The fate of sediment, wood and organic carbon eroded during an extreme flood, Colorado Front Range, USA

Identifying and quantifying the dominant processes of erosion and tracking the fate of sediment, wood, and carbon eroded during floods is important for understanding channel response to floods, downstream sediment and carbon loading, and the influence of extreme events on landscapes and the terrestrial carbon cycle. We quantify sediment, wood, and organic carbon (OC) from source to local sink following an extreme flood in the tectonically quiescent, semi-arid Colorado (USA) Front Range. Erosion of >500,000 m3 or as much as ~115 yr of weathering products occurred through landsliding and channel erosion during September 2013 flooding. More than half of the eroded sediment was deposited at the inlet and delta of a water supply reservoir, resulting in the equivalent of 100 yr of reservoir sedimentation and 2% loss in water storage capacity. The flood discharged 28 Mg C/km2, producing an event OC flux equivalent to humid, tectonically active areas. Post-flood remobilization resulted in a further ~100 yr of reservoir sedimentation plus export of an additional 1.3 Mg C/km2 of wood, demonstrating the ongoing impact of the flood on reservoir capacity and carbon cycling. Pronounced channel widening during the flood created accommodation space for 40% of flood sediment and storage of wood and eroded carbon. We conclude that confined channels, normally dismissed as transport reaches, can store and export substantial amounts of flood constituents

Differences in somatic TP53 mutation type in breast tumors by race and receptor status

Purpose: Somatic driver mutations in TP53 are associated with triple-negative breast cancer (TNBC) and poorer outcomes. Breast cancers in women of African ancestry (AA) are more likely to be TNBC and have somatic TP53 mutations than cancers in non-Hispanic White (NHW) women. Missense driver mutations in TP53 have varied functional impact including loss-of-function (LOF) or gain-of-function (GOF) activity, and dominant negative (DNE) effects. We aimed to determine if there were differences in somatic TP53 mutation types by patient ancestry or TNBC status. Methods: We identified breast cancer datasets with somatic TP53 mutation data, ancestry, age, and hormone receptor status. Mutations were classified for functional impact using published data and type of mutation. We assessed differences using Fisher’s exact test. Results: From 96 breast cancer studies, we identified 2964 women with somatic TP53 mutations: 715 (24.1%) Asian, 258 (8.7%) AA, 1931 (65.2%) NHW, and 60 (2%) Latina. The distribution of TP53 mutation type was similar by ancestry. However, 35.8% of tumors from NHW individuals had GOF mutations compared to 29% from AA individuals (p = 0.04). Mutations with DNE activity were positively associated with TNBC (OR 1.37, p = 0.03) and estrogen receptor (ER) negative status (OR 1.38; p = 0.005). Conclusions: Somatic TP53 mutation types did not differ by ancestry overall, but GOF mutations were more common in NHW women than AA women. ER-negative and TNBC tumors are less likely to have DNE+ TP53 mutations which could reflect biological processes. Larger cohorts and functional studies are needed to further elucidate these findings

Genome-wide association study identifies 30 Loci Associated with Bipolar Disorder

This paper is dedicated to the memory of Psychiatric Genomics Consortium (PGC) founding member and Bipolar disorder working group co-chair Pamela Sklar. We thank the participants who donated their time, experiences and DNA to this research, and to the clinical and scientific teams that worked with them. We are deeply indebted to the investigators who comprise the PGC. The views expressed are those of the authors and not necessarily those of any funding or regulatory body. Analyses were carried out on the NL Genetic Cluster Computer (http://www.geneticcluster.org ) hosted by SURFsara, and the Mount Sinai high performance computing cluster (http://hpc.mssm.edu).Bipolar disorder is a highly heritable psychiatric disorder. We performed a genome-wide association study including 20,352 cases and 31,358 controls of European descent, with follow-up analysis of 822 variants with P<1x10-4 in an additional 9,412 cases and 137,760 controls. Eight of the 19 variants that were genome-wide significant (GWS, p < 5x10-8) in the discovery GWAS were not GWS in the combined analysis, consistent with small effect sizes and limited power but also with genetic heterogeneity. In the combined analysis 30 loci were GWS including 20 novel loci. The significant loci contain genes encoding ion channels, neurotransmitter transporters and synaptic components. Pathway analysis revealed nine significantly enriched gene-sets including regulation of insulin secretion and endocannabinoid signaling. BDI is strongly genetically correlated with schizophrenia, driven by psychosis, whereas BDII is more strongly correlated with major depressive disorder. These findings address key clinical questions and provide potential new biological mechanisms for BD.This work was funded in part by the Brain and Behavior Research Foundation, Stanley Medical Research Institute, University of Michigan, Pritzker Neuropsychiatric Disorders Research Fund L.L.C., Marriot Foundation and the Mayo Clinic Center for Individualized Medicine, the NIMH Intramural Research Program; Canadian Institutes of Health Research; the UK Maudsley NHS Foundation Trust, NIHR, NRS, MRC, Wellcome Trust; European Research Council; German Ministry for Education and Research, German Research Foundation IZKF of Münster, Deutsche Forschungsgemeinschaft, ImmunoSensation, the Dr. Lisa-Oehler Foundation, University of Bonn; the Swiss National Science Foundation; French Foundation FondaMental and ANR; Spanish Ministerio de Economía, CIBERSAM, Industria y Competitividad, European Regional Development Fund (ERDF), Generalitat de Catalunya, EU Horizon 2020 Research and Innovation Programme; BBMRI-NL; South-East Norway Regional Health Authority and Mrs. Throne-Holst; Swedish Research Council, Stockholm County Council, Söderström Foundation; Lundbeck Foundation, Aarhus University; Australia NHMRC, NSW Ministry of Health, Janette M O'Neil and Betty C Lynch

