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BEYOND #BLACKLIVESMATTER THROUGH an UNDERSTANDING of INTERSECTIONALITY and ETHICAL LEADERSHIP: A CRITICAL AUTOETHNOGRAPHY OF A BLACK FEMALE GRADUATE STUDENT LIVING WITH MULTIPLE HIDDEN DIS/ABILITIES
There can be numerous questions to be asked concerning the perspective of a Black female graduate student at a predominately White institution who lives with multiple hidden dis/Abilities (Gillborn, 2015). This critical autoethnography can help discover and uncover new issues and establish transformational changes that could expand knowledge and research surrounding the critical analysis of intersectionality and Disability Studies and Critical Race Theory from an/abled feminist approach. Transformative politics can be identified in this study, which examines socialism and the systematic structures and power within academia at the graduate level (Trevino et al., 2008). The issues of Black disability feminism, race, gender, identity politics, and ableism will be argued in this research study. Also, the importance of equity, one’s sense of belonging, positionality, and academic leadership will be evaluated, which surrounds the experience of a Black female graduate student who lives with multiple hidden disabilities. The critical analysis questions how a Black female at the graduate level is treated at a predominately White institution and lives with multiple dis/Abilities. Through visual technology, this qualitative critical autoethnography captures various experiences of a Black dis/Abled female graduate student inside and outside a post-secondary institution while identifying opportunities and barriers the researcher incurs during graduate studies
Gender differences in relations between social comparison, social support, and sleep disturbance among midlife and older adults.
OBJECTIVE: To examine associations between sleep disturbance, social support, and social comparison among midlife and older adults, including the moderating role of gender.
METHODS: Adults ages ≥40 years (N = 557, MAge = 57, 53% men) completed a cross-sectional survey including validated measures of sleep disturbance, perceptions of social support, and social comparison orientation.
RESULTS: Sleep disturbance was negatively associated with social support (rs = −0.42 to–0.33, ps = 0.001) and associations were stronger for men than women–particularly perceived support from friends (η 2= 0.01). Sleep disturbance was also associated with upward comparison orientation (r = 0.12, p = 0.003), more strongly for women than men (η 2= 0.01).
DISCUSSION: Findings indicate that perceived support from friends (for men) and upward comparison (for women) may have particular influence on sleep among midlife and older adults. Additional work is needed to clarify the nature of these associations and their mechanism(s) of action, to inform potential treatment adaptations for this population
Acceptability of heart rate-based remote monitoring of smoking status.
INTRODUCTION: Digital interventions present a scalable solution to overcome barriers to smoking cessation treatment, and changes in resting heart rate (HR) may offer a viable option for monitoring smoking status remotely. The goal of this study was to explore the acceptability of using smartphone cameras and activity trackers to measure heart rate for use in a smoking cessation intervention.
METHODS: Participants (N=410), most of whom identified as female (75.8 %) with mean age 38.3 years (SD 11.4), were recruited via the Smoke Free app. They rated the perceived comfort, convenience, and likelihood of using smartphone cameras and wrist-worn devices for HR monitoring as an objective measure of smoking abstinence. Wilcoxon signed-rank tests and Kruskal-Wallis tests assessed differences in acceptability across device types and whether the participant owned an activity tracker/smartwatch or smartphone.
RESULTS: Participants reported high levels of acceptability for both HR monitoring methods, with activity trackers/smartwatches rated more favorably in terms of comfort, convenience, and likelihood of use compared to smartphone cameras. Participants indicated a statistically significantly greater likelihood of using the activity tracker/smartwatch over the smartphone camera. Participants viewed the activity tracker/smartwatch as more acceptable than the smartphone camera (87.0% vs 50.0%).
