184 research outputs found
Does gender-fair language pay off? The social perception of professions from a cross-linguistic perspective
No full textIn many languages, masculine forms (e.g., German Lehrer, “teachers, masc.”) have traditionally been used to refer to both women and men, although feminine forms are available, too. Feminine-masculine word pairs (e.g., German Lehrerinnen und Lehrer, “teachers, fem. and teachers, masc.”) are recommended as gender-fair alternatives. A large body of empirical research documents that the use of gender-fair forms instead of masculine forms has a substantial impact on mental representations. Masculine forms activate more male representations even when used in a generic sense, whereas word pairs (e.g., German Lehrerinnen und Lehrer, “teachers, fem. and teachers, masc.”) lead to a higher cognitive inclusion of women (i.e., visibility of women). Some recent studies, however, have also shown that in a professional context word pairs may be associated with lesser status. The present research is the first to investigate both effects within a single paradigm. A cross-linguistic (Italian and German) study with 391 participants shows that word pairs help to avoid a male bias in the gender-typing of professions and increase women's visibility; at the same time, they decrease the estimated salaries of typically feminine professions (but do not affect perceived social status or competence). This potential payoff has implications for language policies aiming at gender-fairness
Merkel cell polyomavirus DNA sequences in the buffy coats of healthy blood donors
No full textMerkel cell polyomavirus (MCPyV), a DNA tumor virus, has been found to be associated with Merkel cell carcinoma and chronic lymphocytic leukemia. MCPyV sequences have also been detected in various normal tissues in tumor-affected patients. Immunologic studies have detected MCPyV antibodies in as many as 80% of healthy blood donors. This high seroprevalence suggests that MCPyV infection is widespread in humans. In our study, buffy coats, which were examined for MCPyV DNA Tag sequences, showed a prevalence of 22%. Viral DNA load was revealed in blood samples from 10 to 100 molecules/100 000 cells. DNA sequencing confirmed that polymerase chain reaction amplicons belong to the MCPyV strain, MKL-1. To interpret the putative role of MCPyV in chronic lymphocytic leukemia, we may infer that, during a long period of viral persistence in blood cells, this DNA tumor virus may generate mutants, which are able to participate as cofactors in the multistep process of cell transformatio
Merkel Cell Polyomavirus (MCV) in Buffy Coats of Healthy Blood Donors.
No full textBackground.
Merkel cell polyomavirus (MCV), a DNA tumor virus, has been found to be associated with Merkel cell carcinoma (MCC) and chronic lymphocytic leukaemia (CLL). MCV sequences have also been detected in various normal tissues in tumor affected patients. Immunologic studies have detected MCV antibodies in as many as 80% of healthy blood donors. This high seroprevalence suggests that MCV infection is widespread in humans.
Materials and methods
DNA from buffy coats (n=60) of healthy blood donors was investigated by two PCR rounds, 35 cycles each, for two different MCV Tag regions, nt 571-879 and nt 1709-1846, respectively. To quantify the MCV DNA load, positive samples were further analyzed by RQ-PCR for Tag sequences. To determine the human cell equivalents of each sample under analysis, RQ-PCR assays were carried out simultaneously with the cellular RNase P gene. The specificity of PCR amplified products, 10 amplicons from the MCV Tag regions, were DNA sequenced.
Results
PCR re-amplifications showed that 13 out of 60 (22%) DNA samples were positive for MCV Tag coding sequences. Buffy coats under analysis indicated that the viral DNA copy numbers were very low, ranging from 10 to 100 copies/100,000 cells. The sequencing result of the PCR amplicons, for both strands, nt 571-879 and nt 1709-nt 1846, identified as belonging to the MCV genome, MKL-1 strain.
Conclusions
MCV sequences were detected in buffy coats from healthy blood donors. This result suggests that MCV is able to infect specific blood leukocyte cells, where it remains in a latent/persistent state in the PBMCs of immune-competent individuals. In the long term, viral persistent infection may allow MCV to generate mutants which can participate in the cell transformation process. Indeed, large T antigen MCV deletion mutants have been detected in CLL or integrated into MCC. This oncogenic process, together with the immune impairment of the host and other factors, is a well-known multistep cell transformation mechanism employed by other DNA tumor viruses, such as human papillomaviruses, which are closely related to the Merkel cell polyomavirus.
Acknowledgements
We thank Prof. Tobias Allander, Karolinska Instituten, Stockolm, Sweden, for his generous gift of the recombinant plasmid pMCV-LT.1
Reference
Pancaldi C, Corazzari V, Maniero S, Mazzoni E, Comar M, Martini F, Tognon M. Merkel cell polyomavirus DNA sequences in the buffy coats of healthy blood donors. Blood 2011, 117:7099-7101
Expression of a neuroendocrine gene signature in gastric tumor cells from CEA 424-SV40 large T antigen-transgenic mice depends on SV40 large T antigen.
