ORCID Profile
0000-0003-4593-3042
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
Publisher: MDPI AG
Date: 21-09-2021
Abstract: Lipid metabolism is tightly linked to adiposity. Comprehensive lipidomic profiling offers new insights into the dysregulation of lipid metabolism in relation to weight gain. Here, we investigated the relationship of the human plasma lipidome and changes in waist circumference (WC) and body mass index (BMI). Adults (2653 men and 3196 women), 25–95 years old who attended the baseline survey of the Australian Diabetes, Obesity and Lifestyle Study (AusDiab) and the 5-year follow-up were enrolled. A targeted lipidomic approach was used to quantify 706 distinct molecular lipid species in the plasma s les. Multiple linear regression models were used to examine the relationship between the baseline lipidomic profile and changes in WC and BMI. Metabolic scores for change in WC were generated using a ridge regression model. Alkyl-diacylglycerol such as TG(O-50:2) [NL-18:1] displayed the strongest association with change in WC (β-coefficient = 0.125 cm increment per SD increment in baseline lipid level, p = 2.78 × 10−11. Many lipid species containing linoleate (18:2) fatty acids were negatively associated with both WC and BMI gain. Compared to traditional models, multivariate models containing lipid species identify in iduals at a greater risk of gaining WC: top quintile relative to bottom quintile (odds ratio, 95% CI = 5.4, 3.8–6.6 for women and 2.3, 1.7–3.0 for men). Our findings define metabolic profiles that characterize in iduals at risk of weight gain or WC increase and provide important insight into the biological role of lipids in obesity.
Publisher: Informa UK Limited
Date: 02-06-2016
DOI: 10.1080/07420528.2016.1189430
Abstract: On trips with multiple transmeridian flights, pilots experience successive non-24 h day/night cycles with circadian and sleep disruption. One study across a 9-day sequence of transpacific flights (no in-flight sleep, 1-day layovers between flights) reported an average period in the core body temperature rhythm of 24.6 h (circadian drift). Consequently, pilots were sometimes flying through the circadian performance nadir and had to readapt to home base time at the end of the trip. The present study examined circadian drift in trip patterns with longer flights and in-flight sleep. Thirty-nine B747-400 pilots (19 captains, 20 first officers, mean age = 55.5 years) were monitored on 9- to 13-day trips with multiple return flights between East Coast USA and Japan (in 4-pilot crews) and between Japan and Hawaii (in 3-pilot crews), with 1-day layovers between each flight. Measures included total in-flight sleep (actigraphy, log books) and top of descent (TOD) measures of sleepiness (Karolinska Sleepiness Scale), fatigue (Samn-Perelli Crew Status Check) and psychomotor vigilance task (PVT) performance. Circadian rhythms of in idual pilots were not monitored. To detect circadian drift, mixed-model analysis of variance examined whether for a given flight, total in-flight sleep and TOD measures varied according to when the flight occurred in the trip sequence. In addition, sleep propensity curves for pre-trip and post-trip days were examined (Chi-square periodogram analyses). Limited data suggest that total in-flight sleep of relief crew at landing may have decreased across successive East Coast USA-Japan (flights 1, 3, 5 or 7 median arrival 03:45 Eastern Daylight Time (EDT)). However, PVT response speed at TOD was faster on East Coast USA-Japan flights later in the trip. On these flights, circadian drift would result in flights later in the trip landing closer to the evening wake maintenance zone, when sleep is difficult and PVT response speeds are fastest. On Japan-East Coast USA flights (flights 2, 4, 6 or 8 median arrival time 14:52 EDT), PVT response speeds were slower on flight 8 than on flight 2. Circadian drift would move these arrivals progressively earlier in the SCN pacemaker cycle, where PVT response speeds are slower. Across the five post-trip days, 12 pilots (Group A) immediately resumed their pre-trip sleep pattern of a single nocturnal sleep episode 9 pilots (Group B) had a daytime nap on most days that moved progressively earlier until it merged with nocturnal sleep and 17 pilots (Group C) had nocturnal sleep and intermittent naps. Chi-square periodogram analyses of the sleep propensity curves for each group across baseline and post-trip days suggest full adaptation to EDT from post-trip day 1 (dominant period = 24 h). However, in Groups B and C, the patterns of split sleep post-trip compared to pre-trip suggest that this may be misleading. We conclude that the trends in total in-flight sleep and significant changes in PVT performance speed at TOD provide preliminary evidence for circadian drift, as do persistent patterns of split sleep post-trip. However, new measures to track circadian rhythms in in idual pilots are needed to confirm these findings.
