KAP1 Recruitment of the 7SK snRNP Complex to Promoters Enables Transcription Elongation by RNA Polymerase II

SummaryThe transition from transcription initiation to elongation at promoters of primary response genes (PRGs) in metazoan cells is controlled by inducible transcription factors, which utilize P-TEFb to phosphorylate RNA polymerase II (Pol II) in response to stimuli. Prior to stimulation, a fraction of P-TEFb is recruited to promoter-proximal regions in a catalytically inactive state bound to the 7SK small nuclear ribonucleoprotein (snRNP) complex. However, it remains unclear how and why the 7SK snRNP is assembled at these sites. Here we report that the transcriptional regulator KAP1 continuously tethers the 7SK snRNP to PRG promoters to facilitate P-TEFb recruitment and productive elongation in response to stimulation. Remarkably, besides PRGs, genome-wide studies revealed that KAP1 and 7SK snRNP co-occupy most promoter-proximal regions containing paused Pol II. Collectively, we provide evidence of an unprecedented mechanism controlling 7SK snRNP delivery to promoter-proximal regions to facilitate "on-site" P-TEFb activation and Pol II elongation

To be young, Black, and living with breast cancer: a systematic review of health-related quality of life in young Black breast cancer survivors

Compared with young White women, young Black women are more likely to present with aggressive breast cancer (BC) subtypes that are potentially linked to worse health-related quality of life (HRQOL); however, there is limited consensus regarding HRQOL needs among young Black BC survivors. Employing Ferrell's framework on QOL in BC (i.e., physical, psychological, social, and spiritual well-being), we conducted a systematic review on HRQOL among Black BC survivors aged <50 years and proposed recommendations for advancing HRQOL research and care for this population

An Innovative Use of Twitter to Disseminate and Promote Medical Student Scholarship During the COVID-19 Pandemic: Usability Study

BACKGROUND: Due to the emergence of the COVID-19 pandemic in March 2020, the cancellation of in-person learning activities forced every aspect of medical education and student engagement to pivot to a web-based format, including activities supporting the performance and dissemination of scholarly work. At that time, social media had been used to augment in-person conference learning, but it had not been used as the sole platform for scholarly abstract presentations. OBJECTIVE: Our aim was to assess the feasibility of using Twitter to provide a completely web-based forum for real-time dissemination of and engagement with student scholarly work as an alternative to a traditional in-person poster presentation session. METHODS: The Brody School of Medicine at East Carolina University launched an online Medical Student Scholarship Forum, using Twitter as a platform for students to present scholarly work and prepare for future web-based presentations. A single student forum participant created posts using a standardized template that incorporated student research descriptions, uniform promotional hashtags, and individual poster presentations. Tweets were released over 5 days and analytic data were collected from the Twitter platform. Outcome measures included impressions, engagements, retweets, likes, media engagements, and average daily engagement rate. RESULTS: During the conference, the student leader published 63 tweets promoting the work of 58 students (55 medical and 3 dental students) over 5 days. During the forum and the following week, tweets from the @BrodyDistinctly Twitter account received 63,142 impressions and 7487 engagements, including 187 retweets, 1427 likes, and 2082 media engagements. During the 5 days of the forum, the average daily engagement rate was 12.72%. CONCLUSIONS: Using Twitter as a means of scholarly dissemination resulted in a larger viewing community compared to a traditional in-person event. Early evidence suggests that social media platforms may be an alternative to traditional scholarly presentations. Presenting via Twitter allowed students to receive instantaneous feedback and effectively network with wider academic communities. Additional research is needed to evaluate the effectiveness of knowledge uptake, feedback, and networking

Motivational Interviewing Counseling to Increase Endocrine Therapy Adherence in Diverse Patients

Background: Oral endocrine therapy (ET) is an inexpensive and effective therapy for hormone receptor-positive (HR+) breast cancer that prevents recurrence but relies upon long-term adherence for up to ten years. More than 80% of breast cancer patients have an HR+ phenotype and are candidates for ET, but approximately half discontinue or become non-adherent by five years. ET underuse is more prevalent in Black and young (18 years old, English speaking, and with stage I–III HR+ breast cancer. Participants were recruited across a large academic medical center and four community sites. Feasibility and acceptability were assessed by measures of participant recruitment, retention, session participation, and patient-reported satisfaction. ET adherence at 12 months was assessed by self-report and medication event monitoring system (MEMS) caps using a continuous measure of the proportion of days covered (PDC) as well as a dichotomous measure of the optimal adherence, defined as >80% PDC. Results: Forty-two women initiated the intervention, of whom thirty-five participants (83%) completed outcome assessments at 12 months, including thirteen Black and twenty-two non-Black participants. The average participant age was 54.8 years (range: 25–73). Overall, 97% completed at least three MI sessions and 83% completed at least four sessions. Participant retention and satisfaction were high, particularly among Black women. Self-reported adherence at 12 months was 88% overall (100% in Black women and 81% in non-Black women). The majority of women also achieved 80% of days adherent using MEMS caps, with a greater adherence in Black women. Conclusions: This study demonstrates the feasibility, acceptability, and early promise of the effectiveness of an MI counseling-based intervention to promote ET adherence and prevent breast cancer recurrence in diverse populations

T2-weighted 3D fast spin echo imaging with water-fat separation in a single acquisition

