The functions of herpesvirus-encoded microRNAs

Bioinformatic and direct cloning approaches have led to the identification of over 100 novel miRNAs expressed in DNA viruses, although the function of the majority of these small regulatory RNA molecules is unclear. Recently, a number of reports have now identified potential targets of viral miRNAs, including cellular and viral genes as well as an ortholog of an important immune-regulatory cellular miRNA. In this review, we will cover the identification and characterization of miRNAs expressed in the herpesvirus family and discuss the potential significance of their role in viral infection

Cultural Expression Through Art

Our project’s goal is to work towards greater cultural awareness within the Missoula community by focusing on educating children about culture through art. Cultural education has been slow to be implemented in schools, although it is increasing in importance as diversity in the Missoula community and the rest of the U.S. continues to increase. Cultural awareness is a broad term that covers multiple aspects of awareness: empathy, competence, safety, and intelligence. Learning cultural awareness begins at a young age, so we designed a hands-on learning experience directed at students in grades 4 through 6. We decided to use art as a way to connect students to culture in an engaging and memorable way. Due to COVID-19, we created a virtual learning experience using materials that students could easily find at home or any store. Our website contains an introductory lesson on what culture is as well as other lessons led by educators who volunteered to partner with us. Educators provided an art tutorial video as well as a lesson about the culture behind the art project. We partnered with a local nonprofit, The Flagship Program, to offer the website to a small group of students in order to test our website’s functionality and obtain feedback from educators and their students about the material and areas for improvement. By encouraging cultural awareness at young ages, we can support students in developing cross-cultural skills that will foster future global awareness and communication skills. Art itself is a cultural activity that fosters growth, inclusivity, and innovation. By looking at art forms originating in different cultures, our project shows one of the many ways that cultural education can be incorporated into classrooms

A Viral microRNA Down-Regulates Multiple Cell Cycle Genes through mRNA 5 ' UTRs

Global gene expression data combined with bioinformatic analysis provides strong evidence that mammalian miRNAs mediate repression of gene expression primarily through binding sites within the 3′ untranslated region (UTR). Using RNA induced silencing complex immunoprecipitation (RISC-IP) techniques we have identified multiple cellular targets for a human cytomegalovirus (HCMV) miRNA, miR-US25-1. Strikingly, this miRNA binds target sites primarily within 5′UTRs, mediating significant reduction in gene expression. Intriguingly, many of the genes targeted by miR-US25-1 are associated with cell cycle control, including cyclin E2, BRCC3, EID1, MAPRE2, and CD147, suggesting that miR-US25-1 is targeting genes within a related pathway. Deletion of miR-US25-1 from HCMV results in over expression of cyclin E2 in the context of viral infection. Our studies demonstrate that a viral miRNA mediates translational repression of multiple cellular genes by targeting mRNA 5′UTRs

Defining Professionalism for Mental Health Services : A Rapid Systematic Review

Background: Efforts have been made to define professionalism across the professions, yet little attention has been paid to the concept in mental health services, where patients’ needs differ to that in other healthcare specialties. Aims: To derive a definition of professionalism for mental health services using the existing literature. Method: A rapid, systematic review was conducted to identify empirical and non-empirical records that described professionalism in a mental health service context from 2006 to 2017. Studies were synthesised narratively using thematic analysis. Results: Seventy records were included in the review. Professionalism was described on two levels; at a societal level, a dynamic social contract between professions and society, and; at an individual level, having intrapersonal, interpersonal, and working professionalism. Utilising emerging themes, an operationalised definition of professionalism, suitable for a mental health service context was derived. Conclusions: Within mental health services, emphasis is placed on the interpersonal aspects of practice such as communication skills, maintaining boundaries and humanity. Themes relating to the vulnerability of patients and the challenge of supporting autonomy and choice whilst maintaining safety and acting in a client’s best interest are also evident. ‘Practical wisdom’ and a flexible approach to working are needed to manage these challenging situations

TREM2 deficiency attenuates neuroinflammation and protects against neurodegeneration in a mouse model of tauopathy

Significance Alzheimer’s disease (AD) is the most common cause of dementia and is a major public health problem for which there is currently no disease-modifying treatment. There is an urgent need for greater understanding of the molecular mechanisms underlying neurodegeneration in patients to create better therapeutic options. Recently, genetic studies uncovered novel AD risk variants in the microglial receptor, triggering receptor expressed on myeloid cells 2 (TREM2). Previous studies suggested that loss of TREM2 function worsens amyloid-β (Aβ) plaque-related toxicity. In contrast, we observe TREM2 deficiency mitigates neuroinflammation and protects against brain atrophy in the context of tau pathology. These findings indicate dual roles for TREM2 and microglia in the context of amyloid versus tau pathology, which are important to consider for potential treatments targeting TREM2.</jats:p