Publisher: Springer Science and Business Media LLC
Date: 27-04-2015
DOI: 10.1038/NCOMMS7970
Abstract: Defining the immune mechanisms underlying protective immunity to helminth infection remains an important challenge. Here we report that lung CD4(+) T cells and Group 2 innate lymphoid cells (ILC2s) work in concert to block Nippostrongylus brasiliensis (Nb) development in the parenchyma within 48 h in mice. Immune-damaged larvae have a striking morphological defect that is dependent on the expansion of IL-13-producing ILC2 and CD4(+) T cells, and the activation of M2 macrophages. This T-cell requirement can be bypassed by administration of IL-2 or IL-33, resulting in expansion of IL-13-producing ILC2s and larval killing. Depletion of ILC2s inhibits larval killing in IL-2-treated mice. Our results broaden understanding of ILC2's role in immunity to helminths by demonstrating that they not only act as alarmin sensors, but can also be sustained by CD4(+) T cells, ensuring both the prompt activation and the maintenance of IL-13-dependent M2 macrophage immunity in the lung.
Publisher: The Endocrine Society
Date: 04-02-2020
Abstract: Insulin resistance (IR) remains a global health challenge. Lipidomics offers an opportunity to identify biomarkers and better understand mechanisms of IR associated with abnormal lipid metabolism. The objective of this article is to determine plasma lipid species associated with indices of IR and evaluate the lipidome response to an oral glucose tolerance test (OGTT). This study was community based and cross-sectional. Plasma s les (collected at 0 and 120 min during an OGTT) from nonobese, young adults age 18 to 34 years (n = 246) were analyzed using liquid chromatography–tandem mass spectrometry. The associations between indices of IR and lipid classes and species (with a sex interaction term), or changes in lipid levels during an OGTT, were tested using linear models (adjusted for age, sex, body mass index, total cholesterol, high-density lipoprotein cholesterol, and triglycerides). Some (213) and (199) lipid species were associated with the homeostatic model assessment of insulin resistance and insulin area under curve (AUC), respectively. Alkylphosphatidylcholine (10), alkenylphosphatidylcholine (23), and alkylphosphatidylethanolamine (6) species were associated with insulin AUC in men only. Species of phosphatidylcholine (7) and sphingomyelin (5) were associated in women only. In response to an OGTT, a perturbation in the plasma lipidome, particularly in acylcarnitine species, was observed and the changes in many lipid species were associated with insulin AUC. The plasma lipidome and changes in lipid levels during an OGTT were associated with indices of IR. These findings underlie the involvement of molecular lipid species in the pathogenesis of IR and possibly crosstalk between IR and sex-specific regulation of lipid metabolism.
Publisher: Wiley
Date: 31-07-2014
DOI: 10.1111/JSR.12197
Abstract: The Karolinska Sleepiness Scale and Samn-Perelli fatigue ratings, and psychomotor vigilance task performance are proposed as measures for monitoring commercial pilot fatigue. In laboratory studies, they are sensitive to sleep/wake history and circadian phase. The present analyses examined whether they reliably reflect sleep/wake history and circadian phase during transmeridian flight operations. Data were combined from four studies (237 pilots, 730 out-and-back flights between 13 city pairs, 1-3-day layovers). Sleep was monitored (wrist actigraphy, logbooks) before, during and after trips. On duty days, sleepiness, fatigue and mean response speed were measured pre-flight and at the top of the descent. Mixed-model analysis of variance examined associations between these measures and sleep/wake history, after controlling for operational factors. Circadian phase was approximated by local (domicile) time in the city where each trip began and ended. More sleep in the 24 h prior to duty was associated with lower pre-flight sleepiness and fatigue and faster response speed. Sleepiness and fatigue were greater before flights departing during the domicile night and early morning. At the top of the descent, pilots felt less sleepy and fatigued after more in-flight sleep and less time awake. Flights arriving in the early-mid-morning (domicile time) had greater sleepiness and fatigue and slower response speeds than flights arriving later. Subjective ratings showed expected associations with sleep/wake history and circadian phase. The response speed showed expected circadian variation but was not associated with sleep/wake history at the top of the descent. This may reflect moderate levels of fatigue at this time and/or atypically fast responses among pilots.
