Recessive ataxia with ocular apraxia: review of 22 Portuguese patients.

Abstract BACKGROUND: The recessive ataxias are a heterogeneous group of neurodegenerative disorders characterized by cerebellar ataxia associated with a number of different neurologic, ophthalmologic, or general signs. They are often difficult to classify in clinical terms, except for Friedreich ataxia, ataxia-telangiectasia, and a relatively small group of rare conditions for which the molecular basis has already been defined. OBJECTIVES: To study the clinical presentation and to define diagnostic criteria in a group of Portuguese patients with ataxia and ocular apraxia, an autosomal recessive form without the essential clinical and laboratory features of ataxia-telangiectasia. PATIENTS AND METHODS: We reviewed 22 patients in 11 kindreds, identified through a systematic survey of hereditary ataxias being conducted in Portugal. RESULTS: Age at onset ranged from 1 to 15 years, with a mean of 4.7 years. The duration of symptoms at the time of last examination varied from 5 to 58 years. All patients presented with progressive cerebellar ataxia, the characteristic ocular apraxia, and a peripheral neuropathy. Associated neurologic signs included dystonia, scoliosis, and pes cavus. Magnetic resonance imaging was performed in 16 patients, all of whom showed cerebellar atrophy. CONCLUSIONS: Ataxia with ocular apraxia may be more frequent than postulated before, and may be identified clinically using the following criteria: (1) autosomal recessive transmission; (2) early onset (for most patients in early childhood); (3) combination of cerebellar ataxia, ocular apraxia, and early areflexia, with later appearance of the full picture of peripheral neuropathy; (4) absence of mental retardation, telangiectasia, and immunodeficiency; and (5) the possibility of a long survival, although with severe motor handicap

Pro-inflammatory polarization and colorectal cancer modulate alternative and intronic polyadenylation in primary human macrophages

Macrophages are essential cells of the immune system that alter their inflammatory profile depending on their microenvironment. Alternative polyadenylation in the 3'UTR (3'UTR-APA) and intronic polyadenylation (IPA) are mechanisms that modulate gene expression, in particular in cancer and activated immune cells. Yet, how polarization and colorectal cancer (CRC) cells microenvironment affect 3'UTR-APA and IPA in primary human macrophages remains unknown. Here, primary human monocytes were isolated from healthy donors, differentiated and polarized into a pro-inflammatory state and ChrRNA-Seq and 3'RNA-Seq were performed to quantify gene expression and characterize new 3’UTR-APA and IPA mRNA isoforms. Our results show that polarization of human macrophages from naïve to a pro-inflammatory state causes a marked increase both in proximal polyA site selection in the 3'UTR and in IPA events, in genes relevant for macrophage functions. Additionally, we found a negative correlation between differential gene expression and IPA during pro-inflammatory polarization of primary human macrophages. As macrophages are abundant immune cells in the CRC microenvironment that either promote or abrogate cancer progression, we investigated how indirect exposure to CRC cells affects macrophage gene expression and 3'UTR-APA and IPA mRNA events. Co-culture with CRC cells alters the inflammatory phenotype of macrophages, increases the expression of pro tumoral genes and induce 3’UTR-APA alterations. Notably, some of these gene expression differences were also found in tumour-associated macrophages of CRC patients, indicating that they are physiological relevant. Upon macrophage pro inflammatory polarization SRSF12 is the pre-mRNA processing gene that is most upregulated. After SRSF12 knockdown in M1 macrophages there is a global downregulation of gene expression, in particular in genes involved in gene expression regulation and in immune responses. Our results reveal new 48 3’UTR-APA and IPA mRNA isoforms produced during pro-inflammatory polarization of primary human macrophages and CRC co-culture that may be used in the future as diagnostic or therapeutic tools

Trinucleotide repeats in 202 families with ataxia: a small expanded (CAG)n allele at the SCA17 locus

