Cycloaddition Reactions Of Cyclopropenones. 4. Reaction Of Some 2-aminopyridines With Methylphenylcyclopropenone

Methylphenylcyclopropenone (2) undergoes a cycloaddition reaction across the PhC-CO bond with 2-aminopyridine (3a) in ether to produce the insoluble cis-3,4-dihydro-3-methyl-4-phenyl-2H-pyrido[1,2-a]pyrimidin-2-one (6a). Rearrangement of 6a to α-methyl-trans-cinnamamide 7a occurs slowly in refluxing chloroform. 2-Amino-3-methyl- and 2-amino-4-methylpyridine react similarly, while 2-amino-5-methylpyridine eventually affords, in addition, the α-(2-pyridylamino) acid 10a. 2-Amino-6-methylpyridine reacts very slowly to give 10b exclusively. A lack of reactivity shown by aniline suggests that both products arise by way of initial nucleophilic attack of the aminopyridine ring nitrogen on the cyclopropenone ring, with steric hindrance at this nitrogen favoring subsequent formation of an intermediate of apparent reaction at the exo nitrogen.41223546354

Myosin Va is developmentally regulated and expressed in the human cerebellum from birth to old age

Myosin Va functions as a processive, actin-based motor molecule highly enriched in the nervous system, which transports and/or tethers organelles, vesicles, and mRNA and protein translation machinery. Mutation of myosin Va leads to Griscelli disease that is associated with severe neurological deficits and a short life span. Despite playing a critical role in development, the expression of myosin Va in the central nervous system throughout the human life span has not been reported. To address this issue, the cerebellar expression of myosin Va from newborns to elderly humans was studied by immunohistochemistry using an affinity-purified anti-myosin Va antibody. Myosin Va was expressed at all ages from the 10th postnatal day to the 98th year of life, in molecular, Purkinje and granular cerebellar layers. Cerebellar myosin Va expression did not differ essentially in localization or intensity from childhood to old age, except during the postnatal developmental period. Structures resembling granules and climbing fibers in Purkinje cells were deeply stained. In dentate neurons, long processes were deeply stained by anti-myosin Va, as were punctate nuclear structures. During the first postnatal year, myosin Va was differentially expressed in the external granular layer (EGL). In the EGL, proliferating prospective granule cells were not stained by anti-myosin Va antibody. In contrast, premigratory granule cells in the EGL stained moderately. Granule cells exhibiting a migratory profile in the molecular layer were also moderately stained. In conclusion, neuronal myosin Va is developmentally regulated, and appears to be required for cerebellar function from early postnatal life to senescence

Biological properties of cardiac mesenchymal stem cells in rats with diabetic cardiomyopathy

Cardiomyopathy is a major outcome in patients with diabetes mellitus (DM) and contributes to the high morbidity/mortality observed in this disease. AIMS: To evaluate several biological properties of cardiac mesenchymal stem cells (cMSCs) in a rat model of streptozotocin-induced DM with concomitant diabetic cardiomyopathy. MAIN METHODS: After 10weeks of DM induction, diabetic and control rats were assessed using ECG and ventricular hemodynamics monitoring. Then, the hearts were excised and processed for histology and for extracting non-cardiomyocytic cells. A pool of these cells was plated for a colony forming units-fibroblasts (CFU-F) assay in order to estimate the number of cMSCs. The remaining cells were expanded to assess their proliferation rate as well as their osteogenic and adipogenic differentiation ability. KEY FINDINGS: DM rats presented intense hyperglycemia and changes in ECG, LV hemodynamic, cardiac mass index and fibrosis, indicating presence of DCM. The CFU-F assay revealed a higher number of cardiac CFU-Fs in DM rats (10.4\ub11.1CFU-F/105 total cells versus 7.6\ub10.7CFU-F/105 total cells in control rats, p<0.05), which was associated with a significantly higher proliferative rate of cMSCs in DM rats. In contrast, cMSCs from DM rats presented a lower capacity to differentiate into both osteogenic (20.8\ub14.2% versus 10.1\ub11.0% in control rats, p<0.05) and adipogenic lineages (4.6\ub11.0% versus 1.3\ub10.5% in control rats, p<0.05). SIGNIFICANCE: The findings suggest, for the first time, that in chronic DM rats with overt DCM, cMSCs increase in number and exhibit changes in several functional properties, which could be implicated in the pathogenesis of diabetic cardiomyopathy

