A large scale prediction of bacteriocin gene blocks suggests a wide functional spectrum for bacteriocins

Bacteriocins are peptide-derived molecules produced by bacteria, whose recently-discovered functions include virulence factors and signalling molecules as well as their better known roles as antibiotics. To date, close to five hundred bacteriocins have been identified and classified. Recent discoveries have shown that bacteriocins are highly diverse and widely distributed among bacterial species. Given the heterogeneity of bacteriocin compounds, many tools struggle with identifying novel bacteriocins due to their vast sequence and structural diversity. Many bacteriocins undergo post-translational processing or modifications necessary for the biosynthesis of the final mature form. Enzymatic modification of bacteriocins as well as their export is achieved by proteins whose genes are often located in a discrete gene cluster proximal to the bacteriocin precursor gene, referred to as \textit{context genes} in this study. Although bacteriocins themselves are structurally diverse, context genes have been shown to be largely conserved across unrelated species. Using this knowledge, we set out to identify new candidates for context genes which may clarify how bacteriocins are synthesized, and identify new candidates for bacteriocins that bear no sequence similarity to known toxins. To achieve these goals, we have developed a software tool, Bacteriocin Operon and gene block Associator (BOA) that can identify homologous bacteriocin associated gene clusters and predict novel ones. We discover that several phyla have a strong preference for bactericon genes, suggesting distinct functions for this group of molecules. Availability: https://github.com/idoerg/BOAComment: Accepted for publication in BMC Bioinformatic

CD46 is phosphorylated at tyrosine 354 upon infection of epithelial cells by Neisseria gonorrhoeae

The Neisseria type IV pilus promotes bacterial adhesion to host cells. The pilus binds CD46, a complement-regulatory glycoprotein present on nucleated human cells (Källström et al., 1997). CD46 mutants with truncated cytoplasmic tails fail to support bacterial adhesion (Källström et al., 2001), suggesting that this region of the molecule also plays an important role in infection. Here, we report that infection of human epithelial cells by piliated Neisseria gonorrhoeae (GC) leads to rapid tyrosine phosphorylation of CD46. Studies with wild-type and mutant tail fusion constructs demonstrate that Src kinase phosphorylates tyrosine 354 in the Cyt2 isoform of the CD46 cytoplasmic tail. Consistent with these findings, infection studies show that PP2, a specific Src family kinase inhibitor, but not PP3, an inactive variant of this drug, reduces the ability of epithelial cells to support bacterial adhesion. Several lines of evidence point to the role of c-Yes, a member of the Src family of nonreceptor tyrosine kinases, in CD46 phosphorylation. GC infection causes c-Yes to aggregate in the host cell cortex beneath adherent bacteria, increases binding of c-Yes to CD46, and stimulates c-Yes kinase activity. Finally, c-Yes immunoprecipitated from epithelial cells is able to phosphorylate the wild-type Cyt2 tail but not the mutant derivative in which tyrosine 354 has been substituted with alanine. We conclude that GC infection leads to rapid tyrosine phosphorylation of the CD46 Cyt2 tail and that the Src kinase c-Yes is involved in this reaction. Together, the findings reported here and elsewhere strongly suggest that pilus binding to CD46 is not a simple static process. Rather, they support a model in which pilus interaction with CD46 promotes signaling cascades important for Neisseria infectivity

Exertional heat stroke: nutritional considerations

Exertional heat stroke (EHS) is a life-threatening illness and an enduring problem among athletes, military servicemen and -women, and occupational labourers who regularly perform strenuous activity, often under hot and humid conditions or when wearing personal protective equipment. Risk factors for EHS and mitigation strategies have generally focused on the environment, health status, clothing, heat acclimatization and aerobic conditioning, but the potential role of nutrition is largely underexplored. Various nutritional and dietary strategies have shown beneficial effects on exercise performance and health and are widely used by athletes and other physically active populations. There is also evidence that some of these practices may dampen the pathophysiological features of EHS, suggesting possible protection or abatement of injury severity. Promising candidates include carbohydrate ingestion, appropriate fluid intake and glutamine supplementation. Conversely, some nutritional factors and low energy availability may facilitate the development of EHS, and individuals should be cognizant of these. Therefore, the aims of this review are to present an overview of EHS along with its mechanisms and pathophysiology, discuss how selected nutritional considerations may influence EHS risk focusing on their impact on the key pathophysiological processes of EHS, and provide recommendations for future research. With climate change expected to increase EHS risk and incidence in the coming years, further investigation on how diet and nutrition may be optimized to protect against EHS would be highly beneficial

High-Input Management Systems Effect on Soybean Seed Yield, Yield Components, and Economic Break-Even Probabilities

