In silico ADMET prediction, evaluation of cytotoxicity in mouse splenocytes and preliminary evaluation of in vitro antimalarial activity of 4-(4-chlorophenyl)thiazole compounds

Abstract In this work, an in silico study and evaluation of the cytotoxicity of 4-(4-chlorophenyl)thiazole compounds against mouse splenocytes and the chloroquine-sensitive Plasmodium falciparum 3D7 strain are reported. The in silico results showed that the compounds have important pharmacokinetic properties for compounds with potential drug candidates. Regarding cytotoxicity assays against splenocytes, the compounds have low cytotoxicity. In addition, they were able to promote activation of these cells by increasing nitric oxide production without promoting cell death. Finally, they were able to promote cell proliferation. Regarding the in vitro anti-P. falciparum activity assays, it was observed that the compounds were able to inhibit the parasite’s growth, presenting IC50 values ranging from 0.79 to greater than 10 µM. These results are promising when compared to chloroquine. Therefore, this study showed that 4-(4-chlorophenyl)thiazole compounds are promising candidates for antimalarials

Análise de polimorfismos do gene da beta-lactoglobulina em vacas da raça Nelore e efeitos sobre o peso à desmama de suas progênies Polimorphism analisys of beta-lactoglobulin gene on Nellore cows and effects on weaning weight of the calves

Informações sobre peso à desmama de bezerros Nelore foram utilizadas após ajuste para idade padrão aos 205 dias, sexo, idade da mãe, touro e mês de desmama, para separar as reprodutrizes em dois grupos, segundo o peso de suas crias. As médias de peso dos bezerros ajustadas pelo método dos quadrados mínimos e erros-padrão (LSM± SE) foram para os grupos pesados (P) e leves (L) 163,21± 2,18kg e 134,44± 2,18kg, respectivamente, com 41 animais em cada grupo. Essas reprodutrizes foram submetidas a coleta de sangue para estudo de polimorfismos do gene da beta-lactoglobulina, por meio da técnica de PCR-RFLP. A amplificação e a digestão de um fragmento do gene da beta-lactoglobulina entre o éxon II e III identificou os genótipos 1AA, 24AB e 56BB, com as freqüências de 0,16 e 0,84 para os alelos A e B, respectivamente. Os 24 animais com genótipo AB apresentaram LSM± SE de peso de seus produtos de 149,50± 4,17kg, e os 56 animais de genótipo BB tiveram média de 148,44± 2,73kg. O teste do qui-quadrado não apresentou significância (P>0,05), isto é, os grupos P e L não diferiram entre si quanto às freqüências alélicas apresentadas para esse gene. O genótipo das reprodutrizes não afetou o peso à desmama de suas crias, o que sugere haver outros fatores genéticos e não genéticos de maior magnitude que afetam o peso à desmama.<br>Weaning weights from a Nelore herd were used after adjustment of means for 205 days of age, sex, age of dam, sire and weaning month, and resulted into two groups of cows that differed by the weaning weight of their calves. The least square means (LSM) and standard error (SE) were for heavy group 163.21± 2.18kg and for light group 134.44± 2.18kg, with 41 animals in each group. These animals were genotyped by DNA polymorphisms of beta -lactoglobulin gene, using PCR-RFLP. After amplification and digestion of a beta-lactoglobulin gene fragment between II and III exon, genotypes 1AA, 24AB and 56BB were identified, with 0.16 and 0.84 frequencies for A and B alleles, respectively. The 24AB and 56BB cows showed calves with LSM± SE of 149.50± 4.17kg and 148.44± 2.73kg respectively, for weaning weight. No difference (P>0.05) was found and the heavy and light groups were similar for the allelic frequencies for this gene. The dam’s genotype did not affect the weaning weight of the calves. This suggests of having other factors, genetic or non-genetic, with major magnitude that affect the weaning weight

Nonradial and nonpolytropic astrophysical outflows. XI. Simulations of the circumstellar environment of RY Tau

Context. There are recent observational evidences that RY Tau may present two different outflow stages, a quiescent one and a more active one. We try to model that phenomenon. Aims. We have performed new 2.5D magneto-hydrodynamical simulations of the possible accretion-outflow environment of RY Tau based on analytical solutions to reduce the relaxation time. Methods. We used as initial conditions the analytical self-similar solution we used to model the RY Tau micro jet. In the closed field line region of the magnetosphere we have reversed the direction of the flow and increased the accretion rate by increasing the density and the velocity. We have also implemented the heating rate and adjusted it according to the velocity of the flow. The accretion disk is treated as a boundary condition. Results. The simulations show that the stellar jet and the accreting magnetosphere attain a steady state in only a few stellar rotations, confirming the robustness and stability of self-similar solutions. Additionally, two types of behavior were observed similar to the one observed in RY Tau. Either the steady stellar outflow and magnetospheric inflow are separated by a low static force free region or the interaction between the stellar jet and the magnetospheric accretion creates coronal episodic mass ejections originating from the disk and bouncing back onto the star. Conclusions. The ratio of mass loss rate to mass accretion rate that coincides with the change of behaviour observed in RY Tau, lays within the range of ratios that have been measured during the period of the micro jet initial analysis