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

Experimental Local Loss Coefficients (Km) Of Some Common Fittings Used In Residential Hydraulic Networks

The loss coefficients values (Km) of hydraulic fittings produce energy losses that are related to the minor ones (hL) and are widely used in hydraulic network designs. In this work, through a loss bank, the most common fittings Km coefficients used in residential hydraulic installations in Colombia were found, such as 90° elbows, universal joints, reductions, and ball valves from ½ to 2 inches in diameter. Among the results found, it was evidenced that the smaller the diameter, the load losses, the velocity, and the loss coefficient increase. An analysis of variance (ANOVA) was performed to corroborate the results obtained and, in most cases, reliability greater than or equal to 90% was achieved

Symmetries of sub-Riemannian surfaces

We obtain some results on symmetries of sub-Riemannian surfaces. In case of a contact sub-Riemannian surface we base on invariants found by Hughen [15]. Using these invariants, we find conditions under which a sub-Riemannian surface does not admit symmetries. If a surface admits symmetries, we show how invariants help to find them. It is worth noting, that the obtained conditions can be explicitly checked for a given contact sub-Riemannian surface. Also, we consider sub-Riemannian surfaces which are not contact and find their invariants along the surface where the distribution fails to be contact. © 2010 Elsevier B.V

Confronting the trans-Planckian question of inflationary cosmology with dissipative effects

We provide a class of QFTs which exhibit dissipation above a threshold energy, thereby breaking Lorentz invariance. Unitarity is preserved by coupling the fields to additional degrees of freedom (heavy fields) which introduce the rest frame. Using the Equivalence Principle, we define these theories in arbitrary curved spacetime. We then confront the trans-Planckian question of inflationary cosmology. When dissipation increases with the energy, the quantum field describing adiabatic perturbations is completely damped at the onset of inflation. However it still exists as a composite operator made with the additional fields. And when these are in their ground state, the standard power spectrum obtains if the threshold energy is much larger that the Hubble parameter. In fact, as the energy redshifts below the threshold, the composite operator behaves as if it were a free field endowed with standard vacuum fluctuations. The relationship between our models and the Brane World scenarios studied by Libanov and Rubakov displaying similar effects is discussed. The signatures of dissipation will be studied in a forthcoming paper.Comment: 30 pages, 1 Figure, to appear in CQ

Geoarqueología y paleontología de los depósitos de Pleistoceno Superior del antiguo Arroyo Abroñigal (Cuenca de Manzanares, Madrid): el yacimiento de Puente de los Tres Ojos

La excavación arqueológica del yacimiento del Puente de los Tres Ojos, próximo a la calle Cerro Negro (Madrid), ha aportado nuevos datos para profundizar en el conocimiento de la ocupación humana y en la reconstrucción paleoambiental del valle del antiguo arroyo Abroñigal, cuyo curso fluvial funcionó como afluente del río Manzanares posiblemente desde antes del Pleistoceno Superior hasta la segunda mitad del siglo XX. En el presente artículo se incluyen los aspectos geomorfológicos y cronoestratigráficos de los niveles excavados, documentándose varias secuencias fluviales y aluviales de relleno de la margen derecha del fondo de valle del Abroñigal en su tramo inferior. Durante la excavación se registró un amplio conjunto lítico, formado en su mayoría por piezas recuperadas en niveles de arenas y gravas correspondientes a episodios fluviales de media energía, a las que hay que añadir un porcentaje menor localizado en niveles de limos arcillosos y arenas finas. La mayor parte del conjunto lítico responde a sistemas técnicos propios del Paleolítico Medio, aunque destaca la presencia testimonial de piezas del Paleolítico Superior, además de restos de fauna de mamíferos correspondientes al Pleistoceno Superior, todo ello en niveles datados por OSL entre 14.400 y 11.170 años BP aproximadament