ORCID Profile
0000-0002-0212-1207
Current Organisation
Deakin University
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: Elsevier BV
Date: 02-2020
Publisher: Wiley
Date: 29-04-2019
DOI: 10.1111/JPC.14436
Abstract: The burden of wheezing illnesses in Australian infants has not been documented since the success of initiatives to reduce maternal cigarette smoking. We aimed to determine the incidence of wheeze and related health-care utilisation during the first year of life among a contemporary Australian birth cohort. A birth cohort of 1074 infants was assembled between 2010 and 2013. Parents completed questionnaires periodically. Several non-exclusive infant respiratory disease phenotypes were defined, including any wheeze, wheeze with shortness of breath and recurrent wheeze. Skin prick testing was performed to determine atopic wheeze. Health-care utilisation for respiratory disease was determined from questionnaires and hospital medical records. Retention to 1 year was 840/1074 (83%). The incidence of any wheeze was 51.8% (95% confidence interval (CI) 48.3-55.2%), wheeze with shortness of breath 20.6% (95% CI 17.9-23.5), recurrent wheeze 19.4% (95% CI 16.8-22.2) and atopic wheeze 6% (95% CI 4.6-7.8). Respiratory illness resulted in primary health-care utilisation in 82.2% (95% CI 79.3-84.8) of participants and hospital presentation in 8.8% (95% CI 7.2-10.6). Maternal smoking during pregnancy was uncommon (15.7%) and was not associated with wheeze or health resource utilisation. Male gender, familial atopy and asthma and smaller household size were associated with a higher incidence of wheeze. The incidence of wheezing illness among Australian infants remains high despite relatively low rates of maternal smoking during pregnancy. The majority of the health-care burden is borne by primary health-care services. Further research is required to inform novel prevention strategies.
Publisher: Frontiers Media SA
Date: 31-03-2017
Publisher: eLife Sciences Publications, Ltd
Date: 06-02-2017
DOI: 10.7554/ELIFE.19944
Abstract: During apoptosis, Bak and Bax undergo major conformational change and form symmetric dimers that coalesce to perforate the mitochondrial outer membrane via an unknown mechanism. We have employed cysteine labelling and linkage analysis to the full length of Bak in mitochondria. This comprehensive survey showed that in each Bak dimer the N-termini are fully solvent-exposed and mobile, the core is highly structured, and the C-termini are flexible but restrained by their contact with the membrane. Dimer-dimer interactions were more labile than the BH3:groove interaction within dimers, suggesting there is no extensive protein interface between dimers. In addition, linkage in the mobile Bak N-terminus (V61C) specifically quantified association between dimers, allowing mathematical simulations of dimer arrangement. Together, our data show that Bak dimers form disordered clusters to generate lipidic pores. These findings provide a molecular explanation for the observed structural heterogeneity of the apoptotic pore.
Publisher: eLife Sciences Publications, Ltd
Date: 29-12-2016
Publisher: Springer Science and Business Media LLC
Date: 24-03-2020
DOI: 10.1038/S41467-020-14552-1
Abstract: In mice, the maternal microbiome influences fetal immune development and postnatal allergic outcomes. Westernized populations have high rates of allergic disease and low rates of gastrointestinal carriage of Prevotella , a commensal bacterial genus that produces short chain fatty acids and endotoxins, each of which may promote the development of fetal immune tolerance. In this study, we use a prebirth cohort ( n = 1064 mothers) to conduct a nested case-cohort study comparing 58 mothers of babies with clinically proven food IgE mediated food allergy with 258 randomly selected mothers. Analysis of the V4 region of the 16S rRNA gene in fecal s les shows maternal carriage of Prevotella copri during pregnancy strongly predicts the absence of food allergy in the offspring. This association was confirmed using targeted qPCR and was independent of infant carriage of P. copri . Larger household size, which is a well-established protective factor for allergic disease, strongly predicts maternal carriage of P. copri .
