Investigation of Gamma-aminobutyric acid (GABA) A receptors genes and migraine susceptibility

Background Migraine is a neurological disorder characterized by recurrent attacks of severe headache, affecting around 12% of Caucasian populations. It is well known that migraine has a strong genetic component, although the number and type of genes involved is still unclear. Prior linkage studies have reported mapping of a migraine gene to chromosome Xq 24–28, a region containing a cluster of genes for GABA A receptors (GABRE, GABRA3, GABRQ), which are potential candidate genes for migraine. The GABA neurotransmitter has been implicated in migraine pathophysiology previously; however its exact role has not yet been established, although GABA receptors agonists have been the target of therapeutic developments. The aim of the present research is to investigate the role of the potential candidate genes reported on chromosome Xq 24–28 region in migraine susceptibility. In this study, we have focused on the subunit GABA A receptors type ε (GABRE) and type θ (GABRQ) genes and their involvement in migraine. Methods We have performed an association analysis in a large population of case-controls (275 unrelated Caucasian migraineurs versus 275 controls) examining a set of 3 single nucleotide polymorphisms (SNPs) in the coding region (exons 3, 5 and 9) of the GABRE gene and also the I478F coding variant of the GABRQ gene. Results Our study did not show any association between the examined SNPs in our test population (P > 0.05). Conclusion Although these particular GABA receptor genes did not show positive association, further studies are necessary to consider the role of other GABA receptor genes in migraine susceptibility

SREB, a GATA Transcription Factor That Directs Disparate Fates in Blastomyces dermatitidis Including Morphogenesis and Siderophore Biosynthesis

Blastomyces dermatitidis belongs to a group of human pathogenic fungi that exhibit thermal dimorphism. At 22°C, these fungi grow as mold that produce conidia or infectious particles, whereas at 37°C they convert to budding yeast. The ability to switch between these forms is essential for virulence in mammals and may enable these organisms to survive in the soil. To identify genes that regulate this phase transition, we used Agrobacterium tumefaciens to mutagenize B. dermatitidis conidia and screened transformants for defects in morphogenesis. We found that the GATA transcription factor SREB governs multiple fates in B. dermatitidis: phase transition from yeast to mold, cell growth at 22°C, and biosynthesis of siderophores under iron-replete conditions. Insertional and null mutants fail to convert to mold, do not accumulate significant biomass at 22°C, and are unable to suppress siderophore biosynthesis under iron-replete conditions. The defect in morphogenesis in the SREB mutant was independent of exogenous iron concentration, suggesting that SREB promotes the phase transition by altering the expression of genes that are unrelated to siderophore biosynthesis. Using bioinformatic and gene expression analyses, we identified candidate genes with upstream GATA sites whose expression is altered in the null mutant that may be direct or indirect targets of SREB and promote the phase transition. We conclude that SREB functions as a transcription factor that promotes morphogenesis and regulates siderophore biosynthesis. To our knowledge, this is the first gene identified that promotes the conversion from yeast to mold in the dimorphic fungi, and may shed light on environmental persistence of these pathogens

The Complete Genome Sequence of Fibrobacter succinogenes S85 Reveals a Cellulolytic and Metabolic Specialist

Fibrobacter succinogenes is an important member of the rumen microbial community that converts plant biomass into nutrients usable by its host. This bacterium, which is also one of only two cultivated species in its phylum, is an efficient and prolific degrader of cellulose. Specifically, it has a particularly high activity against crystalline cellulose that requires close physical contact with this substrate. However, unlike other known cellulolytic microbes, it does not degrade cellulose using a cellulosome or by producing high extracellular titers of cellulase enzymes. To better understand the biology of F. succinogenes, we sequenced the genome of the type strain S85 to completion. A total of 3,085 open reading frames were predicted from its 3.84 Mbp genome. Analysis of sequences predicted to encode for carbohydrate-degrading enzymes revealed an unusually high number of genes that were classified into 49 different families of glycoside hydrolases, carbohydrate binding modules (CBMs), carbohydrate esterases, and polysaccharide lyases. Of the 31 identified cellulases, none contain CBMs in families 1, 2, and 3, typically associated with crystalline cellulose degradation. Polysaccharide hydrolysis and utilization assays showed that F. succinogenes was able to hydrolyze a number of polysaccharides, but could only utilize the hydrolytic products of cellulose. This suggests that F. succinogenes uses its array of hemicellulose-degrading enzymes to remove hemicelluloses to gain access to cellulose. This is reflected in its genome, as F. succinogenes lacks many of the genes necessary to transport and metabolize the hydrolytic products of non-cellulose polysaccharides. The F. succinogenes genome reveals a bacterium that specializes in cellulose as its sole energy source, and provides insight into a novel strategy for cellulose degradation

Factor mobility, government debt and the decline in public investment

Public investment, Factor mobility, Globalisation, Public debt, OECD, EU, H50, H63, H87,

Quality of life scale in parkinson's disease PDQ-39 - (Brazilian Portuguese version) to assess patients with and without levodopa motor fluctuation Escala para qualidade de vida na doença de Parkinson - PDQ 39 (versão do Português falado no Brasil) como instrumento para avaliação de pacientes com e sem flutuação motora decorrente da levodopa

Quality of life (QoL) is an important treatment outcome indicator in Parkinson's disease (PD). The aim of this study is to assess the usefulness of the Parkinson's disease questionnaire - PDQ-39 (Brazilian Portuguese Version) in measuring QoL of PD patients with or without motor fluctuations. Fifty-six PD patients with mean disease duration of 7.4 years were assessed and 41 of them (73.3%) had motor fluctuations. The PDQ-39 has eight dimensions ranging from 0 to 100; being the higher the score, the worse the QoL. Comparing groups with and without motor fluctuations showed that the dimensions mobility, activities of daily living (ADL), communication and bodily discomfort scored higher in the fluctuating group. There was a tendency to see that the higher the Hoehn and Yahr (HY) scale stages, the higher the PDQ-39 scores. Patients suffering from the disease for more than five years had worse PDQ-39 scores only in the items ADL and communication, when compared with those with the disease for < 5 years. The PDQ-39 is an instrument that detects decrease in QoL of PD patients and the presence of motor fluctuations predicts QoL reduction.<br>A qualidade de vida (QdV) é um item importante para se mensurar o sucesso do tratamento na doença de Parkinson (DP). O objetivo deste estudo foi o de avaliar a utilidade do questionário sobre a doença de Parkinson - PDQ-39 (versão em língua portuguesa falada no Brasil) para mensurar a QdV dos pacientes parkinsonianos com e sem flutuação motora. Nós avaliamos 56 pacientes com DP com tempo médio da doença de 7,4 anos, e destes 41 (73,3%) apresentavam flutuação motora. A PDQ-39 tem oito domínios que variam de 0 a 100 e quanto maior o escore pior a QdV. A comparação dos grupos de pacientes com e sem flutuação motora mostrou que os domínios: mobilidade, atividades de vida diária, comunicação e desconforto corporal tinham escores maiores nos flutuadores. Quanto maiores os estágios de Hoehn e Yahr (HY) da doença, maiores os escores da PDQ-39. Pacientes com mais de 5 anos de evolução da doença mostraram escores piores da PDQ39 apenas nos itens atividades da vida diária e comunicação se comparados a pacientes com 5 anos ou menos de doença. A PDQ-39 é um instrumento capaz de detectar declínio da QdV de pacientes com DP e a presença de flutuação motora é um preditor para redução na QdV