Substrate specificity and the effect of calcium on Trypanosomabrucei metacaspase 2

Metacaspases are cysteine peptidases found only in yeast, plants and lower eukaryotes, including the protozoa. To investigate the extended substrate specificity and effects of Ca<sup>2+</sup> on the activation of these enzymes, detailed kinetic, biochemical and structural analyses were carried out on metacaspase 2 from Trypanosoma brucei (TbMCA2). These results reveal that TbMCA2 has an unambiguous preference for basic amino acids at the P<sub>1</sub> position of peptide substrates and that this is most probably a result of hydrogen bonding from the P<sub>1</sub> residue to Asp95 and Asp211 in TbMCA2. In addition, TbMCA2 also has a preference for charged residues at the P<sub>2</sub> and P<sub>3</sub>positions and for small residues at the prime side of a peptide substrate. Studies into the effects of Ca<sup>2+</sup> on the enzyme revealed the presence of two Ca<sup>2+</sup> binding sites and a reversible structural modification of the enzyme upon Ca<sup>2+</sup> binding. In addition, the concentration of Ca<sup>2+</sup> used for activation of TbMCA2 was found to produce a differential effect on the activity of TbMCA2, but only when a series of peptides that differed in P<sub>2</sub> were examined, suggesting that Ca<sup>2+</sup>activation of TbMCA2 has a structural effect on the enzyme in the vicinity of the S2 binding pocket. Collectively, these data give new insights into the substrate specificity and Ca<sup>2+</sup> activation of TbMCA2. This provides important functional details and leads to a better understanding of metacaspases, which are known to play an important role in trypanosomes and make attractive drug targets due to their absence in humans

Qualicafé: seleção de características de qualidade por forma.

bitstream/CNPDIA-2009-09/12003/1/BPD25_2008.pd

A leucine-supplemented diet improved protein content of skeletal muscle in young tumor-bearing rats

Cancer cachexia induces host protein wastage but the mechanisms are poorly understood. Branched-chain amino acids play a regulatory role in the modulation of both protein synthesis and degradation in host tissues. Leucine, an important amino acid in skeletal muscle, is higher oxidized in tumor-bearing animals. A leucine-supplemented diet was used to analyze the effects of Walker 256 tumor growth on body composition in young weanling Wistar rats divided into two main dietary groups: normal diet (N, 18% protein) and leucine-rich diet (L, 15% protein plus 3% leucine), which were further subdivided into control (N or L) or tumor-bearing (W or LW) subgroups. After 12 days, the animals were sacrificed and their carcass analyzed. The tumor-bearing groups showed a decrease in body weight and fat content. Lean carcass mass was lower in the W and LW groups (W = 19.9 ± 0.6, LW = 23.1 ± 1.0 g vs N = 29.4 ± 1.3, L = 28.1 ± 1.9 g, P < 0.05). Tumor weight was similar in both tumor-bearing groups fed either diet. Western blot analysis showed that myosin protein content in gastrocnemius muscle was reduced in tumor-bearing animals (W = 0.234 ± 0.033 vs LW = 0.598 ± 0.036, N = 0.623 ± 0.062, L = 0.697 ± 0.065 arbitrary intensity, P < 0.05). Despite accelerated tumor growth, LW animals exhibited a smaller reduction in lean carcass mass and muscle myosin maintenance, suggesting that excess leucine in the diet could counteract, at least in part, the high host protein wasting in weanling tumor-bearing rats.1589159

In and out and out again: The travails of Brazil as a security provider in Africa

The story of Brazil as a contemporary security actor in Africa can prove a peculiar one. Marked by quick gains and an equally quick recognition over a short period of time, it has also been followed by an equally quick turnaround which has led, as of 2020, to a visible disengagement on the ground. We explore the main travails in this domain, which have compromised much of the gains previously obtained throughout the continent. The chapter begins with a general balance of the progress achieved between 2003 and 2016, followed by the highlights of the recent downturn. We then analyze a specific sub-area, namely, the inroads carried out at the defence industry level, in order to showcase the promises and contradictions often associated to what the country has offered across the Atlantic. We conclude by presenting some opportunities for a new pickup of Brazilian interest in the middle and long run

Correlações entre características relacionadas ao temperamento em animais da raça Canchim.

O temperamento de um animal representa uma interação complexa entre seu genótipo e o ambiente ao qual está exposto. Medidas de temperamento diferentes e realizadas sob diferentes metodologias podem ser aplicadas aos programas de seleção. O objetivo do trabalho foi obter correlações fenotípicas e de ranking entre reatividade e escores de temperamento relacionados ao deslocamento e à tensão na balança de animais da raça Canchim pertencentes a um programa de melhoramento. Dados de 217 animais da safra 2012 foram avaliados à desmama, na balança, por meio de escores de deslocamento (DES10 e DES20) e de tensão (TEN10 e TEN20) aos 10 e aos 20 segundos e do número e intensidade de movimentos do animal (REAT) quantificados por meio de equipamento e software específicos. As correlações foram obtidas por meio do pacote estatístico SAS, tanto para os dados gerais, quanto por sexo e para os grupos de avaliação (de 1 a 4). De maneira geral, as correlações fenotípicas e de ranking entre REAT, TEN10, TEN20, DES10 e DES20 foram altas e positivas, indicando concordância entre as metodologias na avaliação de animais desmamados da raça Canchim. Outras avaliações serão realizadas em idades posteriores e até a finalização do projeto com outras safras, em 2017