The cardioprotective effect of S. africana caerulea/Blue Sage in ischaemia and reperfusion induced oxidative stress.

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.

Public communication for the fight against syphilis: an experience report of the campaign "Eu sei. Você sabe?" (2020­2021) / Comunicação pública de combate à sífilis: um relato de experiência da campanha "Eu sei. Você sabe?" (2020­2021)

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.

#VoteLGBT e o ciberativismo em prol da representação política no Brasil / #VoteLGBT and cyberactivism to political representation in Brazil / #VoteLGBT y el ciberactivismo en favor de la representación política en Brasil

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.

Early cardiovascular changes occurring in diet-induced, obese insulin-resistant rats.

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.

Derepression of INO1 transcription requires cooperation between the Ino2p-Ino4p heterodimer and Cbf1p and recruitment of the ISW2 chromatin-remodeling complex.

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.

Regulated transcription of the Saccharomyces cerevisiae phosphatidylinositol biosynthetic gene, PIS1, yields pleiotropic effects on phospholipid synthesis.

Phosphatidylinositol is an important membrane lipid in Saccharomyces cerevisiae and other eukaryotes. Phosphatidylinositol and its metabolites (phosphoinositides, inositol polyphosphates, etc.) affect many cellular processes with implications in human diseases. Phosphatidylinositol synthesis in S. cerevisiae requires the essential PIS1 gene. Recent studies reveal that PIS1 expression is regulated at the level of transcription in response to carbon source, oxygen, and zinc. However, the consequence of this regulation on phosphatidylinositol levels and functions has not been thoroughly studied. To investigate this, we created a strain with a galactose-inducible GAL1-PIS1 gene. In this strain, the amount of phosphatidylinositol correlated with PIS1 expression but did not exceed c. 25% of the total phospholipid composition. Interestingly, we found that 4% phosphatidylinositol was sufficient for cell growth. We also found that reduced PIS1 expression yielded derepression of two phospholipid biosynthetic genes (INO1 and CHO1) and the INO2 regulatory gene. Consistent with this derepression, reduced PIS1 expression also yielded an overproduction of inositol (Opi(-)) phenotype. The effect on transcription of the INO1, CHO1, and INO2 genes is consistent with the accepted model that phosphatidic acid (PA) is the signal for regulation of these genes because decreased phosphatidylinositol synthesis would affect PA levels.

Phosphatidylinositol biosynthesis: biochemistry and regulation.

Phosphatidylinositol (PI) is a ubiquitous membrane lipid in eukaryotes. It is becoming increasingly obvious that PI and its metabolites play a myriad of very diverse roles in eukaryotic cells. The Saccharomyces cerevisiae PIS1 gene is essential and encodes PI synthase, which is required for the synthesis of PI. Recently, PIS1 expression was found to be regulated in response to carbon source and oxygen availability. It is particularly significant that the promoter elements required for these responses are conserved evolutionarily throughout the Saccharomyces genus. In addition, several genome-wide strategies coupled with more traditional screens suggest that several other factors regulate PIS1 expression. The impact of regulating PIS1 expression on PI synthesis will be discussed along with the possible role(s) that this may have on diseases such as cancer.

Multiple determinants for rapid agonist-induced internalization of a nonmammalian gonadotropin-releasing hormone receptor: a putative palmitoylation site and threonine doublet within the carboxyl-terminal tail Are critical.

The chicken GnRH receptor (cGnRH-R) differs from all mammalian GnRH-Rs in possessing a cytoplasmic carboxyl-terminal tail. We have previously demonstrated that the cGnRH-R undergoes more rapid agonist-induced internalization than the mammalian GnRH-Rs and requires the carboxyl-terminal tail for this process. To investigate the structural determinants mediating this rapid internalization, a series of mutant receptors was generated, including progressive truncations of the tail and substitution of serine and threonine residues with alanine. Truncation of the carboxyl-terminal tail to position 366 and then to position 356 resulted in a progressive attenuation of the rate and total extent of receptor internalization. However, truncation between positions 356 and 346 did not alter the kinetics of internalization further, whereas a further truncation to position 337 resulted in an additional marked reduction of internalization. We show that the membrane-proximal Cys(328) and the Thr(369)Thr(370) doublet located in the distal carboxyl terminus play a critical role in mediating rapid internalization. We demonstrate that the cGnRH-R, when expressed in both COS-7 and HEK 293 cells, preferentially undergoes rapid agonist-induced internalization in a caveolae-like, dynamin-dependent manner. These conclusions are based on our observation that pretreatments with filipin and methyl-beta-cyclodextrin, agents that disrupt lipid rafts such as caveolae, and coexpression of dominant-negative dynamin-1 (K44A) and caveolin-1 (Delta 1-81) mutants, effectively inhibited rapid agonist-induced internalization. Furthermore, cGnRH-Rs appeared to be mobilized to the beta-arrestin- and clathrin-coated, vesicle-mediated endocytic pathway upon beta-arrestin overexpression.