype data and biological s les collected at 14, 20, 28 and 36 weeks gestation and serial ultrasound measures at 20, 28, 36 and 40 weeks, with postpartum follow-up at 6 weeks and 6 months. Biological s les will be used for biomarker discovery and sequencing of the genome, transcriptome, epigenome, microbiome and metabolome. Ethics approval was obtained from Hunter New England Local Health District Ethics Committee (2020/ETH02881). Outcomes will be published in peer-reviewed journals, disseminated to participants through the NEW1000 website, presented at scientific conferences, and written reports to local, state and national government bodies and key stakeholders in the healthcare system to inform policy and evidence-based practice.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 06-09-2019
Abstract: Longitudinal data find a new variant controlling BMI in infancy and reveal genetic differences between infant and adult BMI.
Publisher: Elsevier BV
Date: 10-2016
Publisher: Springer Science and Business Media LLC
Date: 10-05-2023
Publisher: Springer Science and Business Media LLC
Date: 10-02-2023
DOI: 10.1007/S43032-023-01183-2
Abstract: The mechanism by which human labor is initiated in the presence of elevated circulating progesterone levels remains unknown. Recent evidence indicates that the progesterone-metabolizing enzyme, 20α-hydroxysteroid dehydrogenase (20α-HSD), encoded by the gene AKR1C1 , may contribute to functional progesterone withdrawal. We found that AKR1C1 expression significantly increased with labor onset in term myometrium, but not in preterm myometrium. Among preterm laboring deliveries, clinically diagnosed chorioamnionitis was associated with significantly elevated AKR1C1 expression. AKR1C1 expression positively correlated with BMI before labor and negatively correlated with BMI during labor. Analysis by fetal sex showed that AKR1C1 expression was significantly higher in women who delivered male babies compared to women who delivered female babies at term, but not preterm. Further, in pregnancies where the fetus was female, AKR1C1 expression positively correlated with the mother’s age and BMI at the time of delivery. In conclusion, the increase in myometrial AKR1C1 expression with term labor is consistent with 20α-HSD playing a role in local progesterone metabolism to promote birth. Interestingly, this role appears to be specific to term pregnancies where the fetus is male. Upregulated AKR1C1 expression in the myometrium at preterm in-labor with clinical chorioamnionitis suggests that increased 20α-HSD activity is a mechanism through which inflammation drives progesterone withdrawal in preterm labor. The link between AKR1C1 expression and maternal BMI may provide insight into why maternal obesity is often associated with dysfunctional labor. Higher myometrial AKR1C1 expression in male pregnancies may indicate fetal sex-related differences in the mechanisms that precipitate labor onset at term.
Publisher: Springer Science and Business Media LLC
Date: 11-02-2015
DOI: 10.1038/NATURE14132
Publisher: Elsevier BV
Date: 11-2018
Location: Australia
Start Date: 2015
End Date: 2019
Funder: Genome Canada
View Funded ActivityStart Date: 2009
End Date: 2011
Funder: National Heart Foundation of Australia
View Funded ActivityStart Date: 2019
End Date: 2025
Funder: Newcastle University
View Funded ActivityStart Date: 2020
End Date: 2022
Funder: Hunter New England Local Health District
View Funded ActivityStart Date: 2001
End Date: 2003
Funder: Women and Infants Research Foundation
View Funded ActivityStart Date: 2004
End Date: 2006
Funder: Physicians' Services Incorporated Foundation
View Funded ActivityStart Date: 2019
End Date: 2024
Funder: Hunter Medical Research Institute
View Funded ActivityStart Date: 1999
End Date: 1999
Funder: Australian Women and Childrens Research Foundation
View Funded ActivityStart Date: 2008
End Date: 2012
Funder: Alberta Heritage Foundation for Medical Research
View Funded ActivityStart Date: 2005
End Date: 2008
Funder: March of Dimes Foundation
View Funded ActivityStart Date: 2006
End Date: 2007
Funder: Raine Medical Research Foundation
View Funded ActivityStart Date: 2009
End Date: 2012
Funder: March of Dimes Canada
View Funded ActivityStart Date: 2017
End Date: 2017
Funder: National Institute for Health Research
View Funded ActivityStart Date: 2002
End Date: 2005
Funder: Canadian Institutes of Health Research
View Funded ActivityStart Date: 2009
End Date: 2011
Funder: Channel 7 Telethon Trust
View Funded ActivityStart Date: 2016
End Date: 2018
Funder: Department of Health, Government of Western Australia
View Funded ActivityStart Date: 2008
End Date: 2008
Funder: National Health and Medical Research Council
View Funded Activity