Identification of a functional genetic variant driving racially dimorphic platelet gene expression of the thrombin receptor regulator, PCTP.

Platelet activation in response to stimulation of the Protease Activated Receptor 4 (PAR4) receptor differs by race. One factor that contributes to this difference is the expression level of Phosphatidylcholine Transfer Protein (PCTP), a regulator of platelet PAR4 function. We have conducted an expression Quantitative Trait Locus (eQTL) analysis that identifies single nucleotide polymorphisms (SNPs) linked to the expression level of platelet genes. This analysis revealed 26 SNPs associated with the expression level of PCTP at genome-wide significance (p \u3c 5×10(-8)). Using annotation from ENCODE and other public data we prioritised one of these SNPs, rs2912553, for functional testing. The allelic frequency of rs2912553 is racially-dimorphic, in concordance with the racially differential expression of PCTP. Reporter gene assays confirmed that the single nucleotide change caused by rs2912553 altered the transcriptional potency of the surrounding genomic locus. Electromobility shift assays, luciferase assays, and overexpression studies indicated a role for the megakaryocytic transcription factor GATA1. In summary, we have integrated multi-omic data to identify and functionalise an eQTL. This, along with the previously described relationship between PCTP and PAR4 function, allows us to characterise a genotype-phenotype relationship through the mechanism of gene expression

Health evaluation of a pronghorn antelope population in Oregon

During 1996 and 1997, the U.S. Fish and Wildlife Service conducted a study to determine the cause(s) of population decline and low survival of pronghorn antelope (Antilocapra americana) fawns on Hart Mountain National Antelope Refuge (HMNAR) located in southeastern Oregon (USA). As part of that study, blood, fecal, and tissue samples from 104 neonatal fawns, 40 adult does, and nine adult male pronghorns were collected to conduct a health evaluation of the population. Physiological parameters related to nutrition and/or disease were studied. No abnormalities were found in the complete blood cell counts of adults (n = 40) or fawns (n = 44 to 67). Serum total protein and blood urea nitrogen (BUN) levels were lower compared to other pronghorn populations. Does had mean BUN values significantly lower (P < 0.001) in December 1996 than March 1997. Serum copper (Cu) levels in does (range 0.39 to 0.74 ppm) were considered marginal when compared to domestic animals and other wild ungulates. Fawns had low (0.28 ppm) Cu levels at birth and reached the does' marginal values in about 3 days. Whole blood, serum and liver selenium (Se) levels were considered marginal to low in most segments of the pronghorn population. However, serum levels of vitamin E (range 1.98 to 3.27 μg/ml), as determined from the does captured in March, were apparently sufficient to offset any signs of Se deficiency. No clinical signs of Cu or Se deficiency were observed. Fifty-five of 87 dead fawns were necropsied. Trauma, due to predation by coyotes (Canis latrans), accounted for 62% of the mortality during mid-May to mid-July of each year. Other causes included predation by golden eagles (Aquila chrysaetos) (4%), dystocia (2%), septicemic pasteurellosis (4%), starvation (5%), and unknown (23%). Adult females were tested for serum neutralizing antibodies to Brucella spp. (n = 20, negative), Leptospira interrogans (n = 20, negative), bluetongue virus (n = 20, 35% positive), epizootic hemorrhagic disease virus (n = 20, 30% positive), respiratory syncytial virus (n = 18, negative), parainfluenza virus type 3 (n = 18, 67% positive), infectious bovine rhinotracheitis (n = 18, negative), and bovine viral diarrhea (n = 18, negative). Considering the parameters examined, we found no apparent predisposing factors to mortality including those killed by coyotes, but some nutritional parameters suggest that pronghorns on HMNAR exist on a diet low in protein and Se and marginal in Cu. The effect these factors have on the population is not known

Peptidoleukotriene Antagonists State of the Art

Peptidoleukotrienes (LTC4, LTD4, and LTE4) have been proposed as important mediators of asthma. Twenty years of research in the field of peptidoleukotriene (pLT) antagonists have generated a number of biologically active compounds from different structural classes. Several drugs have been or are currently in clinical trials. The first generation peptidoleukotriene antagonists (e.g. FPL 55712) showed disappointing results in asthmatic patients, due to insufficient potency. However, new classes of highly potent antagonists (e.g. ICI 204219) are proving successfull in clinical trials in asthma patients. Thus, peptidoleukotriene antagonists may represent a new principle in asthma therapy. In this paper, the in vitro potency and clinical data of different classes of peptidoleukotriene antagonists are reviewed

Dislocation Dynamics in an Anisotropic Stripe Pattern

The dynamics of dislocations confined to grain boundaries in a striped system are studied using electroconvection in the nematic liquid crystal N4. In electroconvection, a striped pattern of convection rolls forms for sufficiently high driving voltages. We consider the case of a rapid change in the voltage that takes the system from a uniform state to a state consisting of striped domains with two different wavevectors. The domains are separated by domain walls along one axis and a grain boundary of dislocations in the perpendicular direction. The pattern evolves through dislocation motion parallel to the domain walls. We report on features of the dislocation dynamics. The kinetics of the domain motion are quantified using three measures: dislocation density, average domain wall length, and the total domain wall length per area. All three quantities exhibit behavior consistent with power law evolution in time, with the defect density decaying as $t^{-1/3}$, the average domain wall length growing as $t^{1/3}$, and the total domain wall length decaying as $t^{-1/5}$. The two different exponents are indicative of the anisotropic growth of domains in the system.Comment: 8 figures: 7 jpeg and 1 pd

