Centre Occitanie-Montpellier

Abstract The accuracy of the predictions of distributed hydrological models must depend in part on the proper specification of flow pathways. This paper examines some of the problems of deriving flow pathways from raster digital terrain data in the context of hydrological predictions using TOPMODEL. Distributed moisture status is predicted in TOPMODEL on the basis of spatial indices that depend on flow path definition. The sensitivity of this index to flow path algorithm and grid size is examined for the case where the surface topography is a good indicator of local hydraulic gradients. A strategy for the case where downslope subsurface flow pathways may deviate from those indicated by the surface topography is described with an example application.

In this tutorial review we discuss the latest developments in ultra-microporous MOF adsorbents and their use as separating agents<italic>via</italic>thermodynamics and/or kinetics and molecular sieving.

BACKGROUND: The aim of this study is to describe the major evolutionary historical events among Leishmania, sandflies, and the associated animal reservoirs in detail, in accordance with the geographical evolution of the Earth, which has not been previously discussed on a large scale. METHODOLOGY AND PRINCIPAL FINDINGS: Leishmania and sandfly classification has always been a controversial matter, and the increasing number of species currently described further complicates this issue. Despite several hypotheses on the origin, evolution, and distribution of Leishmania and sandflies in the Old and New World, no consistent agreement exists regarding dissemination of the actors that play roles in leishmaniasis. For this purpose, we present here three centuries of research on sandflies and Leishmania descriptions, as well as a complete description of Leishmania and sandfly fossils and the emergence date of each Leishmania and sandfly group during different geographical periods, from 550 million years ago until now. We discuss critically the different approaches that were used for Leishmana and sandfly classification and their synonymies, proposing an updated classification for each species of Leishmania and sandfly. We update information on the current distribution and dispersion of different species of Leishmania (53), sandflies (more than 800 at genus or subgenus level), and animal reservoirs in each of the following geographical ecozones: Palearctic, Nearctic, Neotropic, Afrotropical, Oriental, Malagasy, and Australian. We propose an updated list of the potential and proven sandfly vectors for each Leishmania species in the Old and New World. Finally, we address a classical question about digenetic Leishmania evolution: which was the first host, a vertebrate or an invertebrate? CONCLUSIONS AND SIGNIFICANCE: We propose an updated view of events that have played important roles in the geographical dispersion of sandflies, in relation to both the Leishmania species they transmit and the animal reservoirs of the parasites.

ABSTRACT An edible wheat gluten film was developed and effects of gluten concentration, ethanol concentration (ET) and pH of the film‐forming solution on various film properties were evaluated using Response Surface Methodology. pH and ethanol concentration had strong interactive effects on film opacity, water solubility and water vapor permeability. A simultaneous variation of ethanol concentration and pH between 32.5% ET, pH 4 and 45% ET, pH 2 resulted in homogeneous and transparent film with relatively low water solubility. The lowest water vapor permeability would be expected with 20% ethanol concentration and pH 6. Mechanical properties were mainly affected by gluten concentration and pH. The most resistant film was obtained at high gluten concentration (12.5%) and pH 5.

Over the past 10 years, circulating tumor cells (CTC) and circulating tumor DNA (ctDNA) have received enormous attention as new biomarkers and subjects of translational research. Although both biomarkers are already used in numerous clinical trials, their clinical utility is still under investigation with promising first results. Clinical applications include early cancer detection, improved cancer staging, early detection of relapse, real-time monitoring of therapeutic efficacy, and detection of therapeutic targets and resistance mechanisms. Here, we propose a conceptual framework of CTC and ctDNA assays and point out current challenges of CTC and ctDNA research, which might structure this dynamic field of translational cancer research. SIGNIFICANCE: The analysis of blood for CTCs or cell-free nucleic acids called "liquid biopsy" has opened new avenues for cancer diagnostics, including early detection of tumors, improved risk assessment and staging, as well as early detection of relapse and monitoring of tumor evolution in the context of cancer therapies.

