The Inhibitory Role of miR-486-5p on CSC Phenotype Has Diagnostic and Prognostic Potential in Colorectal Cancer

Colorectal cancer (CRC) is the third most frequent cancer worldwide and the second cause of cancer deaths. Increasing evidences supports the idea that the poor prognosis of patients is related to the presence of cancer stem cells (CSCs), a cell population able to drive cancer recurrence and metastasis. The deregulation of microRNAs (miRNAs) plays a role in the formation of CSC. We investigated the role of hsa-miR-486-5p (miR-486-5p) in CRC, CSCs, and metastasis, in order to reach a better understanding of the biomolecular and epigenetic mechanisms mir-486-5p-related. The expression of miR-486-5p was investigated in three di erent matrices from CRC patients and controls and in CSCs obtained from the CRC cell lines HCT-116, HT-29, and T-84. In the human study, miR-486-5p was up-regulated in serum and stool of CRC patients in comparison with healthy controls but down-regulated in tumor tissue when compared with normal mucosa. miR-486-5p was also down-regulated in the sera of metastatic patients. In vitro, miR-486-5p was down-regulated in CSC models and it induced an inhibitory e ect on stem factors and oncogenes in the main pathways of CSCs. Our results provide a step forward in understanding the role of mir-486-5p in CRC and CSC, and suggest that further studies are needed to investigate its diagnostic and prognostic power, possibly in combination with other biomarkers.Instituto de Salud Carlos III PIE16-00045 DTS19/00145Junta de AndalucíaEuropean Union (EU) SOMM17/6109/UGR (UCE-PP2017-3)Chair "Doctors Galera-Requena in cancer stem cell research" CMC-CTS963Fondazione Banco di Sardegn

Clinical Risk Score to Predict Pathogenic Genotypes in Patients With Dilated Cardiomyopathy

Background: Although genotyping allows family screening and influences risk-stratification in patients with nonischemic dilated cardiomyopathy (DCM) or isolated left ventricular systolic dysfunction (LVSD), its result is negative in a significant number of patients, limiting its widespread adoption. Objectives: This study sought to develop and externally validate a score that predicts the probability for a positive genetic test result (G+) in DCM/LVSD. Methods: Clinical, electrocardiogram, and echocardiographic variables were collected in 1,015 genotyped patients from Spain with DCM/LVSD. Multivariable logistic regression analysis was used to identify variables independently predicting G+, which were summed to create the Madrid Genotype Score. The external validation sample comprised 1,097 genotyped patients from the Maastricht and Trieste registries. Results: A G+ result was found in 377 (37%) and 289 (26%) patients from the derivation and validation cohorts, respectively. Independent predictors of a G+ result in the derivation cohort were: family history of DCM (OR: 2.29; 95% CI: 1.73-3.04; P < 0.001), low electrocardiogram voltage in peripheral leads (OR: 3.61; 95% CI: 2.38-5.49; P < 0.001), skeletal myopathy (OR: 3.42; 95% CI: 1.60-7.31; P = 0.001), absence of hypertension (OR: 2.28; 95% CI: 1.67-3.13; P < 0.001), and absence of left bundle branch block (OR: 3.58; 95% CI: 2.57-5.01; P < 0.001). A score containing these factors predicted a G+ result, ranging from 3% when all predictors were absent to 79% when ≥4 predictors were present. Internal validation provided a C-statistic of 0.74 (95% CI: 0.71-0.77) and a calibration slope of 0.94 (95% CI: 0.80-1.10). The C-statistic in the external validation cohort was 0.74 (95% CI: 0.71-0.78). Conclusions: The Madrid Genotype Score is an accurate tool to predict a G+ result in DCM/LVSD

Decolorization of synthetic melanoidins-containing wastewater by a bacterial consortium

