Vias de Sinalização da Insulina

Insulin is an anabolic hormone with powerful metabolic effects. The events after insulin binds to its receptor are highly regulated and specific. Defining the key steps that lead to the specificity in insulin signaling presents a major challenge to biochemical research, but the outcome should offer new therapeutic approaches for treatment of patients suffering from insulin-resistant states, including type 2 diabetes. The insulin receptor belongs to the large family of growth factor receptors with intrinsic tyrosine kinase activity. Following insulin binding, the receptor undergoes autophosphorylation on multiple tyrosine residues. This results in activation of the receptor kinase and tyrosine phosphorylation of a family of insulin receptor substrate (IRS) proteins. Like other growth factors, insulin uses phosphorylation and the resultant protein-protein interactions as essential tools to transmit and compartmentalize its signal. These intracellular protein-protein interactions are pivotal in transmitting the signal from the receptor to the final cellular effect, such as translocation of vesicles containing GLUT4 glucose transporters from the intracellular pool to the plasma membrane, activation of glycogen or protein synthesis, and initiation of specific gene transcription.A insulina é um hormônio anabólico com efeitos metabólicos potentes. Os eventos que ocorrem após a ligação da insulina são específicos e estritamente regulados. Definir as etapas que levam à especificidade deste sinal representa um desafio para as pesquisas bioquímicas, todavia podem resultar no desenvolvimento de novas abordagens terapêuticas para pacientes que sofrem de estados de resistência à insulina, inclusive o diabetes tipo 2. O receptor de insulina pertence a uma família de receptores de fatores de crescimento que têm atividade tirosina quinase intrínseca. Após a ligação da insulina o receptor sofre autofosforilação em múltiplos resíduos de tirosina. Isto resulta na ativação da quinase do receptor e conseqüente fosforilação em tirosina de um a família de substratos do receptor de insulina (IRS). De forma similar a outros fatores de crescimento, a insulina usa fosforilação e interações proteína-proteína como ferramentas essenciais para transmitir o sinal. Estas interações proteína-proteína são fundamentais para transmitir o sinal do receptor em direção ao efeito celular final, tais como translocação de vesículas contendo transportadores de glicose (GLUT4) do pool intracelular para a membrana plasmática, ativação da síntese de glicogênio e de proteínas, e transcrição de genes específicos.41942

Canine parvovirus 2c infection in central Portugal

Canine parvovirus (CPV) has been evolving, generating new genetic and antigenic variants throughout the world. This Study was conducted to determine the types of CPV circulating in dogs in Figueira da Foz, Portugal. Thirty fecal samples, collected between 2006 and 2007 from dogs with clinical signs of CPV infection, were tested for CPV by a rapid, in-clinic, enzyme-linked immunosorbent assay (ELISA)/immunomigration test, by conventional real-time polymerase chain reaction (PCR), and by minor-groove binding TaqMan PCR. Of the 29 PCR-positive samples, 15 were identified as CPV-2b and 14 as CPV-2c. No CPV-2a was detected. The sensitivity of the ELISA test was 82.76% compared with the PCR assays. No significant associations were found between CPV type, clinical outcome, breed, vaccination status, or age

GnRH use in different times on estrus synchronization and ovulation in Santa Inês ewes.

Proceedings of the 28th Annual Meeting of the Brazilian Embryo Technology Society (SBTE), August, 2014, Natal, RN, Brazil. Abstracts

An Eye for Possibilities in the Development of Children with Cerebral Palsy: Neurobiology and Neuropsychology in a Cultural-Historical Dynamic Understanding

Taking children with Cerebral Palsy (CP) as an example, the article seeks an understanding ofchildren with disabilities that connects neuropsychological theories of neural development withthe situated cognition perspective and the child as an active participant in its social practices. Theearly brain lesion of CP is reconceptualised as a neurobiological constraint that exists in therelations between the neural, cognitive and social levels. Through a multi-method study of twochildren with CP, it is analysed how neurobiological constraints arise, evolve and sometimes areresolved through local matches between the child and its social practices. The result is discussedas support of a developmental science approach that includes processes at the social practice levelalong with knowledge of biological processes

Genotype imputation strategies for Portuguese Holstein cattle using different SNP panels.

Abstract: Although several studies have investigated the factors affecting imputation accuracy, most of these studies involved a large number of genotyped animals. Thus, results from these studies cannot be directly applied to small populations, since the population structure affects imputation accuracy. In addition, factors affecting imputation accuracy may also be intensified in small populations. Therefore, we aimed to compare different imputation strate-gies for the Portuguese Holstein cattle population considering several commercially available single nucleotide poly-morphism (SNP) panels in a relatively small number of genotyped animals. Data from 1359 genotyped animals were used to evaluate imputation in 7 different scenarios. In the S1 to S6 scenarios, imputations were performed from LDv1, 50Kv1, 57K, 77K, HDv3 and Ax58K panels to 50Kv2 panel. In these scenarios, the bulls in 50Kv2 were divided into reference (352) and validation (101) populations based on the year of birth. In the S7 scenario, the validation population consisted of 566 cows genotyped with the Ax58K panel with theirgenotypes masked to LDv1. In general, all sample imputation accuracies were high with correlations ranging from 0.94 to 0.99 and concordance rate rang-ing from 92.59 to 98.18%. SNP-specific accuracy was consistent with that of sample imputation. S4 (40.32% of SNPs imputed) had higher accuracy than S2 and S3, both with less than 7.59% of SNPs imputed. Most probably, this was due to the high number of imputed SNPs with minor allele frequency (MAF) < 0.05 in S2 and S3 (by 18.43% and 16.06% higher than in S4, respectively). Therefore, for these two scenarios, MAF was more relevant than the panel density. These results suggest that genotype imputation using several commercially available SNP panels is feasible for the Portuguese national genomic evaluation

