Produção de novilhos castrados ou não castrados terminados em confinamento em idade jovem ou superjovem / Production of steers or bulls finished in feedlot at a young age or young steers

Avaliaram-se o desempenho produtivo e o rendimento de cortes comercias da carcaça de animais castrados ou não castrados terminados em confinamento e abatidos em idade jovem ou superjovem, alimentados com uma dieta contendo 11,2% de proteína bruta e 3,07Mcal de energia digestível/kg de matéria seca, composta de 50% de volumoso e 50% de concentrado. A idade no início do confinamento dos animais superjovens e jovens foi de nove e 22 meses, respectivamente. Maior PF foi observado para os animais jovens não castrados. O GMD foi 31% superior em favor dos novilhos jovens em relação aos superjovens. O CMS foi 27% superior para os novilhos jovens sobre os superjovens, e os novilhos não castrados consumiram 9% mais kg de matéria seca quando comparados aos castrados. A diferença de peso da meia carcaça entre animais não castrados e castrados foi de 43% para os jovens e de 18% para os superjovens. Maior percentual do corte serrote foi observado nos novilhos jovens castrados. Novilhos jovens apresentaram maior ganho de peso médio diário, bem como novilhos jovens não castrados apresentaram maior peso final. Animais não castrados apresentaram maiores pesos de meia carcaça fria, percentual de dianteiro e porção comestível do dianteiro em relação aos castrados.(AU)

The productive performance and yield of commercial cuts of the carcass of non-castrate or castrated males feedlot finished and slaughtered at a young age or young steers, fed a diet containing 11.2% crude protein and 3.07 Mcal of digestible energy / kg of dry matter, composed of 50% roughage and 50% concentrate were evaluated. The initial age at the beginning of confinement of young steers and steers were 9 and 22 months, respectively. Greater FW was observed for young non-castrate. The ADG was 31% higher for the steers in relation to young steers. The DMI was 27% higher for steers than young steers and non-castrated consumed 9% more dry matter kg compared to the castrated. The half-carcass weight difference between non-castrated and castrated animals was 43% for steers and 18% for young steers. Higher percentage hacksaw cut was observed in castrated steers. Steers showed higher average daily weight gain, as well as non-castrate steers showed higher final weight. Non-castrate animals have higher half cold carcass weights, front percentage, and of edible portion of the front in relation to castrated.(AU)

The dual mTORC1 and mTORC2 inhibitor AZD8055 has anti-tumor activity in acute myeloid leukemia.

The serine/threonine kinase mammalian target of rapamycin (mTOR) is crucial for cell growth and proliferation, and is constitutively activated in primary acute myeloid leukemia (AML) cells, therefore representing a major target for drug development in this disease. We show here that the specific mTOR kinase inhibitor AZD8055 blocked mTORC1 and mTORC2 signaling in AML. Particularly, AZD8055 fully inhibited multisite eIF4E-binding protein 1 phosphorylation, subsequently blocking protein translation, which was in contrast to the effects of rapamycin. In addition, the mTORC1-dependent PI3K/Akt feedback activation was fully abrogated in AZD8055-treated AML cells. Significantly, AZD8055 decreased AML blast cell proliferation and cell cycle progression, reduced the clonogenic growth of leukemic progenitors and induced caspase-dependent apoptosis in leukemic cells but not in normal immature CD34+ cells. Interestingly, AZD8055 strongly induced autophagy, which may be either protective or cell death inducing, depending on concentration. Finally, AZD8055 markedly increased the survival of AML transplanted mice through a significant reduction of tumor growth, without apparent toxicity. Our current results strongly suggest that AZD8055 should be tested in AML patients in clinical trials.

Recent advances in adult T-cell leukemia therapy: focus on a new anti-transferrin receptor monoclonal antibody.

