Release of serine/threonine-phosphorylated adaptors from signaling microclusters down-regulates T cell activation

Serine/threonine phosphorylation of the T cell adaptor proteins SLP76 and GADS by HPK1 induces their release from signaling microclusters and subsequent termination of the T cell response

Concordant Gene Expression in Leukemia Cells and Normal Leukocytes Is Associated with Germline cis-SNPs

The degree to which gene expression covaries between different primary tissues within an individual is not well defined. We hypothesized that expression that is concordant across tissues is more likely influenced by genetic variability than gene expression which is discordant between tissues. We quantified expression of 11,873 genes in paired samples of primary leukemia cells and normal leukocytes from 92 patients with acute lymphoblastic leukemia (ALL). Genetic variation at >500,000 single nucleotide polymorphisms (SNPs) was also assessed. The expression of only 176/11,783 (1.5%) genes was correlated (p<0.008, FDR = 25%) in the two tissue types, but expression of a high proportion (20 of these 176 genes) was significantly related to cis-SNP genotypes (adjusted p<0.05). In an independent set of 134 patients with ALL, 14 of these 20 genes were validated as having expression related to cis-SNPs, as were 9 of 20 genes in a second validation set of HapMap cell lines. Genes whose expression was concordant among tissue types were more likely to be associated with germline cis-SNPs than genes with discordant expression in these tissues; genes affected were involved in housekeeping functions (GSTM2, GAPDH and NCOR1) and purine metabolism

Casein kinase I delta controls centrosome positioning during T cell activation

CK1delta binds and phosphorylates the microtubule plus-end–binding protein EB1 and promotes centrosome translocation to the immunological synapse in T cells

Identification, Replication, and Functional Fine-Mapping of Expression Quantitative Trait Loci in Primary Human Liver Tissue

The discovery of expression quantitative trait loci (“eQTLs”) can help to unravel genetic contributions to complex traits. We identified genetic determinants of human liver gene expression variation using two independent collections of primary tissue profiled with Agilent (n = 206) and Illumina (n = 60) expression arrays and Illumina SNP genotyping (550K), and we also incorporated data from a published study (n = 266). We found that ∼30% of SNP-expression correlations in one study failed to replicate in either of the others, even at thresholds yielding high reproducibility in simulations, and we quantified numerous factors affecting reproducibility. Our data suggest that drug exposure, clinical descriptors, and unknown factors associated with tissue ascertainment and analysis have substantial effects on gene expression and that controlling for hidden confounding variables significantly increases replication rate. Furthermore, we found that reproducible eQTL SNPs were heavily enriched near gene starts and ends, and subsequently resequenced the promoters and 3′UTRs for 14 genes and tested the identified haplotypes using luciferase assays. For three genes, significant haplotype-specific in vitro functional differences correlated directly with expression levels, suggesting that many bona fide eQTLs result from functional variants that can be mechanistically isolated in a high-throughput fashion. Finally, given our study design, we were able to discover and validate hundreds of liver eQTLs. Many of these relate directly to complex traits for which liver-specific analyses are likely to be relevant, and we identified dozens of potential connections with disease-associated loci. These included previously characterized eQTL contributors to diabetes, drug response, and lipid levels, and they suggest novel candidates such as a role for NOD2 expression in leprosy risk and C2orf43 in prostate cancer. In general, the work presented here will be valuable for future efforts to precisely identify and functionally characterize genetic contributions to a variety of complex traits

Enclosure design

There are many advantages to housing reptiles in indoor enclosures. Housing reptiles inside also minimizes the risk of contact with wild reptiles or potential predators and reduces the risk posed by parasites. There is a need to replicate natural environmental cues, with the associated cost of purchasing and maintaining heating and lighting devices and the limitations of available space. Housing a reptile outdoors usually allows for a larger, better ventilated enclosure. When designing enclosures, both indoors and out, there are some basic points to consider: location, design, construction materials, access, furniture, heating and lighting. Ultimately, the choice of enclosure and the design is the owner's choice. Species requirements, individual behavioural needs, owner preference for naturalistic versus utilitarian, cost and ease of maintenance all factor into the choice. From a veterinary perspective, better designed enclosures will tend to lead to healthier animals, as they supply a better microclimate and secure options for the animals

Differential diagnoses: a problem‐based approach

This chapter provides a guide to the differential diagnoses of the most common presenting signs of disease in the four major reptile taxa: snakes, lizards, chelonians and crocodilians. For each presenting sign, a list of differential diagnoses is provided. These lists include circumstances where the presenting sign represents a normal state for that group of reptiles. They also include the husbandry errors that will cause, or predispose to, these presenting signs. The lists are intended to give the clinician a starting point for the diagnostic process

Key changes to NMC programme standards: an opportunity for progress

This document is the Accepted Manuscript version of a Published Work that appeared in final form in [British Journal of Nursing], copyright © MA Education, after peer review and technical editing by the publisher. To access the final edited and published work see [https://www.magonlinelibrary.com/doi/abs/10.12968/bjon.2023.32.17.854]

How many practice hours are required to become a registered nurse?

This document is the Accepted Manuscript version of a Published Work that appeared in final form in [British Journal of Nursing], copyright © MA Education, after peer review and technical editing by the publisher. To access the final edited and published work see [https://www.magonlinelibrary.com/doi/abs/10.12968/bjon.2022.31.17.908].Globally, the number of nurse vacancies is high, and there has been much scrutiny on the preparation of the nursing workforce. The World Health Organization (2020) has called for an acceleration of nurse education to meet future demands. In the UK, nursing is at a critical juncture. Post-pandemic attrition rates are high and, despite ambitious government targets, recruitment is unable to meet demand. A Nursing and Midwifery Council (NMC) report (NMC, 2022a) demonstrated that almost half the number of graduate nurses joining the register for the first time (48% of 48 436) completed nurse education outside the UK. Of this group, 66% were educated in India or the Philippines. Nurse education in the UK is approve