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1.
Front Pharmacol ; 14: 1254561, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37818190

RESUMO

Background: Since antiquity, alternative herbal remedies, such as S. africana caerulea/Blue Sage (BLS) water infusion extract (WIE) has been used by traditional healers, for the effective treatment of various chronic inflammatory disorders associated with reduced cellular antioxidant defense mechanisms and free radical cellular damage. In the heart, ischaemia-reperfusion (I/R) induced oxidative stress becomes an early crucial event in the pathogenesis of ischaemia-reperfusion injury (I/RI) and subsequent heart failure. Purpose/Aim: To investigate whether BLS WIE treatment during ischaemia and/or reperfusion may be cardioprotective. Study design: Isolated perfused rat hearts were exposed to 35 min regional ischaemia (RI) and 60 min reperfusion. The BLS WIE was applied: i) for the last 10 min of RI (PerT) or ii) from onset of reperfusion (PostT) or iii) both (PerT) + (PostT). Methods: Endpoints were functional recovery and infarct size (IS). In another set of experiments, left ventricles were freeze-clamped after RI and 10 min reperfusion for detection of total and phosphorylated p-ERK p44/p42, p-Akt, p-p38-MAPK, p-JNK, Nrf-2, NF-kB, Bax, Bcl-2, Caspase-3, and PGC-1α by Western blot analysis. Results: BLS (PostT) significantly increased ERK p44, p-Akt, Nrf-2, and Bcl-2 levels; significantly decreased p-p38-MAPK as well as p-JNK p46 phosphorylation; did not affect Bax levels and significantly decreased Bax/Bcl-2 ratios. This was associated with significantly reduced Caspase-3 levels and increased PGC-1α phosphorylation, particlarly when BLS WIE was administered as PostT. Conclusion: The administration of polyphenol-rich BLS WIE at different stages of ischaemia and/or reperfusion, activate/inhibit several signaling events simultaneously and mediate cardioprotection in a multitarget manner.

2.
DST j. bras. doenças sex. transm ; 33: 1-6, dez.30, 2021.
Artigo em Inglês | LILACS | ID: biblio-1344700

RESUMO

Introduction: Aiming at strengthening the discourse about syphilis prevention and promoting organic actions with strategies directed to digital communication platforms, the campaign "Eu sei. Você sabe?" ("I know. Do you?") was developed and placed between mid 2020 and early 2021, within the scope of the project "Sífilis, não" ('Syphilis, No'). Objective: In this article, we aim to report the planning and execution of this public communication campaign to combat syphilis by reflecting on the aspects of conception, strategic and creative planning, and placement of the campaign. Methods: The reflection was anchored in a descriptive study and in the report of this experience through a scientific narrative, considering the guidelines established in the planning and the period of execution (still under development). Results: The results of this campaign include the production and placement of various materials for digital circulation to disseminate content, such as cards (posts) for different social media websites in different formats; layouts for posters, banners and handouts (printed and digital); institutional website; card videos; sound spots; layouts for digital booklets and newsletters, among others. Conclusion: From the point of view of planning and production, the goal of the campaign was to contemplate the diversity of audiences with actions and materials, by adapting imagery, language and communication channels. It is not yet feasible to measure the reach or the audience size and response, although we can project it as positive in view of its context.


