Changes in phytoplankton population along the saline gradient of the Júcar estuary and plume

This paper presents the results of phytoplankton counts carried out with epifluorescence at five sampling stations: two in the Júcar River Estuary and the other three in the region of freshwater influence of the Júcar River. From June 2002 to July 2003, nine sampling campaigns were carried out as a part of the EU's ECOSUD project. Two of these campaigns (the 2nd and 8th) were selected for analysis. These sampling campaigns represent two different conditions: in the 2nd campaign the discharge of the Júcar River was almost null, while in the 8th campaign it was significantly higher. Along the salinity gradient, as the influence of fresh water and nutrient loads decreases, a decrease in the population density of eukaryotic phytoplankton was observed. Typical freshwater phytoplankton groups (colonial cyanobacteria and chlorophyceae) clearly decrease in density and percentage as salinity increases. In general, picocyanobacteria exhibit the opposite behavior. The behavior pattern of groups with species adapted to fresh water and seawater is less clear. The density of these groups (diatoms and prymnesiophytes) is highest in the salt-wedge area due to nutrient accumulation. However, the densities are generally higher at the freshwater stations than in the marine environment. The vertical distribution at the estuarine stations shows clear density maximums in the interface area, which seems to have two causes: the retention of senescent phytoplankton affected by saline shock in this quiescent area and the growth of phytoplankton that exploit the accumulated nutrients.González Del Rio Rams, J.; Romero Gil, I.; Falco, S.; Rodilla, M.; Sierra, JP.; Sánchez-Arcilla, A.; Mösso, C. (2007). Changes in phytoplankton population along the saline gradient of the Júcar estuary and plume. Journal of Coastal Research. SI 47:63-68. doi:10.2112/1551-5036-47.sp1.63S6368SI 4

Integrated modelling of cost-effective siting and operation of flow-control infrastructure for river ecosystem conservation

Wetland and floodplain ecosystems along many regulated rivers are highly stressed, primarily due to a lack of environmental flows of appropriate magnitude, frequency, duration, and timing to support ecological functions. In the absence of increased environmental flows, the ecological health of river ecosystems can be enhanced by the operation of existing and new flow-control infrastructure (weirs and regulators) to return more natural environmental flow regimes to specific areas. However, determining the optimal investment and operation strategies over time is a complex task due to several factors including the multiple environmental values attached to wetlands, spatial and temporal heterogeneity and dependencies, nonlinearity, and time-dependent decisions. This makes for a very large number of decision variables over a long planning horizon. The focus of this paper is the development of a nonlinear integer programming model that accommodates these complexities. The mathematical objective aims to return the natural flow regime of key components of river ecosystems in terms of flood timing, flood duration, and interflood period. We applied a 2-stage recursive heuristic using tabu search to solve the model and tested it on the entire South Australian River Murray floodplain. We conclude that modern meta-heuristics can be used to solve the very complex nonlinear problems with spatial and temporal dependencies typical of environmental flow allocation in regulated river ecosystems. The model has been used to inform the investment in, and operation of, flow-control infrastructure in the South Australian River Murray.<br /

Endoplasmic Reticulum Stress-Induced JNK Activation Is a Critical Event Leading to Mitochondria-Mediated Cell Death Caused by β-Lapachone Treatment

β-lapachone (β-lap) is a bioreductive agent that is activated by the two-electron reductase NAD(P)H quinone oxidoreductase 1 (NQO1). Although β-lap has been reported to induce apoptosis in various cancer types in an NQO1-dependent manner, the signaling pathways by which β-lap causes apoptosis are poorly understood.β-lap-induced apoptosis and related molecular signaling pathways in NQO1-negative and NQO1-overexpressing MDA-MB-231 cells were investigated. Pharmacological inhibitors or siRNAs against factors involved in β-lap-induced apoptosis were used to clarify the roles played by such factors in β-lap-activated apoptotic signaling pathways. β-lap leads to clonogenic cell death and apoptosis in an NQO1- dependent manner. Treatment of NQO1-overexpressing MDA-MB-231 cells with β-lap causes rapid disruption of mitochondrial membrane potential, nuclear translocation of AIF and Endo G from mitochondria, and subsequent caspase-independent apoptotic cell death. siRNAs targeting AIF and Endo G effectively attenuate β-lap-induced clonogenic and apoptotic cell death. Moreover, β-lap induces cleavage of Bax, which accumulates in mitochondria, coinciding with the observed changes in mitochondria membrane potential. Pretreatment with Salubrinal (Sal), an endoplasmic reticulum (ER) stress inhibitor, efficiently attenuates JNK activation caused by β-lap, and subsequent mitochondria-mediated cell death. In addition, β-lap-induced generation and mitochondrial translocation of cleaved Bax are efficiently blocked by JNK inhibition.Our results indicate that β-lap triggers induction of endoplasmic reticulum (ER) stress, thereby leading to JNK activation and mitochondria-mediated apoptosis. The signaling pathways that we revealed in this study may significantly contribute to an improvement of NQO1-directed tumor therapies

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Phase Behavior of Aqueous Na-K-Mg-Ca-CI-NO3 Mixtures: Isopiestic Measurements and Thermodynamic Modeling

