A Two-Stage Stochastic Optimization for Robust Operation of Multipurpose Reservoirs

Robust reservoir operation has long been considered a promising solution for addressing water allocation problems in the absence of reliable hydroclimatic forecasts. This study aims to evaluate the performance of this solution using a novel two-stage stochastic optimization model. The model maximizes economic benefits from reservoir deliveries while integrating stochastic inflows into a water allocation system with multiple demands and various constraints. The outcome of the model is a robust set of monthly reservoir releases that perform well under a wide range of hydroclimatic conditions. The model has been applied to the case of the Big Bend Reach of the Rio Grande/Bravo, a transboundary river basin of high importance for Mexico and the United States. The performance of the robust operation policy was assessed by comparing its outcome to those obtained under observed historical operations and an operation policy derived from a deterministic version of the optimization model that assumes perfect hydroclimatic knowledge. The results of this study indicate that the set of robust releases developed here outperforms historical reservoir operations and performs similarly to operations under perfect knowledge. These results show the effectiveness of robust reservoir operation and the usefulness of the proposed optimization model for decision-making under increasing hydroclimatic uncertainty

CD38 Exacerbates Focal Cytokine Production, Postischemic Inflammation and Brain Injury after Focal Cerebral Ischemia

BACKGROUND: Converging evidence suggests that inflammatory processes significantly influence brain injury and clinical impairment in ischemic stroke. Although early studies suggested a key role of lymphocytes, recent data has emphasized the orchestrating function of innate immunity, i.e., macrophages and microglia. The bifunctional receptor and ectoenzyme CD38 synthesizes calcium-mobilizing second messengers (e.g., cyclic ADP-ribose), which have been shown to be necessary for activation and migration of myeloid immune cells. Therefore, we investigated the dynamics of CD38 in stroke and the impact of CD38-deficiency on cytokine production, inflammation and cerebral damage in a mouse model of cerebral ischemia-reperfusion. METHODOLOGY/PRINCIPAL FINDINGS: We show that the local expression of the chemokine MCP-1 was attenuated in CD38-deficient mice compared with wildtype mice after focal cerebral ischemia and reperfusion. In contrast, no significant induction of MCP-1 expression was observed in peripheral blood after 6 hours. Flow cytometry analysis revealed less infiltrating macrophages and lymphocytes in the ischemic hemisphere of CD38-deficient mice, whereas the amount of resident microglia was unaltered. An up-regulation of CD38 expression was observed in macrophages and CD8(+) cells after focal cerebral ischemia in wildtype mice, whereas CD38 expression was unchanged in microglia. Finally, we demonstrate that CD38-deficiency decreases the cerebral ischemic injury and the persistent neurological deficit after three days of reperfusion in this murine temporary middle cerebral artery occlusion (tMCAO) model. CONCLUSION/SIGNIFICANCE: CD38 is differentially regulated following stroke and its deficiency attenuates the postischemic chemokine production, the immune cell infiltration and the cerebral injury after temporary ischemia and reperfusion. Therefore CD38 might prove a therapeutic target in ischemic stroke

CD38 promotes pristane-induced chronic inflammation and increases susceptibility to experimental lupus by an apoptosis-driven and TRPM2-dependent mechanism

In this study, we investigated the role of CD38 in a pristane-induced murine model of lupus. CD38-deficient (Cd38-/-) but not ART2-deficient (Art2-/-) mice developed less severe lupus compared to wild type (WT) mice, and their protective phenotype consisted of (i) decreased IFN-I-stimulated gene expression, (ii) decreased numbers of peritoneal CCR2hiLy6Chi inflammatory monocytes, TNF-α-producing Ly6G+ neutrophils and Ly6Clo monocytes/macrophages, (iii) decreased production of anti-single-stranded DNA and anti-nRNP autoantibodies, and (iv) ameliorated glomerulonephritis. Cd38-/- pristane-elicited peritoneal exudate cells had defective CCL2 and TNF-α secretion following TLR7 stimulation. However, Tnf-α and Cxcl12 gene expression in Cd38-/- bone marrow (BM) cells was intact, suggesting a CD38-independent TLR7/TNF-α/CXCL12 axis in the BM. Chemotactic responses of Cd38-/- Ly6Chi monocytes and Ly6G+ neutrophils were not impaired. However, Cd38-/- Ly6Chi monocytes and Ly6Clo monocytes/macrophages had defective apoptosis-mediated cell death. Importantly, mice lacking the cation channel TRPM2 (Trpm2-/-) exhibited very similar protection, with decreased numbers of PECs, and apoptotic Ly6Chi monocytes and Ly6Clo monocytes/macrophages compared to WT mice. These findings reveal a new role for CD38 in promoting aberrant inflammation and lupus-like autoimmunity via an apoptosis-driven mechanism. Furthermore, given the implications of CD38 in the activation of TRPM2, our data suggest that CD38 modulation of pristane-induced apoptosis is TRPM2-dependent.We would like to thank Dr. Yasuo Mori for providing the Tr pm 2−/− mice, Clara Sánchez for animal husbandry at the IPBLN-CSIC Animal Facility, and Thomas S. Simpler and Uma Mudunuru for animal husbandry at the University of Alabama at Birmingham (UAB). We would also like to thank Laura Montosa from the Centro de Instrumentación Cientifica (CIC) at the Universidad de Granada (UGR) for technical support with microscopy, as well as Mohamed Tassi and Ana Santos at CIC, UGR, and Sandra García-Jiménez, Victoria Romero-del-Amo, Gemma Palencia-López, and Samuel Ruiz-Santiago at Campus Formación Granada for tissue preparations, H&E staining, and other staining procedures. Work performed in the Sancho lab was supported in part by the European Commission in collaboration with the following Funding Agencies: (i) Junta de Andalucía (J.A.), Consejería Innovación Ciencia y Empresa y Consejería Educación y Ciencia, Project: PC08-CTS-04046 to J.S. and M.Z., and (ii) Ministerio de Economía y Competitividad (MINECO), Projects: SAF-2011-27261 to J.S. and M.Z. and SAF2014-55088-R to R.M. Work performed in the Lund lab was supported by funds provided by UAB.S

