Mecanismo de ação não-genômico dos hormônios tireoidianos em testículos de ratos imaturos: efeitos eletrofisiológicos e captação de 45Ca2+

Dissertação (mestrado) - Universidade Federal de Santa Catarina, Centro de Ciências da Saúde. Programa de Pós-Graduação em Farmácia.Os hormônios tireoidianos (HT) regulam a esteroidogênese e a espermatogênese. O mecanismo clássico de ação dos HT ocorre através da ligação com receptores nucleares específicos. Todavia, as iodotironinas podem atuar por vias não-genômicas ou extranucleares, caracterizadas pela rapidez da resposta (de segundos a minutos), e desta forma sinalizam distintas vias de regulação celular. O objetivo do presente estudo foi estudar o envolvimento dos canais de cloreto no efeito hiperpolarizante do T4 em células de Sertoli de túbulos seminíferos de ratos imaturos, e investigar a ação dos HT na captação de cálcio em testículos de ratos imaturos, assim como a caracterização das vias de entrada deste íon estimuladas por iodotironinas. Para isto foram utilizadas as técnicas eletrofisiológica e de captação de 45Ca2+. Nos estudos eletrofisiológicos, os túbulos seminíferos foram mantidos em uma câmara de perfusão com KRb a 32 ºC, pH 7,4 em atmosfera carbogênica (O2:CO2; 95:5 v/v). Quando usado o ácido carboxílico 9-antraceno (9-AC), este era adicionado e após 30 segundos o T4, e o potencial transmembrana monitorado. Para a captação de 45Ca2+, os testículos foram pré-incubados e incubados em KRb na presença de 0,2 µCi 45Ca2+ a 32 ºC, pH 7,4; mantidos em atmosfera carbogênica (O2:CO2, 95:5 v/v). O T3 ou T4 foram adicionados no meio de incubação. Quando usados inibidores, estes eram adicionados 15 minutos antes do hormônio. O efeito hiperpolarizante do T4 foi bloqueado totalmente na presença de 9-AC, indicando o envolvimento de canais de cloreto nesta ação do T4. Este hormônio também estimulou a captação de 45Ca2+, efeito não evidenciado para o T3 nos tempos e doses estudados. O uso de nifedipina e flunarizina, bloqueadores dos canais de Ca2+ dependentes de tensão (CCDT) tipo L e T, respectivamente, bloquearam a ação estimulatória do T4. Este estímulo também foi bloqueado pelo antagonista de canal de K+ dependente de Ca2+, apamina, e pelo 9-AC, antagonista de canal de Cl-, sugerindo um mecanismo de retroalimentação entre o Ca2+ e Cl- e/ou Ca2+ e K+. O inibidor de proteína cinase A (PKA), KT 5720, inibiu completamente o efeito do T4, indicando a ativação desta via no mecanismo de entrada do Ca2+ estimulada por T4. No entanto, este efeito não foi alterado pelo uso de cloreto de estearoilcarnitina, inibidor de proteína cinase C, sendo que este inibidor demonstrou um efeito per se estimulando a captação de 45Ca2+. Destes resultados pode-se concluir que os canais de Cl- são importantes mediadores da ação hiperpolarizante do hormônio T4 em células de Sertoli. O influxo de 45Ca2+ modulado por T4 é dirigido por correntes de canais de cálcio dependentes de tensão, Cl- e K+, bem como, pela atividade da PKA, sinalizando uma via imediata de ação do T4 na membrana plasmática

La conscience morphologique est-elle une variable importante dans l’apprentissage de la lecture?

Le présent article est une revue synthétique des travaux portant sur lesliens entre conscience morphologique et apprentissage de la lecture. Cettesynthèse permet de confirmer que la conscience morphologique contribuebien à l’apprentissage de la lecture (tant au niveau de l’installation deshabiletés de décodage qu’au niveau du développement de la compréhension).Toutefois, il semble que ce ne sont pas tout à fait les mêmes aspects de la conscience morphologique qui sont liés aux capacités de décodage et aux capacités de compréhension. Des recherches doivent donc être développées pour mieux appréhender les rôles respectifs de chacune des composantes de la conscience morphologique

La conscience morphologique est-elle une variable importante dans l’apprentissage de la lecture?