For the past 20 years, the recombination detection program (RDP) project has focused on the development of a fast, flexible, and easy to use Windows-based recombination analysis tool. Whereas previous versions of this tool have relied on considerable user-mediated verification of detected recombination events, the latest iteration, RDP5, is automated enough that it can be integrated within analysis pipelines and run without any user input. The main innovation enabling this degree of automation is the implementation of statistical tests to identify recombination signals that could be attributable to evolutionary processes other than recombination. The additional analysis time required for these tests has been offset by algorithmic improvements throughout the program such that, relative to RDP4, RDP5 will still run up to five times faster and be capable of analyzing alignments containing twice as many sequences (up to 5000) that are five times longer (up to 50 million sites). For users wanting to remove signals of recombination from their datasets before using them for downstream phylogenetics-based molecular evolution analyses, RDP5 can disassemble detected recombinant sequences into their constituent parts and output a variety of different recombination-free datasets in an array of different alignment formats. For users that are interested in exploring the recombination history of their datasets, all the manual verification, data management and data visualization components of RDP5 have been extensively updated to minimize the amount of time needed by users to individually verify and refine the program's interpretation of each of the individual recombination events that it detects.

SUMMARY A strategy for establishing the specificity and safety of an organism as a biological weed control agent is described. A critical first step is to expose to its attack a small group of plants very closely related and exhibiting morphological and biochemical similarities to the weed. To prevent an erroneous negative result tests are also made on selected cultivated plants, including those closely related to the weed, those of which the associated insects and fungi are little known, those that have evolved apart from or been little exposed to the agent, those attacked by closely related organisms and those already recorded as hosts. The circumstances under which the strategy might fail to indicate safety are discussed, i.e. polyphagous organisms attacking plants irregularly distributed throughout many families, organisms highly specific to two alternate hosts, and those attacking two or three phylogenetically widely separated plant groups. The additional crop plant testing, included in the overall strategy to deal with such possible failures, is discussed. It is shown that the strategy would have included Sesamum tndicum in the list of plants challenged by the bug Teleonemia scrupulosa in biological testing for control of Lantana camara , thereby forewarning of the attack that was subsequently observed in Africa.

Progress in the diagnosis of leishmaniases depends on the development of effective methods and the discovery of suitable biomarkers. We propose firstly an update classification of Leishmania species and their synonymies. We demonstrate a global map highlighting the geography of known endemic Leishmania species pathogenic to humans. We summarize a complete list of techniques currently in use and discuss their advantages and limitations. The available data highlights the benefits of molecular markers in terms of their sensitivity and specificity to quantify variation from the subgeneric level to species complexes, (sub) species within complexes, and individual populations and infection foci. Each DNA-based detection method is supplied with a comprehensive description of markers and primers and proposal for a classification based on the role of each target and primer in the detection, identification and quantification of leishmaniasis infection. We outline a genome-wide map of genes informative for diagnosis that have been used for Leishmania genotyping. Furthermore, we propose a classification method based on the suitability of well-studied molecular markers for typing the 21 known Leishmania species pathogenic to humans. This can be applied to newly discovered species and to hybrid strains originating from inter-species crosses. Developing more effective and sensitive diagnostic methods and biomarkers is vital for enhancing Leishmania infection control programs.

Functional diversity (FD), the diversity of organism attributes that relates to their interactions with the abiotic and biotic environment, has been increasingly used for the last two decades in ecology, biogeography and conservation. Yet, FD has many facets and their estimations are not standardized nor embedded in a single tool. mFD (multifaceted functional diversity) is an R package that uses matrices of species assemblages and species trait values as building blocks to compute most FD indices. mFD is firstly based on two functions allowing the user to summarize trait and assemblage data. Then it calculates trait‐based distances between species pairs, informs the user whether species have to be clustered into functional entities and finally computes multidimensional functional space. To let the user choose the most appropriate functional space for computing multidimensional functional diversity indices, two mFD functions allow assessing and illustrating the quality of each functional space. Next, mFD provides 6 core functions to calculate 16 existing FD indices based on trait‐based distances, functional entities or species position in a functional space. The mFD package also provides graphical functions based on the ggplot library to illustrate FD values through customizable and high‐resolution plots of species distribution among functional entities or in a multidimensional space. All functions include internal validation processes to check for errors in data formatting which return detailed error messages. To facilitate the use of mFD framework, we built an associated website hosting five tutorials illustrating the use of all the functions step by step.

