Alanyl-tRNA synthetase genes of Vanderwaltozyma polyspora arose from duplication of a dual-functional predecessor of mitochondrial origin

In eukaryotes, the cytoplasmic and mitochondrial forms of a given aminoacyl-tRNA synthetase (aaRS) are typically encoded by two orthologous nuclear genes, one of eukaryotic origin and the other of mitochondrial origin. We herein report a novel scenario of aaRS evolution in yeast. While all other yeast species studied possess a single nuclear gene encoding both forms of alanyl-tRNA synthetase (AlaRS), Vanderwaltozyma polyspora, a yeast species descended from the same whole-genome duplication event as Saccharomyces cerevisiae, contains two distinct nuclear AlaRS genes, one specifying the cytoplasmic form and the other its mitochondrial counterpart. The protein sequences of these two isoforms are very similar to each other. The isoforms are actively expressed in vivo and are exclusively localized in their respective cellular compartments. Despite the presence of a promising AUG initiator candidate, the gene encoding the mitochondrial form is actually initiated from upstream non-AUG codons. A phylogenetic analysis further revealed that all yeast AlaRS genes, including those in V. polyspora, are of mitochondrial origin. These findings underscore the possibility that contemporary AlaRS genes in V. polyspora arose relatively recently from duplication of a dual-functional predecessor of mitochondrial origin

Women with endometriosis have higher comorbidities: Analysis of domestic data in Taiwan

AbstractEndometriosis, defined by the presence of viable extrauterine endometrial glands and stroma, can grow or bleed cyclically, and possesses characteristics including a destructive, invasive, and metastatic nature. Since endometriosis may result in pelvic inflammation, adhesion, chronic pain, and infertility, and can progress to biologically malignant tumors, it is a long-term major health issue in women of reproductive age. In this review, we analyze the Taiwan domestic research addressing associations between endometriosis and other diseases. Concerning malignant tumors, we identified four studies on the links between endometriosis and ovarian cancer, one on breast cancer, two on endometrial cancer, one on colorectal cancer, and one on other malignancies, as well as one on associations between endometriosis and irritable bowel syndrome, one on links with migraine headache, three on links with pelvic inflammatory diseases, four on links with infertility, four on links with obesity, four on links with chronic liver disease, four on links with rheumatoid arthritis, four on links with chronic renal disease, five on links with diabetes mellitus, and five on links with cardiovascular diseases (hypertension, hyperlipidemia, etc.). The data available to date support that women with endometriosis might be at risk of some chronic illnesses and certain malignancies, although we consider the evidence for some comorbidities to be of low quality, for example, the association between colon cancer and adenomyosis/endometriosis. We still believe that the risk of comorbidity might be higher in women with endometriosis than that we supposed before. More research is needed to determine whether women with endometriosis are really at risk of these comorbidities

Noncanonical SQSTM1/p62-Nrf2 pathway activation mediates proteasome inhibitor resistance in multiple myeloma cells via redox, metabolic and translational reprogramming.

Multiple Myeloma (MM) is a B-cell malignancy characterized by the accumulation of clonal plasma cells in the bone marrow, with drug resistance being a major cause of therapeutic failure. We established a carfilzomib-resistant derivative of the LP-1 MM cell line (LP-1/Cfz) and found that the transcription factor NF-E2 p45-related factor 2 (Nrf2; gene symbol NFE2L2) contributes to carfilzomib resistance. The mechanism of Nrf2 activation involved enhanced translation of Nrf2 as well as its positive regulator, the autophagy receptor sequestosome 1 (SQSTM1)/p62. The eukaryotic translation initiation factor gene EIF4E3 was among the Nrf2 target genes upregulated in LP-1/Cfz cells, suggesting existence of a positive feedback loop. In line with this, we found that siRNA knockdown of eIF4E3 decreased Nrf2 protein levels. On the other hand, elevated SQSTM1/p62 levels were due at least in part to activation of the PERK-eIF2α pathway. LP-1/Cfz cells had decreased levels of reactive oxygen species as well as elevated levels of fatty acid oxidation and prosurvival autophagy. Genetic and pharmacologic inhibition of the Nrf2-EIF4E3 axis or the PERK-eIF2α pathway, disruption of redox homeostasis or inhibition of fatty acid oxidation or autophagy conferred sensitivity to carfilzomib. Our findings were supported by clinical data where increased EIF4E3 expression was predictive of Nrf2 target gene upregulation in a subgroup of patients with chemoresistant minimal residual disease and relapsed/refractory MM. Thus, our data offer a preclinical rationale for including inhibitors of the SQSTM1/p62-Nrf2 pathway to the treatment regimens for certain advanced stage MM patients

Search for the Standard Model Higgs boson produced in association with top quarks and decaying into bb¯ in pp collisions at √s=8 TeV with the ATLAS detector

A search for the Standard Model Higgs boson produced in association with a top-quark pair, tt¯H, is presented. The analysis uses 20.3 fb−1 of pp collision data at √s=8TeV, collected with the ATLAS detector at the Large Hadron Collider during 2012. The search is designed for the H→bb¯ decay mode and uses events containing one or two electrons or muons. In order to improve the sensitivity of the search, events are categorised according to their jet and b-tagged jet multiplicities. A neural network is used to discriminate between signal and background events, the latter being dominated by tt¯+jets production. In the single-lepton channel, variables calculated using a matrix element method are included as inputs to the neural network to improve discrimination of the irreducible tt¯+bb¯ background. No significant excess of events above the background expectation is found and an observed (expected) limit of 3.4 (2.2) times the Standard Model cross section is obtained at 95% confidence level. The ratio of the measured tt¯H signal cross section to the Standard Model expectation is found to be μ=1.5±1.1 assuming a Higgs boson mass of 125GeV

