Endogenous antigen processing drives the primary CD4+ T cell response to influenza.

By convention, CD4+ T lymphocytes recognize foreign and self peptides derived from internalized antigens in combination with major histocompatibility complex class II molecules. Alternative pathways of epitope production have been identified, but their contributions to host defense have not been established. We show here in a mouse infection model that the CD4+ T cell response to influenza, critical for durable protection from the virus, is driven principally by unconventional processing of antigen synthesized within the infected antigen-presenting cell, not by classical processing of endocytosed virions or material from infected cells. Investigation of the cellular components involved, including the H2-M molecular chaperone, the proteasome and γ-interferon-inducible lysosomal thiol reductase revealed considerable heterogeneity in the generation of individual epitopes, an arrangement that ensures peptide diversity and broad CD4+ T cell engagement. These results could fundamentally revise strategies for rational vaccine design and may lead to key insights into the induction of autoimmune and anti-tumor responses

Does vitamin D supplementation alter plasma adipokines concentrations? A systematic review and meta-analysis of randomized controlled trials

We aimed to elucidate the role of vitamin D supplementation on adipokines through a systematic review and a meta-analysis of randomized placebo-controlled trials (RCTs). The search included PUBMED, Scopus, Web of Science and Google Scholar through July 1st, 2015. Finally we identified 9 RCTs and 484 participants. Meta-analysis of data from 7 studies did not find a significant change in plasma adiponectin concentrations following vitamin D supplementation (mean difference [MD]: 4.45%, 95%CI: −3.04, 11.93, p = 0.244; Q = 2.18, I2 = 0%). In meta-regression, changes in plasma adiponectin concentrations following vitamin D supplementation were found to be independent of treatment duration (slope: 0.25; 95%CI: −0.69, 1.19; p = 0.603) and changes in serum 25-hydroxy vitamin D [25(OH)D] levels (slope: −0.02; 95%CI: −0.15, 0.12; p = 0.780). Meta-analysis of data from 6 studies did not find a significant change in plasma leptin concentrations following vitamin D supplementation (MD: −4.51%, 95%CI: −25.13, 16.11, p = 0.668; Q = 6.41, I2 = 21.97%). Sensitivity analysis showed that this effect size is sensitive to one of the studies; removing it resulted in a significant reduction in plasma leptin levels (MD: −12.81%, 95%CI: −24.33, −1.30, p = 0.029). In meta-regression, changes in plasma leptin concentrations following vitamin D supplementation were found to be independent of treatment duration (slope: −1.93; 95%CI: −4.08, 0.23; p = 0.080). However, changes in serum 25(OH)D were found to be significantly associated with changes in plasma leptin levels following vitamin D supplementation (slope: 1.05; 95%CI: 0.08, 2.02; p = 0.033). In conclusion, current data did not indicate a significant effect of vitamin D supplementation on adiponectin and leptin levels

A Comparative Study of Human TLR 7/8 Stimulatory Trimer Compositions in Influenza A Viral Genomes

Background: Variation in the genomes of single-stranded RNA viruses affects their infectivity and pathogenicity in two ways. First, viral genome sequence variations lead to changes in viral protein sequences and activities. Second, viral genome sequence variation produces diversity at the level of nucleotide composition and diversity in the interactions between viral RNAs and host toll-like receptors (TLRs). A viral genome-typing method based on this type of diversity has not yet been established. Methodology/Principal Findings: In this study, we propose a novel genomic trait called the ‘‘TLR stimulatory trimer composition’ ’ (TSTC) and two quantitative indicators, Score S and Score N, named ‘‘TLR stimulatory scores’ ’ (TSS). Using the complete genome sequences of 10,994 influenza A viruses (IAV) and 251 influenza B viruses, we show that TSTC analysis reveals the diversity of Score S and Score N among the IAVs isolated from various hosts. In addition, we show that low values of Score S are correlated with high pathogenicity and pandemic potential in IAVs. Finally, we use Score S and Score N to construct a logistic regression model to recognize IAV strains that are highly pathogenic or have high pandemic potential. Conclusions/Significance: Results from the TSTC analysis indicate that there are large differences between human and avian IAV genomes (except for segment 3), as illustrated by Score S. Moreover, segments 1, 2, 3 and 4 may be majo

Parenting Culture(s): Ideal-Parent Beliefs Across 37 Countries

What is it to be “an ideal parent”? Does the answer differ across countries and social classes? To answer these questions in a way that minimizes bias and ethnocentrism, we used open-ended questions to explore ideal-parent beliefs among 8,357 mothers and 3,517 fathers from 37 countries. Leximancer Semantic Network Analysis was utilized to first determine parenting culture zones (i.e., countries with shared ideal-parent beliefs) and then extract the predominant themes and concepts in each culture zone. The results yielded specific types of ideal-parent beliefs in five parenting culture zones: being “responsible and children/family-focused” for Asian parents, being “responsible and proper demeanor-focused” for African parents, and being “loving and responsible” for Hispanic-Italian parents. Although the most important themes and concepts were the same in the final two zones—being “loving and patient,” there were subtle differences: English-speaking, European Union, and Russian parents emphasized “being caring,” while French-speaking parents valued “listening” or being “present.” Ideal-parent beliefs also differed by education levels within culture zones, but no general pattern was discerned across culture zones. These findings suggest that the country in which parents were born cannot fully explain their differences in ideal-parent beliefs and that differences arising from social class or education level cannot be dismissed. Future research should consider how these differences affect the validity of the measurements in question and how they can be incorporated into parenting intervention research within and across cultures

Parental Burnout Around the Globe: a 42-Country Study

High levels of stress in the parenting domain can lead to parental burnout, a condition that has severe consequences for both parents and children. It is not yet clear, however, whether parental burnout varies by culture, and if so, why it might do so. In this study, we examined the prevalence of parental burnout in 42 countries (17,409 parents; 71% mothers; M_{age} = 39.20) and showed that the prevalence of parental burnout varies dramatically across countries. Analyses of cultural values revealed that individualistic cultures, in particular, displayed a noticeably higher prevalence and mean level of parental burnout. Indeed, individualism plays a larger role in parental burnout than either economic inequalities across countries, or any other individual and family characteristic examined so far, including the number and age of children and the number of hours spent with them. These results suggest that cultural values in Western countries may put parents under heightened levels of stress

Targeting Beclin 1 for viral subversion of macroautophagy

We have recently characterized that influenza A virus blocks autophagosome degradation via its matrix protein 2. Matrix protein 2 seems to achieve this macroautophagy inhibition not by its well-characterized proton channel function, but possibly due to its binding to Atg6/Beclin 1, thereby enhancing the death of its host cell. Here we discuss several viruses that now have been described to compromise macroautophagy via binding to Atg6/Beclin 1 with different outcomes for their replication, and how interaction with one and the same protein could inhibit autophagosome generation or degradation