Review: Unravelling the role of DNA sensing in alum adjuvant activity

No abstract available

Educação de jovens e adultos: qual currículo para qual cidadania? / Youth and adult education: which curriculum for which citizenship?

O presente artigo discute sobre o currículo da Educação de Jovens e Adultos: qual currículo para qual cidadania? Objetivamo-nos refletir sobre o papel do currículo como meio para alcançar o desenvolvimento integral dos sujeitos e atender as especificidades da modalidade de Educação de Jovens e Adultos. Assim, problematizamos: como o currículo da EJA pode contribuir para a conquista da cidadania ativa pelos jovens e adultos? Nesse sentido, o estudo teve como objetivo compreender de que maneira o currículo da EJA pode possibilitar aos jovens e adultos a conquista da cidadania. Utilizamos a abordagem qualitativa para materializar a investigação e para procedimento técnico, a pesquisa bibliográfica. Com o aporte teórico de Apple (2006), Arroyo (2011), Gentili (2009), Goodson (2008), Monteiro (2011), Oliveira (2007), Veiga-Neto (2002), buscamos levantar informações acerca dos conceitos e reflexões dos autores referenciados. Os resultados obtidos através da pesquisa teórica revelam a necessidade de um aprofundamento de estudos sobre as questões curriculares por todos os envolvidos no processo educacional para uma reestruturação acerca das particularidades da EJA no currículo.

Telomerase promoter mutations in cancer: an emerging molecular biomarker?

João Vinagre, Vasco Pinto and Ricardo Celestino contributed equally to the manuscript.Cell immortalization has been considered for a long time as a classic hallmark of cancer cells. Besides telomerase reactivation, such immortalization could be due to telomere maintenance through the “alternative mechanism of telomere lengthening” (ALT) but the mechanisms underlying both forms of reactivation remained elusive. Mutations in the coding region of telomerase gene are very rare in the cancer setting, despite being associated with some degenerative diseases. Recently, mutations in telomerase (TERT) gene promoter were found in sporadic and familial melanoma and subsequently in several cancer models, notably in gliomas, thyroid cancer and bladder cancer. The importance of these findings has been reinforced by the association of TERT mutations in some cancer types with tumour aggressiveness and patient survival. In the first part of this review, we summarize the data on the biology of telomeres and telomerase, available methodological approaches and non-neoplastic diseases associated with telomere dysfunction. In the second part, we review the information on telomerase expression and genetic alterations in the most relevant types of cancer (skin, thyroid, bladder and central nervous system) on record, and discuss the value of telomerase as a new biomarker with impact on the prognosis and survival of the patients and as a putative therapeutic target

Spermidine suppresses DC activation via eIF5A hypusination and metabolic adaptation

Introduction: Cell metabolism plays an important role in immune effector responses and through responding to metabolic signals, immune cells can adapt and regulate their function. Arginine metabolism in Dendritic cells (DC) has been shown to reduce T cell activation; however, it is unclear how this immunosuppressive state is induced. Method: To address this issue, we examined the immunomodulatory capacity of various metabolites from arginine metabolism. Results: Through the use of a recently described DC:T cell interaction assay and flow cytometry we demonstrated that spermidine most significantly inhibited DC activation, preventing subsequent interactions with CD4 T cells. DC function could be restored by addition of inhibitors of spermidine metabolism via the eIF5A-hypusine axis, required for expression of some mitochondrial enzymes. We also demonstrated that the spermidine induced-immunosuppressive state protected DC against activation induced loss of mitochondrial capacity for energy generation, which was also hypusination dependent. Conclusion: Taken together this data demonstrates that spermidine is the key immunomodulatory component downstream of arginine metabolism and that it mediates this effect by stimulating hypusination-dependent protection of OXPHOS in DC, which in turn results in a reduced ability of DC to activate and interact with T cells. This pathway may be utilised by the immune system to regulate excessive immune responses but could also be exploited by pathogens as a method of immune evasion

Cycling of nutrients and silicon in pigeonpea and pearl millet monoculture and intercropping