Measurement of distributions sensitive to the underlying event in inclusive Z-boson production in pp collisions at √s = 7 TeV with the ATLAS detector

A measurement of charged-particle distributions sensitive to the properties of the underlying event is presented for an inclusive sample of events containing a Z-boson, decaying to an electron or muon pair. The measurement is based on data collected using the ATLAS detector at the LHC in proton–proton collisions at a centre-of-mass energy of 7 TeV with an integrated luminosity of 4.6 fb −¹. Distributions of the charged particle multiplicity and of the charged particle transverse momentum are measured in regions of azimuthal angle defined with respect to the Z-boson direction. The measured distributions are compared to similar distributions measured in jet events, and to the predictions of various Monte Carlo generators implementing different underlying event models

A measurement of the ratio of the production cross sections for W and Z bosons in association with jets with the ATLAS detector

The ratio of the production cross sections for W and Z bosons in association with jets has been measured in proton–proton collisions at √s=7TeV with the ATLAS experiment at the Large Hadron Collider. The measurement is based on the entire 2011 dataset, corresponding to an integrated luminosity of 4.6fb−1. Inclusive and differential cross-section ratios for massive vector bosons decaying to electrons and muons are measured in association with jets with transverse momentum pT>30GeV and jet rapidity |y|<4.4. The measurements are compared to next-to-leading-order perturbative QCD calculations and to predictions from different Monte Carlo generators implementing leading-order matrix elements supplemented by parton showers

Search for invisible particles produced in association with single-top-quarks in proton–proton collisions at √s = 8 TeV with the ATLAS detector

A search for the production of single-top-quarks in association with missing energy is performed in proton– proton collisions at a centre-of-mass energy of √s = 8 TeV with the ATLAS experiment at the large hadron collider using data collected in 2012, corresponding to an integrated luminosity of 20.3 fb−1. In this search, the W boson from the top quark is required to decay into an electron or a muon and a neutrino. No deviation from the standard model prediction is observed, and upper limits are set on the production cross-section for resonant and non-resonant production of an invisible exotic state in association with a right-handed top quark. In the case of resonant production, for a spin-0 resonance with a mass of 500 GeV, an effective coupling strength above 0.15 is excluded at 95 % confidence level for the top quark and an invisible spin-1/2 state with mass between 0 and 100 GeV. In the case of non-resonant production, an effective coupling strength above 0.2 is excluded at 95 % confidence level for the top quark and an invisible spin-1 state with mass between 0 and 657 GeV

Discutindo a educação ambiental no cotidiano escolar: desenvolvimento de projetos na escola formação inicial e continuada de professores

A presente pesquisa buscou discutir como a Educação Ambiental (EA) vem sendo trabalhada, no Ensino Fundamental e como os docentes desta escola compreendem e vem inserindo a EA no cotidiano escolar., em uma escola estadual do município de Tangará da Serra/MT, Brasil. Para tanto, realizou-se entrevistas com os professores que fazem parte de um projeto interdisciplinar de EA na escola pesquisada. Verificou-se que o projeto da escola não vem conseguindo alcançar os objetivos propostos por: desconhecimento do mesmo, pelos professores; formação deficiente dos professores, não entendimento da EA como processo de ensino-aprendizagem, falta de recursos didáticos, planejamento inadequado das atividades. A partir dessa constatação, procurou-se debater a impossibilidade de tratar do tema fora do trabalho interdisciplinar, bem como, e principalmente, a importância de um estudo mais aprofundado de EA, vinculando teoria e prática, tanto na formação docente, como em projetos escolares, a fim de fugir do tradicional vínculo “EA e ecologia, lixo e horta”.Facultad de Humanidades y Ciencias de la Educació

Search for the Standard Model Higgs boson produced in association with top quarks and decaying into in collisions at with the ATLAS detector

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecomm ons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. Funded by SCOAP3.We acknowledge the support of ANPCyT, Argentina; YerPhI, Armenia; ARC, Australia; BMWFW and FWF, Austria; ANAS, Azerbaijan; SSTC, Belarus; CNPq and FAPESP, Brazil; NSERC, NRC and CFI, Canada; CERN; CONICYT, Chile; CAS, MOST and NSFC, China; COLCIENCIAS, Colombia; MSMT CR, MPO CR and VSC CR, Czech Republic; DNRF, DNSRC and Lundbeck Foundation, Denmark; EPLANET, ERC and NSRF, European Union; IN2P3-CNRS, CEA-DSM/IRFU, France; GNSF, Georgia; BMBF, DFG, HGF, MPG and AvH Foundation, Germany; GSRT and NSRF, Greece; RGC, Hong Kong SAR, China; ISF, MINERVA, GIF, I-CORE and Benoziyo Center, Israel; INFN, Italy; MEXT and JSPS, Japan; CNRST, Morocco; FOM and NWO, Netherlands; BRF and RCN, Norway; MNiSW and NCN, Poland; GRICES and FCT, Portugal; MNE/IFA, Romania; MES of Russia and ROSATOM, Russian Federation; JINR; MSTD, Serbia; MSSR, Slovakia; ARRS and MIZŠ, Slovenia; DST/NRF, South Africa; MINECO, Spain; SRC and Wallenberg Foundation, Sweden; SER, SNSF and Cantons of Bern and Geneva, Switzerland; NSC, Taiwan; TAEK, Turkey; STFC, the Royal Society and Leverhulme Trust, United Kingdom; DOE and NSF, United States of Americ