Why, how, and how far should microbiological contamination in a coastal zone be mitigated? An application of the systems approach to the Thau lagoon (France)

Full text : http://archimer.ifremer.fr/doc/00136/24775/22959.pdf (Version "auteur", 0.77 Mo)International audienceThis paper describes the building of an integrated simulation tool based on a systems approach, and its contribution to local political discussion of the mitigation of microbiological contamination of the water in a coastal area. Local management schemes view water quality as a high-priority environmental objective. In practice, how far this objective is achieved depends on trade-offs between the costs of improved water treatment facilities and the acceptable impacts of water contamination. An in-the-field experiment in collaboration with local managers was carried out in the Thau lagoon on the French Mediterranean coast during the SPICOSA (Science and Policy Integration for Coastal System Assessment) project, from 2007 through 2011. It consisted of building a modeling platform and an integrated assessment framework for simulating exploratory scenarios. The modeling platform combines a dynamic contamination model, which represents the sources of microbiological contamination, wastewater treatment facilities, and physical mechanisms of lagoon contamination, with a prospective economic model, which estimates the patterns of development of economic activities in the area through a holistic approach. Exploratory scenarios are used to assess the risk of water contamination and the efficiency of management measures, under various assumptions about the evolution of the system. The contamination simulations suggest that the work currently planned by local authorities will be inadequate for preventing increased water pollution, and that additional but fairly inexpensive management measures for maintaining the current level of water quality should be considered. The integrated assessment framework estimates the ecological and socio-economic impacts of the various pollution mitigation policies in the broader context of possible local development patterns. The results illustrate how the systems approach may aid in the design of an applicable water policy based on operational objectives and feasible technical options. (C) 2013 Elsevier Ltd. All rights reserved

More Similarities Than Differences Testing Insulin Glargine 300 Units/mL Versus Insulin Degludec 100 Units/mL in Insulin-Naive Type 2 Diabetes: The Randomized Head-to-Head BRIGHT Trial

OBJECTIVE To compare insulin glargine 300 units/mL (Gla-300) versus insulin degludec 100 units/mL (IDeg-100) in this first head-to-head randomized controlled trial. RESEARCH DESIGN AND METHODS BRIGHT (NCT02738151) was a multicenter, open-label, active-controlled, two-arm, parallel-group, 24-week, noninferiority study in insulin-naive patients with uncontrolled type 2 diabetes. Participants were randomized 1:1 to evening dosing with Gla-300 (N = 466) or IDeg-100 (N = 463), titrated to fasting self-monitored plasma glucose of 80–100 mg/dL. The primary end point was HbA1c change from baseline to week 24. Safety end points included incidence and event rates of hypoglycemia. RESULTS At week 24, HbA1c improved similarly from baseline values of 8.7% (72 mmol/mol) in the Gla-300 group and 8.6% (70 mmol/mol) in the IDeg-100 group to 7.0% (53 mmol/mol)—least squares mean difference −0.05% (95% CI −0.15 to 0.05) (−0.6 mmol/mol [−1.7 to 0.6])—demonstrating noninferiority of Gla-300 versus IDeg-100 (P < 0.0001). Hypoglycemia incidence and event rates over 24 weeks were comparable with both insulins, whereas during the active titration period (0–12 weeks) the incidence and rate of anytime (24-h) confirmed hypoglycemia (≤70 and <54 mg/dL) were lower with Gla-300. Both insulins were properly titrated and exhibited no specific safety concerns. CONCLUSIONS Gla-300 and IDeg-100 provided similar glycemic control improvements with relatively low hypoglycemia risk. Hypoglycemia incidence and rates were comparable with both insulins during the full study period but lower in favor of Gla-300 during the titration period. The choice between these longer-acting basal insulins may be determined by factors such as access and cost, alongside clinical considerations

Overcoming challenges on an international project to advance systems engineering

The Body of Knowledge and Curriculum to Advance Systems Engineering (BKCASE) project's dual product development cycle spanned a three‐year period from the September 2009 to December, 2012. During this timeframe, BKCASE authors met quarterly at various locations, primarily in various regions of the United States, but also in Stockholm, Sweden; Toulouse, France; London, England; and Rome, Italy (BKCASE, 2009–2019). The team successfully worked through challenges and differences to produce The Guide to the Systems Engineering Body of Knowledge (SEBoK) wiki and a Graduate Reference Curriculum for Systems Engineering (GRCSE) publication. This article is a collection of personal stories from the team members that focus on overcoming obstacles to successfully produce the final published products

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Sirtuin 7 promotes 45S pre-rRNA cleavage at site 2 and determines the processing pathway

