Data review of reef related tourism, 1946-1980

This document details the level of tourism to the Great Barrier Ree

Alzheimer's disease pathology explains association between dementia with Lewy bodies and APOE-ε4/TOMM40 long poly-T repeat allele variants.

Introduction: The role of TOMM40-APOE 19q13.3 region variants is well documented in Alzheimer's disease (AD) but remains contentious in dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD). Methods: We dissected genetic profiles within the TOMM40-APOE region in 451 individuals from four European brain banks, including DLB and PDD cases with/without neuropathological evidence of AD-related pathology and healthy controls. Results: TOMM40-L/APOE-ε4 alleles were associated with DLB (OR TOMM40 -L = 3.61; P value = 3.23 × 10-9; OR APOE -ε4 = 3.75; P value = 4.90 × 10-10) and earlier age at onset of DLB (HR TOMM40 -L = 1.33, P value = .031; HR APOE -ε4 = 1.46, P value = .004), but not with PDD. The TOMM40-L/APOE-ε4 effect was most pronounced in DLB individuals with concomitant AD pathology (OR TOMM40 -L = 4.40, P value = 1.15 × 10-6; OR APOE -ε4 = 5.65, P value = 2.97 × 10-8) but was not significant in DLB without AD. Meta-analyses combining all APOE-ε4 data in DLB confirmed our findings (ORDLB = 2.93, P value = 3.78 × 10-99; ORDLB+AD = 5.36, P value = 1.56 × 10-47). Discussion: APOE-ε4/TOMM40-L alleles increase susceptibility and risk of earlier DLB onset, an effect explained by concomitant AD-related pathology. These findings have important implications in future drug discovery and development efforts in DLB

An applied methodology for stakeholder identification in transdisciplinary research

In this paper we present a novel methodology for identifying stakeholders for the purpose of engaging with them in transdisciplinary, sustainability research projects. In transdisciplinary research, it is important to identify a range of stakeholders prior to the problem-focussed stages of research. Early engagement with diverse stakeholders creates space for them to influence the research process, including problem definition, from the start. However, current stakeholder analysis approaches ignore this initial identification process, or position it within the subsequent content-focussed stages of research. Our methodology was designed as part of a research project into a range of soil threats in seventeen case study locations throughout Europe. Our methodology was designed to be systematic across all sites. It is based on a snowball sampling approach that can be implemented by researchers with no prior experience of stakeholder research, and without requiring significant financial or time resources. It therefore fosters transdisciplinarity by empowering physical scientists to identify stakeholders and understand their roles. We describe the design process and outcomes, and consider their applicability to other research projects. Our methodology therefore consists of a two-phase process of design and implementation of an identification questionnaire. By explicitly including a design phase into the process, it is possible to tailor our methodology to other research projects

GRaNIE and GRaNPA: inference and evaluation of enhancer-mediated gene regulatory networks

Enhancers play a vital role in gene regulation and are critical in mediating the impact of noncoding genetic variants associated with complex traits. Enhancer activity is a cell-type-specific process regulated by transcription factors (TFs), epigenetic mechanisms and genetic variants. Despite the strong mechanistic link between TFs and enhancers, we currently lack a framework for jointly analysing them in cell-type-specific gene regulatory networks (GRN). Equally important, we lack an unbiased way of assessing the biological significance of inferred GRNs since no complete ground truth exists. To address these gaps, we present GRaNIE (Gene Regulatory Network Inference including Enhancers) and GRaNPA (Gene Regulatory Network Performance Analysis). GRaNIE (https://git.embl.de/grp-zaugg/GR aNIE) builds enhancer-mediated GRNs based on covariation of chromatin accessibility and RNA-seq across samples (e.g. individuals), while GRaNPA (https://git.embl.de/grp-zaugg/GRaNPA) assesses the performance of GRNs for predicting cell-type-specific differential expression. We demonstrate their power by investigating gene regulatory mechanisms underlying the response of macrophages to infection, cancer and common genetic traits including autoimmune diseases. Finally, our methods identify the TF PURA as a putative regulator of pro-inflammatory macrophage polarisation

Pre‐breakup extension in the northern North Sea defined by complex strain partitioning and heterogeneous extension rates

The early stages of continental rifting are accommodated by the growth of upper‐crustal normal fault systems that are distributed relatively evenly across the rift width. Numerous fault systems define fault arrays , the kinematics of which are poorly understood due to a lack of regional studies drawing on high‐quality subsurface data. Here we investigate the long‐term (~150 Myr) growth of a rift‐related fault array in the East Shetland Basin, northern North Sea, using a regionally extensive subsurface dataset comprising 2D and 3D seismic reflection surveys and 107 boreholes. We show that rift‐related strain during the pre‐Triassic‐to‐Middle Triassic was originally distributed across several sub‐basins. The Middle‐to‐Late Triassic saw a decrease in extension rate (~14 m/Myr) as strain localized in the western part of the basin. Early Jurassic strain initially migrated eastwards, before becoming more diffuse during the main, Middle‐to‐Late Jurassic rift phase. The highest extension rates (~89 m/Myr) corresponded with the main rift event in the East Shetland Basin, before focusing of strain within the rift axis and ultimate abandonment of the East Shetland Basin in the Early Cretaceous. We also demonstrate marked spatial variations in timing and magnitude of slip along‐strike of major fault systems during this protracted rift event. Our results imply that strain migration patterns and extension rates during the initial, pre‐breakup phase of continental rifting may be more complex than previously thought; this reflects temporal and spatial changes in both thermal and mechanical properties of the lithosphere, in addition to varying extension rates

Scholarship on Gender and Sport in Sex Roles and Beyond

In this paper we critically review how research on girls or women and sport has developed over the last 35 years. We use a post-positivist lens to explore the content of the papers published in Sex Roles in the area of women, gender and sport and examine the shifts in how gender and sport have been conceptualized in these accounts. In order to initiate a broader dialogue about the scholarly analysis of gender and sport, we subsequently explore ideas inspired by feminist theorizing that have dominated/guided related research in other outlets over this time period but have received relatively little attention in papers published in Sex Roles. We conclude by briefly making suggestions for further research in this area

Large-scale association analyses identify host factors influencing human gut microbiome composition

To study the effect of host genetics on gut microbiome composition, the MiBioGen consortium curated and analyzed genome-wide genotypes and 16S fecal microbiome data from 18,340 individuals (24 cohorts). Microbial composition showed high variability across cohorts: only 9 of 410 genera were detected in more than 95% of samples. A genome-wide association study of host genetic variation regarding microbial taxa identified 31 loci affecting the microbiome at a genome-wide significant (P < 5 x 10(-8)) threshold. One locus, the lactase (LCT) gene locus, reached study-wide significance (genome-wide association study signal: P = 1.28 x 10(-20)), and it showed an age-dependent association with Bifidobacterium abundance. Other associations were suggestive (1.95 x 10(-10) < P < 5 x 10(-8)) but enriched for taxa showing high heritability and for genes expressed in the intestine and brain. A phenome-wide association study and Mendelian randomization identified enrichment of microbiome trait loci in the metabolic, nutrition and environment domains and suggested the microbiome might have causal effects in ulcerative colitis and rheumatoid arthritis