Publisher: Elsevier BV
Date: 02-2017
DOI: 10.1016/J.CELREP.2017.02.009
Abstract: Intergenic long noncoding RNAs (lincRNAs) are the largest class of transcripts in the human genome. Although many have recently been linked to complex human traits, the underlying mechanisms for most of these transcripts remain undetermined. We investigated the regulatory roles of a high-confidence and reproducible set of 69 trait-relevant lincRNAs (TR-lincRNAs) in human lymphoblastoid cells whose biological relevance is supported by their evolutionary conservation during recent human history and genetic interactions with other trait-associated loci. Their enrichment in enhancer-like chromatin signatures, interactions with nearby trait-relevant protein-coding loci, and preferential location at topologically associated domain (TAD) boundaries provide evidence that TR-lincRNAs likely regulate proximal trait-relevant gene expression in cis by modulating local chromosomal architecture. This is consistent with the positive and significant correlation found between TR-lincRNA abundance and intra-TAD DNA-DNA contacts. Our results provide insights into the molecular mode of action by which TR-lincRNAs contribute to complex human traits.
Publisher: Springer Science and Business Media LLC
Date: 12-05-2011
Publisher: Aerospace Medical Association
Date: 08-2015
Publisher: MDPI AG
Date: 21-12-2011
DOI: 10.3390/GENES3010035
Publisher: Aerospace Medical Association
Date: 08-2014
Publisher: Public Library of Science (PLoS)
Date: 22-03-2018
Publisher: Elsevier BV
Date: 07-2020
Publisher: EMBO
Date: 23-01-2023
Abstract: C. elegans develops through four larval stages that are rhythmically terminated by molts, that is, the synthesis and shedding of a cuticular exoskeleton. Each larval cycle involves rhythmic accumulation of thousands of transcripts, which we show here relies on rhythmic transcription. To uncover the responsible gene regulatory networks (GRNs), we screened for transcription factors that promote progression through the larval stages and identified GRH‐1, BLMP‐1, NHR‐23, NHR‐25, MYRF‐1, and BED‐3. We further characterize GRH‐1, a Grainyhead/LSF transcription factor, whose orthologues in other animals are key epithelial cell‐fate regulators. We find that GRH‐1 depletion extends molt durations, impairs cuticle integrity and shedding, and causes larval death. GRH‐1 is required for, and accumulates prior to, each molt, and preferentially binds to the promoters of genes expressed during this time window. Binding to the promoters of additional genes identified in our screen furthermore suggests that we have identified components of a core molting‐clock GRN. Since the mammalian orthologues of GRH‐1, BLMP‐1 and NHR‐23, have been implicated in rhythmic homeostatic skin regeneration in mouse, the mechanisms underlying rhythmic C. elegans molting may apply beyond nematodes.
Publisher: MDPI AG
Date: 13-09-2020
DOI: 10.3390/NU12092804
Abstract: This is a follow-up of our previous postprandial study and it focused on the plasma lipidomic responses to 30 days of krill oil (KO) versus fish oil (FO) supplementations in healthy women. Eleven women (aged 18–50 years) consumed KO or FO for 30 days in a randomized, cross-over study, with at least a four-week washout period between supplementations. The daily supplements provided 1.27 g/day of long-chain (LC) omega-3 polyunsaturated fatty acids (PUFA) from KO (containing 0.76 g eicosapentaenoic acid (EPA), 0.42 g docosahexaenoic acid (DHA)) and 1.44 g/day from FO (containing 0.79 g EPA, 0.47 g DHA). Fasting plasma s les at days 0, 15, and 30 were analyzed using gas chromatography and liquid chromatography electrospray ionisation-tandem mass spectrometry. KO resulted in a significantly greater relative area under the curve (relAUC) for plasma EPA after 30 days. Lipidomic analysis showed that 26 of 43 lipid molecular species had a significantly greater relAUC in the KO group, while 17/43 showed a significantly lower relAUC compared with the FO group. More than 38% of the lipids species which increased more following KO contained omega-3 PUFA, while where FO was greater than KO, only 12% contained omega-3 PUFA. These data show that KO and FO do not have equivalent effects on the plasma lipidome.
