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The Drosophila testis is a close-ended muscular tube sheathed by pigment cells and acto-myosin of genital disc origin29. Here, paralleled division between GSCs and CySCs gives rise to units of gonialblasts (GBs) surrounded by daughter cyst cells30. Due to the highly-coordinated manner in which this event occurs, cell-to-cell signalling across the niche microenvironment is vital. We have demonstrated how males overexpressing CTPSynIsoC have a much greater tendency to produce bulged testes. Tissue overgrowth is always exclusive to the apical tip, where the stem cell niche resides and associated intercellular communication events transpire. In such situations where it is found in excess, is CTPSyn then capable of disturbing the delicate balance observed between these signalling molecules, leading to uncontrolled cell proliferation? Several cancer cell lines of hepatoma16, leukaemia17,31,32,33 and colon34 origin are known to intrinsically express higher levels of CTPSyn. Conversely, a more recent study has demonstrated how RNAi-mediated knockdown of the gene could reduce tumour overgrowth significantly in Drosophila larvae35. With this study, we ask whether the overexpression of CTPSyn alone could generate tissues or organs with cancerous properties.
In this study, we demonstrate that CTPSynIsoC overexpression causes a lengthening of cytoophidia in testes tissue. For a third of males, this culminates in the form of apical tip bulging. Higher numbers of germline cells and spermatocytes is shown to be main cause of testicular overgrowth, as these are stained by Anti-Vasa and Anti-Coilin, respectively. A miRNA i.e. miR-975 is also found to induce the bulged-testes phenotype in 20% of males overexpressing it, although cytoophidia length, size, and compaction is not visibly altered. RT-qPCR nonetheless reveals that a significant increment in CTPSynIsoC levels does accompany miR-975 overexpression. This is not a two-way relationship, CTPSynIsoC overexpression does not cause miR-975 upregulation. Quantification of several cancer-related genes further show how differentially either overexpression events affect genetic expression, suggesting that CTPSyn might be closely related to these genes, if not at least by parts. They both also affect Myc expression positively. As a potent oncogene, it is possible that the defining induction event in testes overexpressing either CTPSynIsoC or miR-975 is Myc-protein production, the combination effects of which would have eventually led to excessive proliferation, and therefore tissue-overgrowth. Though the findings presented here are insufficient to solidly link CTPsyn via miR-975 to tumorigenesis, this study has demonstrated that the overexpression of either gene could affect tissue growth in such a way that it culminates a germline cells hyper-growth. For this reason, we also propose greater utilization of testes as a source of germline cells and its stem cells niche studies. In the future, simultaneous overexpression of CTPSynIsoC and miR-975 could be employed to further investigate if there is a connection between the enzyme and the miRNA. Knock-down experiments using RNAi and transcriptomics as well as RNA sequencing will also be implemented to identify the causes of the bulging phenotype, and to clarify once and for all whether these underlying mechanisms are indeed cancerous by nature.
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In the United States, disparities in health literacy parallel disparities in health outcomes. Our research contributes to how diverse indicators of social inequalities (i.e., objective social class, relational social class, and social resources) contribute to understanding disparities in health literacy.
Our findings are consistent with previous research on the social and SES determinants of health literacy. However, our findings reveal the importance of relational social status for understanding health literacy disparities in the United States. Objective indicators of social status are persistent and robust indicators of health literacy. Measures of relational social status such as civic engagement (i.e., voting, volunteering, and library use) are associated with higher health literacy levels net of objective resources. Social resources including speaking English and marital status are associated with higher health literacy levels.
There are limitations to the use of income, educational attainment, and occupational status as determinants of health literacy. The rationale for using income follows that increased income provides additional access to health resources [33]. However, the relationship between income and health is confounded by reverse causality [34]; not only are poverty and low income a significant risk for poor health outcomes, but the experience of a severe chronic illness or disability may also reduce overall earning potential [17]. The connection between educational attainment and health is linear and positive. Yet, education does not completely capture access to resources, and is only significant to the extent that the associated skills and knowledge are socially valuable [4, 34]. Occupational prestige is the mutual assessment of the status associated with the title of an employment position. Occupational status, however, is only applicable for working-age adults in the labor force [3, 34] and occupational status may not capture all the social connections related to health literacy such as social empowerment. Moreover, income, educational attainment, and occupational status are of limited utility in terms of offering insight into the effect of SES position on health literacy as previous research indicates health literacy independently predicts health outcomes when controlling for structural indicators of socioeconomic position [8, 15].
Social resources are normative social means that provide economic protection and benefits. Measures of social resources may include language spoken, marital status, and methods of seeking out health information [37, 38]. Speaking the primary or dominant language is an essential component to integrate and navigate within a given social context [49, 50]. In the United States, previous research reveals that Hispanics who only speak Spanish, compared to Hispanics who speak English and Spanish, experience greater disparities in use of healthcare services and health outcomes [50, 51]. Marriage or living as a married couple confers increased economic stability, lower levels of depression, and higher levels of life satisfaction compared to people who never marry [52, 53]. Access to multiple sources of health information provides the benefit of informed health decision making [10] and is associated with less ambiguous knowledge of health conditions [54].
Relational social class and social resources are examined in this study to provide greater insight into social inequality in health literacy. In general, we expect relational and social resource measures will have additional value in understanding the disparities in health literacy. Thus, we hypothesize that relational social class measures (i.e., full-time employment, voting, and volunteering) are significant positive predictors of higher health literacy levels, net of the demographic and objective SES (i.e., income, educational attainment, and occupational prestige) resources measures. We also hypothesize that access to social resources (i.e., native English speaker, marriage, and the number of health information sources) is significantly associated with higher levels of health literacy, net of the demographic and objective SES resources measures.
Data come from the 2003 National Assessment of Adult Literacy (NAAL). The NAAL is a unique nationally representative data set that includes an Item Response Theory (IRT) based measure of health literacy as well as measures of relational social class, social resources, and objective social resources. The written informed consent for participation in the NAAL, sampling design, and complete sample size are described elsewhere [55]. The complete NAAL household sample of more than 18,000 respondents was limited to adults (i.e., 18 years of age and older) for an analytical sample of 14,592 respondents. The analyses were performed with approval from the Institutional Review Board at North Carolina State University.
Health literacy scores were significantly lower for those who grew up speaking Spanish and now speak English, those who speak Spanish only, and those who grew up speaking a language other than English or Spanish (Model 5). Health literacy was significantly lower for respondents who never married compared to married or co-habitating respondents. Model 5 accounted for 28.6 % of the variation in health literacy scores which represented a 110.3 % increase over the baseline model. Overall, the results suggest that measures of relational social class and social resources improve our understanding of disparities in health literacy. 041b061a72