Extracellular human immunodeficiency virus type-1 Tat protein activates phosphatidylinositol 3-kinase in PC12 neuronal cells

We have here investigated the effect of the regulatory Tat protein of the human immunodeficiency virus type 1 (HIV-1) on the PI 3-kinase catalytic activity in PC12 rat pheochromocytoma cells. After as early as 1 min from the beginning of the treatment with recombinant HIV-1 Tat protein, a significant increase in the tyrosine phosphorylation levels of the p85 regulatory subunit of PI 3-kinase was noticed in 48 h serum-starved PC12 cells. Moreover, the addition of Tat to PC12 cells induced a great increase in PI 3-kinase immunoprecipitated with an anti-phosphotyrosine antibody with a peak of activity (19-fold increase with respect to the basal levels) after a 15-min treatment. This increase in PI 3-kinase activity was significantly higher in PC12 cell cultures supplemented with Tat protein than in cultures stimulated by 100 ng/ml nerve growth factor (NGF; 8-fold increase with respect to the basal levels). Further experiments showed that Tat protein was able to specifically activate PI 3-kinase at picomolar concentrations. In fact: (i) maximal activation of PI 3-kinase was observed at concentrations as low as 1 ng/ml and was specifically blocked by anti-Tat neutralizing antibody; (ii) a Tat-dependent activation was also observed in experiments in which PI 3-kinase activity was evaluated in either anti-Tyr(P) or anti-p85 immunoprecipitates; (iii) 100 nM wortmannin completely blocked the Tat-mediated increase in PI 3-kinase activity both in vitro and in vivo. Our data strongly support the concept that extracellular Tat acts as a cell stimulator, inducing intracellular signal transduction in uninfected cells

Introduction: rupture and continuity in the Italian literary field 1926-1960

Introduction to the Special Issu

Diversità e diritto internazionale privato: il ripudio islamico e la sua rilevanza nell’ordinamento giuridico italiano alla luce di due recenti pronunce della Corte di Cassazione

SOMMARIO: 1. Dal riconoscimento degli effetti civili delle sentenze ecclesiastiche di nullità matrimoniale alla trascrizione del ripudio islamico - 2. Le specificità dell’istituto del ripudio - 3. I dubbi di compatibilità sollevati dal ripudio alla prova della recente giurisprudenza di legittimità - 4. La sentenza n. 16804 del 7 agosto 2020 e l’intrascrivibilità di un ripudio sciaraitico pronunciato in Palestina - 5. L’ordinanza n. 17170 del 14 agosto 2020 sulla trascrivibilità di un divorzio unilaterale pronunciato in Iran - 6. Annotazioni conclusive: ordine pubblico e diversità religiosa alla prova degli effetti generati dalla trascrizione. Diversity and Private International Law: Islamic repudiation and its relevance into the Italian legal system in the light of two recent judgments of the Court of Cassation ABSTRACT: Two recent judgments of the Court of Cassation lead to the center of attention the issue of recognition in Italy of repudiation orders issued abroad by Sharia courts. The general clause of international public order becomes thus the filter to measure the degree of openness of our legal system to other values, clearly foreign to the Italian and European legal horizon

Quando l'interruzione volontaria della gravidanza solleva ancora discussioni nello Stato e nella Chiesa

Contributo sottoposto a valutazioneSOMMARIO: 1. Obiezione di coscienza e aborto fra diritti riconosciuti e negati in attuazione della legge n. 194 del 1978. - 2. La Chiesa cattolica di fronte alla soppressione del concepito: foro interno e peccato. - 3. (segue) … foro esterno e delitto. - 4. Apparenti (?) divergenze di opinione tra Chiesa universale e locale di fronte all'aborto di una “madre-bambina”. - 5. (segue) … il diritto alla vita: una legge naturale obiettiva non derogabile in sede civil