Elevated soybean [Glycine max (L.) Merr.] prices have spurred interest in maximizing soybean seed yield and has led growers to increase the number of inputs in their production systems. However, little information exists about the effects of high-input management on soybean yield and profitability. The purpose of this study was to investigate the effects of individual inputs, as well as combinations of inputs marketed to protect or increase soybean seed yield, yield components, and economic break-even probabilities. Studies were established in nine states and three soybean growing regions (North, Central, and South) between 2012 and 2014. In each site-year both individual inputs and combination high-input (SOYA) management systems were tested. When averaged between 2012 and 2014, regional results showed no seed yield responses in the South region, but multiple inputs affected seed yield in the North region. In general, the combination SOYA inputs resulted in the greatest yield increases (up to 12%) compared to standard management, but Bayesian economic analysis indicated SOYA had low break-even probabilities. Foliar insecticide had the greatest break-even probabilities across all environments, although insect pressure was generally low across all site-years. Soybean producers in North region are likely to realize a greater response from increased inputs, but producers across all regions should carefully evaluate adding inputs to their soybean management systems and ensure that they continue to follow the principles of integrated pest management

Characterizing Genotype X Management Interactions on Soybean Seed Yield

Increased soybean [Glycine max (L.) Merr.] commodity prices in recent years have generated interest in high-input systems to increase yield. The objective of this study was to evaluate the effects of current, high-yielding cultivars under high- and low-input systems on soybean yield and yield components. Research trials were conducted at 19 locations spanning nine states from 2012 to 2014. At each location, six high-yielding cultivars were grown under three input systems: (i) standard practice (SP, current recommended practices), (ii) high-input treatment consisting of a seed treatment fungicide, insecticide, nematistat, inoculant, and lipo-chitooligosaccharide (LCO); soil-applied N fertilizer; foliar LCO, fertilizer, antioxidant, fungicide and insecticide (SOYA), and (iii) SOYA minus foliar fungicide (SOYA-FF). An individual site-year yield analysis found only 3 of 53 (5.7%) site-years examined had a significant cultivar × input system interaction, suggesting cultivar selection and input system decisions can remain independent. Across all site-years, the SOYA and SOYA-FF treatments yielded 231 (5.5%) and 147 kg ha–1 (3.5%) more than the SP, and input system differences were found among maturity groups. Yield component measurements (seeds m–2, seed mass, early-season and final plant stand, pods plant–1, and seeds pod–1) indicated positive yield responses were due to increased seeds m–2 and seed mass. While both high-input systems increased yield on average, grower return on investment (ROI) would be negative given today’s commodity prices. These results further support the use of integrated pest management principles for making input decisions instead of using prophylactic applications to maximize soybean yield and profitability

ARTICLE Pooled Association Tests for Rare Variants in Exon-Resequencing Studies

Deep sequencing will soon generate comprehensive sequence information in large disease samples. Although the power to detect association with an individual rare variant is limited, pooling variants by gene or pathway into a composite test provides an alternative strategy for identifying susceptibility genes. We describe a statistical method for detecting association of multiple rare variants in protein-coding genes with a quantitative or dichotomous trait. The approach is based on the regression of phenotypic values on individuals' genotype scores subject to a variable allele-frequency threshold, incorporating computational predictions of the functional effects of missense variants. Statistical significance is assessed by permutation testing with variable thresholds. We used a rigorous population-genetics simulation framework to evaluate the power of the method, and we applied the method to empirical sequencing data from three disease studies

Financing Direct Democracy: Revisiting the Research on Campaign Spending and Citizen Initiatives

The conventional view in the direct democracy literature is that spending against a measure is more effective than spending in favor of a measure, but the empirical results underlying this conclusion have been questioned by recent research. We argue that the conventional finding is driven by the endogenous nature of campaign spending: initiative proponents spend more when their ballot measure is likely to fail. We address this endogeneity by using an instrumental variables approach to analyze a comprehensive dataset of ballot propositions in California from 1976 to 2004. We find that both support and opposition spending on citizen initiatives have strong, statistically significant, and countervailing effects. We confirm this finding by looking at time series data from early polling on a subset of these measures. Both analyses show that spending in favor of citizen initiatives substantially increases their chances of passage, just as opposition spending decreases this likelihood

Multi-modal Single-Cell Analysis Reveals Brain Immune Landscape Plasticity during Aging and Gut Microbiota Dysbiosis

Phenotypic and functional plasticity of brain immune cells contribute to brain tissue homeostasis and disease. Immune cell plasticity is profoundly influenced by tissue microenvironment cues and systemic factors. Aging and gut microbiota dysbiosis that reshape brain immune cell plasticity and homeostasis has not been fully delineated. Using Cellular Indexing of Transcriptomes and Epitopes by sequencing (CITE-seq), we analyze compositional and transcriptional changes of the brain immune landscape in response to aging and gut dysbiosis. Discordance between canonical surface-marker-defined immune cell types and their transcriptomes suggest transcriptional plasticity among immune cells. Ly6C+ monocytes predominate a pro-inflammatory signature in the aged brain, while innate lymphoid cells (ILCs) shift toward an ILC2-like profile. Aging increases ILC-like cells expressing a T memory stemness (Tscm) signature, which is reduced through antibiotics-induced gut dysbiosis. Systemic changes due to aging and gut dysbiosis increase propensity for neuroinflammation, providing insights into gut dysbiosis in age-related neurological diseases