Cryptic Polyketide Synthase Genes in Non-Pathogenic Clostridium SPP

Modular type I polyketide synthases (PKS) produce a vast array of bacterial metabolites with highly diverse biological functions. Notably, all known polyketides were isolated from aerobic bacteria, and yet no example has been reported for strict anaerobes. In this study we explored the diversity and distribution of PKS genes in the genus Clostridium. In addition to comparative genomic analyses combined with predictions of modular type I polyketide synthase (PKS) gene clusters in sequenced genomes of Clostridium spp., a representative selection of other species inhabiting a variety of ecological niches was investigated by PCR screening for PKS genes. Our data reveal that all studied pathogenic Clostridium spp. are devoid of putative PKS genes. In stark contrast, cryptic PKS genes are widespread in genomes of non-pathogenic Clostridium species. According to phylogenetic analyses, the Clostridium PKS genes have unusual and diverse origins. However, reverse transcription quantitative PCR demonstrates that these genes are silent under standard cultivation conditions, explaining why the related metabolites have been overlooked until now. This study presents clostridia as a putative source for novel bioactive polyketides

Hydro-Economic Modeling of Water Resources Management Challenges: Current Applications and Future Directions

Hydro-economic modeling (HEM) addresses research and policy questions from socioeconomic and biophysical perspectives under a broad range of water-related topics. Applications of HEM include economic evaluations of existing and new water projects, alternative water management actions or policies, risk assessments from hydro-climatic uncertainty (e.g., climate change), and the costs and benefits of mitigation and/or adaptation to such events. This paper reviews applications of HEM in five different categories: (1) climate change impacts and adaptation, (2) water–food–energy–ecosystems nexus management, (3) capability to link to other models, (4) innovative water management options, and (5) the ability to address and integrate uncertainty. We find that (i) the increasing complexity and heterogeneity of water resource management problems due to the growing demand and competition for water across economic sectors, (ii) limited availability and high costs of developing additional supplies, and (iii) emerging recognition and consideration of environmental water demands and value, have inspired new integrated hydro-economic problems and models to address issues of water–food–energy nexus sustainability, resilience, reliability through water (re)allocation based on the relative “value” of water uses. In the past decade, the field of HEM has improved the integration of ecosystem needs, but their representation is still insufficient and mostly ineffective. HEM studies address how to sustainably manage water resources, including groundwater which has become an area of particular interest in climate change adaptation. The current most used spatial and temporal resolutions (basin-scale and yearly time-step) are appropriate for planning but not for operational decisions and could be underestimating impacts from extreme events (e.g., flood risk) captured only by sub-monthly time scales. In addition, HEM primarily focuses on biophysical and economic indicators but often overlooks preferences and perspectives of stakeholders. Lastly, HEM has been widely used to analyze transboundary cooperation, showing benefits for increasing water security and economic development, particularly as climate change develops. We conclude that the field of HEM would benefit from developing more operational models and enhancing the integration of commonly neglected variables, such as social equity components, ecosystem requirements, and water quality

Successful Long-Term Preservation of Rat Sperm by Freeze-Drying

Background: Freeze-drying sperm has been developed as a new preservation method where liquid nitrogen is no longer necessary. An advantage of freeze-drying sperm is that it can be stored at 4uC and transported at room temperature. Although the successful freeze-drying of sperm has been reported in a number of animals, the possibility of long-term preservation using this method has not yet been studied. Methodology/Principal Findings: Offspring were obtained from oocytes fertilized with rat epididymal sperm freeze-dried using a solution containing 10 mM Tris and 1 mM EDTA adjusted to pH 8.0. Tolerance of testicular sperm to freeze-drying was increased by pre-treatment with diamide. Offspring with normal fertility were obtained from oocytes fertilized with freeze-dried epididymal sperm stored at 4uC for 5 years. Conclusions and Significance: Sperm with –SS – cross-linking in the thiol-disulfide of their protamine were highly tolerant to freeze-drying, and the fertility of freeze-dried sperm was maintained for 5 years without deterioration. This is the first report to demonstrate the successful freeze-drying of sperm using a new and simple method for long-term preservation