Severe experimental autoimmune encephalomyelitis (EAE) is ameliorated by human olfactory-derived mesenchymal stromal cell transplantation

Currently, bone marrow-derived mesenchymal stromal cells (BM-MSCs) are being tested in the clinic for the treatment of the demyelinating disease, Multiple Sclerosis (MS). Their immunomodulatory action, which targets the inflammatory component of the disease, is thought to make them ideal candidates. However, a treatment which suppresses disease activity whilst also promoting endogenous remyelination would be considered to be advantageous. We have identified a novel MSC type from the human olfactory mucosa (OM-MSCs), which we have shown to enhance CNS myelination in vitro to a greater extent than those derived from bone marrow. In addition, we have demonstrated that OM-MSCs secrete less of the pro-inflammatory chemokines, IL-6, IL-8 and CCL2 than BM-MSCs and skew microglia to an anti-inflammatory phenotype. We, therefore, postulated that OM-MSCs may have therapeutic benefits over BM-MSCs in the treatment of MS, as a result of their secreted chemokine milieu and their enhanced myelinating capabilities. In this investigation, we have compared the reparative properties of OM-MSCs to BM-MSCs using the animal model of MS, experimental autoimmune encephalomyelitis (EAE). We have shown that both MSC types are capable of ameliorating the disease compared to PBS control injected animals, if cells are delivered intravenously (1 x 106 cells) at early disease i.e. when animals achieve a score of 1 on the EAE score (loss of tail tone). However, when administered during established severe disease (score of 3 or above; hindlimb paralysis), only OM-MSCs significantly improved disease outcome. Furthermore, histological examination revealed an increased number of remyelinated axons, and a reduction in the inflammatory infiltrate after treatment with OM-MSCs compared to BM-MSCs or PBS control injected animals. This research has shown that OM-MSCs may have therapeutic benefits over BM-MSCs in the treatment of demyelinating conditions, such as MS, especially if administered during progressive disease. Thus OM-MSCs could be a better cell choice for use in the clinic

Spatial patterns in markers of contaminant exposure, glucose and glycogen metabolism, and immunological response in juvenile winter flounder (Pseudopleuronectes americanus)

Inshore winter flounder (Pseudopleuronectes americanus) populations in NY, USA have reached record low numbers in recent years, and recruitment into the fishery appears to be limited by survival of post-settlement juvenile fish. In order to identify cellular pathways associated with site-specific variation in condition and mortality, we examined differential mRNA expression in juvenile winter flounder collected from six different bays across a gradient in human population density and sewage inputs. Illumina sequencing of pooled samples of flounder from contrasting degraded sites and less impacted sites was used to guide our choice of targets for qPCR analysis. 253 transcripts of > 100 bp were differentially expressed, with 60% showing strong homology to mostly teleost sequences within the NCBI database. Based on these data, transcripts representing nine genes of interest associated with contaminant exposure, immune response and glucose and glycogen metabolism were examined by qPCR in individual flounder from each site. Statistically significant site-specific differences were observed in expression of all but one gene, although patterns in expression were complex with only one, (vitellogenin) demonstrating a west to east gradient consistent with known loadings of municipal sewage effluent. Principal components analysis (PCA) identified relationships among the genes evaluated. Our data indicate that juvenile winter flounder are responding to estrogenic chemicals in more urbanized coastal bays, and suggests potential mechanistic links between immune response, contaminant exposure and energy metabolism