Biology subjects

Clark, V.

Publications and source records attributed to Clark, V..

4 recordsLinked to original sources

bioRxiv2024

Deepening biomedical research training: Community-Building Wellness Workshops for Post-Baccalaureate Research Education Program (PREP) Trainees

ProblemAll trainees, especially those from historically minoritized backgrounds, experience stresses that may reduce their continuation in science, technology, engineering, math, and medicine (STEMM) careers. The Johns Hopkins University School of Medicine is one of [~]45 institutions with a National Institutes of Health funded Postbaccalaureate Research Education Program (PREP) that provides mentoring and a year of fulltime research to prepare students from historically excluded groups for graduate school. Having experienced the conflation of stresses during the COVID-19 pandemic and related shutdown, we realized our program lacked a component that explicitly helped PREP Scholars recognize and cope with non-academic stresses (financial, familial, social, mental) that might threaten their confidence and success as scientists and future in STEMM. InterventionWe developed an early-intervention program to help Scholars develop life-long skills to become successful and resilient scientists. We developed a year-long series comprised of 9 workshops focused on community, introspection, financial fitness, emotional intelligence, mental health, and soft-skills. We recruited and compensated a cohort of PhD students and postdoctoral fellows to serve as Peer Mentors, to provide a community and the safest space for Scholars to discuss personal concerns. Peer Mentors were responsible for developing and facilitating these Community-Building Wellness Workshops (CBWW). ContextCBWW were created and exectued as part of the larger PREP program. Workshops included a PowerPoint presentation by Peer Mentors that featured several case studies that prompted discussion and provided time for small-group discussions between Scholars and Peer Mentors. We also included pre- and post-work for each workshop. These touch-points helped Scholars cultivate the habit of introspection. ImpactThe CBWW exceeded our goals. Both Peer Mentors and Scholars experienced strong mutual support, and Scholars developed life-long skills. Notably, several Scholars who had been experiencing financial, mental or mentor-related stress immediately brought this to the attention of program leadership, allowing early and successful intervention. At the completion of CBWW, PREP Scholars reported implementing many workshop skills into practice, were reshaping their criteria for choosing future mentors, and evaluating career decisions. Strikingly, Peer Mentors found they also benefitted from the program as well, suggesting a potential larger scope for the role of CBWW in academia. Lessons LearnedPeer Mentors were essential in creating a safe supportive environment that facilitated discussions, self-reflection, and self-care. Providing fair compensation to Peer Mentors for their professional mentoring and teaching contributions was essential and contributed meaningfully to the positive energy and impact of this program.

scientific communication and education↗

bioRxiv2023

Profiling plasma extracellular vesicle-derived microRNAs for noninvasive diagnosis of alpha-1 antitrypsin deficiency associated liver disease

Alpha-1 antitrypsin deficiency (AATD) is a rare genetic disease characterized by reduced circulating levels of alpha-1 antitrypsin (AAT) due to the retention of misfolded AAT in the hepatocytes. The toxic AAT aggregates in hepatocytes cause liver fibrosis, cirrhosis, and hepatocellular carcinoma. Most patients remain asymptomatic until the final stage in which liver transplantation becomes the only treatment. Timely diagnosis of AATD liver disease plays a critical role in intervention and finding curative solutions. Assessing the prevalence and severity of AATD liver disease remains challenging due to limitations in current methods. Liver biopsy, the gold standard for evaluating the hepatic AAT accumulation, the initiating stage for AATD liver disease, is hindered by invasiveness and sampling errors. To address these limitations, we conducted a study using unique and precious clinical samples. We analyzed plasma extracellular vesicle (EV) derived miRNAs and liver transcriptomes from AATD individuals to develop a sensitive and noninvasive diagnostic approach for AATD liver disease. In the testing stage of our study, we enrolled 17 AATD individuals with different stages of liver disease, as determined by liver biopsy, and 20 controls. We identified differential expression of 178 miRNAs within the AATD group compared to controls by miRNA sequencing. Among those miRNAs, we selected miR-223-3p, miR-23a-3p, miR-15b-5p, let-7a-5p, let-7f-5p, and miR-374a-5p for further validation in an independent cohort of 45 AATD individuals. Using a logistic model that combined three miRNAs, we achieved an AUC of 0.737 for detecting AATD liver disease. Adding a fourth miRNA into this model increased the AUC to 0.751. The changes in EV miRNAs are correlated to dysregulated expression of liver mRNAs in AATD individuals with different stages of liver disease. We propose that plasma-circulating EV exhibit distinct miRNAs in AATD individuals and could serve as clinically significant biomarkers for the early detection of AATD liver disease.

molecular biology↗

bioRxiv2020

Colonies of Acropora formosa with greater survival show conserved calcification rates

Coral reefs are facing increasingly devasting impacts from ocean warming and acidification due to anthropogenic climate change. In addition to reducing greenhouse gas emissions, potential solutions have focused either on reducing light stress during heating, or the potential for identifying or engineering "super corals". These studies, however, have tended to focus primarily on the bleaching response of corals, and assume that corals that bleach earlier in a thermal event are more likely to die. Here, we explore how survival, potential bleaching, and coral skeletal growth (as branch extension and densification) varies for conspecifics collected from distinctive reef zones at Heron Island on the Southern Great Barrier Reef. A series of reciprocal transplantation experiments were undertaken using the dominant reef building coral (Acropora formosa) between the highly variable reef flat and the less variable reef slope environments. Coral colonies originating from the reef flat had higher rates of survival and thicker tissues but reduced rates of calcification than conspecifics originating from the reef slope. The energetics of both populations however benefited from greater light intensity offered in the shallows. Reef flat origin corals moved to the lower light intensity of reef slope reduced protein density and calcification rates. For A. formosa, genetic difference, or long-term entrainment to a highly variable environment, appeared to promote coral survival at the expense of calcification. The response divorces coral resilience from carbonate coral reef resilience, a response that was further exacerbated by reductions in irradiance. As we begin to discuss interventions necessitated by the CO2 that has already been released to the atmosphere, we need to prioritise our focus on the properties that maintain valuable carbonate ecosystems. Rapid and dense calcification by corals such as branching Acropora is essential to the ability of carbonate coral reefs to rebound following disturbances events, but may be the first property that is sacrificed to enable coral genet survival under stress.

ecology↗

bioRxiv2020

Genetic characterisation of a large antibiotic resistant environmental ST131 E. coli plasmid using a long read hybrid assembly approach

Escherichia coli Strain Type 131 are a globally disseminated environmental E. coli that has been linked to the capture and spread of plasmid mediated blaCTX-M type extended spectrum beta-lactamase (ESBLs). Accurately identifying such resistance genes in their wider genetic context provides a greater understanding of the mechanisms of selection and persistence in the environment. In this study we use a novel DNA extraction and enrichment method in combination with a custom long-read scaffold hybrid-assembly and polishing pipe line to identify the genetic context of the plasmid borne blaCTX-M gene previously identified in an ST131 environmental E. coli isolate. This has allowed us to discern the complete structure of a ~100kb environmental plasmid and further resolve the blaCTX-M variant to the group 9 blaCTX-M-27 gene. The upstream IS26 insertion element associated with the global capture and dissemination of blaCTX-M-15 was also identified in proximity to blaCTX-M-27. Furthermore, the lack of conjugative machinery identified on this plasmid, in combination with a toxin-antitoxin and plasmid partitioning system, indicates a mechanism of vertical transmission to maintain persistence in a population.

molecular biology↗