Understanding the molecular pathogenesis of HIV-associated Burkitt Lymphoma – the impact of HIV-1 protein Tat on lymphoma driver genes

Burkitt Lymphoma (BL) is a B cell non-Hodgkin lymphoma that occurs as three distinct subtypes, namely: endemic, sporadic, and immunodeficiency/HIV-associated. This cancer represents a frequent cause of mortality among HIV+ people in Southern Africa which has the highest incidence of HIV/AIDS worldwide. Recent reports associate a direct oncogenic function of HIV in BL development. However, the molecular mechanisms underlying this HIV-associated malignancy are not well understood. This study explores the oncogenic potential of HIV-1 protein Tat in BL via its ability to manipulate the expression of c-MYC and activation-induced cytidine deaminase (AID), two key drivers of BL progression. Using dual-luciferase reporter assays, HIV-1 Tat was shown to enhance the activity of the cMYC promoter (-2324 bp - +537 bp), which corresponded with elevated c-MYC protein levels in BL cells (Ramos) expressing HIV-1 Tat. By generating sequential promoter deletions, the minimal promoter region mediating HIV-1 Tat induced activation was identified. Site-directed mutagenesis indicated that this response was mediated by AP-1 binding elements, and coimmunoprecipitation assays revealed that HIV-1 Tat and the AP-1 factor JunB interacted within the same complex. Chromatin immunoprecipitation assays confirmed that JunB bound the c-MYC promoter in vivo under the influence of HIV-1 Tat. The effect of HIV-1 Tat on the expression of the DNA editing enzyme AID was also investigated. Dual-luciferase assays revealed that HIV-1 Tat could enhance the activity of the three regulatory regions of the AICDA gene, namely R1, R2 and R4. This translated into elevated AID protein expression in Ramos cells expressing HIV-1 Tat, which was also reflected in an increase in genomic instability as shown by enhanced phosphorylated H2AX expression. Sequential promoter deletions of the R1 promoter did not lead to a loss in HIV-1 Tat-mediated activation, pointing to potential post-transcriptional regulation. Indeed, HIV-1 Tat was found to downregulate the expression of hsa-miRNA-181b-5p, a known repressor of the murine Aicda gene. Furthermore, using reporter assays, we show that an hsa-miRNA-181b5p mimic could repress AICDA via the full-length 3'UTR which contains three putative binding elements for the miRNA. To date, this study reveals that HIV-1 Tat induced c-MYC promoter activation is mediated by two AP-1 binding sites. HIV-1 Tat was shown to couple with JunB and bind to both AP-1 sites on the c-MYC promoter inducing promoter activation. Furthermore, this study reveals a novel mechanism of AID deregulation via HIV-1 Tat-mediated miRNA perturbation. Lastly, we show that HIV-1 Tat interferes with hsa-miRNA-181b-5p expression in B cells, alleviating AICDA 3'UTR repression

ARBITRAGEM NO DIREITO SOCIETÁRIO

O presente artigo trata da aplicação do instituto da arbitragem no Direito Societário brasileiro, mais especificamente nos contratos sociais das sociedades limitadas e nos estatutos sociais das sociedades anônimas. O artigo também irá discutir a relação do Direito Societário junto a Arbitragem, ressaltando suas vantagens e ressaltando os principais problemas que podem ocorrer com a inclusão da cláusula compromissória arbitral nos instrumentos constitutivos das sociedades empresárias acima mencionadas. Além disso, será abordada a necessidade da preservação do princípio da maioria adotado pela legislação societária para a conservação dos interesses da empresa, sócios e acionistas. PALAVRAS CHAVE: Direito Societário – Arbitragem – Contrato social – Estatuto social Abstract: This article addresses the implementation of arbitration in Brazilian Corporate Law, more specifically in the articles of association of limited liability companies and the bylaws of joint-stock companies. The paper will also discuss the relationship between Corporate Law and Arbitration, emphasizing the advantages and highlighting the main problems that might arise in virtue of the inclusion of an arbitration clause in the acts of incorporation of the companies aforementioned. Besides, it will be exposed the necessity of preserving the principle of majority adopted by the corporate legislation for the conservation of the interests of the company, quotaholders and stockholders. Keywords: Corporate Law – Arbitration– Articles of Association– Bylaw