Publisher: SPIE
Date: 04-10-1999
DOI: 10.1117/12.364023
Publisher: Springer Science and Business Media LLC
Date: 16-10-2023
Publisher: Elsevier BV
Date: 06-2007
DOI: 10.1016/J.JTBI.2007.01.025
Abstract: Consider the appearance of a duplicate copy of a gene at a locus linked loosely, if at all, to the locus at which the gene is usually found. If all copies of the gene are subject to non-functionalizing mutations, then two fates are possible: loss of functional copies at the duplicate locus (loss of duplicate expression), or loss of functional copies at the original locus (map change). This paper proposes a simple model to address the probability of map change, the time taken for a map change and/or loss of duplicate expression, and considers where in the spectrum between loss of duplicate expression and map change such a duplicate complex is likely to be found. The findings are: the probability of map change is always half the reciprocal of the population size N, the time for a map change to occur is order NlogN generations, and that there is a marked tendency for duplicates to remain near equi-frequency with the gene at the original locus for a large portion of that time. This is in excellent agreement with simulations.
Publisher: Cambridge University Press (CUP)
Date: 17-12-2019
DOI: 10.1017/S2040174419000849
Abstract: Gut bacteria from the genus Prevotella are found in high abundance in faeces of non-industrialised communities but low abundance in industrialised, Westernised communities. Prevotella copri is one of the principal Prevotella species within the human gut. As it has been associated with developmental health and disease states, we sought to (i) develop a real-time polymerase chain reaction (PCR) to rapidly determine P. copri abundance and (ii) investigate its abundance in a large group of Australian pregnant mothers. The Barwon Infant Study is a pre-birth cohort study ( n = 1074). Faecal s les were collected from mothers at 36 weeks gestation. Primers with a probe specific to the V3 region of P. copri 16S rRNA gene were designed and optimised for real-time PCR. Universal 16S rRNA gene primers lified pan-bacterial DNA in parallel. Relative abundance of P. copri was calculated using a 2 -Δ Ct method. Relative abundance of P. copri by PCR was observed in 165/605 (27.3%) women. The distribution was distinctly bimodal, defining women with substantial ( n = 115/165, 69.7%) versus very low P. copri expression ( n = 50/165, 30.3%). In addition, abundance of P. copri by PCR correlated with 16S rRNA gene MiSeq sequencing data ( r 2 = 0.67, P 0.0001, n = 61). We have developed a rapid and cost-effective technique for identifying the relative abundance of P. copri using real-time PCR. The expression of P. copri was evident in only a quarter of the mothers, and either at substantial or very low levels. PCR detection of P. copri may facilitate assessment of this species in large, longitudinal studies across multiple populations and in various clinical settings.
Publisher: Elsevier BV
Date: 06-2007
DOI: 10.1016/J.TPB.2007.01.003
Abstract: Suppose one chromosome in one member of a population somehow acquires a duplicate copy of the gene, fully linked to the original gene's locus. Preservation is the event that eventually every chromosome in the population is a descendant of the one which initially carried the duplicate. For a haploid population in which the absence of all copies of the gene is lethal, the probability of preservation has recently been estimated via a diffusion approximation. That approximation is shown to carry over to the case of diploids and arbitrary strong selection against the absence of the gene. The techniques used lead to some new results. In the large population limit, it is shown that the relative probability that descendants of a small number of in iduals carrying multiple copies of the gene fix in the population is proportional to the number of copies carried. The probability of preservation is approximated when chromosomes carrying two copies of the gene are subject to additional, fully non-functionalizing mutations, thereby modelling either an additional cost of replicating a longer genome, or a partial duplication of the gene. In the latter case the preservation probability depends only on the mutation rate to null for the duplicated portion of the gene.
