IL-21 enhances influenza vaccine responses in aged macaques with suppressed SIV infection.

Natural aging and HIV infection are associated with chronic low-grade systemic inflammation, immune senescence, and impaired antibody responses to vaccines such as the influenza (flu) vaccine. We investigated the role of IL-21, a CD4+ T follicular helper cell (Tfh) regulator, on flu vaccine antibody response in nonhuman primates (NHPs) in the context of age and controlled SIV mac239 infection. Three doses of the flu vaccine with or without IL-21-IgFc were administered at 3-month intervals in aged SIV+ NHPs following virus suppression with antiretroviral therapy. IL-21-treated animals demonstrated higher day 14-postboost antibody responses, which associated with expanded CD4+ T central memory cells and peripheral Tfh-expressing (pTfh-expressing) T cell immunoreceptor with Ig and ITIM domains (TIGIT), expanded activated memory B cells, and contracted CD11b+ monocytes. Draining lymph node (LN) tissue from IL-21-treated animals revealed direct association between LN follicle Tfh density and frequency of circulating TIGIT+ pTfh cells. We conclude that IL-21 enhances flu vaccine-induced antibody responses in SIV+ aged rhesus macaques (RMs), acting as an adjuvant modulating LN germinal center activity. A strategy to supplement IL-21 in aging could be a valuable addition in the toolbox for improving vaccine responses in an aging HIV+ population

Impact of time of ART initiation on HIV specific T cell functionality in perinatally infected children

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Accelerated CD8+ T cell maturation in infants with perinatal HIV infection

in perinatal HIV infection, early antiretroviral therapy (ART) initiation is recommended but questions remain regarding infant immune responses to HIV and its impact on immune development. using single cell transcriptional and phenotypic analysis we evaluated the T cell compartment at pre-ART initiation of infants with perinatally acquired HIV from maputo, mozambique (Towards AIDS remission approaches cohort). CD8+ T cell maturation subsets exhibited altered distribution in HIV exposed infected (HEI) infants relative to HIV exposed uninfected infants with reduced naive, increased effectors, higher frequencies of activated T cells, and lower frequencies of cells with markers of self-renewal. additionally, a cluster of CD8+ T cells identified in HEI displayed gene profiles consistent with cytotoxic T lymphocytes and showed evidence for hyper expansion. longitudinal phenotypic analysis revealed accelerated maturation of CD8+ T cells was maintained in HEI despite viral control. the results point to an HIV-directed immune response that is likely to influence reservoir establishment

Physiological and biochemical response to higher temperature stress in hot pepper (Capsicum annuum L.)

The present study was conducted to evaluate the physiological and biochemical changes in some thermotolerant and thermosensitive chilli (Capsicum annuum L.) genotypes. Fourteen chilli genotypes (SL 461, PP 404, DL 161, MS 341, VR 521, PB 405, PS 403, SD 463, FL 201, AC 102, S 343, SL 462 and SL 464 along with sensitive check [Royal Wonder of bell pepper] were evaluated for heat tolerance. The observations on morpho-physiological and biochemical parameters were recorded at 45, 65, 85 and 105 days after transplanting (DAT) (high temperature period). On the basis of our studies, genotypes S 343, AC 102 and FL 201 were found to be relatively thermotolerant. However, high temperature markedly decreased the photosynthetic activity of chilli plants by decreasing the photosynthetic pigments in leaf chloroplasts of all the genotypes. The levels of ascorbic acid, total soluble sugars and total phenols increased in the leaves of all the genotypes with the maturity of the crop. Electrolyte leakage and proline content also increased with rise in temperature. Genotypes AC 102 and S 343 were able to accumulate the maximum ascorbic acid, proline, total soluble sugars and total phenols under heat stress conditions. Decrease in fruit set percent led to reduction in the total yield per plant. Maximum yield was observed in genotype S 343 followed by FL 201

On the Critical Role of Ferroelectric Thickness for Negative Capacitance Device-Circuit Interaction