CONCLUSIONS: HR monitoring via smartphone cameras and wrist-worn devices was deemed acceptable among people interested in quitting smoking. Wrist-worn devices, in particular, were preferred, suggesting their potential as a scalable, user-friendly method for remotely monitoring smoking status. These findings support the need for further exploration and implementation of HR monitoring technology in smoking cessation research and interventions
DISSECTING THE INTERPLAY OF PROTEIN SYNTHESIS AND DEGRADATION PATHWAYS IN CELLULAR ADAPTATION TO STRESS
Adaptation to stress requires cells to reprogram transcription, translation, and proteolytic pathways. Although much is known about the response of each program, it remains unclear how they coordinate following stress. My studies in S. cerevisiae identified the Cdk8 kinase module (CKM) of the Mediator complex as a new player in coordinating these processes. It is well established that the CKM consists of four highly conserved proteins (cyclin C, its cognate kinase Cdk8, and two structural proteins Med12 and Med13) and predominantly represses a subset of stress responsive genes in yeast. We demonstrated for the first time that the CKM also positively regulates the transcription of a subset of translation initiation factor (TIF) and ribosomal protein (RP) genes through an indirect mechanism. Consistent with this, we observed that the CKM is important for survival under conditions which alter or inhibit protein synthesis. Moreover, during nutrient deprivation, cells repress translation by degrading specific TIFs and storing mRNA in processing bodies (P-bodies). We found that nitrogen starvation causes Med13 to relocate to P-bodies, where it aids in the degradation of Edc3, showing a novel cytoplasmic role for Med13. Lastly, I demonstrated the degradation of the TIF eIF4G1 during nitrogen starvation involves K33 and K63-linked ubiquitination by the Cul3 E3 ligase complex and requires Atg8’s ubiquitin (Ub) interacting motif (UIM), indicating a new role of Ub in selective autophagy. Given the conserved nature of all the players, these studies are highly relevant to the control of proteostasis in higher eukaryotes
Nanofiber-Hydrogel Composite Scaffold Fabrication Methods for Peripheral Nerve Regeneration
Nerve graft conduits (NGCs) are a rapidly advancing field for treating peripheral nerve injuries that aim to guide the growth of regenerating axons across damaged gaps. A more effective NGC can be manufactured by combining the use of nanofibers to act as guidewires within a 3-D hydrogel that imitates the extracellular matrix of nerve tissue. Several methods have been developed to embed aligned nanofibers in an ordered architecture within a hydrogel matrix. The first method involves layer-by-layer additive manufacturing to create NGCs with rows of polycaprolactone (PCL) nanofibers surrounded by a gelatin methacrylate (GelMe) hydrogel in a 3-D structure. A second method where individual films of fibers embedded in hydrogel were rolled was developed, introducing void space throughout the scaffold that allows for easier cell infiltration. The final method uses a sacrificial hydrogel scaffold template to manufacture the scaffold. The desired hydrogel is infiltrated into the template hydrogel and crosslinked before the template’s removal, allowing for a much wider variety of hydrogels such as pH or ion responsive materials. It was found that GelMe and hyaluronic acid-based hydrogels limited axon infiltration in a sciatic nerve gap model at the studied weight percent and degrees of crosslinking. This result highlights how the infiltration manufacturing approach may be critical for fabricating aligned nanofiber-hydrogel composite grafts from next generation hydrogels
A Comparison of the Safety and Efficacy of Tapinarof and Roflumilast Topical Therapies in the Management of Mild-to-Moderate Plaque Psoriasis
INTRODUCTION: Psoriasis is an immune-mediated inflammatory skin disease. First-line topical treatments include steroids, calcineurin inhibitors, vitamin D analogs, and anthralin. Recently, novel topical therapeutics like tapinarof and roflumilast have emerged with unique anti-inflammatory mechanisms and promising efficacy profiles.
MATERIALS AND METHODS: This review utilized PubMed, SCOPUS, and Web of Science databases to identify recent studies on tapinarof and roflumilast. Criteria focused on efficacy, safety profiles, and therapeutic roles in psoriasis treatment.
RESULTS: Four primary literature articles were identified for tapinarof and five for roflumilast. Both drugs demonstrated strong efficacy with minimal adverse events in treating mild-to-moderate plaque psoriasis. Tapinarof showed more frequent but mild adverse effects, while roflumilast had less frequent but more severe side effects.
DISCUSSION: Tapinarof and roflumilast offer once-daily dosing and successful treatment in restricted areas, potentially enhancing patient adherence. Cost remains a limiting factor, necessitating future comparative studies to evaluate the efficacy, safety, and cost-effectiveness between the two drugs.
