Integrated methodological framework fos assesing the risk of failure in water supply incorporating drought forecast. Case study: Andean regulated river basin

[EN] Hydroclimatic drought conditions can affect the hydrological services offered by mountain river basins causing severe impacts on the population, becoming a challenge for water resource managers in Andean river basins. This study proposes an integrated methodological framework for assessing the risk of failure in water supply, incorporating probabilistic drought forecasts, which assists in making decisions regarding the satisfaction of consumptive, non-consumptive and environmental requirements under water scarcity conditions. Monte Carlo simulation was used to assess the risk of failure in multiple stochastic scenarios, which incorporate probabilistic forecasts of drought events based on a Markov chains (MC) model using a recently developed drought index (DI). This methodology was tested in the Machángara river basin located in the south of Ecuador. Results were grouped in integrated satisfaction indexes of the system (DSIG). They demonstrated that the incorporation of probabilistic drought forecasts could better target the projections of simulation scenarios, with a view of obtaining realistic situations instead of optimistic projections that would lead to riskier decisions. Moreover, they contribute to more effective results in order to propose multiple alternatives for prevention and/or mitigation under drought conditions.This study was part of the doctoral thesis of Aviles A. at the Technical University of Valencia. This research was funded by the University of Cuenca through its Research Department (DIUC) and the Municipal public enterprise of telecommunications, drinking water, sewage and sanitation of Cuenca (ETAPA) through the projects: BIdentificacion de los procesos hidrometeorologicos que desencadenan inundaciones en la ciudad de Cuenca usando un radar de precipitacion" and "Ciclos meteorologicos y evapotranspiracion a lo largo de una gradiente altitudinal del Parque Nacional Cajas". The authors also thank INAMHI and the CBRM for providing the information for this study. The authors wish to thank the Spanish Ministry of Economy and Competitiveness for its financial support through the ERAS project (CTM2016-77804-P). We thank Angel Vazquez, who helped in the programming of the multiple simulations. Also we thank to the TropiSeca project.Avilés-Añazco, A.; Solera Solera, A.; Paredes Arquiola, J.; Pedro Monzonís, M. (2018). Integrated methodological framework fos assesing the risk of failure in water supply incorporating drought forecast. Case study: Andean regulated river basin. Water Resources Management. 32(4):1209-1223. https://doi.org/10.1007/s11269-017-1863-7S12091223324Andreu J, Capilla J, Sanchís E (1996) AQUATOOL, a generalized decision-support system for water-resources planning and operational management. 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Regulation of Tumor Suppressor p53 and HCT116 Cell Physiology by Histone Demethylase JMJD2D/KDM4D

JMJD2D, also known as KDM4D, is a histone demethylase that removes methyl moieties from lysine 9 on histone 3 and from lysine 26 on histone 1.4. Here, we demonstrate that JMJD2D forms a complex with the p53 tumor suppressor in vivo and interacts with the DNA binding domain of p53 in vitro. A luciferase reporter plasmid driven by the promoter of p21, a cell cycle inhibitor and prominent target gene of p53, was synergistically activated by p53 and JMJD2D, which was dependent on JMJD2D catalytic activity. Likewise, overexpression of JMJD2D induced p21 expression in U2OS osteosarcoma cells in the absence and presence of adriamycin, an agent that induces DNA damage. Furthermore, downregulation of JMJD2D inhibited cell proliferation in wild-type and even more so in p53−/− HCT116 colon cancer cells, suggesting that JMJD2D is a pro-proliferative molecule. JMJD2D depletion also induced more strongly apoptosis in p53−/− compared to wild-type HCT116 cells. Collectively, our results demonstrate that JMJD2D can stimulate cell proliferation and survival, suggesting that its inhibition may be helpful in the fight against cancer. Furthermore, our data imply that activation of p53 may represent a mechanism by which the pro-oncogenic functions of JMJD2D become dampened

A Role for TLR4 in Clostridium difficile Infection and the Recognition of Surface Layer Proteins

Clostridium difficile is the etiological agent of antibiotic-associated diarrhoea (AAD) and pseudomembranous colitis in humans. The role of the surface layer proteins (SLPs) in this disease has not yet been fully explored. The aim of this study was to investigate a role for SLPs in the recognition of C. difficile and the subsequent activation of the immune system. Bone marrow derived dendritic cells (DCs) exposed to SLPs were assessed for production of inflammatory cytokines, expression of cell surface markers and their ability to generate T helper (Th) cell responses. DCs isolated from C3H/HeN and C3H/HeJ mice were used in order to examine whether SLPs are recognised by TLR4. The role of TLR4 in infection was examined in TLR4-deficient mice. SLPs induced maturation of DCs characterised by production of IL-12, TNFα and IL-10 and expression of MHC class II, CD40, CD80 and CD86. Furthermore, SLP-activated DCs generated Th cells producing IFNγ and IL-17. SLPs were unable to activate DCs isolated from TLR4-mutant C3H/HeJ mice and failed to induce a subsequent Th cell response. TLR4−/− and Myd88−/−, but not TRIF−/− mice were more susceptible than wild-type mice to C. difficile infection. Furthermore, SLPs activated NFκB, but not IRF3, downstream of TLR4. Our results indicate that SLPs isolated from C. difficile can activate innate and adaptive immunity and that these effects are mediated by TLR4, with TLR4 having a functional role in experimental C. difficile infection. This suggests an important role for SLPs in the recognition of C. difficile by the immune system

Activation of PKR Causes Amyloid ß-Peptide Accumulation via De-Repression of BACE1 Expression

