Perseus plugin “Metis” for metabolic-pathway-centered quantitative multi-omics data analysis for static and time-series experimental designs

We introduce Metis, a new plugin for the Perseus software aimed at analyzing quantitative multi-omics data based on metabolic pathways. Data from different omics types are connected through reactions of a genome-scale metabolic-pathway reconstruction. Metabolite concentrations connect through the reactants, while transcript, protein, and protein post-translational modification (PTM) data are associated through the enzymes catalyzing the reactions. Supported experimental designs include static comparative studies and time-series data. As an example for the latter, we combine circadian mouse liver multi-omics data and study the contribution of cycles of phosphoproteome and metabolome to enzyme activity regulation. Our analysis resulted in 52 pairs of cycling phosphosites and metabolites connected through a reaction. The time lags between phosphorylation and metabolite peak show non-uniform behavior, indicating a major contribution of phosphorylation in the modulation of enzymatic activity.publishedVersio

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 new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Determinants of intensive insulin therapeutic regimens in patients with type 1 diabetes: data from a nationwide multicenter survey in Brazil

Background: To evaluate the determinants of intensive insulin regimens (ITs) in patients with type 1 diabetes (T1D).Methods: This multicenter study was conducted between December 2008 and December 2010 in 28 public clinics in 20 Brazilian cities. Data were obtained from 3,591 patients (56.0% female, 57.1% Caucasian). Insulin regimens were classified as follows: group 1, conventional therapy (CT) (intermediate human insulin, one to two injections daily); group 2 (three or more insulin injections of intermediate plus regular human insulin); group 3 (three or more insulin injections of intermediate human insulin plus short-acting insulin analogues); group 4, basal-bolus (one or two insulin injections of long-acting plus short-acting insulin analogues or regular insulin); and group 5, basal-bolus with continuous subcutaneous insulin infusion (CSII). Groups 2 to 5 were considered IT groups.Results: We obtained complete data from 2,961 patients. Combined intermediate plus regular human insulin was the most used therapeutic regimen. CSII was used by 37 (1.2%) patients and IT by 2,669 (90.2%) patients. More patients on IT performed self-monitoring of blood glucose and were treated at the tertiary care level compared to CT patients (p < 0.001). the majority of patients from all groups had HbA1c levels above the target. Overweight or obesity was not associated with insulin regimen. Logistic regression analysis showed that economic status, age, ethnicity, and level of care were associated with IT (p < 0.001).Conclusions: Given the prevalence of intensive treatment for T1D in Brazil, more effective therapeutic strategies are needed for long term-health benefits.Farmanguinhos/Fundacao Oswaldo Cruz/National Health MinistryBrazilian Diabetes SocietyFundacao do Amparo a Pesquisa do Estado do Rio de JaneiroConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Univ Estado Rio de Janeiro, Unit Diabet, BR-20551030 Rio de Janeiro, BrazilBaurus Diabet Assoc, São Paulo, BrazilFed Univ São Paulo State, Diabet Unit, São Paulo, BrazilFed Univ Hosp Porto Alegre, Porto Alegre, BrazilUniv Hosp São Paulo, Diabet Unit, São Paulo, BrazilUniv Fed Rio de Janeiro, Rio de Janeiro, BrazilUniv Fed Ceara, Fortaleza, Ceara, BrazilSanta Casa Misericordia, Belo Horizonte, MG, BrazilSanta Casa Misericordia São Paulo, São Paulo, BrazilUniv Fed Amazonas, Manaus, Amazonas, BrazilHosp Geral de Bonsucesso, Rio de Janeiro, BrazilHosp Univ Clementino Fraga Filho IPPMG, Rio de Janeiro, BrazilUniv Hosp São Paulo, São Paulo, BrazilFac Ciencias Med Santa Casa São Paulo, São Paulo, BrazilUniv São Paulo, Inst Crianca, Hosp Clin, São Paulo, BrazilUniv São Paulo, Fac Med Ribeirao Preto, Hosp Clin, Ribeirao Preto, BrazilAmbulatorio Fac Estadual Med Sao Jose Rio Preto, Ribeirao Preto, BrazilEscola Paulista Med, Ctr Diabet, Ribeirao Preto, BrazilClin Endocrinol Santa Casa Belo Horizonte, Belo Horizonte, MG, BrazilUniv Estadual Londrina, Londrina, BrazilUniv Fed Parana, Hosp Clin, Porto Alegre, RS, BrazilInst Crianca Com Diabet Rio Grande Sul, Rio Grande Do Sul, RS, BrazilGrp Hosp Conceicao, Inst Crianca Com Diabet, Porto Alegre, RS, BrazilHosp Univ Santa Catarina, Florianopolis, SC, BrazilInst Diabet Endocrinol Joinville, Joinville, BrazilHosp Reg Taguatinga, Brasilia, DF, BrazilHosp Geral Goiania, Goiania, Go, BrazilCtr Diabet & Endocrinol Estado Bahia, Goiania, Go, BrazilUniv Fed Maranhao, Sao Luis, BrazilCtr Integrado Diabet & Hipertensao Ceara, Fortaleza, Ceara, BrazilUniv Fed Sergipe, Aracaju, BrazilHosp Univ Alcides Carneiro, Campina Grande, BrazilHosp Univ Joao de Barros Barreto, Belem, Para, BrazilFed Univ São Paulo State, Diabet Unit, São Paulo, BrazilUniv Hosp São Paulo, Diabet Unit, São Paulo, BrazilUniv Hosp São Paulo, São Paulo, BrazilEscola Paulista Med, Ctr Diabet, Ribeirao Preto, BrazilWeb of Scienc

