Search

Transcription coupled-nucleotide excision repair (TC-NER) removes DNA lesions that block RNA polymerase II (Pol II) transcription. A key step in TC-NER is the recruitment of the TFIIH complex, which initiates DNA unwinding and damage verification; however, the mechanism by which TFIIH is recruited during TC-NER, particularly in yeast, remains unclear. Here, we show that the C-terminal domain (CTD) of elongation factor-1 (Elf1) plays a critical role in TC-NER in yeast by binding TFIIH. Analysis of genome-wide repair of UV-induced cyclobutane pyrimidine dimers (CPDs) using CPD-seq indicates that the Elf1 CTD in yeast is required for efficient TC-NER. We show that the Elf1 CTD binds to the pleckstrin homology (PH) domain of the p62 subunit of TFIIH in vitro, and identify a putative TFIIH-interaction region (TIR) in the Elf1 CTD that is important for PH binding and TC-NER. The Elf1 TIR shows functional, structural, and sequence similarities to a conserved TIR in the mammalian UV sensitivity syndrome A (UVSSA) protein, which recruits TFIIH during TC-NER in mammalian cells. These findings suggest that the Elf1 CTD acts as a functional counterpart to mammalian UVSSA in TC-NER by recruiting TFIIH in response to Pol II stalling at DNA lesions.

Coronaviruses infect multiple mammal species, and SARS-CoV-2, the etiologic agent of COVID-19, likely jumped to humans from a mammal source (1). Although the virus is currently spreading person-toperson, the angiotensin [...]

Renal osteodystrophy (ROD) leads to increased fractures, potentially due to underlying low bone turnover in chronic kidney disease (CKD). We hypothesized that indoxyl sulfate (IS), a circulating toxin elevated in CKD and a ligand for the aryl hydrocarbon receptor (AhR), may target the osteocytes leading to bone cell uncoupling in ROD. The IDG-SW3 osteocytes were cultured for 14 days (early) and 35 days (mature osteocytes) and incubated with 500 μM of IS after dose finding studies to confirm AhR activation. Long-term incubation of IS for 14 days led to decreased expression of Tnfsf11/Tnfrsf11b ratio (RANKL/OPG), which would increase osteoclast activity, and increased expression of Wnt inhibitors Sost and Dkk1, which would decrease bone formation in addition to decreased mineralization and alkaline phosphatase (ALP) activity. When osteocytes were incubated with IS and the AhR translocation inhibitor CH223191, mineralization and ALP activity were restored. However, the Tnfsf11/Tnfrsf11b ratio and Sost, Dkk1 expression were not altered compared with IS alone, suggesting more complex signaling. In both early and mature osteocytes, co-culture with parathyroid hormone (PTH) and IS reversed the IS-induced upregulation of Sost and Dkk1, and IS enhanced the PTH-induced increase of the Tnfsf11/Tnfrsf11b ratio. Co-culture of IS with PTH additively enhanced the AhR activity assessed by Cyp1a1 and Cyp1b1 expression. In summary, IS in the absence of PTH increased osteocyte messenger RNA (mRNA) Wnt inhibitor expression in both early and mature osteocytes, decreased mRNA expression ofTnfsf11/Tnfrsf11b ratio and decreased mineralization in early osteocytes. These changes would lead to decreased resorption and formation resulting in low bone remodeling. These data suggest IS may be important in the underlying low turnover bone disease observed in CKD when PTH is not elevated. In addition, when PTH is elevated, IS interacts to further increase Tnfsf11/Tnfrsf11b ratio for osteoclast activity in both early and mature osteocytes, which would worsen bone resorption. [ABSTRACT FROM AUTHOR]

Purpose: Stroke is a leading cause of long-term disability in the US, yet a feasible assessment measure with predictive value for components of the International Classification of Functioning, Disability, and Health (ICF) Core Set for Stroke is lacking. The purpose of the present study was to explore the predictive value of potential assessment measures on factors within each ICF component in stroke survivors. Materials and Methods: Demographic, anthropometric, blood-based biomarker, physical functioning, and Global Physical Activity Questionnaire data were collected on stroke survivors in the 2011–2018 NHANES cycles. Potential predictors (handgrip strength relative to weight, age, sex, race, education level, marital status, poverty ratio, stroke chronicity) of physical function, activities of daily living (ADLs), participation in social activities, metabolic syndrome, and meeting physical activity recommendations were evaluated using weighted linear and ordinal logistic regression. Results: Relative handgrip strength was a significant predictor of physical function, difficulty participating in ADLs and social activities, and odds of meeting physical activity recommendations. As relative handgrip strength increased, these factors improved among stroke survivors. Conclusions: To decrease disability rates and optimize function among stroke survivors, the use of assessment measures like relative handgrip strength that may predict multiple ICF components is warranted. IMPLICATIONS FOR REHABILITATION: Handgrip strength relative to weight may be a significant predictor of multiple components of the International Classification of Functioning, Disability, and Health (ICF) Core Set for Stroke, including physical function, difficulty completing activities of daily living, difficulty participating in social activities, and the odds of meeting physical activity recommendations. Environmental and personal factors, such as income and education, may influence outcomes; thus, education and appropriate resources may need to be included as an aspect of stroke rehabilitation. The heterogenous and pervasive effects of chronic stroke highlight the need to identify outcome measures, like relative handgrip strength, that can influence multiple domains of stroke recovery. [ABSTRACT FROM AUTHOR]

