1,795 research outputs found

    Pertussis toxin induces structural changes in G alpha proteins independently of ADP-ribosylation.

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    Allelic database and accession divergence of a Brazilian mango collection based on microsatellite markers.

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    Allelic patterns and genetic distances were examined in a collection of 103 foreign and Brazilian mango (Mangifera indica) accessions in order to develop a reference database to support cultivar protection and breeding programs. An UPGMA dendrogram was generated using Jaccard coefficients from a distance matrix based on 50 alleles of 12 microsatellite loci. The base pair number was estimated by the method of inverse mobility. The cophenetic correlation was 0.8. The accessions had a coefficient of similarity of from 30 to 100%, which reflects high genetic variability. Three groups were observed in the UPGMA dendrogram; the first group was formed predominantly by foreign accessions, the second group was formed by Brazilian accessions, and the Dashehari accession was isolated from the others. The 50 microsatellite alleles did not separate all 103 accessions, indicating that there are duplicates in this mango collection. These 12 microsatellites need to be validated in order to establish a reliable set to identify mango cultivars

    The RNA-binding protein, ZFP36L2, influences ovulation and oocyte maturation

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    ZFP36L2 protein destabilizes AU-rich element-containing transcripts and has been implicated in female fertility. In the C57BL/6NTac mouse, a mutation in Zfp36l2 that results in the decreased expression of a form of ZFP36L2 in which the 29 N-terminal amino acid residues have been deleted, ΔN-ZFP36L2, leads to fertilized eggs that arrest at the two-cell stage. Interestingly, homozygous ΔN-Zfp36l2 females in the C57BL/6NTac strain release 40% fewer eggs than the WT littermates (Ramos et al., 2004), suggesting an additional defect in ovulation and/or oocyte maturation. Curiously, the same ΔN-Zfp36l2 mutation into the SV129 strain resulted in anovulation, prompting us to investigate a potential problem in ovulation and oocyte maturation. Remarkably, only 20% of ΔN-Zfp36l2 oocytes in the 129S6/SvEvTac strain matured ex vivo, suggesting a defect on the oocyte meiotic maturation process. Treatment of ΔN-Zfp36l2 oocytes with a PKA inhibitor partially rescued the meiotic arrested oocytes. Furthermore, cAMP levels were increased in ΔN-Zfp36l2 oocytes, linking the cAMP/PKA pathway and ΔN-Zfp36l2 with meiotic arrest. Since ovulation and oocyte maturation are both triggered by LHR signaling, the downstream pathway was investigated. Adenylyl cyclase activity was increased in ΔN-Zfp36l2 ovaries only upon LH stimulation. Moreover, we discovered that ZFP36L2 interacts with the 3′UTR of LHR mRNA and that decreased expression levels of Zfp36l2 correlates with higher levels of LHR mRNA in synchronized ovaries. Furthermore, overexpression of ZFP36L2 decreases the endogenous expression of LHR mRNA in a cell line. Therefore, we propose that lack of the physiological down regulation of LHR mRNA levels by ZFP36L2 in the ovaries is associated with anovulation and oocyte meiotic arrest.Fil: Ball, Christopher B.. University of North Carolina; Estados UnidosFil: Rodriguez, Karina F.. National Institutes of Health; Estados UnidosFil: Stumpo, Deborah J.. National Institutes of Health; Estados UnidosFil: Ribeiro Neto, Fernando. National Institutes of Health; Estados UnidosFil: Korach, Kenneth S.. National Institutes of Health; Estados UnidosFil: Blackshear, Perry J.. University of Duke; Estados Unidos. National Institutes of Health; Estados UnidosFil: Birnbaumer, Lutz. National Institutes of Health; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ramos, Silvia B. V.. University of North Carolina; Estados Unido

    Genotype-phenotype correlations and BH4 estimated responsiveness in patients with phenylketonuria from Rio de Janeiro, Southeast Brazil

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    Background: Genetic heterogeneity and compound heterozygosis give rise to a continuous spectrum of phenylalanine hydroxylase deficiency and metabolic phenotypes in phenylketonuria (PKU). The most used parameters for evaluating phenotype in PKU are pretreatment phenylalanine (Phe) levels, tolerance for dietary Phe, and Phe overloading test. Phenotype can vary from a "classic" (severe) form to mild hyperphenylalaninemia, which does not require dietary treatment. A subset of patients is responsive to treatment by the cofactor tetrahydrobiopterin (BH4 ). Genotypes of PKU patients from Rio de Janeiro, Brazil, were compared to predicted and observed phenotypes. Genotype-based estimations of responsiveness to BH4 were also conducted. Methods: Phenotype was defined by pretreatment Phe levels. A standard prediction system based on arbitrary assigned values was employed to measure genotype-phenotype concordance. Patients were also estimated as BH4 -responders according to the responsiveness previously reported for their mutations and genotypes. Results: A 48.3% concordance rate between genotype-predicted and observed phenotypes was found. When the predicted phenotypes included those reported at the BIOPKU database, the concordance rate reached 77%. A total of 18 genotypes from 30 patients (29.4%) were estimated as of potential or probable BH4 responsiveness. Inconsistencies were observed in genotypic combinations including the common "moderate" mutations p.R261Q, p.V388M, and p.I65T and the mild mutations p.L48S, p.R68S, and p.L249F. Conclusion: The high discordance rate between genotype-predicted and observed metabolic phenotypes in this study seems to be due partially to the high frequency of the so-called "moderate" common mutations, p.R261Q, p.V388M, and p.I65T, which are reported to be associated to erratic or more severe than expected metabolic phenotypes. Although our results of BH4 estimated responsiveness must be regarded as tentative, it should be emphasized that genotyping and genotype-phenotype association studies are important in selecting patients to be offered a BH4 overload test, especially in low-resource settings like Brazil.Dr. Vieira Neto reports two public grants from Coordination for the Improvement of Higher Level Personnel (Capes) of the Ministry of Education, Brazil, and private grants from FBM Pharmaceutical Industry Ltd., Anápolis, Goiás, Brazil, and from Danone Ltd., São Paulo, Brazil, during the conduct of the study.info:eu-repo/semantics/publishedVersio

    Transformer-based language models for semantic search and mobile applications retrieval

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    Search engines are being extensively used by Mobile App Stores, where millions of users world-wide use them every day. However, some stores still resort to simple lexical-based search engines, despite the recent advances in Machine Learning, Information Retrieval, and Natural Language Processing, which allow for richer semantic strategies. This work proposes an approach for semantic search of mobile applications that relies on transformer-based language models, fine-tuned with the existing textual information about known mobile applications. Our approach relies solely on the application name and on the unstructured textual information contained in its description. A dataset of about 500 thousand mobile apps was extended in the scope of this work with a test set, and all the available textual data was used to fine-tune our neural language models. We have evaluated our models using a public dataset that includes information about 43 thousand applications, and 56 manually annotated non- exact queries. The results show that our model surpasses the performance of all the other retrieval strategies reported in the literature. Tests with users have confirmed the performance of our semantic search approach, when compared with an existing deployed solution.info:eu-repo/semantics/acceptedVersio

    Da ação colagoga da cinarína

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    Da ação diurética da cinarína e de sua obtenção em estado cristalino

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