CONCLUSION: Tapinarof and roflumilast present promising topical treatments for psoriasis, showing efficacy and manageable safety profiles. Further research is crucial to fully elucidate their comparative benefits and drawbacks in clinical practice
Correspondence to A Preliminary Study of Collaborative Group Intervention with Recovered Peer Supporters for Eating Disorders: Analyses Including Comparisons Between In-Person and Online Sessions
We read with pleasure the article by Mochizuki et al., 1 titled “A preliminary study of collaborative group intervention with recovered peer supporters for eating disorders: Analyses including comparisons between in‐person and online sessions.” We would like to offer additional commentary on the conclusions regarding group intervention and peer support and its heavy influence on combating eating disorders. We hope these perspectives may provide insight into areas that may require further research and improvement
Unveiling the Unique RAS Isoform and Domain Specific Regulation of BRAF Kinase
BRAF kinase is a key member of the MAPK pathway, important for cell growth and division. Upstream signals promote BRAF activation by interaction with the membrane bound GTPase, RAS, which leads to relief of autoinhibition and dimerization. The N-terminal regulatory domains of BRAF, including the BRAF specific region (BSR), the RAS binding domain (RBD), and the cysteine rich domain (CRD), govern the conformational state of the cytosolic, autoinhibited monomer and drive the RAS-RAF interaction. Active BRAF phosphorylates and activates its substrate MEK, which in turn phosphorylates and activates ERK. Mutations in RAS and BRAF are the cause of many cancers and RASopathy developmental disorders; however, therapeutic approaches are limited due to challenges in BRAF and RAS inhibition and an incomplete understanding of BRAF and RAS biochemistry. Here, we shed light on the details of BRAF activation and interaction with RAS in three parts: 1) we investigated the roles of the BSR, RBD, and CRD in regulating the RAS-RAF interaction and membrane recruitment; 2) we developed chemical probes to disrupt the RAS-RAF interaction and eliminate MAPK signaling in cancer; and 3) we elucidated the intramolecular interactions involved in RAF autoinhibition. Our findings point to unique contributions of each BRAF N-terminal domain in the regulation of autoinhibition and in determining isoform-specific RAS interactions
Digital Clock Drawing as an Alzheimer\u27s Disease Susceptibility Biomarker: Associations with Genetic Risk Score and APOE in Older Adults
BACKGROUND: Alzheimer\u27s disease (AD) is the leading cause of dementia in older adults, but most people are not diagnosed until significant neuronal loss has likely occurred along with a decline in cognition. Non-invasive and cost-effective digital biomarkers for AD have the potential to improve early detection.
OBJECTIVE: We examined the validity of DCTclockTM (a digitized clock drawing task) as an AD susceptibility biomarker.
DESIGN: We used two primary independent variables, Apolipoprotein E (APOE) ε4 allele carrier status and polygenic risk score (PRS). We examined APOE and PRS associations with DCTclockTM composite scores as dependent measures.
SETTING: We used existing data from the Framingham Heart Study (FHS), a community-based study with the largest dataset of digital clock drawing data to date.
PARTICIPANTS: The sample consisted of 2,398 older adults ages 60-94 with DCTclockTM data (mean age of 72.3, 55% female and 92% White).
MEASUREMENTS: PRS was calculated using 38 variants identified in a recent large genome-wide association study (GWAS) and meta-analysis of late-onset AD (LOAD).
RESULTS: Results showed that DCTclockTM performance decreased with advancing age, lower education, and the presence of one or more copies of APOE ε4. Lower DCTclockTM Total Score as well as lower composite scores for Information Processing Speed (both command and copy conditions) and Drawing Efficiency (command condition) were significantly associated with higher PRS levels and more copies of APOE ε4. APOE and PRS associations displayed similar effect sizes in both men and women.
CONCLUSIONS: Our results indicate that higher AD genetic risk is associated with poorer DCTclockTM performance in older adults without dementia. This is the first study to demonstrate significant differences in clock drawing performance on the basis of APOE status or PRS
Fused In Sarcoma Regulates Glutamate Signaling and Oxidative Stress Response
Mutations in fused in sarcoma (fust-1) are linked to ALS. However, how these ALS causative mutations alter physiological processes and lead to the onset of ALS remains largely unknown. By obtaining humanized fust-1 ALS mutations via CRISPR-CAS9, we generated a C. elegans ALS model. Homozygous fust-1 ALS mutant and fust-1 deletion animals are viable in C. elegans. This allows us to better characterize the molecular mechanisms of fust-1-dependent responses. We found FUST-1 plays a role in regulating superoxide dismutase, glutamate signaling, and oxidative stress. FUST-1 suppresses SOD-1 and VGLUT/EAT-4 in the nervous system. FUST-1 also regulates synaptic AMPA-type glutamate receptor GLR-1. We found that fust-1 ALS mutations act as loss-of-function in SOD-1 and VGLUT/EAT-4 phenotypes, whereas the fust-1 ALS mutations act as gain-of-function in redox homeostasis and the microbe-induced oxidative stress response. We hypothesized that FUST-1 is a link between glutamate signaling and SOD-1. Our results may provide new insights into the human ALS alleles and their roles in pathological mechanisms that lead to ALS