Objective: To compare dietary intakes between LGBTQ + and non-LGBTQ + college students. Participants: Participants were LGBTQ+ (n = 92) and non-LGBTQ+ (n = 491) college students. Methods: The 26-item Dietary Screener Questionnaire assessed intakes of added sugars, fiber, whole grains, fruits and vegetables, dairy, and calcium. Percentage of participants meeting Dietary Guidelines for Americans were also computed. Multivariate ANCOVA assessed differences in dietary intake. Chi-square analyses assessed differences in proportions of LGBTQ + and non-LGBTQ + students meeting recommendations. Results: LGBTQ + students reported lower intakes of fiber, whole grains, fruit, and fruits and vegetables both including and excluding French fries (all p < 0.05). Fewer LGBTQ + students met recommendations for fruit (5.7%) compared to their non-LGBTQ + counterparts (14.2%; p =.03). Conclusions: LGBTQ + students report poorer indices of diet quality compared to non-LGBTQ + students. Health promotion programming efforts to improve these outcomes may need to be tailored differently for students who identify as LGBTQ+. [ABSTRACT FROM AUTHOR]

Suicide in young people (YP) is of increasing concern. Online mental health (MH) support platforms are becoming increasingly prevalent and may offer a way to support YP's MH. However, there are challenges to safeguarding YP on these platforms, such as the inability to see or respond to behaviours that pose risk. The present study aims to explore the experience of online, anonymous, text-based services provided by Kooth, an online MH platform, to YP previously at risk of suicide during the COVID-19 pandemic. Five female YP previously at risk of suicide were interviewed through online chat-based semi-structured interviews, and data were analysed with Interpretative Phenomenological Analysis. Results discuss three superordinate themes: a safe space to share; control; and need for connection. Thematic results highlight the desire for anonymity and control of therapeutic conversations due to concerns regarding confidentiality, and the perceived consequences of seeking help. Participants were successfully able to build connections through chats with online MH support staff. However, miscommunication was an issue throughout their experience, and could exacerbate negative feelings. Themes suggest that anonymous, online services can overcome access barriers and enable YP to share and process their experiences. Implications for clinical practice are discussed. [ABSTRACT FROM AUTHOR]

Action learning is seen under many guises, being adapted into different contexts (Marsick and O'Neil [1999. "The Many Faces of Action Learning." "Management Learning" 30 (2): 159-176.]). This is especially true in higher education, due to the divergent requirements and challenges of multiple action learning programmes and stakeholders within Liverpool Business School. We embed action learning with our DBA, MBA and bespoke leadership development programmes to support and enhance learning, development and workplace practices. Additionally, we use action learning to support knowledge transfer with industry and business growth activities with SMEs. In this account of practice, two action learning practitioners and advocates came together to share their experiences and practices of action learning. In doing so, a need for a Community of Practice (CoP) emerged. CoPs refer to groups of people who share a passion about a topic and who deepen their knowledge and expertise by interacting on an ongoing basis. CoPs recognise knowledge-based social structures and groupings of people who interact around their practices. In developing an action learning CoP, we can learn from each other's successes, challenges and even failures, with the aim of developing a supportive and collaborative learning system. This is true of action learning and communities of practice.

To contribute to current debate concerning approaches to teaching and learning for researching complex work-based problems, we focus on the Doctorate of Business Administration (DBA) programme. We examine the development of an integrated action learning approach as part of a part-time DBA offered by a university in the UK. In adopting the lens of socio-technical systems (STS) theory we address two important questions; how can action learning be adapted on a DBA programme to enhance students' learning together and learning apart? And, what insights can be drawn from conceptualising DBA learning as a socio-technical system? Through the collection of natural data from student feedback, meeting notes, action logs and the facilitators reflections, we develop a framework of integrated action learning as a socio-technical system. Through this framework we propose a model of action learning that enhances the ability of students to learn together and learn whilst apart. We also reflect on how technology has enabled distance learners to interrogate their complex work-based problems through collaborative questioning, focused on research-based inquiry, both together, and apart on their own learning journey.

Academic self-efficacy, the belief that one can achieve desired academic goals plays an important role in learning. This study aimed to determine the extent to which academic self-efficacy mediates relationships between students' perceptions of feedback and their academic attainment. An opportunity sample of 232 students (123 female) in their first year of higher education reported their academic self-efficacy and evaluated their assessment experience, including the perceived quantity and quality of feedback and the extent to which this feedback elicited an active response. Positive associations were observed between academic attainment and students' confidence that they could achieve their desired grades and adopt appropriate study behaviours. A negative association was identified between attainment and confidence to talk about their studies. Attainment was not related to the perceived quantity or quality of feedback, but did bear a significant association with the reported use to which feedback was put. Positive associations were generally identified between academic self-efficacy and perceptions of feedback. Path models revealed that inter-relationships were best represented by a model wherein academic self-efficacy mediated links between students' perceptions of feedback and academic attainment. The findings highlight the need to incorporate characteristics of the individual into an understanding of student engagement with feedback.

Exercise training (EX) and weight loss (WL) improve lower extremity physical function (LEPF) in older overweight women; however, effects on rate of torque development (RTD) are unknown. This study aimed to determine the effects of WL + EX or WL alone on RTD, and relatedly LEPF, in overweight older women. Leg strength was assessed using isokinetic dynamometry, and RTD was calculated (RTD200 = RTD at 200 ms, RTDPeak = peak RTD, T2P = time to 1st peak). LEPF was determined via clinical functional tasks. Women (n = 44, 69.1 ± 3.6 years, 30.6 ± 4.3 kg/m2) completed a 6-month trial in EX + WL or WL groups with similar weight loss (−9.8 ± 4.2%, p >.95). EX + WL had greater improvements in (a) most LEPF tasks (p <.001) and (b) RTD200, compared with WL (36% vs. −16%, p =.031); no other RTD parameters differed. Changes in RTD parameters and LEPF were not related (all p >.05). RTD is responsive to EX but is not associated with LEPF in older women. [ABSTRACT FROM AUTHOR]