Publisher: Springer Science and Business Media LLC
Date: 16-04-2013
DOI: 10.1038/LEU.2013.116
Publisher: Springer Science and Business Media LLC
Date: 23-04-2015
Abstract: The mitochondrial pathway of apoptosis is initiated by Bcl-2 homology region 3 (BH3)-only members of the Bcl-2 protein family. On upregulation or activation, certain BH3-only proteins can directly bind and activate Bak and Bax to induce conformation change, oligomerization and pore formation in mitochondria. BH3-only proteins, with the exception of Bid, are intrinsically disordered and therefore, functional studies often utilize peptides based on just their BH3 domains. However, these reagents do not possess the hydrophobic membrane targeting domains found on the native BH3-only molecule. To generate each BH3-only protein as a recombinant protein that could efficiently target mitochondria, we developed recombinant Bid chimeras in which the BH3 domain was replaced with that of other BH3-only proteins (Bim, Puma, Noxa, Bad, Bmf, Bik and Hrk). The chimeras were stable following purification, and each immunoprecipitated with full-length Bcl-x L according to the specificity reported for the related BH3 peptide. When tested for activation of Bak and Bax in mitochondrial permeabilization assays, Bid chimeras were ~1000-fold more effective than the related BH3 peptides. BH3 sequences from Bid and Bim were the strongest activators, followed by Puma, Hrk, Bmf and Bik, while Bad and Noxa were not activators. Notably, chimeras and peptides showed no apparent preference for activating Bak or Bax. In addition, within the BH3 domain, the h0 position recently found to be important for Bax activation, was important also for Bak activation. Together, our data with full-length proteins indicate that most BH3-only proteins can directly activate both Bak and Bax.
Publisher: The American Association of Immunologists
Date: 15-02-2021
Abstract: Vitamin D has shown immune-modulatory effects but mostly in in vitro and animal studies. Regulatory T cells (Treg) are important for a balanced immune system. The relationship between vitamin D on the number of circulating neonatal Treg is unclear. We sought to investigate the association between maternal and neonatal vitamin D metabolites and cord blood (CB) Treg subsets. In a cohort of Australian infants (n = 1074), recruited using an unselected antenatal s ling frame, 158 mother–infant pairs had data on the following: 1) 25-hydroxyvitamin D3 (25(OH)D3) measures in both maternal peripheral blood (28- to 32-wk gestation) and infant CB 2) proportions (percentage of CD4+ T cells) of CB Treg subsets (CD4+CD45RA+ FOXP3low naive Treg, and CD4+CD45RA− FOXP3high activated Treg [aTreg]) and 3) possible confounders, including maternal personal UV radiation. Multiple regression analyses were used. The median 25(OH)D3 was 85.4 and 50.7 nmol/l for maternal and CB s les, respectively. Higher maternal 25(OH)D3 levels were associated with increased CB naive Treg (relative adjusted mean difference [AMD] per 25 nmol/l increase: 5% 95% confidence interval [CI]: 1–9%), and aTreg (AMD per 25 nmol/l increase: 17% 95% CI: 6–28%). Furthermore, a positive association between CB 25(OH)D3 levels and CB aTreg (AMD per 25 nmol/l increase: 29% 95% CI: 13–48%) was also evident. These results persisted after adjustment for other factors such as maternal personal UV radiation and season of birth. 25(OH)D3, may play a role in the adaptive neonatal immune system via induction of FOXP3+ Tregs. Further studies of immune priming actions of antenatal 25(OH)D3 are warranted.
Publisher: Elsevier BV
Date: 10-2019
Publisher: Springer Science and Business Media LLC
Date: 06-05-2006
DOI: 10.1007/S00285-006-0001-6
Abstract: Consider a haploid population and, within its genome, a gene whose presence is vital for the survival of any in idual. Each copy of this gene is subject to mutations which destroy its function. Suppose one member of the population somehow acquires a duplicate copy of the gene, where the duplicate is fully linked to the original gene's locus. Preservation is said to occur if eventually the entire population consists of in iduals descended from this one which initially carried the duplicate. The system is modelled by a finite state-space Markov process which in turn is approximated by a diffusion process, whence an explicit expression for the probability of preservation is derived. The event of preservation can be compared to the fixation of a selectively neutral gene variant initially present in a single in idual, the probability of which is the reciprocal of the population size. For very weak mutation, this and the probability of preservation are equal, while as mutation becomes stronger, the preservation probability tends to double this reciprocal. This is in excellent agreement with simulation studies.
