Mutational mechanism for DAB1 (ATTTC) n insertion in SCA37: ATTTT repeat lengthening and nucleotide substitution

Dynamic mutations by microsatellite instability are the molecular basis of a growing number of neuromuscular and neurodegenerative diseases. Repetitive stretches in the human genome may drive pathogenicity, either by expansion above a given threshold, or by insertion of abnormal tracts in nonpathogenic polymorphic repetitive regions, as is the case in spinocerebellar ataxia type 37 (SCA37). We have recently established that this neurodegenerative disease is caused by an (ATTTC)n insertion within an (ATTTT)n in a noncoding region of DAB1. We now investigated the mutational mechanism that originated the (ATTTC)n insertion within an ancestral (ATTTT)n . Approximately 3% of nonpathogenic (ATTTT)n alleles are interspersed by AT-rich motifs, contrarily to mutant alleles that are composed of pure (ATTTT)n and (ATTTC)n stretches. Haplotype studies in unaffected chromosomes suggested that the primary mutational mechanism, leading to the (ATTTC)n insertion, was likely one or more T>C substitutions in an (ATTTT)n pure allele of approximately 200 repeats. Then, the (ATTTC)n expanded in size, originating a deleterious allele in DAB1 that leads to SCA37. This is likely the mutational mechanism in three similar (TTTCA)n insertions responsible for familial myoclonic epilepsy. Because (ATTTT)n tracts are frequent in the human genome, many loci could be at risk for this mutational process.We are grateful to the families and individuals who participated in this work. We thank Patricia Ribeiro for technical assistance. This study was financed by Fundo Europeu de Desenvolvimento Regional (FEDER), through the COMPETE 2020 Operational Pro- gram for Competitiveness and Internationalization (POCI) of Portugal 2020, and by the Fundacão para a Ciência e a Tecnologia (FCT) and Ministério da Ciência, Tecnologia e Ensino Superior (Portugal), in the framework of the project POCI-01-0145-FEDER-029255; (PTDC/MED-GEN/29255/2017) to I.S. J.R.L. and C.L.O. were sup- ported by scholarships from PEst-C/SAU/LA0002/2013. S.M. is funded by the project IF/00930/2013/ CP1184/CT0002 from FCT. This work was also funded by the Porto Neurosciences and Neurologic Disease Research Initiative at the Instituto de Investigação e Inovação em Saúde (Norte-01-0145-FEDER- 000008), supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTU- GAL 2020 Partnership Agreement with FEDER

Factors associated with thrombocytopenia in severe leptospirosis (Weil's disease)

OBJECTIVE: This study was conducted to investigate factors associated with thrombocytopenia in a large cohort of patients with leptospirosis in an endemic area. METHODS: This retrospective study included 374 consecutive patients with leptospirosis who were admitted to tertiary hospitals in Fortaleza, Brazil. All patients had a diagnosis of severe leptospirosis (Weil's disease). Acute kidney injury was defined according to the RIFLE criteria. Thrombocytopenia was defined as a platelet coun

Nonlinear analysis of structural elements under unilateral contact constraints by a Ritz type approach.

A nonlinear modal solution methodology capable of solving equilibrium and stability problems of uni-dimensional structural elements (beams, columns and arches) with unilateral contact constraints is presented in this work. The contact constraints are imposed by an elastic foundation of the Winkler type, where special attention is given to the case in which the foundation reacts in compression only, characterizing the contact as unilateral. A Ritz type approach with moveable boundaries, where the coordinates defining the limits of the contact regions are considered as additional variables of the problem, is proposed to solve this class of unilateral contact problems. The methodology is illustrated by particular problems involving beams, beam-columns and arches, and the results are compared with available results obtained by finite element and mathematical programming techniques. It is concluded that the Ritz type approach proposed is particularly suited for the analysis of structural problems where the number, but not the length, of the contact regions between the bodies are known a priori. Therefore, it can substitute in these cases finite element applications and be used as a benchmark for more general and complex formulations as well

Barragem subterrânea: transformando vidas no Semiárido brasileiro.

