Tissue-specific regulation of IRS-1 in unilaterally nephrectomized rats

FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ – CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOInsulin stimulates the tyrosine kinase activity of its receptor, resulting in the phosphorylation of its cytosolic substrate, insulin receptor substrate 1 (IRS-1). IRS-1 is also a substrate for different peptides and growth factors, and a transgenic mouse knockout for this protein does not have normal growth. However, the role of IRS-1 in kidney hypertrophy and/or hyperplasia was not investigated. In the present study we investigated IRS-1 protein and tyrosine phosphorylation levels in the remnant kidney after unilateral nephrectomy (UNX) in 6-week-old male Wistar rats. After insulin stimulation the levels of insulin receptor and IRS-1 tyrosine phosphorylation were reduced to 79 ± 5% (P<0.005) and 58 ± 6% (P<0.0001), respectively, of the control (C) levels, in the remnant kidney. It is possible that a circulating factor and/or a local (paracrine) factor playing a role in kidney growth can influence the early steps of insulin action in parallel. To investigate the hypothesis of a circulating factor, we studied the early steps of insulin action in liver and muscle of unilateral nephrectomized rats. There was no change in pp185 tyrosine phosphorylation levels in liver (C 100 ± 12% vs UNX 89 ± 9%, NS) and muscle (C 100 ± 22% vs UNX 91 ± 17%, NS), and also there was no change in IRS-1 phosphorylation levels in both tissues. These data demonstrate that after unilateral nephrectomy there is a decrease in insulin-induced insulin receptor and IRS-1 tyrosine phosphorylation levels in kidney but not in liver and muscle. It will be of interest to investigate which factors, probably paracrine ones, regulate these early steps of insulin action in the contralateral kidney of unilaterally nephrectomized rats.Insulin stimulates the tyrosine kinase activity of its receptor, resulting in the phosphorylation of its cytosolic substrate, insulin receptor substrate 1 (IRS-1). IRS-1 is also a substrate for different peptides and growth factors, and a transgenic mouse knockout for this protein does not have normal growth. However, the role of IRS-1 in kidney hypertrophy and/or hyperplasia was not investigated. In the present study we investigated IRS-1 protein and tyrosine phosphorylation levels in the remnant kidney after unilateral nephrectomy (UNX) in 6-week-old male Wistar rats. After insulin stimulation the levels of insulin receptor and IRS-1 tyrosine phosphorylation were reduced to 79 ± 5% (P<0.005) and 58 ± 6% (P<0.0001), respectively, of the control (C) levels, in the remnant kidney. It is possible that a circulating factor and/or a local (paracrine) factor playing a role in kidney growth can influence the early steps of insulin action in parallel. To investigate the hypothesis of a circulating factor, we studied the early steps of insulin action in liver and muscle of unilateral nephrectomized rats. There was no change in pp185 tyrosine phosphorylation levels in liver (C 100 ± 12% vs UNX 89 ± 9%, NS) and muscle (C 100 ± 22% vs UNX 91 ± 17%, NS), and also there was no change in IRS-1 phosphorylation levels in both tissues. These data demonstrate that after unilateral nephrectomy there is a decrease in insulin-induced insulin receptor and IRS-1 tyrosine phosphorylation levels in kidney but not in liver and muscle. It will be of interest to investigate which factors, probably paracrine ones, regulate these early steps of insulin action in the contralateral kidney of unilaterally nephrectomized rats301011631167FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ – CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ – CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOsem informaçãosem informaçã

An activating mutation in the CRHR1 gene is rarely associated with pituitary-dependent hyperadrenocorticism in poodles

OBJECTIVES: Pituitary-dependent hyperadrenocorticism is the most common cause of naturally occurring hypercortisolism in dogs. CRHR1 expression in human and dog corticotrophinomas suggested that this gene affects pituitary tumorigenesis. The present study aimed to investigate mutations in the CRHR1 coding region in poodles with pituitary-dependent hyperadrenocorticism. METHODS: Fifty poodles with pituitary-dependent hyperadrenocorticism and 50 healthy poodles were studied. Genomic DNA was amplified by PCR and analyzed by Sanger sequencing. RESULTS: The novel CRHR1 p.V97M mutation was identified in one dog. This valine residue, located in the amino-terminal extracellular domain, exhibits high affinity for its corticotropin-releasing hormone (CRH) ligand. Bioinformatic analysis revealed structural rearrangements in the mutant protein, with a 17% increase in the surface binding affinity between CRHR1 and CRH. In vitro functional studies showed that mutant CRHR1 induced higher ACTH secretion than the wild type after stimulation with human CRH. CONCLUSION: These results suggest that germline activating mutations in CRHR1 may be a rare cause of pituitary hyperadrenocorticism in poodles

