MUTATION OF AN IQ-MOTIF: EVIDENCE FOR AN EXOSITE IN CALPAIN-2?

These studies aimed to test the hypothesis that calcium regulates calpain activity by a mechanism analogous to that used by Ca2+- calmodulin (CaM) to regulate its target enzymes. Site directed mutagenesis of a putative IQ motif, IQ413xxxR417 generated catalytic subunits modified at both, or each, of the key residues of the motif to yield ISxxxQ, ISxxxR, and IQxxxQ. Each of the mutant catalytic subunits was co-expressed with a truncated (21k) small subunit in E. coli. The heterodimeric enzymes were purified by standard methods suggesting each was properly folded. Electrophoresis under native conditions, in the absence of calcium, showed no differences between wt and enzyme mutated at R417Q. Each of these enzymes was also stable to incubation at 45 ºC. In contrast enzymes containing Q413S were resolved into multiple bands on native gels and were not stable at 45 ºC. Two calcium dependent activities were assessed: casein hydrolysis and autoproteolysis. Each of the mutants retained significant autolytic activity but lost much of their caseinolytic activity. We propose two interpretations of the results based in part on the calcium-free structures determined for calpain-2 (Hosfield et al , 1999 EMBO J. 18, 6880 and Strobl et al 2000, PNAS 97, 588). The ability of the enzymes to autoproteolyze suggests that the conformational change required for alignment of the catalytic residues is unimpaired in the mutants. Impaired casein hydrolysis may result from 1) inability to release product after cleavage or 2) failure to form a required substrate binding exosite. The latter concept is consistent with many previously known calpain attributes. Exosites provide a mechanism for achieving high substrate specificity amongst enzymes that share conserved active sites, such as those of the thrombin family and perhaps the calpain family. Confirmation and definition of such exosites will be important as they could provide targets for design of isoform selective inhibitors

Atividade física, qualidade de vida e depressão durante a gravidez

This study examines physical activity patterns among women, from pre-pregnancy to the second trimester of pregnancy, and the relationship between physical activity status based on physical activity guidelines and health-related quality of life (HRQoL) and depression over pregnancy. 56 healthy pregnant women self reported physical activity, HRQoL and depression at 10-15 and 19-24 weeks of pregnancy and physical activity before pregnancy. Whereas vigorous leisure physical activity decreased after conception, moderate leisure physical activity and work related physical activity remained stable over time. The prevalence of recommended physical activity was 39.3% and 12.5% in the 1st and 2nd trimesters of pregnancy respectively, and 14.3% pre-pregnancy. From the 1st to the 2nd pregnancy trimester, most physical HRQoL dimensions scores decreased and only mental component increased, independently of physical activity status. No changes in mean depression scores were observed. These data suggest that physical activity patterns change with pregnancy and that physical and mental components are differentially affected by pregnancy course, independently of physical activity status.Este estudo examina os padrões de atividade física antes da concepção até o segundo trimestre de gravidez e a relação entre o nível de atividade física, com base nas recomendações de atividade física, a qualidade de vida relacionada à saúde (QVRS) e depressão ao longo da gravidez. Cinquenta e seis grávidas saudáveis reportaram nível de atividade física, QVRS e depressão às 10-15 e 19-24 semanas de gravidez, além de atividade física antes da concepção. Enquanto a atividade física vigorosa no lazer diminuiu depois da concepção, as atividades físicas moderadas no lazer e no trabalho mantiveram-se estáveis. A prevalência de atividade fí- sica recomendada foi de 39,3%, 12,5% e 14,3% antes, no primeiro e no segundo trimestres de gravidez, respectivamente. Independentemente do estatuto de atividade física, a maior parte dos escores nas dimensões físicas da QVRS diminui do primeiro para o segundo trimestre de gestação, e apenas o componente mental aumenta. Não se verificaram alterações nos escores médios de depressão. Estes dados sugerem que, com a gravidez, há alteração nos padrões de atividade física; além disso, os componentes físico e mental são diferentemente afetados pelo curso da gestação, independentemente do nível de atividade física

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal

Study of Bc+B_c^+ decays to the K+K−π+K^+K^-\pi^+ final state and evidence for the decay Bc+→χc0π+B_c^+\to\chi_{c0}\pi^+

A study of $B_c^+\to K^+K^-\pi^+$ decays is performed for the first time using data corresponding to an integrated luminosity of 3.0 $\mathrm{fb}^{-1}$ collected by the LHCb experiment in $pp$ collisions at centre-of-mass energies of $7$ and $8$ TeV. Evidence for the decay $B_c^+\to\chi_{c0}(\to K^+K^-)\pi^+$ is reported with a significance of 4.0 standard deviations, resulting in the measurement of $\frac{\sigma(B_c^+)}{\sigma(B^+)}\times\mathcal{B}(B_c^+\to\chi_{c0}\pi^+)$ to be $(9.8^{+3.4}_{-3.0}(\mathrm{stat})\pm 0.8(\mathrm{syst}))\times 10^{-6}$. Here $\mathcal{B}$ denotes a branching fraction while $\sigma(B_c^+)$ and $\sigma(B^+)$ are the production cross-sections for $B_c^+$ and $B^+$ mesons. An indication of $\bar b c$ weak annihilation is found for the region $m(K^-\pi^+)<1.834\mathrm{\,Ge\kern -0.1em V\!/}c^2$, with a significance of 2.4 standard deviations.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2016-022.html, link to supplemental material inserted in the reference