Proteome analysis is becoming a powerful tool in the functional characterization of plants. Due to the availability of vast nucleotide sequence information and based on the progress achieved in sensitive and rapid protein identification by mass spectrometry, proteome approaches open up new perspectives to analyze the complex functions of model plants and crop species at different levels. In this review, an overview is given on proteome studies performed to analyze whole plants or specific tissues with particular emphasis on important physiological processes such as germination. The chapter on subcellular proteome analysis of plants focuses on the progress achieved for plastids and mitochondria but also mentions the difficulties associated with membrane-bound proteins of these organelles. Separate chapters are dedicated to the challenging analysis of woody plants and to the use of proteome approaches to investigate the interaction of plants with pathogens or with symbiotic organisms. Limitations of current techniques and recent conceptual and technological perspectives for plant proteomics are briefly discussed in the final chapter.

The development of functional-structural plant models requires an increasing amount of computer modelling. All these models are developed by different teams in various contexts and with different goals. Efficient and flexible computational frameworks are required to augment the interaction between these models, their reusability, and the possibility to compare them on identical datasets. In this paper, we present an open-source platform, OpenAlea, that provides a user-friendly environment for modellers, and advanced deployment methods. OpenAlea allows researchers to build models using a visual programming interface and provides a set of tools and models dedicated to plant modelling. Models and algorithms are embedded in OpenAlea 'components' with well defined input and output interfaces that can be easily interconnected to form more complex models and define more macroscopic components. The system architecture is based on the use of a general purpose, high-level, object-oriented script language, Python, widely used in other scientific areas. We present a brief rationale that underlies the architectural design of this system and we illustrate the use of the platform to assemble several heterogeneous model components and to rapidly prototype a complex modelling scenario.

Journal Article Detection of ehrlichiae in African ticks by polymerase chain reaction Get access Philippe Parola, Philippe Parola 1Unité des Rickettsies, CNRS UPRES A 6020, Université de la Méditerranée, Faculté de Médecine, 27 Bd Jean Moulin, 13385 Marseille Cedex 5, France Search for other works by this author on: Oxford Academic PubMed Google Scholar Veronique Roux, Veronique Roux 1Unité des Rickettsies, CNRS UPRES A 6020, Université de la Méditerranée, Faculté de Médecine, 27 Bd Jean Moulin, 13385 Marseille Cedex 5, France Search for other works by this author on: Oxford Academic PubMed Google Scholar Jean-Louis Camicas, Jean-Louis Camicas 2Centre IRD (ex ORS-TOM), Montpellier, France Search for other works by this author on: Oxford Academic PubMed Google Scholar Issa Baradji, Issa Baradji 3Laboratoire Central Vétérinaire, Bamako, Mali Search for other works by this author on: Oxford Academic PubMed Google Scholar Philippe Brouqui, Philippe Brouqui 1Unité des Rickettsies, CNRS UPRES A 6020, Université de la Méditerranée, Faculté de Médecine, 27 Bd Jean Moulin, 13385 Marseille Cedex 5, France Search for other works by this author on: Oxford Academic PubMed Google Scholar Didier Raoult Didier Raoult ∗ 1Unité des Rickettsies, CNRS UPRES A 6020, Université de la Méditerranée, Faculté de Médecine, 27 Bd Jean Moulin, 13385 Marseille Cedex 5, France ∗Author for correspondence; phone +33 4 91 32 43 75, fax +33 4 91 83 03 90. didier.raoult@medecine.univ-mrs.fr Search for other works by this author on: Oxford Academic PubMed Google Scholar Transactions of The Royal Society of Tropical Medicine and Hygiene, Volume 94, Issue 6, November-December 2000, Pages 707–708, https://doi.org/10.1016/S0035-9203(00)90243-8 Published: 01 November 2000 Article history Received: 17 January 2000 Revision received: 26 April 2000 Accepted: 16 May 2000 Published: 01 November 2000