The presence of melanoidins in molasses wastewater leads to water pollution both due to its dark brown color and its COD contents. In this study, a bacterial consortium isolated from waterfall sediment was tested for its decolorization. The identification of culturable bacteria by 16S rDNA based approach showed that the consortium composed of Klebsiella oxytoca, Serratia mercescens, Citrobacter sp. and unknown bacterium. In the context of academic study, prevention on the difficulties of providing effluent as well as its variations in compositions, several synthetic media prepared with respect to color and COD contents based on analysis of molasses wastewater, i.e., Viandox sauce (13.5% v/v), caramel (30% w/v), beet molasses wastewater (41.5% v/v) and sugarcane molasses wastewater (20% v/v) were used for decolorization using consortium with color removal 9.5, 1.13, 8.02 and 17.5%, respectively, within 2 days. However, Viandox sauce was retained for further study. The effect of initial pH and Viandox concentration on decolorization and growth of bacterial consortium were further determined. The highest decolorization of 18.3% was achieved at pH 4 after 2 day of incubation. Experiments on fresh or used medium and used or fresh bacterial cells, led to conclusion that the limitation of decolorization was due to nutritional deficiency. The effect of aeration on decolorization was also carried out in 2 L laboratory-scale suspended cell bioreactor. The maximum decolorization was 19.3% with aeration at KLa = 2.5836 h-1 (0.1 vvm)

Extended X-ray emission around FR II radio galaxies: Hot spots, lobes, and galaxy clusters

We present a systematic analysis of the extended X-ray emission discovered around 35 FR II radio galaxies from the revised Third Cambridge Catalog (3CR) Chandra Snapshot Survey with redshifts between 0.05 and 0.9. We aimed to (i) test for the presence of extended X-ray emission around FR II radio galaxies, (ii) investigate whether the extended emission origin is due to inverse Compton (IC) scattering of seed photons arising from the cosmic microwave background (CMB) or thermal emission from an intracluster medium (ICM), and (iii) test the impact of this extended emission on hot-spot detection. We investigated the nature of the extended X-ray emission by studying its morphology and compared our results with low-frequency radio observations (i.e., ~150 MHz) in the TGSS and LOFAR archives, as well as with optical images from Pan-STARRS. In addition, we optimized a search for X-ray counterparts of hot spots in 3CR FR II radio galaxies. We found statistically significant extended emission (>3s confidence level) along the radio axis of ~90% and in the perpendicular direction of ~60% of the galaxies in our sample. We confirmed the detection of seven hot spots in the 0.5-3 keV energy range. In the cases where the emission in the direction perpendicular to the radio axis is comparable to that along the radio axis, we suggest that the underlying radiative process is thermal emission from the ICM. Otherwise, the dominant radiative process is likely nonthermal IC/CMB emission from lobes. We found that nonthermal IC/CMB is the dominant process in ~70% of the sources in our sample, while thermal emission from the ICM dominates in ~15% of them

Powerful Radio Sources in the Southern Sky. II. A SWIFT X-Ray Perspective

We recently constructed the G4Jy-3CRE, a catalog of extragalactic radio sources based on the GLEAM 4-Jy (G4Jy) sample, with the aim of increasing the number of powerful radio galaxies and quasars with similar selection criteria to those of the revised release of the Third Cambridge catalog (3CR). The G4Jy-3CRE consists of a total of 264 radio sources mainly visible from the Southern Hemisphere. Here, we present an initial X-ray analysis of 89 G4Jy-3CRE radio sources with archival X- ray observations from the Neil Gehrels Swift Observatory. We reduced a total of 615 Swift observations, for about 0.89 Msec of integrated exposure time, we found X-ray counterparts for 61 radio sources belonging to the G4Jy-3CRE, 11 of them showing extended X-ray emission. The remaining 28 sources do not show any X-ray emission associated with their radio cores. Our analysis demonstrates that X-ray snapshot observations, even if lacking uniform exposure times, as those carried out with Swift, allow us to (i) verify and/or re ne the host galaxy identi cation; (ii) discover the extended X-ray emission around radio galaxies of the intracluster medium when harbored in galaxy clusters, as the case of G4Jy 1518 and G4Jy 1664, and (iii) detect X-ray radiation arising from their radio lobes, as for G4Jy 1863.Comment: 35 pages, 17 figures, 2 tables; second paper of a series, pre-proof versio

