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International audience; The only enzyme responsible for cadaverine production in the major multidrug-resistant human pathogen Pseudomonas aeruginosa is the lysine decarboxylase LdcA. This enzyme modulates the general polyamine homeostasis, promotes growth, and reduces bacterial persistence during carbenicillin treatment. Here we present a 3.7-Å resolution cryoelectron microscopy structure of LdcA. We introduce an original approach correlating phylogenetic signal with structural information and reveal possible recombination among LdcA and arginine decarboxylase subfamilies within structural domain boundaries. We show that LdcA is involved in full virulence in an insect pathogenesis model. Furthermore, unlike its enterobacterial counterparts, LdcA is regulated neither by the stringent response alarmone ppGpp nor by the AAA+ ATPase RavA. Instead, the P. aeruginosa ravA gene seems to play a defensive role. Altogether, our study identifies LdcA as an important player in P. aeruginosa physiology and virulence and as a potential drug target.

International audience; Importance sampling (IS) methods are broadly used to approximate posterior distributions or their moments. In the standard IS approach, samples are drawn from a single proposal distribution and weighted adequately. However, since the performance in IS depends on the mismatch between the targeted and the proposal distributions, several proposal densities are often employed for the generation of samples. Under this multiple importance sampling (MIS) scenario, extensive literature has addressed the selection and adaptation of the proposal distributions, interpreting the sampling and weighting steps in different ways. In this paper, we establish a novel general framework with sampling and weighting procedures when more than one proposal is available. The new framework encompasses most relevant MIS schemes in the literature, and novel valid schemes appear naturally. All the MIS schemes are compared and ranked in terms of the variance of the associated estimators. Finally, we provide illustrative examples revealing that, even with a good choice of the proposal densities, a careful interpretation of the sampling and weighting procedures can make a significant difference in the performance of the method.

International audience; The latitudinal diversity gradient (LDG) is one of the most widely debated patterns in ecology and evolution, associated with hundreds of papers, dozens of hypotheses, and disagreements about its underlying processes. The lack of agreement stems from 1) the verbal nature of existing hypotheses, 2) the failure to mechanistically integrate all relevant ecological and evolutionary processes to the LDG, and 3) the degree to which many empirical patterns are consistent with multiple LDG explanations. We show how mapping LDG hypotheses to a set of key ecological and evolutionary processes leads to a better understanding of the internal logic of those hypotheses. The codification of those processes within a mechanistic eco-evolutionary model is essential for contrasting support for hypotheses and for understanding the relative importance of the processes themselves.

International audience; Simple Summary: Stress Granules (SGs) were discovered in 1999 and while the first decade of research has focused on some fundamental questions, the field is now investigating their role in human pathogenesis. Since then, evidences of a link between SGs and cancerology are accumulating in vitro and in vivo. In this work we summarized the role of SGs proteins in cancer development and their prognostic values. We find that level of expression of protein involved in SGs formation (and not mRNA level) could serve a prognostic marker in cancer. With this review we strongly suggest that SGs (proteins) could be targets of choice to block cancer development and counteract resistance to improve patients care. Abstract: Cancer treatments are constantly evolving with new approaches to improve patient outcomes. Despite progresses, too many patients remain refractory to treatment due to either the development of resistance to therapeutic drugs and/or metastasis occurrence. Growing evidence suggests that these two barriers are due to transient survival mechanisms that are similar to those observed during stress response. We review the literature and current available open databases to study the potential role of stress response and, most particularly, the involvement of Stress Granules (proteins) in cancer. We propose that Stress Granule proteins may have prognostic value for patients. According to the World Health Organization, cancer is the second leading cause of death worldwide. In most cases, mortality is not due to the primary tumor itself, but to the occurrence of metastasis. At diagnosis, non-metastatic diseases are treated with first line systemic adjuvant (post-operative) and/or neoadjuvant (pre-operative) treatments in order to avoid tumor relapse by eradicating potential residual or micro-metastatic foci. In case of metastatic disease, the aim of systemic treatment is to achieve clinical remissions as durable as possible, which remains a palliative situation for most of solid cancers. In both situations, if the therapy does not eliminate all malignant cells, residual cancer cells may acquire migratory properties and develop drug resistance mechanisms, further contributing to difficult-to-treat metastasis [1].

The field of energy forecasting has attracted many researchers from different fields (e.g., meteorology, data sciences, mechanical or electrical engineering) over the last decade. Solar forecasting is a fast-growing subdomain of energy forecasting. Despite several previous attempts, the methods and measures used for verification of deterministic (also known as single-valued or point) solar forecasts are still far from being standardized, making forecast analysis and comparison difficult. To analyze and compare solar forecasts, the well-established Murphy–Winkler framework for distribution-oriented forecast verification is recommended as a standard practice. This framework examines aspects of forecast quality, such as reliability, resolution, association, or discrimination, and analyzes the joint distribution of forecasts and observations, which contains all time-independent information relevant to verification. To verify forecasts, one can use any graphical display or mathematical/statistical measure to provide insights and summarize the aspects of forecast quality. The majority of graphical methods and accuracy measures known to solar forecasters are specific methods under this general framework. Additionally, measuring the overall skillfulness of forecasters is also of general interest. The use of the root mean square error (RMSE) skill score based on the optimal convex combination of climatology and persistence methods is highly recommended. By standardizing the accuracy measure and reference forecasting method, the RMSE skill score allows—with appropriate caveats—comparison of forecasts made using different models, across different locations and time periods. Refereed/Peer-reviewed

International audience; Transparent statistics is a philosophy of statistical reporting whose purpose is scientific advancement rather than persuasion. At our CHI 2017 workshop, Moving Transparent Statistics Forward, we identified that an important first step is to develop detailed guidelines for authors and reviewers in order to help them practice and promote transparent statistics. We propose a SIG to solicit feedback from the CHI community on a first working draft of Transparent Statistics Guidelines and engage potential contributors to push the transparent statistics movement forward.

BackgroundDietary exposure to the cyanotoxin BMAA is suspected to be the cause of amyotrophic lateral sclerosis in the Western Pacific Islands. In Europe and North America, this toxin has been identified in the marine environment of amyotrophic lateral sclerosis clusters but, to date, only few dietary exposures have been described.ObjectivesWe aimed at identifying cluster(s) of amyotrophic lateral sclerosis in the Hérault district, a coastal district from Southern France, and to search, in the identified area(s), for the existence of a potential dietary source of BMAA.MethodsA spatio-temporal cluster analysis was performed in the district, considering all incident amyotrophic lateral sclerosis cases identified from 1994 to 2009 by our expert center. We investigated the cluster area with serial collections of oysters and mussels that were subsequently analyzed blind for BMAA concentrations.ResultsWe found one significant amyotrophic lateral sclerosis cluster (p = 0.0024), surrounding the Thau lagoon, the most important area of shellfish production and consumption along the French Mediterranean coast. BMAA was identified in mussels (1.8 µg/g to 6.0 µg/g) and oysters (0.6 µg/g to 1.6 µg/g). The highest concentrations of BMAA were measured during summer when the highest picocyanobacteria abundances were recorded.ConclusionsWhile it is not possible to ascertain a direct link between shellfish consumption and the existence of this ALS cluster, these results add new data to the potential association of BMAA with sporadic amyotrophic lateral sclerosis, one of the most severe neurodegenerative disorder.