Assessment of the contribution of groundwater discharges to rivers using monthly flow statistics and flow seasonality

Groundwater discharge is believed to dominate dry season flows in perennial river systems and to sustain aquatic biodiversity. River flow statistics, extracted from the SPATSIM modelling system, were used to estimate the contribution of groundwater to river flow regimes. The flow statistics were compared for the principal aquifer types (based on major geological formations) in South Africa. This analysis focused on seasonal variation in flows rather than the annual totals or Baseflow Index. Groundwater discharge is expected to reduce flow variability and sustain flows, making flow concentrations lower than rainfall concentrations. Catchments dominated by carbonates have the greatest proportion of baseflow (37%), followed by basement complex (31%) and extrusive aquifer types (31%). The weak relationships between river flow indexes (particularly the Baseflow Index, Coefficient of Variation and Hydrological Index) and the seasonality or concentration statistics imply that catchment storage characteristics and other non-climatic factors play an important role in flow regulation. The geographic distribution of total flow concentrations differs markedly from rainfall concentrations, further evidence that non-climatic factors are important determinants of flow regimes. Karoo dykes and sills, extrusives and unconsolidated deposits are under-represented and the TMG sub-type, carbonates and basement complex and younger granites are over-represented among catchments with evenly distributed baseflows. The Baseflow Index and groundwater-fed baseflow are ecologically meaningful variables but lack clear thresholds that correspond with ecologically important changes in river flow regimes, for example perennial versus seasonal flow. Flow concentrations and percentage zero flows are useful and potentially ecologically important variables and should be tested as predictors of the aquatic and riparian biodiversity of river systems at a range of scales.Keywords: river flow statistics, baseflow, flow concentration, principal aquifer types, groundwater discharg

Zinc homeostasis and signaling in health and diseases: Zinc signaling

The essential trace element zinc (Zn) is widely required in cellular functions, and abnormal Zn homeostasis causes a variety of health problems that include growth retardation, immunodeficiency, hypogonadism, and neuronal and sensory dysfunctions. Zn homeostasis is regulated through Zn transporters, permeable channels, and metallothioneins. Recent studies highlight Zn’s dynamic activity and its role as a signaling mediator. Zn acts as an intracellular signaling molecule, capable of communicating between cells, converting extracellular stimuli to intracellular signals, and controlling intracellular events. We have proposed that intracellular Zn signaling falls into two classes, early and late Zn signaling. This review addresses recent findings regarding Zn signaling and its role in physiological processes and pathogenesis

Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes

Australian Pancreatic Cancer Genome Initiative members: Nam Q. Nguyen, Andrew R. Ruszkiewicz and Chris Worthley of the Royal Adelaide Hospital.Pancreatic cancer is a highly lethal malignancy with few effective therapies. We performed exome sequencing and copy number analysis to define genomic aberrations in a prospectively accrued clinical cohort (n = 142) of early (stage I and II) sporadic pancreatic ductal adenocarcinoma. Detailed analysis of 99 informative tumours identified substantial heterogeneity with 2,016 non-silent mutations and 1,628 copy-number variations. We define 16 significantly mutated genes, reaffirming known mutations (KRAS, TP53, CDKN2A, SMAD4, MLL3, TGFBR2, ARID1A and SF3B1), and uncover novel mutated genes including additional genes involved in chromatin modification (EPC1 and ARID2), DNA damage repair (ATM) and other mechanisms (ZIM2, MAP2K4, NALCN, SLC16A4 and MAGEA6). Integrative analysis with in vitro functional data and animal models provided supportive evidence for potential roles for these genetic aberrations in carcinogenesis. Pathway-based analysis of recurrently mutated genes recapitulated clustering in core signalling pathways in pancreatic ductal adenocarcinoma, and identified new mutated genes in each pathway. We also identified frequent and diverse somatic aberrations in genes described traditionally as embryonic regulators of axon guidance, particularly SLIT/ROBO signalling, which was also evident in murine Sleeping Beauty transposon-mediated somatic mutagenesis models of pancreatic cancer, providing further supportive evidence for the potential involvement of axon guidance genes in pancreatic carcinogenesis.International Cancer Genome Consortiu

Genomic analyses identify molecular subtypes of pancreatic cancer

© 2016 Macmillan Publishers Limited. All rights reserved.Integrated genomic analysis of 456 pancreatic ductal adenocarcinomas identified 32 recurrently mutated genes that aggregate into 10 pathways: KRAS, TGF-β, WNT, NOTCH, ROBO/SLIT signalling, G1/S transition, SWI-SNF, chromatin modification, DNA repair and RNA processing. Expression analysis defined 4 subtypes: (1) squamous; (2) pancreatic progenitor; (3) immunogenic; and (4) aberrantly differentiated endocrine exocrine (ADEX) that correlate with histopathological characteristics. Squamous tumours are enriched for TP53 and KDM6A mutations, upregulation of the TP63ΔN transcriptional network, hypermethylation of pancreatic endodermal cell-fate determining genes and have a poor prognosis. Pancreatic progenitor tumours preferentially express genes involved in early pancreatic development (FOXA2/3, PDX1 and MNX1). ADEX tumours displayed upregulation of genes that regulate networks involved in KRAS activation, exocrine (NR5A2 and RBPJL), and endocrine differentiation (NEUROD1 and NKX2-2). Immunogenic tumours contained upregulated immune networks including pathways involved in acquired immune suppression. These data infer differences in the molecular evolution of pancreatic cancer subtypes and identify opportunities for therapeutic development