Exosomal chaperones and miRNAs in gliomagenesis: State-of-art and theranostics perspectives

Gliomas have poor prognosis no matter the treatment applied, remaining an unmet clinical need. As background for a substantial change in this situation, this review will focus on the following points: (i) the steady progress in establishing the role of molecular chaperones in carcinogenesis; (ii) the recent advances in the knowledge of miRNAs in regulating gene expression, including genes involved in carcinogenesis and genes encoding chaperones; and (iii) the findings about exosomes and their cargo released by tumor cells. We would like to trigger a discussion about the involvement of exosomal chaperones and miRNAs in gliomagenesis. Chaperones may be either targets for therapy, due to their tumor-promoting activity, or therapeutic agents, due to their antitumor growth activity. Thus, chaperones may well represent a Janus-faced approach against tumors. This review focuses on extracellular chaperones as part of exosomes’ cargo, because of their potential as a new tool for the diagnosis and management of gliomas. Moreover, since exosomes transport chaperones and miRNAs (the latter possibly related to chaperone gene expression in the recipient cell), and probably deliver their cargo in the recipient cells, a new area of investigation is now open, which is bound to generate significant advances in the understanding and treatment of gliomas

Monocitose é um marcador de risco independente para a doença arterial coronariana

Reseña de la obra de George L. MOSSE: Soldados caídos. La transformación de la memoria de las guerras mundiales, traducción de Ángel Alcalde, Zaragoza, Prensas Universitarias de Zaragoza, 2016 [ed. original en inglés de 1990], 310 pp. ISBN: 978-84-16515-39-4. A cargo de Claudio Hernández Burgos

Can being gay provide a boost in the hiring process? Maybe if the boss is female

Purpose – The purpose of this study was to investigate whether men and women differentially prefer hiring gay and lesbian job applicants relative to equally qualified heterosexual job applicants. Design/methodology/approach – Data were collected from two samples of non-student participants. Each participant evaluated the perceived hirability of an ostensibly real job applicant by reviewing the applicant’s resume. In reality, all participants were randomly assigned to evaluate the same fictitious resume that differed only in the gender and sexual orientation of the applicant. Findings – We find that men perceived gay and lesbian job applicants as less hirable, while women perceived gay and lesbian job applicants as more hirable than heterosexual job applicants. Additionally, we show perceptions of hirability are mediated by perceptions of gay and lesbian job applicants’ competence. Implications – These results show that bias against gays and lesbians is much more nuanced than previous work suggests. One implication is that placing more women in selection roles within organizations could be a catalyst for the inclusion of gay and lesbian employees. Additionally, these results could influence when and how gays and lesbians disclose their gay identities at work. Originality/value –These studies are the first to identify a positive bias in favor of gay and lesbian job applicants. As attitudes toward gays and lesbians become more positive, results like these are important to document as they signal a shift in intergroup relations. These results will also help managers and organizations design selection processes to minimize bias towards applicants. Keywords: gender, sexual orientation, selection, bia

Id1 Interacts and Stabilizes the Epstein-Barr Virus Latent Membrane Protein 1 (LMP1) in Nasopharyngeal Epithelial Cells

The EBV-encoded latent membrane protein 1 (LMP1) functions as a constitutive active form of tumor necrosis factor receptor (TNFR) and activates multiple downstream signaling pathways similar to CD40 signaling in a ligand-independent manner. LMP1 expression in EBV-infected cells has been postulated to play an important role in pathogenesis of nasopharyngeal carcinoma. However, variable levels of LMP1 expression were detected in nasopharyngeal carcinoma. At present, the regulation of LMP1 levels in nasopharyngeal carcinoma is poorly understood. Here we show that LMP1 mRNAs are transcribed in an EBV-positive nasopharyngeal carcinoma (NPC) cell line (C666-1) and other EBV-negative nasopharyngeal carcinoma cells stably re-infected with EBV. The protein levels of LMP1 could readily be detected after incubation with proteasome inhibitor, MG132 suggesting that LMP1 protein is rapidly degraded via proteasome-mediated proteolysis. Interestingly, we observed that Id1 overexpression could stabilize LMP1 protein in EBV-infected cells. In contrary, Id1 knockdown significantly reduced LMP1 levels in cells. Co-immunoprecipitation studies revealed that Id1 interacts with LMP1 by binding to the CTAR1 domain of LMP1. N-terminal region of Id1 is required for the interaction with LMP1. Furthermore, binding of Id1 to LMP1 suppressed polyubiquitination of LMP1 and may be involved in stabilization of LMP1 in EBV-infected nasopharyngeal epithelial cells

Epstein-Barr Virus Associated Modulation of Wnt Pathway Is Not Dependent on Latent Membrane Protein-1

Previous studies have indicated that Epstein-Barr virus (EBV) can modulate the Wnt pathway in virus-infected cells and this effect is mediated by EBV-encoded oncogene latent membrane protein 1 (LMP1). Here we have reassessed the role of LMP1 in regulating the expression of various mediators of the canonical Wnt cascade. Contradicting the previous finding, we found that the levels of E-cadherin, β-catenin, Glycogen Synthase Kinase 3ß (GSK3β), axin and α-catenin were not affected by the expression of LMP1 sequences from normal B cells or nasopharyngeal carcinoma. Moreover, we also show that LMP1 expression had no detectable effect on the E-cadherin and β-catenin interaction and did not induce transcriptional activation of β-catenin. Taken together these studies demonstrate that EBV-mediated activation of Wnt pathway is not dependent on the expression of LMP1