BACKGROUND: Ten neurodegenerative disorders characterized by spinocerebellar ataxia (SCA) are known to be caused by trinucleotide repeat (TNR) expansions. However, in some instances the molecular diagnosis is considered indeterminate because of the overlap between normal and affected allele ranges. In addition, the mechanism that generates expanded alleles is not completely understood. OBJECTIVE: To examine the clinical and molecular characteristics of a large group of Portuguese and Brazilian families with ataxia to improve knowledge of the molecular diagnosis of SCA. PATIENTS AND METHODS: We have (1) assessed repeat sizes at all known TNR loci implicated in SCA; (2) determined frequency distributions of normal alleles and expansions; and (3) looked at genotype-phenotype correlations in 202 unrelated Portuguese and Brazilian patients with SCA. Molecular analysis of TNR expansions was performed using polymerase chain reaction amplification. RESULTS: Patients from 110 unrelated families with SCA showed TNR expansions at 1 of the loci studied. Dominantly transmitted cases had (CAG)(n) expansions at the Machado-Joseph disease gene (MJD1) (63%), at SCA2 (3%), the gene for dentatorubropallidoluysian atrophy (DRPLA) (2%), SCA6 (1%), or SCA7 (1%) loci, or (CTG)(n) expansions at the SCA8 (2%) gene, whereas (GAA)(n) expansions in the Freidreich ataxia gene (FRDA) were found in 64% of families with recessive ataxia. Isolated patients also had TNR expansions at the MJD1 (6%), SCA8 (6%), or FRDA (8%) genes; in addition, an expanded allele at the TATA-binding protein gene (TBP), with 43 CAGs, was present in a patient with ataxia and mental deterioration. Associations between frequencies of SCA2 and SCA6 and a frequency of large normal alleles were found in Portuguese and Brazilian individuals, respectively. Interestingly, no association between the frequencies of DRPLA and large normal alleles was found in the Portuguese group. CONCLUSIONS: Our results show that (1) a significant number of isolated cases of ataxia are due to TNR expansions; (2) expanded DRPLA alleles in Portuguese families may have evolved from an ancestral haplotype; and (3) small (CAG)(n) expansions at the TBP gene may cause SCA17

Produção de água para obtenção de alimentos em barragens subterrâneas no sertão de Pernambuco.

O presente trabalho tem como objetivo mostrar as experiências, com barragem subterrânea, de duas famílias agricultoras, na microrregião do Araripe, no Estado de Pernambuco, visando a estimular a multiplicação desta tecnologia no meio rural do semiárid

Pro-inflammatory polarization and colorectal cancer modulate alternative and intronic polyadenylation in primary human macrophages

Introduction: Macrophages are essential cells of the immune system that alter their inflammatory profile depending on their microenvironment. Alternative polyadenylation in the 3’UTR (3’UTR-APA) and intronic polyadenylation (IPA) are mechanisms that modulate gene expression, particularly in cancer and activated immune cells. Yet, how polarization and colorectal cancer (CRC) cells affect 3’UTR-APA and IPA in primary human macrophages was unclear. Methods: In this study, we isolated primary human monocytes from healthy donors, differentiated and polarized them into a pro-inflammatory state and performed indirect co-cultures with CRC cells. ChrRNA-Seq and 3’RNA-Seq was performed to quantify gene expression and characterize new 3’UTR-APA and IPA mRNA isoforms. Results: Our results show that polarization of human macrophages from naïve to a pro-inflammatory state causes a marked increase of proximal polyA site selection in the 3’UTR and IPA events in genes relevant to macrophage functions. Additionally, we found a negative correlation between differential gene expression and IPA during pro-inflammatory polarization of primary human macrophages. As macrophages are abundant immune cells in the CRC microenvironment that either promote or abrogate cancer progression, we investigated how indirect exposure to CRC cells affects macrophage gene expression and 3’UTR-APA and IPA events. Co-culture with CRC cells alters the inflammatory phenotype of macrophages, increases the expression of pro-tumoral genes and induces 3’UTR-APA alterations. Notably, some of these gene expression differences were also found in tumor-associated macrophages of CRC patients, indicating that they are physiologically relevant. Upon macrophage pro-inflammatory polarization, SRSF12 is the pre-mRNA processing gene that is most upregulated. After SRSF12 knockdown in M1 macrophages there is a global downregulation of gene expression, in particular in genes involved in gene expression regulation and in immune responses. Discussion: Our results reveal new 3’UTR-APA and IPA mRNA isoforms produced during pro-inflammatory polarization of primary human macrophages and CRC co-culture that may be used in the future as diagnostic or therapeutic tools. Furthermore, our results highlight a function for SRSF12 in pro-inflammatory macrophages, key cells in the tumor response

Parâmetros físico-químicos e microbiológicos do leite tipo A comercializado no Distrito Federal.