miRNAs as Influencers of Cell-Cell Communication in Tumor Microenvironment

microRNAs (miRNAs) are small noncoding RNAs that regulate gene expression at the posttranscriptional level, inducing the degradation of the target mRNA or translational repression. MiRNAs are involved in the control of a multiplicity of biological processes, and their absence or altered expression has been associated with a variety of human diseases, including cancer. Recently, extracellular miRNAs (ECmiRNAs) have been described as mediators of intercellular communication in multiple contexts, including tumor microenvironment. Cancer cells cooperate with stromal cells and elements of the extracellular matrix (ECM) to establish a comfortable niche to grow, to evade the immune system, and to expand. Within the tumor microenvironment, cells release ECmiRNAs and other factors in order to influence and hijack the physiological processes of surrounding cells, fostering tumor progression. Here, we discuss the role of miRNAs in the pathogenesis of multicomplex diseases, such as Alzheimer's disease, obesity, and cancer, focusing on the contribution of both intracellular miRNAs, and of released ECmiRNAs in the establishment and development of cancer niche. We also review growing evidence suggesting the use of miRNAs as novel targets or potential tools for therapeutic applications

Avaliação da capacidade para o trabalho entre auxiliares de enfermagem

O envelhecimento da força de trabalho gera a necessidade de se desenvolver estudos a fim de avaliar a capacidade para o trabalho. O objetivo deste estudo foi analisar a capacidade para o trabalho de auxiliares de enfermagem de uma instituição pública de saúde. Foi desenvolvido um estudo transversal sobre capacidade para o trabalho desses profissionais em relação às características demográficas, de trabalho e estilo de vida (n=241). Uma análise de regressão logística univariada foi desenvolvida tendo a capacidade para o trabalho inadequada (menor que 37 pontos) como variável dependente. Foi encontrada associação em relação à idade (os mais velhos), ao tempo de trabalho na instituição (o mais antigo), o índice de massa corpórea (obesidade) e o item 1 do índice de capacidade para o trabalho: capacidade de trabalho atual. Essas informações podem ser utilizadas para medidas preventivas e para restaurar a capacidade para o trabalho.Work force aging generates the need to develop studied with the purpose to evaluate work capacity. The objective of this study was to analyze the work capacity of the nursing aides of a public health institute. A cross-sectional study was developed on the work capacity of these professionals regarding their demographic, work and lifestyle characteristics (n=241). A univariate logistic regression analysis was performed with inadequate work capacity (score below 37) as the dependent variable. There was an association with age (the eldest), work time at the institution (the oldest), body mass index (obesity) and item 1 of the work capacities index: present work capacity. This information can be used to create preventive measures and restore work capacity.El envejecimiento de la fuerza laborar genera la necesidad de desarrollar estudios que evalúen la capacidad para el trabajo. Este estudio objetivó analizar la capacidad para el trabajo de auxiliares de enfermería de una institución pública de salud. Se desarrolló estudio transversal sobre capacidad para el trabajo de auxiliares de enfermería en relación a características demográficas, laborales y estilo de vida (n=241). Fue efectuado un análisis de regresión logística univariada, teniendo la capacidad inadecuada para el trabajo

Upregulation of SOCS-1 by Nutlin-3 in acute myeloid leukemia cells but not in primary normal cells

