138 research outputs found
P07-08. Spermatozoa capture HIV-1 through heparan sulfate and efficiently transmit the virus to dendritic cells
Inmate Recidivism as a Measure of Private Prison Performance
The growth of the private corrections industry has elicited interest in the comparative performance of state and private prisons. One way to measure the service quality of private prisons is to examine inmates' postrelease performance. Current empirical evidence is limited to four studies, all conducted in Florida. This analysis replicates and adds to the Florida measures in a different state and enhances previous methods. It uses data for a large cohort of Oklahoma state prison inmates released between 1997 and 2001. Controlling for known covariates, multivariate survival analysis revealed comparative rates of reincarceration for inmates in multiple exposure and comparison groups. These results are unique among prior studies on this topic; private prison inmates had a greater hazard of recidivism in all eight models tested, six of which were statistically significant. Finding no empirical support for claims of superior service from private corrections, the authors discuss policy implications and prospects for future research.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline
Rab27a controls HIV-1 assembly by regulating plasma membrane levels of phosphatidylinositol 4,5-bisphosphate
During the late stages of the HIV-1 replication cycle, the viral polyprotein Pr55(Gag) is recruited to the plasma membrane (PM), where it binds phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) and directs HIV-1 assembly. We show that Rab27a controls the trafficking of late endosomes carrying phosphatidylinositol 4-kinase type 2 α (PI4KIIα) toward the PM of CD4(+) T cells. Hence, Rab27a promotes high levels of PM phosphatidylinositol 4-phosphate and the localized production of PI(4,5)P2, therefore controlling Pr55(Gag) membrane association. Rab27a also controls PI(4,5)P2 levels at the virus-containing compartments of macrophages. By screening Rab27a effectors, we identified that Slp2a, Slp3, and Slac2b are required for the association of Pr55(Gag) with the PM and that Slp2a cooperates with Rab27a in the recruitment of PI4KIIα to the PM. We conclude that by directing the trafficking of PI4KIIα-positive endosomes toward the PM, Rab27a controls PI(4,5)P2 production and, consequently, HIV-1 replication.Universidad de Buenos Aires and CONICET doctoral fellowships, Agencia Nacional de Pro-
moción CientÃfica y Tecnológica (Argentina) grants: (2010-1681, 2012-00353), Creative and Novel
Ideas in HIV Research Program, University of Alabama at Birmingham Center for AIDS Research funding grant P30 AI027767-24
Taming trilogues: the EU's law-making process in a comparative perspective.
Trilogues have become the modus operandi of EU decision-making. They are an informal but institutionalised mechanism providing for in camera discussions of legislative texts between the three main EU decision-making institutions, with a view to securing legislative compromises. Trilogues present risks to an organ of parliamentary representation through their potential to depoliticise conflict and by reducing the accountability and transparency of the decision-making process. We examine how the European Parliament (EP) has responded to trilogues and what this response tells us about the development of the EP as an institutionalised organ of representative democracy. We compare these with arrangements for bicameral conflict resolution in the United States, where similar issues are presented by informal mechanisms of decision-making. We assess the institutionalisation of trilogues from a democratic perspective, highlighting achievements and future challenges, and the value of these findings for the ongoing reflection on the EP as a normal parliament and the role of informal institutions in EU law-making
Evolving neural network optimization of cholesteryl ester separation by reversed-phase HPLC
Cholesteryl esters have antimicrobial activity and likely contribute to the innate immunity system. Improved separation techniques are needed to characterize these compounds. In this study, optimization of the reversed-phase high-performance liquid chromatography separation of six analyte standards (four cholesteryl esters plus cholesterol and tri-palmitin) was accomplished by modeling with an artificial neural network–genetic algorithm (ANN-GA) approach. A fractional factorial design was employed to examine the significance of four experimental factors: organic component in the mobile phase (ethanol and methanol), column temperature, and flow rate. Three separation parameters were then merged into geometric means using Derringer’s desirability function and used as input sources for model training and testing. The use of genetic operators proved valuable for the determination of an effective neural network structure. Implementation of the optimized method resulted in complete separation of all six analytes, including the resolution of two previously co-eluting peaks. Model validation was performed with experimental responses in good agreement with model-predicted responses. Improved separation was also realized in a complex biological fluid, human milk. Thus, the first known use of ANN-GA modeling for improving the chromatographic separation of cholesteryl esters in biological fluids is presented and will likely prove valuable for future investigators involved in studying complex biological samples
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Novel Loci For Major Depression Identified By Genome-wide Association Study Of Sequenced Treatment Alternatives To Relieve Depression And Meta-analysis Of Three Studies
We report a genome-wide association study (GWAS) of major depressive disorder (MDD) in 1221 cases from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study and 1636 screened controls. No genome-wide evidence for association was detected. We also carried out a meta-analysis of three European-ancestry MDD GWAS data sets: STAR*D, Genetics of Recurrent Early-onset Depression and the publicly available Genetic Association Information Network–MDD data set. These data sets, totaling 3957 cases and 3428 controls, were genotyped using four different platforms (Affymetrix 6.0, 5.0 and 500 K, and Perlegen). For each of 2.4 million HapMap II single-nucleotide polymorphisms (SNPs), using genotyped data where available and imputed data otherwise, single-SNP association tests were carried out in each sample with correction for ancestry-informative principal components. The strongest evidence for association in the meta-analysis was observed for intronic SNPs in ATP6V1B2 (P=6.78 × 10^−7), SP4 (P=7.68 × 10^−7) and GRM7 (P=1.11 × 10^−6). Additional exploratory analyses were carried out for a narrower phenotype (recurrent MDD with onset before age 31, N=2191 cases), and separately for males and females. Several of the best findings were supported primarily by evidence from narrow cases or from either males or females. On the basis of previous biological evidence, we consider GRM7 a strong MDD candidate gene. Larger samples will be required to determine whether any common SNPs are significantly associated with MDD
Transcriptional correlates of the pathological phenotype in a Huntington’s disease mouse model
Huntington disease (HD) is a fatal neurodegenerative disorder without a cure that is caused by an
aberrant expansion of CAG repeats in exon 1 of the huntingtin (HTT) gene. Although a negative
correlation between the number of CAG repeats and the age of disease onset is established, additional
factors may contribute to the high heterogeneity of the complex manifestation of symptoms
among patients. This variability is also observed in mouse models, even under controlled genetic
and environmental conditions. To better understand this phenomenon, we analysed the R6/1 strain
in search of potential correlates between pathological motor/cognitive phenotypical traits and
transcriptional alterations. HD-related genes (e.g., Penk, Plk5, Itpka), despite being downregulated
across the examined brain areas (the prefrontal cortex, striatum, hippocampus and cerebellum),
exhibited tissue-specific correlations with particular phenotypical traits that were attributable to
the contribution of the brain region to that trait (e.g., striatum and rotarod performance, cerebellum
and feet clasping). Focusing on the striatum, we determined that the transcriptional dysregulation
associated with HD was partially exacerbated in mice that showed poor overall phenotypical scores,
especially in genes with relevant roles in striatal functioning (e.g., Pde10a, Drd1, Drd2, Ppp1r1b).
However, we also observed transcripts associated with relatively better outcomes, such as Nfya
(CCAAT-binding transcription factor NF-Y subunit A) plus others related to neuronal development,
apoptosis and differentiation. In this study, we demonstrated that altered brain transcription can be
related to the manifestation of HD-like symptoms in mouse models and that this can be extrapolated to
the highly heterogeneous population of HD patients
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