Mice deficient in CD38 develop an attenuated form of collagen type II-induced arthritis

CD38, a type II transmembrane glycoprotein expressed in many cells of the immune system, is involved in cell signaling, migration and differentiation. Studies in CD38 deficient mice (CD38 KO mice) indicate that this molecule controls inflammatory immune responses, although its involvement in these responses depends on the disease model analyzed. Here, we explored the role of CD38 in the control of autoimmune responses using chicken collagen type II (col II) immunized C57BL/6-CD38 KO mice as a model of collagen-induced arthritis (CIA). We demonstrate that CD38 KO mice develop an attenuated CIA that is accompanied by a limited joint induction of IL-1β and IL-6 expression, by the lack of induction of IFNγ expression in the joints and by a reduction in the percentages of invariant NKT (iNKT) cells in the spleen. Immunized CD38 KO mice produce high levels of circulating IgG1 and low of IgG2a anti-col II antibodies in association with reduced percentages of Th1 cells in the draining lymph nodes. Altogether, our results show that CD38 participates in the pathogenesis of CIA controlling the number of iNKT cells and promoting Th1 inflammatory responses

Taxonomic and Functional Microbial Signatures of the Endemic Marine Sponge Arenosclera brasiliensis

The endemic marine sponge Arenosclera brasiliensis (Porifera, Demospongiae, Haplosclerida) is a known source of secondary metabolites such as arenosclerins A-C. In the present study, we established the composition of the A. brasiliensis microbiome and the metabolic pathways associated with this community. We used 454 shotgun pyrosequencing to generate approximately 640,000 high-quality sponge-derived sequences (∼150 Mb). Clustering analysis including sponge, seawater and twenty-three other metagenomes derived from marine animal microbiomes shows that A. brasiliensis contains a specific microbiome. Fourteen bacterial phyla (including Proteobacteria, Cyanobacteria, Actinobacteria, Bacteroidetes, Firmicutes and Cloroflexi) were consistently found in the A. brasiliensis metagenomes. The A. brasiliensis microbiome is enriched for Betaproteobacteria (e.g., Burkholderia) and Gammaproteobacteria (e.g., Pseudomonas and Alteromonas) compared with the surrounding planktonic microbial communities. Functional analysis based on Rapid Annotation using Subsystem Technology (RAST) indicated that the A. brasiliensis microbiome is enriched for sequences associated with membrane transport and one-carbon metabolism. In addition, there was an overrepresentation of sequences associated with aerobic and anaerobic metabolism as well as the synthesis and degradation of secondary metabolites. This study represents the first analysis of sponge-associated microbial communities via shotgun pyrosequencing, a strategy commonly applied in similar analyses in other marine invertebrate hosts, such as corals and algae. We demonstrate that A. brasiliensis has a unique microbiome that is distinct from that of the surrounding planktonic microbes and from other marine organisms, indicating a species-specific microbiome

The FPR2-induced rise in cytosolic calcium in human neutrophils relies on an emptying of intracellular calcium stores and is inhibited by a gelsolin-derived PIP2-binding peptide

<p>Abstract</p> <p>Background</p> <p>The molecular basis for neutrophil recognition of chemotactic peptides is their binding to specific G-protein-coupled cell surface receptors (GPCRs). Human neutrophils express two pattern recognition GPCRs, FPR1 and FPR2, which belong to the family of formyl peptide receptors. The high degree of homology between these two receptors suggests that they share many functional and signal transduction properties, although they exhibit some differences with respect to signaling. The aims of this study were to determine whether FPR2 triggers a unique signal that allows direct influx of extracellular calcium without the emptying of intracellular calcium stores, and whether the gelsolin-derived PIP₂-binding peptide, PBP10, selectively inhibits FPR2-mediated transient rise in intracellular Ca²⁺.</p> <p>Results</p> <p>The transient rise in intracellular Ca²⁺induced by agonists for FPR1 or FPR2 in human neutrophils occurred also in the presence of a chelator of Ca²⁺(EGTA). PBP10 inhibited not only FPR2-induced oxidase activity, but also the transient rise in intracellular Ca²⁺.</p> <p>Conclusions</p> <p>Ca²⁺signaling mediated <it>via </it>FPR2 follows the same route as FPR1, which involves initial emptying of the intracellular stores. PBP10 inhibits selectively the signals generated by FPR2, both with respect to NADPH-oxidase activity and the transient rise in intracellular Ca²⁺induced by agonist exposure.</p