Publisher: Oxford University Press (OUP)
Date: 10-12-2008
DOI: 10.1093/BIOINFORMATICS/BTN637
Abstract: Summary: The R package SIMoNe (Statistical Inference for MOdular NEtworks) enables inference of gene-regulatory networks based on partial correlation coefficients from microarray experiments. Modelling gene expression data with a Gaussian graphical model (hereafter GGM), the algorithm estimates non-zero entries of the concentration matrix, in a sparse and possibly high-dimensional setting. Its originality lies in the fact that it searches for a latent modular structure to drive the inference procedure through adaptive penalization of the concentration matrix. Availability: Under the GNU General Public Licence at eb ackages/simone/ Contact: julien.chiquet@genopole.cnrs.fr
Publisher: Springer Science and Business Media LLC
Date: 06-06-2022
DOI: 10.1038/S41467-022-30875-7
Abstract: We integrated lipidomics and genomics to unravel the genetic architecture of lipid metabolism and identify genetic variants associated with lipid species putatively in the mechanistic pathway for coronary artery disease (CAD). We quantified 596 lipid species in serum from 4,492 in iduals from the Busselton Health Study. The discovery GWAS identified 3,361 independent lipid-loci associations, involving 667 genomic regions (479 previously unreported), with validation in two independent cohorts. A meta-analysis revealed an additional 70 independent genomic regions associated with lipid species. We identified 134 lipid endophenotypes for CAD associated with 186 genomic loci. Associations between independent lipid-loci with coronary atherosclerosis were assessed in ∼456,000 in iduals from the UK Biobank. Of the 53 lipid-loci that showed evidence of association ( P 1 × 10 −3 ), 43 loci were associated with at least one lipid endophenotype. These findings illustrate the value of integrative biology to investigate the aetiology of atherosclerosis and CAD, with implications for other complex diseases.
Publisher: The Endocrine Society
Date: 04-2020
DOI: 10.1210/JENDSO/BVAA046.1262
Abstract: Nrf2 (Nfe2l2) is a transcription factor that regulates a series of cytoprotective and antioxidant enzymes. Its cytoplasmic inhibitor Keap1 senses the presence of oxidative or electrophilic stress though the interaction of sulfhydryl groups of its cysteines with reactive species and ceases to bind Nrf2. Thus, Nrf2 can transfer to the nucleus and induce its target genes. Follicular thyroid cells have physiologically high levels of reactive oxygen species as oxidation of iodine is essential for iodination of thyroglobulin and thyroid hormones synthesis. We have shown previously that Nrf2 pathway is active in thyroid and regulates the transcription of thyroglobulin. We thus hypothesized that the response of thyroid to iodine excess should comprise Nrf2-dependent and -independent pathways. To this end, 3 months-old male C57Bl6J WT or Nrf2 knockout (KO) mice were exposed to 0.05% sodium iodide in their water for 7 days. Thyroids were excised and used for RNA extraction RNA-seq was performed by Exiqon, with a fold-change cutoff set at 2. Selected representative genes of the enriched pathways were quantified by real-time qPCR to validate RNA-seq results. Pathway analysis of the differentially expressed genes was performed using the Ingenuity Pathway Analysis (IPA) software. Pathways that were enriched with a p-value& .05 were considered significant. 828 genes were differentially expressed in response to iodine exposure 66% were upregulated, as were most of the highly enriched pathways (related to inflammatory-immune response, antioxidant response, xenobiotic metabolism, platelet activation and calcium signaling). About 300 genes were differentially expressed between WT and KO mice highly enriched pathways were related to glutathione and xenobiotic metabolism, Ahr signaling and Nrf2 signaling and were all downregulated in KO mice. Analysis of the potential upstream regulators of these highly enriched pathways revealed that Nrf2 and NfkB are major regulators of the antioxidant and inflammatory response induction upon iodine exposure and that Tgfβ-Smad cascade regulates the induction of fibrosis signaling. Last, we performed an analysis limited to already known thyroid pathways. A few genes were enriched following this method upregulation of Duoxa1 (hydrogen peroxide generator) and downregulation of Nis (sodium iodide symporter) upon iodine exposure, which are expected responses, and the downregulation of thyroglobulin and upregulation of Duoxa1 in KO mice that confirm our previous findings. In conclusion, Nrf2-driven cytoprotective response is upregulated after iodine overload along with induction of inflammatory pathways. Nrf2 regulates transcriptomic responses in the thyroid, including a small but significant part of the response to iodine challenge. Hence, Nrf2 can be considered a novel player in the frontiers of thyroid antioxidant response and thyroid economy.