Publisher: Springer Science and Business Media LLC
Date: 10-07-2019
DOI: 10.1038/S41467-019-10703-1
Abstract: Maternal immune dysregulation seems to affect fetal or postnatal immune development. Preecl sia is a pregnancy-associated disorder with an immune basis and is linked to atopic disorders in offspring. Here we show reduction of fetal thymic size, altered thymic architecture and reduced fetal thymic regulatory T (Treg) cell output in preecl tic pregnancies, which persists up to 4 years of age in human offspring. In germ-free mice, fetal thymic CD4 + T cell and Treg cell development are compromised, but rescued by maternal supplementation with the intestinal bacterial metabolite short chain fatty acid (SCFA) acetate, which induces upregulation of the autoimmune regulator (AIRE), known to contribute to Treg cell generation. In our human cohorts, low maternal serum acetate is associated with subsequent preecl sia, and correlates with serum acetate in the fetus. These findings suggest a potential role of acetate in the pathogenesis of preecl sia and immune development in offspring.
Publisher: Cambridge University Press (CUP)
Date: 03-2001
Abstract: An annihilating process is an interacting particle system in which the only interaction is that a particle may kill a neighbouring particle. Since there is no birth and no movement, once a particle has no neighbours its site remains occupied for ever. It is shown that with initial configuration ℤ the distribution of particles at all times is a renewal process and that the probability that a site remains occupied for all time tends to 1/e. Time-dependent behaviour is also calculated for the tree 𝕋 r .
Publisher: Elsevier BV
Date: 09-2003
DOI: 10.1016/S0040-5809(03)00084-4
Abstract: Case-control studies are used to map loci associated with a genetic disease. The usual case-control study tests for significant differences in frequencies of alleles at marker loci. In this paper, we consider the problem of comparing two or more marker loci simultaneously and testing for significant differences in haplotype rather than allele frequencies. We consider two situations. In the first, genotypes at marker loci are resolved into haplotypes by making use of biochemical methods or by genotyping family members. In the second, genotypes at marker loci are not resolved into haplotypes, but, by assuming random mating, haplotypes can be inferred using a likelihood method such as the expectation-maximization (EM) algorithm. We assume that a causative locus has two alleles with a multiplicative effect on the penetrance of a disease, with one allele increasing the penetrance by a factor pi. We find, for small values of pi-1 and large s le sizes, asymptotic results that predict the statistical power of a test for significant differences in haplotype frequencies between cases and a random s le of the population, both when haplotypes can be resolved and when haplotypes have to be inferred. The increase in power when haplotypes can be resolved can be expressed as a ratio R, which is the increase in s le size needed to achieve the same power when haplotypes are resolved over when they are not resolved. In general, R depends on the pattern of linkage disequilibrium between the causative allele and the marker haplotypes but is independent of the frequency of the causative allele and, to a first approximation, is independent of pi. For the special situation of two di-allelic marker loci, we obtain a simple expression for R and its upper bound.