Evidence shows the importance of food systems for sustainable development: they are at the nexus that links food security, nutrition, and human health, the viability of ecosystems, climate change, and social justice. However, agricultural policies tend to focus on food supply, and sometimes, on mechanisms to address negative externalities. We propose an alternative. Our starting point is that agriculture and food systems' policies should be aligned to the 2030 Agenda for Sustainable Development. This calls for deep changes in comparison with the paradigms that prevailed when steering the agricultural change in the XXth century. We identify the comprehensive food systems transformation that is needed. It has four parts: first, food systems should enable all people to benefit from nutritious and healthy food. Second, they should reflect sustainable agricultural production and food value chains. Third, they should mitigate climate change and build resilience. Fourth, they should encourage a renaissance of rural territories. The implementation of the transformation relies on (i) suitable metrics to aid decision-making, (ii) synergy of policies through convergence of local and global priorities, and (iii) enhancement of development approaches that focus on territories. We build on the work of the "Milano Group," an informal group of experts convened by the UN Secretary General in Milan in 2015. Backed by a literature review, what emerges is a strategic narrative linking climate, agriculture and food, and calling for a deep transformation of food systems at scale. This is critical for achieving the Sustainable Development Goals and the Paris Agreement. The narrative highlights the needed consistency between global actions for sustainable development and numerous local-level innovations. It emphasizes the challenge of designing differentiated paths for food systems transformation responding to local and national expectations. Scientific and operational challenges are associated with the alignment and arbitration of local action within the context of global priorities.

From tropical forests to gut microbiomes, ecological communities host notably high numbers of coexisting species. Beyond high biodiversity, communities exhibit a range of complex dynamics that are difficult to explain under a unified framework. Using bacterial microcosms, we performed a direct test of theory predicting that simple community-level features dictate emergent behaviors of communities. As either the number of species or the strength of interactions increases, we show that microbial ecosystems transition between three distinct dynamical phases, from a stable equilibrium in which all species coexist to partial coexistence to emergence of persistent fluctuations in species abundances, in the order predicted by theory. Under fixed conditions, high biodiversity and fluctuations reinforce each other. Our results demonstrate predictable emergent patterns of diversity and dynamics in ecological communities.

The family Geminiviridae includes viruses with mono- or bipartite single-stranded, circular DNA genomes of 2.5–5.2 kb. They cause economically important diseases in most tropical and subtropical regions of the world. Geminiviruses infect dicot and monocot plants and are transmitted by insect vectors. DNA satellites are associated with some geminiviruses. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Geminiviridae which is available at ictv.global/report/geminiviridae .

BACKGROUND: Lixisenatide, a glucagon-like peptide-1 receptor agonist used for the treatment of diabetes, has shown neuroprotective properties in a mouse model of Parkinson's disease. METHODS: In this phase 2, double-blind, randomized, placebo-controlled trial, we assessed the effect of lixisenatide on the progression of motor disability in persons with Parkinson's disease. Participants in whom Parkinson's disease was diagnosed less than 3 years earlier, who were receiving a stable dose of medications to treat symptoms, and who did not have motor complications were randomly assigned in a 1:1 ratio to daily subcutaneous lixisenatide or placebo for 12 months, followed by a 2-month washout period. The primary end point was the change from baseline in scores on the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III (range, 0 to 132, with higher scores indicating greater motor disability), which was assessed in patients in the on-medication state at 12 months. Secondary end points included other MDS-UPDRS subscores at 6, 12, and 14 months and doses of levodopa equivalent. RESULTS: A total of 156 persons were enrolled, with 78 assigned to each group. MDS-UPDRS part III scores at baseline were approximately 15 in both groups. At 12 months, scores on the MDS-UPDRS part III had changed by -0.04 points (indicating improvement) in the lixisenatide group and 3.04 points (indicating worsening disability) in the placebo group (difference, 3.08; 95% confidence interval, 0.86 to 5.30; P = 0.007). At 14 months, after a 2-month washout period, the mean MDS-UPDRS motor scores in the off-medication state were 17.7 (95% CI, 15.7 to 19.7) with lixisenatide and 20.6 (95% CI, 18.5 to 22.8) with placebo. Other results relative to the secondary end points did not differ substantially between the groups. Nausea occurred in 46% of participants receiving lixisenatide, and vomiting occurred in 13%. CONCLUSIONS: In participants with early Parkinson's disease, lixisenatide therapy resulted in less progression of motor disability than placebo at 12 months in a phase 2 trial but was associated with gastrointestinal side effects. Longer and larger trials are needed to determine the effects and safety of lixisenatide in persons with Parkinson's disease. (Funded by the French Ministry of Health and others; LIXIPARK ClinicalTrials.gov number, NCT03439943.).

sensing and ROS homeostasis to suppress plant immunity, suggesting a principle for breeding disease-resistant, high-yield crops.

