On the conservation of the slow conformational dynamics within the amino acid kinase family: NAGK the paradigm

N-Acetyl-L-Glutamate Kinase (NAGK) is the structural paradigm for examining the catalytic mechanisms and dynamics of amino acid kinase family members. Given that the slow conformational dynamics of the NAGK (at the microseconds time scale or slower) may be rate-limiting, it is of importance to assess the mechanisms of the most cooperative modes of motion intrinsically accessible to this enzyme. Here, we present the results from normal mode analysis using an elastic network model representation, which shows that the conformational mechanisms for substrate binding by NAGK strongly correlate with the intrinsic dynamics of the enzyme in the unbound form. We further analyzed the potential mechanisms of allosteric signalling within NAGK using a Markov model for network communication. Comparative analysis of the dynamics of family members strongly suggests that the low-frequency modes of motion and the associated intramolecular couplings that establish signal transduction are highly conserved among family members, in support of the paradigm sequence→structure→dynamics→function © 2010 Marcos et al

Multidrug resistant pulmonary tuberculosis treatment regimens and patient outcomes: an individual patient data meta-analysis of 9,153 patients.

Treatment of multidrug resistant tuberculosis (MDR-TB) is lengthy, toxic, expensive, and has generally poor outcomes. We undertook an individual patient data meta-analysis to assess the impact on outcomes of the type, number, and duration of drugs used to treat MDR-TB

Search for supersymmetry in events with b-quark jets and missing transverse energy in pp collisions at 7 TeV

Results are presented from a search for physics beyond the standard model based on events with large missing transverse energy, at least three jets, and at least one, two, or three b-quark jets. The study is performed using a sample of proton-proton collision data collected at sqrt(s) = 7 TeV with the CMS detector at the LHC in 2011. The integrated luminosity of the sample is 4.98 inverse femtobarns. The observed number of events is found to be consistent with the standard model expectation, which is evaluated using control samples in the data. The results are used to constrain cross sections for the production of supersymmetric particles decaying to b-quark-enriched final states in the context of simplified model spectra.Comment: Submitted to Physical Review

Incidence and mortality of ischemic stroke subtypes in Joinville, Brazil: a population-based study

Aims To measure the incidence and mortality rates of ischemic stroke (IS) subtypes in Joinville, Brazil. Methods All first-ever IS patients that occurred in Joinville from January 2005 to December 2006 were identified. The IS subtypes were classified by the TOAST criteria, and the patients were followed-up for one year after IS onset. Results The age-adjusted incidence per 100,000 inhabitants was 26 (17-39) for large-artery atherosclerosis (LAA), 17 (11-27) for cardioembolic (CE), 29 (20-41) for small vessel occlusion (SVO), 2 (0.6-7) for stroke of other determined etiology (OTH) and 30 (20-43) for stroke of undetermined etiology (UND). The 1-year mortality rate per 100,000 inhabitants was 5 (2-11) for LAA, 6 (3-13) for CE, 1 (0.1-6) for SVO, 0.2 (0-0.9) for OTH and 9 (4-17) for UND. Conclusion In the population of Joinville, the incidences of IS subtypes were similar to those found in other populations. These findings highlight the importance of better detection and control of atherosclerotic risk factors