Rainfall analysis and its influence in forest fire occurrence in the Serra de Itabaiana National Park, Sergipe, Brazil

Este trabalho teve como objetivo verificar a influência da variável climática precipitação na ocorrência de incêndios florestais, dentro do Parque Nacional Serra de Itabaiana. Para tanto, foram obtidos os dados de precipitação para o município de Itabaiana e os de ocorrência de incêndios florestais dentro do Parque, para o período de 10 anos (1999-2008). Inicialmente, os dados de precipitação foram agrupados pela Análise de Variância, de acordo com os meses do ano e, em seguida, correlacionados com a quantidade de registro de incêndios florestais, pelo coeficiente de correlação de Pearson. Para verificar a significância da correlação obtida, esta foi aplicada ao teste de significância “t”. De acordo com os resultados obtidos, os meses de novembro e dezembro formaram o grupo com os menores valores de precipitação anual, enquanto os meses de maio, junho e julho representaram o grupo com os maiores valores. Correlacionando a precipitação com a quantidade de incêndios, foi obtida uma correlação negativa e significativa (r= -0,61, p= 0,03). Entretanto, os meses que formaram o grupo mais seco não foram os que apresentaram maior ocorrência de incêndios. _________________________________________________________________________________ ABSTRACT: The objective of this research was to verify the influence of the climatic variable precipitation in the forest fire occurrence at the National Park Serra de Itabaiana. For this propose, precipitation data for the Itabaiana county, and forest fire occurrence data inside the Park were analyzed for a period of 10 years (1999-2008). Initially, the precipitation data had been grouped using Analysis of Variance considering the months of the year and, after that, a Pearson’s coefficient of correlation was performed between precipitation data and number of registered forest fires. The “t” test of significance was applied to verify the correlation significance. The results showed that the months of November and December formed the group with lower annual precipitation values, while the months of May, June and July represented the group with highest values. Correlating the precipitation with the number of fires, a negative and significant correlation coefficient (r= -0.61, p= 0.03) was obtained. However, the driest months did not have the highest number of fire occurrences

Effect of rest interval length on the volume completed during upper body resistance exercise

The purpose of the current study was to compare the workout volume (sets x resistance x repetitions per set) completed during two upper body resistance exercise sessions that incorporated 1 minute versus 3 minute rest intervals between sets and exercises. Twelve trained men completed two experimental sessions that consisted of 5 upper body exercises (i.e. barbell bench press, incline barbell bench press, pec deck flye, barbell lying triceps extension, triceps pushdown) performed for three sets with an 8- RM load. The two experimental sessions differed only in the length of the rest interval between sets and exercises; one session with a 1-minute and the other session with a 3-minute rest interval. The results demonstrated that for each exercise, significantly greater workout volume was completed when resting 3 minutes between sets and exercises (p \u3c 0.05). These results indicate that during a resistance exercise session, if sufficient time is available, resting 3 minutes between sets and exercises allows greater workout volume for the upper body exercises examined

Dimensioning the relationship between availability and data center energy flow metrics

The advancement of technology and the growing number of applications available to network users have increased the demand for services hosted in cloud environments. In 2020, more than 4 billion of people access these services through the Internet, a value 7% higher in comparison to the same period in 2019. To support the demand for such services, an environment that provides such conditions for applications available whenever needed has grown in importance. These environments are generally available from large data centers, which consume large amounts of electricity to provide such demand service capacity. In this context, this work proposes an integrated and dynamic strategy that demonstrates the impact of the availability on the energyconsumption of the devices that compose the data center system architecture. In order to accomplish this, colored Petri net models were proposed for quantifying the cost, environmental impact and availability of the electric energy infrastructure ofdata centers. The models presented in this work are supported by the developed prototype. Two case studies illustrate the applicability of the proposed models and strategy. Significant results were obtained, showing an increase close to 100% in the system availability, with practically the same operational cost and environmental impact