In a no-tillage system, cover crops must be used that combine shoot dry matter production and nutrient recycling. The aim of this study was to evaluate shoot dry matter production, decomposition rate and macronutrient and silicon release from pigeonpea and pearl millet in monoculture and intercropping systems. A randomized block design was used with a 3 x 6 factorial arrangement, with four replications. The first factor consisted of three cover crops (pigeonpea, pearl millet and intercropping of these cover crops) and the second consisted of six sampling times [0, 18, 32, 46, 74 and 91 days after desiccation (DAD)]. Pearl millet produced greater amounts of shoot dry matter and content of N, P, K, Ca, Mg, S, C and Si and had a higher decomposition rate and macronutrient and Si release than the other cover crops. The rates of decomposition and daily nutrient release from shoot dry matter were highest in the first period of evaluation (0-18 DAD). Over time, the C/N, C/P and C/S ratios increased, while C/Si and the decomposition rate decreased. Potassium was the nutrient most quickly released to the soil, especially from pearl millet residue. Silicon had the lowest release rate, with 62, 82 and 74 % of the total content in the shoot dry matter remaining in the last evaluation of pearl millet, pigeonpea and in the intercrop system, respectively. The shoot dry matter from the intercrop system had a different decomposition rate than that from the pearl millet monoculture and pigeonpea. Plants with greater shoot dry matter production and lower C/Si ratio are more effective in a no-tillage system for providing a more complete and persistent soil cover.As características mais importantes na escolha de plantas de cobertura para o sistema plantio direto são a quantidade e a durabilidade da fitomassa produzida, bem como a capacidade de reciclar nutrientes. Este estudo objetivou avaliar a produção de fitomassa, taxa de decomposição e ciclagem de macronutrientes e silício pelo guandu-anão e milheto, em cultivo solteiro e consorciado. O delineamento experimental foi em blocos casualizados, com quatro repetições, em esquema fatorial 3 x 6, constituído por três tipos de cobertura vegetal (guandu-anão, milheto e o consórcio dessas espécies) e seis épocas de coleta [0, 18, 32, 46, 74 e 91 dias, após a dessecação (DAD)]. O milheto produziu maior quantidade de fitomassa, acumulou mais N, P, K, Ca, Mg, S, C e Si e teve maior taxa de decomposição e de liberação de macronutrientes e Si que as demais coberturas vegetais. As maiores taxas de decomposição e liberação diária de nutrientes das fitomassas ocorreram no primeiro período de avaliação (0 a 18 DAD). Com o passar do tempo ocorreu aumento das relações C/N, C/P e C/S e redução na relação C/Si e na taxa de decomposição da fitomassa. O K foi o nutriente mais rapidamente disponibilizado ao solo, especialmente pela fitomassa do milheto. O Si foi o elemento que teve a menor taxa de liberação, restando na última avaliação 62, 82 e 74 % do total acumulado na fitomassa, respectivamente de milheto, guandu-anão e consórcio. A taxa de decomposição da fitomassa do consórcio milheto e guandu-anão foi diferente da proveniente dos cultivos solteiros. Plantas com maior produção de fitomassa e com menor relação C/Si são mais interessantes para utilização no SPD, por proporcionarem maior e mais persistente cobertura do solo.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)São Paulo State University College of Agricultural Sciences Department of Crop ScienceUNESP FCAUNESP FCA Department of Crop ScienceSão Paulo State University College of Agricultural Sciences Department of Crop ScienceUNESP FCAUNESP FCA Department of Crop ScienceFAPESP: 04/10361-

Crimean-Congo hemorrhagic fever: epidemiological trends and controversies in treatment

Crimean-Congo hemorrhagic fever (CCHF) virus has the widest geographic range of all tick-borne viruses and is endemic in more than 30 countries in Eurasia and Africa. Over the past decade, new foci have emerged or re-emerged in the Balkans and neighboring areas. Here we discuss the factors influencing CCHF incidence and focus on the main issue of the use of ribavirin for treating this infection. Given the dynamics of CCHF emergence in the past decade, development of new anti-viral drugs and a vaccine is urgently needed to treat and prevent this acute, life-threatening disease

P73 regulates cisplatin-induced apoptosis in ovarian cancer cells via a calcium/calpain-dependent mechanism

