Ikaros has a crucial role in regulation of B cell receptor signaling

transcription factor Ikaros, a key regulator of hematopoiesis, has an essential role in lymphocyte development. In mice, fetal lymphoid differentiation is blocked in the absence of Ikaros, and whereas T cells develop postnatally, B cells are totally absent. The significance of Ikaros in the B cell development is evident, but how Ikaros regulates B cell function has neither been established nor previously been studied with B cells that lack Ikaros expression. Here we show that disruption of Ikaros in the chicken B cell line DT40 induces a B cell receptor (BCR) signaling defect with reduced phospholipase C gamma 2 phosphorylation and impaired intracellular calcium mobilization, which is restored by Ikaros reintroduction. Furthermore, we show that lack of Ikaros induces hyperphosphorylation of Casitas B lymphoma protein subsequent to BCR activation. These results indicate that the absolute need of Ikaros for development, cell fate decisions and maintenance of B cells is due to the enhancement of BCR signaling

Isoscalar-isovector mass splittings in excited mesons

Mass splittings between the isovector and isoscalar members of meson nonets arise in part from hadronic loop diagrams which violate the Okubo-Zweig-Iizuka rule. Using a model for these loop processes which works qualitatively well in the established nonets, I tabulate predictions for the splittings and associated isoscalar mixing angles in the remaining nonets below about 2.5 GeV, and explain some of their systematic features. The results for excited vector mesons compare favorably with experiment.Comment: 8 RevTeX pages, including 1 LaTeX figure. CMU-HEP93-23/DOE-ER-40682-4

The effects of meson mixing on dilepton spectra

The effect of scalar and vector meson mixing on the dilepton radiation from hot and dense hadronic matter is estimated in different isospin channels. In particular, we study the effect of $\sigma$-$\omega$ and $\rho-a_0$ mixing and calculate the corresponding rates. Effects are found to be significant compared to standard $\pi$-$\pi$ and $K$-${\bar K}$ annihilations. While the mixing in the isoscalar channel mostly gives a contribution in the invariant mass range between the two-pion threshold and the $\omega$ peak, the isovector channel mixing induces an additional peak just below that of the $\phi$. Experimentally, the dilepton signals from $\rho$-$a_0$ mixing seem to be more tractable than those from $\sigma$-$\omega$ mixing.Comment: 10 pages, 9 figure

Elements of Good Training in Anatomic Pathology

The American College of Veterinary Pathologists’ (ACVP’s) 2007–2012 strategic plan recognized the crisis confronting academic training programs and formed a task force to address these concerns. One area of concern identified by the ACVP Training Program Development Task Force was the lack of guidelines to make training more consistent across all programs and provide justification for maintaining or increasing faculty numbers and training resources. Training guidelines for clinical pathology have been outlined in three publications.1,2,4 The current document addresses the need for training guidelines in veterinary anatomic pathology

C16 ceramide is crucial for triacylglycerol-induced apoptosis in macrophages

Triacylglycerol (TG) accumulation caused by adipose triglyceride lipase (ATGL) deficiency or very low-density lipoprotein (VLDL) loading of wild-type (Wt) macrophages results in mitochondrial-mediated apoptosis. This phenotype is correlated to depletion of Ca2+ from the endoplasmic reticulum (ER), an event known to induce the unfolded protein response (UPR). Here, we show that ER stress in TG-rich macrophages activates the UPR, resulting in increased abundance of the chaperone GRP78/BiP, the induction of pancreatic ER kinase-like ER kinase, phosphorylation and activation of eukaryotic translation initiation factor 2A, the translocation of activating transcription factor (ATF)4 and ATF6 to the nucleus and the induction of the cell death executor CCAAT/enhancer-binding protein homologous protein. C16:0 ceramide concentrations were increased in Atgl–/– and VLDL-loaded Wt macrophages. Overexpression of ceramide synthases was sufficient to induce mitochondrial apoptosis in Wt macrophages. In accordance, inhibition of ceramide synthases in Atgl–/– macrophages by fumonisin B1 (FB1) resulted in specific inhibition of C16:0 ceramide, whereas intracellular TG concentrations remained high. Although the UPR was still activated in Atgl–/– macrophages, FB1 treatment rescued Atgl–/– macrophages from mitochondrial dysfunction and programmed cell death. We conclude that C16:0 ceramide elicits apoptosis in Atgl–/– macrophages by activation of the mitochondrial apoptosis pathway

tau-->eta(eta')2pi nu, 3pi nu and WZW anomaly

The effects of the anomalous contact terms are taken into account in tau to eta(eta')2pi nu decay. tau to 3pi nu is computed. Theoretical result agrees with data. It is the first time the anomalous vertex eta aa is tested. An a_{1} resonance is predicted in the final state. The decay rate of tau to eta'3pi nu is predicted.Comment: 15 pages, one latex file for the paper and one p-script file for the figur

Rhegmatogenous retinal detachment in Scotland: research design and methodology

<p>Abstract</p> <p>Background</p> <p>Rhegmatogenous retinal detachment (RRD) is a potentially blinding condition and a common cause of ocular morbidity. Establishing an accurate estimate of disease incidence and distribution is an important first step in assessing the healthcare burden related to this condition and in subsequent planning and provision of treatment strategies. The aim of this study is to obtain a first estimate incidence of RRD in Scotland, to estimate the incidence of familial RRD and to describe the known associations of RRD within the study population.</p> <p>Methods/Design</p> <p>We have established a national prospective observational study seeking to identify and recruit all incident cases of RRD in the Scottish population over a 2 year period. After fully informed consent, all participants will have a blood sample taken and a full medical history and clinical examination performed including visual acuity, refraction, slit-lamp examination, intra-ocular pressure measurement and detailed fundal examination. We describe the study design and protocol.</p> <p>Conclusion</p> <p>This study will provide the first estimate of the annual incidence of RRD in Scotland. The findings of this study will be important in estimating the burden of disease and in the planning of future health care policy related to this condition. This study will also establish a genetic resource for a genome wide association study to investigate if certain genetic variants predispose to RRD.</p

Integration of P2Y receptor-activated signal transduction pathways in G protein-dependent signalling networks

The role of nucleotides in intracellular energy provision and nucleic acid synthesis has been known for a long time. In the past decade, evidence has been presented that, in addition to these functions, nucleotides are also autocrine and paracrine messenger molecules that initiate and regulate a large number of biological processes. The actions of extracellular nucleotides are mediated by ionotropic P2X and metabotropic P2Y receptors, while hydrolysis by ecto-enzymes modulates the initial signal. An increasing number of studies have been performed to obtain information on the signal transduction pathways activated by nucleotide receptors. The development of specific and stable purinergic receptor agonists and antagonists with therapeutical potential largely contributed to the identification of receptors responsible for nucleotide-activated pathways. This article reviews the signal transduction pathways activated by P2Y receptors, the involved second messenger systems, GTPases and protein kinases, as well as recent findings concerning P2Y receptor signalling in C6 glioma cells. Besides vertical signal transduction, lateral cross-talks with pathways activated by other G protein-coupled receptors and growth factor receptors are discussed