Yale University

About: Yale University is a education organization based out in New Haven, Connecticut, United States. It is known for research contribution in the topics: Population & Poison control. The organization has 89824 authors who have published 220665 publications receiving 12834776 citations. The organization is also known as: Yale & Collegiate School.

Embryonic lethality and liver degeneration in mice lacking the RelA component of NF-kappa B.

Abstract: NF-κB, which consists of two polypeptides, p50 (Mr 50K) and p65/RelA (Mr 65K), is thought to be a key regulator of genes involved in responses to infection, inflammation and stress1. Indeed, although developmentally normal, mice deficient in p50 display functional defects in immune responses2. Here we describe the generation of mice deficient in the RelA subunit of NF-κB. Disruption of the relA locus leads to embryonic lethality at 15–16 days of gestation, concomitant with a massive degeneration of the liver by programmed cell death or apoptosis. Embryonic fibroblasts from RelA-deficient mice are defective in the tumour necrosis factor (TNF)-mediated induction of messenger RNAs for IκBα and granulocyte/macrophage colony stimulating factor (GM-CSF), although basal levels of these transcripts are unaltered. These results indicate that RelA controls inducible, but not basal, transcription in NF-κB-regulated pathways.

Genome-wide association study identifies new susceptibility loci for Crohn disease and implicates autophagy in disease pathogenesis

Abstract: We present a genome-wide association study of ileal Crohn disease and two independent replication studies that identify several new regions of association to Crohn disease. Specifically, in addition to the previously established CARD15 and IL23R associations, we identified strong and significantly replicated associations (combined P < 10(-10)) with an intergenic region on 10q21.1 and a coding variant in ATG16L1, the latter of which was also recently reported by another group. We also report strong associations with independent replication to variation in the genomic regions encoding PHOX2B, NCF4 and a predicted gene on 16q24.1 (FAM92B). Finally, we demonstrate that ATG16L1 is expressed in intestinal epithelial cell lines and that functional knockdown of this gene abrogates autophagy of Salmonella typhimurium. Together, these findings suggest that autophagy and host cell responses to intracellular microbes are involved in the pathogenesis of Crohn disease.

How does sexual minority stigma “get under the skin”? A psychological mediation framework.

Abstract: Sexual minorities are at increased risk for multiple mental health burdens compared with heterosexuals. The field has identified 2 distinct determinants of this risk, including group-specific minority stressors and general psychological processes that are common across sexual orientations. The goal of the present article is to develop a theoretical framework that integrates the important insights from these literatures. The framework postulates that (a) sexual minorities confront increased stress exposure resulting from stigma; (b) this stigma-related stress creates elevations in general emotion dysregulation, social/interpersonal problems, and cognitive processes conferring risk for psychopathology; and (c) these processes in turn mediate the relationship between stigma-related stress and psychopathology. It is argued that this framework can, theoretically, illuminate how stigma adversely affects mental health and, practically, inform clinical interventions. Evidence for the predictive validity of this framework is reviewed, with particular attention paid to illustrative examples from research on depression, anxiety, and alcohol-use disorders.

Actin, a Central Player in Cell Shape and Movement

Abstract: The protein actin forms filaments that provide cells with mechanical support and driving forces for movement. Actin contributes to biological processes such as sensing environmental forces, internalizing membrane vesicles, moving over surfaces, and dividing the cell in two. These cellular activities are complex; they depend on interactions of actin monomers and filaments with numerous other proteins. Here, we present a summary of the key questions in the field and suggest how those questions might be answered. Understanding actin-based biological phenomena will depend on identifying the participating molecules and defining their molecular mechanisms. Comparisons of quantitative measurements of reactions in live cells with computer simulations of mathematical models will also help generate meaningful insights.

QCD and instantons at finite temperature

Abstract: The current understanding of the behavior of quantum chromodynamics at finite temperature is presented. Perturbative methods are used to explore the high-temperature dynamics. At sufficiently high temperatures the plasma of thermal excitations screens all color electric fields and quarks are unconfined. It is believed that the high-temperature theory develops a dynamical mass gap. However in perturbation theory the infrared behavior of magnetic fluctuations is so singular that beyond some order the perturbative expansion breaks down. The topological classification of finite-energy, periodic fields is presented and the classical solutions which minimize the action in each topological sector are examined. These include periodic instantons and magnetic monopoles. At sufficiently high temperature only fields with integral topological charge can contribute to the functional integral. Electric screening completely suppresses the contribution of fields with nonintegral topological charge. Consequently the $\ensuremath{\theta}$ dependence of the free energy at high temperature is dominated by the contribution of instantons. The complete temperature dependence of the instanton density is explicitly computed and large-scale instantons are found to be suppressed. Therefore the effects of instantons may be reliably calculated at sufficiently high temperature. The behavior of the theory in the vicinity of the transition from the high-temperature quark phase to the low-temperature hadronic phase cannot be accurately computed. However, at least in the absence of light quarks, semiclassical techniques and lattice methods may be combined to yield a simple picture of the dynamics valid for both high and low temperature, and to estimate the transition temperature.