Publisher: Elsevier BV
Date: 2021
Publisher: Springer Science and Business Media LLC
Date: 10-11-2020
DOI: 10.1038/S41467-020-19473-7
Abstract: Changes to lipid metabolism are tightly associated with the onset and pathology of Alzheimer’s disease (AD). Lipids are complex molecules comprising many isomeric and isobaric species, necessitating detailed analysis to enable interpretation of biological significance. Our expanded targeted lipidomics platform (569 species across 32 classes) allows for detailed lipid separation and characterisation. In this study we examined peripheral s les of two cohorts (AIBL, n = 1112 and ADNI, n = 800). We are able to identify concordant peripheral signatures associated with prevalent AD arising from lipid pathways including ether lipids, sphingolipids (notably GM 3 gangliosides) and lipid classes previously associated with cardiometabolic disease (phosphatidylethanolamine and triglycerides). We subsequently identified similar lipid signatures in both cohorts with future disease. Lastly, we developed multivariate lipid models that improved classification and prediction. Our results provide a holistic view between the lipidome and AD using a comprehensive approach, providing targets for further mechanistic investigation.
Publisher: Elsevier BV
Date: 12-2014
DOI: 10.1016/J.SLEEP.2014.07.007
Abstract: To compare the prevalence of self-reported abnormal sleep duration and excessive daytime sleepiness in pregnancy among Māori (indigenous New Zealanders) and non-Māori women versus the general population, and to examine the influence of socio-demographic factors. Self-reported total sleep time (TST) in 24-hrs, Epworth Sleepiness Scale scores and socio-demographic information were obtained from nullipara and multipara women aged 20-46 yrs at 35-37 weeks pregnant (358 Māori and 717 non-Māori), and women in the general population (381 Māori and 577 non-Māori). After controlling for ethnicity, age, socio-economic status, and employment status, pregnant women average 30 min less TST than women in the general population. The distribution of TST was also greater in pregnant women, who were 3 times more likely to be short sleepers (≤6 h) and 1.9 times more likely to be long sleepers (>9 h). In addition, pregnant women were 1.8 times more likely to report excessive daytime sleepiness (EDS). Pregnant women >30 years of age experienced greater age-related declines in TST. Identifying as Māori, being unemployed, and working at night increased the likelihood of reporting abnormal sleep duration across all women population in this study. EDS also more likely occurred among Māori women and women who worked at night. Pregnancy increases the prevalence of abnormal sleep duration and EDS, which are also higher among Māori than non-Māori women and those who do night work. Health professionals responsible for the care of pregnant women need to be well-educated about the importance of sleep and discuss sleep issues with the women they care for.
Publisher: Rockefeller University Press
Date: 02-12-2016
DOI: 10.1084/JEM.20160470
Abstract: The dendritic cell signals required for the in vivo priming of IL-4–producing T cells are unknown. We used RNA sequencing to characterize DCs from skin LN of mice exposed to two different Th2 stimuli: the helminth parasite Nippostrongylus brasiliensis (Nb) and the contact sensitizer dibutyl phthalate (DBP)-FITC. Both Nb and DBP-FITC induced extensive transcriptional changes that involved multiple DC subsets. Surprisingly, these transcriptional changes were highly distinct in the two models, with only a small number of genes being similarly regulated in both conditions. Pathway analysis of expressed genes identified no shared pathways between Nb and DBP-FITC, but revealed a type-I IFN (IFN-I) signature unique to DCs from Nb-primed mice. Blocking the IFN-I receptor at the time of Nb treatment had little effect on DC migration and antigen transport to the LN, but inhibited the up-regulation of IFN-I–induced markers on DCs and effectively blunted Th2 development. In contrast, the response to DBP-FITC was not affected by IFN-I receptor blockade, a finding consistent with the known dependence of this response on the innate cytokine TSLP. Thus, the priming of Th2 responses is associated with distinct transcriptional signatures in DCs in vivo, reflecting the erse environments in which Th2 immune responses are initiated.
Publisher: Springer Science and Business Media LLC
Date: 17-11-2013
Abstract: Millions of protein database entries are not assigned reliable functions, preventing the full understanding of chemical ersity in living organisms. Here, we describe an integrated strategy for the discovery of various enzymatic activities catalyzed within protein families of unknown or little known function. This approach relies on the definition of a generic reaction conserved within the family, high-throughput enzymatic screening on representatives, structural and modeling investigations and analysis of genomic and metabolic context. As a proof of principle, we investigated the DUF849 Pfam family and unearthed 14 potential new enzymatic activities, leading to the designation of these proteins as β-keto acid cleavage enzymes. We propose an in vivo role for four enzymatic activities and suggest key residues for guiding further functional annotation. Our results show that the functional ersity within a family may be largely underestimated. The extension of this strategy to other families will improve our knowledge of the enzymatic landscape.
