Tissue memory CD4+ T cells expressing IL-7 receptor-alpha (CD127) preferentially support latent HIV-1 infection.

The primary reservoir for HIV is within memory CD4+ T cells residing within tissues, yet the features that make some of these cells more susceptible than others to infection by HIV is not well understood. Recent studies demonstrated that CCR5-tropic HIV-1 efficiently enters tissue-derived memory CD4+ T cells expressing CD127, the alpha chain of the IL7 receptor, but rarely completes the replication cycle. We now demonstrate that the inability of HIV to replicate in these CD127-expressing cells is not due to post-entry restriction by SAMHD1. Rather, relative to other memory T cell subsets, these cells are highly prone to undergoing latent infection with HIV, as revealed by the high levels of integrated HIV DNA in these cells. Host gene expression profiling revealed that CD127-expressing memory CD4+ T cells are phenotypically distinct from other tissue memory CD4+ T cells, and are defined by a quiescent state with diminished NFκB, NFAT, and Ox40 signaling. However, latently-infected CD127+ cells harbored unspliced HIV transcripts and stimulation of these cells with anti-CD3/CD28 reversed latency. These findings identify a novel subset of memory CD4+ T cells found in tissue and not in blood that are preferentially targeted for latent infection by HIV, and may serve as an important reservoir to target for HIV eradication efforts

Atmospheric water balance

Submitted to Office of Water Resources Research, U.S. Department of Interior.Includes bibliographical references.OWRR project no. B-035-COLO

Electronic Chart of the Future: The Hampton Roads Project

ECDIS is evolving from a two-dimensional static display of chart-related data to a decision support system capable of providing real-time or forecast information. While there may not be consensus on how this will occur, it is clear that to do this, ENC data and the shipboard display environment must incorporate both depth and time in an intuitively understandable way. Currently, we have the ability to conduct high-density hydrographic surveys capable of producing ENCs with decimeter contour intervals or depth areas. Yet, our existing systems and specifications do not provide for a full utilization of this capability. Ideally, a mariner should be able to benefit from detailed hydrographic data, coupled with both forecast and real-time water levels, and presented in a variety of perspectives. With this information mariners will be able to plan and carry out transits with the benefit of precisely determined and easily perceived underkeel, overhead, and lateral clearances. This paper describes a Hampton Roads Demonstration Project to investigate the challenges and opportunities of developing the “Electronic Chart of the Future.” In particular, a three-phase demonstration project is being planned: 1. Compile test datasets from existing and new hydrographic surveys using advanced data processing and compilation procedures developed at the University of New Hampshire’s Center for Coastal and Ocean Mapping/Joint Hydrographic Center (CCOM/JHC); 2. Investigate innovative approaches being developed at the CCOM/JHC to produce an interactive time- and tide-aware navigation display, and to evaluate such a display on commercial and/or government vessels; 3. Integrate real-time/forecast water depth information and port information services transmitted via an AIS communications broadcast

CD8αα intestinal intraepithelial lymphocytes derived from two thymic precursors seed the intestine in early life

TCRαβ CD4 CD8αα intestinal intraepithelial lymphocytes (CD8αα IEL) descend from thymic precursors. To better define this IEL precursor (IELp) population, we analyzed their maturation, localization, and emigration. Using rigorous lineage exclusion criteria, we defined two precursors among DN TCRβ thymocytes: a nascent PD-1 population and a T-bet population that accumulates with age. Both gave rise to intestinal CD8αα IEL upon adoptive transfer. In adult mice, PD-1 cells contained more self-reactive clones, localized to the cortex, and were dominant in S1PR1-dependent thymic egress. Gut homing α4β7 was already expressed by these IELp at a thymic stage. To understand the kinetics of CD8αα IEL seeding the intestine, we performed "timestamp" experiments: We crossed Cd4 with Rosa26 (stop-floxed tdTomato) mice. In these mice, tamoxifen or its metabolite 4-OHT permanently labels every CD4 expressing cell. As TCRαβ T cells (including CD8αα IEL) go through a CD4 CD8 stage during thymic development, a single dose of tamoxifen or 4-OHT will label thymic IEL precursors permanently, so that they can be tracked when seeding the gut. Our results indicate that these cells enter the intestine during a narrow time window in early life and that this influx is almost completely shut down by the age of 3 weeks. These data provide an important foundation for understanding the biology of this abundant population of barrier surface T cells

