Depletion of angiotensin-converting enzyme 2 reduces brain serotonin and impairs the running-induced neurogenic response

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this recordPhysical exercise induces cell proliferation in the adult hippocampus in rodents. Serotonin (5-HT) and angiotensin (Ang) II are important mediators of the pro-mitotic effect of physical activity. Here, we examine precursor cells in the adult brain of mice lacking angiotensin-converting enzyme (ACE) 2, and explore the effect of an acute running stimulus on neurogenesis. ACE2 metabolizes Ang II to Ang-(1-7) and is essential for the intestinal uptake of tryptophan (Trp), the 5-HT precursor. In ACE2-deficient mice, we observed a decrease in brain 5-HT levels and no increase in the number of BrdU-positive cells following exercise. Targeting the Ang II/AT1 axis by blocking the receptor, or experimentally increasing Trp/5-HT levels in the brain of ACE2-deficient mice, did not rescue the running-induced effect. Furthermore, mice lacking the Ang-(1-7) receptor, Mas, presented a normal neurogenic response to exercise. Our results identify ACE2 as a novel factor required for exercise-dependent modulation of adult neurogenesis and essential for 5-HT metabolism

Brazilian obstetrician-gynecologists and abortion: a survey of knowledge, opinions and practices

BACKGROUND: Abortion laws are extremely restrictive in Brazil. The knowledge, opinions of abortion laws, and abortion practices of obstetrician-gynecologists can have a significant impact on women's access to safe abortion. METHODS: We conducted a mail-in survey with a 10% random sample of obstetrician-gynecologists affiliated with the Brazilian Federation of Obstetricians and Gynecologists. We documented participants' experiences performing abortion under a range of legal and illegal circumstances, and asked about which abortion techniques they had experience with. We used chi-square tests and crude logistic regression models to determine which sociodemographic, knowledge-related, or practice-related variables were associated with physician opinion. RESULTS: Of the 1,500 questionnaires that we mailed out, we received responses from 572 (38%). Less than half (48%) of the respondents reported accurate knowledge about abortion law and 77% thought that the law should be more liberal. One-third of respondents reported having previous experience performing an abortion, and very few of these physicians reported having experience with manual vacuum aspiration (MVA) or with misoprostol with either mifepristone or methotrexate. Physicians that favored liberalization of the law were more likely to have correct knowledge about abortion law, and to be in favor of public funding for abortion services. CONCLUSION: Brazilian obstetrician-gynecologists need more information on abortion laws and on safe, effective abortion procedures

Soil water-holding capacity and monodominance in Southern Amazon tropical forests

Background and aims: We explored the hypothesis that low soil water-holding capacity is the main factor driving the monodominance of Brosimum rubescens in a monodominant forest in Southern Amazonia. Tropical monodominant forests are rare ecosystems with low diversity and high dominance of a single tree species. The causes of this atypical condition are still poorly understood. Some studies have shown a relationship between monodominance and waterlogging or soil attributes, while others have concluded that edaphic factors have little or no explanatory value, but none has accounted for soil-moisture variation other than waterlogging. This study is the first to explicitly explore how low soil water-holding capacity influences the monodominance of tropical forests. Methods: We conducted in situ measurements of vertical soil moisture using electrical resistance collected over 1 year at 0–5; 35–40 and 75–80 cm depths in a B. rubescens monodominant forest and in an adjacent mixed-species forest in the Amazon-Cerrado transition zone, Brazil. Minimum leaf water potential (Ψmin) of the seven most common species, including B. rubescens, and soil water-holding capacity for both forests were determined. Results: The vertical soil moisture decay pattern was similar in both forests for all depths. However, the slightly higher water availability in the monodominant forest and Ψmin similarity between B. rubescens and nearby mixed forest species indicate that low water-availability does not cause the monodominance. Conclusions: We reject the hypothesis that monodominance of B. rubescens is primarily determined by low soil water-holding capacity, reinforcing the idea that monodominance in tropical forests is not determined by a single factor

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