Stephen J. O'Brien

Bio: Stephen J. O'Brien is an academic researcher from Saint Petersburg State University of Information Technologies, Mechanics and Optics. The author has contributed to research in topics: Population & Gene. The author has an hindex of 153, co-authored 1062 publications receiving 93025 citations. Previous affiliations of Stephen J. O'Brien include University College Cork & QIMR Berghofer Medical Research Institute.

Epizootiology and management of feline leukemia virus in the florida puma

Abstract: Feline leukemia virus (FeLV) was not detected in Florida pumas (Puma concolor coryi) in almost 20 yr of surveillance; however, the finding of two FeLV antigen-positive pumas during the 2002–2003 capture season led to an investigation of FeLV in the population. Between January 1990 and April 2007, the proportion of pumas testing FeLV antibody positive increased, with antibody-positive pumas concentrated in the northern portion of puma range. Five of 131 (4%) pumas sampled between July 2000 and April 2007 were viremic, with all cases clustered in Okaloacoochee Slough (OKS). Clinical signs and clinical pathology at capture were absent or included lymphadenopathy, moderate-to-severe anemia, and lymphopenia. All viremic pumas died; causes of death were septicemia (n=2), intraspecific aggression (n=2), and anemia/dehydration (n=1). Outcome after FeLV exposure in pumas was similar to that in domestic cats, with evidence of regressive, latent, and persistent infections. Management of the epizootic included vaccin...

Public Stem Cell Banks: Considerations of Justice in Stem Cell Research and Therapy

Abstract: If stem cells fulfill their therapeutic promise, moving them from the laboratory into the clinic will raise several concerns about justice. One concern is that, for biological reasons alone, stem cell-based therapies might not be available for every patient who needs one. Worse, depending on how we address the problem of biological access, they might benefit primarily white Americans. We can avoid this outcome—although at a cost—by carefully selecting the stem cells we make available.

Olfactory receptor subgenomes linked with broad ecological adaptations in Sauropsida

Abstract: Olfactory receptors (ORs) govern a prime sensory function. Extant birds have distinct olfactory abilities, but the molecular mechanisms underlining diversification and specialization remain mostly unknown. We explored OR diversity in 48 phylogenetic and ecologically diverse birds and 2 reptiles (alligator and green sea turtle). OR subgenomes showed species- and lineage-specific variation related with ecological requirements. Overall 1,953 OR genes were identified in reptiles and 16,503 in birds. The two reptiles had larger OR gene repertoires (989 and 964 genes, respectively) than birds (182-688 genes). Overall, birds had more pseudogenes (7,855) than intact genes (1,944). The alligator had significantly more functional genes than sea turtle, likely because of distinct foraging habits. We found rapid species-specific expansion and positive selection in OR14 (detects hydrophobic compounds) in birds and in OR51 and OR52 (detect hydrophilic compounds) in sea turtle, suggestive of terrestrial and aquatic adaptations, respectively. Ecological partitioning among birds of prey, water birds, land birds, and vocal learners showed that diverse ecological factors determined olfactory ability and influenced corresponding olfactory-receptor subgenome. OR5/8/9 was expanded in predatory birds and alligator, suggesting adaptive specialization for carnivory. OR families 2/13, 51, and 52 were correlated with aquatic adaptations (water birds), OR families 6 and 10 were more pronounced in vocal-learning birds, whereas most specialized land birds had an expanded OR family 14. Olfactory bulb ratio (OBR) and OR gene repertoire were correlated. Birds that forage for prey (carnivores/piscivores) had relatively complex OBR and OR gene repertoires compared with modern birds, including passerines, perhaps due to highly developed cognitive capacities facilitating foraging innovations.

Biological activity of FGF-23 fragments.