LMO2 expression reflects the different stages of blast maturation and genetic features in B-cell acute lymphoblastic leukemia and predicts clinical outcome

BACKGROUND: LMO2 is highly expressed at the most immature stages of lymphopoiesis. In T-lymphocytes, aberrant LMO2 expression beyond those stages leads to T-cell acute lymphoblastic leukemia, while in B cells LMO2 is also expressed in germinal center lymphocytes and diffuse large B-cell lymphomas, where it predicts better clinical outcome. The implication of LMO2 in B-cell acute lymphoblastic leukemia must still be explored. DESIGN AND METHODS: We measured LMO2 expression by real time RT-PCR in 247 acute lymphoblastic leukemia patient samples with cytogenetic data (144 of them also with survival and immunophenotypical data) and in normal hematopoietic and lymphoid cells. RESULTS: B-cell acute lymphoblastic leukemia cases expressed variable levels of LMO2 depending on immunophenotypical and cytogenetic features. Thus, the most immature subtype, pro-B cells, displayed three-fold higher LMO2 expression than pre-B cells, common-CD10+ or mature subtypes. Additionally, cases with TEL-AML1 or MLL rearrangements exhibited two-fold higher LMO2 expression compared to cases with BCR-ABL rearrangements or hyperdyploid karyotype. Clinically, high LMO2 expression correlated with better overall survival in adult patients (5-year survival rate 64.8% (42.5%-87.1%) vs. 25.8% (10.9%-40.7%), P= 0.001) and constituted a favorable independent prognostic factor in B-ALL with normal karyotype: 5-year survival rate 80.3% (66.4%-94.2%) vs. 63.0% (46.1%-79.9%) (P= 0.043). CONCLUSIONS: Our data indicate that LMO2 expression depends on the molecular features and the differentiation stage of B-cell acute lymphoblastic leukemia cells. Furthermore, assessment of LMO2 expression in adult patients with a normal karyotype, a group which lacks molecular prognostic factors, could be of clinical relevance

Measurement of the t-channel single top quark production cross section in pp collisions at √s =7 TeV

Peer reviewe

Effect of an edible nanomultilayer coating by electrostatic self-assembly on the shelf life of fresh-cut mangoes

This work aims at evaluating the effect of an alginate-chitosan nanomultilayer coating, obtained by electrostatic layer-by-layer self-assembling, in the quality and shelf life of fresh-cut mangoes. Coated and uncoated fresh-cut mangoes were stored under refrigeration (8 °C) for 14 days. The changes in mass loss, titratable acidity, pH, ascorbic acid content, total soluble solids, malondialdehyde content, browning rate, and microbial count were evaluated during storage. At the end of the storage period, lower values of mass loss, pH, malondialdehyde content, browning rate, soluble solids, microorganisms proliferation, and higher titratable acidity were observed in the coated mangoes. The nanomultilayer coating did not improve the retention of vitamin C during storage of fresh-cut mangoes. Results suggest that chitosan-alginate nanomultilayer edible coating extends the shelf life of fresh-cut mangoes up to 8 days.Author Marthyna Pessoa de Souza thanks Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES/PDEE-Brazil) and Fundacao de Amparo a Ciencia e Tecnologia do Estado de Pernambuco (FACEPE, Brazil) for granting her scholarships. The authors thank the Fundacao para a Ciencia e a Tecnologia (FCT) Strategic Project PEst-OE/EQB/LA0023/2013 and the Project "BioInd-Biotechnology and Bioengineering for improved Industrial and Agro-Food processes", REF. NORTE-07-0124-FEDER-000028, co-funded by the Programa Operacional Regional do Norte (ON.2-O Novo Norte), QREN, and FEDER (Portugal)