Visando ao fortalecimento do discurso de prevenção à sífilis e de promoção de ações de comunicação orgânicas com estratégias voltadas para plataformas de comunicação digital, foi desenvolvida a campanha "Eu sei. Você sabe?", entre o segundo semestre de 2020 e o primeiro de 2021, no âmbito do projeto "Sífilis Não". Objetivo: Neste artigo, objetivamos relatar a experiência das etapas do planejamento à execução dessa campanha de comunicação pública de combate à sífilis. Para tanto, refletimos sobre aspectos que envolvem desde a concepção, percorrendo as planificações estratégicas e criativas, até a veiculação da referida campanha. Métodos: Essa reflexão ancora-se em estudo descritivo e no relato de experiência como narrativa científica, levando em conta as diretrizes estabelecidas no planejamento e o período de execução (ainda em desenvolvimento). Resultados: Constituem-se como resultados dessa campanha a produção e a veiculação de diversos materiais direcionados para a circulação digital, com vista à divulgação de conteúdo, a saber: cards (publicações) para diferentes sites de redes sociais em formatos variados; layouts para cartazes, banners e panfletos (impressos e digitais); site institucional; vídeos cartelados; spots sonoros; layouts para cartilhas digitais e newsletters, entre outros. Conclusão: É possível verificar que a campanha "Eu sei. Você sabe?", do ponto de vista do planejamento e da produção, buscou contemplar, nas ações e peças, a diversidade dos públicos, adequando aspectos imagéticos, de linguagem e de canais de comunicação. Quanto à dimensão da audiência, ou seja, da repercussão, ainda não é viável mensurá-la, embora possamos projetar que será possível considerá-la positiva, em face do contexto de sua realização.


Assuntos
Humanos , Sífilis , Publicidade , Rede Social , Infecções Sexualmente Transmissíveis , Saúde Pública , Política de Saúde
3.
J Acquir Immune Defic Syndr ; 88(5): 477-486, 2021 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-34506343

RESUMO

BACKGROUND: Out-of-facility multi-month dispensing (MMD) is a differentiated service delivery model which provides antiretroviral treatment (ART) at intervals of up to 6 monthly in the community. Limited randomized evidence investigating out-of-facility MMD is available. We evaluated participant outcomes and compared out-of-facility MMD models using data from cluster-randomized trials in Southern Africa. SETTING: Eight districts in Zimbabwe and Lesotho. METHODS: Individual-level participant data from 2 cluster-randomized trials that included stable adults receiving ART at 60 facilities were pooled. Both trials had 3 arms: ART collected 3-monthly at healthcare facilities (3MF, control); ART provided three-monthly in community ART groups (CAGs) (3MC); and ART provided 6-monthly in either CAGs or on an individual provider-patient basis (6MC). Participant retention, viral suppression and incidence of unscheduled facility visits were compared. RESULTS: Ten thousand one hundred thirty-six participants were included, 3817 (37.7%), 2893 (28.5%) and 3426 (33.8%) in arms 3MF, 3MC and 6MC, respectively. After 12 months, retention was non-inferior for 3MC (95.7%) vs. 3MF (95.0%) {adjusted risk difference (aRD) = 0.3 [95% confidence interval (CI): -0.8 to 1.4]}; and 6MC (95.1%) vs. 3MF [aRD = -0.2 (95% CI: -1.4 to 1.0)]. Retention was greater amongst intervention arm participants in CAGs versus 6MC participants not in CAGs, aRD = 1.5% (95% CI: 0.2% to 2.9%). Viral suppression was excellent (≥98%) and unscheduled facility visits were not increased in the intervention arms. CONCLUSIONS: Three and 6-monthly out-of-facility MMD was non-inferior versus facility-based care for stable ART patients. Out-of-facility 6-monthly MMD should incorporate small group peer support whenever possible. CLINICALTRIAL REGISTRATION: ClinicalTrials.gov NCT03238846 and NCT03438370.


Assuntos
Terapia Antirretroviral de Alta Atividade , Infecções por HIV/tratamento farmacológico , Adolescente , Adulto , África Austral , Fármacos Anti-HIV/uso terapêutico , COVID-19 , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Retenção nos Cuidados , Fatores de Tempo , Adulto Jovem
5.
RECIIS (Online) ; 13(3): 457-470, jul.-set. 2019. ilus
Artigo em Português | LILACS | ID: biblio-1016410

RESUMO

Este artigo discute a emergência de iniciativas ciberativistas centradas na representação política LGBT, assim como a sua contribuição para a consolidação das demandas do movimento e para o aprofundamento da democracia. Com abordagem qualitativa e procedimento monográfico, objetiva-se compreender a atuação da campanha #VoteLGBT, desenvolvida nas redes de comunicação digital distribuída nas eleições de 2014 e 2016. Delimitam-se, como corpus, as ferramentas sociais digitais utilizadas e os conteúdos das publicações realizadas no Facebook. Conclui-se que a iniciativa #VoteLGBT produz uma tripla visibilização (das candidaturas para os eleitores; dos eleitores para os candidatos; das demandas e temáticas para os candidatos e eleitores); expõe desigualdades políticas veladas no próprio regime democrático; cumpre a função, ao usar ferramentas digitais, de aproximar as dimensões civil e política em uma mesma ambiência; busca, ao produzir conteúdo, sensibilizar e convocar os eleitores, demonstrando a legitimidade das pautas e a importância da participação e da representação política.