No full textA large fraction of murine tumors induced by transgenic expression of SV40 large T antigen (SV40 TAg) exhibits a neuroendocrine phenotype. It is unclear whether SV40 TAg induces the neuroendocrine phenotype by preferential transformation of progenitor cells committed to the neuroendocrine lineage or by transcriptional activation of neuroendocrine genes. To address this question we analyzed CEA424-SV40 TAg-transgenic mice that develop spontaneous tumors in the antral stomach region. Immunohistology revealed expression of the neuroendocrine marker chromogranin A in tumor cells. By ELISA an 18-fold higher level of serotonin could be detected in the blood of tumor-bearing mice in comparison to nontransgenic littermates. Transcriptome analyses of antral tumors combined with gene set enrichment analysis showed significant enrichment of genes considered relevant for human neuroendocrine tumor biology. This neuroendocrine gene signature was also expressed in 424GC, a cell line derived from a CEA424-SV40 TAg tumor, indicating that the tumor cells exhibit a similar neuroendocrine phenotype also in vitro. Treatment of 424GC cells with SV40 TAg-specific siRNA downregulated expression of the neuroendocrine gene signature. SV40 TAg thus appears to directly induce a neuroendocrine gene signature in gastric carcinomas of CEA424-SV40 TAg-transgenic mice. This might explain the high incidence of neuroendocrine tumors in other murine SV40 TAg tumor models. Since the oncogenic effect of SV40 TAg is caused by inactivation of the tumor suppressor proteins p53 and RB1 and loss of function of these proteins is commonly observed in human neuroendocrine tumors, a similar mechanism might cause neuroendocrine phenotypes in human tumors
Proposal for a Performance Dashboard for the Monitoringof Water and Sewage Service Companies (WaSCs)
No full textThe water and sewage industry provides an essential service to the community, but it is characterized by natural monopoly tendencies of service suppliers. In this framework, it is very important to assist regulators with a small set of critical indicators (performance dashboard) for the evaluation and monitoring of the service provided by Water and Sewage Companies (WaSCs). The paper originates from the analysis of situation of Piemonte (Italy), where each regional and local body adopts a proprietary Performance Measurement System (PMS). In order to improve the coordination of information flow and to support the definition of common service standards, a methodology to merge existing PMSs and define a unique shared reference system is proposed. The Kaplan and Norton's Balanced Scorecard (BSC) is adopted as the reference model of this approach. BSC is widely recognized to be an exhaustive and balanced framework in describing the performances of an organization and ensures that all the operational aspects of WaSCs are adequately monitored. The output of the proposed procedure is a general performance dashboard for the monitoring of WaSCs. The dashboard is shown and some remarks about indicators properties are developed. In particular, this analysis highlights some common pitfalls originated by a ‘rushed' aggregation of several performance indicators. Description is supported by several example
New attempts at Electronic Documents in Transport. Bolero - the end of the experiment, the beginning of the future?
No full textIn this thesis the author examines a 'revolution' taking place in the shipping industry brought on by the development of computerisation, electronic commerce and the change from paper documentation to electronic documentation in the carriage of goods by sea. The focus of the paper is on Bolero, a project of the European Community beginning in the early 1990s and which has been used commercially since September 1999. In this paper the author follows the Bolero project from its inception as an experiment through to its commercial application. The question is asked to what extent Bolero has become an alternative to, or in fact replaced paper documentation in the carriage of goods by sea. As an introduction the author looks at the paper bill of lading and other forms of sea transport documentation with a focus on their advantages and disadvantages. He then examines the development of EDI and paperless sea transport documentation, in particular Bolero and the history of its development. Following this is an in depth investigation of the Bolero system in its current form, the contractual relations involved and the position of Bolero in the surrounding legal framework in a South African and international context. Finally the author looks at the future of Bolero as a commercial enterprise
Prognostic value of antibodies to Merkel cell polyomavirus T antigens and VP1 protein in patients with Merkel cell carcinoma
No full textInternational audienceMerkel cell polyomavirus (MCPyV) is the main etiological agent of Merkel cell carcinoma (MCC). Serum antibodies against the major MCPyV capsid protein (VP1) are detected in the general population, whereas antibodies against MCPyV oncoproteins (T-antigens) have been reported specifically in patients with MCC. The primary aim of this study was to assess whether detection of serum antibodies against MCPyV proteins at baseline was associated with disease outcome in patients with MCC. The secondary aim was to establish whether evolution of these antibodies during follow-up was associated with the course of the disease. Serum T-antigen and VP1 antibodies were assessed by ELISA using recombinant proteins in a cohort of 143 patients with MCC, including 84 patients with serum samples available at baseline. Low levels of VP1 antibodies at baseline (<10,000) were significantly and independently associated with increased risk of recurrence (HR 2.71, 95% CI 1.13-6.53, p=0.026) and death (HR 3.74, 95% CI 1.53-9.18, p=0.004), whereas T-antigen antibodies were not found to be associated with outcome. VP1 antibodies did not differ between patients in remission and those with recurrence or progression during follow up. However, T-antigen antibodies were more frequently detected in patients with recurrence or progression at 12 months (p=0.020) and 24 months (p=0.016) after diagnosis. VP1 antibodies constitute a prognostic marker at baseline whereas T-antigen antibodies constitute a marker of disease recurrence or progression if detected more than 12 months after diagnosis. This article is protected by copyright. All rights reserved
Specificity of squamous cell carcinoma antigen (SCCA)-IgM detection in patients with HCV infection and rheumatoid factor seropositivity.