Publisher: Wiley
Date: 17-01-2019
DOI: 10.1111/ALL.14159
Abstract: A few studies have investigated the antecedents and outcomes of infants who demonstrate IgE sensitization to foods that they clinically tolerate. Improved understanding of this sensitized-tolerant phenotype may inform strategies for the prevention of food allergy. In an Australian birth cohort (n = 1074), assembled using an unselected antenatal s ling frame, participants were categorized as nonsensitized (NS), sensitizedtolerant (ST), or food allergic (FA) based on skin prick testing and food challenge at 12 months of age. Environmental exposures were recorded throughout. Cord blood regulatory T-cell populations were measured at birth. Subsequent childhood allergic disease was assessed by parent report, clinical examination, and repeat skin prick testing. The covariates of interest varied between NS (n = 698), ST (n = 27), and FA (n = 61) groups as follows, suggesting that across these measures, the ST group was more similar to the NS than the FA group: family history of eczema NS 44.6%, ST. 44.6%, FA 65.6% pet ownership at 12 months: NS 71.5%, ST 81.5%, FA 45.8% eczema during the first 12 months: NS 19%, ST 32%, FA 64% and aeroallergen sensitization at 4 years: NS 19.1%, ST 28.6%, FA 44.4%. At birth, a higher proportion of activated regulatory T cells was associated with ST (OR = 2.89, 95% CI 1.03-8.16, P = .045). Food-sensitized-tolerance in infancy appears to be associated with a similar pattern of exposures, immunity, and outcomes to nonsensitized infants. In addition, we found some evidence that an elevated proportion of activated regulatory T cells at birth was specific to the sensitized-tolerant infants, which may be relevant to suppression of clinical disease.
Publisher: Wiley
Date: 02-06-2019
DOI: 10.1111/ALL.13822
Abstract: In previous studies, deficits in regulatory T-cell (Treg) number and function at birth have been linked with subsequent allergic disease. However, longitudinal studies that account for relevant perinatal factors are required. The aim of this study was to investigate the relationship between perinatal factors, naïve Treg (nTreg) over the first postnatal year and development of food allergy. In a birth cohort (n = 1074), the proportion of nTreg in the CD4 A higher proportion of nTreg at birth, larger birth size and male sex was each associated with higher nTreg in infancy. Exposure to labour, as compared to delivery by prelabour Caesarean section, was associated with a transient decrease nTreg. Infants that developed food allergy had decreased nTreg at birth, and the labour-associated decrease in nTreg at birth was more evident among infants with subsequent food allergy. Mode of birth was not associated with risk of food allergy, and there was no evidence that nTreg at either 6 or 12 months were related to food allergy. The proportion of nTreg at birth is a major determinant of the proportion present throughout infancy, highlighting the importance of prenatal immune development. Exposure to the inflammatory stimulus of labour appears to reveal differences in immune function among infants at risk of food allergy.
Publisher: Elsevier BV
Date: 05-2020
Publisher: Elsevier BV
Date: 09-2020
Publisher: Elsevier BV
Date: 1996
Publisher: Oxford University Press (OUP)
Date: 10-05-2012
DOI: 10.1093/BIOINFORMATICS/BTS286
Abstract: Summary: Sequencing by hybridization to oligonucleotides has evolved into an inexpensive, reliable and fast technology for targeted sequencing. Hundreds of human genes can now be sequenced within a day using a single hybridization to a resequencing microarray. However, several issues inherent to these arrays (e.g. cross-hybridization, variable probe/target affinity) cause sequencing errors and have prevented more widespread applications. We developed an R package for resequencing microarray data analysis that integrates a novel statistical algorithm, sequence robust multi-array analysis (SRMA), for rare variant detection with high sensitivity (false negative rate, FNR 5%) and accuracy (false positive rate, FPR 1×10−5). The SRMA package consists of five modules for quality control, data normalization, single array analysis, multi-array analysis and output analysis. The entire workflow is efficient and identifies rare DNA single nucleotide variations and structural changes such as gene deletions with high accuracy and sensitivity. Availability: cran.r-project.org/, odin.mdacc.tmc.edu/~wwang7/SRMAIndex.html Contact: wwang7@mdanderson.org Supplementary information: Supplementary data are available at Bioinformatics online.
Publisher: Elsevier BV
Date: 06-2020
Publisher: Springer Science and Business Media LLC
Date: 2001
Publisher: Wiley
Date: 09-2016
DOI: 10.1111/IMJ.37_13197
No related grants have been discovered for Martin O'Hely.