Le présent article est une revue synthétique des travaux portant sur lesliens entre conscience morphologique et apprentissage de la lecture. Cettesynthèse permet de confirmer que la conscience morphologique contribuebien à l’apprentissage de la lecture (tant au niveau de l’installation deshabiletés de décodage qu’au niveau du développement de la compréhension).Toutefois, il semble que ce ne sont pas tout à fait les mêmes aspects de la conscience morphologique qui sont liés aux capacités de décodage et aux capacités de compréhension. Des recherches doivent donc être développées pour mieux appréhender les rôles respectifs de chacune des composantes de la conscience morphologique

Receptores e função do estrógeno no sistema reprodutor masculino

A substantial advance in our understanding on the estrogen signaling occurred in the last decade. Estrogens interact with two receptors, ESR1 and ESR2, also known as ERα and ERβ, respectively. ESR1 and ESR2 belong to the nuclear receptor family of transcription factors. In addition to the well established transcriptional effects, estrogens can mediate rapid signaling, triggered within seconds or minutes. These rapid effects can be mediated by ESRs or the G protein-coupled estrogen receptor GPER, also known as GPR30. The effects of estrogen on cell proliferation, differentiation and apoptosis are often mediated by growth factors. The understanding of the cross-talk between androgen, estrogen and growth factors signaling pathways is therefore essential to understand the physiopathological mechanisms of estrogen action. In this review we focused on recent discoveries about the nature of the estrogen receptors, and on the signaling and function of estrogen in the male reproductive system.Durante a última década, ocorreu um avanço substancial no conhecimento da sinalização do estrógeno. Estrógenos interagem com dois receptores, ESR1 e ESR2, também conhecidos como ERα e ERβ, respectivamente. ESR1 e ESR2 pertencem à família de receptores nucleares, que funcionam como fatores de transcrição. Além dos bem estabelecidos efeitos transcricionais, os estrógenos medeiam a sinalização rápida, desencadeada dentro de segundos ou minutos. Esses efeitos rápidos podem ser mediados por ESRs ou pelo receptor de estrógeno acoplado à proteína G, GPER, também conhecido como GPR30. Os efeitos de estrógenos sobre a proliferação celular, diferenciação e apoptose são, muitas vezes, mediados por fatores de crescimento. Portanto, a compreensão da interação entre as vias de sinalização de andrógeno, estrógeno e fatores de crescimento é essencial para entender os mecanismos fisiopatológicos envolvidos na ação estrogênica. Nesta revisão, foram abordadas descobertas recentes sobre a estrutura dos receptores, a sinalização e a função do estrógeno no sistema reprodutor masculino.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de FarmacologiaUNIFESP, EPM, Depto. de FarmacologiaSciEL

GQ-16, a TZD-derived partial PPARγ agonist, induces the expression of thermogenesis- related genes in brown fat and visceral white fat and decreases visceral adiposity in obese and hyperglycemic mice

Background Beige adipocytes comprise a unique thermogenic cell type in the white adipose tissue (WAT) of rodents and humans, and play a critical role in energy homeostasis. In this scenario, recruitment of beige cells has been an important focus of interest for the development of novel therapeutic strategies to treat obesity. PPARγ activation by full agonists (thiazolidinediones, TZDs) drives the appearance of beige cells, a process so-called browning of WAT. However, this does not translate into increased energy expenditure, and TZDs are associated with weight gain. Partial PPARγ agonists, on the other hand, do not induce weight gain, but have not been shown to drive WAT browning. The present study was designed to investigate the effects of GQ-16 on BAT and on browning of WAT in obese mice. Methods Male Swiss mice with obesity and hyperglycemia induced by high fat diet were treated with vehicle, rosiglitazone (4 mg/kg/d) or the TZD-derived partial PPARγ agonist GQ-16 (40 mg/ kg/d) for 14 days. Fasting blood glucose, aspartate aminotransferase, alanine aminotransferase and lipid profile were measured. WAT and brown adipose tissue (BAT) depots were excised for determination of adiposity, relative expression of Ucp-1, Cidea, Prdm16, Cd40 and Tmem26 by RT-qPCR, histological analysis, and UCP-1 protein expression analysis by immunohistochemistry. Liver samples were also removed for histological analysis and determination of hepatic triglyceride content. Results GQ-16 treatment reduced high fat diet-induced weight gain in mice despite increasing energy intake. This was accompanied by reduced epididymal fat mass, reduced liver triglyceride content, morphological signs of increased BAT activity, increased expression of thermogenesis- related genes in interscapular BAT and epididymal WAT, and increased UCP-1 protein expression in interscapular BAT and in epididymal and inguinal WAT. Conclusion This study suggests for the first time that a partial PPARγ agonist may increase BAT activity and induce the expression of thermogenesis-related genes in visceral WAT. General Significance These findings suggest that PPARγ activity might be modulated by partial agonists to induce WAT browning and treat obesity