P73 is important in drug-induced apoptosis in some cancer cells, yet its role in the regulation of chemosensitivity in ovarian cancer (OVCA) is poorly understood. Furthermore, if and how the deregulation of p73-mediated apoptosis confers resistance to cisplatin (CDDP) treatment is unclear. Here we demonstrate that TAp73α over-expression enhanced CDDP-induced PARP cleavage and apoptosis in both chemosensitive (OV2008 and A2780s) and their resistant counterparts (C13* and A2780cp) and another chemoresistant OVCA cells (Hey); in contrast, the effect of ΔNp73α over-expression was variable. P73α downregulation attenuated CDDP-induced PUMA and NOXA upregulation and apoptosis in OV2008 cells. CDDP decreased p73α steady-state protein levels in OV2008, but not in C13*, although the mRNA expression was identical. CDDP-induced p73α downregulation was mediated by a calpain-dependent pathway. CDDP induced calpain activation and enhanced its cytoplasmic interaction and co-localization with p73α in OV2008, but not C13* cells. CDDP increased the intracellular calcium concentration ([Ca2+]i) in OV2008 but not C13* whereas cyclopiazonic acid (CPA), a Ca2+-ATPase inhibitor, caused this response and calpain activation, p73α processing and apoptosis in both cell types. CDDP-induced [Ca2+]i increase in OV2008 cells was not effected by the elimination of extracellular Ca2+, but this was attenuated by the depletion of internal Ca2+ store, indicating that mobilization of intracellular Ca2+] stores was potentially involved. These findings demonstrate that p73α and its regulation by the Ca2+-mediated calpain pathway are involved in CDDP-induced apoptosis in OVCA cells and that dysregulation of Ca2+/calpain/p73 signaling may in part be the pathophysiology of CDDP resistance. Understanding the cellular and molecular mechanisms of chemoresistance will direct the development of effective strategies for the treatment of chemoresistant OVCA

Decreased expression of cardiac troponin C is associated with cardiac lesions in Amorimia exotropica poisoned cattle

The plants which cause sudden death of cattle in Brazil occupy a leading position for losses in the cattle industry. Amorimia exotropica is one of the plants pertaining to this group. Diagnostic findings in these cases may be inconclusive; further knowledge is necessary. This paper identifies cardiac lesions through anti-cardiac troponin C (cTnC) immunehistochemistry performed in tissues from cattle poisoned after consumption of A.exotropica in southern Brazil. Heart fragments from nine A. exotropica-poisoned cattle were studied immunohistochemically using anti-human cTnC as the primary antibody. In the hearts from all of the poisoned cattle, there was a sharp decrease in the cTnC expression level in the cytoplasm of groups of cardiomyocytes. A significant decrease in anti-cTnC immunoreactivity occurred particularly in degenerated or necrotic cardiomyocytes. Occasional groups of cells showed complete loss of immunolabeling. In the remaining intact cardiomyocytes from poisoned cattle and in cardiomyocytes from six cattle that died from other causes there was intense cytoplasmic staining

Sex- and age-related differences in the management and outcomes of chronic heart failure: an analysis of patients from the ESC HFA EORP Heart Failure Long-Term Registry

Aims: This study aimed to assess age- and sex-related differences in management and 1-year risk for all-cause mortality and hospitalization in chronic heart failure (HF) patients. Methods and results: Of 16 354 patients included in the European Society of Cardiology Heart Failure Long-Term Registry, 9428 chronic HF patients were analysed [median age: 66 years; 28.5% women; mean left ventricular ejection fraction (LVEF) 37%]. Rates of use of guideline-directed medical therapy (GDMT) were high (angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, beta-blockers and mineralocorticoid receptor antagonists: 85.7%, 88.7% and 58.8%, respectively). Crude GDMT utilization rates were lower in women than in men (all differences: P\ua0 64 0.001), and GDMT use became lower with ageing in both sexes, at baseline and at 1-year follow-up. Sex was not an independent predictor of GDMT prescription; however, age >75 years was a significant predictor of GDMT underutilization. Rates of all-cause mortality were lower in women than in men (7.1% vs. 8.7%; P\ua0=\ua00.015), as were rates of all-cause hospitalization (21.9% vs. 27.3%; P\ua075 years. Conclusions: There was a decline in GDMT use with advanced age in both sexes. Sex was not an independent predictor of GDMT or adverse outcomes. However, age >75 years independently predicted lower GDMT use and higher all-cause mortality in patients with LVEF 6445%