HTLV-I is an endemic retrovirus responsible for the adult T-cell leukemia/lymphoma (ATLL). This aggressive lymphoid proliferation is associated with a bad prognosis due to the resistance of HTLV-I-infected cells to most classical chemotherapeutic agents. Here we review recent advances in ATLL immunotherapy. We particularly focus on promising data from our group, characterizing a new mouse monoclonal antibody (mAb A24) against the human transferrin receptor (TfR-1). Monoclonal antibodies to target cell differentiation markers on ATLL cells have already been proposed as therapeutic agents. However, in clinical trials acute forms of ATLL were resistant to these immunotherapies. A24 binds TfR-1 (K(d) 2.7 nM) and competes with transferrin for receptor binding. It blocks the proliferation of malignant cells (TfR-1(high)), such as HTLV-I-infected T cells but not of resting cells. A24 induces TfR-1 endocytosis in lysosomal compartments where the receptor is degraded leading to intracellular iron deprivation. In HTLV-I-infected cells, A24 targets and induces apoptosis of both chronic and acute ATLL forms, independent of antibody aggregation, antibody-dependent cellular cytotoxicity and/or complement addition. The antibody efficacy was confirmed in animal models. We are currently developing strategies to use A24 in clinical trials.

Confiabilidadeintra e interexaminadores e repetibilidade da avaliacao postural pela fotogrametria / Intra and inter-examiner reliability and method repeatability of postural evaluation via photogrammetry

Propor avaliacao quantitativa das assimetrias posturais e verificar a confiabilidade intra e interexaminadores e a repetibilidade do metodo. Metodos: participaram 21 voluntarios (24+-1,9 anos) que tiveram fotografados a face e o corpo todo nos planos frontal anterior, posterior e sagital. Os angulos estudados form tracados nas fotos digitais, a partir de marcadores fixos a pele em varios pontos anatomicos, que sao referencias frequentes na avaliacao postural tradicional. A analise da confiabilidade foi efetuada a partir das medidas angulares de uma mesma foto, obtidas por um unico examinador em duas ocasioes (intra-examinadores) intervaladas por um mes e de uma so medida realizada por um terceiro examinador (interexaminadores). Arepetibilidade do metodo foi analisada pelas medidas angulares tomadas por um examinador em 2 fotos diferentes do mesmo sujeito, realizadas com intervalos de uma semana. O coeficiente de correlacao intraclasse (ICC) foi aplicado com nivel de significancia de 5 por cento. Resultados: O metodo proposto apresenta significativa confiabilidade intra e interexaminadores para a maioria dos angulos estudados. No entanto, a cifose toracica apresentou niveis nao aceitaveis de confiabilidade para a analise inter (ICC=0,603) e intra-examinador (ICC=0,031). Na repetibilidade do metodo, a maioria dos angulos estudados apresentou baixo nivel de confiabildade, exceto pelos angulos de inclinacao do pe direito (ICC=0,863) e triangulos de Talles (esquerdo ICC=0,922 e direito = 0,867). Conclusao: nessas condicoes experimentais a maioria dos valores angulares obtidos pelo metodo proposto apresentou confiabilidade intra e interexaminadores. No entanto, sua repetibilidade e baixa, sugerindo que o metodo e pouco indicado para o acompanhamento de mudancas posturais

Limonene arrests parasite development and inhibits isoprenylation of proteins in Plasmodium falciparum.

Isoprenylation is an essential protein modification in eukaryotic cells. Herein, we report that in Plasmodium falciparum, a number of proteins were labeled upon incubation of intraerythrocytic forms with either [(3)H]farnesyl pyrophosphate or [(3)H]geranylgeranyl pyrophosphate. By thin-layer chromatography, we showed that attached isoprenoids are partially modified to dolichol and other, uncharacterized, residues, confirming active isoprenoid metabolism in this parasite. Incubation of blood-stage P. falciparum treated with the isoprenylation inhibitor limonene significantly decreased the parasites' progression from the ring stage to the trophozoite stage and at 1.22 mM, 50% of the parasites died after the first cycle. Using Ras- and Rap-specific monoclonal antibodies, putative Rap and Ras proteins of P. falciparum were immunoprecipitated. Upon treatment with 0.5 mM limonene, isoprenylation of these proteins was significantly decreased, possibly explaining the observed arrest of parasite development.

