Bromodomain and Extraterminal Inhibition by JQ1 Produces Divergent Transcriptional Regulation of Suppressors of Cytokine Signaling Genes in Adipocytes

© Endocrine Society 2019. All rights reserved. For permissions, please e-mail: [email protected]. The Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway has cell-specific functions. Suppressors of cytokine signaling (SOCS) proteins are negative-feedback regulators of JAK-STAT signaling. STAT5 plays a significant role in adipocyte development and function, and bromodomain and extraterminal (BET) proteins may be involved in STAT5 transcriptional activity. We treated 3T3-L1 adipocytes with the BET inhibitor JQ1 and observed that growth hormone (GH)-induced expression of 2 STAT5 target genes from the SOCS family, Socs3 and Cish, were inversely regulated (increased and decreased, respectively) by BET inhibition. Chromatin immunoprecipitation analyses revealed that changes in STAT5 binding did not correlate with gene expression changes. GH promoted the recruitment of the BET protein BRD2 to the Cish, but not Socs3, promoter. JQ1 treatment ablated this effect as well as the GH-induced binding of ribonucleic acid polymerase II (RNA Pol II) to the Cish transcription start site. BRD2 knockdown also suppressed GH induction of Cish, further supporting the role of BRD2 in Cish transcriptional activation. In contrast, JQ1 increased the binding of activated Pol II to the Socs3 coding region, suggesting enhanced messenger RNA (mRNA) elongation. Our finding that JQ1 transiently reduced the interaction between the positive transcription elongation factor (P-TEFb) and its inhibitor hexamethylene bis-acetamide inducible 1 (HEXIM1) is consistent with a previously described off-target effect of JQ1, whereby P-TEFb becomes more available to be recruited by genes that do not depend on BET proteins for activating transcription. These results demonstrate substantially different transcriptional regulation of Socs3 and Cish and suggest distinct roles in adipocytes for these 2 closely related proteins

Delayed epistaxis secondary to intracavernous pseudoaneurysm of internal carotid artery

Post-traumatic pseudoaneurysm of the internal carotid artery is a very rare but potentially fatal cause of epistaxis. Early diagnosis is essential for an adequate management of this entity. The authors present a case of pseudoaneurysm of the internal carotid artery that developed massive epistaxis six months after skull base trauma.Pseudoaneurisma traumático da artéria carótida interna é uma causa rara de epistaxe, porém potencialmente fatal. O diagnóstico precoce é essencial para um adequado manejo da patologia. Os autores relatam um caso de pseudoaneurisma da carótida interna que se apresentou como epistaxe maciça após seis meses de trauma craniano prévio.Hospital do Servidor Público do Estado de São Paulo Serviço de Otorrinolaringologia/Cabeça e PescoçoUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de MedicinaUNIFESP, EPMSciEL

Subglottic stenosis as a clinical manifestation of Wegener's granulomatosis in adolescents: report of a case and review of literature

Wegener's Granulomatosis is a well-characterized systemic vasculitis and necrotising granulomatous inflammation of the upper, lower respiratory tracts and the kidneys. The initial manifestations of the disease usually occur in patients over than twenty years old. The otolaryngologic symptoms like rhinorrhea, recurrent sinusitis and epistaxis are commonly present in early course of the disease. It seems that subglottic stenosis is correlated to Wegener's granumatosis in adolescents. We describe a case of a patient that developed subglottic stenosis associated with Wegener's granulomatosis in childhood during the course of the disease.A Granulomatose de Wegener é uma patologia caracterizada por vasculite sistêmica e inflamação granulomatosa necrotizante que compromete o trato respiratório alto, pulmões e rins, cujas manifestações iniciais, na maioria das vezes, ocorre em maiores de 20 anos de idade. As queixas clínicas otorrinolaringológicas estão, com freqüência, presentes nas fases iniciais da doença, sendo rinite, sinusopatia de repetição e epistaxe as mais comuns. A estenose subglógica parece estar correlacionada com a Granulomatose de Wegener em adolescentes. Relatamos o caso de uma paciente portadora de Granulomatose de Wegener cujo início dos sintomas foi na infância, tendo evoluído com estenose laríngea durante o curso da doença.Hospital do Servidor Público do Estado de São Paulo Serviço de Otorrinolaringologia/Cabeça e PescoçoFaculdade de Medicina de São Paulo Divisão de Clínica OtorrinolaringológicaUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de MedicinaUNIFESP, EPMSciEL

A partial factors methodology for structural safety assessment in non-linear analysis

In the present structural codes the safety verification is based on a linear analysis of the structure and the satisfaction of ultimate and serviceability limit states, using a semi-probabilistic security format through the consideration of partial safety factors, which affect the action values and the characteristic values of the material properties. In this context, if a non-linear structural analysis is wanted a difficulty arises, because the global safety coefficient, which could be obtained in a straightforward way from the non-linear analysis, is not directly relatable to the different safety coefficient values usually used for the different materials, as is the case for reinforced concrete structures. The work here presented aims to overcome this difficulty by proposing a methodology that generalises the format of safety verification based on partial safety factors, well established in structural codes within the scope of linear analysis, for cases where non-linear analysis is needed. The methodology preserves the principal assumptions made in the codes as well as a reasonable simplicity in its use, including a realistic definition of the material properties and the structural behaviour, and it is based on the evaluation of a global safety coefficient. Some examples are presented aiming to clarify and synthesise all the options that were taken in the application of the proposed methodology, namely how to transpose the force distributions obtained with a non-linear analysis into design force distributions. One of the most important features of the proposed methodology, the ability for comparing the simplified procedures for second order effects evaluation prescribed in the structural codes, is also presented in a simple and systematic way. The potential of the methodology for the development and assessment of alternative and more accurate procedures to those already established in codes of practice, where non-linear effects must be considered, is also indicated

