Using a physically-based model, tRIBS-Erosion, for investigating the effects of climate change in semi-arid headwater basins.

Soil erosion due to rainfall detachment and flow entrainment of soil particles is a physical process responsible for a continuous evolution of landscapes. The rate and spatial distribution of this phenomenon depend on several factors such as climate, hydrologic regime, geomorphic characteristics, and vegetation of a basin. Many studies have demonstrated that climate-erosion linkage in particular influences basin sediment yield and landscape morphology. Although soil erosion rates are expected to change in response to climate, these changes can be highly non-linear and thus require mechanistic understanding of underlying causes. In this study, an integrated geomorphic component of the physically-based, spatially distributed hydrological model, tRIBS, the TIN-based Real-time Integrated Basin Simulator, is used to analyze the sensitivity of semi-arid headwater basins to climate change. Downscaled outputs of global circulation models are used to inform a stochastic weather generator that produces an ensemble of climate scenarios for an area in the Southwest U.S. The ensemble is used as input to the integrated model that is applied to different headwater basins of the Walnut Gulch Experimental Watershed to understand basin response to climate change in terms of runoff and sediment yield. Through a model application to multiple catchments, a scaling relationship between specific sediment yield and drainage basin area is also addressed and probabilistic inferences on future changes in catchment runoff and yield are drawn. Geomorphological differences among catchments do not influence specific changes in runoff and sediment transport that are mostly determined by precipitation changes. Despite a large uncertainty dictated by climate change projections and stochastic variability, sediment transport is predicted to decrease despite a non-negligible possibility of larger runoff rates

HDAC inhibitor confers radiosensitivity to prostate stem-like cells

Background: Radiotherapy can be an effective treatment for prostate cancer, but radiorecurrent tumours do develop. Considering prostate cancer heterogeneity, we hypothesised that primitive stem-like cells may constitute the radiation-resistant fraction. Methods: Primary cultures were derived from patients undergoing resection for prostate cancer or benign prostatic hyperplasia. After short-term culture, three populations of cells were sorted, reflecting the prostate epithelial hierarchy, namely stem-like cells (SCs, α2β1integrinhi/CD133+), transit-amplifying (TA, α2β1integrinhi/CD133−) and committed basal (CB, α2β1integrinlo) cells. Radiosensitivity was measured by colony-forming efficiency (CFE) and DNA damage by comet assay and DNA damage foci quantification. Immunofluorescence and flow cytometry were used to measure heterochromatin. The HDAC (histone deacetylase) inhibitor Trichostatin A was used as a radiosensitiser. Results: Stem-like cells had increased CFE post irradiation compared with the more differentiated cells (TA and CB). The SC population sustained fewer lethal double-strand breaks than either TA or CB cells, which correlated with SCs being less proliferative and having increased levels of heterochromatin. Finally, treatment with an HDAC inhibitor sensitised the SCs to radiation. Interpretation: Prostate SCs are more radioresistant than more differentiated cell populations. We suggest that the primitive cells survive radiation therapy and that pre-treatment with HDAC inhibitors may sensitise this resistant fraction

Low-temperature plasma treatment induces DNA damage leading to necrotic cell death in primary prostate epithelial cells

Background:In recent years, the rapidly advancing field of low-temperature atmospheric pressure plasmas has shown considerable promise for future translational biomedical applications, including cancer therapy, through the generation of reactive oxygen and nitrogen species.Method:The cytopathic effect of low-temperature plasma was first verified in two commonly used prostate cell lines: BPH-1 and PC-3 cells. The study was then extended to analyse the effects in paired normal and tumour (Gleason grade 7) prostate epithelial cells cultured directly from patient tissue. Hydrogen peroxide (H2O2) and staurosporine were used as controls throughout.Results:Low-temperature plasma (LTP) exposure resulted in high levels of DNA damage, a reduction in cell viability, and colony-forming ability. H2O2 formed in the culture medium was a likely facilitator of these effects. Necrosis and autophagy were recorded in primary cells, whereas cell lines exhibited apoptosis and necrosis.Conclusions:This study demonstrates that LTP treatment causes cytotoxic insult in primary prostate cells, leading to rapid necrotic cell death. It also highlights the need to study primary cultures in order to gain more realistic insight into patient response

Assessment of climate impacts on hydrology and geomorphology of semiarid headwater basins using a physically-based model.

The response of watershed erosion rates to changes in climate is expected to be highly non-linear and thus demands for mechanistic approaches to improve our understanding of the underlying causes. In this study, the integrated geomorphic component tRIBS-Erosion of the physically-based, spatially distributed hydrological model, tRIBS, the TIN-based Real-time Integrated Basin Simulator, is used to analyze the sensitivity of small semi-arid headwater basins to projected climate conditions. Observed historic climate and downscaled realizations of general circulation models from CMIP3 inform the stochastic weather generator AWE-GEN (Advanced WEather GENerator), which is used to produce two climate ensembles representative of the past historic and future climate conditions for the Walnut Gulch Experimental Watershed (WGEW) area in the Southwest U.S. The former ensemble incorporates the stochastic variability of the observed climate, while the latter includes the stochastic variability and the uncertainty of CMIP3 multi-model climate change projections. The climate ensembles are used as forcing input to the hydrogeomorphic model that is applied to seven headwater basins of WGEW. The basin response in terms of runoff and sediment yield for climate ensembles representative of the historic past and future is simulated and probabilistic inferences on future changes in catchment runoff and sediment transport are drawn. The application of the model to multiple catchments also identifies the scaling relationship between specific sediment yield/runoff and drainage basin area. The study reveals that geomorphic differences among catchments influence the variability of sediment yield, as affected by possible future climates, much more as compared to runoff, which is instead strongly dominated by the climate forcing. Despite a large uncertainty inherent to climate change projections and imposed by the stochastic climate variability, the basin sediment yield is predicted to decrease in almost all of the considered cases despite a slight possibility of runoff increase. The study further highlights the importance of addressing watershed sediment dynamics within a stochastic framework that explores the wide range of responses corresponding to natural variability