Immediate early splicing controls translation in activated T-cells and is mediated by hnRNPC2 phosphorylation

The fast and transient induction of immediate early genes orchestrates the cellular response to various stimuli. These stimuli trigger phosphorylation cascades that promote immediate early gene transcription independent of de novo protein synthesis. Here we show that the same phosphorylation cascades also target the splicing machinery, inducing an analogous splicing switch that we call immediate early splicing (IES). We characterize hnRNPC2-controlled IES, which depends on the MEK-ERK pathway and the T cell-specific kinase PKCθ. This splicing switch mainly targets components of the translation machinery, such as mRNAs encoding ribosomal proteins and eIF5A. Inducing the eIF5A IES protein variant is by itself sufficient to reduce global translation, and consistently, we observe reduced de novo protein synthesis early after T cell activation. We suggest that immediate early splicing and the ensuing transient decrease in translation efficiency help to coordinate the extensive changes in gene expression during T cell activation. Together, these findings set a paradigm for fast and transient alternative splicing in the immediate cellular response to activation, and provide evidence for its functional relevance during T-cell stimulation

Learning an Alternative Car-Following Technique to Avoid Congestion with an Instructional Driving Simulator

This paper addresses the problem of traffic congestion through a learning perspective, highlighting the capabilities of Information and Communication Technologies to transform society. Recent physical and mathematical analysis of congestion reveals that training drivers to keep a safe distance systematically contributes to the emergence and maintenance of interference congestion (so-called phantom traffic jam). This paper presents the WaveDriving Course (WDC), a simulated learning environment designed to help drivers progress from the traditional Drive-to-keep-Distance (DD) technique to a new car-following (CF) principle better suited for wave-like traffic, Drive-to-keep-Inertia (DI). The WDC is based on the ordinary knowledge of the driver (e.g., going through a series of traffic lights), and presents this situation in terms of two possible simultaneous behavioral strategies. The driver has the opportunity to verify that it is possible to achieve the same objective with different consequences. Finally, the WDC checks to what extent this learning generates transfer patterns in the analogous case of CF. The paper focuses on results concerning the first WDC module: the traffic-light analogy. Forty-two participants followed the whole learning procedure for about 30 min. An evaluative CF test was administered before and after visioning the tutorial and practicing on the simulator. Overall, transference from this traffic-light analog to the CF situation (posttest) was successful. Results confirm the adoption of the expected DI strategies (speed variability decreased, distance and distance variability to leader increased, fuel consumption decreased, platoon elongation decreased etc.). The need to improve the WDC teaching of the appropriate CF distance is discussed

Box-Behnken Design-Based Optimization of Treatment Parameters for Soluble Reactive Phosphorus Removal of Synthetic Wastewater using Immobilized Spirulina platensis Beads

Soluble reactive phosphorus (SRP), a bioavailable phosphorus form, contributes to over-eutrophication by stimulating uncontrolled algal growth. This study aims to determine the optimum treatment parameters for the SRP removal from synthetic wastewater using the alginate-immobilized cyanobacteria Spirulina platensis. S. platensis was immobilized in alginate beads with varying alginate concentrations (2.5%, 3%, and 3.5% w/v), and subjected to varying operation time (1, 2, and 3 days), and bead dosage (1.5, 2, and 2.5 beads/mL) for SRP removal using Box-Behnken experimental design. Resulting model indicated a strong predictive relationship with R2 = 0.9253 and p = 0.0212. Main effects of bead dosage (p = 0.01372), its quadratic effect (p = 0.01643), and its interaction with alginate concentration (p = 0.00465) were found to be statistically significant. Predicted optimum parameters (2.5% w/v alginate, 3 days, and 1.5 beads/mL) were validated and resulted in a lower SRP removal of 92.80 ± 0.73% with a percent error of 5.22% relative to a predicted SRP removal of 97.91%. Extrapolation of the prediction model to 100% outside the experimental region was verified resulting in SRP removal of 97.39 ± 0.08% with a percent error of 2.61% was achieved by adjusting the operation time to 3.4 days. The study shows promising potential of immobilized S. platensis beads in addressing over-eutrophication through significant phosphorus reduction