Study of ATLAS sensitivity to FCNC top decays

The ATLAS experiment sensitivity to top quark Flavour Changing Neutral Current (FCNC) decays was studied at LHC using ttbar events. While one of the top quarks is expected to follow the dominant Standard Model decay t->bW, the other decays through a FCNC channel, i.e. t-> Z u(c), t-> gamma u(c) or t-> g u(c). Different types of analyses, applied to each FCNC decay mode, were compared. The FCNC branching ratio sensitivity (assuming a 5sigma signal significance) and 95% confidence level limits on the branching ratios (in the hypothesis of signal absence) were obtained

Reliability and validity of body weight and body image perception in children and adolescents from the South American Youth/Child Cardiovascular and Environmental (SAYCARE) Study

Objective: To assess the reliability and validity of body weight (BW) and body image (BI) perception reported by parents (in children) and by adolescents in a South American population. Design: Cross-sectional study. BW perception was evaluated by the question, "Do you think you/your child are/is: severely wasted, wasted, normal weight, overweight, obese?" BI perception was evaluated using the Gardner scale. To evaluate reliability, BW and BI perceptions were reported twice, two weeks apart. To evaluate validity, the BW and BI perceptions were compared with WHO BMI Z-scores. Kappa and Kendall's tau-c coefficients were obtained. Setting: Public and private schools and high schools from six countries of South America (Argentina, Peru, Colombia, Uruguay, Chile, Brazil). Participants: Children aged 3-10 years (n 635) and adolescents aged 11-17 years (n 400). Results: Reliability of BW perception was fair in children's parents (k=0·337) and substantial in adolescents (k=0·709). Validity of BW perception was slight in children's parents (k=0·176) and fair in adolescents (k=0·268). When evaluating BI, most children were perceived by parents as having lower weight. Reliability of BI perception was slight in children's parents (k=0·124) and moderate in adolescents (k=0·599). Validity of BI perception was poor in children's parents (k=-0·018) and slight in adolescents (k=0·023). Conclusions: Reliability of BW and BI perceptions was higher in adolescents than in children's parents. Validity of BW perception was good among the parents of the children and adolescents with underweight and normal weight

Structural properties of mixed conductor Ba1−xGd1−yLax+yCo2O6−δ

BaGdLaCoO (BGLC) compositions with large compositional ranges of Ba, Gd, and La have been characterised with respect to phase compositions, structure, and thermal and chemical expansion. The results show a system with large compositional flexibility, enabling tuning of functional properties and thermal and chemical expansion. We show anisotropic chemical expansion and detailed refinements of emerging phases as La is substituted for Ba and Gd. The dominating phase is the double perovskite structure Pmmm, which is A-site ordered along the c-axes and with O vacancy ordering along the b-axis in the Ln-layer. Phases emerging when substituting La for Ba are orthorhombic Ba-deficient Pbnm and cubic LaCoO-based R3̄c. When La is almost completely substituted for Gd, the material can be stabilised in Pmmm, or cubic Pm3̄m, depending on thermal and atmospheric history. We list thermal expansion coefficients for x = 0-0.3, y = 0.2.The research has been supported by the National Science Centre Poland (2016/22/Z/ST5/00691), the Spanish Ministry of Science and Innovation (PCIN-2017-125, RTI2018-102161 and IJCI-2017-34110), and the Research Council of Norway (Grant no. 272797 “GoPHy MiCO”) through the M-ERA.NET Joint Call 2016. The authors acknowledge the skilful assistance from the staff of the Swiss–Norwegian Beamline (SNBL) at the European Synchrotron Radiation Facility (ESRF), Grenoble, France. Dr. Cheng Li at POWGEN, SNS, Oak Ridge, US and Dr. Chiu C. Tang at beamline I11 at Diamond, Didcot, UK are gratefully acknowledged for PND and SR-PXD measurements, respectively

Soil organisms in organic and conventional cropping systems.

Apesar do crescente interesse pela agricultura orgânica, são poucas as informações de pesquisa disponíveis sobre o assunto. Assim, num Argissolo Vermelho-Amarelo distrófico foram comparados os efeitos de sistemas de cultivo orgânico e convencional, para as culturas do tomate (Lycopersicum esculentum) e do milho (Zea mays), sobre a comunidade de organismos do solo e suas atividades. As populações de fungos,bactérias e actinomicetos, determinadas pela contagem de colônias em meio de cultura, foram semelhantes para os dois sistemas de produção. A atividade microbiana, avaliada pela evolução de CO2, manteve-se superior no sistema orgânico, sendo que em determinadas avaliações foi o dobro da evolução verificada no sistema convencional. O número de espécimes de minhoca foi praticamente dez vezes maior no sistema orgânico. Não foi observada diferença na taxa de decomposição de matéria orgânica entre os dois sistemas. De modo geral, o número de indivíduos de microartrópodos foi superior no sistema orgânico do que no sistema convencional, refletindo no maior índice de diversidade de Shannon. As maiores populações de insetos foram as da ordem Collembola, enquanto para os ácaros a maior população foi a da superfamília Oribatuloidea. Indivíduos dos grupos Aranae, Chilopoda, Dyplopoda, Pauropoda, Protura e Symphyla foram ocasionalmente coletados e de forma similar entre os sistemas