RESUMO
The Drinking Water Tool (DWT) is a community-driven online tool that provides diverse users with information about drinking water sources and threats to drinking water quality and access due to drought. Development of the DWT was guided by the Community Water Center (CWC) as part of the Water Equity Science Shop (WESS), a research partnership integrating elements of community-based participatory research and the European Science Shop model. The WESS engages in scientific projects that inform policy change, advance water justice, and reduce cumulative exposure and disproportionate health burdens among impacted communities in California. WESS researchers conducted qualitative analysis of 15 stakeholder interviews regarding the DWT, including iterative feedback and the stakeholder consultation process as well as stakeholder perceptions of the tool's impact on California water policy, organizing, and research. Results indicate that the DWT and the stakeholder engagement process which developed it were effective in influencing policy priorities and in promoting interagency coordination at multiple levels to address water equity challenges and their disproportionate burdens, particularly among rural and low socioeconomic status areas and communities of color.
Assuntos
Água Potável , Pesquisa Participativa Baseada na Comunidade/métodos , Visualização de Dados , Humanos , Políticas , Justiça SocialRESUMO
Recent prostate-specific antigen-based screening trials indicate an urgent need for novel and noninvasive biomarker identification strategies to improve the prediction of prostate cancer behavior. Noncoding microRNAs (miRNA) in the serum and plasma have been shown to have potential as noninvasive markers for physiologic and pathologic conditions. To identify serum miRNAs that diagnose and correlate with the prognosis of prostate cancer, we developed a multiplex quantitative reverse transcription PCR method involving the purification of multiplex PCR products followed by uniplex analysis on a microfluidics chip to evaluate 384 human miRNAs. Using Dgcr8 and Dicer knockout (small RNA-deficient) mouse ES cells as the benchmark, we confirmed the validity of our technique and uncovered a considerable lack of accuracy in previously published methods. Profiling 48 sera from healthy men and untreated prostate cancer patients with differing CAPRA scores, we identified miRNA signatures that allow us to diagnose cancer patients and correlate with a prognosis. These serum signatures include oncogenic and tumor-suppressive miRNAs, suggesting functional roles in prostate cancer progression.
Assuntos
MicroRNAs/sangue , Técnicas Analíticas Microfluídicas/métodos , Neoplasias da Próstata/sangue , Neoplasias da Próstata/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Estudos de Casos e Controles , Humanos , Masculino , MicroRNAs/genética , Prognóstico , Neoplasias da Próstata/diagnósticoRESUMO
Dicer, which is required for the processing of both microRNAs (miRNAs) and small interfering RNAs (siRNAs), is essential for oocyte maturation [1, 2]. Oocytes express both miRNAs and endogenous siRNAs (endo-siRNAs) [3, 4]. To determine whether the abnormalities in Dicer knockout oocytes during meiotic maturation are secondary to the loss of endo-siRNAs and/or miRNAs, we deleted Dgcr8, which encodes an RNA-binding protein specifically required for miRNA processing. In striking contrast to Dicer, Dgcr8-deficient oocytes matured normally and, when fertilized with wild-type sperm, produced healthy-appearing offspring, even though miRNA levels were reduced to similar levels as Dicer-deficient oocytes. Furthermore, the deletion of both maternal and zygotic Dgcr8 alleles did not impair preimplantation development, including the determination of the inner cell mass and trophectoderm. Most surprisingly, the mRNA profiles of wild-type and Dgcr8 null oocytes were essentially identical, whereas Dicer null oocytes showed hundreds of misregulated transcripts. These findings show that miRNA function is globally suppressed during oocyte maturation and preimplantation development and that endo-siRNAs, rather than miRNAs, underlie the Dicer knockout phenotype in oocytes.
Assuntos
Blastocisto/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Oócitos/metabolismo , Animais , RNA Helicases DEAD-box/deficiência , RNA Helicases DEAD-box/genética , Endorribonucleases/deficiência , Endorribonucleases/genética , Feminino , Masculino , Camundongos , Camundongos Knockout , Modelos Biológicos , Oócitos/crescimento & desenvolvimento , Fenótipo , Gravidez , Proteínas/genética , Proteínas/metabolismo , Processamento Pós-Transcricional do RNA , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas de Ligação a RNA , Ribonuclease IIIRESUMO
Dgcr8 knockout embryonic stem (ES) cells lack microprocessor activity and hence all canonical microRNAs (miRNAs). These cells proliferate slowly and accumulate in G1 phase of the cell cycle. Here, by screening a comprehensive library of individual miRNAs in the background of the Dgcr8 knockout ES cells, we report that multiple ES cell-specific miRNAs, members of the miR-290 family, rescue the ES cell proliferation defect. Furthermore, rescued cells no longer accumulate in the G1 phase of the cell cycle. These miRNAs function by suppressing several key regulators of the G1-S transition. These results show that post-transcriptional regulation by miRNAs promotes the G1-S transition of the ES cell cycle, enabling rapid proliferation of these cells. Our screening strategy provides an alternative and powerful approach for uncovering the role of individual miRNAs in biological processes, as it overcomes the common problem of redundancy and saturation in the miRNA system.
