Genes involved in TGFβ1-driven epithelial-mesenchymal transition of renal epithelial cells are topologically related in the human interactome map

<p>Abstract</p> <p>Background</p> <p>Understanding how mesenchymal cells arise from epithelial cells could have a strong impact in unveiling mechanisms of epithelial cell plasticity underlying kidney regeneration and repair.</p> <p>In primary human tubular epithelial cells (HUTEC) under different TGFβ1 concentrations we had observed epithelial-to-mesenchymal transition (EMT) but not epithelial-myofibroblast transdifferentiation. We hypothesized that the process triggered by TGFβ1 could be a dedifferentiation event. The purpose of this study is to comprehensively delineate genetic programs associated with TGFβ1-driven EMT in our in vitro model using gene expression profile on large-scale oligonucleotide microarrays.</p> <p>Results</p> <p>In HUTEC under TGFβ1 stimulus, 977 genes were found differentially expressed. Thirty genes were identified whose expression depended directly on TGFβ1 concentration. By mapping the differentially expressed genes in the Human Interactome Map using Cytoscape software, we identified a single scale-free network consisting of 2630 interacting proteins and containing 449 differentially expressed proteins. We identified 27 hub proteins in the interactome with more than 29 edges incident on them and encoded by differentially expressed genes. The Gene Ontology analysis showed an excess of up-regulated proteins involved in biological processes, such as "morphogenesis", "cell fate determination" and "regulation of development", and the most up-regulated genes belonged to these categories. In addition, 267 genes were mapped to the KEGG pathways and 14 pathways with more than nine differentially expressed genes were identified. In our model, Smad signaling was not the TGFβ1 action effector; instead, the engagement of RAS/MAPK signaling pathway seems mainly to regulate genes involved in the cell cycle and proliferation/apoptosis.</p> <p>Conclusion</p> <p>Our present findings support the hypothesis that context-dependent EMT generated in our model by TGFβ1 might be the outcome of a dedifferentiation. In fact: 1) the principal biological categories involved in the process concern morphogenesis and development; 2) the most up-regulated genes belong to these categories; and, finally, 3) some intracellular pathways are involved, whose engagement during kidney development and nephrogenesis is well known. These long-term effects of TGFβ1 in HUTEC involve genes that are highly interconnected, thereby generating a scale-free network that we named the "TGFβ1 interactome", whose hubs represent proteins that may have a crucial role for HUTEC in response to TGFβ1.</p

Search for anomalies in the neutrino sector with muon spectrometers and large LArTPC imaging detectors at CERN

A new experiment with an intense ~2 GeV neutrino beam at CERN SPS is proposed in order to definitely clarify the possible existence of additional neutrino states, as pointed out by neutrino calibration source experiments, reactor and accelerator experiments and measure the corresponding oscillation parameters. The experiment is based on two identical LAr-TPCs complemented by magnetized spectrometers detecting electron and muon neutrino events at Far and Near positions, 1600 m and 300 m from the proton target, respectively. The ICARUS T600 detector, the largest LAr-TPC ever built with a size of about 600 ton of imaging mass, now running in the LNGS underground laboratory, will be moved at the CERN Far position. An additional 1/4 of the T600 detector (T150) will be constructed and located in the Near position. Two large area spectrometers will be placed downstream of the two LAr-TPC detectors to perform charge identification and muon momentum measurements from sub-GeV to several GeV energy range, greatly complementing the physics capabilities. This experiment will offer remarkable discovery potentialities, collecting a very large number of unbiased events both in the neutrino and antineutrino channels, largely adequate to definitely settle the origin of the observed neutrino-related anomalies.Comment: Contribution to the European Strategy for Particle Physics - Open Symposium Preparatory Group, Kracow 10-12 September 201

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Antonio Bavusi, Vito L'Erario, "La via del grano. Geoitinerario storico",&nbsp;Alfagrafica Volonnino,&nbsp;Lavello 2021, 140 p.Antonio Bavusi, Vito L’Erario, "La via del grano. Geoitinerario storico", Alfagrafica Volonnino,&nbsp;Lavello 2021, 140 p

ESBL-producing E. coli and K. pneumoniae: prevalence and antimicrobial susceptibility

Infections caused by extended-spectrum beta-lactamase (ESBL) producing E. coli and K. pneumoniae limit therapeutical options.The objective of this study was to evaluate the activity of ciprofloxacin, imipenem, amikacin and piperacillin/tazobactam against ESBL-producing E. coli and K. pneumoniae strains isolated from patients admitted to Ospedali Riuniti, Foggia, over the period January-December 2007. A total of 1013 E. coli and 146 K. pneumoniae were isolated from various clinical specimens. 111/1013 (10.9%) and 24/146 (16.4%) were confirmed as ESBL-producing strains by both the Phoenix system (Becton &amp; Dickinson) and the E-test (bioMérieux, Italia). Both the ESBL producing enterobacteria showed a high degree resistance to ciprofloxacin; in addition, K. pneumoniae exhibited resistance also to piperacillin/tazobactam. Imipenem was the most effective antibiotic with the exception of one strain ESBL-positive K. pneumoniae. A similar pattern was showed by amikacin. In view of the increasing prevalence of ESBL strains it appears important a continuous antimicrobial monitoring