Development of a Multivariate Prediction Model for Early-Onset Bronchiolitis Obliterans Syndrome and Restrictive Allograft Syndrome in Lung Transplantation.

Chronic lung allograft dysfunction and its main phenotypes, bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS), are major causes of mortality after lung transplantation (LT). RAS and early-onset BOS, developing within 3 years after LT, are associated with particularly inferior clinical outcomes. Prediction models for early-onset BOS and RAS have not been previously described. LT recipients of the French and Swiss transplant cohorts were eligible for inclusion in the SysCLAD cohort if they were alive with at least 2 years of follow-up but less than 3 years, or if they died or were retransplanted at any time less than 3 years. These patients were assessed for early-onset BOS, RAS, or stable allograft function by an adjudication committee. Baseline characteristics, data on surgery, immunosuppression, and year-1 follow-up were collected. Prediction models for BOS and RAS were developed using multivariate logistic regression and multivariate multinomial analysis. Among patients fulfilling the eligibility criteria, we identified 149 stable, 51 BOS, and 30 RAS subjects. The best prediction model for early-onset BOS and RAS included the underlying diagnosis, induction treatment, immunosuppression, and year-1 class II donor-specific antibodies (DSAs). Within this model, class II DSAs were associated with BOS and RAS, whereas pre-LT diagnoses of interstitial lung disease and chronic obstructive pulmonary disease were associated with RAS. Although these findings need further validation, results indicate that specific baseline and year-1 parameters may serve as predictors of BOS or RAS by 3 years post-LT. Their identification may allow intervention or guide risk stratification, aiming for an individualized patient management approach

The wide-field, multiplexed, spectroscopic facility WEAVE : survey design, overview, and simulated implementation

Funding for the WEAVE facility has been provided by UKRI STFC, the University of Oxford, NOVA, NWO, Instituto de Astrofísica de Canarias (IAC), the Isaac Newton Group partners (STFC, NWO, and Spain, led by the IAC), INAF, CNRS-INSU, the Observatoire de Paris, Région Île-de-France, CONCYT through INAOE, Konkoly Observatory (CSFK), Max-Planck-Institut für Astronomie (MPIA Heidelberg), Lund University, the Leibniz Institute for Astrophysics Potsdam (AIP), the Swedish Research Council, the European Commission, and the University of Pennsylvania.WEAVE, the new wide-field, massively multiplexed spectroscopic survey facility for the William Herschel Telescope, will see first light in late 2022. WEAVE comprises a new 2-degree field-of-view prime-focus corrector system, a nearly 1000-multiplex fibre positioner, 20 individually deployable 'mini' integral field units (IFUs), and a single large IFU. These fibre systems feed a dual-beam spectrograph covering the wavelength range 366-959 nm at R ∼ 5000, or two shorter ranges at R ∼ 20,000. After summarising the design and implementation of WEAVE and its data systems, we present the organisation, science drivers and design of a five- to seven-year programme of eight individual surveys to: (i) study our Galaxy's origins by completing Gaia's phase-space information, providing metallicities to its limiting magnitude for ∼ 3 million stars and detailed abundances for ∼ 1.5 million brighter field and open-cluster stars; (ii) survey ∼ 0.4 million Galactic-plane OBA stars, young stellar objects and nearby gas to understand the evolution of young stars and their environments; (iii) perform an extensive spectral survey of white dwarfs; (iv) survey  ∼ 400 neutral-hydrogen-selected galaxies with the IFUs; (v) study properties and kinematics of stellar populations and ionised gas in z 1 million spectra of LOFAR-selected radio sources; (viii) trace structures using intergalactic/circumgalactic gas at z > 2. Finally, we describe the WEAVE Operational Rehearsals using the WEAVE Simulator.PostprintPeer reviewe

