Transmission of Vibrio cholerae Is Antagonized by Lytic Phage and Entry into the Aquatic Environment

Cholera outbreaks are proposed to propagate in explosive cycles powered by hyperinfectious Vibrio cholerae and quenched by lytic vibriophage. However, studies to elucidate how these factors affect transmission are lacking because the field experiments are almost intractable. One reason for this is that V. cholerae loses the ability to culture upon transfer to pond water. This phenotype is called the active but non-culturable state (ABNC; an alternative term is viable but non-culturable) because these cells maintain the capacity for metabolic activity. ABNC bacteria may serve as the environmental reservoir for outbreaks but rigorous animal studies to test this hypothesis have not been conducted. In this project, we wanted to determine the relevance of ABNC cells to transmission as well as the impact lytic phage have on V. cholerae as the bacteria enter the ABNC state. Rice-water stool that naturally harbored lytic phage or in vitro derived V. cholerae were incubated in a pond microcosm, and the culturability, infectious dose, and transcriptome were assayed over 24 h. The data show that the major contributors to infection are culturable V. cholerae and not ABNC cells. Phage did not affect colonization immediately after shedding from the patients because the phage titer was too low. However, V. cholerae failed to colonize the small intestine after 24 h of incubation in pond water—the point when the phage and ABNC cell titers were highest. The transcriptional analysis traced the transformation into the non-infectious ABNC state and supports models for the adaptation to nutrient poor aquatic environments. Phage had an undetectable impact on this adaptation. Taken together, the rise of ABNC cells and lytic phage blocked transmission. Thus, there is a fitness advantage if V. cholerae can make a rapid transfer to the next host before these negative selective pressures compound in the aquatic environment

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Continuum of Risk Analysis Methods to Assess Tillage System Sustainability at the Experimental Plot Level

This study applied a broad continuum of risk analysis methods including mean-variance and coefficient of variation (CV) statistical criteria, second-degree stochastic dominance (SSD), stochastic dominance with respect to a function (SDRF), and stochastic efficiency with respect to a function (SERF) for comparing income-risk efficiency sustainability of conventional and reduced tillage systems. Fourteen years (1990–2003) of economic budget data derived from 35 treatments on 36 experimental plots under corn ( Zea mays L.) and soybean ( Glycine max L.) at the Iowa State University Northeast Research Station near Nashua, IA, USA were used. In addition to the other analyses, a visually-based Stoplight or “probability of target value” procedure was employed for displaying gross margin and net return probability distribution information. Mean-variance and CV analysis of the economic measures alone provided somewhat contradictive and inconclusive sustainability rankings, i.e ., corn/soybean gross margin and net return showed that different tillage system alternatives were the highest ranked depending on the criterion and type of crop. Stochastic dominance analysis results were similar for SSD and SDRF in that both the conventional and reduced tillage system alternatives were highly ranked depending on the type of crop and tillage system. For the SERF analysis, results were dependent on the type of crop and level of risk aversion. The conventional tillage system was preferred for both corn and soybean for the Stoplight analysis. The results of this study are unique in that they highlight the potential of both traditional stochastic dominance and SERF methods for distinguishing economically sustainable choices between different tillage systems across a range of risk aversion. This study also indicates that the SERF risk analysis method appears to be a useful and easily understood tool to assist farm managers, experimental researchers, and potentially policy makers and advisers on problems involving agricultural risk and sustainability.agriculture; tillage systems; stochastic dominance; economic budgeting; risk analysis; sustainability