Sinkhole development in the Sivas gypsum karst, Turkey

The extensive gypsum karst of Sivas, Turkey is one of the most outstanding examples of bare gypsum karst in the world. It displays a number of remarkable geomorphic features, including: (1) two stepped planation surfaces cut-across folded gypsum developed during an initial phase of slow base level deepening punctuated by periods of stability; (2) unusual deeply entrenched gypsum canyons related to a subsequent phase of rapid fluvial incision and water table lowering; (3) a polygonal karst of superlative quality mainly developed in the upper surface; (4) relict valleys disrupted by sinkholes in the lower erosional surface; (5) a large number of bedrock collapse sinkholes mostly associated with the lower surface; and (6) numerous cover subsidence sinkholes developed in the valley floors. This work analyses the spatial distribution, characteristics and evolution of the sinkholes within the broad Plio-Quaternary geomorphological and paleohydrological evolution of the epigene karst system dominated by autogenic recharge. A cartographic sinkhole inventory has been produced in an area covering 2820 km(2) with morphometric data and including 295 bedrock collapse sinkholes and 302 cover subsidence sinkholes. The different sinkhole types show a general spatial zonation controlled by the hydrogeological functioning of the different sectors: (1) solution sinkholes (polygonal karst) in the upper recharge area; (2) bedrock collapse sinkholes in the lower denudation surface and close to the base level, where well developed caves are inferred; and (3) cover subsidence sinkholes, with high densities probably associated with areas of preferred groundwater discharge. The morphology of the bedrock collapse sinkholes, varying from small cylindrical holes to large and deep tronco-conical depressions with gentle slopes reflect to geomorphic evolution of these sinkholes that reach exceptionally large hectometre-scale diameters. Their evolution, involving substantial enlargement and deepening, is attributed to the solutional removal as solute load of large volumes of gypsum by downward vadose flow. This type of morphological evolution with significant post-collapse solutional denudation differs from that observed in carbonate rocks characterised by lower solubility and erodibility. The analysis of historical imagery reveals that bedrock collapse sinkholes currently have a very low probability of occurrence and that buried cover subsidence sinkholes are used for urban development creating risk situations. (C) 2021 The Author(s). Published by Elsevier B.V

Role of Androgen Receptor CAG Repeat Polymorphism and X-Inactivation in the Manifestation of Recurrent Spontaneous Abortions in Indian Women

The aim of the present study was to investigate the role of CAG repeat polymorphism and X-chromosome Inactivation (XCI) pattern in Recurrent Spontaneous Abortions among Indian women which has not been hitherto explored. 117 RSA cases and 224 Controls were included in the study. Cases were recruited from two different hospitals - Lakshmi Fertility Clinic, Nellore and Fernandez Maternity Hospital, Hyderabad. Controls were roughly matched for age, ethnicity and socioeconomic status. The CAG repeats of the Androgen Receptor gene were genotyped using a PCR-based assay and were analysed using the GeneMapper software to determine the CAG repeat length. XCI analysis was also carried out to assess the inactivation percentages. RSA cases had a significantly greater frequency of allele sizes in the polymorphic range above 19 repeats (p = 0.006), which is the median value of the controls, and in the biallelic mean range above 21 repeats (p = 0.002). We found no evidence of abnormal incidence of skewed X-inactivation. We conclude that longer CAG repeat lengths are associated with increased odds for RSA with statistical power estimated to be ∼90%

