BMPs, TGFbetas and integrins in muscle and germ cell development in mice

We characterized the expression of PSmad1/5/8 (BMP R-Smads) and PSmad2 (TGFbeta R-Smad) during peri-implantation and gastrulation in the mouse, and further characterized the expression of PSmad2 until E12.5, showing were the BMP and TGFbeta Smad-dependent signalling pathways are active (Chapter 2, 3 and 4). The role of ALK2 (BMP signalling) and ALK5 (TGFbeta signalling) in the development of PGCs in the mouse was studied in detail. ALK2 is needed for the formation of PGCs before gastrulation occurs and it signals in the visceral endoderm, a tissue that was previously not associated with primordial germ cell formation (Chapter 3). In contrast to suggestions derived from studies in vitro, ALK5 is probably not involved in PGC migration through the hindgut and to the gonadal ridges and TGF 1 is unlikely to be a chemoattractant for PGCs as proposed (Chapter 4). However, there may be a role for TGF signalling in PGC development in controlling mitotic arrest of PGCs in the gonadal ridges. Beta1 integrin was also implicated in PGC migration to the genital ridges. Beta1 integrin has two isoforms in mice: a more common one beta1A and a muscle specific beta1D that is upregulated late during development. We studied whether the replacement of beta1A by beta1D influenced the development of PGCs, but this occurred normally and we found no evidence of an effect on migration on the genetic background used. Furthermore, beta1 integrin has been implicated in heart development. We showed that the replacement of beta1A by beta1D did not cause heart abnormalities during development. However, we were able to show a clear role for beta1A during myogenesis. The differentiation of primary myoblasts was abnormal when only beta1D was expressed, while secondary myoblasts were formed normally. Furthermore, we showed a novel role of beta1 integrin during placentation, in particular the development of the labyrinthine layer (Chapter 5). CTGF is known to crosstalk with both TGFbeta and BMP in vitro. We studied possible interactions between them, focusing on heart development, where BMP and TGFbeta are known to play prominent roles. However, we were not able to detect direct crosstalk. Both CTGF and TGFbeta are associated with fibrosis. We investigated whether CTGF and TGFbeta were expressed following experimental induction of myocardial infarction in the mouse and showed that both genes are present in particular in the scar tissue and that TGFbeta Smad-dependent signalling is transient 1 week post-infarction and largely restricted to cardiac fibroblasts (Chapter 6)

Glutamate-N-methyl-D-aspartate receptor modulation and minocycline for the treatment of patients with schizophrenia: an update

Growing consistent evidence indicates that hypofunction of N-methyl-D-aspartate (NMDA) transmission plays a pivotal role in the neuropathophysiology of schizophrenia. Hence, drugs which modulate NMDA neurotransmission are promising approaches to the treatment of schizophrenia. The aim of this article is to review clinical trials with novel compounds acting on the NMDA receptor (NMDA-R). This review also includes a discussion and translation of neuroscience into schizophrenia therapeutics. Although the precise mechanism of action of minocycline in the brain remains unclear, there is evidence that it blocks the neurotoxicity of NMDA antagonists and may exert a differential effect on NMDA signaling pathways. We, therefore, hypothesize that the effects of minocycline on the brain may be partially modulated by the NMDA-R or related mechanisms. Thus, we have included a review of minocycline neuroscience. The search was performed in the PubMed, Web of Science, SciELO, and Lilacs databases. The results of glycine and D-cycloserine trials were conflicting regarding effectiveness on the negative and cognitive symptoms of schizophrenia. D-serine and D-alanine showed a potential effect on negative symptoms and on cognitive deficits. Sarcosine data indicated a considerable improvement as adjunctive therapy. Finally, minocycline add-on treatment appears to be effective on a broad range of psychopathology in patients with schizophrenia. The differential modulation of NMDA-R neurosystems, in particular synaptic versus extrasynaptic NMDA-R activation and specific subtypes of NMDA-R, may be the key mediators of neurogenesis and neuroprotection. Thus, psychotropics modulating NMDA-R neurotransmission may represent future monotherapy or add-on treatment strategies in the treatment of schizophrenia

β-thalassemia Intermedia In A Brazilian Patient With - 101 (c > T) And Codon 39 (c > T) Mutations

Context: We verified molecular alterations in a 72-year-old Brazilian male patient with a clinical course of homozygous β-thalassemia intermedia, who had undergone splenectomy and was surviving without regular blood transfusions. The blood cell count revealed microcytic and hypochromic anemia (hemoglobin = 6.5 g/dl, mean cell volume = 74 ft, mean cell hemoglobin = 24 pg) and hemoglobin electrophoresis showed fetal hemoglobin = 1.3%, hemoglobin A 2 = 6.78% and hemoglobin A = 79.4%. Objective: To identify mutations in a patient with the symptoms of β-thalassemia intermedia. Design: Molecular inquiry into the mutations possibly responsible for the clinical picture described. Setting: The structural molecular biology and genetic engineering center of the Universidade Estadual de Campinas, Campinas, Brazil. Procedures: DNA extraction was performed on the patient's blood samples. The polymerase chain reaction (PCR) was done using five specific primers that amplified exons and the promoter region of the β globin gene. The samples were sequenced and then analyzed via computer programs. Results: Two mutations that cause the disease were found: -101 (C > T) and codon 39 (C > T). Conclusions: This cases represents the first description of -101 (C > T) mutation in a Brazilian population and it is associated with a benign clinical course.12112830Baysal, E., Carver, M.F.H., The beta and delta-thalassemia repository (1995) Hemoglobin., 19 (3-4), pp. 213-236Zago, M.A., Costa, F., Bottura, C., Beta-thalassemia in Brazil (1981) Braz. J. Med. Biol. Res., 14 (6), pp. 383-388Ewing, B., Green, P., Base-calling of automated sequencer traces using Phred. II Error probabilities (1998) Genome Res., 8 (3), pp. 186-194Green, P., (2002), http://bozeman.genome.washington.edu/phrap.docs/phrap.html, The Phred/Phrap/Consed System Home Page. Phrap Assembler. Available at URL September 30Gordon, D., Abajian, C., Green, P., Consed: A graphical tool for sequence finishing (1998) Genome Res., 8 (3), pp. 195-20

