Honouring heroes by branding in bronze: theorizing the UK's football statuary

As of 1 August 2012, there were 60 figurative subject-specific statues of association football players, managers, chairmen, owners or founding fathers sited at stadia or city centres within the UK, with all but three of these erected in the last 20 years. Clubs, their supporters and local authorities are investing substantial financial and logistical resources in adding to the cultural landscape. Their motivations are posited as a multifaceted marketing strategy that includes branding through success, the evocation of nostalgia and the creation of identity through heritage objects; a statement of cultural change, ownership and environmental improvement; and sympathy, as part of a developing mourning culture within football. Statues have been facilitated by the increasing availability of funding, and by spare capacity in fan organizations. Statue projects may be beneficial in bringing supporters together, but as a conduit for engaging the wider public in social history they are limited by subject choices driven by memory or sympathy. © 2013 © 2013 Taylor & Francis

Functional neuroanatomy of speech signal decoding in primary progressive aphasias

This work was supported by the Alzheimer’s Society (AS-PG-16-007), the National Institute for Health Research University College London Hospitals Biomedical Research Centre (CBRC 161), the UCL Leonard Wolfson Experimental Neurology Centre (PR/ ylr/18575), and the Economic and Social Research Council (ES/ K006711/1). Individual authors were supported by the Medical Research Council (PhD Studentship to CJDH; MRC Clinician Scientist Fellowship to JDR), the Wolfson Foundation (Clinical Research Fellowship to CRM), the National Brain AppealeFrontotemporal Dementia Research Fund (CNC), Alzheimer’s Research UK (ARTSRF2010-3 to SJC), and the Wellcome Trust (091673/Z/10/Z to JDW)

Discovery and functional prioritization of Parkinson's disease candidate genes from large-scale whole exome sequencing.

BACKGROUND: Whole-exome sequencing (WES) has been successful in identifying genes that cause familial Parkinson's disease (PD). However, until now this approach has not been deployed to study large cohorts of unrelated participants. To discover rare PD susceptibility variants, we performed WES in 1148 unrelated cases and 503 control participants. Candidate genes were subsequently validated for functions relevant to PD based on parallel RNA-interference (RNAi) screens in human cell culture and Drosophila and C. elegans models. RESULTS: Assuming autosomal recessive inheritance, we identify 27 genes that have homozygous or compound heterozygous loss-of-function variants in PD cases. Definitive replication and confirmation of these findings were hindered by potential heterogeneity and by the rarity of the implicated alleles. We therefore looked for potential genetic interactions with established PD mechanisms. Following RNAi-mediated knockdown, 15 of the genes modulated mitochondrial dynamics in human neuronal cultures and four candidates enhanced α-synuclein-induced neurodegeneration in Drosophila. Based on complementary analyses in independent human datasets, five functionally validated genes-GPATCH2L, UHRF1BP1L, PTPRH, ARSB, and VPS13C-also showed evidence consistent with genetic replication. CONCLUSIONS: By integrating human genetic and functional evidence, we identify several PD susceptibility gene candidates for further investigation. Our approach highlights a powerful experimental strategy with broad applicability for future studies of disorders with complex genetic etiologies

Altered phobic reactions in frontotemporal dementia: A behavioural and neuroanatomical analysis

Introduction: Abnormal behavioural and physiological reactivity to emotional stimuli is a hallmark of frontotemporal dementia (FTD), particularly the behavioural variant (bvFTD). As part of this repertoire, altered phobic responses have been reported in some patients with FTD but are poorly characterised. Methods: We collected data (based on caregiver reports) concerning the prevalence and nature of any behavioural changes related to specific phobias in a cohort of patients representing canonical syndromes of FTD and Alzheimer's disease (AD), relative to healthy older controls. Neuroanatomical correlates of altered phobic reactivity were assessed using voxel-based morphometry. Results: 46 patients with bvFTD, 20 with semantic variant primary progressive aphasia, 25 with non-fluent variant primary progressive aphasia, 29 with AD and 55 healthy age-matched individuals participated. Changes in specific phobia were significantly more prevalent in the combined FTD cohort (15.4% of cases) and in the bvFTD group (17.4%) compared both to healthy controls (3.6%) and patients with AD (3.5%). Attenuation of phobic reactivity was reported for individuals in all participant groups, however new phobias developed only in the FTD cohort. Altered phobic reactivity was significantly associated with relative preservation of grey matter in left posterior middle temporal gyrus, right temporo-occipital junction and right anterior cingulate gyrus, brain regions previously implicated in contextual decoding, salience processing and reward valuation. Conclusion: Altered phobic reactivity is a relatively common issue in patients with FTD, particularly bvFTD. This novel paradigm of strong fear experience has broad implications: clinically, for diagnosis and patient well-being; and neurobiologically, for our understanding of the pathophysiology of aversive sensory signal processing in FTD and the neural mechanisms of fear more generally.Alzheimer's Research UK (ARUK) Brain Research Trust Wolfson Foundation Alzheimer's Society Leonard Wolfson Experimental Neurology Centre Medical Research Council UK (MRC) NIHR UCLH/UCL Biomedical Research Centre Chilean Government (CONICYT PFCHA/Becas Chile) 2017e76180041 Pauline Ashley Action on Hearing Loss-Dunhill Medical Trust Fellowship PA_23 MRC PhD studentships Wellcome Trust Medical Research Council UK (MRC) MR/M018288/1 Medical Research Council UK (MRC) MR/M008525/1 NIHR Rare Disease Translational Research Collaboration BRC149/NS/M

Frontotemporal dementia and its subtypes: A genome-wide association study

Background: Frontotemporal dementia (FTD) is a complex disorder characterised by a broad range of clinical manifestations, differential pathological signatures, and genetic variability. Mutations in three genes-MAPT, GRN, and C9orf72-have been associated with FTD. We sought to identify novel genetic risk loci associated with the disorder. Methods: We did a two-stage genome-wide association study on clinical FTD, analysing samples from 3526 patients with FTD and 9402

Mendelian randomization implies no direct causal association between leukocyte telomere length and amyotrophic lateral sclerosis

We employed Mendelian randomization (MR) to evaluate the causal relationship between leukocyte telomere length (LTL) and amyotrophic lateral sclerosis (ALS) with summary statistics from genome-wide association studies (n = ~ 38,000 for LTL and ~ 81,000 for ALS in the European population; n = ~ 23,000 for LTL and ~ 4,100 for ALS in the Asian population). We further evaluated mediation roles of lipids in the pathway from LTL to ALS. The odds ratio per standard deviation decrease of LTL on ALS was 1.10 (95% CI 0.93–1.31, p = 0.274) in the European population and 0.75 (95% CI 0.53–1.07, p = 0.116) in the Asian population. This null association was also detected between LTL and frontotemporal dementia in the European population. However, we found that an indirect effect of LTL on ALS might be mediated by low density lipoprotein (LDL) or total cholesterol (TC) in the European population