Metallochaperones Are Needed for Mycobacterium tuberculosis and Escherichia coli Nicotinamidase-Pyrazinamidase Activity.

Mycobacterium tuberculosis nicotinamidase-pyrazinamidase (PZAse) is a metalloenzyme that catalyzes conversion of nicotinamide-pyrazinamide to nicotinic acid-pyrazinoic acid. This study investigated whether a metallochaperone is required for optimal PZAse activity. M. tuberculosis and Escherichia coli PZAses (PZAse-MT and PZAse-EC, respectively) were inactivated by metal depletion (giving PZAse-MT-Apo and PZAse-EC-Apo). Reactivation with the E. coli metallochaperone ZnuA or Rv2059 (the M. tuberculosis analog) was measured. This was repeated following proteolytic and thermal treatment of ZnuA and Rv2059. The CDC1551 M. tuberculosis reference strain had the Rv2059 coding gene knocked out, and PZA susceptibility and the pyrazinoic acid (POA) efflux rate were measured. ZnuA (200 μM) achieved 65% PZAse-EC-Apo reactivation. Rv2059 (1 μM) and ZnuA (1 μM) achieved 69% and 34.3% PZAse-MT-Apo reactivation, respectively. Proteolytic treatment of ZnuA and Rv2059 and application of three (but not one) thermal shocks to ZnuA significantly reduced the capacity to reactivate PZAse-MT-Apo. An M. tuberculosis Rv2059 knockout strain was Wayne positive and susceptible to PZA and did not have a significantly different POA efflux rate than the reference strain, although a trend toward a lower efflux rate was observed after knockout. The metallochaperone Rv2059 restored the activity of metal-depleted PZAse in vitro Although Rv2059 is important in vitro, it seems to have a smaller effect on PZA susceptibility in vivo. It may be important to mechanisms of action and resistance to pyrazinamide in M. tuberculosis Further studies are needed for confirmation.IMPORTANCE Tuberculosis is an infectious disease caused by the bacterium Mycobacterium tuberculosis and remains one of the major causes of disease and death worldwide. Pyrazinamide is a key drug used in the treatment of tuberculosis, yet its mechanism of action is not fully understood, and testing strains of M. tuberculosis for pyrazinamide resistance is not easy with the tools that are presently available. The significance of the present research is that a metallochaperone-like protein may be crucial to pyrazinamide's mechanisms of action and of resistance. This may support the development of improved tools to detect pyrazinamide resistance, which would have significant implications for the clinical management of patients with tuberculosis: drug regimens that are appropriately tailored to the resistance profile of a patient's individual strain lead to better clinical outcomes, reduced onward transmission of infection, and reduction of the development of resistant strains that are more challenging and expensive to treat

Determining R-parity violating parameters from neutrino and LHC data

In supersymmetric models neutrino data can be explained by R-parity violating operators which violate lepton number by one unit. The so called bilinear model can account for the observed neutrino data and predicts at the same time several decay properties of the lightest supersymmetric particle. In this paper we discuss the expected precision to determine these parameters by combining neutrino and LHC data and discuss the most important observables. We show that one can expect a rather accurate determination of the underlying R-parity parameters assuming mSUGRA relations between the R-parity conserving ones and discuss briefly also the general MSSM as well as the expected accuracies in case of a prospective e+ e- linear collider. An important observation is that several parameters can only be determined up to relative signs or more generally relative phases.Comment: 13 pages, 13 figure

The effect of Co and Zn addition on densification and electrical properties of ceria-based nanopowders

CNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOCAPES - COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIORIn this work, cobalt and zinc-doped Ce0.8Gd0.2O1.9 samples were prepared starting from a commercial nanopowder and compared to the undoped material. The powder samples were pressed and afterwards sintered by a two-step procedure, before characterization by X-Ray Diffraction (XRD), X-ray photoelectron spectroscopy (XPS), Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM) and Impedance Spectroscopy (IS) in air. Cobalt or zinc additions are effective as sintering aid, allowing peak sintering temperatures around 1000 degrees C to reach densifications above of 93% of theoretical density, showing no evidence for the presence of secondary phases. The total conductivity at 800 degrees C of pressed Zn-doped samples (6.7x10(-2) S/cm) and Co-doped samples (7.5x10(-2) S/cm) is similar for undoped samples (7.2x10(-2) S/cm) showing that Zn and Co has a positive effect on densification without compromising the electrical conductivity.In this work, cobalt and zinc-doped Ce0.8Gd0.2O1.9 samples were prepared starting from a commercial nanopowder and compared to the undoped material. The powder samples were pressed and afterwards sintered by a two-step procedure, before characterization by X-Ray Diffraction (XRD), X-ray photoelectron spectroscopy (XPS), Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM) and Impedance Spectroscopy (IS) in air. Cobalt or zinc additions are effective as sintering aid, allowing peak sintering temperatures around 1000 degrees C to reach densifications above of 93% of theoretical density, showing no evidence for the presence of secondary phases. The total conductivity at 800 degrees C of pressed Zn-doped samples (6.7x10(-2) S/cm) and Co-doped samples (7.5x10(-2) S/cm) is similar for undoped samples (7.2x10(-2) S/cm) showing that Zn and Co has a positive effect on densification without compromising the electrical conductivity.19510571063CNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOCAPES - COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIORCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOCAPES - COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIORSem informaçãoSem informaçãoFinancial supports from CAPES and CNPq are greatly appreciated. We would like to thank Rita C. G. Vinhas (State University of Campinas, Campinas Campus, Brazil), for helping with the XPS measurements

Kalman Filtering in the Air Quality Monitoring

Data assimilation is a process where an improved prediction is obtained from a weighted combination between experimental measurements and mathematical model data. In the present work this procedure is applied to pollutant atmospheric dispersion by using a Kalman filter (KF). This is interesting approach, because the KF gives an output in which the balance between the data from the diffusion model and the experimental data is done automaticaly, through the Kalman gain. In addition, the Kalman filter computes the propagation of the error