Accelerated expansion from structure formation

We discuss the physics of backreaction-driven accelerated expansion. Using the exact equations for the behaviour of averages in dust universes, we explain how large-scale smoothness does not imply that the effect of inhomogeneity and anisotropy on the expansion rate is small. We demonstrate with an analytical toy model how gravitational collapse can lead to acceleration. We find that the conjecture of the accelerated expansion being due to structure formation is in agreement with the general observational picture of structures in the universe, and more quantitative work is needed to make a detailed comparison.Comment: 44 pages, 1 figure. Expanded treatment of topics from the Gravity Research Foundation contest essay astro-ph/0605632. v2: Added references, clarified wordings. v3: Published version. Minor changes and corrections, added a referenc

Characterisation of iunH gene knockout strain from Mycobacterium tuberculosis

BACKGROUND Tuberculosis (TB) is an infectious disease caused mainly by the bacillus Mycobacterium tuberculosis. The better understanding of important metabolic pathways from M. tuberculosis can contribute to the development of novel therapeutic and prophylactic strategies to combat TB. Nucleoside hydrolase (MtIAGU-NH), encoded by iunH gene (Rv3393), is an enzyme from purine salvage pathway in M. tuberculosis. MtIAGU-NH accepts inosine, adenosine, guanosine, and uridine as substrates, which may point to a pivotal metabolic role. OBJECTIVES Our aim was to construct a M. tuberculosis knockout strain for iunH gene, to evaluate in vitro growth and the effect of iunH deletion in M. tuberculosis in non-activated and activated macrophages models of infection. METHODS A M. tuberculosis knockout strain for iunH gene was obtained by allelic replacement, using pPR27xylE plasmid. The complemented strain was constructed by the transformation of the knockout strain with pNIP40::iunH. MtIAGU-NH expression was analysed by Western blot and LC-MS/MS. In vitro growth was evaluated in Sauton’s medium. Bacterial load of non-activated and interferon-γ activated RAW 264.7 cells infected with knockout strain was compared with wild-type and complemented strains. FINDINGS Western blot and LC-MS/MS validated iunH deletion at protein level. The iunH knockout led to a delay in M. tuberculosis growth kinetics in Sauton’s medium during log phase, but did not affect bases and nucleosides pool in vitro. No significant difference in bacterial load of knockout strain was observed when compared with both wild-type and complemented strains after infection of non-activated and interferon-γ activated RAW 264.7 cells. MAIN CONCLUSION The disruption of iunH gene does not influence M. tuberculosis growth in both non-activated and activated RAW 264.7 cells, which show that iunH gene is not important for macrophage invasion and virulence. Our results indicated that MtIAGU-NH is not a target for drug development

Biochemical Characterization of Uracil Phosphoribosyltransferase from Mycobacterium tuberculosis

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Uracil phosphoribosyltransferase (UPRT) catalyzes the conversion of uracil and 5-phosphoribosyl-alpha-1-pyrophosphate (PRPP) to uridine 5'-monophosphate (UMP) and pyrophosphate (PPi). UPRT plays an important role in the pyrimidine salvage pathway since UMP is a common precursor of all pyrimidine nucleotides. Here we describe cloning, expression and purification to homogeneity of upp-encoded UPRT from Mycobacterium tuberculosis (MtUPRT). Mass spectrometry and N-terminal amino acid sequencing unambiguously identified the homogeneous protein as MtUPRT. Analytical ultracentrifugation showed that native MtUPRT follows a monomer-tetramer association model. MtUPRT is specific for uracil. GTP is not a modulator of MtUPRT ativity. MtUPRT was not significantly activated or inhibited by ATP, UTP, and CTP. Initial velocity and isothermal titration calorimetry studies suggest that catalysis follows a sequential ordered mechanism, in which PRPP binding is followed by uracil, and PPi product is released first followed by UMP. The pH-rate profiles indicated that groups with pK values of 5.7 and 8.1 are important for catalysis, and a group with a pK value of 9.5 is involved in PRPP binding. The results here described provide a solid foundation on which to base upp gene knockout aiming at the development of strategies to prevent tuberculosis.82Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)"Embrapa Recursos Geneticos e Biotecnologia", BrazilFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)CNPq [520182/99-5, 304051/1975-06, 304034/2008-8

Appropriateness of carotid plaque and intima-media thickness assessment in routine clinical practice

<p>Abstract</p> <p>Objectives</p> <p>To describe the findings and evaluate appropriateness of a carotid artery study including the measurement of IMT, the presence of atherosclerotic plaque, and their correlation with cardiovascular risk factors.</p> <p>Methods</p> <p>555 patients (220 men; 67.06 ± 12.44 years) were included in the study. 120 patients (21.62%) presented carotid plaque: 108 (19.45%) in patients with at least one risk factor and 12 (2.1%) in patients without risk factors. With respect to appropriateness of the present studies: 65% were appropriate, 22% were uncertain and 13% were inappropriate. The IMT medians were higher in males (0.0280; 95% CI, 00.82 to 0.478; <it>p </it>= 0.0057) and in hypertensive patients (0.391; 95% CI, 0.0190 to 0.0592; <it>p </it>= 0,001). There was a linear increase in mean IMT for each year increased in age (0.0059; 95% CI; 0.0050 to 0.0067). Carotid plaque was more frequent in patients with CAD (<it>p </it>= 0.0002), diabetes (<it>p </it>= 0.024) and hypertension (<it>p </it>= 0.036).</p> <p>Conclusion</p> <p>Assessment of carotid arteries identified increased incidence of plaque in patients with CAD, diabetes and hypertension. IMT was increased in older patients, hypertensive patients and males. Forty-five percent of the patients were studied based on uncertain and inappropriate reasons.</p