Clinical and molecular phenotype of Aicardi-Goutières syndrome

Aicardi-Goutières syndrome (AGS) is a genetic encephalopathy whose clinical features mimic those of acquired in utero viral infection. AGS exhibits locus heterogeneity, with mutations identified in genes encoding the 3′→5′ exonuclease TREX1 and the three subunits of the RNASEH2 endonuclease complex. To define the molecular spectrum of AGS, we performed mutation screening in patients, from 127 pedigrees, with a clinical diagnosis of the disease. Biallelic mutations in TREX1, RNASEH2A, RNASEH2B, and RNASEH2C were observed in 31, 3, 47, and 18 families, respectively. In five families, we identified an RNASEH2A or RNASEH2B mutation on one allele only. In one child, the disease occurred because of a de novo heterozygous TREX1 mutation. In 22 families, no mutations were found. Null mutations were common in TREX1, although a specific missense mutation was observed frequently in patients from northern Europe. Almost all mutations in RNASEH2A, RNASEH2B, and RNASEH2C were missense. We identified an RNASEH2C founder mutation in 13 Pakistani families. We also collected clinical data from 123 mutation-positive patients. Two clinical presentations could be delineated: an early-onset neonatal form, highly reminiscent of congenital infection seen particularly with TREX1 mutations, and a later-onset presentation, sometimes occurring after several months of normal development and occasionally associated with remarkably preserved neurological function, most frequently due to RNASEH2B mutations. Mortality was correlated with genotype; 34.3% of patients with TREX1, RNASEH2A, and RNASEH2C mutations versus 8.0% RNASEH2B mutation-positive patients were known to have died (P = .001). Our analysis defines the phenotypic spectrum of AGS and suggests a coherent mutation-screening strategy in this heterogeneous disorder. Additionally, our data indicate that at least one further AGS-causing gene remains to be identified. © 2007 by The American Society of Human Genetics. All rights reserved.

A survey of DNA methylation across social insect species, life stages, and castes reveals abundant and caste-associated methylation in a primitively social wasp

DNA methylation plays an important role in the epigenetic control of developmental and behavioral plasticity, with connections to the generation of striking phenotypic differences between castes (larger, reproductive queens and smaller, non-reproductive workers) in honeybees and ants. Here, we provide the first comparative investigation of caste- and life stage-associated DNA methylation in several species of bees and vespid wasps displaying different levels of social organization. Our results reveal moderate levels of DNA methylation in most bees and wasps, with no clear relationship to the level of sociality. Strikingly, primitively social Polistes dominula paper wasps show unusually high overall DNA methylation and caste-related differences in site-specific methylation. These results suggest DNA methylation may play a role in the regulation of behavioral and physiological differences in primitively social species with more flexible caste differences. © 2013 Springer-Verlag Berlin Heidelberg.

Localização sub-celular de proteínas marcadas com GFP em Xanthomonas axonopodis pv. citri por microscopia de fluorescência

Pós-graduação em Ciências Biológicas (Microbiologia Aplicada) - IBRC

Achados anatomopatológicos em perdizes (Rhynchotus rufescens) criadas em cativeiro

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Serotonergic modulation in neuropathy induced by oxaliplatin: Effect on the 5HT(2C) receptor

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

O inventário portage operacionalizado e o desenvolvimento de bebês

O acompanhamento do desenvolvimento de bebês implica na consideração de fatores de risco para os mesmos e na utilização de instrumentos que possibilitem a identificação de defasagens, comportamentais, visando à elaboração de intervenções pontuais junto a pais e outros cuidadores. O presente estudo prendendeu descrever variáveis distais e proximais do desenvolvimento de uma amostra de bebês, a partir de suas características peculiares, bem como das dos seus familiares e avaliar o repertório comportamental dos bebês, correlacionando-o com variáveis de risco como prematuridade, baixo peso ao nascer e filhos de mães adolescentes, comparando-o com bebês sem condição de risco identificada. Pretendeu, também, identificar comportamentos típicos nas áres do desenvolvimento avaliadas pelo inventário portage operacionalizado, mês a mês, durante o primeiro ano de vida, utilizando os critérios de estabilização, normalização e aparecimento destes comportamentos entre os meninos e meninas. Participaram do estudo 217 bebês que foram avaliados no decorrer do primeiro ano de vida, sendo que 33% eram prematuros, 28% filhos de mães adolescentes, 11% com baixo peso nascidos a termo, 3% sindrômicos ou filhos de mães portadoras de HIV+ e 25% do Grupo Controle, sem condições de risco identificado no nascimento. Os dados foram coletados a partir da entrevista inicial e da avaliação mensal do inventário. Os dados foram coletados a partir da entrevista inicial e da aplicação mensal do inventário portage operacionalizado (IPO), em um Centro de Psicologia Aplicada de uma universidade pública. Os desempenhos dos bebês no IPO e as condições de risco identificadas foram submetidas ao tratamento por meio do Statistic Package Social for Science (SPSS, versão 12.0). para a identificação de comportamentos típicos utilizaram-se os critérios de Estabilização... (Resumo completo, clicar acesso eletrônico abaixo)