Devido à irregularidade das chuvas, os agricultores do Semiárido estão sempre enfrentando riscos de perdas totais ou parciais de suas safras e de sua criação. A falta de água nas comunidades do meio rural proporciona baixa qualidade de vida, êxodo rural e insegurança alimentar devido a não obtenção da colheita e consumo de alimentos com agrotóxicos. A barragem funciona como um barramento de água subterrânea, proveniente das chuvas, através de uma parede/septo impermeável que pode ser construído com alvenaria ou com uma lona plástica, ambos eficientes, diferenciando principalmente em relação ao custo. Essa tecnologia vem promovendo grandes mudanças na realidade rural, principalmente por manter uma continuidade de produção durante o período seco, permitindo assim que os agricultores diversifiquem sua alimentação e comercializem os excedentes, gerando renda e principalmente promovendo a segurança alimentar das famílias. O trabalho teve como objetivo construir o conhecimento coletivo através da pesquisa-ação, experimentação e sistematização para promover estratégias de usos eficientes e a manutenção da quantidade e qualidade da água de chuva em agroecossistemas com barragens subterrâneas nos territórios rurais do Semiárido do Nordeste Brasileiro. Os resultados deste estudo constituem oportunidade de aumento na eficiência da produção agropecuária nos agroecossistemas do sertão nordestino, aperfeiçoando a organização da família, proporcionando maior segurança alimentar pelo estímulo da diversificação do sistema produtivo e apropriação de novos conhecimentos. As barragens subterrâneas influenciam a sustentabilidade dos agroecossistemas do semiárido ao mesmo tempo em que cumpre um papel importante na democratização do acesso a água no semiárido, influenciando também, na dinâmica social destas comunidades

Identifying Variability in Process Performance Indicators

The performance perspective of business processes is concerned with the definition of performance requirements usually specified as a set of Process Performance Indicators (PPIs). Like other business process perspectives such as control-flow or data, there are cases in which PPIs are subject to variability. However, although the modelling of business process variability (BPV) has evolved significantly, there are very few contributions addressing the variability in the performance perspective of business processes. Modelling PPI variants with tools and techniques non-suitable for variability may generate redundant models, thus making it difficult its maintenance and future adaptations, also increasing possibility of errors in its managing. In this paper we present different cases of PPI variability detected as result of the analysis of several processes where BPV is present. Based on an existent metamodel used for defining PPIs over BPs, we propose its formal extension that allows the definition of PPI variability according to the cases identified.Ministerio de Economía y Competitividad TIN2015-70560-RJunta de Andalucía P12-TIC-1867Junta de Andalucía P10-TIC-590

Linear and non-linear perturbations in dark energy models

I review the linear and second-order perturbation theory in dark energy models with explicit interaction to matter in view of applications to N-body simulations and non-linear phenomena. Several new or generalized results are obtained: the general equations for the linear perturbation growth; an analytical expression for the bias induced by a species-dependent interaction; the Yukawa correction to the gravitational potential due to dark energy interaction; the second-order perturbation equations in coupled dark energy and their Newtonian limit. I also show that a density-dependent effective dark energy mass arises if the dark energy coupling is varying.Comment: 12 pages, submitted to Phys. Rev; v2: added a ref. and corrected a typ

Biometrical, biological, biochemical and molecular characteristics of Meloidogyne incognita isolates and related species.

Made available in DSpace on 2018-07-01T01:25:01Z (GMT). No. of bitstreams: 1 Santos2012ArticleBiometricalBiologicalBiochemic.pdf: 638119 bytes, checksum: 495622a30d001ee33809191979da7cde (MD5) Previous issue date: 2013-02-27bitstream/item/179299/1/Santos2012-Article-BiometricalBiologicalBiochemic.pd

Abundância e sazonalidade de cigarrinhas (Hemiptera, Cicadellidae, Cicadellinae) em vegetação herbácea de pomar de laranja doce, no município de Montenegro, Estado do Rio Grande do Sul, Brasil.

O presente estudo teve por objetivo conhecer a flutuação populacional e a constância de cicadelíneos presentes na vegetação herbácea de um pomar de laranja doce (Citrus sinensis (L.) Osbeck), variedade Valência, em Montenegro, RS. O levantamento foi realizado com a metodologia da rede-de-varredura, tendo início em fevereiro de 2001 e finalizando-se em janeiro de 2002. Mensalmente foram coletadas dez amostras, sendo cada uma destas composta por 50 golpes de rede em movimento de avanço sobre a vegetação herbácea e cultura intercalar nas entrelinhas do pomar (n = 500 golpes/ocasião de coleta). No total foram coletados 928 cicadelíneos,pertencentes a nove espécies: Bucephalogonia xanthophis (Berg, 1879), Diedrocephala variegata(Fabricius, 1775), Hortensia similis(Walker, 1851), Macugonalia leucomelas (Walker, 1851), Parathona gratiosa (Blanchard, 1840), Plesiommata corniculata Young,1977, Sibovia sagata (Signoret, 1854), Sonesimia grossa (Signoret, 1854) e Tapajosa rubromarginata (Signoret, 1855). O período de maior abundância da comunidade de cicadelíneos foi durante a primavera e o verão. Hortensia similis e M. leucomelas foram as únicas espécies consideradas constantes durante o levantamento. A menor abundância dos cicadelíneos em abril e dezembro provavelmente devese a efeitos causados por fatores abióticos (pluviosidade) e aqueles relativos à estrutura da vegetação (altura das plantas) sobre a comunidade