Quantum properties of dichroic silicon vacancies in silicon carbide

The controlled generation and manipulation of atom-like defects in solids has a wide range of applications in quantum technology. Although various defect centres have displayed promise as either quantum sensors, single photon emitters or light-matter interfaces, the search for an ideal defect with multi-functional ability remains open. In this spirit, we investigate here the optical and spin properties of the V1 defect centre, one of the silicon vacancy defects in the 4H polytype of silicon carbide (SiC). The V1 centre in 4H-SiC features two well-distinguishable sharp optical transitions and a unique S=3/2 electronic spin, which holds promise to implement a robust spin-photon interface. Here, we investigate the V1 defect at low temperatures using optical excitation and magnetic resonance techniques. The measurements, which are performed on ensemble, as well as on single centres, prove that this centre combines coherent optical emission, with up to 40% of the radiation emitted into the zero-phonon line (ZPL), a strong optical spin signal and long spin coherence time. These results single out the V1 defect in SiC as a promising system for spin-based quantum technologies

Effects of the Soluble Fiber Complex PolyGlycopleX® on Glucose Homeostasis and Body Weight in Young Zucker Diabetic Rats

Dietary fiber can reduce insulin resistance, body weight, and hyperlipidemia depending on fiber type, water solubility, and viscosity. PolyGlycopleX® (PGX®) is a natural, novel water soluble, non-starch polysaccharide complex that with water forms a highly viscous gel compared to other naturally occurring dietary fiber. We determined the effect of dietary PGX® vs. cellulose and inulin on the early development of insulin resistance, body weight, hyperlipidemia, and glycemia-induced tissue damage in young Zucker diabetic rats (ZDFs) in fasted and non-fasted states. ZDFs (5 weeks old) were fed a diet containing 5% (wgt/wgt) cellulose, inulin, or PGX® for 8 weeks. Body weight, lipids, insulin, and glucose levels were determined throughout the study and homeostasis model assessment (HOMA) was used to measure insulin sensitivity throughout the study in fasted animals. At study termination, insulin sensitivity (oral glucose tolerance test, OGTT) and kidney, liver, and pancreatic histopathology were determined. Body weight and food intake were significantly reduced by PGX® vs. inulin and cellulose. Serum insulin in fasted and non-fasted states was significantly reduced by PGX® as was non-fasted blood glucose. Insulin resistance, measured as a HOMA score, was significantly reduced by PGX® in weeks 5 through 8 as well as terminal OGTT scores in fed and fasted states. Serum total cholesterol was also significantly reduced by PGX®. PGX® significantly reduced histological kidney and hepatic damage in addition to reduced hepatic steatosis and cholestasis. A greater mass of pancreatic β-cells was found in the PGX® group. PGX® therefore may be a useful dietary additive in the control of the development of the early development of the metabolic syndrome

Campylobacter concisus Impairs Sodium Absorption in Colonic Epithelium via ENaC Dysfunction and Claudin-8 Disruption

The epithelial sodium channel (ENaC) can increase the colonic absorptive capacity for salt and water. Campylobacter concisus is a common pathogenic epsilonproteobacterium, causing enteritis and diarrhea. It can induce barrier dysfunction in the intestine, but its influence on intestinal transport function is still unknown. Therefore, our study aimed to characterize C. concisus effects on ENaC using the HT-29/B6-GR/MR (epithelial cell line HT-29/B6 transfected with glucocorticoid and mineralocorticoid receptors) cell model and mouse colon. In Ussing chambers, C. concisus infection inhibited ENaC-dependent Na+ transport as indicated by a reduction in amiloride-sensitive short circuit current (-55%, n = 15, p < 0.001). This occurred via down-regulation of β- and γ-ENaC mRNA expression and ENaC ubiquitination due to extracellular signal-regulated kinase (ERK)1/2 activation, predicted by Ingenuity Pathway Analysis (IPA). In parallel, C. concisus reduced the expression of the sealing tight junction (TJ) protein claudin-8 and induced claudin-8 redistribution off the TJ domain of the enterocytes, which facilitates the back leakage of Na+ ions into the intestinal lumen. In conclusion, C. concisus caused ENaC dysfunction via interleukin-32-regulated ERK1/2, as well as claudin-8-dependent barrier dysfunction-both of which contribute to Na+ malabsorption and diarrhea

A computational model for sex-specific genetic architecture of complex traits in humans: Implications for mapping pain sensitivity

Understanding differences in the genetic architecture of complex traits between the two sexes has significant implications for evolutionary studies and clinical diagnosis. However, our knowledge about sex-specific genetic architecture is limited largely because of a lack of analytical models that can detect and quantify the effects of sex on the complexity of quantitative genetic variation. Here, we derived a statistical model for mapping DNA sequence variants that contribute to sex-specific differences in allele frequencies, linkage disequilibria, and additive and dominance genetic effects due to haplotype diversity. This model allows a genome-wide search for functional haplotypes and the estimation and test of haplotype by sex interactions and sex-specific heritability. The model, validated by simulation studies, was used to detect sex-specific functional haplotypes that encode a pain sensitivity trait in humans. The model could have important implications for mapping complex trait genes and studying the detailed genetic architecture of sex-specific differences