A comprehensive model has been established for calculating thermodynamic properties of multicomponent aqueous systems containing the Na{sup +}, K{sup +}, Mg{sup 2+}, Ca{sup 2+}, Cl{sup -}, and NO{sub 3}{sup -} ions. The thermodynamic framework is based on a previously developed model for mixed-solvent electrolyte solutions. The framework has been designed to reproduce the properties of salt solutions at temperatures ranging from the freezing point to 300 C and concentrations ranging from infinite dilution to the fused salt limit. The model has been parameterized using a combination of an extensive literature database and new isopiestic measurements for thirteen salt mixtures at 140 C. The measurements have been performed using Oak Ridge National Laboratory's (ORNL) previously designed gravimetric isopiestic apparatus, which makes it possible to detect solid phase precipitation. Water activities are reported for mixtures with a fixed ratio of salts as a function of the total apparent salt mole fraction. The isopiestic measurements reported here simultaneously reflect two fundamental properties of the system, i.e., the activity of water as a function of solution concentration and the occurrence of solid-liquid transitions. The thermodynamic model accurately reproduces the new isopiestic data as well as literature data for binary, ternary and higher-order subsystems. Because of its high accuracy in calculating vapor-liquid and solid-liquid equilibria, the model is suitable for studying deliquescence behavior of multicomponent salt systems

Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing

Chromothripsis is a mutational phenomenon characterized by massive, clustered genomic rearrangements that occurs in cancer and other diseases. Recent studies in selected cancer types have suggested that chromothripsis may be more common than initially inferred from low-resolution copy-number data. Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), we analyze patterns of chromothripsis across 2,658 tumors from 38 cancer types using whole-genome sequencing data. We find that chromothripsis events are pervasive across cancers, with a frequency of more than 50% in several cancer types. Whereas canonical chromothripsis profiles display oscillations between two copy-number states, a considerable fraction of events involve multiple chromosomes and additional structural alterations. In addition to non-homologous end joining, we detect signatures of replication-associated processes and templated insertions. Chromothripsis contributes to oncogene amplification and to inactivation of genes such as mismatch-repair-related genes. These findings show that chromothripsis is a major process that drives genome evolution in human cancer

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Neuroendocrine challenge studies of serotonin and gaba function in mania and in the mechanism of action of the mood stabilizer divalproex sodium

In this thesis, we report on studies that investigated the roles of serotonin (5- hydroxytryptamine; 5-HT) and y-aminobutyric acid (GABA) in the pathophysiology of mania and in the mechanism of action of the mood stabilizer, divalproex sodium (DVP) using neuroendocrine challenge paradigm. Pharmacological challenges with the 5-HTiA receptor agonist, ipsapirone and the GABAB receptor agonist, baclofen were administered to patients with mania and normal healthy volunteers. Following the administration of challenge agents, hormonal, hypothermic, and/or behavioral responses were measured at regular intervals. We found that 1) manic patients had significantly enhanced ACTH and Cortisol responses to ipsapirone when compared to normal controls, but the hypothermic response to ipsapirone did not differ between the two groups; 2) one-week treatment with DVP significantly attenuated hypothermic response to ipsapirone in healthy controls but this did not modify the ACTH or Cortisol response to ipsapirone; 3) GH response to baclofen was significantly increased in manic patients compared to normal controls; 4) one-week treatment with DVP significantly attenuated the GH response to baclofen in healthy controls. The results of 5-HT neuroendocinre challenge studies suggest that manic patients have an increase in postsynaptic 5-HT]A receptor sensitivity, which may be secondary to diminished 5-HT availability in central 5-HT synapses, and that DVP enhances 5-HT neurotransmission via a subsensitization of 5-HTIA autoreceptors. These appear to support hypotheses that a 5-HT deficit is involved in mania and that enhancement of 5-HT neurotransmission exerts a mood stabilizing effect. The findings of GABA neuroendocrine challenge studies suggest that manic patients also have an up-regulated hypothalamic GABAB receptor function, presumably resulting from a GABA deficit in brain, and that DVP treatment restores this deficit by enhancing GABAergic neurotransmission, thus leading to a down-regulation in hypothalamic GABAB receptor function. These experiments have provided some evidence for the contribution of 5-HT and GABA in mania and in the mechanism of action of DVP. However, it is very likely that other neurotransmitters such as norepinephrine and dopamine and their interaction with 5-HT and GABA also play important roles. More neurobiological studies on manic patients are warranted to enhance our understanding of this illness and its treatment.Medicine, Faculty ofGraduat

Concurrent hypokalemic periodic paralysis and bipolar disorder

Primary periodic paralysis is a rare autosomal dominant disorder of ion-channel dysfunction, manifested by episodic flaccid paresis secondary to abnormal sarcolemma excitability. Membrane destabilization involving Na, K-ATPase has been hypothesized to be a biological etiology of the bipolar disorder (BD) and the mechanisms underlying lithium therapy have been linked to it. To date, there has been only one reported case of BD comorbid with periodic paralysis. Herein, we reported another case of concurrent bipolar mania and hypokalemic periodic paralysis (HPP), one special form of periodic paralysis. Consistent with the previous case, our patient responded well to lithium treatment for both bipolar mania and HPP. This might provide some support to the hypothesis that the therapeutic effects of lithium in both BD and HPP could be due to the correction of the underlying common pathophysiology