Genome-wide association analyses of physical activity and sedentary behavior provide insights into underlying mechanisms and roles in disease prevention

Although physical activity and sedentary behavior are moderately heritable, little is known about the mechanisms that influence these traits. Combining data for up to 703,901 individuals from 51 studies in a multi-ancestry meta-analysis of genome-wide association studies yields 99 loci that associate with self-reported moderate-to-vigorous intensity physical activity during leisure time (MVPA), leisure screen time (LST) and/or sedentary behavior at work. Loci associated with LST are enriched for genes whose expression in skeletal muscle is altered by resistance training. A missense variant in ACTN3 makes the alpha-actinin-3 filaments more flexible, resulting in lower maximal force in isolated type IIA muscle fibers, and possibly protection from exercise-induced muscle damage. Finally, Mendelian randomization analyses show that beneficial effects of lower LST and higher MVPA on several risk factors and diseases are mediated or confounded by body mass index (BMI). Our results provide insights into physical activity mechanisms and its role in disease prevention.Multi-ancestry meta-analyses of genome-wide association studies for self-reported physical activity during leisure time, leisure screen time, sedentary commuting and sedentary behavior at work identify 99 loci associated with at least one of these traits

Data Descriptor: A global multiproxy database for temperature reconstructions of the Common Era

Reproducible climate reconstructions of the Common Era (1 CE to present) are key to placing industrial-era warming into the context of natural climatic variability. Here we present a community-sourced database of temperature-sensitive proxy records from the PAGES2k initiative. The database gathers 692 records from 648 locations, including all continental regions and major ocean basins. The records are from trees, ice, sediment, corals, speleothems, documentary evidence, and other archives. They range in length from 50 to 2000 years, with a median of 547 years, while temporal resolution ranges from biweekly to centennial. Nearly half of the proxy time series are significantly correlated with HadCRUT4.2 surface temperature over the period 1850-2014. Global temperature composites show a remarkable degree of coherence between high-and low-resolution archives, with broadly similar patterns across archive types, terrestrial versus marine locations, and screening criteria. The database is suited to investigations of global and regional temperature variability over the Common Era, and is shared in the Linked Paleo Data (LiPD) format, including serializations in Matlab, R and Python.(TABLE)Since the pioneering work of D'Arrigo and Jacoby1-3, as well as Mann et al. 4,5, temperature reconstructions of the Common Era have become a key component of climate assessments6-9. Such reconstructions depend strongly on the composition of the underlying network of climate proxies10, and it is therefore critical for the climate community to have access to a community-vetted, quality-controlled database of temperature-sensitive records stored in a self-describing format. The Past Global Changes (PAGES) 2k consortium, a self-organized, international group of experts, recently assembled such a database, and used it to reconstruct surface temperature over continental-scale regions11 (hereafter, ` PAGES2k-2013').This data descriptor presents version 2.0.0 of the PAGES2k proxy temperature database (Data Citation 1). It augments the PAGES2k-2013 collection of terrestrial records with marine records assembled by the Ocean2k working group at centennial12 and annual13 time scales. In addition to these previously published data compilations, this version includes substantially more records, extensive new metadata, and validation. Furthermore, the selection criteria for records included in this version are applied more uniformly and transparently across regions, resulting in a more cohesive data product.This data descriptor describes the contents of the database, the criteria for inclusion, and quantifies the relation of each record with instrumental temperature. In addition, the paleotemperature time series are summarized as composites to highlight the most salient decadal-to centennial-scale behaviour of the dataset and check mutual consistency between paleoclimate archives. We provide extensive Matlab code to probe the database-processing, filtering and aggregating it in various ways to investigate temperature variability over the Common Era. The unique approach to data stewardship and code-sharing employed here is designed to enable an unprecedented scale of investigation of the temperature history of the Common Era, by the scientific community and citizen-scientists alike

Comparison of Amino Acid Positron Emission Tomographic Radiotracers for Molecular Imaging of Primary and Metastatic Brain Tumors

Positron emission tomography (PET) is an imaging technology that can detect and characterize tumors based on their molecular and biochemical properties, such as altered glucose, nucleoside, or amino acid metabolism. PET plays a significant role in the diagnosis, prognostication, and treatment of various cancers, including brain tumors. In this article, we compare uptake mechanisms and the clinical performance of the amino acid PET radiotracers (L-[methyl- 11 C]methionine [MET], 18 F-fluoroethyl-tyrosine [FET], 18 F-fluoro-L- dihydroxy-phenylalanine [FDOPA], and 11 C-alpha-methyl-L-tryptophan [AMT]) most commonly used for brain tumor imaging. First, we discuss and compare the mechanisms of tumoral transport and accumulation, the basis of differential performance of these radioligands in clinical studies. Then we summarize studies that provided direct comparisons among these amino acid tracers and to clinically used 2-deoxy-2[ 18 F]fluoro-D-glucose [FDG] PET imaging. We also discuss how tracer kinetic analysis can enhance the clinical information obtained from amino acid PET images. We discuss both similarities and differences in potential clinical value for each radioligand. This comparative review can guide which radiotracer to favor in future clinical trials aimed at defining the role of these molecular imaging modalities in the clinical management of brain tumor patients

Oncological Applications of Positron Emission Tomography with Fluorine-18 Fluorodeoxyglucose

Positron emission tomography (PET) is now primarily used in oncological indication owing to the successful application of fluorine-18 fluorodeoxyglucose (FDG) in an increasing number of clinical indications at different stages of diagnosis, and for staging and follow-up. This review first considers the biological characteristics of FDG and then discusses methodological considerations regarding its use. Clinical indications are considered, and the results achieved in respect of various organs and tumour types are reviewed in depth. The review concludes with a brief consideration of the ways in which clinical PET might be improved