Publications by authors named "J J Tyler"

897 Publications

Monitoring beliefs and physiological measures in students at risk for COVID-19 using wearable sensors and smartphone technology: Protocol for a mobile health study.

JMIR Res Protoc 2021 Jun 4. Epub 2021 Jun 4.

Division of Pediatric Hematology Oncology, Department of Pediatrics, University of Michigan, 1500 E. Medical Center DrD4118 Medical Professional Building, Ann Arbor, US.

Background: The COVID-19 pandemic has impacted lives significantly and greatly affected an already vulnerable population, college students, in relation to mental health and public safety. Social distancing and isolation have brought about challenges to student's mental health. Mobile health apps and wearable sensors may help to monitor students at risk for COVID-19 and support their mental well-being.

Objective: Through the use of a wearable sensor and smartphone-based survey completion, this study aimed to monitor students at risk for COVID-19.

Methods: We conducted a prospective study of students, undergraduate and graduate, at a public university in the Midwest. Students were instructed to download the Fitbit, Social Rhythms, and Roadmap 2.0 apps onto their personal mobile devices (Android or iOS). Subjects consented to provide up to 10 saliva samples during the study period. Surveys were administered through the Roadmap 2.0 app at five timepoints - at baseline, 1-month later, 2-months later, 3-months later, and at study completion. The surveys gathered information regarding demographics, COVID-19 diagnoses and symptoms, and mental health resilience, with the aim of documenting the impact of COVID-19 on the college student population.

Results: This study enrolled 2,158 college students between September 2020 and January 2021. Subjects are currently being followed on-study for one academic year. Data collection and analysis are ongoing.

Conclusions: This study examined student health and well-being during the COVID-19 pandemic. It also assessed the feasibility of wearable sensor use and survey completion in a college student population, which may inform the role of our mobile health tools on student health and well-being. Finally, using wearable sensor data, biospecimen collection, and self-reported COVID-19 diagnosis, our results may provide key data towards the development of a model for the early prediction and detection of COVID-19.

Clinicaltrial: ClinicalTrials.gov NCT04766788.
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http://dx.doi.org/10.2196/29561DOI Listing
June 2021

Maximizing remission from cognitive-behavioral therapy in medicated adults with obsessive-compulsive disorder.

Behav Res Ther 2021 May 29;143:103890. Epub 2021 May 29.

New York State Psychiatric Institute, New York, NY, 10032, USA.

Practice guidelines for adults with obsessive-compulsive disorder (OCD) recommend augmenting serotonin reuptake inhibitors (SRIs) with exposure and ritual prevention (EX/RP). However, fewer than half of patients remit after a standard 17-session EX/RP course. We studied whether extending the course increased overall remission rates and which patient factors predicted remission. Participants were 137 adults with clinically significant OCD (Yale-Brown Obsessive Compulsive Scale [Y-BOCS] score ≥18) despite an adequate SRI trial (≥12 weeks). Continuing their SRI, patients received 17 sessions of twice-weekly EX/RP (standard course). Patients who did not remit (Y-BOCS ≤12) received up to 8 additional sessions (extended course). Of 137 entrants, 123 completed treatment: 49 (35.8%) remitted with the standard course and another 46 (33.6%) with the extended course. Poorer patient homework adherence, more Obsessive-Compulsive Personality Disorder (OCPD) traits, and the Brain-Derived Neurotrophic Factor (BDNF) Val66MET genotype were associated with lower odds of standard course remission. Only homework adherence differentiated non-remitters from extended course remitters. Extending the EX/RP course from 17 to 25 sessions enabled many (69.3%) OCD patients on SRIs to achieve remission. Although behavioral (patient homework adherence), psychological (OCPD traits), and biological (BDNF genotype) factors influenced odds of EX/RP remission, homework adherence was the most potent patient factor overall.
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http://dx.doi.org/10.1016/j.brat.2021.103890DOI Listing
May 2021

Operational research for the safe and effective design of COVID-19 mass vaccination centres.

Vaccine 2021 Jun 14;39(27):3537-3540. Epub 2021 May 14.

Centre for Healthcare Improvement and Innovation, School of Management, University of Bath, Bath, UK.

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http://dx.doi.org/10.1016/j.vaccine.2021.05.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120437PMC
June 2021

Sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) activity is required for V(D)J recombination.

J Exp Med 2021 Aug 25;218(8). Epub 2021 May 25.

Department of Medicine, Division of Hematology and Oncology, University of Alabama at Birmingham School of Medicine, Birmingham, AL.

A whole-genome CRISPR/Cas9 screen identified ATP2A2, the gene encoding the Sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) 2 protein, as being important for V(D)J recombination. SERCAs are ER transmembrane proteins that pump Ca2+ from the cytosol into the ER lumen to maintain the ER Ca2+ reservoir and regulate cytosolic Ca2+-dependent processes. In preB cells, loss of SERCA2 leads to reduced V(D)J recombination kinetics due to diminished RAG-mediated DNA cleavage. SERCA2 deficiency in B cells leads to increased expression of SERCA3, and combined loss of SERCA2 and SERCA3 results in decreased ER Ca2+ levels, increased cytosolic Ca2+ levels, reduction in RAG1 and RAG2 gene expression, and a profound block in V(D)J recombination. Mice with B cells deficient in SERCA2 and humans with Darier disease, caused by heterozygous ATP2A2 mutations, have reduced numbers of mature B cells. We conclude that SERCA proteins modulate intracellular Ca2+ levels to regulate RAG1 and RAG2 gene expression and V(D)J recombination and that defects in SERCA functions cause lymphopenia.
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http://dx.doi.org/10.1084/jem.20201708DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8155808PMC
August 2021

Phosphorylation of the WH2 domain in yeast Las17/WASP regulates G-actin binding and protein function during endocytosis.

Sci Rep 2021 May 6;11(1):9718. Epub 2021 May 6.

Department of Biomedical Science, Firth Court, University of Sheffield, Sheffield, S10 2TN, UK.

Actin nucleation is the key rate limiting step in the process of actin polymerization, and tight regulation of this process is critical to ensure actin filaments form only at specific times and at defined regions of the cell. WH2 domains are short sequence motifs found in many different actin binding proteins including WASP family proteins which regulate the actin nucleating complex Arp2/3. In this study we reveal a phosphorylation site, Serine 554, within the WH2 domain of the yeast WASP homologue Las17. Both phosphorylation and a phospho-mimetic mutation reduce actin monomer binding affinity while an alanine mutation, generated to mimic the non-phosphorylated state, increases actin binding affinity. The effect of these mutations on the Las17-dependent process of endocytosis in vivo was analysed and leads us to propose that switching of Las17 phosphorylation states may allow progression through distinct phases of endocytosis from site assembly through to the final scission stage. While the study is focused on Las17, the sole WASP family protein in yeast, our results have broad implications for our understanding of how a key residue in this conserved motif can underpin the many different actin regulatory roles with which WH2 domains have been associated.
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http://dx.doi.org/10.1038/s41598-021-88826-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102491PMC
May 2021