No full textIgM antibodies bound to different cancer antigens have shown recently a higher diagnostic value, compared with the corresponding free molecule, giving rise to a new family of biomarkers. High or increasing levels of Squamous Cell Carcinoma Antigen (SCCA)-IgM immune complexes were associated with more advanced liver disease and increased risk of development of HCC. Rheumatoid factor (RF) represents a long-standing problem of interference for immunometric assays. The aim of the present study was to examine the specificity of SCCA-IgM in relation to the presence of RF reactivity in patients infected with hepatitis C virus (HCV). Sera of 73 patients with cirrhosis, infected with HCV, (mean age ± SD: 66 ± 13 years; M/F: 45/28), including 21 patients with HCC, were studied. SCCA-IgM immune complexes levels were measured by a commercial ELISA. To evaluate the possible interfering effect of RF, the standard calibrator, positive for SCCA-IgM, was spiked with serial dilutions of a RF positive or negative serum. SCCA-IgM immune complexes were positive in 35 out of 73 (48%) patients, while RF activity was found in 10 out of 73 (14%) patients. Patients with cirrhosis with RF activity had significantly higher levels of SCCA-IgM, compared to RF negative cases; however, no significant correlation between SCCA-IgM and RF values was observed. In samples created artificially the same results in terms of reactivity for SCCA-IgM were obtained, regardless of the presence of RF activity. These findings support the lack of correlation between the two parameters found in sera of patients infected with HCV
Characterization of molecular mechanisms driving Merkel cell polyomavirus oncogene transcription and tumorigenic potential
No full textMerkel cell polyomavirus (MCPyV) is associated with approximately 80% of cases of Merkel cell carcinoma (MCC), an aggressive type of skin cancer. The incidence of MCC has tripled over the past twenty years, but there are currently very few effective targeted treatments. A better understanding of the MCPyV life cycle and its oncogenic mechanisms is needed to unveil novel strategies for the prevention and treatment of MCC. MCPyV infection and oncogenesis are reliant on the expression of the early viral oncoproteins, which drive the viral life cycle and MCPyV+ MCC tumor cell growth. To date, the molecular mechanisms regulating the transcription of the MCPyV oncogenes remain largely uncharacterized. In this study, we investigated how MCPyV early transcription is regulated to support viral infection and MCC tumorigenesis. Our studies established the roles of multiple cellular factors in the control of MCPyV gene expression. Inhibitor screening experiments revealed that the histone acetyltransferases p300 and CBP positively regulate MCPyV transcription. Their regulation of viral gene expression occurs through coactivation of the transcription factor NF-κB, which binds to the viral genome to drive MCPyV oncogene expression in a manner that is tightly controlled through a negative feedback loop. Furthermore, we discovered that small molecule inhibitors specifically targeting p300/CBP histone acetyltransferase activity are effective at blocking MCPyV tumor antigen expression and MCPyV+ MCC cell proliferation. Together, our work establishes key cellular factors regulating MCPyV transcription, providing the basis for understanding the largely unknown mechanisms governing MCPyV transcription that defines its infectious host cell tropism, viral life cycle, and oncogenic potential. Our studies also identify a novel therapeutic strategy against MCPyV+ MCC through specific blockage of MCPyV oncogene expression and MCC tumor growth. Author summary MCPyV is a ubiquitous skin infection that can cause one of the most aggressive and highly fatal skin cancers, MCC, which has been increasing in incidence in the decades since its initial discovery. Despite the growing concern presented by this cancer, there are currently no effective targeted therapies to treat MCC. MCC metastasizes rapidly and resists currently available chemotherapy and immune checkpoint inhibitor treatment strategies in a significant portion of patients. Approximately 80% of MCCs are caused by MCPyV, which normally maintains asymptomatic infection within the skin but in rare cases drives MCPyV+ MCC oncogenesis through the expression of the viral oncogenes. Our characterization of the largely unknown molecular mechanisms controlling MCPyV gene expression furthers our understanding of the link between MCPyV infection and MCC oncogenesis. Our study also identifies druggable targets that are exploitable to specifically repress MCPyV oncogene expression and MCC tumor growth. This work demonstrates that hampering viral oncogene transcription is a novel and effective therapeutic strategy to obliterate MCPyV-induced MCC tumorigenesis
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