23 research outputs found

    A guanosine 5′-triphosphate-dependent protein kinase is localized in the outer envelope membrane of pea chloroplasts

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    A guanosine 5-triphosphate (GTP)-dependent protein kinase was detected in preparations of outer chloroplast envelope membranes of pea (Pisum sativum L.) chloroplasts. The protein-kinase activity was capable of phosphorylating several envelope-membrane proteins. The major phosphorylated products were 23- and 32.5-kilo-dalton proteins of the outer envelope membrane. Several other envelope proteins were labeled to a lesser extent. Following acid hydrolysis of the labeled proteins, most of the label was detected as phosphoserine with only minor amounts detected as phosphothreonine. Several criteria were used to distinguish the GTP-dependent protein kinase from an ATP-dependent kinase also present in the outer envelope membrane. The ATP-dependent kinase phosphorylated a very different set of envelope-membrane proteins. Heparin inhibited the GTP-dependent kinase but had little effect upon the ATP-dependent enzyme. The GTP-dependent enzyme accepted phosvitin as an external protein substrate whereas the ATP-dependent enzyme did not. The outer membrane of the chloroplast envelope also contained a phosphotransferase capable of transferring labeled phosphate from [-32P]GTP to ADP to yield (-32P]ATP. Consequently, addition of ADP to a GTP-dependent protein-kinase assay resulted in a switch in the pattern of labeled products from that seen with GTP to that typically seen with ATP

    Improving Genetic Prediction by Leveraging Genetic Correlations Among Human Diseases and Traits

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    Genomic prediction has the potential to contribute to precision medicine. However, to date, the utility of such predictors is limited due to low accuracy for most traits. Here theory and simulation study are used to demonstrate that widespread pleiotropy among phenotypes can be utilised to improve genomic risk prediction. We show how a genetic predictor can be created as a weighted index that combines published genome-wide association study (GWAS) summary statistics across many different traits. We apply this framework to predict risk of schizophrenia and bipolar disorder in the Psychiatric Genomics consortium data, finding substantial heterogeneity in prediction accuracy increases across cohorts. For six additional phenotypes in the UK Biobank data, we find increases in prediction accuracy ranging from 0.7 for height to 47 for type 2 diabetes, when using a multi-trait predictor that combines published summary statistics from multiple traits, as compared to a predictor based only on one trait. © 2018 The Author(s)

    Genome-wide association study identifies 30 Loci Associated with Bipolar Disorder

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    This paper is dedicated to the memory of Psychiatric Genomics Consortium (PGC) founding member and Bipolar disorder working group co-chair Pamela Sklar. We thank the participants who donated their time, experiences and DNA to this research, and to the clinical and scientific teams that worked with them. We are deeply indebted to the investigators who comprise the PGC. The views expressed are those of the authors and not necessarily those of any funding or regulatory body. Analyses were carried out on the NL Genetic Cluster Computer (http://www.geneticcluster.org ) hosted by SURFsara, and the Mount Sinai high performance computing cluster (http://hpc.mssm.edu).Bipolar disorder is a highly heritable psychiatric disorder. We performed a genome-wide association study including 20,352 cases and 31,358 controls of European descent, with follow-up analysis of 822 variants with P<1x10-4 in an additional 9,412 cases and 137,760 controls. Eight of the 19 variants that were genome-wide significant (GWS, p < 5x10-8) in the discovery GWAS were not GWS in the combined analysis, consistent with small effect sizes and limited power but also with genetic heterogeneity. In the combined analysis 30 loci were GWS including 20 novel loci. The significant loci contain genes encoding ion channels, neurotransmitter transporters and synaptic components. Pathway analysis revealed nine significantly enriched gene-sets including regulation of insulin secretion and endocannabinoid signaling. BDI is strongly genetically correlated with schizophrenia, driven by psychosis, whereas BDII is more strongly correlated with major depressive disorder. These findings address key clinical questions and provide potential new biological mechanisms for BD.This work was funded in part by the Brain and Behavior Research Foundation, Stanley Medical Research Institute, University of Michigan, Pritzker Neuropsychiatric Disorders Research Fund L.L.C., Marriot Foundation and the Mayo Clinic Center for Individualized Medicine, the NIMH Intramural Research Program; Canadian Institutes of Health Research; the UK Maudsley NHS Foundation Trust, NIHR, NRS, MRC, Wellcome Trust; European Research Council; German Ministry for Education and Research, German Research Foundation IZKF of Münster, Deutsche Forschungsgemeinschaft, ImmunoSensation, the Dr. Lisa-Oehler Foundation, University of Bonn; the Swiss National Science Foundation; French Foundation FondaMental and ANR; Spanish Ministerio de Economía, CIBERSAM, Industria y Competitividad, European Regional Development Fund (ERDF), Generalitat de Catalunya, EU Horizon 2020 Research and Innovation Programme; BBMRI-NL; South-East Norway Regional Health Authority and Mrs. Throne-Holst; Swedish Research Council, Stockholm County Council, Söderström Foundation; Lundbeck Foundation, Aarhus University; Australia NHMRC, NSW Ministry of Health, Janette M O'Neil and Betty C Lynch

    Tratamento térmico para controle da lanosidade em pêssegos 'Dourado-2' refrigerados Heat treatment to alleviation of woolliness of cold stored 'Dourado-2' peach