Publisher: Elsevier BV
Date: 02-2020
DOI: 10.1016/J.SLEH.2019.11.004
Abstract: To investigate the association between measures of sleep quality, sleep duration and sleep disorder symptoms in late pregnancy and likelihood of emergency caesarean section. Population-based prospective cohort study SETTING: New Zealand PARTICIPANTS: 310 Māori (Indigenous New Zealanders) and 629 non-Māori women MEASUREMENTS: Multivariable logistic regression models were used to investigate the association between type of delivery (emergency caesarean section vs. spontaneous vaginal delivery) and self-reported sleep duration, sleep quality and sleep-related symptoms, (e.g. snoring, breathing pauses during sleep, legs twitching/jerking) in the third trimester of pregnancy. Models were adjusted by ethnicity (ref=non-Māori), age (ref=16-19 y), parity (ref=nulliparous), clinical indicators (any vs. none), area deprivation (ref=least deprived quintile), BMI and for some models smoking. Women who reported poor quality sleep as measured by the General Sleep Disturbance Scale in later pregnancy had almost twice the odds of delivering via emergency caesarean than women with good sleep quality (OR=1.98, 95% CI 1.18-3.31). Reporting current breathing pauses during sleep (OR=3.27, 95% CI 1.38-7.74) or current snoring (OR=1.65, 95% CI 1.00-2.72) were also independently associated with a higher likelihood of an emergency caesarean. Short sleep duration and leg twitching/jerking were not independently associated with emergency caesarean section in this study. Supporting healthy sleep during pregnancy could be a novel intervention to reduce the risks associated with emergency caesarean section. Research on the effectiveness of sleep interventions for reducing caesarean section risk is required.
Publisher: Aerospace Medical Association
Date: 12-2014
Publisher: Public Library of Science (PLoS)
Date: 31-05-2012
Publisher: Aerospace Medical Association
Date: 02-2014
Abstract: Implementation of Fatigue Risk Management Systems (FRMS) is gaining momentum however, agreed safety performance indicators (SPIs) are lacking. This paper proposes an initial set of SPIs based on measures of crewmember sleep, performance, and subjective fatigue and sleepiness, together with methods for interpreting them. Data were included from 133 landing crewmembers on 2 long-range and 3 ultra-long-range trips (4-person crews, 3 airlines, 220 flights). Studies had airline, labor, and regulatory support, and underwent independent ethical review. SPIs evaluated preflight and at top of descent (TOD) were: total sleep in the prior 24 h and time awake at duty start and at TOD (actigraphy) subjective sleepiness (Karolinska Sleepiness Scale) and fatigue (Samn-Perelli scale) and psychomotor vigilance task (PVT) performance. Kruskal-Wallis nonparametric ANOVA with post hoc tests was used to identify significant differences between flights for each SPI. Visual and preliminary quantitative comparisons of SPIs between flights were made using box plots and bar graphs. Statistical analyses identified significant differences between flights across a range of SPls. In an FRMS, crew fatigue SPIs are envisaged as a decision aid alongside operational SPIs, which need to reflect the relevant causes of fatigue in different operations. We advocate comparing multiple SPIs between flights rather than defining safe/unsafe thresholds on in idual SPIs. More comprehensive data sets are needed to identify the operational and biological factors contributing to the differences between flights reported here. Global sharing of an agreed core set of SPIs would greatly facilitate implementation and improvement of FRMS.
Publisher: MDPI AG
Date: 18-09-2020
Abstract: Background: Thyroid follicular cells have physiologically high levels of reactive oxygen species because oxidation of iodide is essential for the iodination of thyroglobulin (Tg) during thyroid hormone synthesis. Thyroid follicles (the functional units of the thyroid) also utilize incompletely understood autoregulatory mechanisms to defend against exposure to excess iodide. To date, no transcriptomic studies have investigated these phenomena in vivo. Nuclear erythroid factor 2 like 2 (Nrf2 or Nfe2l2) is a transcription factor that regulates the expression of numerous antioxidant and other cytoprotective genes. We showed previously that the Nrf2 pathway regulates the antioxidant defense of follicular cells, as well as Tg transcription and Tg iodination. We, thus, hypothesized that Nrf2 might be involved in the transcriptional response to iodide overload. Methods: C57BL6/J wild-type (WT) or Nrf2 knockout (KO) male mice were administered regular water or water supplemented with 0.05% sodium iodide for seven days. RNA from their thyroids was prepared for next-generation RNA sequencing (RNA-Seq). Gene expression changes were assessed and pathway analyses were performed on the sets of differentially expressed genes. Results: Analysis of differentially expressed messenger RNAs (mRNAs) indicated that iodide overload upregulates inflammatory-, immune-, fibrosis- and oxidative stress-related pathways, including the Nrf2 pathway. Nrf2 KO mice showed a more pronounced inflammatory–autoimmune transcriptional response to iodide than WT mice. Compared to previously published datasets, the response patterns observed in WT mice had strong similarities with the patterns typical of Graves’ disease and papillary thyroid carcinoma (PTC). Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) also responded to iodide overload, with the latter targeting mRNAs that participate mainly in inflammation pathways. Conclusions: Iodide overload induces the Nrf2 cytoprotective response and upregulates inflammatory, immune, and fibrosis pathways similar to autoimmune hyperthyroidism (Graves’ disease) and PTC.
