Woodsconradsen1586

These results indicate that within a neuron RNA editing can recode genetic information in a region-specific manner. © The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.BACKGROUND Resting metabolic rate (RMR) tends to decline with aging. The age-trajectory of decline in RMR is similar to changes that occur in muscle mass, muscle strength and fitness but while the decline in these phenotypes have been related to changes of mitochondrial function and oxidative capacity, whether lower RMR is associated with poorer mitochondrial oxidative capacity is unknown. METHODS In 619 participants of the Baltimore Longitudinal Study of Aging, we analyzed the cross-sectional association between RMR (kcal/day), assessed by indirect calorimetry, and skeletal muscle maximal oxidative phosphorylation capacity, assessed as post-exercise phosphocreatine recovery time constant (τPCr), by phosphorous magnetic resonance spectroscopy. Linear regression models were used to evaluate the relationship between τPCr and RMR, adjusting for potential confounders. RESULTS Independent of age, sex, lean body mass, muscle density and fat mass, higher RMR was significantly associated with shorter τPCr, indicating greater mitochondrial oxidative capacity. CONCLUSION Higher RMR is associated with a higher mitochondrial oxidative capacity in skeletal muscle. This association may reflect a relationship between better muscle quality and greater mitochondrial health. Published by Oxford University Press on behalf of The Gerontological Society of America 2020. This work is written by (a) US Government employee(s) and is in the public domain in the US.Recently, the genetic variability in lysosomal storage disorders has been implicated in the pathogenesis of Parkinson's disease. Here, we found that variants in prosaposin (PSAP), a rare causative gene of various types of lysosomal storage disorders, are linked to Parkinson's disease. Genetic mutation screening revealed three pathogenic mutations in the saposin D domain of PSAP from three families with autosomal dominant Parkinson's disease. Whole-exome sequencing revealed no other variants in previously identified Parkinson's disease-causing or lysosomal storage disorder-causing genes. A case-control association study found two variants in the intronic regions of the PSAP saposin D domain (rs4747203 and rs885828) in sporadic Parkinson's disease had significantly higher allele frequencies in a combined cohort of Japan and Taiwan. We found the abnormal accumulation of autophagic vacuoles, impaired autophagic flux, altered intracellular localization of prosaposin, and an aggregation of α-synuclein in patient-derived skin fibroblasts or induced pluripotent stem cell-derived dopaminergic neurons. In mice, a Psap saposin D mutation caused progressive motor decline and dopaminergic neurodegeneration. Our data provide novel genetic evidence for the involvement of the PSAP saposin D domain in Parkinson's disease. © The Author(s) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please email journals.permissions@oup.com.Direct-acting antivirals (DAA) targeting hepatitis C virus (HCV) have revolutionized outcomes in HIV co-infection. We examined early events in liver and plasma through A5335S, a substudy of trial A5329 (paritaprevir/ritonavir, ombitasvir, dasabuvir, with ribavirin) that enrolled chronic genotype 1a HCV-infected persons co-infected with suppressed HIV 5/6 treatment-naïve enrollees completed A5335S. Mean baseline plasma HCV RNA=6.7 log10 IU/mL and changed by -4.1 log10 IU/mL by Day 7. In liver, laser capture microdissection was used to quantify HCV. At liver biopsy 1, mean (95% CI) %HCV-infected cells=25.2% (7.4%, 42.9%), correlating with plasma HCV RNA (Spearman rank correlation r=0.9); biopsy 2 (Day 7 in 4/5 participants) mean (95% CI) %HCV-infected cells=1.0% (0.2%, 1.7%)(p less then 0.05 for change), and DAAs were detectable in liver. Plasma CXCL10 concentrations changed by mean=-160 pg/mL/day at 24 hours, but no further after Day 4. We conclude that HCV infection is rapidly cleared from liver with DAA leaving less then 2% HCV-infected hepatocytes at Day 7. We extrapolate that HCV eradication could occur in these participants by 63 days, although immune activation might persist. Single-cell longitudinal estimates of HCV clearance from liver have never been reported previously and could be applied to estimating the minimum treatment duration required for HCV infection. © The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.OBJECTIVE A previous systematic review on pelvic floor muscle function (PFMF) identified a miscellaneity of terms. The lack of consensual terminology might have come from the complexity of neuromusculoskeletal function itself. This study sought to link the previously identified PFMF terms to the International Classification of Functioning, Disability and Health (ICF) terminology. METHODS In this secondary analysis study, 10 linkage rules were applied to link the 196 previously identified PFMF terms to the ICF. Two researchers performed the linking process independently. Disagreements were solved by open dialogue with a third researcher. Percentage agreement was computed for main outcome. DL-Alanine RESULTS A total of 184 (93.9%) PFMF terms were subsumed into the following 6 ICF terms Tone, Involuntary movement reaction, Control, Coordination, Strength, and Endurance. The most frequently investigated PFMF was Strength (25.5%), followed by Involuntary movement reaction (22.9%), Endurance (17.2%), Control (14.1%), Coordination (9.9%), and Tone (4.2%). Only 6.2% PFMF could not be linked to ICF terminology. A wide variation of instruments/methods was used to measure PFMF. Vaginal palpation was the only method employed to measure all six PFMF. Percentage agreement between raters was 73.2%. CONCLUSIONS Linking PFMF terminology to the ICF was feasible and valid. It allowed the identification of the most investigated PFMF and their measuring methods. ICF terminology to describe PFMF should be used since it may improve communication, data gathering and the advance in scientific knowledge. IMPACT Standardized terminology anchored in a theoretical framework is crucial to data gathering, communication, and dissemination of evidence-based practice. The PFMF terminology based on ICF can be used to improve data pooling and communication. © 2020 American Physical Therapy Association.