We elucidate grapevine evolution and domestication histories with 3525 cultivated and wild accessions worldwide. In the Pleistocene, harsh climate drove the separation of wild grape ecotypes caused by continuous habitat fragmentation. Then, domestication occurred concurrently about 11,000 years ago in Western Asia and the Caucasus to yield table and wine grapevines. The Western Asia domesticates dispersed into Europe with early farmers, introgressed with ancient wild western ecotypes, and subsequently diversified along human migration trails into muscat and unique western wine grape ancestries by the late Neolithic. Analyses of domestication traits also reveal new insights into selection for berry palatability, hermaphroditism, muscat flavor, and berry skin color. These data demonstrate the role of the grapevines in the early inception of agriculture across Eurasia.

The objectives of this study were to assess the safety, pharmacokinetics, and efficacy of pegylated interferon alfa-2b (PEG-Intron) plus ribavirin in patients with chronic hepatitis C. A total of 72 patients (35 men/37 women, age range 20-68 years) with clinically compensated chronic hepatitis C virus (HCV) were enrolled into this open-label, randomized, active controlled study. Patients received either PEG-Intron 0.35, 0.7, or 1.4 microg/kg subcutaneously weekly for 24 weeks alone, or in combination with ribavirin 600, 800, or 1,000 to 1,200 mg orally daily. Patients were evaluated during treatment and after a 24-week follow-up period for safety and efficacy. Detailed pharmacokinetic assessments were performed at weeks 1 and 4. PEG-Intron alone produced expected dose-related reductions in white cells, neutrophils and platelets. Addition of ribavirin reduced hemoglobin levels in a dose-related manner, did not further reduce PEG-Intron-induced decreases in neutrophil or white cell count, and increased platelet counts. Neutrophil function tests (C5a and FMLP migration, killing curves) were unaltered. Reported adverse events (flu-like symptoms, asthenia) were qualitatively similar in all dose groups. Anti-HCV activity, as measured by loss of detectable serum HCV RNA (i.e. <100 copies/mL) at the end of treatment (week 24) and after 24 weeks of follow-up (week 48) showed dose-response trends for PEG-Intron. At each PEG-Intron dose level, anti-HCV activity was higher in patients coadministered ribavirin than in patients treated with PEG-Intron monotherapy. There was no evidence of pharmacokinetic interactions with either drug. We conclude that the safety and tolerability of combined PEG-Intron/ribavirin and PEG-Intron alone were comparable. Combined PEG-Intron/ribavirin showed dose-related synergistic anti-HCV effects, which were numerically superior to those obtained with PEG-Intron monotherapy.

OBJECTIVES: To assess efficacy and safety of rituximab (RTX) as induction therapy, maintenance of remission and treatment of relapses in a cohort of IgG4-related disease (IgG4-RD) patients. METHODS: Nationwide retrospective multicenter study of IgG4-RD patients treated with at least one course of RTX. Clinical, biological and radiological response, relapse rate and drug tolerance were analyzed. Kaplan-Meier curves were plotted and risk factors for relapse studied with a Cox regression model. RESULTS: Among 156 IgG4-RD patients included in the French database, 33 received rituximab. Clinical response was noted in 29/31 (93.5%) symptomatic patients. Glucocorticoids withdrawal was achieved in 17 (51.5%) patients. During a mean follow-up of 24.8 ±21 months, 13/31 (41.9%) responder patients relapsed after a mean delay of 19 ±11 months after RTX. Active disease, as defined by an IgG4-RD Responder Index >9 before RTX, was significantly associated with relapse (HR = 3.68, 95% CI: 1.1, 12.6) (P = 0.04), whereas maintenance therapy with systematic (i.e. before occurrence of a relapse) RTX retreatment was associated with longer relapse-free survival (41 versus 21 months; P = 0.02). Eight severe infections occurred in 4 patients during follow-up (severe infections rate of 12.1/100 patient-years) and hypogammaglobulinemia ≤5 g/l in 3 patients. CONCLUSION: RTX is effective for both induction therapy and treatment of relapses in IgG4-RD, but relapses are frequent after B-cell reconstitution. Maintenance therapy with systematic RTX infusions is associated with longer relapse-free survival and might represent a novel treatment strategy. Yet, the high rate of infections and the temporary effect of RTX might be hindrances to such strategy.