RESUMO: As alterações na qualidade do leite causam prejuízos econômicos à cadeia produtiva de leite e seus derivados e riscos à saúde dos consumidores. Nesse sentido este trabalho teve como objetivo analisar quatro marcas de leite pasteurizado tipo A integral comercializadas no Distrito Federal, entre 2015 e 2016. Foram realizadas análises físico-químicas, microbiológicas além de pesquisas de fraudes e de resíduos de antibióticos. Dentre as quatro marcas, apenas uma apresentou resultados em conformidade às análises físico-químicas, segundo os padrões estabelecidos pela IN Nº 76. As demais marcas apresentaram a adição de sacarose em 76,29% das amostras analisadas, índice crioscópico (50 %) e acidez (25 %). Nenhuma das marcas analisadas apresentaram microrganismos contaminantes e resultados positivos para resíduos de lactâmicose Tetracilinas

Resposta de Metamasius hemipterus a compostos sisntéticos atrativos testados em plantio de coqueiro anão-verde no estado do Ceará.

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Seleção de linhagens de feijoeiro-comum carioca com arquitetura ereta e escurecimento lento de grãos.

O objetivo desse trabalho foi identificar linhagens com escurecimento lento dos grãos, que associem arquitetura ereta e alta produtividade de grãos e verificar o efeito do ambiente no escurecimento dos grãos.CONAF

Levantamento do uso e cobertura da terra de seis áreas amostrais relacionadas ao Projeto BiosBrasil (Conservation and Sustainable Management of Below-Ground Biodiversity: phase I), Município de Benjamin Constant (AM).

O presente trabalho tem como objetivo identificar o uso e a cobertura da terra e sua distribuição espacial, utilizando técnicas de sensoriamento remoto, em seis áreas selecionadas para o estudo da biodiversidade do solo, reunir informações sobre a história do uso nas áreas amostradas e identificar a intensidade do uso da terra. Ele integra o projeto de pesquisa "Conservation and Sustainable Management of Below-Ground Biodiversity: Phase I" desenvolvido em sete países, financiado pelo Global Environment Facility (GEF) e implementado pelo United Nations Environment Programme (UNEP). A área de estudo no Brasil está localizada na Amazônia Ocidental, no município de Benjamin Constant, estado do Amazonas, e inclui seis áreas amostrais. As classes predominantes de uso e cobertura da terra são: floresta, floresta secundária, agrofloresta, agricultura e pastagem. Há três sistemas, os quais se baseiam predominantemente em a) produtos florestais, b) culturas anuais e c) produtos animais. As práticas culturais empregadas são muito similares em cada um dos três sistemas identificados, indicando não haver diferenças acentuadas em termos de intensidade de uso em cada sistema. Em todos eles não são utilizados corretivos, fertilizantes ou produtos para controle de pragas e doenças, bem como irrigação. Os pontos amostrais classificados como agricultura diferem em relação às espécies cultivadas e histórico de uso, incluindo os períodos de pousio. Nos pontos amostrais sob sistema em que predominam culturas anuais, são mais freqüentes os pousios curtos a longos, com valores de R calculados entre 16,67 e 50,00. Somente um ponto amostral encontra-se sob sistema de cultura permanente, correspondendo a 5,6% de todos os pontos sob agricultura. Os pontos de agrofloresta apresentam diversidade no número de indivíduos e de espécies úteis.bitstream/CNPS-2010/14919/1/bpd71-2005-usocobertseisareasamostrais.pd