Fatty acid metabolism of Mycobacterium tuberculosis: a double-edged sword

Mycobacterium tuberculosis can cocatabolize a range of carbon sources. Fatty acids are among the carbons available inside the host’s macrophages. Here, we investigated the metabolic changes of the fatty acid-induced dormancy-like state of M. tuberculosis and its involvement in the acquisition of drug tolerance. We conducted metabolomics profiling using a phosphoenolpyruvate carboxykinase (PEPCK)-deficient M. tuberculosis strain in an acetate-induced dormancy-like state, highlighting an overaccumulation of methylcitrate cycle (MCC) intermediates that correlates with enhanced drug tolerance against isoniazid and bedaquiline. Further metabolomics analyses of two M. tuberculosis mutants, an ICL knockdown (KD) strain and PrpD knockout (KO) strain, each lacking an MCC enzyme—isocitrate lyase (ICL) and 2-methylcitrate dehydratase (PrpD), respectively—were conducted after treatment with antibiotics. The ICL KD strain, which lacks the last enzyme of the MCC, showed an overaccumulation of MCC intermediates and a high level of drug tolerance. The PrpD KO strain, however, failed to accumulate MCC intermediates as it lacks the second step of the MCC and showed only a minor level of drug tolerance compared to the ICL KD mutant and its parental strain (CDC1551). Notably, addition of authentic 2-methylisocitrate, an MCC intermediate, improved the M. tuberculosis drug tolerance against antibiotics even in glycerol medium. Furthermore, wild-type M. tuberculosis displayed levels of drug tolerance when cultured in acetate medium significantly greater than those in glycerol medium. Taken together, the fatty acid-induced dormancy-like state remodels the central carbon metabolism of M. tuberculosis that is functionally relevant to acquisition of M. tuberculosis drug tolerance

Современные технические средства в работе секретаря

The article examines the technical devices used in the secretary work. Guided books and magazines for secretarial business, makes recommendations for the proper selection and use of technical devices. Furthermore, in this article the author gives examples of the most popular and commonly used programs for personal computers. All of these techniques can significantly reduce the cost of working time and improve the quality of performing their job duties

Search for a W' boson decaying to a bottom quark and a top quark in pp collisions at sqrt(s) = 7 TeV

Results are presented from a search for a W' boson using a dataset corresponding to 5.0 inverse femtobarns of integrated luminosity collected during 2011 by the CMS experiment at the LHC in pp collisions at sqrt(s)=7 TeV. The W' boson is modeled as a heavy W boson, but different scenarios for the couplings to fermions are considered, involving both left-handed and right-handed chiral projections of the fermions, as well as an arbitrary mixture of the two. The search is performed in the decay channel W' to t b, leading to a final state signature with a single lepton (e, mu), missing transverse energy, and jets, at least one of which is tagged as a b-jet. A W' boson that couples to fermions with the same coupling constant as the W, but to the right-handed rather than left-handed chiral projections, is excluded for masses below 1.85 TeV at the 95% confidence level. For the first time using LHC data, constraints on the W' gauge coupling for a set of left- and right-handed coupling combinations have been placed. These results represent a significant improvement over previously published limits.Comment: Submitted to Physics Letters B. Replaced with version publishe

Search for the standard model Higgs boson decaying into two photons in pp collisions at sqrt(s)=7 TeV

A search for a Higgs boson decaying into two photons is described. The analysis is performed using a dataset recorded by the CMS experiment at the LHC from pp collisions at a centre-of-mass energy of 7 TeV, which corresponds to an integrated luminosity of 4.8 inverse femtobarns. Limits are set on the cross section of the standard model Higgs boson decaying to two photons. The expected exclusion limit at 95% confidence level is between 1.4 and 2.4 times the standard model cross section in the mass range between 110 and 150 GeV. The analysis of the data excludes, at 95% confidence level, the standard model Higgs boson decaying into two photons in the mass range 128 to 132 GeV. The largest excess of events above the expected standard model background is observed for a Higgs boson mass hypothesis of 124 GeV with a local significance of 3.1 sigma. The global significance of observing an excess with a local significance greater than 3.1 sigma anywhere in the search range 110-150 GeV is estimated to be 1.8 sigma. More data are required to ascertain the origin of this excess.Comment: Submitted to Physics Letters

Measurement of the Lambda(b) cross section and the anti-Lambda(b) to Lambda(b) ratio with Lambda(b) to J/Psi Lambda decays in pp collisions at sqrt(s) = 7 TeV

The Lambda(b) differential production cross section and the cross section ratio anti-Lambda(b)/Lambda(b) are measured as functions of transverse momentum pt(Lambda(b)) and rapidity abs(y(Lambda(b))) in pp collisions at sqrt(s) = 7 TeV using data collected by the CMS experiment at the LHC. The measurements are based on Lambda(b) decays reconstructed in the exclusive final state J/Psi Lambda, with the subsequent decays J/Psi to an opposite-sign muon pair and Lambda to proton pion, using a data sample corresponding to an integrated luminosity of 1.9 inverse femtobarns. The product of the cross section times the branching ratio for Lambda(b) to J/Psi Lambda versus pt(Lambda(b)) falls faster than that of b mesons. The measured value of the cross section times the branching ratio for pt(Lambda(b)) > 10 GeV and abs(y(Lambda(b))) < 2.0 is 1.06 +/- 0.06 +/- 0.12 nb, and the integrated cross section ratio for anti-Lambda(b)/Lambda(b) is 1.02 +/- 0.07 +/- 0.09, where the uncertainties are statistical and systematic, respectively.Comment: Submitted to Physics Letters