Hsp60 Is Actively Secreted by Human Tumor Cells

Background: Hsp60, a Group I mitochondrial chaperonin, is classically considered an intracellular chaperone with residence in the mitochondria; nonetheless, in the last few years it has been found extracellularly as well as in the cell membrane. Important questions remain pertaining to extracellular Hsp60 such as how generalized is its occurrence outside cells, what are its extracellular functions and the translocation mechanisms that transport the chaperone outside of the cell. These questions are particularly relevant for cancer biology since it is believed that extracellular chaperones, like Hsp70, may play an active role in tumor growth and dissemination. Methodology/Principal Findings: Since cancer cells may undergo necrosis and apoptosis, it could be possible that extracellular Hsps are chiefly the result of cell destruction but not the product of an active, physiological process. In this work, we studied three tumor cells lines and found that they all release Hsp60 into the culture media by an active mechanism independently of cell death. Biochemical analyses of one of the cell lines revealed that Hsp60 secretion was significantly reduced, by inhibitors of exosomes and lipid rafts. Conclusions/Significance: Our data suggest that Hsp60 release is the result of an active secretion mechanism and, since extracellular release of the chaperone was demonstrated in all tumor cell lines investigated, our observations most likel

Metadherin Contributes to the Pathogenesis of Diffuse Large B-cell Lymphoma

BACKGROUND: Metadherin (MTDH) has been demonstrated as a potentially crucial mediator of various types of human malignancies. However, the expression and role of MTDH in diffuse large-B-cell lymphoma (DLBCL) have not been reported yet. This study aimed to illuminate the role of MTDH in the pathogenesis of DLBCL. METHODOLOGY/PRINCIPAL FINDINGS: A remarkable elevation of MTDH on mRNA level was detected in DLBCL tissues by quantitative polymerase chain reaction (PCR). Using Western-blot analysis we found that the expression of MTDH protein was significantly upregulated in DLBCL cell lines and DLBCL tissues compared with peripheral blood mononuclear cells (PBMCs) from healthy samples and tissues from patients of reactive hyperplasia of lymph node. The results showed high expression of MTDH in 23 of 30 (76.67%) DLBCL tissues by using immunohistochemical analysis and the over expression of MTDH was strongly correlated to the clinical staging of patients with DLBCL (P<0.05). Furthermore, the finding suggested that the increase of MTDH in DLBCL cells could distinctly enhance cell proliferation and inhibit cell apoptosis; meanwhile, inhibition of MTDH expression by specific siRNA clearly enhanced LY8 cell apoptosis. Upregulation of MTDH elevated the protein level of total β-catenin and translocation of β-catenin to the nucleus directly or indirectly. Knockdown of MTDH decreased the level of total, cytoplasmic β-catenin and reduced nuclear accumulation of β-catenin protein. This indicated that the function of MTDH on the development of DLBCL was mediated through regulation of Wnt/β-catenin signaling pathway. CONCLUSIONS/SIGNIFICANCE: Our results suggest that MTDH contributes to the pathogenesis of DLBCL mediated by activation of Wnt/β-catenin pathway. This novel study may contribute to further investigation on the useful biomarkers and potential therapeutic target in the DLBCL patients

Police officers and post traumatic stress disorder: discussing the deficit in research, identification and prevention in England and Wales

This article will review available literature regarding Post Traumatic Stress Disorder (PTSD) within policing in England and Wales, with a particular focus on its early identification and prevention. An overview of PTSD will be given as well as an exploration of why police officers are potentially more susceptible to this mental health condition compared to other members of society. Key factors in the early identification and prevention of PTSD will be outlined, with a focus on crisis intervention techniques which have been subject to considerable academic study. There is limited research available from England and Wales that looks specifically at PTSD in policing, this research deficit will be highlighted and key areas of research which need to be explored further will be given so that this problem can be both identified and prevented in officers

Ethnic Minority–Majority Unions in Estonia

Ethnic minority–majority unions—also referred to as mixed ethnic unions—are often seen as the ultimate evidence of the integration of ethnic minorities into their host societies. We investigated minority–majority unions in Estonia, where ethnic minorities account for one-third of the total population (Russians 26%, followed by Ukrainians, Byelorussians, Finns and other smaller groups). Using data from the 2000 Estonian census and regression models, we found that Slavic women are less likely to be in minority–majority unions than are members of other minority groups, with Russians being the least likely. Finns, who are culturally most similar to the Estonian majority population, are the most likely to form a union with an Estonian. For ethnic minority women, the likelihood of being in minority–majority unions is highest in rural areas and increases over generations, with third-generation immigrants being the most likely. Estonian women are most likely to have a minority partner when they or their parents were born abroad and when they live in urban areas. Our findings suggest that both the opportunity to meet potential partners and openness to other ethnic groups are important factors for understanding the dynamics of minority–majority unions