Observation of Bc+ →j /ψD (∗)K (∗) decays

A search for the decays B+c→J/ψD(*)0K+ and B+c→J/ψD(*)+K*0 is performed with data collected at the LHCb experiment corresponding to an integrated luminosity of 3 fb−1. The decays B+c→J/ψ0K+ and B+c→J/ψD*0K+ are observed for the first time, while first evidence is reported for the B+c→JψD*+K*0 and B+c→J/ψD+K*0 decays. The branching fractions of these decays are determined relative to the B+c→J/ψπ+ decay. The B+c mass is measured, using the J/ψD0K+ final state, to be 6274.28±1.40(stat)±0.32(syst) MeV/c2. This is the most precise single measurement of the B+c mass to date

The Extracellular Matrix Component Psl Provides Fast-Acting Antibiotic Defense in Pseudomonas aeruginosa Biofilms

Bacteria within biofilms secrete and surround themselves with an extracellular matrix, which serves as a first line of defense against antibiotic attack. Polysaccharides constitute major elements of the biofilm matrix and are implied in surface adhesion and biofilm organization, but their contributions to the resistance properties of biofilms remain largely elusive. Using a combination of static and continuous-flow biofilm experiments we show that Psl, one major polysaccharide in the Pseudomonas aeruginosa biofilm matrix, provides a generic first line of defense toward antibiotics with diverse biochemical properties during the initial stages of biofilm development. Furthermore, we show with mixed-strain experiments that antibiotic-sensitive “non-producing” cells lacking Psl can gain tolerance by integrating into Psl-containing biofilms. However, non-producers dilute the protective capacity of the matrix and hence, excessive incorporation can result in the collapse of resistance of the entire community. Our data also reveal that Psl mediated protection is extendible to E. coli and S. aureus in co-culture biofilms. Together, our study shows that Psl represents a critical first bottleneck to the antibiotic attack of a biofilm community early in biofilm development.National Institutes of Health (U.S.). National Institute of Environmental Health Sciences (Training Grant in Toxicology 5 T32 ES7020-37

Fatores associados ao equilíbrio funcional e à mobilidade em idosos diabéticos ambulatoriais

OBJECTIVES: To characterize balance and mobility among diabetic elderly outpatients and to estimate the extent to which functional balance and mobility abnormalities can be influenced by sociodemographic, clinical and other functional factors in a cross-sectional study. METHODS: Ninety-one elderly (65+ years) outpatients were assessed. Mobility was evaluated by the Timed Up and Go Test (TUGT) and the balance, by the Berg Balance Scale (BS). RESULTS: TUGT mean score was 15.65 ± 5.9 seconds and BS mean score was 49.31 ± 7.3 points. Using linear regression analysis (α < 0.05), significant and independent positive relationships were obtained between TUGT and age, daily activities (ADL/IADL), step strategy, and proprioceptive sensitivity. Factors negatively associated with BS were: ADL/IADL, step strategy, proprioceptive sensitivity, orthostatic hypotension (OH) and conflictive sensory conditions. CONCLUSION: Elderly diabetic outpatients show abnormal balance and mobility related mainly to advanced age, disability, absence of step strategy, absence of proprioceptive sensitivity and presence of OH.OBJETIVOS: Caracterizar o equilíbrio e a mobilidade de idosos diabéticos ambulatoriais e estimar o quanto suas anormalidades podem ser influenciadas por fatores sociodemográficos, clínicos e funcionais globais em um estudo transversal. MÉTODOS: 91 idosos (65 + anos) ambulatoriais foram avaliados quanto à mobilidade pelo Timed Up and Go Test (TUGT) e ao equilíbrio, pela Berg Balance Scale (BS). RESULTADOS: A média dos escores do TUGT foi de 15,65 ± 5,9 segundos e da BS, de 49,31 ± 7,3 pontos. Empregando-se análise de regressão linear (α < 0,05), associações significantes positivas e independentes foram obtidas entre o TUGT e idade, atividades cotidianas, estratégia do passo atrás e sensibilidade proprioceptiva. Os fatores associados negativamente à BS foram: atividades cotidianas, estratégia do passo, sensibilidade proprioceptiva, hipotensão ortostática (HO) e condições sensoriais conflituosas. CONCLUSÃO: Idosos diabéticos ambulatoriais apresentam equilíbrio e mobilidade prejudicados, relacionados principalmente à idade avançada, limitação para atividades diárias, ausência de estratégia de equilíbrio, prejuízo na sensibilidade proprioceptiva e a presença de HO.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Universidade Federal de São Paulo (UNIFESP) Departamento de Medicina PreventivaUniversidade Cidade de São PauloUNIFESP Departamento de MedicinaUNIFESP, Depto. de Medicina PreventivaUNIFESP, Depto. de MedicinaSciEL

Complexity Theory for a New Managerial Paradigm: A Research Framework

In this work, we supply a theoretical framework of how organizations can embed complexity management and sustainable development into their policies and actions. The proposed framework may lead to a new management paradigm, attempting to link the main concepts of complexity theory, change management, knowledge management, sustainable development, and cybernetics. We highlight how the processes of organizational change have occurred as a result of the move to adapt to the changes in the various global and international business environments and how this transformation has led to the shift toward the present innovation economy. We also point how organizational change needs to deal with sustainability, so that the change may be consistent with present needs, without compromising the future

Prenatal exposures and exposomics of asthma

This review examines the causal investigation of preclinical development of childhood asthma using exposomic tools. We examine the current state of knowledge regarding early-life exposure to non-biogenic indoor air pollution and the developmental modulation of the immune system. We examine how metabolomics technologies could aid not only in the biomarker identification of a particular asthma phenotype, but also the mechanisms underlying the immunopathologic process. Within such a framework, we propose alternate components of exposomic investigation of asthma in which, the exposome represents a reiterative investigative process of targeted biomarker identification, validation through computational systems biology and physical sampling of environmental medi