International audienceIn humans, ribosome biogenesis mainly occurs in nucleoli following two alternative pre-rRNA processing pathways differing in the order in which cleavages take place but not by the sites of cleavage. To uncover the role of nucleolar NAD+-dependent deacetylase Sirtuin 7 in the synthesis of ribosomal subunits, pre-rRNA processing was analyzed after sirtinol-inhibition of Sirtuin 7 activity or depletion of Sirtuin 7 protein. We thus reveal that Sirtuin 7 activity is a critical regulator of processing of 45S, 32S and 30S pre-rRNAs. Sirtuin 7 protein is primarily essential to 45S pre-rRNA cleavage at site 2, which is the first step of processing pathway 2. Furthermore, we demonstrate that Sirtuin 7 physically interacts with Nop56 and the GAR domain of fibrillarin, and propose that this could interfere with fibrillarin-dependent cleavage. Sirtuin 7 depletion results in the accumulation of 5’ extended forms of 32S pre-rRNA, and also influences the localization of fibrillarin. Thus, we establish a close relationship between Sirtuin 7 and fibrillarin which might determine the processing pathway used for ribosome biogenesis

Sirtuin 7 promotes 45S pre-rRNA cleavage at site 2 and determines the processing pathway

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OMICS Approaches to Assess Dinoflagellate Responses to Chemical Stressors

Dinoflagellates are important primary producers known to biosynthesize metabolites of interest and toxins and form Harmful Algae Blooms (HABs). Water conditions such as nutrient availability, anthropogenic contaminants or pH impact dinoflagellate toxin productions, and HABs' formation remains unclear. In this review, we present the recent contributions of OMICs approaches to the investigation of dinoflagellate responses to water chemical stressors. Transcriptomic and proteomic studies highlight whole-cell strategies to cope with nutrient deficiencies. Metabolomic studies offer a great view of toxin, lipid and sugar productions under stressors. However, the confrontation of different OMICs studies is tedious, as approaches are conducted in different species. As for other model organisms, it would be interesting to use multi-OMIC approaches to build a complete view of dinoflagellate responses to chemical stressors. Overcoming the complex genome of dinoflagellates and increasing their genomic resources is therefore essential to push further. The combination of OMICs studies will provide a much-needed global view of molecular processes, which is essential to optimize the production of dinoflagellate metabolites of interest and identify markers of HABs' formation and toxin production events

Environmental DNA surveillance for invertebrate species: advantages and technical limitations to detect invasive crayfish <i>Procambarus clarkii</i> in freshwater ponds

The introduction of non‐native species is a major threat to biodiversity. While eradication programs of well‐established invaders are costly and hazardous for non‐target species, the early detection of a non‐native species at low density is critical for preventing biological invasions in recipient ecosystems. Recent studies reveal that environmental DNA (eDNA) is a powerful tool for detecting target species in aquatic ecosystems, but these studies focus mostly on fish and amphibians. We examine the reliability of using eDNA to detect the presence of an invasive freshwater crustacean species, the red swamp crayfish Procambarus clarkii. Species‐specific primers and probes were designed; their specificity was tested using in silico PCR simulations and against tissues of other crayfish species. Limits of detection and quantification were specified for the target DNA sequence by means of quantitative PCR amplifications on dilution series of known amount of P. clarkii DNA. The method was applied to water samples collected in 158 ponds in a French Nature Park, and results were compared to a traditional method using food‐baited funnel traps. Environmental DNA had a better detection efficiency but predominantly led to divergent results compared with the trapping method. While habitat features partly explained the failure of crayfish detection by trapping, detection by eDNA was problematic at low crayfish abundances. When P. clarkii was detected, the estimated concentrations of crayfish DNA in water samples were always below the limit of quantification for the target DNA sequence. Synthesis and applications. The combination of environmental DNA (eDNA) and conventional trapping methods is recommended to monitor the invasion by P. clarkii in small waterbodies such as ponds. However, the risk of mortality for non‐target species, notably amphibians, has to be carefully evaluated before large‐scale deployment of traps. Contrary to fish and amphibians, a low amount of extracellular DNA in water is suspected to be the major limitation for crayfish detection by molecular approaches. Current advancements in PCR technology, together with optimization of the water sampling method, promise upcoming developments of eDNA detection for aquatic invertebrate species

Involvement of SIRT7 in resumption of rDNA transcription at the exit from mitosis

Sirtuins, also designated class III histone deacetylases, are implicated in the regulation of cell division, apoptosis, DNA damage repair, genomic silencing and longevity. The nucleolar Sirtuin7 (SIRT7) was reported to be involved in the regulation of ribosomal gene (rDNA) transcription, but there are no data concerning the regulation of SIRT7 during the cell cycle. Here we have analyzed the behavior of endogenous SIRT7 during mitosis, while rDNA transcription is repressed. SIRT7 remains associated with nucleolar organizer regions, as does the RNA polymerase I machinery. SIRT7 directly interacts with the rDNA transcription factor UBF. Moreover, SIRT7 is phosphorylated via the CDK1-cyclin B pathway during mitosis and dephosphorylated by a phosphatase sensitive to okadaic acid at the exit from mitosis before onset of rDNA transcription. Interestingly, dephosphorylation events induce a conformational modification of the carboxy-terminal region of SIRT7 before the release of mitotic repression of rDNA transcription. As SIRT7 activity is required to resume rDNA transcription in telophase, we propose that this conformational modification regulates onset of rDNA transcription