A global database of Holocene paleotemperature records

A comprehensive database of paleoclimate records is needed to place recent warming into the longer-term context of natural climate variability. We present a global compilation of quality-controlled, published, temperature-sensitive proxy records extending back 12,000 years through the Holocene. Data were compiled from 679 sites where time series cover at least 4000 years, are resolved at sub-millennial scale (median spacing of 400 years or finer) and have at least one age control point every 3000 years, with cut-off values slackened in data-sparse regions. The data derive from lake sediment (51%), marine sediment (31%), peat (11%), glacier ice (3%), and other natural archives. The database contains 1319 records, including 157 from the Southern Hemisphere. The multi-proxy database comprises paleotemperature time series based on ecological assemblages, as well as biophysical and geochemical indicators that reflect mean annual or seasonal temperatures, as encoded in the database. This database can be used to reconstruct the spatiotemporal evolution of Holocene temperature at global to regional scales, and is publicly available in Linked Paleo Data (LiPD) format.Fil: Kaufman, Darrell. Northern Arizona University.; Estados UnidosFil: McKay, Nicholas. Northern Arizona University.; Estados UnidosFil: Routson, Cody. Northern Arizona University.; Estados UnidosFil: Erb, Michael. Northern Arizona University.; Estados UnidosFil: Davis, Basil. University Of Lausanne; SuizaFil: Heiri, Oliver. University Of Basel; SuizaFil: Jaccard, Samuel. University Of Bern; SuizaFil: Tierney, Jessica. University of Arizona; Estados UnidosFil: Dätwyler, Christoph. University Of Bern; SuizaFil: Axford, Yarrow. Northwestern University; Estados UnidosFil: Brussel, Thomas. University of Utah; Estados UnidosFil: Cartapanis, Olivier. University Of Bern; SuizaFil: Chase, Brian. Universite de Montpellier; FranciaFil: Dawson, Andria. Mount Royal University; CanadáFil: de Vernal, Anne. Université du Québec a Montreal; CanadáFil: Engels, Stefan. University of London; Reino UnidoFil: Jonkers, Lukas. University Of Bremen; AlemaniaFil: Marsicek, Jeremiah. University of Wisconsin-Madison; Estados UnidosFil: Moffa Sánchez, Paola. University of Durham; Reino UnidoFil: Morrill, Carrie. University of Colorado; Estados UnidosFil: Orsi, Anais. Université Paris-Saclay; FranciaFil: Rehfeld, Kira. Heidelberg University; AlemaniaFil: Saunders, Krystyna. Australian Nuclear Science And Technology Organisation; AustraliaFil: Sommer, Philipp. University Of Lausanne; SuizaFil: Thomas, Elizabeth. University At Buffalo; Estados UnidosFil: Tonello, Marcela Sandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Marinas y Costeras. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Marinas y Costeras; ArgentinaFil: Tóth, Mónika. Balaton Limnological Institute; HungríaFil: Vachula, Richard. Brown University; Estados UnidosFil: Andreev, Andrei. Alfred Wegener Institut Helmholtz Centre for Polar and Marine Research; AlemaniaFil: Bertrand, Sebastien. Ghent University; BélgicaFil: Massaferro, Julieta. Administración de Parques Nacionales. Parque Nacional "Nahuel Huapi"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Observer variability of absolute and relative thrombus density measurements in patients with acute ischemic stroke

Introduction: Thrombus density may be a predictor for acute ischemic stroke treatment success. However, only limited data on observer variability for thrombus density measurements exist. This study assesses the variability and bias of four common thrombus density measurement methods by expert and non-expert observers. Methods: For 132 consecutive patients with acute ischemic stroke, three experts and two trained observers determined thrombus density by placing three standardized regions of interest (ROIs) in the thrombus and corresponding contralateral arterial segment. Subsequently, absolute and relative thrombus densities were determined using either one or three ROIs. Intraclass correlation coefficient (ICC) was determined, and Bland–Altman analysis was performed to evaluate interobserver and intermethod agreement. Accuracy of the trained observer was evaluated with a reference expert observer using the same statistical analysis. Results: The highest interobserver agreement was obtained for absolute thrombus measurements using three ROIs (ICCs ranging from 0.54 to 0.91). In general, interobserver agreement was lower for relative measurements, and for using one instead of three ROIs. Interobserver agreement of trained non-experts and experts was similar. Accuracy of the trained observer measurements was comparable to the expert interobserver agreement and was better for absolute measurements and with three ROIs. The agreement between the one ROI and three ROI methods was good. Conclusion: Absolute thrombus density measurement has superior interobserver agreement compared to relative density measurement. Interobserver variation is smaller when multiple ROIs are used. Trained non-expert observers can accurately and reproducibly assess absolute thrombus densities using three ROIs

Genome-wide analysis of 53,400 people with irritable bowel syndrome highlights shared genetic pathways with mood and anxiety disorders