This article discusses the emergence of cyberactivist initiatives centered on LGBT political representation and its contribution to the consolidation of demands required by that movement and to deepen the democracy. With a qualitative approach and monographic procedure, the objective of this study is to understand the performance of the #VoteLGBT campaign, developed in distributed digital communication networks before the Brazilian elections in 2014 and 2016. It was delimited as corpus the digital social tools used to those campaigns and the contents of the information posted in Facebook. We concluded that the #VoteLGBT initiative produces a triple visibility (of candidates to voters, of voters to candidates, of demands and themes to candidates and voters); exposes veiled political inequalities in the democratic regime itself; in using digital tools, it fulfills the function of approaching the civil and political dimensions in the same environment; in producing content, it seeks to sensitize the voters to LGBT's issues and to choose their representant, demonstrating the legitimacy of those issues and the importance of political participation and representation.


Este artículo discute la emergencia de iniciativas ciberactivistas centradas en la representación política LGBT y su contribución para la consolidación de las demandas del movimiento y para la profundización de la democracia. Con un enfoque cualitativo y un procedimiento monográfico, el objetivo del estudio es comprender la actuación de la campaña #VoteLGBT, desarrollada en redes de comunicación digital distribuida antes de las elecciones brasileñas de 2014 y 2016. Delimitamos como corpus las herramientas sociales digitales utilizadas en las campañas y los contenidos de las informaciones publicadas en Facebook. Concluimos que la iniciativa #VoteLGBT produce una triple visibilidad (de candidatos para votantes, de votantes para candidatos, de demandas y temas para candidatos y votantes); expone desigualdades políticas veladas en el proprio régimen democrático; al emplear herramientas digitales, cumple la función de acercar las dimensiones civil y política en el mismo ambiente; al producir contenido, busca sensibilizar los votantes para las cuestiones LGBT y para elegir sus candidatos , demostrando la legitimidad de los temas y la importancia de la participación y representación política.


Assuntos
Humanos , Acesso à Informação , Minorias Sexuais e de Gênero , Redes Sociais Online , Política , Brasil , Comunicação , Democracia , Disseminação de Informação , Identidade de Gênero
8.
J Physician Assist Educ ; 27(4): 156-161, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27820784

RESUMO

PURPOSE: Medical simulation has recently been used in medical education, and evidence indicates that it is a valuable tool for teaching and evaluation. Very few studies have evaluated the integration of medical simulation in medical physiology education, particularly in PA programs. This study was designed to assess the value of integrating medical simulation into the PA physiology curriculum. METHODS: Seventy-five students from the PA program at Central Michigan University participated in this study. Mannequin-based simulation was used to simulate a patient with hemorrhagic shock and congestive heart failure to demonstrate the Frank-Starling force and cardiac function curve. Before and after the medical simulation, students completed a questionnaire as a self-assessment. A knowledge test was also delivered after the simulation. RESULTS: Our study demonstrated a significant improvement in student confidence in understanding congestive heart failure, hemorrhagic shock, and the Frank-Starling curve after the simulation. CONCLUSIONS: Medical simulation may be an effective way to enhance basic science learning experiences for students and an ideal supplement to traditional, lecture-based teaching in PA education.