Classroom Activity for Critical Analysis of News Propagation Online

We present an educational activity for college students to think critically about the truthfulness of news propagated in social media. This activity utilizes TwitterTrails, a visual tool to analyze Twitter claims, events, and memes. This tool provides views such as a propagation graph of a story’s bursting activity, and the co-ReTweeted network of the more prominent members of the audience. Using a response and reflection form, students are guided through these different facets of a story. The classroom activity was iteratively designed over the course of three semesters. Here, we present the learning outcomes from our final semester’s evaluation with 43 students. Our findings demonstrate that the activity provided students with both the conceptual tools and motivation to investigate the reliability of stories in social media. Our contribution also includes access to the tool and materials to conduct this activity. We hope that other educators will further improve and run this activity with their own students

Looking ahead to the future of GeogEd: Creating spaces of exchange between communities of practice

As part of the special issue marking the transition of the Higher Education Research Group to the Geography and Education Research Group, in this final paper we argue that the reformed group has a key role to play in promoting spaces of exchange between the communities of practice that have a stake in the shared endeavours of geography and education. We draw on structured conversations from the group’s launch event, existing literature, and our particular vantage points to identify a range of influences – both heritages that we work with and challenges that we face – that shape the interplay of geography and education in our pedagogical contexts. We argue that the GeogEd Research Group can create spaces of productive exchange between three communities of practice: geographies of education research, geography education research, and pedagogic research. As the research group brings these communities of practice together, it facilitates dialogue, creates new avenues for research, and connects and enhances geography teaching practice across education levels

Looking ahead to the future of GeogEd: creating spaces of exchange between communities of practice

As part of the special issue marking the transition of the Higher Education Research Group to the Geography and Education Research Group, in this final paper we argue that the reformed group has a key role to play in promoting spaces of exchange between the communities of practice that have a stake in the shared endeavours of geography and education. We draw on structured conversations from the group’s launch event, existing literature, and our particular vantage points to identify a range of influences – both heritages that we work with and challenges that we face – that shape the interplay of geography and education in our pedagogical contexts. We argue that the GeogEd Research Group can create spaces of productive exchange between three communities of practice: geographies of education research, geography education research, and pedagogic research. As the research group brings these communities of practice together, it facilitates dialogue, creates new avenues for research, and connects and enhances geography teaching practice across education levels

Effect of genetic variability in 20 pharmacogenes on concentrations of tamoxifen and its metabolites

Background: Tamoxifen, as a treatment of estrogen receptor positive (ER+) breast cancer, is a weak anti-estrogen that requires metabolic activation to form metabolites with higher anti-estrogenic activity. Endoxifen is the most-studied active tamoxifen metabolite, and endoxifen concentrations are highly associated with CYP2D6 activity. Associations of tamoxifen efficacy with measured or CYP2D6-predicted endoxifen concentrations have been inconclusive. Another active metabolite, 4-OHtam, and other, less active metabolites, Z-4′-endoxifen and Z-4′-OHtam, have also been reported to be associated with tamoxifen efficacy. Method: Genotype for 20 pharmacogenes was determined by VeriDose® Core Panel and VeriDose®CYP2D6 CNV Panel, followed by translation to metabolic activity phenotype following standard activity scoring. Concentrations of tamoxifen and seven metabolites were measured by UPLC-MS/MS in serum samples collected from patients receiving 20 mg tamoxifen per day. Metabolic activity was tested for association with tamoxifen and its metabolites using linear regression with adjustment for upstream metabolites to identify genes associated with each step in the tamoxifen metabolism pathway. Results: A total of 187 patients with genetic and tamoxifen concentration data were included in the analysis. CYP2D6 was the primary gene associated with the tamoxifen metabolism pathway, especially the conversion of tamoxifen to endoxifen. CYP3A4 and CYP2C9 were also responsible for the metabolism of tamoxifen. CYP2C9 especially impacted the hydroxylation to 4-OHtam, and this involved the OATP1B1 (SLCO1B1) transporter. Conclusion: Multiple genes are involved in tamoxifen metabolism and multi-gene panels could be useful to predict active metabolite concentrations and guide tamoxifen dosing.publishedVersio