P2X receptors: epithelial ion channels and regulators of salt and water transport.

When the results from electrophysiological studies of renal epithelial cells are combined with data from in vivo tubule microperfusion experiments and immunohistochemical surveys of the nephron, the accumulated evidence suggests that ATP-gated ion channels, P2X receptors, play a specialized role in the regulation of ion and water movement across the renal tubule and are integral to electrolyte and fluid homeostasis. In this short review, we discuss the concept of P2X receptors as regulators of salt and water salvage pathways, as well as acknowledging their accepted role as ATP-gated ion channels

Power fluctuations in stochastic models of dissipative systems

We consider different models of stochastic dissipative equations and theoretically compute the probability distribution functions (actually the associated large deviation functions) of the time averaged injected power required to sustain a nontrivial stationary state. We discuss the results and in particular draw from our results some general features shared by these distributions in realistic dissipative systems

Gene expression and methylation signatures of MAN2C1 are associated with PTSD

As potential regulators of DNA accessibility and activity, epigenetic modifications offer a mechanism by which the environment can moderate the effects of genes. To date, however, there have been relatively few studies assessing epigenetic modifications associated with post-traumatic stress disorder (PTSD). Here we investigate PTSD-associated methylation differences in 33 genes previously shown to differ in whole blood-derived gene expression levels between those with vs. without the disorder. Drawing on DNA samples similarly obtained from whole blood in 100 individuals, 23 with and 77 without lifetime PTSD, we used methylation microarray data to assess whether these 33 candidate genes showed epigenetic signatures indicative of increased risk for, or resilience to, PTSD. Logistic regression analyses were performed to assess the main and interacting effects of candidate genes' methylation values and number of potentially traumatic events (PTEs), adjusting for age and other covariates. Results revealed that only one candidate gene-MAN2C1}-showed a significant methylation x PTE interaction, such that those with both higher MAN2C1 methylation and greater exposure to PTEs showed a marked increase in risk of lifetime PTSD (OR 4.35, 95% CI: 1.07, 17.77, p=0.04). These results indicate that MAN2C1 methylation levels modify cumulative traumatic burden on risk of PTSD, and suggest that both gene expression and epigenetic changes at specific loci are associated with this disorder

Navier-Stokes transport coefficients of dd-dimensional granular binary mixtures at low density

The Navier-Stokes transport coefficients for binary mixtures of smooth inelastic hard disks or spheres under gravity are determined from the Boltzmann kinetic theory by application of the Chapman-Enskog method for states near the local homogeneous cooling state. It is shown that the Navier-Stokes transport coefficients are not affected by the presence of gravity. As in the elastic case, the transport coefficients of the mixture verify a set of coupled linear integral equations that are approximately solved by using the leading terms in a Sonine polynomial expansion. The results reported here extend previous calculations [V. Garz\'o and J. W. Dufty, Phys. Fluids {\bf 14}, 1476 (2002)] to an arbitrary number of dimensions. To check the accuracy of the Chapman-Enskog results, the inelastic Boltzmann equation is also numerically solved by means of the direct simulation Monte Carlo method to evaluate the diffusion and shear viscosity coefficients for hard disks. The comparison shows a good agreement over a wide range of values of the coefficients of restitution and the parameters of the mixture (masses and sizes).Comment: 6 figures, to be published in J. Stat. Phy

Coalescent-based genome analyses resolve the early branches of the euarchontoglires

Despite numerous large-scale phylogenomic studies, certain parts of the mammalian tree are extraordinarily difficult to resolve. We used the coding regions from 19 completely sequenced genomes to study the relationships within the super-clade Euarchontoglires (Primates, Rodentia, Lagomorpha, Dermoptera and Scandentia) because the placement of Scandentia within this clade is controversial. The difficulty in resolving this issue is due to the short time spans between the early divergences of Euarchontoglires, which may cause incongruent gene trees. The conflict in the data can be depicted by network analyses and the contentious relationships are best reconstructed by coalescent-based analyses. This method is expected to be superior to analyses of concatenated data in reconstructing a species tree from numerous gene trees. The total concatenated dataset used to study the relationships in this group comprises 5,875 protein-coding genes (9,799,170 nucleotides) from all orders except Dermoptera (flying lemurs). Reconstruction of the species tree from 1,006 gene trees using coalescent models placed Scandentia as sister group to the primates, which is in agreement with maximum likelihood analyses of concatenated nucleotide sequence data. Additionally, both analytical approaches favoured the Tarsier to be sister taxon to Anthropoidea, thus belonging to the Haplorrhine clade. When divergence times are short such as in radiations over periods of a few million years, even genome scale analyses struggle to resolve phylogenetic relationships. On these short branches processes such as incomplete lineage sorting and possibly hybridization occur and make it preferable to base phylogenomic analyses on coalescent methods

Urinary ATP as an indicator of infection and inflammation of the urinary tract in patients with lower urinary tract symptoms