OBJECTIVE: It has been shown that SOCS-1 plays an important role in the proper control of cytokine/growth factor responses and acts as a tumor suppressor in acute myeloid leukemias. Therefore, the objective of the present study was to evaluate the in vitro effect of treatment with Nutlin-3, a small molecule inhibitor of the MDM2/p53 interaction, on the expression of the suppressor of cytokine signaling 1 in primary acute myeloid leukemia cells and in myeloid cell lines with differential p53 status. METHOD: The expression of the suppressor of cytokine signaling 1 was quantitatively analyzed by real-time PCR in myeloid p53wild-type (OCI and MOLM) and p53null HL-60, leukemic cell lines, in patient-derived acute myeloid leukemia blasts, and in primary normal cell types, such as macrophages, endothelial cells, and bone marrow mesenchymal stem cells. The p53-dependence of the suppressor of cytokine signaling 1 upregulation that is induced by Nutlin-3 was analyzed in experiments performed using siRNA for p53, while the functional upregulation of the suppressor of cytokine signaling 1 was analyzed by assessing the levels of phosphorylated STAT-3. RESULTS: Nutlin-3 significantly upregulated the transcription of the suppressor of cytokine signaling 1 in p53wild-type OCI and MOLM but not in p53deleted p53null HL60, myeloid leukemic cell lines, as well as in primary acute myeloid leukemia blasts. Conversely, and somewhat unexpectedly, Nutlin-3 did not modulate the suppressor of cytokine signaling 1 expression in primary normal macrophages, endothelial cells, and bone marrow mesenchymal stem cells. The p53-dependent upregulation of the suppressor of cytokine signaling 1 by Nutlin-3 was associated with the downregulation of phosphorylated STAT-3, a major molecular target of the suppressor of cytokine signaling 1. CONCLUSION: Overall, our data suggest a potential role for the suppressor of cytokine signaling 1 as a therapeutic target of Nutlin-3 in p53 wild-type acute myeloid leukemias

Sex/Gender-Specific Imbalance in CVD: Could Physical Activity Help to Improve Clinical Outcome Targeting CVD Molecular Mechanisms in Women?

In the last two decades, new insights have been gained regarding sex/gender-related differences in cardiovascular disease (CVD). CVD represents the leading cause of death worldwide in both men and women, accounting for at least one-third of all deaths in women and half of deaths in women over 50 years in developing countries. Important sex-related differences in prevalence, presentation, management, and outcomes of different CVDs have been recently discovered, demonstrating sex/gender-specific pathophysiologic features in the presentation and prognosis of CVD in men and women. A large amount of evidence has highlighted the role of sex hormones in protecting women from CVDs, providing an advantage over men that is lost when women reach the menopause stage. This hormonal-dependent shift of sex-related CVD risk consequently affects the overall CVD epidemiology, particularly in light of the increasing trend of population aging. The benefits of physical activity have been recognized for a long time as a powerful preventive approach for both CVD prevention and aging-related morbidity control. Exercise training is indeed a potent physiological stimulus, which reduces primary and secondary cardiovascular events. However, the underlying mechanisms of these positive effects, including from a sex/gender perspective, still need to be fully elucidated. The aim of this work is to provide a review of the evidence linking sex/gender-related differences in CVD, including sex/gender-specific molecular mediators, to explore whether sex- and gender-tailored physical activity may be used as an effective tool to prevent CVD and improve clinical outcomes in women

EDUCAÇÃO EM SAÚDE: UMA ESTRATÉGIA A SER DESENVOLVIDA COM ADOLESCENTES NAS INSTITUIÇÕES DE ENSINO

A Educação em Saúde torna-se uma construção partilhada do conhecimento, que envolve as práticas e experiências dos sujeitos envolvidos, que buscam intervenções nas relações sociais que podem influenciar na qualidade de vida, e consequentemente produzir mudanças comportamentais. Este trabalho tem como objetivo: realizar educação em saúde com escolares da 7° série, a fim de proporcionar momentos de interação e promoção de assuntos relacionados à saúde. O desenvolvimento das atividades educativas foi baseado na discussão de assuntos pertinentes a saúde,considerando a contribuição dessa atividade para a prevençãode doenças e promoção da saúde. Neste contexto entendemoso profissional enfermeiro como coparticipe, comprometido e preocupado com a saúde dos adolescentes, seres em formação ecom capacidade de escolhas saudáveis. Portanto, a realização de trabalhos educativos em instituições de Ensino contribui, instiga e sensibiliza os adolescentes a assumirem uma vida saudável e com responsabilidade, comprometidos com a sua saúde