Signaling thresholds govern heterogeneity in IL-7-receptor-mediated responses of naïve CD8+ T cells

Variable sensitivity to T-cell-receptor (TCR)- and IL-7-receptor (IL-7R)-mediated homeostatic signals among naïve T cells has thus far been largely attributed to differences in TCR specificity. We show here that even when withdrawn from self-peptide-induced TCR stimulation, CD8+ T cells exhibit heterogeneous responses to interleukin-7 (IL-7) that are mechanistically associated with IL-7R expression differences that correlate with relative CD5 expression. Whereas CD5hi and CD5lo T cells survive equivalently in the presence of saturating IL-7 levels in vitro, CD5hi T cells proliferate more robustly. Conversely, CD5lo T cells exhibit prolonged survival when withdrawn from homeostatic stimuli. Through quantitative experimental analysis of signaling downstream of IL-7R, we find that the enhanced IL-7 responsiveness of CD5hi T cells is directly related to their greater surface IL-7R expression. Further, we identify a quantitative threshold in IL-7R-mediated signaling capacity required for proliferation that lies well above an analogous threshold requirement for survival. These distinct thresholds allow subtle differences in IL-7R expression between CD5lo and CD5hi T cells to give rise to significant variations in their respective IL-7-induced proliferation, without altering survival. Heterogeneous IL-7 responsiveness is observed similarly in vivo, with CD5hi naïve T cells proliferating preferentially in lymphopenic mice or lymphoreplete mice administered with exogenous IL-7. However, IL-7 in lymphoreplete mice appears to be maintained at an effective level for preserving homeostasis, such that neither CD5hi IL-7Rhi nor CD5lo IL-7Rlo T cells proliferate or survive preferentially. Our findings indicate that IL-7R-mediated signaling not only maintains the size but also impacts the diversity of the naïve T-cell repertoire

Analysis of genetic diversity among tropical and subtropical maize inbred lines using SSR markers

Genetic diversity of 24 tropical and subtropical elite maize lines was assessed at molecular level employ-ing 42 Simple Sequence Repeats. A total of 107 alleles with an average of 2.55 alleles per locus were detected. The Polymorphism Information Content (PIC) values of 42 SSR loci ranged from 0.08 (UMC1428) to 0.68 (UMC2189 and UMC2332) with the overall calculated PIC mean value of 0.44, whereas the Discrimination Rate (DR) value for SSR markers ranged from 0.09 (UMC2089) to 0.42 (UMC1311) with the average DR value of 0.26. Pair-wise genet-ic similarity (GS) values, calculated by Jaccard’s coefficients, ranged between 0.25 and 0.78 with a mean genetic similarity of 0.63, indicating the existence of adequate amount of genetic divergence among the genotypes selected for the study. The cluster dendrogram separated all the inbred lines into six main clusters with sub clusters based on genetic similarity. Factorial analysis also confirmed a nearly similar pattern for grouping these inbred lines as pre-sented by cluster dendrogram. In this study, SSR markers were found to be powerful tool for detection of genetic diversity in maize inbred lines. These findings could provide information for effective utilization of these materials for development of maize hybrids as well as for genetic improvement of inbred lines

2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation: executive summary.

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New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

withdrawn 2017 hrs ehra ecas aphrs solaece expert consensus statement on catheter and surgical ablation of atrial fibrillation

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Striking Immune Phenotypes in Gene-Targeted Mice Are Driven by a Copy-Number Variant Originating from a Commercially Available C57BL/6 Strain

We describe a homozygous copy-number variant that disrupts the function of Dock2 in a commercially available C57BL/6 mouse strain that is widely used for backcrossing. This Dock2 allele was presumed to have spontaneously arisen in a colony of Irf5 knockout mice. We discovered that this allele has actually been inadvertently backcrossed into multiple mutant mouse lines, including two engineered to be deficient in Siae and Cmah. This particular commercially obtained subline of C57BL/6 mice also exhibits several striking immune phenotypes that have been previously described in the context of Dock2 deficiency. Inadvertent backcrossing of a number of gene-targeted mice into this background has complicated the interpretation of several immunological studies. In light of these findings, published studies involving immune or hematopoietic phenotypes in which these C57BL/6 mice have been used as controls, as experimental animals, or for backcrossing will need to be reinterpreted

Effect of Flavonoid-mediated Free IAA Regulation on Growth and Development of in Vitro-Grown Tobacoo Seedlings.

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Not AvailableFrench bean (Phaseolus vulgaris L.) is an important vegetable known as green beans, which is widely cultivated during winter in the subtropics and early spring to fall in temperate zones throughout the world. In India, it is grown in the foothills to higher hills (northwestern Himalayan regions) and North Indian plains (subtropical zone) in different seasons of the year. In India, the French bean breeding program was strengthened with the commencement of the All India Coordinated Research Project on Vegetable Crops (AICRP-VC) in 1971. Only a few bushtype cultivars such as VL Bauni Bean 1, Arka Komal, Contender, and Pant Anupama have been released through AICRP-VC for cultivation in Agro-ecological Zones I (temperate zone) of India (Rai et al., 2004). Because of the dwarf plant habit, short duration, and quality pods, ‘Contender’ has been widely cultivated by the Indian farmers of northwestern Himalayan states (Uttarakhand, Himachal Pradesh, Jammu, and Kashmir). Hence, in this article, we report the release of ‘VL Bean 2’, a cultivar with high green pod yield and better horticultural traits such as pod color, shape, and length as compared with those of current cultivars, including ‘Contender’, available to Indian farmers. This cultivar may be adapted to other temperate regions of the world having similar climatic conditions.Not Availabl