Publisher: CSIRO Publishing
Date: 2016
DOI: 10.1071/AH15126
Abstract: Objective Residential aged care services are challenged by an increasing number of residents and a shortage of nursing staff. Developing strategies to overcome this challenge requires an understanding of nursing staff work patterns. The aim of the present study was to investigate the work processes followed by nursing staff and how nursing time is allocated in a residential aged care home. Methods An observational time–motion study was conducted at two aged care units for 12 morning shifts. Seven nurses were observed, one per shift. Results In all, there were 91 h of observation. The results showed that there was a common work process followed by all nurse participants. Medication administration, documentation and verbal communication were the most time-consuming activities and were conducted most frequently. No significant difference between the two units was found in any category of activities. The average duration of most activities was less than 1 min. There was no difference in time utilisation between the endorsed enrolled nurses and the personal carers in providing nursing care. Conclusion Medication administration, documentation and verbal communication were the major tasks in morning shifts in a residential aged care home. Future research can investigate how verbal communication supports nursing care. What is known about the topic? The aging population will substantially increase the demand for residential aged care services. There is a lack of research on nurses’ work patterns in residential aged care homes. What does this paper add? The present study provides a comprehensive understanding of nurses’ work patterns in a residential aged care home. There is a common work process followed by nurses in providing nursing care. Medication administration, verbal communication and documentation are the most time-consuming activities and they are frequently conducted in the same period of time. Wound care, physical review and documentation on desktop computers are arranged flexibly by the nurses. What are the implications for practitioners? When developing a task reallocation strategy to improve work efficiency, effort can be put into tasks that can be arranged more flexibly.
Publisher: Elsevier BV
Date: 09-2019
DOI: 10.1016/J.NUT.2019.03.021
Abstract: There is no convincing evidence that krill oil (KO) consumption results in a higher incorporation of long chain ω-3 polyunsaturated fatty acids into blood lipid fractions than fish oil (FO). This study examined the postprandial plasma lipidomic responses to KO supplementation compared with FO supplementation in healthy women. Ten women (aged 18-45 y) consumed a high-fat (15 g of olive oil) breakfast, supplemented with 5 g of KO or FO in a randomized crossover study with a minimum 7-d washout period between the supplementations. Plasma s les collected at the fasting state and at 3 and 5 h postprandially were analyzed using liquid chromatography electrospray ionization-tandem mass spectrometry. After the supplementations, 5 out of 34 lipid classes or subclasses had significantly greater concentrations from KO compared with FO. There were 27 molecular species including 5 ether-phospholipid species, out of a total of 701, which had significant differences between supplementations in the postprandial period. Eicosapentaenoic acid and docosahexaenoic acid from KO were preferentially partitioned toward phospholipid molecular species, whereas eicosapentaenoic acid and docosahexaenoic acid from FO were preferentially partitioned toward neutral lipids.