Funder: Kennedy Trust Rheumatology Research Prize StudentshipFunder: DFG Cluster of Excellence “Precision Medicine in Chronic In-flammation” (PMI; ID: EXC2167)Funder: EC | EC Seventh Framework Programm | FP7 Ideas: European Research Council (FP7-IDEAS-ERC - Specific Programme: “Ideas” Implementing the Seventh Framework Programme of the European Community for Research, Technological Development and Demonstration Activities (2007 to 2013)); doi: https://doi.org/10.13039/100011199; Grant(s): 715772Funder: NWO-VIDI grant 016.178.056, the Netherlands Heart Foundation CVON grant 2018-27, and NWO Gravitation grant ExposomeNLFunder: Li Ka Shing Foundation (Li Ka Shing Foundation Limited); doi: https://doi.org/10.13039/100007421Abstract: Irritable bowel syndrome (IBS) results from disordered brain–gut interactions. Identifying susceptibility genes could highlight the underlying pathophysiological mechanisms. We designed a digestive health questionnaire for UK Biobank and combined identified cases with IBS with independent cohorts. We conducted a genome-wide association study with 53,400 cases and 433,201 controls and replicated significant associations in a 23andMe panel (205,252 cases and 1,384,055 controls). Our study identified and confirmed six genetic susceptibility loci for IBS. Implicated genes included NCAM1, CADM2, PHF2/FAM120A, DOCK9, CKAP2/TPTE2P3 and BAG6. The first four are associated with mood and anxiety disorders, expressed in the nervous system, or both. Mirroring this, we also found strong genome-wide correlation between the risk of IBS and anxiety, neuroticism and depression (rg > 0.5). Additional analyses suggested this arises due to shared pathogenic pathways rather than, for example, anxiety causing abdominal symptoms. Implicated mechanisms require further exploration to help understand the altered brain–gut interactions underlying IBS

Specification of ACMG/AMP variant classification guidelines for Familial Hypercholesterolemia – a ClinGen FH Variant Curation Committee Pilot Study

Familial hypercholesterolemia (FH) is a common autosomal dominant disorder (~1:250 individuals affected) of lipid metabolism, associated with an increased risk of cardiovascular disease. Individuals with FH characteristically present with severely elevated blood cholesterol levels, which leads to atherosclerotic plaque formation and subsequently, myocardial infarction due to premature coronary artery disease. Three main causative genes have been associated with FH: LDLR, APOB and PCSK9. Diagnosis is critical for early intervention and treatment, and it is imperative that family members of affected individuals be identified as early as possible.N/

Adaptation of ACMG/AMP guidelines for variant interpretation in familial hypercholesterolemia – a ClinGen FH Expert Panel pilot study

Familial hypercholesterolemia (FH) is an autosomal dominant disorder of lipid metabolism associated with premature atherosclerosis and increased cardiovascular risk. Over 3,000 variants in LDLR, APOB, and PCSK9 have been identified in FH patients; however, <10% of these have been functionally proven to cause disease. The recent ACMG/AMP guidelines for standardized variant interpretation in Mendelian disorders are being used to help further classify FH-associated variants. Despite such efforts, these existing ACMG/AMP guidelines need to be modified to become more disease-specific for FH. In 2016, the Clinical Genome Resource (ClinGen) consortium FH Expert Panel was created with the goal to develop FH-specific variant interpretation guidelinesJR Chora was funded by SFRH/BD/108503/2015. The ClinGen Consortium is funded by the NHGRI, in conjunction with additional funding from the NICHD and NCI, through the following grants and contracts: 1U41HG006834-01A1 (Rehm), 1U01HG007437-01 (Berg), 1U01HG007436-01 (Bustamante), and HHSN261200800001E.N/

Publisher Correction: A global database of Holocene paleotemperature records

In an earlier version of this Data Descriptor the figure images 4, 5 and 6 were swapped. Both the HTML and PDF versions have been updated to reflect this change

Publisher Correction: A global database of Holocene paleotemperature records

In an earlier version of this Data Descriptor the figure images 4, 5 and 6 were swapped. Both the HTML and PDF versions have been updated to reflect this change

Cooperation between bHLH transcription factors and histones for DNA access.

The basic helix-loop-helix (bHLH) family of transcription factors recognizes DNA motifs known as E-boxes (CANNTG) and includes 108 members1. Here we investigate how chromatinized E-boxes are engaged by two structurally diverse bHLH proteins: the proto-oncogene MYC-MAX and the circadian transcription factor CLOCK-BMAL1 (refs. 2,3). Both transcription factors bind to E-boxes preferentially near the nucleosomal entry-exit sites. Structural studies with engineered or native nucleosome sequences show that MYC-MAX or CLOCK-BMAL1 triggers the release of DNA from histones to gain access. Atop the H2A-H2B acidic patch4, the CLOCK-BMAL1 Per-Arnt-Sim (PAS) dimerization domains engage the histone octamer disc. Binding of tandem E-boxes5-7 at endogenous DNA sequences occurs through direct interactions between two CLOCK-BMAL1 protomers and histones and is important for circadian cycling. At internal E-boxes, the MYC-MAX leucine zipper can also interact with histones H2B and H3, and its binding is indirectly enhanced by OCT4 elsewhere on the nucleosome. The nucleosomal E-box position and the type of bHLH dimerization domain jointly determine the histone contact, the affinity and the degree of competition and cooperativity with other nucleosome-bound factors