BACE1 is a key enzyme involved in the production of amyloid ß-peptide (Aß) in Alzheimer's disease (AD) brains. Normally, its expression is constitutively inhibited due to the presence of the 5′untranslated region (5′UTR) in the BACE1 promoter. BACE1 expression is activated by phosphorylation of the eukaryotic initiation factor (eIF)2-alpha, which reverses the inhibitory effect exerted by BACE1 5′UTR. There are four kinases associated with different types of stress that could phosphorylate eIF2-alpha. Here we focus on the double-stranded (ds) RNA-activated protein kinase (PKR). PKR is activated during viral infection, including that of herpes simplex virus type 1 (HSV1), a virus suggested to be implicated in the development of AD, acting when present in brains of carriers of the type 4 allele of the apolipoprotein E gene. HSV1 is a dsDNA virus but it has genes on both strands of the genome, and from these genes complementary RNA molecules are transcribed. These could activate BACE1 expression by the PKR pathway. Here we demonstrate in HSV1-infected neuroblastoma cells, and in peripheral nervous tissue from HSV1-infected mice, that HSV1 activates PKR. Cloning BACE1 5′UTR upstream of a luciferase (luc) gene confirmed its inhibitory effect, which can be prevented by salubrinal, an inhibitor of the eIF2-alpha phosphatase PP1c. Treatment with the dsRNA analog poly (I∶C) mimicked the stimulatory effect exerted by salubrinal over BACE1 translation in the 5′UTR-luc construct and increased Aß production in HEK-APPsw cells. Summarizing, our data suggest that PKR activated in brain by HSV1 could play an important role in the development of AD

Excessive substance use in bipolar disorder is associated with impaired functioning rather than clinical characteristics, a descriptive study

<p>Abstract</p> <p>Background</p> <p>There is a strong association between bipolar disorder (BD) and substance use disorder (SUD). The clinical and functional correlates of SUD in BD are still unclear and little is known about the role of excessive substance use that does not meet SUD criteria. Thus, the aims of the current study were to investigate lifetime rates of illicit substance use in BD relative to the normal population and if there are differences in clinical and functional features between BD patients with and without excessive substance use.</p> <p>Methods</p> <p>125 consecutively recruited BD in- and outpatients from the Oslo University Hospitals and 327 persons randomly drawn from the population in Oslo, Norway participated. Clinical and functional variables were assessed. Excessive substance use was defined as DSM-IV SUD and/or excessive use according to predefined criteria.</p> <p>Results</p> <p>The rate of lifetime illicit substance use was significantly higher among patients compared to the reference population (OR = 3.03, CI = 1.9-4.8, p < .001). Patients with excessive substance use (45% of total) had poorer educational level, occupational status, GAF-scores and medication compliance, with a trend towards higher suicidality rates, compared to patients without. There were no significant group differences in current symptom levels or disease course between groups.</p> <p>Conclusion</p> <p>The percentage of patients with BD that had tried illicit substances was significantly higher than in the normal population. BD patients with excessive substance use clearly had impaired functioning, but not a worse course of illness compared to patients without excessive substance use. An assessment of substance use beyond SUD criteria in BD is clinically relevant.</p

Population ecology of the sea lamprey (Petromyzon marinus) as an invasive species in the Laurentian Great Lakes and an imperiled species in Europe

The sea lamprey Petromyzon marinus (Linnaeus) is both an invasive non-native species in the Laurentian Great Lakes of North America and an imperiled species in much of its native range in North America and Europe. To compare and contrast how understanding of population ecology is useful for control programs in the Great Lakes and restoration programs in Europe, we review current understanding of the population ecology of the sea lamprey in its native and introduced range. Some attributes of sea lamprey population ecology are particularly useful for both control programs in the Great Lakes and restoration programs in the native range. First, traps within fish ladders are beneficial for removing sea lampreys in Great Lakes streams and passing sea lampreys in the native range. Second, attractants and repellants are suitable for luring sea lampreys into traps for control in the Great Lakes and guiding sea lamprey passage for conservation in the native range. Third, assessment methods used for targeting sea lamprey control in the Great Lakes are useful for targeting habitat protection in the native range. Last, assessment methods used to quantify numbers of all life stages of sea lampreys would be appropriate for measuring success of control in the Great Lakes and success of conservation in the native range

Characterization of the macrophage transcriptome in glomerulonephritis-susceptible and -resistant rat strains

Crescentic glomerulonephritis (CRGN) is a major cause of rapidly progressive renal failure for which the underlying genetic basis is unknown. WKY rats show marked susceptibility to CRGN, while Lewis rats are resistant. Glomerular injury and crescent formation are macrophage-dependent and mainly explained by seven quantitative trait loci (Crgn1-7). Here, we used microarray analysis in basal and lipopolysaccharide (LPS)-stimulated macrophages to identify genes that reside on pathways predisposing WKY rats to CRGN. We detected 97 novel positional candidates for the uncharacterised Crgn3-7. We identified 10 additional secondary effector genes with profound differences in expression between the two strains (>5-fold change, <1% False Discovery Rate) for basal and LPS-stimulated macrophages. Moreover, we identified 8 genes with differentially expressed alternatively spliced isoforms, by using an in depth analysis at probe-level that allowed us to discard false positives due to polymorphisms between the two rat strains. Pathway analysis identified several common linked pathways, enriched for differentially expressed genes, which affect macrophage activation. In summary, our results identify distinct macrophage transcriptome profiles between two rat strains that differ in susceptibility to glomerulonephritis, provide novel positional candidates for Crgn3-7, and define groups of genes that play a significant role in differential regulation of macrophage activity