Desempenho de vacas leiteiras em pastagem de alfafa suplementada com silagem de milho e concentrado e viabilidade econômica do sistema

Avaliou-se o efeito da substituição parcial de silagem de milho por pastagem de alfafa no desempenho de vacas leiteiras e na viabilidade econômica do sistema. Utilizaram-se 24 vacas da raça Holandesa, em estádio médio de lactação, em delineamento em blocos ao acaso. Os tratamentos foram: dieta à base de silagem de milho em confinamento, silagem de milho substituída parcialmente por pastejo restrito (PR) e pastejo irrestrito (PI) de alfafa. O sistema de pastejo foi rotacionado, e a quantidade de concentrado igual em todos os tratamentos. A massa de forragem foi de 2.338 e de 1.878kg de MS/ha, e a oferta de 1,8 e 4,2kg de MS/100kg de peso vivo, nos tratamentos PR e PI, respectivamente. A produção de leite não diferiu entre os tratamentos, cujas médias foram de 25,9; 25,8 e 25,2 litros por vaca por dia no confinamento, no PR e no PI, respectivamente. A produção diária de leite por área foi de 59,3L/ha no PR e de 63,0L/ha no PI, enquanto no confinamento foi de 45,7L/ha. A substituição parcial de silagem de milho por alfafa em pastejo não limitou o desempenho produtivo dos animais e mostrou-se economicamente vantajosa em relação ao confinamento

Identificação e modelagem da autocorrelação residual no ajuste do modelo de Wood às curvas de lactação de cabras Identification and modeling of residual autocorrelation in the adjustments of Wood’s model to lactation curves of goats

Objetivou-se com este trabalho apresentar uma metodologia de identificação e modelagem da autocorrelação residual considerando ajustes individuais do modelo de Wood às lactações de cabras leiteiras e também avaliar a influência de tal modelagem na qualidade do ajuste. O modelo de Wood foi ajustado individualmente às lactações, considerando três estruturas residuais. Na primeira, assumiu-se independência dos erros (EI) para todas as lactações, na segunda, assumiu-se a estrutura de erros autoregressivos de primeira ordem (AR1) para todas as lactações e, na terceira, nomeada por EI-AR1, foi utilizada a estrutura de erros AR1 somente para as lactações que apresentaram autocorrelação residual, segundo o teste de Durbin-Watson, e de EI para as demais. As três situações de ajuste foram comparadas pelos percentuais de convergência e pelas médias dos quadrados médios dos erros (QME) e dos coeficientes de determinação ajustados (R²aj). As médias dos QME e dos R²aj apresentaram valores semelhantes nas três situações de estrutura residual. No entanto, o modelo com estrutura EI-AR1 apresentou maior convergência, o que consiste em uma vantagem, já que permite que um maior número de animais seja avaliado quanto à sua curva de lactação. Portanto, em função da maior convergência obtida, o ajuste do modelo de Wood com a estrutura EI-AR1 consiste na opção mais indicada para grandes conjuntos de dados.<br>The objective of this research was to present a methodology for identification and modeling of residual autocorrelation considering individual adjustments of the Wood's model to lactation dairy goats and evaluate the influence of such modeling in the quality of adjustment. The Wood's model was adjusted individually for lactations in three different ways, the first have assumed independence of errors (IE) for all lactations, the second have assumed autoregressives first order errors (AR1) for all lactations and the third, named (IE-AR1), was used the AR1 errors structure only for lactations that showed residual autocorrelation according to Durbin-Watson test, and the IE errors structure for the other lactations. The three ways of adjustment were compared by the percentage of convergence and the average of the mean square errors (MSE) and coefficients of determination adjusted (R²adj). The average of MSE and R²aj were very similar in the three cases of residual structure. However, the model with IE-AR1 residual structure showed a higher rate of convergence, which is an advantage, as it allows a greater number of animals are evaluated for their lactation curve. Therefore, due to the increasing convergence obtained, the fit of the Wood's model with IE-AR1 residual structure is the option most suitable for large data sets