Assuntos
Manequins , Assistentes Médicos/educação , Fisiologia/educação , Treinamento por Simulação , Currículo , Autorrelato
9.
J Physician Assist Educ ; 27(2): 51-5, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27123595

RESUMO

PURPOSE: This research surveyed physician assistant (PA) program admissions personnel to determine how the Central Application Service for Physician Assistants (CASPA) personal statements are used, what influence the statements had on certain admissions processes, whether there was any concern about authorship of the statements, and how important certain previously identified content themes were to admissions committees and personnel. METHODS: The PA programs participating in CASPA were contacted and interviewed using a computer-assisted telephone interview system. Participants were asked a series of open-ended questions related to the usefulness of the personal statement and asked to score certain items using a Likert-type scale. RESULTS: The response rate for the telephone survey was 75%. Most of the programs (93%) used the personal statement in the applicant review process, and almost two-thirds (62%) indicated that the statement was useful or very useful. Three-fourths (76%) of respondents sometimes or always used the statement for the selection of candidates for interviews. Only 29% of respondents were very to extremely concerned that the statements were not written by the applicants. CONCLUSIONS: Despite the observation that the statements were relatively homogeneous in content, respondents ranked identified content themes as an important influence on decision-making. Almost all respondents used the personal statement in their admissions process, usually in the selection of interviewees. Although there was some concern that the statements were not the original work of the applicant, less than a third of respondents were very concerned about this possibility. The homogeneity of the statements was also a concern, but the importance placed on the identified theme content areas validates the applicants' inclusion of these themes in the statements.


Assuntos
Assistentes Médicos/educação , Critérios de Admissão Escolar , Humanos , Entrevistas como Assunto , Estados Unidos , Redação
10.
Mol Plant Pathol ; 16(3): 251-61, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25040464

RESUMO

Dollar spot, caused by Sclerotinia homoeocarpa, is a prevalent turfgrass disease, and the fungus exhibits widespread fungicide resistance in North America. In a previous study, an ABC-G transporter, ShatrD, was associated with practical field resistance to demethylation inhibitor (DMI) fungicides. Mining of ABC-G transporters, also known as pleiotropic drug resistance (PDR) transporters, from RNA-Seq data gave an assortment of transcripts, several with high sequence similarity to functionally characterized transporters from Botrytis cinerea, and others with closest blastx hits from Aspergillus and Monilinia. In addition to ShatrD, another PDR transporter showed significant over-expression in replicated RNA-Seq data, and in a collection of field-resistant isolates, as measured by quantitative polymerase chain reaction. These isolates also showed reduced sensitivity to unrelated fungicide classes. Using a yeast complementation system, we sought to test the hypothesis that this PDR transporter effluxes DMI as well as chemically unrelated fungicides. The transporter (ShPDR1) was cloned into the Gal1 expression vector and transformed into a yeast PDR transporter deletion mutant, AD12345678. Complementation assays indicated that ShPDR1 complemented the mutant in the presence of propiconazole (DMI), iprodione (dicarboximide) and boscalid (SDHI, succinate dehydrogenase inhibitor). Our results indicate that the over-expression of ShPDR1 is correlated with practical field resistance to DMI fungicides and reduced sensitivity to dicarboximide and SDHI fungicides. These findings highlight the potential for the eventual development of a multidrug resistance phenotype in this pathogen. In addition, this study presents a pipeline for the discovery and validation of fungicide resistance genes using de novo next-generation sequencing and molecular biology techniques in an unsequenced plant pathogenic fungus.


Assuntos
Ascomicetos/fisiologia , Farmacorresistência Fúngica/efeitos dos fármacos , Proteínas Fúngicas/metabolismo , Fungicidas Industriais/farmacologia , Proteínas de Membrana Transportadoras/metabolismo , Aminoimidazol Carboxamida/análogos & derivados , Aminoimidazol Carboxamida/farmacologia , Ascomicetos/efeitos dos fármacos , Ascomicetos/genética , Ascomicetos/isolamento & purificação , Compostos de Bifenilo/farmacologia , Resistência à Doença/efeitos dos fármacos , Proteínas Fúngicas/genética , Regulação Fúngica da Expressão Gênica/efeitos dos fármacos , Teste de Complementação Genética , Hidantoínas/farmacologia , Modelos Lineares , Proteínas de Membrana Transportadoras/genética , Niacinamida/análogos & derivados , Niacinamida/farmacologia , Filogenia , Doenças das Plantas/imunologia , Doenças das Plantas/microbiologia , Reação em Cadeia da Polimerase , Saccharomyces cerevisiae/efeitos dos fármacos , Análise de Sequência de RNA , Transcriptoma/genética , Triazóis/farmacologia
11.
J Water Health ; 12(3): 418-25, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25252345

