Ketone Body Utilization for Lipid Synthesis in the Murine Sciatic Nerve: Alterations in the Dysmyelinating Trembler Mutant

This work demonstrates that in vitro sciatic nerves of normal and trembler adult mice can use ketone bodies (beta-hydroxybutyrate and acetoacetate) and butyrate for lipid synthesis. In normal sciatic nerves, beta-hydroxybutyrate is incorporated in total lipids to a larger extent than acetoacetate (141% and 33%, respectively, of acetate incorporation), whereas for trembler sciatic nerves, these percentages are only 69% and 27%. Incorporation of ketone bodies is greater into sterols than into other lipids. Lipid metabolism of ketone bodies in trembler nerves is altered and could reflect a process similar to Wallerian degeneration: a dramatic decrease of sterol and free fatty acid synthesis and an increased synthesis of triglycerides. Moreover, differences seen in precursor incorporation into lipids between normal and trembler sciatic nerves suggest that their lipid metabolism is not the same.     

Kinetics of induction of error-prone repair of bacteriophage lambda by temperature shift in an Escherichia coli dnaB mutant.

Summary Preincubation at 42^o, before infection at permissive temperature by phage , of an Escherichia coli dnaB mutant, provokes a significant increase in survival and mutagenesis of ultraviolet irradiated phage as well as mutagenesis of untreated phage. Similarly to UV irradiation and many chemical mutagens, the inhibition of DNA synthesis by temperature shift of this dnaB mutant induces SOS repair. This work shows that replication blockage in bacterial DNA is not only mutagenic for bacterial DNA itself (Witkin, 1975) but also for normally replicating DNA, probably due to induction of diffusible products.     

Influence of Vectors’ Risk-Spreading Strategies and Environmental Stochasticity on the Epidemiology and Evolution of Vector-Borne Diseases: The Example of Chagas’ Disease

Insects are known to display strategies that spread the risk of encountering unfavorable conditions, thereby decreasing the extinction probability of genetic lineages in unpredictable environments. To what extent these strategies influence the epidemiology and evolution of vector-borne diseases in stochastic environments is largely unknown. In triatomines, the vectors of the parasite Trypanosoma cruzi, the etiological agent of Chagas’ disease, juvenile development time varies between individuals and such variation most likely decreases the extinction risk of vector populations in stochastic environments. We developed a simplified multi-stage vector-borne SI epidemiological model to investigate how vector risk-spreading strategies and environmental stochasticity influence the prevalence and evolution of a parasite. This model is based on available knowledge on triatomine biodemography, but its conceptual outcomes apply, to a certain extent, to other vector-borne diseases. Model comparisons between deterministic and stochastic settings led to the conclusion that environmental stochasticity, vector risk-spreading strategies (in particular an increase in the length and variability of development time) and their interaction have drastic consequences on vector population dynamics, disease prevalence, and the relative short-term evolution of parasite virulence. Our work shows that stochastic environments and associated risk-spreading strategies can increase the prevalence of vector-borne diseases and favor the invasion of more virulent parasite strains on relatively short evolutionary timescales. This study raises new questions and challenges in a context of increasingly unpredictable environmental variations as a result of global climate change and human interventions such as habitat destruction or vector control.     

Non contiguous-finished genome sequence and description of Enorma massiliensis gen. nov., sp. nov., a new member of the Family Coriobacteriaceae

Enorma massiliensis strain phI^T is the type strain of E. massiliensis gen. nov., sp. nov., the type species of a new genus within the family Coriobacteriaceae, Enorma gen. nov. This strain, whose genome is described here, was isolated from the fecal flora of a 26-year-old woman suffering from morbid obesity. E. massiliensis strain phI^T is a Gram-positive, obligately anaerobic bacillus. Here we describe the features of this organism, together with the complete genome sequence and annotation. The 2,280,571 bp long genome (1 chromosome but no plasmid) exhibits a G+C content of 62.0% and contains 1,901 protein-coding and 51 RNA genes, including 3 rRNA genes.     

Non-contiguous finished genome sequence and description of Kallipyga massiliensis gen. nov., sp. nov., a new member of the family Clostridiales Incertae Sedis XI

Kallipyga massiliensis strain ph2^T is the type strain of Kallipyga massiliensis gen. nov., sp. nov., the type species of the new genus Kallipyga within the family Clostridiales Incertae Sedis XI. This strain, whose genome is described here, was isolated from the fecal flora of a 26-year-old woman suffering from morbid obesity. K. massiliensis is an obligate anaerobic coccus. Here we describe the features of this organism, together with the complete genome sequence and annotation. The 1,770,679 bp long genome (1 chromosome but no plasmid) contains 1,575 protein-coding and 50 RNA genes, including 4 rRNA genes.     

Mate limitation in populations of the endangered Convolvulus lineatus L.: A case for genetic rescue?