O processo de construção da sequência didática La vida universitaria

Este artigo tem como finalidade apresentar a descrição e a reflexão oriundas do processo de elaboração e da aplicação da sequência didática (SD) La Vida Universitaria, para a disciplina de Espanhol I do curso de Letras da Universidade Federal do Rio Grande do Sul (UFRGS). O material foi criado com o propósito de oferecer oportunidades de aprendizado com base em temas relevantes aos alunos ingressantes na universidade e proporcionar interações significativas a partir de gêneros discursivos que circulam nas práticas sociais desempenhadas por esse público. O artigo inicia apresentando a metodologia utilizada na construção da SD e a fundamentação teórica que sustentou sua produção: gêneros do discurso, multiletramentos e ensino com base em tarefas. Posteriormente, é descrita a composição do material, seguida dos produtos finais elaborados pelos alunos. Como resultado, verificou-se que o engajamento do grupo de alunos de Espanhol I, no primeiro semestre do curso de Letras da UFRGS, foi evidenciado pelos textos produzidos. Foi possível perceber nos produtos finais o uso da língua para fazer coisas no mundo, refletindo a própria definição de multiletramentos.This paper presents the description and reflection on the production and teaching of the didactic sequence (DS) La Vida Universitaria, for the Spanish I course of the Universidade Federal do Rio Grande do Sul (UFRGS) Languages and Arts Program. The material was created as a way to offer learning opportunities based on relevant topics for university students and to provide significant interactions from discursive genres that circulate in the social practices performed by freshmen. The article begins by presenting the methodology used in the construction of the DS and the theoretical framework that supported its production: discourse genres, multiliteracies and task-based learning. Subsequently, the composition of the material is described followed by the final products prepared by the students. As a result, it was verified that the engagement of the group of Spanish I students in the first semester of the UFRGS Languages and Arts Program was evidenced by the texts produced. Students’ final productions displayed the use of language to do things in the world, reflecting the very definition of multiliteracies

Avaliação da citotoxicidade de dois cimentos endodônticos em cultura de macrófagos

