A nomenclature for restriction enzymes, DNA methyltransferases, homing endonucleases and their genes

A nomenclature is described for restriction endonucleases, DNA methyltransferases, homing endonucleases and related genes and gene products. It provides explicit categories for the many different Type II enzymes now identified and provides a system for naming the putative genes found by sequence analysis of microbial genome

Defining the causes of sporadic Parkinson's disease in the global Parkinson's genetics program (GP2)

The Global Parkinson’s Genetics Program (GP2) will genotype over 150,000 participants from around the world, and integrate genetic and clinical data for use in large-scale analyses to dramatically expand our understanding of the genetic architecture of PD. This report details the workflow for cohort integration into the complex arm of GP2, and together with our outline of the monogenic hub in a companion paper, provides a generalizable blueprint for establishing large scale collaborative research consortia

Multi-ancestry genome-wide association meta-analysis of Parkinson?s disease

Although over 90 independent risk variants have been identified for Parkinson’s disease using genome-wide association studies, most studies have been performed in just one population at a time. Here we performed a large-scale multi-ancestry meta-analysis of Parkinson’s disease with 49,049 cases, 18,785 proxy cases and 2,458,063 controls including individuals of European, East Asian, Latin American and African ancestry. In a meta-analysis, we identified 78 independent genome-wide significant loci, including 12 potentially novel loci (MTF2, PIK3CA, ADD1, SYBU, IRS2, USP8, PIGL, FASN, MYLK2, USP25, EP300 and PPP6R2) and fine-mapped 6 putative causal variants at 6 known PD loci. By combining our results with publicly available eQTL data, we identified 25 putative risk genes in these novel loci whose expression is associated with PD risk. This work lays the groundwork for future efforts aimed at identifying PD loci in non-European populations

High-intensity interval running impairs subsequent upper limb strength performance

BACKGROUND: This study compared the effect of treadmill running on subsequent upper limb exercise performance in young men. METHODS: Seventeen young men (24.8±5.2 years) completed a (1) bench press resistance exercise control session; (2) treadmill interval running protocol followed by the bench press session; (3) treadmill continuous running protocol followed by the bench press session. Four sets of the bench press exercise were performed at 80% of 1RM up to volitional failure. In the interval protocol, eight sprints of 40s at 100% of the velocity of maximal oxygen uptake, with 20s of passive interval between them were performed, whereas in the continuous protocol 30-min of treadmill running at 90% of the heart rate corresponding to second ventilatory threshold was performed. The number of maximal repetitions completed in each set and condition was recorded and compared using a two-way repeated measures ANOVA. RESULTS: The interval protocol (18.7 ± 4.9 repetitions) resulted in a reduction in the number of bench press repetitions compared to the control protocol (21.4 ± 5.4 repetitions) (p=0.002); whereas continuous running did not affect the bench press performance (20.6 ± 4.4 repetitions). The total number of repetitions reduced from set to set in all protocols (p<0.001). CONCLUSION: The results evidenced an impairment in the upper limb strength performance after high intensity interval, but not moderate intensity continuous running, which has implication for concurrent training planning and prescription

Effectiveness of m-health-based core strengthening exercise and health education for public safety workers with chronic non-specific low back pain: study protocol for a superiority randomized controlled trial (SAFEBACK)

Abstract Background Low back pain (LBP) is the leading cause of years lived with disability worldwide. Public safety workers are highly exposed to physically demanding activities and inappropriate postures, increasing the risk of experiencing LBP. Smartphone app-based self-managed interventions may be an alternative for chronic non-specific LBP (CNSLBP) treatment. This study aims to evaluate the effectiveness of a smartphone app-based self-managed exercise program plus health education, compared to a health education program alone, on neuromuscular and perceptual outcomes in police officers and firefighters with CNSLBP. Methods This is a parallel, two-armed, blinded evaluator randomized clinical trial. Police officers and firefighters (from public safety institutions in the Rio Grande do Sul state, Brazil) will be randomly assigned to a m-health self-managed exercise program (twice a week) plus health education or health education alone. Self-management exercise program components are mobility and core resistance exercises, available on the app. Follow-ups will be conducted post-treatment (8 weeks) and 16 weeks after randomization. The co-primary outcomes will be pain intensity and disability post-treatment (8 weeks). Secondary outcomes will be biopsychosocial factors related to CNSLBP. Discussion We hypothesize that the effects of a smartphone app-based self-managed exercise program on co-primary and secondary outcomes will be superior, compared to the health education only in public safety workers with CNSLBP. Trial registration The study was prospectively registered at ClinicalTrials.gov (NCT05481996. Registered on August 01, 2022)