Novel glassy behavior in a ferromagnetic p-spin model

Recent work has suggested the existence of glassy behavior in a ferromagnetic model with a four-spin interaction. Motivated by these findings, we have studied the dynamics of this model using Monte Carlo simulations with particular attention being paid to two-time quantities. We find that the system shares many features in common with glass forming liquids. In particular, the model exhibits: (i) a very long-lived metastable state, (ii) autocorrelation functions that show stretched exponential relaxation, (iii) a non-equilibrium timescale that appears to diverge at a well defined temperature, and (iv) low temperature aging behaviour characteristic of glasses.Comment: 6 pages, 5 figure

PRIMUS: The Effect of Physical Scale on the Luminosity-Dependence of Galaxy Clustering via Cross-Correlations

We report small-scale clustering measurements from the PRIMUS spectroscopic redshift survey as a function of color and luminosity. We measure the real-space cross-correlations between 62,106 primary galaxies with PRIMUS redshifts and a tracer population of 545,000 photometric galaxies over redshifts from z=0.2 to z=1. We separately fit a power-law model in redshift and luminosity to each of three independent color-selected samples of galaxies. We report clustering amplitudes at fiducial values of z=0.5 and L=1.5 L*. The clustering of the red galaxies is ~3 times as strong as that of the blue galaxies and ~1.5 as strong as that of the green galaxies. We also find that the luminosity dependence of the clustering is strongly dependent on physical scale, with greater luminosity dependence being found between r=0.0625 Mpc/h and r=0.25 Mpc/h, compared to the r=0.5 Mpc/h to r=2 Mpc/h range. Moreover, over a range of two orders of magnitude in luminosity, a single power-law fit to the luminosity dependence is not sufficient to explain the increase in clustering at both the bright and faint ends at the smaller scales. We argue that luminosity-dependent clustering at small scales is a necessary component of galaxy-halo occupation models for blue, star-forming galaxies as well as for red, quenched galaxies.Comment: 13 pages, 6 figures, 5 tables; published in ApJ (revised to match published version

Existence, Regularity, and Properties of Generalized Apparent Horizons

We prove a conjecture of Tom Ilmanen's and Hubert Bray's regarding the existence of the outermost generalized apparent horizon in an initial data set and that it is outer area minimizing.Comment: 16 pages, thoroughly revised, no major changes, to appear in Comm. Math. Phy

Nonsteroidal Anti-Inflammatory Agents in the Therapy for Experimental Pneumococcal Meningitis

An increased inflammatory mass in the subarachnoid space during bacterial meningitis may correlate with a poor outcome of disease. Using a rabbit model of pneumococcal meningitis, we sought to reduce this inflammatory process. The ability of the pneumococcal cell wall to cause death and to generate leukocytosis and abnormal chemistry in cerebrospinal fluid was prevented when animals were treated with inhibitors of the cyclooxygenase pathway of arachidonate metabolism. Bacterial lysis by ampicillin led to release of cell wall that caused a significant, transient increase in meningeal inflammation. This inflammatory burst was also prevented by administering cyclooxygenase inhib-itors concurrently with the antibioti

Dark Matter Halo Models of Stellar Mass-Dependent Galaxy Clustering in PRIMUS+DEEP2 at 0.2<z<1.2

We utilize $\Lambda$CDM halo occupation models of galaxy clustering to investigate the evolving stellar mass dependent clustering of galaxies in the PRIsm MUlti-object Survey (PRIMUS) and DEEP2 Redshift Survey over the past eight billion years of cosmic time, between $0.2<z<1.2$. These clustering measurements provide new constraints on the connections between dark matter halo properties and galaxy properties in the context of the evolving large-scale structure of the universe. Using both an analytic model and a set of mock galaxy catalogs, we find a strong correlation between central galaxy stellar mass and dark matter halo mass over the range $M_\mathrm{halo}\sim10^{11}$-$10^{13}~h^{-1}M_\odot$, approximately consistent with previous observations and theoretical predictions. However, the stellar-to-halo mass relation (SHMR) and the mass scale where star formation efficiency reaches a maximum appear to evolve more strongly than predicted by other models, including models based primarily on abundance-matching constraints. We find that the fraction of satellite galaxies in haloes of a given mass decreases significantly from $z\sim0.5$ to $z\sim0.9$, partly due to the fact that haloes at fixed mass are rarer at higher redshift and have lower abundances. We also find that the $M_1/M_\mathrm{min}$ ratio, a model parameter that quantifies the critical mass above which haloes host at least one satellite, decreases from $\approx20$ at $z\sim0$ to $\approx13$ at $z\sim0.9$. Considering the evolution of the subhalo mass function vis-\`{a}-vis satellite abundances, this trend has implications for relations between satellite galaxies and halo substructures and for intracluster mass, which we argue has grown due to stripped and disrupted satellites between $z\sim0.9$ and $z\sim0.5$.Comment: 17 pages, 9 figures and 4 tables; Astrophysical Journal, publishe

Dynamic Phase Transitions in Cell Spreading

We monitored isotropic spreading of mouse embryonic fibroblasts on fibronectin-coated substrates. Cell adhesion area versus time was measured via total internal reflection fluorescence microscopy. Spreading proceeds in well-defined phases. We found a power-law area growth with distinct exponents a_i in three sequential phases, which we denote basal (a_1=0.4+-0.2), continous (a_2=1.6+-0.9) and contractile (a_3=0.3+-0.2) spreading. High resolution differential interference contrast microscopy was used to characterize local membrane dynamics at the spreading front. Fourier power spectra of membrane velocity reveal the sudden development of periodic membrane retractions at the transition from continous to contractile spreading. We propose that the classification of cell spreading into phases with distinct functional characteristics and protein activity patterns serves as a paradigm for a general program of a phase classification of cellular phenotype. Biological variability is drastically reduced when only the corresponding phases are used for comparison across species/different cell lines.Comment: 4 pages, 5 figure