In self-incompatible clonal plants, the spread of individual plants can exacerbate mate limitation to the point that it becomes a serious constraint on long-term population persistence, especially in small, isolated populations. In such species, it may be necessary to introduce new genetic material from other populations to restore seed production, a strategy termed “genetic rescue”. In this study we assess the potential pertinence of such genetic rescue in the clonal perennial plant Convolvulus lineatus L., whose populations are often highly reduced in spatial extent and are currently being fragmented by land development projects in Mediterranean France. To do so, we quantify fruit production in a range of populations of different size over four years and perform a series of hand-pollination experiments in natural populations to assess whether fruit set is limited by mate availability. We found that C. lineatus is a self-incompatible species that shows extremely low values of fruit set in natural populations and that a principal cause of this low fruit set is a lack of compatible pollen. This may be primarily due to clonal spread that causes individual populations to be comprised of patches containing one or very few incompatibility types. In small populations fragmented by human activities and which show an absence of fruit production, we thus argue that genetic rescue represents a promising conservation management strategy to avoid inevitable long-term future population decline. We discuss how best to introduce new genetic material into the study populations.     

Impact of Aldosterone Antagonists on Sudden Cardiac Death Prevention in Heart Failure and Post-Myocardial Infarction Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background and Objectives

Sudden cardiac death (SCD) is a severe burden of modern medicine. Aldosterone antagonist is publicized as effective in reducing mortality in patients with heart failure (HF) or post myocardial infarction (MI). Our study aimed to assess the efficacy of AAs on mortality including SCD, hospitalization admission and several common adverse effects.

Methods

We searched Embase, PubMed, Web of Science, Cochrane library and clinicaltrial.gov for randomized controlled trials (RCTs) assigning AAs in patients with HF or post MI through May 2015. The comparator included standard medication or placebo, or both. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Event rates were compared using a random effects model. Prospective RCTs of AAs with durations of at least 8 weeks were selected if they included at least one of the following outcomes: SCD, all-cause/cardiovascular mortality, all-cause/cardiovascular hospitalization and common side effects (hyperkalemia, renal function degradation and gynecomastia).

Results

Data from 19,333 patients enrolled in 25 trials were included. In patients with HF, this treatment significantly reduced the risk of SCD by 19% (RR 0.81; 95% CI, 0.67–0.98; p = 0.03); all-cause mortality by 19% (RR 0.81; 95% CI, 0.74–0.88, p<0.00001) and cardiovascular death by 21% (RR 0.79; 95% CI, 0.70–0.89, p<0.00001). In patients with post-MI, the matching reduced risks were 20% (RR 0.80; 95% CI, 0.66–0.98; p = 0.03), 15% (RR 0.85; 95% CI, 0.76–0.95, p = 0.003) and 17% (RR 0.83; 95% CI, 0.74–0.94, p = 0.003), respectively. Concerning both subgroups, the relative risks respectively decreased by 19% (RR 0.81; 95% CI, 0.71–0.92; p = 0.002) for SCD, 18% (RR 0.82; 95% CI, 0.77–0.88, p < 0.0001) for all-cause mortality and 20% (RR 0.80; 95% CI, 0.74–0.87, p < 0.0001) for cardiovascular mortality in patients treated with AAs. As well, hospitalizations were significantly reduced, while common adverse effects were significantly increased.

Conclusion

Aldosterone antagonists appear to be effective in reducing SCD and other mortality events, compared with placebo or standard medication in patients with HF and/or after a MI.     

Differential expression and accumulation of 14-3-3 paralogs in 3T3-L1 preadipocytes and differentiated cells

The 14-3-3 protein family interacts with more than 2000 different proteins in mammals, as a result of its specific phospho-serine/phospho-threonine binding activity. Seven paralogs are strictly conserved in mammalian species. Here, we show that during adipogenic differentiation of 3T3-L1 preadipocytes, the level of each 14-3-3 protein paralog is regulated independently. For instance 14-3-3β, γ, and η protein levels are increased compared to untreated cells. In contrast, 14-3-3ε protein levels decreased after differentiation while others remained constant. In silico analysis of the promoter region of each gene showed differences that explain the results obtained at mRNA and protein levels.     

Role of the acquisition of a type 3 secretion system in the emergence of novel pathogenic strains of Xanthomonas

Cases of emergence of novel plant-pathogenic strains are regularly reported that reduce the yields of crops and trees. However, the molecular mechanisms underlying such emergence are still poorly understood. The acquisition by environmental non-pathogenic strains of novel virulence genes by horizontal gene transfer has been suggested as a driver for the emergence of novel pathogenic strains. In this study, we tested such an hypothesis by transferring a plasmid encoding the type 3 secretion system (T3SS) and four associated type 3 secreted proteins (T3SPs) to the non-pathogenic strains of Xanthomonas CFBP 7698 and CFBP 7700, which lack genes encoding T3SS and any previously known T3SPs. The resulting strains were phenotyped on Nicotiana benthamiana using chlorophyll fluorescence imaging and image analysis. Wild-type, non-pathogenic strains induced a hypersensitive response (HR)-like necrosis, whereas strains complemented with T3SS and T3SPs suppressed this response. Such suppression depends on a functional T3SS. Amongst the T3SPs encoded on the plasmid, Hpa2, Hpa1 and, to a lesser extent, XopF1 collectively participate in suppression. Monitoring of the population sizes in planta showed that the sole acquisition of a functional T3SS by non-pathogenic strains impairs growth inside leaf tissues. These results provide functional evidence that the acquisition via horizontal gene transfer of a T3SS and four T3SPs by environmental non-pathogenic strains is not sufficient to make strains pathogenic. In the absence of a canonical effector, the sole acquisition of a T3SS seems to be counter-selective, and further acquisition of type 3 effectors is probably needed to allow the emergence of novel pathogenic strains.