Powerful Radio Sources in the Southern Sky. I. Optical Identifications

Since the early sixties, our view of radio galaxies and quasars has been drastically shaped by discoveries made thanks to observations of radio sources listed in the Third Cambridge catalog and its revised version (3CR). However, the largest fraction of data collected to date on 3CR sources was performed with relatively old instruments, rarely repeated and/or updated. Importantly, the 3CR contains only objects located in the Northern Hemisphere thus having limited access to new and innovative astronomical facilities. To mitigate these limitations we present a new catalog of powerful radio sources visible from the Southern Hemisphere, extracted from the GLEAM 4-Jy (G4Jy) catalog and based on equivalent selection criteria as the 3CR. This new catalog, named G4Jy- 3CRE, where the E stands for "equivalent", lists a total of 264 sources at declination below -5 degrees and with 9 Jy limiting sensitivity at ~178 MHz. We explored archival radio maps obtained with different surveys and compared then with optical images available in the Pan-STARRS, DES and DSS databases to search for optical counterparts of their radio cores. We compared mid-infrared counterparts, originally associated in the G4Jy, with the optical ones identified here and we present results of a vast literature search carried out to collect redshift estimates for all G4Jy-3CRE sources resulting in a total of 145 reliable z measurements.Comment: 72 pages, 35 figures, 5 Table

Complex scaffold remodeling in plant triterpene biosynthesis

Triterpenes with complex scaffold modifications are widespread in the plant kingdom. Limonoids are an exemplary family that are responsible for the bitter taste in citrus (e.g., limonin) and the active constituents of neem oil, a widely used bioinsecticide (e.g., azadirachtin). Despite the commercial value of limonoids, a complete biosynthetic route has not been described. We report the discovery of 22 enzymes, including a pair of neofunctionalized sterol isomerases, that catalyze 12 distinct reactions in the total biosynthesis of kihadalactone A and azadirone, products that bear the signature limonoid furan. These results enable access to valuable limonoids and provide a template for discovery and reconstitution of triterpene biosynthetic pathways in plants that require multiple skeletal rearrangements and oxidations

Measurement of the cross-section and charge asymmetry of WW bosons produced in proton-proton collisions at s=8\sqrt{s}=8 TeV with the ATLAS detector

This paper presents measurements of the $W^+ \rightarrow \mu^+\nu$ and $W^- \rightarrow \mu^-\nu$ cross-sections and the associated charge asymmetry as a function of the absolute pseudorapidity of the decay muon. The data were collected in proton--proton collisions at a centre-of-mass energy of 8 TeV with the ATLAS experiment at the LHC and correspond to a total integrated luminosity of 20.2~\mbox{fb^{-1}}. The precision of the cross-section measurements varies between 0.8% to 1.5% as a function of the pseudorapidity, excluding the 1.9% uncertainty on the integrated luminosity. The charge asymmetry is measured with an uncertainty between 0.002 and 0.003. The results are compared with predictions based on next-to-next-to-leading-order calculations with various parton distribution functions and have the sensitivity to discriminate between them.Comment: 38 pages in total, author list starting page 22, 5 figures, 4 tables, submitted to EPJC. All figures including auxiliary figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2017-13

Search for chargino-neutralino production with mass splittings near the electroweak scale in three-lepton final states in √s=13 TeV pp collisions with the ATLAS detector

A search for supersymmetry through the pair production of electroweakinos with mass splittings near the electroweak scale and decaying via on-shell W and Z bosons is presented for a three-lepton final state. The analyzed proton-proton collision data taken at a center-of-mass energy of √s=13  TeV were collected between 2015 and 2018 by the ATLAS experiment at the Large Hadron Collider, corresponding to an integrated luminosity of 139  fb−1. A search, emulating the recursive jigsaw reconstruction technique with easily reproducible laboratory-frame variables, is performed. The two excesses observed in the 2015–2016 data recursive jigsaw analysis in the low-mass three-lepton phase space are reproduced. Results with the full data set are in agreement with the Standard Model expectations. They are interpreted to set exclusion limits at the 95% confidence level on simplified models of chargino-neutralino pair production for masses up to 345 GeV

Search for squarks and gluinos in events with isolated leptons, jets and missing transverse momentum at s√=8 TeV with the ATLAS detector

The results of a search for supersymmetry in final states containing at least one isolated lepton (electron or muon), jets and large missing transverse momentum with the ATLAS detector at the Large Hadron Collider are reported. The search is based on proton-proton collision data at a centre-of-mass energy s√=8 TeV collected in 2012, corresponding to an integrated luminosity of 20 fb−1. No significant excess above the Standard Model expectation is observed. Limits are set on supersymmetric particle masses for various supersymmetric models. Depending on the model, the search excludes gluino masses up to 1.32 TeV and squark masses up to 840 GeV. Limits are also set on the parameters of a minimal universal extra dimension model, excluding a compactification radius of 1/R c = 950 GeV for a cut-off scale times radius (ΛR c) of approximately 30