Compared to gutta-percha, the endodontic cements are used in small quantity to seal root canals, but are indispensable to achieve hermetically sealed margins, where its biocompatibility depends on the sum of responses of each cell present in the periapical region. The object of this study was to evaluate the cytotoxicity of two endodontic cements, one based on epoxy resin (Sealer 26) and the other containing zinc oxide eugenol (Endofill) by using cultured peritoneal macrophages from Swiss mice to measure the induced production of nitric oxide. After solidification and pulverization, aliquots of 100mul of suspension containing 18mg/mL of the respective cements were added to 96-well tissue culture plates containing the tissue culture of macrophages at a concentration of 5.0X10(6) cells/ml. In the positive control group the cell culture was treated with 10mg/mL of lipopolyssaccharide from Escherichia coli 026:B6 and the cell culture alone represented the negative control. After 48 hours of incubation, at 37ºC, in 5% CO2, the cultures were placed in an ELISA automatic reader to evaluate the release of nitric oxide. The production of nitric oxide for cement Sealer 26 was between 36.1 and 313.0 mumols, with a mean of 143.82±111.03mumols, while for the Endofill these values were significantly less (p=0.01), varying from 50.8 to 125.7mumols, with a mean of 80.33±28.42 mumols. In the positive and negative control groups the mean release of nitric oxide was of 162.75mumols and 4.42mumols, respectively. There was no significant difference between the positive control group and cement Sealer 26 (p>;0.05). Therefore, the cement Sealer 26 caused significantly greater toxicity to the macrophages, possibly due to the components from the epoxy resin and formaldehyde release during polymerization.Comparativamente à guta-percha, os cimentos endodônticos são utilizados em pequena quantidade nas obturações dos canais radiculares, mas são imprescindíveis para obtenção do hermético selamento marginal, sendo sua biocompatibilidade dependente do somatório das respostas de cada célula presente na região periapical. Por conseguinte, o objetivo deste estudo foi avaliar em cultura de macrófagos peritoneais de seis camundongos Swiss, a citotoxicidade de dois cimentos endodônticos, um à base de resina epóxica (Sealer 26) e outro contendo óxido de zinco e eugenol (Endofill), quanto a indução da produção de óxido nítrico. Após a presa e pulverização, alíquotas de 100ml da suspensão contendo 18mg/mL dos respectivos cimentos foram adicionados em placa de cultura de tecido de 96 poços, contendo a cultura de macrófagos na concentração de 5,0X10(6) células/ml. Após 48 horas de incubação, a 37ºC, em 5% de CO2, foi feita a leitura em um leitor ELISA automático para se averiguar a liberação de óxido nítrico. Verificou-se, para o cimento Sealer 26, que a produção de óxido nítrico oscilou de 36,1 a 313,0 mimols, com média de 143,82±111,03, enquanto para o Endofill estes valores foram significativamente menores (p=0.01), variando de 50,8 a 125,7, com média de 80.33±28,42 mols. Nos grupos controles positivo e negativo a média de liberação de óxido nítrico foi de 162,75mimols e 4,42mimols, respectivamente. Não houve diferença significativa entre o grupo controle positivo e o cimento Sealer 26 (p>;0.05). Portanto, o cimento Sealer 26 causou, significativamente, maior toxicidade aos macrófagos, possivelmente devido aos seus componentes, a exemplo da resina epóxica e ao formaldeído, liberados durante a sua reação de polimerização

Metástases Cutâneas como Primeira Manifestação de Carcinoma Urotelial

Cutaneous metastases of visceral neoplasms are rare conditions, and urothelial or transitional cell carcinomas are responsible for less than 1% of cases. We report the case of a 50-year-old male patient who progressively developed multiple cutaneous nodules on his head, abdomen, axilla, and groin, some with ulceration. Skin biopsy and immunohistochemistry were consistent with cutaneous metastasis of urothelial carcinoma. Computed tomography scan revealed generalized metastasis in internal organs. In this rare case, cutaneous metastases were the presenting sign of the disease and, as reported, a sign of bad prognosis.Metástases cutâneas de neoplasias viscerais são raras, e os carcinomas uroteliais ou de células transicionais são responsáveis por menos de 1% dos casos. Relatamos o caso de um paciente de 50 anos que desenvolveu progressivamente múltiplos nódulos cutâneos (cabeça, abdômen, axila e virilha), alguns com ulceração, antes de qualquer outra sintomatologia. A biópsia cutânea e o estudo imuno-histoquímico foram consistentes com metástases cutâneas de um carcinoma urotelial. O exame tomográfico revelou metástase generalizada nos órgãos internos. Além da raridade destes tipos de metástases cutâneas, neste caso foi o sinal inaugural e, como habitualmente descrito, associado a mau prognóstico

Caracterização dos materiais combustíveis em diferentes povoamentos florestais na região nordeste de Portugal

Objetivou-se com este estudo caracterizar o material combustível superficial, a partir da sua quantificação e classificação de perigosidade em duas estações do ano e em quatro povoamentos florestais (Pinhal manso, Castinçal, Sobreiral e Carvalhal) no nordeste de Portugal. O material combustível foi classificado em perigosos (1cm) e verdes, a umidade foi avaliada com secagem em estufa. O povoamento de Castanheiro é o que possui a maior quantidade de material combustível (30,547; 16,40 ton/ha). O pinhal apresenta o maior risco, devido a elevada quantidade de material combustível atrelada a baixa umidade no período crítico (verão).info:eu-repo/semantics/publishedVersio