This paper demonstrates the critical role that Ferroelectric (FE) layer thickness (tFE) plays in Negative Capacitance (NC) transistors connecting device and circuit levels together. The study is done through fully-calibrated TCAD simulations for a 14nm FDSOI technology node, exploring the impact of tFE on the figures of merit of n-type and p-type devices, voltage transfer characteristic (VTC) and noise margin of inverter as well as the speed of buffer circuits. First, we analyze the device electrical parameters (e.g., ION, SS, ION/IOFF and Cgg) by varying tFE up to the maximum level at which hysteresis in the I-V characteristic starts. Then, we analyze the deleterious impact of Negative Differential Resistance (NDR), due to the drain to gate coupling, demonstrating how it imposes an additional constraint limiting the maximum tFE. We show the consequences of NDR effects on the VTC and noise margin of inverter, which are essential components for constructing robust clock trees in any chip. We demonstrate how the considerable increase in the gate’s capacitance due to FE seriously degrades the circuit’s performance imposing further constraints limiting the maximum tFE. Further, we analyze the impact of tFE on the SRAM cell static performance metrics such hold noise margin (HNM), read noise margin (RNM) and write noise margin (WNM) at supply voltages of 0.7V and 0.4V. We demonstrate that the HNM and RNM in a NC-FDSOI FET based SRAM cell are higher then those of the baseline FDSOI FET based SRAM cell noise margin and further increase with tFE. However, the WNM in general follows a non monotonic trend w.r.t tFE, and the trend also depends on the supply voltage. Finally, we optimize the design of the SRAM cell considering overall performance metrics. All in all, our analysis provides guidance for device and circuit designers to select the optimal FE thickness for NCFETs in which hysteresis-free operations, reliability, and performance are optimized

Rescue medication use as a patient-reported outcome in COPD: a systematic review and regression analysis.

BACKGROUND: Reducing rescue medication use is a guideline-defined goal of asthma treatment, however, little is known about the validity of rescue medicine use as a marker of symptoms in chronic obstructive pulmonary disease (COPD). To improve patient outcomes, greater insight is needed into the relationship between rescue medication use and alternative COPD outcomes. METHODS: A systematic search of electronic databases (Embase®, MEDLINE® and Cochrane CENTRAL) was conducted from database start to 26 May, 2015. Studies of bronchodilator therapy with a duration of ≥24 weeks were included if they reported either mean change from baseline (CFB) in rescue medication use in puffs/day or % rescue-free days (%RFD), and at least one other COPD endpoint. Correlation and meta-regression analyses were undertaken to test the association between rescue medication use and other COPD outcomes using weighted means (weights proportional to the sample size of the treatment group) and unweighted means (equal weight for each treatment group). Each association was assessed at 6 months and study end. RESULTS: Forty-six studies involving 46,531 patients provided mean data from 145 treatment groups for evaluation. Changes in both measures of rescue medication use were correlated with changes in trough forced expiratory volume in one second ([FEV1]; Pearson correlation coefficients |r| ≥ 0.63; p < 0.0001) and with St George's Respiratory Questionnaire (SGRQ) score (|r| ≥ 0.70; p < 0.0001) at study end. Change in rescue medication use in puffs/day during the study correlated with annualized rates of moderate/severe exacerbations at 6 months and study end (both r = 0.66; p ≤ 0.0028). CFB in puffs/day was not well correlated with Transition Dyspnoea Index (TDI), but %RFD did correlate with TDI score at 6 months and study end (both r = 0.69; p < 0.0001). The values for CFB in puffs/day corresponding to the proposed minimal clinically important differences for trough FEV1 and SGRQ score were -1.3 and -0.6 puffs/day, respectively. A -1.0 puffs/day CFB in rescue use corresponded to a change of 0.26 events/patient-year in moderate/severe exacerbations. CONCLUSION: This analysis provides clear evidence of associations at a patient group level between rescue medication use and other clinically important COPD outcomes