RESUMO

The recovery of microorganisms to different fabrics was evaluated after a washing process combined with a food-grade non-oxidizing acidic formulation and low washing water temperature. Cotton, polyester and a polyester/cotton blend fabric samples were inoculated with Escherichia coli, Listeria innocua and Saccharomyces cerevisiae, then dried for 1 day. They were separately placed in a simulated fabric washer and decontaminated for 1 and 10 min with the acidic formulation at 23 °C water washing temperature. The combination of direct detecting and dilution methods was used to detect survivors on fabrics. The use of ≥ 0.1% acidic formulation in the washing process significantly increased the efficacy of the washing for all fabric samples. Microorganisms on the cotton and mixed fabric appeared to bind more strongly and were more resistant to the washing process. No viability was observed on the fabric swatches at 1 cfu/sample detection limit when the washing process was combined with 0.5% acidic formulation in the 10 min washing cycle. These findings can be used to increase the efficiency of sanitizing fabrics in an environmentally friendly way, for remove harmful microorganisms from them and reduce cross-contamination.


Assuntos
Benzenossulfonatos/farmacologia , Ácido Cítrico/farmacologia , Microbiologia Ambiental , Escherichia coli , Listeria , Saccharomyces cerevisiae , Têxteis/microbiologia , Aderência Bacteriana , Contagem de Colônia Microbiana , Relação Dose-Resposta a Droga , Escherichia coli/efeitos dos fármacos , Escherichia coli/isolamento & purificação , Humanos , Lavanderia , Listeria/efeitos dos fármacos , Listeria/isolamento & purificação , Saccharomyces cerevisiae/efeitos dos fármacos , Saccharomyces cerevisiae/isolamento & purificação , Tensoativos/farmacologia , Temperatura
12.
G3 (Bethesda) ; 4(4): 761-7, 2014 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-24558266

RESUMO

The overproduction and secretion of inositol (i.e., Opi(-)) phenotype is associated with defects in regulation of phospholipid biosynthesis in yeast. Here we report a screen of the essential yeast gene set using a conditional-expression library. This screen identified novel functions previously unknown to affect phospholipid synthesis.


Assuntos
Genes Essenciais , Inositol/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/genética , Análise por Conglomerados , Histona Acetiltransferases/genética , Histona Acetiltransferases/metabolismo , Fenótipo , Fosfolipídeos/biossíntese , Proteínas de Saccharomyces cerevisiae/metabolismo
13.
J Physician Assist Educ ; 25(4): 43-6, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25622374

RESUMO

PURPOSE: Personal statements are a required component of the Central Application Service for Physician Assistants (CASPA) application package submitted to physician assistant (PA) programs that participate in the service. Prior research involving the use of personal statements in the selection process of graduate and professional programs has found a significant amount of homogeneity within the statements. This study sought to determine the major theme content and frequency of occurrence of these themes in the personal statements submitted by applicants to a Midwestern PA program. METHODS: After receiving signed consent, personal statements were extracted from the application packages of 63 students. Statements were identified with a random number. Each statement was reviewed and content themes were identified and manually coded by two separate reviewers. The reviewers and primary investigator then met and determined the major content categories by consensus. RESULTS: The review identified seven major content themes. Four of these themes were present in 70% or more of the statements: health care experience, altruism, patient interaction, medical profession. CONCLUSION: The personal statements reviewed contained similar content, confirming prior research that these statements may follow some formula for success. This may be evidence that applicants feel these attributes demonstrate that they are qualified candidates for admission. Further study should be conducted to see how these statements are used in the PA program admissions process.


