Alluvial terrace development and changing landscape connectivity in the Great Karoo, South Africa. Insights from the Wilgerbosch Riyer catchment, Sneeuberg

Dendritic channel networks in the Wilgerbosch River catchment draining the south side of the Sneeuberg, South Africa, are deeply incised exposing terrace fills of varying thickness and extent. Channel long sections exhibit ‘stepped’ profiles where resistant rock strata cross valley floors but are now partially or completely breached. Using a combination of aerial image analysis, geomorphological mapping, sedimentological investigations (field logging, grain size, and magnetic susceptibility analyses), and geochronology (OSL, 14C), this study demonstrates the patterns and controls on erosion and sedimentation and, to a lesser extent, the age structure of fills in two low-order tributaries (Africanders Kloof and Wilgerbosch Kloof) and several reaches of the higher-order Wilgerbosch River. A conceptual model of terrace development in relation to changing conditions of connectivity is presented. Valley headwaters are dominated by discontinuous palaeochannel and floodout sediments; whilst in second- to fourth-order tributaries, four sedimentologically and stratigraphically distinct terrace fills that exceed the scale and complexity of deposits on the northward side of the Sneeuberg were identified and analysed. The early part of this regional terrace succession highlights the importance of interactions between periglacial and fluvial activity on cut, fill, and pedogenesis around the time of the deglacial period. Terrace development is shown to have been a complex response to reconnection of the channel network with upland colluvial stores resulting in the valleys becoming choked with sediment. This caused a rise in groundwater and formation of extensive calcretised rootmats on valley floors and slopes acting to ‘blanket’ terraces 1 and 2. The thickness and longevity of this blanket is shown to restrict depth of incision in subsequent phases (T3, T4). The deposits in these headwater valleys have, until now, been overlooked as a source of palaeoenvironmental information. This study is the first to demonstrate the role and importance of changing connectivity in 'cut and fill' phases that predate the late eighteenth century European incursion in the Sneeuberg

Amplification of HER2 is a marker for global genomic instability

<p>Abstract</p> <p>Background</p> <p>Genomic alterations of the proto-oncogene c-erbB-2 (HER-2/neu) are associated with aggressive behavior and poor prognosis in patients with breast cancer. The variable clinical outcomes seen in patients with similar HER2 status, given similar treatments, suggests that the effects of amplification of HER2 can be influenced by other genetic changes. To assess the broader genomic implications of structural changes at the HER2 locus, we investigated relationships between genomic instability and HER2 status in patients with invasive breast cancer.</p> <p>Methods</p> <p>HER2 status was determined using the PathVysion^®assay. DNA was extracted after laser microdissection from the 181 paraffin-embedded HER2 amplified (n = 39) or HER2 negative (n = 142) tumor specimens with sufficient tumor available to perform molecular analysis. Allelic imbalance (AI) was assessed using a panel of microsatellite markers representing 26 chromosomal regions commonly altered in breast cancer. Student t-tests and partial correlations were used to investigate relationships between genomic instability and HER2 status.</p> <p>Results</p> <p>The frequency of AI was significantly higher (<it>P </it>< 0.005) in HER2 amplified (27%) compared to HER2 negative tumors (19%). Samples with HER2 amplification showed significantly higher levels of AI (<it>P </it>< 0.05) at chromosomes 11q23, 16q22-q24 and 18q21. Partial correlations including ER status and tumor grade supported associations between HER2 status and alterations at 11q13.1, 16q22-q24 and 18q21.</p> <p>Conclusion</p> <p>The poor prognosis associated with HER2 amplification may be attributed to global genomic instability as cells with high frequencies of chromosomal alterations have been associated with increased cellular proliferation and aggressive behavior. In addition, high levels of DNA damage may render tumor cells refractory to treatment. In addition, specific alterations at chromosomes 11q13, 16q22-q24, and 18q21, all of which have been associated with aggressive tumor behavior, may serve as genetic modifiers to HER2 amplification. These data not only improve our understanding of HER in breast pathogenesis but may allow more accurate risk profiles and better treatment options to be developed.</p

Quantifying system disturbance and recovery from historical mining-derived metal contamination at Brotherswater, northwest England

The final publication is available at Springer via https://doi.org/10.1007/s10933-016-9907-1Metal ore extraction in historical times has left a legacy of severe contamination in aquatic ecosystems around the world. In the UK, there are ongoing nationwide surveys of present-day pollution discharged from abandoned mines but few assessments of the magnitude of contamination and impacts that arose during historical metal mining have been made. We report one of the first multi-centennial records of lead (Pb), zinc (Zn) and copper (Cu) fluxes into a lake (Brotherswater, northwest England) from point-sources in its catchment (Hartsop Hall Mine and Hogget Gill processing plant) and calculate basin-scale inventories of those metals. The pre-mining baseline for metal contamination has been established using sediment cores spanning the past 1,500 years and contemporary material obtained through sediment trapping. These data enabled the impact of 250 years of local, small-scale mining (1696 – 1942) to be quantified and an assessment of the trajectory towards system recovery to be made. The geochemical stratigraphy displayed in twelve sediment cores show strong correspondence to the documented history of metal mining and processing in the catchment. The initial onset in 1696 was detected, peak Pb concentrations (>10,000 µg g-1) and flux (39.4 g m-2 y-1) corresponded to the most intensive mining episode (1863-1871) and 20th century technological enhancements were reflected as a more muted sedimentary imprint. After careful evaluation, we used these markers to augment a Bayesian age-depth model of the independent geochronology obtained using radioisotope dating (14C, 210Pb, 137Cs and 241Am). Total inventories of Pb, Zn and Cu for the lake basin during the period of active mining were 15,415 kg, 5,897 kg and 363 kg, respectively. The post-mining trajectories for Pb and Zn project a return to pre-mining levels within 54-128 years for Pb and 75-187 years for Zn, although future remobilisation of metal-enriched catchment soils and floodplain sediments could perturb this recovery. We present a transferable paleolimnological approach that highlights flux-based assessments are vital to accurately establish the baseline, impact and trajectory of mining-derived contamination for a lake catchment

Comprehensive molecular characterization of the hippo signaling pathway in cancer

Hippo signaling has been recognized as a key tumor suppressor pathway. Here, we perform a comprehensive molecular characterization of 19 Hippo core genes in 9,125 tumor samples across 33 cancer types using multidimensional “omic” data from The Cancer Genome Atlas. We identify somatic drivers among Hippo genes and the related microRNA (miRNA) regulators, and using functional genomic approaches, we experimentally characterize YAP and TAZ mutation effects and miR-590 and miR-200a regulation for TAZ. Hippo pathway activity is best characterized by a YAP/TAZ transcriptional target signature of 22 genes, which shows robust prognostic power across cancer types. Our elastic-net integrated modeling further reveals cancer-type-specific pathway regulators and associated cancer drivers. Our results highlight the importance of Hippo signaling in squamous cell cancers, characterized by frequent amplification of YAP/TAZ, high expression heterogeneity, and significant prognostic patterns. This study represents a systems-biology approach to characterizing key cancer signaling pathways in the post-genomic era