Publisher: MDPI AG
Date: 06-05-2021
Abstract: Plasmalogens or alkenylphospholipids are a sub-class of glycerophospholipids with numerous biological functions and are thought to have protective effects against metabolic disease. Dietary supplementation with alkylglycerols (AKGs) has been shown to increase endogenous plasmalogen levels, however effective modulation of different molecular plasmalogen species has not yet been demonstrated. In this study, the effects of an orally-administered AKG mix (a mixture of chimyl, batyl and selachyl alcohol at a 1:1:1 ratio) on plasma and tissue lipids, including plasmalogens, was evaluated. Mice on a Western-type diet were treated with either an AKG mix or vehicle (lecithin) for 1, 2, 4, 8 and 12 weeks. Treatment with the AKG mix significantly increased the total plasmalogen content of plasma, liver and adipose tissue as a result of elevations in multiple plasmalogen species with different alkenyl chains. Alkylphospholipids, the endogenous precursors of plasmalogens, showed a rapid and significant increase in plasma, adipose tissue, liver and skeletal muscle. A significant accumulation of alkyl-diacylglycerol and lyso-ether phospholipids was also observed in plasma and tissues. Additionally, the dynamics of plasmalogen-level changes following AKG mix supplementation differed between tissues. These findings indicate that oral supplementation with an AKG mix is capable of upregulating and maintaining stable expression of multiple molecular plasmalogen species in circulation and tissues.
Publisher: Springer Science and Business Media LLC
Date: 20-02-2020
DOI: 10.1038/S41598-020-60020-7
Abstract: Colorectal cancer is a major contributor to death and disease worldwide. The Apc Min mouse is a widely used model of intestinal neoplasia, as it carries a mutation also found in human colorectal cancers. However, the method most commonly used to quantify tumour burden in these mice is manual adenoma counting, which is time consuming and poorly suited to standardization across different laboratories. We describe a method to produce suitable photographs of the small intestine of Apc Min mice, process them with an ImageJ macro, FeatureCounter , which automatically locates image features potentially corresponding to adenomas, and a machine learning pipeline to identify and quantify them. Compared to a manual method, the specificity (or True Negative Rate, TNR) and sensitivity (or True Positive Rate, TPR) of this method in detecting adenomas are similarly high at about 80% and 87%, respectively. Importantly, total adenoma area measures derived from the automatically-called tumours were just as capable of distinguishing high-burden from low-burden mice as those established manually. Overall, our strategy is quicker, helps control experimenter bias, and yields a greater wealth of information about each tumour, thus providing a convenient route to getting consistent and reliable results from a study.
Publisher: American Diabetes Association
Date: 28-10-2020
DOI: 10.2337/DB20-0653
Abstract: The incidence of atrial fibrillation (AF) is higher in patients with diabetes. The goal of this study was to assess if the addition of plasma lipids to traditional risk factors could improve the ability to detect and predict future AF in patients with type 2 diabetes. Logistic regression models were used to identify lipids associated with AF or future AF from plasma lipids (n = 316) measured from participants in the ADVANCE trial (n = 3,772). To gain mechanistic insight, follow-up lipid analysis was undertaken in a mouse model that has an insulin-resistant heart and is susceptible to AF. Sphingolipids, cholesteryl esters, and phospholipids were associated with AF prevalence, whereas two monosialodihexosylganglioside (GM3) ganglioside species were associated with future AF. For AF detection and prediction, addition of six and three lipids, respectively, to a base model (n = 12 conventional risk factors) increased the C-statistics (detection: from 0.661 to 0.725 prediction: from 0.674 to 0.715) and categorical net reclassification indices. The GM3(d18:1/24:1) level was lower in patients in whom AF developed, improved the C-statistic for the prediction of future AF, and was lower in the plasma of the mouse model susceptible to AF. This study demonstrates that plasma lipids have the potential to improve the detection and prediction of AF in patients with diabetes.
Publisher: MDPI AG
Date: 27-05-2022
DOI: 10.3390/PH15060669
Abstract: Hookworm infections cause a neglected tropical disease (NTD) affecting ~740 million people worldwide, principally those living in disadvantaged communities. Infections can cause high morbidity due to their impact on nutrient uptake and their need to feed on host blood, resulting in a loss of iron and protein, which can lead to severe anaemia and impaired cognitive development in children. Currently, only one drug, albendazole is efficient to treat hookworm infection and the scientific community fears the rise of resistant strains. As part of on-going efforts to control hookworm infections and its associated morbidities, new drugs are urgently needed. We focused on targeting the blood-feeding pathway, which is essential to the parasite survival and reproduction, using the laboratory hookworm model Nippostrongylus brasiliensis (a nematode of rodents with a similar life cycle to hookworms). We established an in vitro-drug screening assay based on a fluorescent-based measurement of parasite viability during blood-feeding to identify novel therapeutic targets. A first screen of a library of 2654 natural compounds identified four that caused decreased worm viability in a blood-feeding-dependent manner. This new screening assay has significant potential to accelerate the discovery of new drugs against hookworms.
Publisher: Public Library of Science (PLoS)
Date: 28-09-2020
No related grants have been discovered for Adam SMITH.