Isolation and culture of colon cancer stem cells.

Cancer stem cells (CSCs) resemble normal stem cells in several ways. Both cell types are self-renewing and when they divide, one of the daughter cells differentiates while the other retains stem cell properties, including the ability to divide in the same way again. CSCs have been demonstrated to exist in several solid tumors, including colon carcinoma; these cells are able to initiate and sustain tumor growth. There are essentially three different methods to isolate CSCs: establishment culture, the MACS (magnetic cell sorting) technology, and the FACS (fluorescence-activated cell sorting) technology

Topical treatment of chronic venous ulcers with sucralfate: A placebo controlled randomized study

Venous leg ulcers are an important medical issue due to their high incidence in the elderly and the lack of a standard curative approach. Apart from surgical therapy, different medical treatments to effect ulcer wound repair and regeneration are currently being investigated. Sucralfate is a cytoprotective agent employed to prevent or treat several gastrointestinal diseases such as gastroesophageal reflux, gastritis, peptic ulcer, stress ulcer and dyspepsia. In this study we evaluated the efficacy, safety and tolerability of topical sucralfate (SUC-LIS 95) on the healing of chronic venous leg ulcers in 50 patients by a double-blind, placebo-controlled, randomized study. Our results indicated that the daily application of SUC-LIS 95 to non-infected post-phlebitis/vascular ulcers, for a median period of 42.0 days, led to complete healing in 95.6% of patients, against only 10.9% of cases with a matched placebo. A significant improvement was obtained in the SUC-LIS 95-treated patient group with regard to local tissue inflammation as well as pain and burning, and consequently, in ulcer size and the evolution of granulation tissue. Our findings were corroborated for selected patients by the morphological analysis of biopsies obtained before and after treatment. Using ultrastructural analysis we demonstrated that the topical use of SUC-LIS 95 was able to affect neoangiogenesis, increase wound contraction, promote re-epithelialization of the wound area and diminish the inflammatory reaction. Overall, our results indicated that patients with chronic venous ulcers show improvement after the use of topical sucralfate

GJB2 and GJB6 genetic variant curation in a non-syndromic hearing loss cohort from argentina

Hereditary hearing impairment affects 1-500 newborn children. It is characterized by the large amount of genes involved (more than 100) and its phenotype heterogeneity. Despite the wide genetic variety of hearing impairment, the most commonly mutated genes in severe to profound autosomal recessive non-syndromic hearing loss are GJB2 and GJB6, accounting for nearly 50% of the cases in most populations around the Mediterranean Sea. Molecular diagnosis enables proper genetic counseling and medical prognosis to patients. Therefore, correct interpretation of the phenotypic consequences of genetic variants is crucial in genetic diagnosis, since discrepancies in sequence variant interpretation and classification has been reported to lead to serious impact in patient health maintenance.In this study we aimed to identify the genetic causes of hearing loss and performed a manual genetic variant curation following the American College of Medical Genetics and Genomics/Association for Molecular Pathology ACMG/AMP standards and hearing-loss-gene-specific criteria of the ClinGen Hearing Loss Expert Panel.A total of 600 patients were studied for genetic variants in GJB2 and GJB6 genes by Sanger Sequencing technique and Multiplex Gap-PCR, respectively.Overall, 48 different sequence variants were detected in our cohort of patients, being the c.35delG the most common causative variant identified. Besides, more than 50% of sequence variants were reclassified from their previous categorization in ClinVar after careful manual analysis. These results provide an accurately analysed and interpreted set of variants to be taken into account by clinicians and the scientific community, and hence, aid the precise genetic counseling to patients.Fil: Buonfiglio, Paula Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Bruque, Carlos David. Hospital de Alta Complejidad Gobernador Cepernic - Presidente Kirchner; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Menazzi, S.. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Francipane, S.. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Lotersztein, Vanesa. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán". Centro Nacional de Genética Médica; ArgentinaFil: Elgoyhen, Ana Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Cátedra de Farmacología. 3º Cátedra de Farmacología; ArgentinaFil: Dalamon, Viviana Karina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaReunión de Sociedades de Biociencias 2021; LXVI Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXIX Reunión Anual de la Sociedad Argentina de Inmunología; LIII Reunión Anual de la Asociación Argentina de Farmacología Experimental; XI Reunión Anual de la Asociación Argentina de NanomedicinasCiudad Autónoma de Buenos AiresArgentinaSociedad Argentina de Investigación ClínicaSociedad Argentina de InmunologíaAsociación Argentina de Farmacología ExperimentalAsociación Argentina de Nanomedicina