Abstract: The phosphaturic activity of intact, full-length, fibroblast growth factor-23 (FGF-23) is well documented. FGF-23 circulates as the intact protein and as fragments generated as the result of proteolysis of the full-length protein. To assess whether short fragments of FGF-23 are phosphaturic, we compared the effect of acute, equimolar infusions of full-length FGF-23 and various FGF-23 fragments carboxyl-terminal to amino acid 176. In rats, intravenous infusions of full-length FGF-23 and FGF-23 176-251 significantly and equivalently increased fractional phosphate excretion (FE Pi) from 14 +/- 3 to 32 +/- 5% and 15 +/- 2 to 33 +/- 2% (p < 0.001), respectively. Chronic administration of FGF-23 176-251 reduced serum Pi and serum concentrations of 1alpha,25-dihydroxyvitamin D. Shorter forms of FGF-23 (FGF-23 180-251 and FGF-23 184-251) retained phosphaturic activity. Further shortening of the FGF-23 carboxyl-terminal domain, however, abolished phosphaturic activity, as infusion of FGF-23 206-251 did not increase urinary phosphate excretion. Infusion of a short fragment of the FGF-23 molecule, FGF-23 180-205, significantly increased FE Pi in rats and reduced serum Pi in hyperphosphatemic Fgf-23 ( -/- ) knockout mice. The activity of FGF-23 180-251 was confirmed in opossum kidney cells in which the peptide reduced Na(+)-dependent Pi uptake and enhanced internalization of the Na(+)-Pi IIa co-transporter. We conclude that carboxyl terminal fragments of FGF-23 are phosphaturic and that a short, 26-amino acid fragment of FGF-23 retains significant phosphaturic activity.

A comparative gene map of the horse (Equus caballus).

Abstract: A comparative gene map of the horse genome composed of 127 loci was assembled based on the new assignment of 68 equine type I loci and on data published previously. PCR primers based on consensus gene sequences conserved across mammalian species were used to amplify markers for assigning 68 equine type I loci to 27 horse synteny groups established previously with a horse-mouse somatic cell hybrid panel (SCHP, UC Davis). This increased the number of coding genes mapped to the horse genome by over 2-fold and allowed refinements of the comparative mapping data available for this species. In conjunction with 57 previous assignments of type I loci to the horse genome map, these data have allowed us to confirm the assignment of 24 equine synteny groups to their respective chromosomes, to provisionally assign nine synteny groups to chromosomes, and to further refine the genetic composition established with Zoo-FISH of two horse chromosomes. The equine type I markers developed in this study provide an important resource for the future development of the horse linkage and physical genome maps.

Initial sequencing and analysis of the human genome.

Abstract: The human genome holds an extraordinary trove of information about human development, physiology, medicine and evolution. Here we report the results of an international collaboration to produce and make freely available a draft sequence of the human genome. We also present an initial analysis of the data, describing some of the insights that can be gleaned from the sequence.

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls

Abstract: There is increasing evidence that genome-wide association ( GWA) studies represent a powerful approach to the identification of genes involved in common human diseases. We describe a joint GWA study ( using the Affymetrix GeneChip 500K Mapping Array Set) undertaken in the British population, which has examined similar to 2,000 individuals for each of 7 major diseases and a shared set of similar to 3,000 controls. Case-control comparisons identified 24 independent association signals at P < 5 X 10(-7): 1 in bipolar disorder, 1 in coronary artery disease, 9 in Crohn's disease, 3 in rheumatoid arthritis, 7 in type 1 diabetes and 3 in type 2 diabetes. On the basis of prior findings and replication studies thus-far completed, almost all of these signals reflect genuine susceptibility effects. We observed association at many previously identified loci, and found compelling evidence that some loci confer risk for more than one of the diseases studied. Across all diseases, we identified a large number of further signals ( including 58 loci with single-point P values between 10(-5) and 5 X 10(-7)) likely to yield additional susceptibility loci. The importance of appropriately large samples was confirmed by the modest effect sizes observed at most loci identified. This study thus represents a thorough validation of the GWA approach. It has also demonstrated that careful use of a shared control group represents a safe and effective approach to GWA analyses of multiple disease phenotypes; has generated a genome-wide genotype database for future studies of common diseases in the British population; and shown that, provided individuals with non-European ancestry are excluded, the extent of population stratification in the British population is generally modest. Our findings offer new avenues for exploring the pathophysiology of these important disorders. We anticipate that our data, results and software, which will be widely available to other investigators, will provide a powerful resource for human genetics research.