The wide-field, multiplexed, spectroscopic facility WEAVE: Survey design, overview, and simulated implementation

WEAVE, the new wide-field, massively multiplexed spectroscopic survey facility for the William Herschel Telescope, will see first light in late 2022. WEAVE comprises a new 2-degree field-of-view prime-focus corrector system, a nearly 1000-multiplex fibre positioner, 20 individually deployable 'mini' integral field units (IFUs), and a single large IFU. These fibre systems feed a dual-beam spectrograph covering the wavelength range 366$-$959\,nm at $R\sim5000$, or two shorter ranges at $R\sim20\,000$. After summarising the design and implementation of WEAVE and its data systems, we present the organisation, science drivers and design of a five- to seven-year programme of eight individual surveys to: (i) study our Galaxy's origins by completing Gaia's phase-space information, providing metallicities to its limiting magnitude for $\sim$3 million stars and detailed abundances for $\sim1.5$ million brighter field and open-cluster stars; (ii) survey $\sim0.4$ million Galactic-plane OBA stars, young stellar objects and nearby gas to understand the evolution of young stars and their environments; (iii) perform an extensive spectral survey of white dwarfs; (iv) survey $\sim400$ neutral-hydrogen-selected galaxies with the IFUs; (v) study properties and kinematics of stellar populations and ionised gas in $z<0.5$ cluster galaxies; (vi) survey stellar populations and kinematics in $\sim25\,000$ field galaxies at $0.3\lesssim z \lesssim 0.7$; (vii) study the cosmic evolution of accretion and star formation using $>1$ million spectra of LOFAR-selected radio sources; (viii) trace structures using intergalactic/circumgalactic gas at $z>2$. Finally, we describe the WEAVE Operational Rehearsals using the WEAVE Simulator.Comment: 41 pages, 27 figures, accepted for publication by MNRA

The wide-field, multiplexed, spectroscopic facility WEAVE: Survey design, overview, and simulated implementation

WEAVE, the new wide-field, massively multiplexed spectroscopic survey facility for the William Herschel Telescope, will see first light in late 2022. WEAVE comprises a new 2-degree field-of-view prime-focus corrector system, a nearly 1000-multiplex fibre positioner, 20 individually deployable 'mini' integral field units (IFUs), and a single large IFU. These fibre systems feed a dual-beam spectrograph covering the wavelength range 366−959\,nm at R∼5000, or two shorter ranges at R∼20000. After summarising the design and implementation of WEAVE and its data systems, we present the organisation, science drivers and design of a five- to seven-year programme of eight individual surveys to: (i) study our Galaxy's origins by completing Gaia's phase-space information, providing metallicities to its limiting magnitude for ∼3 million stars and detailed abundances for ∼1.5 million brighter field and open-cluster stars; (ii) survey ∼0.4 million Galactic-plane OBA stars, young stellar objects and nearby gas to understand the evolution of young stars and their environments; (iii) perform an extensive spectral survey of white dwarfs; (iv) survey ∼400 neutral-hydrogen-selected galaxies with the IFUs; (v) study properties and kinematics of stellar populations and ionised gas in z1 million spectra of LOFAR-selected radio sources; (viii) trace structures using intergalactic/circumgalactic gas at z>2. Finally, we describe the WEAVE Operational Rehearsals using the WEAVE Simulator

Effects of strogen receptors activation in the regulation and function of rat Sertoli cells

BV UNIFESP: Teses e dissertaçõe