Ionicity-dependent proton-coupled electron transfer of supramolecular self-assembled electroactive heterocycles

Herein, we investigate the electrochemical properties of a class of Supramolecular Self-associated Amphiphilic salts (SSAs). We show that varying ionic strength of an SSA solution can cause a switching of the thermodynamics and kinetics of electron transfer. The effect of self-assembly on proton-coupled electron transfer has implications for the understanding of electron transfer kinetics in aqueous organic redox flow batteries, especially at high concentration where organic–organic intermolecular interactions become dominant even for highly soluble organic species

HIV specific CD8+ TRM-like cells in tonsils express exhaustive signatures in the absence of natural HIV control

Lymphoid tissues are an important HIV reservoir site that persists in the face of antiretroviral therapy and natural immunity. Targeting these reservoirs by harnessing the antiviral activity of local tissue-resident memory (TRM) CD8+ T-cells is of great interest, but limited data exist on TRM-like cells within lymph nodes of people living with HIV (PLWH). Here, we studied tonsil CD8+ T-cells obtained from PLWH and uninfected controls from South Africa. We show that these cells are preferentially located outside the germinal centers (GCs), the main reservoir site for HIV, and display a low cytolytic and a transcriptionally TRM-like profile distinct from blood CD8+ T-cells. In PLWH, CD8+ TRM-like cells are expanded and adopt a more cytolytic, activated, and exhausted phenotype not reversed by antiretroviral therapy (ART). This phenotype was enhanced in HIV-specific CD8+ T-cells from tonsils compared to matched blood suggesting a higher antigen burden in tonsils. Single-cell transcriptional and clonotype resolution showed that these HIV-specific CD8+ T-cells in the tonsils express heterogeneous signatures of T-cell activation, clonal expansion, and exhaustion ex-vivo. Interestingly, this signature was absent in a natural HIV controller, who expressed lower PD-1 and CXCR5 levels and reduced transcriptional evidence of T-cell activation, exhaustion, and cytolytic activity. These data provide important insights into lymphoid tissue-derived HIV-specific CD8+ TRM-like phenotypes in settings of HIV remission and highlight their potential for immunotherapy and targeting of the HIV reservoirs

Socioeconomic disparities in behavioral risk factors and health outcomes by gender in the Republic of Korea

<p>Abstract</p> <p>Background</p> <p>Few studies have examined socioeconomic disparities in health and behavioral risk factors by gender in Asian countries and in South Korea, specifically. We investigated the relationship between socioeconomic position (education, income, and occupation) and subjective and acute and chronic health outcomes and behavioral risk factors by gender, and compared results from 1998 and 2005, in the Republic of Korea.</p> <p>Methods</p> <p>We examined data from a nationally representative stratified random sample of 4213 men and 4618 women from the 1998 Korea National Health and Nutrition Examination Survey, and 8289 men and 8827 women from the 2005 Korea National Health and Nutrition Examination Survey using General Linear Modeling and multiple logistic regression methods.</p> <p>Results</p> <p>Controlling for behavioral risk factors (smoking, drinking, obesity, exercise, and sleep), those in lower socioeconomic positions had poorer health outcomes in both self-reported acute and chronic disease and subjective measures; differences were especially pronounced among women. A socioeconomic gradient for education and income was found for both men and women for morbidity and self-reported health status, but the gradient was more pronounced in women. In 1998, the odds ratios (ORs) of higher morbidity for illiterate vs. college educated females was 5.4:1 and 1.9:1 for females in the lowest income quintile vs. the highest. The OR for education decreased in 2005 to 2.9:1 and that for income quintiles remained the same at 1.9:1. The OR of lower self-reported health status for illiterate vs. college educated females was 2.9:1 and 1.6:1 for females in the lowest income quintile vs. the highest in 1998, and 3.3:1 and 2.3:1 in 2005.</p> <p>Conclusions</p> <p>Among Korean adults, men and women in lower socioeconomic position, as denoted by education, income, and somewhat less by occupation, experience significantly higher levels of morbidity and lower self-reported health status, even after controlling for standard behavioral risk factors. Disparities were more pronounced for women than for men. Efforts to reduce health disparities in South Korea require attention to the root causes of socioeconomic inequality and gender differences in the impact of socioeconomic position on health.</p

Membrane vesicles from Pseudomonas aeruginosa activate the non-canonical inflammasome through caspase-5 in human monocytes

Outer membrane vesicles (OMVs) are constitutively produced by Gram-negative bacteria both in vivo and in vitro. These lipid-bound structures carry a range of immunogenic components derived from the parent cell, which are transported into host target cells and activate the innate immune system. Recent advances in the field have shed light on some of the multifaceted roles of OMVs in host-pathogen interactions. In this study, we investigated the ability of OMVs from two clinically important pathogens, Pseudomonas aeruginosa and Helicobacter pylori, to activate canonical and non-canonical inflammasomes. P.\ua0aeruginosa OMVs induced inflammasome activation in mouse macrophages, as evidenced by "speck" formation, as well as the cleavage and secretion of interleukin-1β and caspase-1. These responses were independent of AIM2 and NLRC4 canonical inflammasomes, but dependent on the non-canonical caspase-11 pathway. Moreover, P.\ua0aeruginosa OMVs alone were able to activate the inflammasome in a TLR-dependent manner, without requiring an exogenous priming signal. In contrast, H.\ua0pylori OMVs were not able to induce inflammasome activation in macrophages. Using CRISPR/Cas9 knockout THP-1 cells lacking the human caspase-11 homologs, caspase-4 and -5, we demonstrated that caspase-5 but not caspase-4 is required for inflammasome activation by P. aeruginosa OMVs in human monocytes. In contrast, free P.\ua0aeruginosa LPS transfected into cells induced inflammasome responses via caspase-4. This suggests that caspase-4 and caspase-5 differentially recognize LPS depending on its physical form or route of delivery into the cell. These findings have relevance to Gram-negative infections in humans and the use of OMVs as novel vaccines. This article is protected by copyright. All rights reserved