Embracing Monogenic Parkinson's Disease: The MJFF Global Genetic PD Cohort

BACKGROUND: As gene-targeted therapies are increasingly being developed for Parkinson's disease (PD), identifying and characterizing carriers of specific genetic pathogenic variants is imperative. Only a small fraction of the estimated number of subjects with monogenic PD worldwide are currently represented in the literature and availability of clinical data and clinical trial-ready cohorts is limited. OBJECTIVE: The objectives are to (1) establish an international cohort of affected and unaffected individuals with PD-linked variants; (2) provide harmonized and quality-controlled clinical characterization data for each included individual; and (3) further promote collaboration of researchers in the field of monogenic PD. METHODS: We conducted a worldwide, systematic online survey to collect individual-level data on individuals with PD-linked variants in SNCA, LRRK2 VPS35, PRKN, PINK1, DJ-1, as well as selected pathogenic and risk variants in GBA and corresponding demographic, clinical, and genetic data. All registered cases underwent thorough quality checks, and pathogenicity scoring of the variants and genotype-phenotype relationships were analyzed. RESULTS: We collected 3888 variant carriers for our analyses, reported by 92 centers (42 countries) worldwide. Of the included individuals 3185 had a diagnosis of PD (ie, 1306 LRRK2, 115 SNCA, 23 VPS35 429 PRKN, 75 PINK1, 13 DJ-1, and 1224 GBA) and 703 were unaffected (ie, 328 LRRK2, 32 SNCA, 3 VPS35, 1 PRKN, 1 PINK1, and 338 GBA). In total, we identified 269 different pathogenic variants; 1322 individuals in our cohort (34\%) were indicated as not previously published. CONCLUSIONS: Within the MJFF Global Genetic PD Study Group, we (1) established the largest international cohort of affected and unaffected individuals carrying PD-linked variants; (2) provide harmonized and quality-controlled clinical and genetic data for each included individual; (3) promote collaboration in the field of genetic PD with a view toward clinical and genetic stratification of patients for gene-targeted clinical trials. 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Defining the causes of sporadic Parkinson’s disease in the global Parkinson’s genetics program (GP2)

The Global Parkinson’s Genetics Program (GP2) will genotype over 150,000 participants from around the world, and integrate genetic and clinical data for use in large-scale analyses to dramatically expand our understanding of the genetic architecture of PD. This report details the workflow for cohort integration into the complex arm of GP2, and together with our outline of the monogenic hub in a companion paper, provides a generalizable blueprint for establishing large scale collaborative research consortia

Multi-ancestry genome-wide association meta-analysis of Parkinson’s disease

Although over 90 independent risk variants have been identified for Parkinson’s disease using genome-wide association studies, most studies have been performed in just one population at a time. Here we performed a large-scale multi-ancestry meta-analysis of Parkinson’s disease with 49,049 cases, 18,785 proxy cases and 2,458,063 controls including individuals of European, East Asian, Latin American and African ancestry. In a meta-analysis, we identified 78 independent genome-wide significant loci, including 12 potentially novel loci (MTF2, PIK3CA, ADD1, SYBU, IRS2, USP8, PIGL, FASN, MYLK2, USP25, EP300 and PPP6R2) and fine-mapped 6 putative causal variants at 6 known PD loci. By combining our results with publicly available eQTL data, we identified 25 putative risk genes in these novel loci whose expression is associated with PD risk. This work lays the groundwork for future efforts aimed at identifying PD loci in non-European populations