Assuntos
Assistentes Médicos/educação , Assistentes Médicos/psicologia , Critérios de Admissão Escolar/estatística & dados numéricos , Humanos , Meio-Oeste dos Estados Unidos
14.
JAAPA ; 26(10): 46-50, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24201923

RESUMO

Physician assistants (PAs) are more frequently finding themselves in positions where they are responsible for staff recruitment and retention. Staff turnover is associated with significant financial costs for organizations. Motivational theories focusing on job design indicate that paying attention to a combination of factors related to the work itself, in addition to the environment where the work is performed, increases satisfaction. This study asked a convenience sample of practicing PAs to rate the importance of a number of work-related factors known to influence job satisfaction. The results may be used as a basis for designing an environment to increase job satisfaction and improve recruitment and retention of highly qualified staff.


Assuntos
Satisfação no Emprego , Motivação , Assistentes Médicos/psicologia , Adulto , Idoso , Efeito de Coortes , Humanos , Pessoa de Meia-Idade , Seleção de Pessoal
15.
J Mol Biol ; 425(3): 457-65, 2013 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-23174187

RESUMO

Mechanisms for coregulation of transcription of tandem genes in yeast remain largely speculative. This study focused on inositol-mediated regulation of the tandem gene pair SNA3-INO1. While the pattern of regulation of these two genes was similar, results showed that intermediate levels of inositol repressed INO1 and induced SNA3. Results also showed that inositol-mediated regulation of the SNA3 gene was not a function of its promoter but occurred from factors within the SNA3-INO1 intergenic region. The basic helix-loop-helix proteins, Ino2p and Ino4p, mediated this regulation through the upstream activation sequence (UAS)(INO) (E-box) sequences in the intergenic region. These results provide a model for studying coregulation of yeast tandem genes. This is especially significant given that many tandem gene pairs in yeast are coregulated even though context-specific UAS sequences are known only for one gene in the pair.


Assuntos
Regulação Fúngica da Expressão Gênica , Proteínas de Membrana/biossíntese , Mio-Inositol-1-Fosfato Sintase/biossíntese , Proteínas de Saccharomyces cerevisiae/biossíntese , Saccharomyces cerevisiae/genética , Transcrição Gênica , Inositol/metabolismo , Proteínas de Membrana/genética , Mio-Inositol-1-Fosfato Sintase/genética , Proteínas de Saccharomyces cerevisiae/genética
17.
Mol Cell Biochem ; 368(1-2): 37-45, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22638648

RESUMO

The metabolic syndrome is recognized as a cluster of disturbances associated with obesity, type 2 diabetes and hypertension. Over the past two decades, the number of people with the metabolic syndrome has increased at an alarming rate. This increase is associated with the global epidemic of both obesity and diabetes. Cardiovascular mortality is increased among diabetics and obesity-related insulin-resistant patients, and obesity is currently recognized as independent risk factor for cardiovascular disease. We aimed to establish the effects of a short period of an altered diet on the heart using a rat model of hyperphagia-induced obesity (diet supplemented with sucrose and condensed milk for 8 weeks = DIO) compared to age-matched controls. Isolated, perfused hearts were subjected to global or regional ischaemia/reperfusion. Function on reperfusion was recorded and infarct size determined. A plasma lipid profile was established via HPLC-based methods and proteins involved in metabolic signalling determined either by western blotting or RT-PCR. 8 weeks of diet resulted in whole-body but not myocardial insulin resistance, increased plasma triglyceride and phospholipid levels as well as increased lipid peroxidation. Despite the similar baseline function, hearts from DIO animals showed significantly poorer postischaemic recovery than controls (41.9 % RPP recovery vs 57.9 %, P < 0.05, n = 7-11/group) but surprisingly, smaller infarct size (24.95 ± 1.97 vs 47.26 ± 4.05 % of the area at risk, P < 0.005, n = 8/group). Basal phosphorylation of PKB/Akt was elevated but IRS-1 and SERCA-2 expression severely downregulated. In conclusion, after only 8 weeks of a slight change in diet, the rat heart shows signs of metabolic remodelling. Some of these changes may be protective but others may be detrimental and eventually lead to maladaptation.


