Graphical AbstractHighlights d 132 zebrafish mutants for genes located in schizophreniaassociated genomic regions d Phenotypes for many understudied genes with previously unknown functions d Phenotype atlas for abnormal behavior and brain activity d More than 30 genes prioritized for future study
20Genomic studies have identified hundreds of candidate genes near loci associated with risk for 21 schizophrenia. To define candidates and their functions, we mutated zebrafish orthologues of 132 22 human schizophrenia-associated genes and created a phenotype atlas consisting of whole-brain 23 activity maps, brain structural differences, and profiles of behavioral abnormalities. Phenotypes 24 were diverse but specific, including altered forebrain development and decreased prepulse 25 inhibition. Exploration of these datasets identified promising candidates in more than 10 gene-26 rich regions, including the magnesium transporter cnnm2 and the translational repressor gigyf2, 27 and revealed shared anatomical sites of activity differences, including the pallium, hypothalamus 28 or tectum. Single-cell RNA sequencing uncovered an essential role for the understudied 29 transcription factor znf536 in the development of forebrain neurons implicated in social behavior 30 and stress. This phenotypic landscape of schizophrenia-associated genes prioritizes more than 30 31 candidates for further study and provides hypotheses to bridge the divide between genetic 32 association and biological mechanism. 33 2 1 Keywords 2 GWAS; neuropsychiatric disorder; schizophrenia; zebrafish; behavior; whole-brain activity; 3 neurodevelopment; forebrain; prepulse inhibition; single-cell RNA-sequencing 4 5
The increasing global prevalence of SARS-CoV-2 and the resulting COVID-19 disease pandemic pose significant concerns for clinical management of solid organ transplant recipients (SOTR). Wearable devices that can measure physiologic changes in biometrics including heart rate, heart rate variability, body temperature, respiratory, activity (such as steps taken per day) and sleep patterns, and blood oxygen saturation show utility for the early detection of infection before clinical presentation of symptoms. Recent algorithms developed using preliminary wearable datasets show that SARS-CoV-2 is detectable before clinical symptoms in >80% of adults. Early detection of SARS-CoV-2, influenza, and other pathogens in SOTR, and their household members, could facilitate early interventions such as self-isolation and early clinical management of relevant infection(s). Ongoing studies testing the utility of wearable devices such as smartwatches for early detection of SARS-CoV-2 and other infections in the general population are reviewed here, along with the practical challenges to implementing these processes at scale in pediatric and adult SOTR, and their household members. The resources and logistics, including transplant-specific analyses pipelines to account for confounders such as polypharmacy and comorbidities, required in studies of pediatric and adult SOTR for the robust early detection of SARS-CoV-2, and other infections are also reviewed.
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