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    O objetivo deste trabalho foi avaliar o efeito de tratamentos térmicos na incidência de lanosidade em pêssegos 'Dourado-2' armazenados a 0ºC e na fisiologia e bioquímica dos frutos. Foram realizados condicionamentos térmicos antes da refrigeração, por meio da exposição dos frutos a 50ºC por 2 horas ou a 20ºC por 48 horas e do aquecimento intermitente durante o armazenamento refrigerado; os frutos foram submetidos a 25ºC durante 24 horas, a cada cinco dias de armazenamento a 0ºC, ou durante 48 horas, a cada dez dias de armazenamento a 0ºC. Frutos continuamente armazenados a 0ºC serviram de controle. Após 30 dias de armazenamento mais três dias de comercialização simulada, foram determinados os efeitos dos tratamentos sobre a incidência de lanosidade, podridões, teor de sólidos solúveis, acidez, teor de ácido ascórbico, coloração, firmeza da polpa, taxa respiratória, produção de etileno, atividade das enzimas poligalacturonase e pectinametilesterase. O aquecimento intermitente com ciclos de cinco ou dez dias e o condicionamento a 20ºC durante 48 horas foram mais eficazes para reduzir a incidência de lanosidade, mas acelerou a perda de firmeza dos frutos. A produção de etileno foi maior nos frutos submetidos a aquecimento intermitente. Os tratamentos térmicos provocaram poucas alterações no teor de sólidos solúveis, acidez, ácido ascórbico, coloração e incidência de podridões.<br>The work was carried out with the objective to verify the effect of heat treatments on the incidence of woolliness in 'Dourado-2' peaches stored at 0ºC. Heat treatments were applied as conditioning temperature (50ºC during 2 hours or 20ºC during 48 hours) before cold storage. In intermittent warming, fruit treatments were warmed each five days at 25ºC during 24 hours or each ten days during 48 hours. Control fruit were continuously stored at 0ºC. The variables evaluated after 30 days at 0ºC (plus three days at room temperature) were: incidence of woolliness and decay, soluble solids content (SSC), acidity, ascorbic acid, skin color, firmness, respiratory rate, ethylene production and activity of polygalacturonase (PG) and pectinmethylesterase (PME). The intermittent warming with cycles of five or ten days and the conditioning temperature at 20ºC during 48 hours before cold storage was the most effective treatment to reduce incidence of woolliness. However, heat treatment hastened fruit softening. Ethylene production was higher in fruits intermittently warmed and this can be related to the higher activity of PG and PME and consequently to alleviation of woolliness of the fruit. Heat treatment caused little variations on SSC, acidity, ascorbic acid and skin color

    Balanço eletrolítico para suínos machos castrados em crescimento mantidos em ambiente de alta temperatura Electrolyte balance of growing males castrated swines in a high temperature environment

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    Avaliou-se o efeito do balanço eletrolítico (BE) em rações com diferentes níveis de eletrólitos para suínos na fase de crescimento criados em alta temperatura. Foram utilizados 200 suínos machos castrados, com peso inicial de 25,3±1,3 kg e final de 68,8±3,4 kg, distribuídos em delineamento experimental inteiramente casualizado com cinco tratamentos e quatro repetições com dez animais por unidade experimental, para a fase de crescimento T1(testemunha) ração sem suplementação de eletrólitos 191 mEq/kg; T2 (NaHCO3) ração suplementada bicarbonato de sódio (NaHCO3) 250 mEq/kg; T3 (NaHCO3+KCl) ração suplementada NaHCO3 e cloreto de potássio (KCl) 250 mEq/kg; T4 (NaHCO3) ração suplementada NaHCO3 300 mEq/kg; e T5 (NaHCO3+KCl) ração suplementada com NaHCO3 e KCl 300 mEq/kg. As variáveis avaliadas foram consumo de ração, ganho de peso, consumo de nitrogênio, consumo de lisina, eficiência de utilização de nitrogênio para ganho, eficiência de utilização de lisina para ganho, conversão alimentar e os parâmetros fisiológicos, frequência respiratória e temperatura retal. Foi coletado sangue para mensurar as concentrações sorológicas de Na, Cl e K. A temperatura média foi 29,65±3,80º C com UR do ar 69,6±10,4%, Temperatura do Globo Negro de 31,95±1,98º C e Índice de Temperatura do Globo Úmido em 80,51±2,44. Os níveis de BE reduziram (P<0,05) consumo de ração e melhoram o consumo de nitrogênio. Os demais parâmetros de desempenho avaliados não foram afetados pelos diferentes balanços eletrolíticos (P>0,05). A correção do BE não influenciou o desempenho dos suínos.<br>The effect of electrolyte balance (EB) in diets with different levels of electrolytes for growing swine under high environmental temperature was evaluated. Two hundred castrated pigs with initial weight of 25.3±1.3 kg and final weight of 68.8±3.4 kg were allotted in a completely randomized experimental design with five treatments and four replicates with 10 pigs per experimental unit, for the growing phase T1 (control) diet without electrolyte 191 mEq/kg; T2 (NaHCO3) diet supplemented with sodium bicarbonate (NaHCO3) 250 mEq/kg; T3 (NaHCO3+KCl) diet supplemented with (NaHCO3) and potassium chloride (KCl) 250 mEq/kg; T4 (NaHCO3) diet supplemented with (NaHCO3) 300 mEq/kg; T5 (NaHCO3+KCl) diet supplemented with NaHCO3 and (KCl) 300 mEq/kg. The performance parameters evaluated were: feed intake, daily gain, nitrogen intake, lysine intake, efficiency of nitrogen use for weight gain, efficiency of lysine use for weight gain and the gain-to-feed ratio and the physiological parameters, respiratory frequency and rectal temperature. Blood was colleted to measure serum concentration of Na, Cl and K. The average temperature was 29.65±3.80º C with relative humidity of 69.6±10.4%, Black Globe Temperature of 31.95±1.98º C and temperature index calculated of 80.51±2.44. The levels of EB decreased (P<0.05) the feed intake and improved nitrogen intake. The other performance parameters evaluated were not influenced by the treatment (P>0.05). The correction of EB did not influence the growth of the swine
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