Purpose: To develop a robust 3D fast spin echo (FSE) T2-weighted imaging method with uniform water and fat separation in a single acquisition, amenable to high-quality multiplanar reformations. Materials and Methods: The Iterative Decomposition of water and fat with Echo Asymmetry and Least squares estimation (IDEAL) method was integrated with modulated refocusing flip angle 3D-FSE. Echoes required for IDEAL processing were acquired by shifting the readout gradient with respect to the Carr-Purcell-Meiboom-Gill echo. To reduce the scan time, an alternative data acquisition using two gradient echoes per repetition was implemented. Using the latter approach, a total of four gradient echoes were acquired in two repetitions and used in the modified IDEAL reconstruction. Results: 3D-FSE T2-weighted images with uniform water-fat separation were successfully acquired in various anatomies including breast, abdomen, knee, and ankle in clinically feasible scan times, ranging from 5:30-8:30 minutes. Using water-only and fat-only images, in-phase and out-of-phase images were reconstructed. Conclusion: 3D-FSE-IDEAL provides volumetric T2-weighted images with uniform water and fat separation in a single acquisition. High-resolution images with multiple contrasts can be reformatted to any orientation from a single acquisition. This could potentially replace 2D-FSE acquisitions with and without fat suppression and in multiple planes, thus improving overall imaging efficiency. © 2010 Wiley-Liss, Inc

The Grizzly, October 7, 2010

Career Services Recognized as LGBTQA Certified • Berman Museum Celebrates Community within Collegeville • Residents of Reimert Hall Collect Can Tabs for Troops • UC Goes Pink \u2710 • Novak\u27s Art Exhibit Shares History of Baseball • CAB October Preview • Ursinus Dance Group Knows How to Move It • Seeking Tenure: Professor Gregory Scranton, MCS • School Spirit with Mucus • Sounding Off on UC Ginkgo Trees • Men\u27s Lacrosse Joins in the Fight Against Cancerhttps://digitalcommons.ursinus.edu/grizzlynews/1820/thumbnail.jp

The Grizzly, November 18, 2010

B\u27Naturals Sing Their Way to Success • Mellon Teaching and Learning Initiative Introduced to Ursinus • Ursinus College Facilities Continues to Shape Campus • Seismic Step Team Holds Fundraiser • Open Mic Night • Ursinus Students Take a STAND for Justice • Merchant of Venice • UCARE Promotes Wismer on Wheels • Fight the Yawn With Up \u27Til Dawn • An Empire of Dirt • Internship Profile: Maggie Stauffer • Opinions: UC Should Remain a Wet Campus; Ursinus Should Become a Dry Campus; U.S. and India Look to Strengthen International Ties • Football Clinches Three-Way Tie for C.C. Titlehttps://digitalcommons.ursinus.edu/grizzlynews/1825/thumbnail.jp

The international generalisability of evidence for health policy: a cross country comparison of medication adherence following policy change

Copayments for prescriptions may increase morbidity and mortality via reductions in adherence to medications. Relevant data can inform policy to minimise such unintended effects. We explored the generalisability of evidence for copayments by comparing two international copayment polices, one in Massachusetts and one in Ireland, to assess whether effects on medication adherence were comparable. We used national prescription data for public health insurance programmes in Ireland and Medicaid data in the U.S. New users of oral anti-hypertensive, anti-hyperlipidaemic and diabetic drugs were included (total n = 14,259 in U.S. and n = 43,843 in Ireland). We examined changes in adherence in intervention and comparator groups in each setting using segmented linear regression with generalised estimating equations. In Massachusetts, a gradual decrease in adherence to anti-hypertensive medications of −1% per month following the policy occurred. In contrast, the response in Ireland was confined to a −2.9% decrease in adherence immediately following the policy, with no further decrease over the 8 month follow-up. Reductions in adherence to oral diabetes drugs were larger in the U.S. group in comparison to the Irish group. No difference in adherence changes between the two settings for anti-hyperlipidaemic drugs occurred. Evidence on cost-sharing for prescription medicines is not ‘one size fits all’. Time since policy implementation and structural differences between health systems may influence the differential impact of copayment policies in international settings

Disordered Microbial Communities in the Upper Respiratory Tract of Cigarette Smokers

Cigarette smokers have an increased risk of infectious diseases involving the respiratory tract. Some effects of smoking on specific respiratory tract bacteria have been described, but the consequences for global airway microbial community composition have not been determined. Here, we used culture-independent high-density sequencing to analyze the microbiota from the right and left nasopharynx and oropharynx of 29 smoking and 33 nonsmoking healthy asymptomatic adults to assess microbial composition and effects of cigarette smoking. Bacterial communities were profiled using 454 pyrosequencing of 16S sequence tags (803,391 total reads), aligned to 16S rRNA databases, and communities compared using the UniFrac distance metric. A Random Forest machine-learning algorithm was used to predict smoking status and identify taxa that best distinguished between smokers and nonsmokers. Community composition was primarily determined by airway site, with individuals exhibiting minimal side-of-body or temporal variation. Within airway habitats, microbiota from smokers were significantly more diverse than nonsmokers and clustered separately. The distributions of several genera were systematically altered by smoking in both the oro- and nasopharynx, and there was an enrichment of anaerobic lineages associated with periodontal disease in the oropharynx. These results indicate that distinct regions of the human upper respiratory tract contain characteristic microbial communities that exhibit disordered patterns in cigarette smokers, both in individual components and global structure, which may contribute to the prevalence of respiratory tract complications in this population