Acolhimento de refugiados: alimentação e necessidades nutricionais em situações de emergência

A Europa é neste momento um dos principais destinos de um intenso fluxo migratórioprovocado por diferentes conflitos armados no Médio Oriente e em África, tendo a ComissãoEuropeia (CE) acordado na distribuição de uma parte destas pessoas em clara necessidade deproteção nacional, pelos diversos Estados Membros. As populações em trânsito e ascaracterísticas do seu acolhimento possuem especificidades que podem comprometer oacesso a uma alimentação adequada e a cuidados básicos de saúde, influenciando amorbilidade e a mortalidade nos grupos afetados.Este manual pretende estabelecer um referencial para a intervenção alimentar e nutricionalaos refugiados que chegam a Portugal. Destina-se a todos aqueles que prestam apoio, quer anível individual, quer a nível institucional, e que sejam responsáveis por qualquer aspetorelacionado com a saúde e a alimentação dessas populações, facilitando a operacionalizaçãoda assistência e fornecendo ferramentas para a tomada de decisões.O manual está organizado em 3 partes. Inicia-se com a avaliação do estado nutricional dapopulação a acolher, apresenta depois diversas estratégias para o desenho da intervençãoalimentar e nutricional tendo por base as necessidades nutricionais previstas para estes grupospopulacionais e, na parte final, aborda a importância de garantir a higiene e segurança dosalimentos na prestação desta assistência alimentar. Este manual apresenta ainda algumasconsiderações relacionadas com os cuidados básicos na área da psicologia destinados àsequipas que estão no terrenoEurope is now a major destination of an intense migratory flow caused by armed conflicts inthe Middle East and Africa. In this sense, the European Commission (EC) agreed on thedistribution of some of these people in clear need of international protection by variousMember States. The populations in transit and the characteristics of its reception havespecificities that can compromise the access to adequate food and basic health care. They canalso influence morbidity and mortality in affected groups.This manual aims to establish a framework of nutrition and food intervention to refugees inPortugal. It is aimed at all those who support it, either individually or institutionally, and areresponsible for any aspect related to the health and nutrition of these populations, facilitatingthe implementation of care and providing tools for decision making. The manual is organizedinto 3 parts. It begins with the assessment of nutritional status of the population. Then presents several strategies to support the design of food and nutrition intervention based onthe estimated nutritional needs for these population groups. In the final section it addressesthe importance of ensuring food safety and hygiene when providing this food assistance. Thismanual also addresses some considerations towards basic psychological interventionprinciples, destined to help the teams on the field

AVALIAÇÃO HISTOPATOLÓGICA, HORMONAL E BACTERIOLÓGICA DA PIOMETRA NA CADELA

O presente estudo teve como objetivo analisar os níveis hormonais, as alterações histopatológicas e os agentes etiológicos encontrados na piometra aberta e fechada em cadelas. Foram colhidas 30 amostras de fêmeas ovariohisterectomizadas em clínicas veterinárias da cidade de Curitiba, no Estado do Paraná, no período de outubro de 2002 a maio de 2003. Procedeu-se a exames bacteriológicos, análises histopatológicas dos cornos uterinos e dosagem hormonal da progesterona e do estradiol pela quimioluminescência. A bactéria isolada em maior porcentagem (36%) foi a Escherichia coli, e a alteração histológica de hiperplasia cística endometrial encontrada variou do grau I ao grau III. A proporção entre a progesterona e estradiol teve uma variação significativa nos dois tipos de piometra, porém não foi possível relacionar o agente etiológico, o tipo de lesão e a dosagem hormonal com o tipo de piometra, aberta ou fechada. Histopathological, hormonal, bacterial evaluation in the bitch pyometra Abstract The aim of the present study was to carry out an evaluation of the hormone levels, the histological changes and the etiological agents found in the open and closed pyometra. The uterine horns were collected from 30 bitches subjected to ovariectomy in different veterinary clinics from Curitiba, State of Parana, during the period of October 2002 to May, 2003. Bacteriological cultures, histological analysis and assays of progesterone and estradiol by the chemoluminescent method were performed. Escherichia coli showed to be the most frequent (36%) of the isolated bateria. It has been found the histological analysis that cystic endometrial hyperplasia varied from type I to type III. The progesterone/ estradiol ratio showed a significant variation in regard to the two types of piometra. However, it was not possible to corrrelate the etiological agent, the lesion and the hormonal levels with the open or closed pyometra

Phiclust: a clusterability measure for single-cell transcriptomics reveals phenotypic subpopulations

The ability to discover new cell phenotypes by unsupervised clustering of single-cell transcriptomes has revolutionized biology. Currently, there is no principled way to decide whether a cluster of cells contains meaningful subpopulations that should be further resolved. Here, we present phiclust (phi(clust)), a clusterability measure derived from random matrix theory that can be used to identify cell clusters with non-random substructure, testably leading to the discovery of previously overlooked phenotypes.Theoretical PhysicsBiological and Soft Matter Physic

A importância do potássio e da alimentação na regulação da pressão arterial

Publicação no âmbito do Programa Nacional para a Promoção da Alimentação Saudável da DGS