BACKGROUND: Adenosine-5'-triphosphate (ATP) is a neurotransmitter and inflammatory cytokine implicated in the pathophysiology of lower urinary tract disease. ATP additionally reflects microbial biomass thus has potential as a surrogate marker of urinary tract infection (UTI). The optimum clinical sampling method for ATP urinalysis has not been established. We tested the potential of urinary ATP in the assessment of lower urinary tract symptoms, infection and inflammation, and validated sampling methods for clinical practice. METHODS: A prospective, blinded, cross-sectional observational study of adult patients presenting with lower urinary tract symptoms (LUTS) and asymptomatic controls, was conducted between October 2009 and October 2012. Urinary ATP was assayed by a luciferin-luciferase method, pyuria counted by microscopy of fresh unspun urine and symptoms assessed using validated questionnaires. The sample collection, storage and processing methods were also validated. RESULTS: 75 controls and 340 patients with LUTS were grouped as without pyuria (n = 100), pyuria 1-9 wbc ?l(-1) (n = 120) and pyuria ?10 wbc ?l(-1) (n = 120). Urinary ATP was higher in association with female gender, voiding symptoms, pyuria greater than 10 wbc ?l(-1) and negative MSU culture. ROC curve analysis showed no evidence of diagnostic test potential. The urinary ATP signal decayed with storage at 23°C but was prevented by immediate freezing at ??-20°C, without boric acid preservative and without the need to centrifuge urine prior to freezing. CONCLUSIONS: Urinary ATP may have a role as a research tool but is unconvincing as a surrogate, clinical diagnostic marker

Transport coefficients for inelastic Maxwell mixtures

The Boltzmann equation for inelastic Maxwell models is used to determine the Navier-Stokes transport coefficients of a granular binary mixture in $d$ dimensions. The Chapman-Enskog method is applied to solve the Boltzmann equation for states near the (local) homogeneous cooling state. The mass, heat, and momentum fluxes are obtained to first order in the spatial gradients of the hydrodynamic fields, and the corresponding transport coefficients are identified. There are seven relevant transport coefficients: the mutual diffusion, the pressure diffusion, the thermal diffusion, the shear viscosity, the Dufour coefficient, the pressure energy coefficient, and the thermal conductivity. All these coefficients are {\em exactly} obtained in terms of the coefficients of restitution and the ratios of mass, concentration, and particle sizes. The results are compared with known transport coefficients of inelastic hard spheres obtained analytically in the leading Sonine approximation and by means of Monte Carlo simulations. The comparison shows a reasonably good agreement between both interaction models for not too strong dissipation, especially in the case of the transport coefficients associated with the mass flux.Comment: 9 figures, to be published in J. Stat. Phy

Evidence of a Conserved Molecular Response to Selection for Increased Brain Size in Primates

The adaptive significance of human brain evolution has been frequently studied through comparisons with other primates. However, the evolution of increased brain size is not restricted to the human lineage but is a general characteristic of primate evolution. Whether or not these independent episodes of increased brain size share a common genetic basis is unclear. We sequenced and de novo assembled the transcriptome from the neocortical tissue of the most highly encephalized nonhuman primate, the tufted capuchin monkey ($\textit{Cebus apella}$). Using this novel data set, we conducted a genome-wide analysis of orthologous brain-expressed protein coding genes to identify evidence of conserved gene-phenotype associations and species-specific adaptations during three independent episodes of brain size increase. We identify a greater number of genes associated with either total brain mass or relative brain size across these six species than show species-specific accelerated rates of evolution in individual large-brained lineages. We test the robustness of these associations in an expanded data set of 13 species, through permutation tests and by analyzing how genome-wide patterns of substitution co-vary with brain size. Many of the genes targeted by selection during brain expansion have glutamatergic functions or roles in cell cycle dynamics. We also identify accelerated evolution in a number of individual capuchin genes whose human orthologs are associated with human neuropsychiatric disorders. These findings demonstrate the value of phenotypically informed genome analyses, and suggest at least some aspects of human brain evolution have occurred through conserved gene-phenotype associations. Understanding these commonalities is essential for distinguishing human-specific selection events from general trends in brain evolution.This work was supported by the National Science Foundation, grant award numbers BCS-0751508, BCS-0827546, and BCS-1061370 for AMB and DEW. Professor Chet Sherwood (The George Washington University) provided useful guidance in the initial stages of this project. S.H.M. is grateful for support from a BBSRC doctoral training grant and a Research Fellowship from the Royal Commission for the Exhibition of 1851. N.I.M. is grateful for support from the Leverhulme Trust and Murray Edwards College, Cambridge

Diffusion of impurities in a granular gas

Diffusion of impurities in a granular gas undergoing homogeneous cooling state is studied. The results are obtained by solving the Boltzmann--Lorentz equation by means of the Chapman--Enskog method. In the first order in the density gradient of impurities, the diffusion coefficient $D$ is determined as the solution of a linear integral equation which is approximately solved by making an expansion in Sonine polynomials. In this paper, we evaluate $D$ up to the second order in the Sonine expansion and get explicit expressions for $D$ in terms of the restitution coefficients for the impurity--gas and gas--gas collisions as well as the ratios of mass and particle sizes. To check the reliability of the Sonine polynomial solution, analytical results are compared with those obtained from numerical solutions of the Boltzmann equation by means of the direct simulation Monte Carlo (DSMC) method. In the simulations, the diffusion coefficient is measured via the mean square displacement of impurities. The comparison between theory and simulation shows in general an excellent agreement, except for the cases in which the gas particles are much heavier and/or much larger than impurities. In theses cases, the second Sonine approximation to $D$ improves significantly the qualitative predictions made from the first Sonine approximation. A discussion on the convergence of the Sonine polynomial expansion is also carried out.Comment: 9 figures. to appear in Phys. Rev.