Assuntos
Dieta/efeitos adversos , Resistência à Insulina , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/fisiopatologia , Obesidade/metabolismo , Obesidade/fisiopatologia , Animais , Hiperfagia/induzido quimicamente , Hiperfagia/metabolismo , Hiperfagia/patologia , Hiperfagia/fisiopatologia , Proteínas Substratos do Receptor de Insulina/metabolismo , Proteínas Musculares/metabolismo , Infarto do Miocárdio/induzido quimicamente , Infarto do Miocárdio/mortalidade , Miocárdio/metabolismo , Miocárdio/patologia , Obesidade/induzido quimicamente , Obesidade/patologia , Fosfolipídeos/sangue , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Wistar , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismo , Triglicerídeos/sangue
18.
Mol Microbiol ; 83(2): 395-407, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22182244

RESUMO

The Saccharomyces cerevisiae PHO5 gene product accounts for a majority of the acid phosphatase activity. Its expression is induced by the basic helix-loop-helix (bHLH) protein, Pho4p, in response to phosphate depletion. Pho4p binds predominantly to two UAS elements (UASp1 at -356 and UASp2 at -247) in the PHO5 promoter. Previous studies from our lab have shown cross-regulation of different biological processes by bHLH proteins. This study tested the ability of all yeast bHLH proteins to regulate PHO5 expression and identified inositol-mediated regulation via the Ino2p/Ino4p bHLH proteins. Ino2p/Ino4p are known regulators of phospholipid biosynthetic genes. Genetic epistasis experiments showed that regulation by inositol required a third UAS site (UASp3 at -194). ChIP assays showed that Ino2p:Ino4p bind the PHO5 promoter and that this binding is dependent on Pho4p binding. These results demonstrate that phospholipid biosynthesis is co-ordinated with phosphate utilization via the bHLH proteins.


Assuntos
Fosfatase Ácida/biossíntese , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Regulação Fúngica da Expressão Gênica , Inositol/metabolismo , Proteínas de Saccharomyces cerevisiae/biossíntese , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/genética , Fatores de Transcrição/metabolismo , Transcrição Gênica , Imunoprecipitação da Cromatina , DNA Fúngico/metabolismo , Elementos Facilitadores Genéticos , Modelos Biológicos , Fosfolipídeos/metabolismo , Regiões Promotoras Genéticas , Ligação Proteica , Saccharomyces cerevisiae/metabolismo
19.
Eukaryot Cell ; 9(12): 1845-55, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20935143

RESUMO

The Saccharomyces cerevisiae INO1 gene encodes the structural enzyme inositol-3-phosphate synthase for the synthesis de novo of inositol and inositol-containing phospholipids. The transcription of INO1 is completely derepressed in the absence of inositol and choline (I(-) C(-)). Derepression requires the binding of the Ino2p-Ino4p basic helix-loop-helix (bHLH) heterodimer to the UAS(INO) promoter element. We report here the requirement of a third bHLH protein, centromere-binding factor 1 (Cbf1p), for the complete derepression of INO1 transcription. We found that Cbf1p regulates INO1 transcription by binding to sites distal to the INO1 promoter and encompassing the upstream SNA3 open reading frame (ORF) and promoter. The binding of Cbf1p requires Ino2p-Ino4p binding to the UAS(INO) sites in the INO1 promoter and vice versa, suggesting a cooperative mechanism. Furthermore, Cbf1p binding to the upstream sites was required for the binding of the ISW2 chromatin-remodeling complex to the Ino2p-Ino4p-binding sites on the INO1 promoter. Consistent with this, ISW2 was also required for the complete derepression of INO1 transcription.


Assuntos
Adenosina Trifosfatases/metabolismo , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Montagem e Desmontagem da Cromatina , Regulação Fúngica da Expressão Gênica , Mio-Inositol-1-Fosfato Sintase/genética , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Fatores de Transcrição/metabolismo , Adenosina Trifosfatases/genética , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Cromatina/genética , Cromatina/metabolismo , Dimerização , Mio-Inositol-1-Fosfato Sintase/metabolismo , Regiões Promotoras Genéticas , Ligação Proteica , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Fatores de Transcrição/genética , Transcrição Gênica
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