Flow sorting and exome sequencing reveal the oncogenome of primary Hodgkin and Reed-Sternberg cells

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

The genomes of two key bumblebee species with primitive eusocial organization

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Guidelines for the management and treatment of periodic fever syndromes Familial Mediterranean Fever

To establish guidelines based on scientific evidence for the management of familial Mediterranean fever. The Guideline was prepared from 5 clinical questions that were structured through PICO (Patient, Intervention or indicator, Comparison and Outcome), to search in key primary scientific information databases. After defining the potential studies to support the recommendations, these were graduated considering their strength of evidence and grade of recommendation. 10,341 articles were retrieved and evaluated by title and abstract; from these, 46 articles were selected to support the recommendations. 1. The diagnosis of FMF is based on clinical manifestations, characterized by recurrent febrile episodes associated with abdominal pain, chest or arthritis of large joints; 2. FMF is a genetic disease presenting an autosomal recessive trait, caused by mutation in the MEFV gene; 3. Laboratory tests are not specific, demonstrating high serum levels of inflammatory proteins in the acute phase of the disease, but also often showing high levels even between attacks. SAA serum levels may be especially useful in monitoring the effectiveness of treatment; 4. The therapy of choice is colchicine; this drug has proven effectiveness in preventing acute inflammatory episodes and progression towards amyloidosis in adults; 5. Based on the available information, the use of biological drugs appears to be an alternative for patients with FMF who do not respond or are intolerant to therapy with colchicine.

Population histories of right whales (Cetacea: Eubalaena) Inferred from Mitochondrial Sequence Diversities and Divergences of Their Whale Lice (Amphipoda: Cyamus)

Right whales carry large populations of three ‘whale lice’ (Cyamus ovalis, Cyamus gracilis, Cyamus erraticus) that have no other hosts. We used sequence variation in the mitochondrial COI gene to ask (i) whether cyamid population structures might reveal associations among right whale individuals and subpopulations, (ii) whether the divergences of the three nominally conspecific cyamid species on North Atlantic, North Pacific, and southern right whales (Eubalaena glacialis, Eubalaena japonica, Eubalaena australis) might indicate their times of separation, and (iii) whether the shapes of cyamid gene trees might contain information about changes in the population sizes of right whales. We found high levels of nucleotide diversity but almost no population structure within oceans, indicating large effective population sizes and high rates of transfer between whales and subpopulations. North Atlantic and Southern Ocean populations of all three species are reciprocally monophyletic, and North Pacific C. erraticus is well separated from North Atlantic and southern C. erraticus. Mitochondrial clock calibrations suggest that these divergences occurred around 6 million years ago (Ma), and that the Eubalaena mitochondrial clock is very slow. North Pacific C. ovalis forms a clade inside the southern C. ovalis gene tree, implying that at least one right whale has crossed the equator in the Pacific Ocean within the last 1–2 million years (Myr). Low-frequency polymorphisms are more common than expected under neutrality for populations of constant size, but there is no obvious signal of rapid, interspecifically congruent expansion of the kind that would be expected if North Atlantic or southern right whales had experienced a prolonged population bottleneck within the last 0.5 Myr.

Novel Relapsing Fever Spirochete in Bat Tick

Tick-borne relapsing fever in western North America is a zoonosis caused by spirochetes in the genus Borrelia that are transmitted by argasid ticks of the genus Ornithodoros (1). Human disease occurs in many focal areas and is associated with infections of Borrelia hermsii, B. turicatae, and possibly B. parkeri (2,3). Although the ecologic parameters that maintain B. hermsii and B. turicatae differ, human infections usually occur in rustic cabins (B. hermsii) and caves (B. turicatae) inhabited by ticks and their terrestrial vertebrate hosts (1). Recently, Gill et al. (4) provided evidence that the argasid bat tick, Carios kelleyi, feeds upon humans. Subsequently, Loftis et al. (5) used PCR analysis and DNA sequencing to detect in C. kelleyi an unidentifi ed Borrelia species that was closely related to B. turicatae and B. parkeri.

A preliminary linkage map of the tick, Ixodes scapularis

A linkage map of the Ixodes scapularis genome was constructed based upon segregation amongst 127 loci. These included 84 random amplified polymorphic DNA (RAPD) markers, 32 Sequence-Tagged RAPD (STAR) markers, 5 cDNAs, and 5 microsatellites in 232 F1 intercross progeny from a single, field-collected P1 female. A preliminary linkage map of 616 cM was generated across 14 linkage groups with one marker every 10.8 cM. Assuming a genome size of ∼109 bp, the relationship of physical to genetic distance is ∼300 kb/cM in the I. scapularis genome.