Genetic substructure in cynomolgus macaques (Macaca fascicularis) on the island of Mauritius

Background: Nonhuman primates are commonly used in biomedical research as animal models of human disease and behavior. Compared to common rodent models, nonhuman primates are genetically, physiologically, behaviorally and neurologically more similar to humans owing to more recent shared ancestry and therefore provide the advantage of greater translational validity in preclinical studies. The cynomolgus macaque (Macaca fascicularis) is one of the most commonly used nonhuman primates in academic and industry settings, yet population genetic research has revealed significant substructure throughout the species distribution that may confound studies. Cynomolgus monkeys introduced to Mauritius specifically have previously been thought to maintain the least genetic heterogeneity of all cynomolgus monkeys, although recent work, including work from our lab, suggests macaques from Mauritius too may harbor cryptic substructure. Results: To evaluate putative substructure in Mauritian cynomolgus macaques, we designed a panel of 96 single nucleotide polymorphisms based on preliminary findings from previous work to screen 246 of cynomolgus monkeys from two primary suppliers. Results from this study support substructure in Mauritian macaques and suggest a minimum of two populations and maybe three on Mauritius, with moderate admixture. Conclusion: These findings inform the natural history of these monkeys suggesting either a previously unrecognized physical or ecological barrier to gene flow on Mauritius and/or the breakdown of historic substructure resulting from the history of macaque introduction to the island. These findings are relevant to ongoing research using these models in part because of increased appreciation of segregating common variation with functional effects and may be used to better inform animal selection in preclinical research. Electronic supplementary material The online version of this article (doi:10.1186/1471-2164-15-748) contains supplementary material, which is available to authorized users

Evolutionary conservation in genes underlying human psychiatric disorders

Many psychiatric diseases observed in humans have tenuous or absent analogs in other species. Most notable among these are schizophrenia and autism. One hypothesis has posited that these diseases have arisen as a consequence of human brain evolution, for example, that the same processes that led to advances in cognition, language, and executive function also resulted in novel diseases in humans when dysfunctional. Here, the molecular evolution of the protein-coding regions of genes associated with these and other psychiatric disorders are compared among species. Genes associated with psychiatric disorders are drawn from the literature and orthologous sequences are collected from eleven primate species (human, chimpanzee, bonobo, gorilla, orangutan, gibbon, macaque, baboon, marmoset, squirrel monkey, and galago) and 34 non-primate mammalian species. Evolutionary parameters, including dN/dS, are calculated for each gene and compared between disease classes and among species, focusing on humans and primates compared to other mammals, and on large-brained taxa (cetaceans, rhinoceros, walrus, bear, and elephant) compared to their small-brained sister species. Evidence of differential selection in humans to the exclusion of non-human primates was absent, however elevated dN/dS was detected in catarrhines as a whole, as well as in cetaceans, possibly as part of a more general trend. Although this may suggest that protein changes associated with schizophrenia and autism are not a cost of the higher brain function found in humans, it may also point to insufficiencies in the study of these diseases including incomplete or inaccurate gene association lists and/or a greater role of regulatory changes or copy number variation. Through this work a better understanding of the molecular evolution of the human brain, the pathophysiology of disease, and the genetic basis of human psychiatric disease is gained

Perceptions of Healthcare Providers about HIV/STD Prevention Education Among American Indian Populations: A Qualitative Descriptive Survey Study

Paper submitted to the University of Kansas School of Nursing in partial fulfillment of the requirements for the Nursing Honors Program.The University of Kansas School of Nursing Bachelor of Science Nursing Honors Progra

Large-scale polymorphism discovery in macaque G-protein coupled receptors

Background: G-protein coupled receptors (GPCRs) play an inordinately large role in human health. Variation in the genes that encode these receptors is associated with numerous disorders across the entire spectrum of disease. GPCRs also represent the single largest class of drug targets and associated pharmacogenetic effects are modulated, in part, by polymorphisms. Recently, non-human primate models have been developed focusing on naturally-occurring, functionally-parallel polymorphisms in candidate genes. This work aims to extend those studies broadly across the roughly 377 non-olfactory GPCRs. Initial efforts include resequencing 44 Indian-origin rhesus macaques (Macaca mulatta), 20 Chinese-origin rhesus macaques, and 32 cynomolgus macaques (M. fascicularis). Results: Using the Agilent target enrichment system, capture baits were designed for GPCRs off the human and rhesus exonic sequence. Using next generation sequencing technologies, nearly 25,000 SNPs were identified in coding sequences including over 14,000 non-synonymous and more than 9,500 synonymous protein-coding SNPs. As expected, regions showing the least evolutionary constraint show greater rates of polymorphism and greater numbers of higher frequency polymorphisms. While the vast majority of these SNPs are singletons, roughly 1,750 non-synonymous and 2,900 synonymous SNPs were found in multiple individuals. Conclusions: In all three populations, polymorphism and divergence is highly concentrated in N-terminal and C-terminal domains and the third intracellular loop region of GPCRs, regions critical to ligand-binding and signaling. SNP frequencies in macaques follow a similar pattern of divergence from humans and new polymorphisms in primates have been identified that may parallel those seen in humans, helping to establish better non-human primate models of disease