Influence of psychosocial risk factors on the trajectory of mental health problems from childhood to adolescence: a longitudinal study

Background\ud Longitudinal epidemiological studies involving child/adolescent mental health problems are scarce in developing countries, particularly in regions characterized by adverse living conditions. We examined the influence of psychosocial factors on the trajectory of child/adolescent mental health problems (CAMHP) over time.\ud \ud Methods\ud A population-based sample of 6- to 13-year-olds with CAMHP was followed-up from 2002–2003 (Time 1/T1) to 2007–2008 (Time 2/T2), with 86 out of 124 eligible children/adolescents at T1 being reassessed at T2 (sample loss: 30.6%). Outcome: CAMHP at T2 according to the Child Behavior Checklist/CBCL’s total problem scale. Psychosocial factors: T1 variables (child/adolescent’s age, family socioeconomic status); trajectory of variables from T1 to T2 (child/adolescent exposure to severe physical punishment, mother exposure to severe physical marital violence, maternal anxiety/depression); and T2 variables (maternal education, child/adolescent’s social support and pro-social activities).\ud \ud Results\ud Multivariate analysis identified two risk factors for child/adolescent MHP at T2: aggravation of child/adolescent physical punishment and aggravation of maternal anxiety/depression.\ud \ud Conclusions\ud The current study shows the importance of considering child/adolescent physical punishment and maternal anxiety/depression in intervention models and mental health care policies.We thank all study participants, professionals and employees from the health centre where data were collected, Embu Health Secretariat and Mental Health Coordination, and all research team members of the Brazilian Studies of Abuse in the Family Environment (BrazilSAFE) and it’s Follow-Up Study for the valuable collaboration.The study was financially supported by the São Paulo State Research Foundation (Fundação de Amparo à Pesquisa do Estado de São Paulo/FAPESP – Process no. 00/14555-4) in 2002/2003 and by Mackpesquisa of the Mackenzie Presbyterian University in 2007

Preparation of biodegradable composite with palm heart agroindustry waste biomass.

Peach palm (Bactris gasipaes) is a multi-purpose palm tree, mainly utilized for food industry (fruits and palm core), being important cash income for smallholders. During the production process the palm core large amount of waste is generated and this can cause environmental problems. As a way to reuse the waste from peach palm agroindustry the aim this work was to produce biodegradable composites using different proportions (50, 55 e 60%) of peach palm residues (external sheaths) incorporated with polyurethane foam obtained from vegetable oils. Residues will be collected, dried in an oven at 65-70o C for 72 h, cut into small lengths on a Wiley mill and sifted through a mesh 35(500 ?m). Then, incorporated with polyurethane rigid foam derived from vegetable oil. Both the raw materials and their composites will be characterized. Composites produced from the residues of the palm heart agroindustry have adequate thermo-mechanical characteristics, being a water-resistant and thermo-stable material

Late Aptian paleoclimate reconstruction of the Brazilian equatorial margin: inferences from palynology

This study conducted high-resolution paleoclimatic analyses based on the identification of palynological groups of late Aptian age (biozone Sergipea veriverrucata) in the Bragança and Codó formations within the Bragança–Viseu, São Luís, and Parnaíba basins. The analysis comprised 40 palynological samples, with 200 palynomorphs per slide counted when possible. Bioclimatic analysis was mainly supported by the identification of botanical affinities, and ecological and climatic parameters such as the wet/arid trend (Fs/X), Shannon–Wiener diversity, and indicator species analysis (IndVal) were used. Statistical analyses such as principal component and cluster analyses were employed to support the paleoclimatic interpretations. The study recognized 69 genera distributed among the main groups of living plants, including bryophytes, ferns, lycophytes, gymnosperms, and angiosperms. It was possible to attribute botanical affinity in 94.2 % of the taxa, and nine genera occurred in all sections studied: Afropollis, Araucariacites, Callialasporites, Cicatricosisporites, Classopollis, Cyathidites, Deltoidospora, Equisetosporites, and Verrucosisporites, with Classopollis being the most abundant. The stratigraphic distribution of the bioclimatic groups (hydrophytes, hygrophytes, lowland tropical flora, upland flora, and xerophytes) allowed for the identification of climatic phases: pre-evaporitic, evaporitic, and post-evaporitic. In the pre-evaporitic phase, the most significant abundances were between the hygrophytes and upland flora, indicating a certain level of humidity. Xerophytes were the most abundant in all phases, with a conspicuous increase in the evaporitic phase, reflecting an increase in aridity. In the post-evaporitic phase, there was a significant increase in the upland flora with the return of wetter conditions. This study confirmed an increasing humidity trend in the analyzed sections, probably owing to the influence of the Intertropical Convergence Zone that was already operating during the late Aptian.</p

Agricultura orgânica: quando o passado é futuro

Bibliografia: p. 33-34Apresenta-se a agricultura orgânica como uma retomada do uso de antigas práticas agrícolas, porém adaptando-as às mais modernas tecnologias de produção agropecuária com o objetivo de aumentar a produtividade e causar o mínimo de interferência nos ecossistemas, além de ser uma das alternativas para viabilizar a pequena propriedade. O estudo também procura identificar e analisar os principais entraves para o desenvolvimento do setor, como custos, crédito, embalagem, certificação, além de apresentar, de forma esquemática, o relacionamento entre os principais agentes da cadeia produtiva