Identification of the transferrin receptor as a novel immunoglobulin (Ig)A1 receptor and its enhanced expression on mesangial cells in IgA nephropathy.

The biological functions of immunoglobulin (Ig)A antibodies depend primarily on their interaction with cell surface receptors. Four IgA receptors are presently characterized. The FcalphaRI (CD89) expressed by myeloid cells selectively binds IgA1 and IgA2 antibodies, whereas the poly-IgR, Fcalpha/muR, and asialoglycoprotein receptors bind other ligands in addition to IgA. IgA binding by mesangial cells, epithelial cells, and proliferating lymphocytes is also well documented, but the nature of the IgA receptors on these cells remains elusive. A monoclonal antibody (A24) is described here that specifically blocks IgA binding to epithelial and B lymphocyte cell lines. Both the A24 antibody and IgA1 myelomas bind a cell surface protein that is identified as the transferrin receptor (CD71). The transferrin receptor selectively binds IgA1 antibodies, monomeric better than polymeric forms, and the IgA1 binding is inhibitable by transferrin. Transferrin receptor expression is upregulated on cultured mesangial cells as well as on glomerular mesangial cells in patients with IgA nephropathy. The characterization of transferrin receptor as a novel IgA1 receptor on renal mesangial cells suggests its potential involvement in the pathogenesis of IgA nephropathy.

Genetic immunization of BALB/c mice with a plasmid bearing the gene coding for a hybrid merozoite surface protein 1-hepatitis B virus surface protein fusion protects mice against lethal Plasmodium chabaudi chabaudi PC1 infection.

The genetic immunization of rodents with a plasmid coding for a Plasmodium chabaudi merozoite surface protein 1 (C terminus)-hepatitis B virus surface fusion protein (pPcMSP1(19)-HBs) provided protection of mice against subsequent lethal challenge with P. chabaudi chabaudi PC1-infected red blood cells. The percentage of survivor mice was higher in DNA-immunized mice than in animals immunized with a recombinant rPcMSP1(19)- glutathione S-transferase fusion protein administered in Freund adjuvant. In all mice immunized with the pPcMSP1(19)-HBs, a Th1-specific response, including the production of anti-MSP1(19)-specific immunoglobulins predominantly of the immunoglobulin G2a subtype and reacting almost exclusively against discontinuous epitopes, was elicited. The coinjection of Th1-type cytokine-expressing plasmids (gamma interferon, interleukin-2, and granulocyte-macrophage colony-stimulating factor) mostly abolished protection and boosting of MSP1(19)-specific antibodies. The inclusion of a lymph node-targeting signal did not significantly increase protection. These data provide further evidence that MSP1(19)-HBs DNA constructs might be useful as components of a genetic vaccine against the asexual blood stages of Plasmodium.

A Plasmodium chabaudi chabaudi high molecular mass glycoprotein translocated to the host cell membrane by a non-classical secretory pathway.

We have purified and characterized a novel high molecular mass glycoprotein of P. chabaudi chabaudi (Pc550gp) that is transported to the erythrocyte membrane during the intraerythrocytic cycle. Immuno fluorescence assays with polyclonal monospecific antibodies against Pc550gp show that the protein to be localized in the periphery of young trophozoite stages i.e., on the plasma membrane or parasitophorous vacuole membrane. However, in late trophozoites and schizonts the antigen is distributed in both parasite and host cell membranes. These results were confirmed by immunoblotting of isolated parasites and infected host cell membranes at different stages of parasite development. Moreover, alkali extraction of purified infected erythrocyte membranes at mature stages of parasite development does not solubilize Pc550gp, suggesting that it is an integral membrane protein. In addition proteinase K digestion of intact infected host cells induced the disappearance of Pc550gp. Further indicating its transmembrane nature and that it presents extracellular domains susceptible to proteolysis. Brefeldin A or low temperature (15 degrees C) treatment did not affect the translocation of Pc550gp from the parasite compartments to the erythrocyte membrane, indicating that the secretion of Pc550gp does not follow the classical transport pathway described in most eukaryotic cells.