The Medical Segmentation Decathlon

International challenges have become the de facto standard for comparative assessment of image analysis algorithms given a specific task. Segmentation is so far the most widely investigated medical image processing task, but the various segmentation challenges have typically been organized in isolation, such that algorithm development was driven by the need to tackle a single specific clinical problem. We hypothesized that a method capable of performing well on multiple tasks will generalize well to a previously unseen task and potentially outperform a custom-designed solution. To investigate the hypothesis, we organized the Medical Segmentation Decathlon (MSD) - a biomedical image analysis challenge, in which algorithms compete in a multitude of both tasks and modalities. The underlying data set was designed to explore the axis of difficulties typically encountered when dealing with medical images, such as small data sets, unbalanced labels, multi-site data and small objects. The MSD challenge confirmed that algorithms with a consistent good performance on a set of tasks preserved their good average performance on a different set of previously unseen tasks. Moreover, by monitoring the MSD winner for two years, we found that this algorithm continued generalizing well to a wide range of other clinical problems, further confirming our hypothesis. Three main conclusions can be drawn from this study: (1) state-of-the-art image segmentation algorithms are mature, accurate, and generalize well when retrained on unseen tasks; (2) consistent algorithmic performance across multiple tasks is a strong surrogate of algorithmic generalizability; (3) the training of accurate AI segmentation models is now commoditized to non AI experts

Monitoring activities of teenagers to comprehend their habits: study protocol for a mixed-methods cohort study

Abstract: Background: Efforts to increase physical activity in youth need to consider which activities are most likely to be sustained over time in order to promote lifelong participation in physical activity. The Monitoring Activities of Teenagers to Comprehend their Habits (MATCH) study is a prospective cohort study that uses quantitative and qualitative methods to develop new knowledge on the sustainability of specific physical activities. Methods/design: Eight hundred and forty-three grade 5 and 6 students recruited from 17 elementary schools in New Brunswick, Canada, are followed-up three times per year. At each survey cycle, participants complete self-report questionnaires in their classroom under the supervision of trained data collectors. A sub-sample of 24 physically active students is interviewed annually using a semi-structured interview protocol. Parents (or guardians) complete telephone administered questionnaires every two years, and a health and wellness school audit is completed for each school. Discussion: MATCH will provide a description of the patterns of participation in specific physical activities in youth, and enable identification of the determinants of maintenance, decline, and uptake of participation in each activity. These data will inform the development of interventions that take into account which activities are the most likely to be maintained and why activities are maintained or dropped

Targeting A20 Decreases Glioma Stem Cell Survival and Tumor Growth

The A20 protein is a known inhibitor of apoptosis that here is shown to be a novel cancer stem cell-promoting factor associated with poor glioma patient survival

Sixteen diverse laboratory mouse reference genomes define strain-specific haplotypes and novel functional loci.

We report full-length draft de novo genome assemblies for 16 widely used inbred mouse strains and find extensive strain-specific haplotype variation. We identify and characterize 2,567 regions on the current mouse reference genome exhibiting the greatest sequence diversity. These regions are enriched for genes involved in pathogen defence and immunity and exhibit enrichment of transposable elements and signatures of recent retrotransposition events. Combinations of alleles and genes unique to an individual strain are commonly observed at these loci, reflecting distinct strain phenotypes. We used these genomes to improve the mouse reference genome, resulting in the completion of 10 new gene structures. Also, 62 new coding loci were added to the reference genome annotation. These genomes identified a large, previously unannotated, gene (Efcab3-like) encoding 5,874 amino acids. Mutant Efcab3-like mice display anomalies in multiple brain regions, suggesting a possible role for this gene in the regulation of brain development

Physiological Correlates of Volunteering

We review research on physiological correlates of volunteering, a neglected but promising research field. Some of these correlates seem to be causal factors influencing volunteering. Volunteers tend to have better physical health, both self-reported and expert-assessed, better mental health, and perform better on cognitive tasks. Research thus far has rarely examined neurological, neurochemical, hormonal, and genetic correlates of volunteering to any significant extent, especially controlling for other factors as potential confounds. Evolutionary theory and behavioral genetic research suggest the importance of such physiological factors in humans. Basically, many aspects of social relationships and social activities have effects on health (e.g., Newman and Roberts 2013; Uchino 2004), as the widely used biopsychosocial (BPS) model suggests (Institute of Medicine 2001). Studies of formal volunteering (FV), charitable giving, and altruistic behavior suggest that physiological characteristics are related to volunteering, including specific genes (such as oxytocin receptor [OXTR] genes, Arginine vasopressin receptor [AVPR] genes, dopamine D4 receptor [DRD4] genes, and 5-HTTLPR). We recommend that future research on physiological factors be extended to non-Western populations, focusing specifically on volunteering, and differentiating between different forms and types of volunteering and civic participation