Tufts University

About: Tufts University is a education organization based out in Medford, Massachusetts, United States. It is known for research contribution in the topics: Population & Medicine. The organization has 32800 authors who have published 66881 publications receiving 3451152 citations. The organization is also known as: Tufts College & Universitatis Tuftensis.

National Kidney Foundation's Kidney Disease Outcomes Quality Initiative clinical practice guidelines for chronic kidney disease in children and adolescents: evaluation, classification, and stratification.

Abstract: Objectives. A series of new guidelines has been developed by the National Kidney Foundation’s Kidney Disease Outcomes Quality Initiative to improve the detection and management of chronic kidney disease (CKD). In most instances of CKD, the earliest manifestations of the disorder may be identified by relatively simple tests. Unfortunately, CKD is often “underdiagnosed,” in part because of the absence of a common definition of CKD and a classification of the stages in its progression. The Kidney Disease Outcomes Quality Initiative clinical practice guidelines for CKD evaluation, classification, and stratification provide a basis to remedy these deficits. The specific goals of the guidelines described in this review are to provide: 1) an overview of the clinical practice guidelines as they pertain to children and adolescents, 2) a simple classification of the stages of CKD, and 3) a practical approach to the laboratory assessment of kidney disease in children and adolescents. Methods. The guidelines were developed as part of an evidence-based evaluation of CKD and its consequences in patients of all ages. The data that were used to generate the guidelines in this article were extracted from a structured analysis of articles that reported on children with CKD. Results and Conclusions. This review presents the definition and 5-stage classification system of CKD developed by the work group assigned to develop the guidelines, and summarizes the major recommendations regarding the early detection of CKD. Major emphasis is placed on the identification of children and adolescents with CKD by measuring the protein-to-creatinine ratio in spot urine specimens and by estimating the glomerular filtration rate from serum creatinine using prediction equations.

Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways

Abstract: Genome-wide association studies (GWAS) of psychiatric disorders have identified multiple genetic associations with such disorders, but better methods are needed to derive the underlying biological mechanisms that these signals indicate. We sought to identify biological pathways in GWAS data from over 60,000 participants from the Psychiatric Genomics Consortium. We developed an analysis framework to rank pathways that requires only summary statistics. We combined this score across disorders to find common pathways across three adult psychiatric disorders: schizophrenia, major depression and bipolar disorder. Histone methylation processes showed the strongest association, and we also found statistically significant evidence for associations with multiple immune and neuronal signaling pathways and with the postsynaptic density. Our study indicates that risk variants for psychiatric disorders aggregate in particular biological pathways and that these pathways are frequently shared between disorders. Our results confirm known mechanisms and suggest several novel insights into the etiology of psychiatric disorders.

Observation of a centrality-dependent dijet asymmetry in lead-lead collisions at √sNN=2.76 Tev with the ATLAS detector at the LHC

Abstract: By using the ATLAS detector, observations have been made of a centrality-dependent dijet asymmetry in the collisions of lead ions at the Large Hadron Collider. In a sample of lead-lead events with a per-nucleon center of mass energy of 2.76 TeV, selected with a minimum bias trigger, jets are reconstructed in fine-grained, longitudinally segmented electromagnetic and hadronic calorimeters. The transverse energies of dijets in opposite hemispheres are observed to become systematically more unbalanced with increasing event centrality leading to a large number of events which contain highly asymmetric dijets. This is the first observation of an enhancement of events with such large dijet asymmetries, not observed in proton-proton collisions, which may point to an interpretation in terms of strong jet energy loss in a hot, dense medium.

Bacterial Secretion Systems – An overview

Abstract: Bacterial pathogens utilize a multitude of methods to invade mammalian hosts, damage tissue sites, and thwart the immune system from responding. One essential component of these strategies for many bacterial pathogens is the secretion of proteins across phospholipid membranes. Secreted proteins can play many roles in promoting bacterial virulence, from enhancing attachment to eukaryotic cells, to scavenging resources in an environmental niche, to directly intoxicating target cells and disrupting their functions. Many pathogens use dedicated protein secretion systems to secrete virulence factors from the cytosol of the bacteria into host cells or the host environment. In general, bacterial protein secretion apparatuses can be divided into classes, based on their structures, functions, and specificity. Some systems are conserved in all classes of bacteria and secrete a broad array of substrates, while others are only found in a small number of bacterial species and/or are specific to only one or a few proteins. In this chapter, we review the canonical features of several common bacterial protein secretion systems, as well as their roles in promoting the virulence of bacterial pathogens. Additionally, we address recent findings that indicate that the innate immune system of the host can detect and respond to the presence of protein secretion systems during mammalian infection.

Nucleosome: A major immunogen for pathogenic autoantibody-inducing T cells of lupus

Abstract: Only a fraction (12%) of 268 "autoreactive" T cell clones derived from lupus-prone mice can selectively induce the production of pathogenic anti-DNA autoantibodies in vitro and accelerate the development of lupus nephritis when transferred in vivo. The CDR3 loops of T cell receptor beta chains expressed by these pathogenic T helper (Th) clones contain a recurrent motif of anionic residues suggesting that they are selected by autoantigens with cationic residues. Herein, we found that approximately 50% of these pathogenic Th clones were specific for nucleosomal antigens, but none of them responded to cationic idiopeptides shared by variable regions of pathogenic anti-DNA autoantibodies. Nucleosomes did not stimulate the T cells as a nonspecific mitogen or superantigen. Only the pathogenic Th cells of lupus responded to nucleosomal antigens that were processed and presented via the major histocompatibility class II pathway. Although the presentation of purified mononucleosomes to the Th clones could be blocked by inhibitors of endosomal proteases, neither of the two components of the nucleosomes--free DNA or histones by themselves--could stimulate the Th clones. Thus critical peptide epitopes for the Th cells were probably protected during uptake and processing of the nucleosome particle as a whole. The nucleosome-specific Th clones preferentially augmented the production of IgG autoantibodies to histone-DNA complex in vitro. In vivo, nucleosome-specific, CD4+ T cells were not detectable in normal mice, but they were found in the spleens of lupus-prone mice as early as 1 mo of age, long before other autoimmune manifestations. Immunization of young, preautoimmune lupus mice with nucleosomes augmented the production of autoantibodies and markedly accelerated the development of severe glomerulonephritis. Previously, crude preparations containing nucleosomes were shown by others to have polyclonal mitogenic activity for B cells from normal as well as lupus mice. Identification here of pure mononucleosome as a lupus-specific immunogen for the Th cells that selectively help the pathogenic anti-DNA autoantibody producing B cells of lupus could lead to the design of specific therapy against this pathogenic autoimmune response.