Physical Exercise Reduces Circulating Lipopolysaccharide and TLR4 Activation and Improves Insulin Signaling in Tissues of DIO Rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)OBJECTIVE-Insulin resistance in diet-induced obesity (DIO) is associated with a chronic systemic low-grade inflammation, and Toll-like receptor 4 (TLR4) plays an important role in the link among insulin resistance, inflammation, and obesity. The current study aimed to analyze the effect of exercise on TLR4 expression and activation in obese rats and its consequences on insulin sensitivity and signaling. RESEARCH DESIGN AND METHODS-The effect of chronic and acute exercise was investigated on insulin sensitivity, insulin signaling, TLR4 activation, c-Jun NH(2)-terminal kinase (JNK) and I kappa B kinase (IKK beta) activity, and lipopolysaccharide (LPS) serum levels in tissues of DIO rats. RESULTS-The results showed that chronic exercise reduced TLR4 mRNA and protein expression in liver, muscle, and adipose tissue. However, both acute and chronic exercise blunted TLR4 signaling in these tissues, including a reduction in JNK and IKK beta phosphorylation and IRS-1 serine 307 phosphorylation, and, in parallel, improved insulin-induced IR, IRS-1 tyrosine phosphorylation, and Akt serine phosphorylation, and reduced LPS serum levels. CONCLUSIONS-Our results show that physical exercise in DIO rats, both acute and chronic, induces an important suppression in the TLR4 signaling pathway in the liver, muscle, and adipose tissue, reduces LPS serum levels, and improves insulin signaling and sensitivity. These data provide considerable progress in our understanding of the molecular events that link physical exercise to an improvement in inflammation and insulin resistance. Diabetes 60:784-796, 2011603784796Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de PesquisaINCT-Obesidade e DiabetesFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Partial sequencing of recent Portuguese myxoma virus field isolates exhibits a high degree of genetic stability

To study genetic changes underlying myxoma virus evolution in its new host, the European rabbit (Oryctolagus cuniculus), we sequenced selected genomic regions of nine recent virulent field strains and a live attenuated vaccine strain ("MAV", Germany). DNA was extracted from cell culture passaged myxoma virus. A total of 4863 bp (approximately 3% of the genome) of 10 regions spanning 12 genes of the myxoma viruses was sequenced and compared to the original virulent strain "Lausanne" and its attenuated field derivative strain "6918". The field strains displayed a maximum of three (strains C43, C95) and a minimum of one (strains CD01, CD05) nucleotide substitutions. These were distributed through all analysed coding regions, except gene M022L (major envelope protein), where all strains were identical to "Lausanne" and "6918". Two new single nucleotide insertions were observed in some of the field strains: within the intergenic region M014L/M015L and within gene M009L, where it leads to a frameshift. These insertions were located after homopolymeric regions. The vaccine strain displayed 37 nucleotide substitutions, predominantly (95%) located in genes M022L and M036L. Interestingly, regions M009L and M014L/M015L of the vaccine were not amplified successfully, suggesting major genomic changes that could account for its attenuated phenotype. Our results support a high degree of genetic stability of myxoma virus over the past five decades. None of the analysed genome regions by its own seems sufficient for the genetic characterisation of field strains

Fyn Mediates Leptin Actions in the Thymus of Rodents

BACKGROUND:Several effects of leptin in the immune system rely on its capacity to modulate cytokine expression and apoptosis in the thymus. Surprisingly, some of these effects are dependent on signal transduction through the IRS1/PI3-kinase, but not on the activation of JAK2. Since all the well known effects of leptin in different cell types and tissues seem to be dependent on JAK2 activation, we hypothesized that, at least for the control of thymic function, another, unknown kinase could mediate the transduction of the leptin signal from the ObR towards the IRS1/PI3-kinase signaling cascade. METHODOLOGY/PRINCIPAL FINDINGS:Here, by employing immunoblot, real-time PCR and flow citometry we show that the tyrosine kinase, Fyn, is constitutively associated with the ObR in thymic cells. Following a leptin stimulus, Fyn undergoes an activating tyrosine phosphorylation and a transient association with IRS1. All these effects are independent of JAK2 activation and, upon Fyn inhibition, the signal transduction towards IRS1/PI3-kinase is abolished. In addition, the inhibition of Fyn significantly modifies the effects of leptin on thymic cytokine expression. CONCLUSION/SIGNIFICANCE:Therefore, in the thymus, Fyn acts as a tyrosine kinase that transduces the leptin signal independently of JAK2 activation, and mediates some of the immunomodulatory effects of leptin in this tissue