The Journal of BSN Honors Research, Volume 7, Issue 1, Summer 2014

Papers submitted to the University of Kansas School of Nursing in partial fulfillment of the requirements for the Nursing Honors Program.The University of Kansas School of Nursing Bachelor of Science Nursing Honors Progra

Disappearance of back-to-back high pTp_T hadron correlations in central Au+Au collisions at sNN\sqrt{s_{NN}} = 200 GeV

Azimuthal correlations for large transverse momentum charged hadrons have been measured over a wide pseudo-rapidity range and full azimuth in Au+Au and p+p collisions at $\sqrt{s_{NN}}$ = 200 GeV. The small-angle correlations observed in p+p collisions and at all centralities of Au+Au collisions are characteristic of hard-scattering processes already observed in elementary collisions. A strong back-to-back correlation exists for p+p and peripheral Au + Au. In contrast, the back-to-back correlations are reduced considerably in the most central Au+Au collisions, indicating substantial interaction as the hard-scattered partons or their fragmentation products traverse the medium.Comment: submitted to Phys. Rev. Let

System-Size Independence of Directed Flow Measured at the BNL Relativistic Heavy-Ion Collider

We measure directed flow (ν_1) for charged particles in Au+Au and Cu+Cu collisions at √S_(NN)=200 and 62.4 GeV, as a function of pseudorapidity (η), transverse momentum (p_t), and collision centrality, based on data from the STAR experiment. We find that the directed flow depends on the incident energy but, contrary to all available model implementations, not on the size of the colliding system at a given centrality. We extend the validity of the limiting fragmentation concept to ν_1 in different collision systems, and investigate possible explanations for the observed sign change in ν_1(p_t)

Azimuthal anisotropy and correlations in the hard scattering regime at RHIC

Azimuthal anisotropy ($v_2$) and two-particle angular correlations of high $p_T$ charged hadrons have been measured in Au+Au collisions at $\sqrt{s_{NN}}$=130 GeV for transverse momenta up to 6 GeV/c, where hard processes are expected to contribute significantly. The two-particle angular correlations exhibit elliptic flow and a structure suggestive of fragmentation of high $p_T$ partons. The monotonic rise of $v_2(p_T)$ for $p_T<2$ GeV/c is consistent with collective hydrodynamical flow calculations. At \pT>3 GeV/c a saturation of $v_2$ is observed which persists up to $p_T=6$ GeV/c.Comment: As publishe

Spin alignment measurements of the K∗0(892)K^{*0}(892) and ϕ(1020)\phi(1020) vector mesons at RHIC

We present the first spin alignment measurements for the $K^{*0}(892)$ and $\phi(1020)$ vector mesons produced at mid-rapidity with transverse momenta up to 5 GeV/c at $\sqrt{s_{NN}}$ = 200 GeV at RHIC. The diagonal spin density matrix elements with respect to the reaction plane in Au+Au collisions are $\rho_{00}$ = 0.32 $\pm$ 0.04 (stat) $\pm$ 0.09 (syst) for the $K^{*0}$ ($0.8<p_T<5.0$ GeV/c) and $\rho_{00}$ = 0.34 $\pm$ 0.02 (stat) $\pm$ 0.03 (syst) for the $\phi$ ($0.4<p_T<5.0$ GeV/c), and are constant with transverse momentum and collision centrality. The data are consistent with the unpolarized expectation of 1/3 and thus no evidence is found for the transfer of the orbital angular momentum of the colliding system to the vector meson spins. Spin alignments for $K^{*0}$ and $\phi$ in Au+Au collisions were also measured with respect to the particle's production plane. The $\phi$ result, $\rho_{00}$ = 0.41 $\pm$ 0.02 (stat) $\pm$ 0.04 (syst), is consistent with that in p+p collisions, $\rho_{00}$ = 0.39 $\pm$ 0.03 (stat) $\pm$ 0.06 (syst), also measured in this work. The measurements thus constrain the possible size of polarization phenomena in the production dynamics of vector mesons.Comment: 7 pages, 4 figures. fig.1 updated; one more reference added, one typo corrected, published in PRC.77.06190

Longitudinal double-spin asymmetry for inclusive jet production in p+p collisions at sqrt(s)=200 GeV

We report a new STAR measurement of the longitudinal double-spin asymmetry A_LL for inclusive jet production at mid-rapidity in polarized p+p collisions at a center-of-mass energy of sqrt(s) = 200 GeV. The data, which cover jet transverse momenta 5 < p_T < 30 GeV/c, are substantially more precise than previous measurements. They provide significant new constraints on the gluon spin contribution to the nucleon spin through the comparison to predictions derived from one global fit of polarized deep-inelastic scattering measurements.Comment: 7 pages, 4 figures + 1 tabl