Systems Biology in ELIXIR: modelling in the spotlight

In this white paper, we describe the founding of a new ELIXIR Community - the Systems Biology Community - and its proposed future contributions to both ELIXIR and the broader community of systems biologists in Europe and worldwide. The Community believes that the infrastructure aspects of systems biology - databases, (modelling) tools and standards development, as well as training and access to cloud infrastructure - are not only appropriate components of the ELIXIR infrastructure, but will prove key components of ELIXIR\u27s future support of advanced biological applications and personalised medicine. By way of a series of meetings, the Community identified seven key areas for its future activities, reflecting both future needs and previous and current activities within ELIXIR Platforms and Communities. These are: overcoming barriers to the wider uptake of systems biology; linking new and existing data to systems biology models; interoperability of systems biology resources; further development and embedding of systems medicine; provisioning of modelling as a service; building and coordinating capacity building and training resources; and supporting industrial embedding of systems biology. A set of objectives for the Community has been identified under four main headline areas: Standardisation and Interoperability, Technology, Capacity Building and Training, and Industrial Embedding. These are grouped into short-term (3-year), mid-term (6-year) and long-term (10-year) objectives

Community-driven ELIXIR activities in single-cell omics

Single-cell omics (SCO) has revolutionized the way and the level of resolution by which life science research is conducted, not only impacting our understanding of fundamental cell biology but also providing novel solutions in cutting-edge medical research. The rapid development of single-cell technologies has been accompanied by the active development of data analysis methods, resulting in a plethora of new analysis tools and strategies every year. Such a rapid development of SCO methods and tools poses several challenges in standardization, benchmarking, computational resources and training. These challenges are in line with the activities of ELIXIR, the European coordinated infrastructure for life science data. Here, we describe the current landscape of and the main challenges in SCO data, and propose the creation of the ELIXIR SCO Community, to coordinate the efforts in order to best serve SCO researchers in Europe and beyond. The Community will build on top of national experiences and pave the way towards integrated long-term solutions for SCO research. Keywor

Caffeine and the analog CGS 15943 inhibit cancer cell growth by targeting the phosphoinositide 3-kinase/Akt pathway

Caffeine is a naturally occurring methylxanthine that acts as a non-selective adenosine receptor antagonist. Epidemiological studies demonstrated habitual coffee drinking to be significantly associated with liver cancer survival. We aimed to investigate the effects of caffeine and its analog CGS 15943 on hepatocellular carcinoma (HCC) and pancreatic cancer adenocarcinoma (PDAC). We demonstrate that caffeine and CGS 15943 block proliferation in HCC and PDAC cell lines by inhibiting the PI3K/Akt pathway. Importantly a kinase profiling assay reveals that CGS 15943 targets specifically the catalytic subunit of the class IB PI3K isoform (p110ƴ). These data give mechanistic insight into the action of caffeine and its analogs and they identify these compounds as promising lead compounds to develop drugs that can specifically target this PI3K isoform whose key role in cancer progression is emerging

British Journal of Cancer / Loss of CUL4A expression is underlying cisplatin hypersensitivity in colorectal carcinoma cells with acquired trabectedin resistance

Background: Colorectal carcinoma (CRC) is the third most common cancer worldwide. Platinum-based anticancer compounds still constitute one mainstay of systemic CRC treatment despite limitations due to adverse effects and resistance development. Trabectedin has shown promising antitumor effects in CRC, however, again resistance development may occur. In this study, we aimed to develop strategies to circumvent or even exploit acquired trabectedin resistance in novel CRC treatment regimens. Methods: Human HCT116 CRC cells were selected for acquired trabectedin resistance in vitro and characterised by cell biological as well as bioinformatic approaches. In vivo xenograft experiments were conducted. Results: Selection of HCT116 cells for trabectedin resistance resulted in p53-independent hypersensitivity of the selected subline against cisplatin. Bioinformatic analyses of mRNA microarray data suggested deregulation of nucleotide excision repair and particularly loss of the ubiquitin ligase CUL4A in trabectedin-selected cells. Indeed, transient knockdown of CUL4A sensitised parental HCT116 cells towards cisplatin. Trabectedin selected but not parental HCT116 xenografts were significantly responsive towards cisplatin treatment. Conclusions: Trabectedin selection-mediated CUL4A loss generates an Achilles heel in CRC cancer cells enabling effective cisplatin treatment. Hence, inclusion of trabectedin in cisplatin-containing cancer treatment regimens might cause profound synergism based on reciprocal resistance prevention.(VLID)486740