Search for new physics in events with opposite-sign leptons, jets, and missing transverse energy in pp collisions at sqrt(s) = 7 TeV

A search is presented for physics beyond the standard model (BSM) in final states with a pair of opposite-sign isolated leptons accompanied by jets and missing transverse energy. The search uses LHC data recorded at a center-of-mass energy sqrt(s) = 7 TeV with the CMS detector, corresponding to an integrated luminosity of approximately 5 inverse femtobarns. Two complementary search strategies are employed. The first probes models with a specific dilepton production mechanism that leads to a characteristic kinematic edge in the dilepton mass distribution. The second strategy probes models of dilepton production with heavy, colored objects that decay to final states including invisible particles, leading to very large hadronic activity and missing transverse energy. No evidence for an event yield in excess of the standard model expectations is found. Upper limits on the BSM contributions to the signal regions are deduced from the results, which are used to exclude a region of the parameter space of the constrained minimal supersymmetric extension of the standard model. Additional information related to detector efficiencies and response is provided to allow testing specific models of BSM physics not considered in this paper.Comment: Replaced with published version. Added journal reference and DO

Measurement of isolated photon production in pp and PbPb collisions at sqrt(sNN) = 2.76 TeV

Isolated photon production is measured in proton-proton and lead-lead collisions at nucleon-nucleon centre-of-mass energies of 2.76 TeV in the pseudorapidity range |eta|<1.44 and transverse energies ET between 20 and 80 GeV with the CMS detector at the LHC. The measured ET spectra are found to be in good agreement with next-to-leading-order perturbative QCD predictions. The ratio of PbPb to pp isolated photon ET-differential yields, scaled by the number of incoherent nucleon-nucleon collisions, is consistent with unity for all PbPb reaction centralities.Comment: Submitted to Physics Letters

A importância da associação obesidade e gravidez

Characteristics of the evolution of pregnancy in obese women were studied for their effect on newborn infants. Two control groups were observed - one of normal weight pregnant women, one of obese. The variables selected were: the socio-economic status of the family and the mother's age, height, arm circunference, prepregancy weight, total number of pregnancies, parity, weight gain during pregnancy, obstetric complications, birth weight, and fetal vitality. Results showed that pregnancy in obese women differs from that in normal weight women and that they show a larger incidence of obstetric complications. Children of obese mothers had a higher mortality rate principally in the perinatal period; moreover, there was also a higher rate of prematurity and a higher proportion of overweight babies among obese mothers. As a result, the distribution of the curve of the birth weight of infants of obese morthers was higher than that of infants of normal weight mothers. The conclusion reached was that whenever a pregnant obese woman reduced foot intake, with resultant insufficient weight gain, intrauterine growth was affected. Thus, it follows that pregnancy is not the best time for the obese mother to lose weight; for this reason, it is important that she receive adequate guidance in regard to diet. Obesity, therefore, is a factor contributing to high-risk pregnancy which can affect both mother and child.Foram estudados dois grupos de gestantes, sendo um de grávidas normais e outro de obesas, com a finalidade de reconhecer algumas características da evolução da gravidez, em mulheres obesas, e suas repercussões sobre o concepto. Foram relacionadas as seguintes variáveis: status sócio-econômico familiar, idade, altura, perímetro braquial, peso habitual, número de gestações anteriores, paridade materna, ganho de peso durante a gestação, idade gestacional, intercorrências durante a gestação, peso ao nascer e vitalidade do recém-nascido. Pelos resultados concluiu-se que as gestantes obesas são diferentes das normais e apresentam maior incidência de complicações obstétricas. Os recém-nascidos, filhos de obesas, registraram índice maior de mortalidade, principalmente no período perinatal. Houve maior incidência de prematuridade e de fetos macrossômicos, sendo a curva de distribuição de peso ao nascer diferente da dos recém-nascidos das gestantes normais. A média de peso ao nascer das crianças das gestantes obesas é maior que o das normais. Concluiu-se ainda que toda vez que a gestante obesa sofre restrição alimentar, com ganho de peso inadequado, o crescimento intra-uterino é afetado; não sendo, portanto, a época da gravidez a melhor para a obesa perder peso, mas, ao contrário, ela deveria receber uma orientação alimentar adequada. A obesidade é pois um fator de aumento do risco gravídico, que pode afetar tanto a mãe como o concepto

Search for leptophobic Z ' bosons decaying into four-lepton final states in proton-proton collisions at root s=8 TeV

Peer reviewe

Search for black holes and other new phenomena in high-multiplicity final states in proton-proton collisions at root s=13 TeV

Peer reviewe