183 research outputs found
An investigation of the three-way joint coaching alliance: a social identity theory perspective
This study builds upon the previous research that recognised coaching as a triangular political space generating power relationships. We integrate social identity theory into this power negotiation process and consider that the ultimate purpose of coaching is to facilitate a shared coaching identity among all related collaborators. To gain in-depth understanding of factors that promote a three-way joint coaching identity; we conducted 25 critical incident interviews and two levels of Q-sorting (n = 10) with coaches, coachees and organisational stakeholders. The research results indicated that a workplace coaching identity is a flexible space underpinned by coachesâ attitude, all collaboratorsâ positions and the contracting process. Coachesâ accommodated communication techniques determine the relationship climate (instrumental or influential). Coachesâ position in the coaching space regulates their self-interests and motivation to change. Moreover, a transparent contracting process encourages communication flows and psychological exchanges among all collaborators that may gain more support from stakeholders
Selective Enrichment and Sequencing of Whole Mitochondrial Genomes in the Presence of Nuclear Encoded Mitochondrial Pseudogenes (Numts)
Numts are an integral component of many eukaryote genomes offering a snapshot of the evolutionary process that led from the incorporation of an α-proteobacterium into a larger eukaryotic cell some 1.8 billion years ago. Although numt sequence can be harnessed as molecular marker, these sequences often remain unidentified and are mistaken for genuine mtDNA leading to erroneous interpretation of mtDNA data sets. It is therefore indispensable that during the process of amplifying and sequencing mitochondrial genes, preventive measures are taken to ensure the exclusion of numts to guarantee the recovery of genuine mtDNA. This applies to mtDNA analyses in general but especially to studies where mtDNAs are sequenced de novo as the launch pad for subsequent mtDNA-based research. By using a combination of dilution series and nested rolling circle amplification (RCA), we present a novel strategy to selectively amplify mtDNA and exclude the amplification of numt sequence. We have successfully applied this strategy to de novo sequence the mtDNA of the Black Field Cricket Teleogryllus commodus, a species known to contain numts. Aligning our assembled sequence to the reference genome of Teleogryllus emma (GenBank EU557269.1) led to the identification of a numt sequence in the reference sequence. This unexpected result further highlights the need of a reliable and accessible strategy to eliminate this source of error
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Mead-halls of the Oiscingas: a new Kentish perspective on the Anglo-Saxon great hall complex phenomenon
Widely cited as a metaphor for the emergence of kingship in early medieval England, the great hall complex represents one of the most distinctive and evocative expressions of the Anglo-Saxon settlement record, yet interpretation of these sites remains underdeveloped and heavily weighted towards Yeavering. Inspired by the results of recent excavations at Lyminge, this paper undertakes a detailed comparative interrogation of three great hall complexes in Kent and exploits this new regional perspective to advance understanding of the agency and embodied meanings of these settlements as âtheatres of powerâ. Explored through the thematic prisms of place, social memory and monumental hybridity, this examination leads to a new appreciation of the involvement of great hall sites in the genealogical strategies of 7th-century royal dynasties and a fresh perspective on how this remarkable yet short-lived monumental idiom was adapted to harness the symbolic capital of Romanitas
Frontotemporal dementia and its subtypes: a genome-wide association study
SummaryBackground Frontotemporal dementia (FTD) is a complex disorder characterised by a broad range of clinical manifestations, differential pathological signatures, and genetic variability. Mutations in three genesâMAPT, GRN, and C9orf72âhave 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 healthy controls. To reduce genetic heterogeneity, all participants were of European ancestry. In the discovery phase (samples from 2154 patients with {FTD} and 4308 controls), we did separate association analyses for each {FTD} subtype (behavioural variant FTD, semantic dementia, progressive non-fluent aphasia, and {FTD} overlapping with motor neuron disease FTD-MND), followed by a meta-analysis of the entire dataset. We carried forward replication of the novel suggestive loci in an independent sample series (samples from 1372 patients and 5094 controls) and then did joint phase and brain expression and methylation quantitative trait loci analyses for the associated (p<5 Ă 10â8) single-nucleotide polymorphisms. Findings We identified novel associations exceeding the genome-wide significance threshold (p<5 Ă 10â8). Combined (joint) analyses of discovery and replication phases showed genome-wide significant association at 6p21.3, \{HLA\} locus (immune system), for rs9268877 (p=1·05 Ă 10â8; odds ratio=1·204 95% \{CI\} 1·11â1·30), rs9268856 (p=5·51 Ă 10â9; 0·809 0·76â0·86) and rs1980493 (p value=1·57 Ă 10â8, 0·775 0·69â0·86) in the entire cohort. We also identified a potential novel locus at 11q14, encompassing RAB38/CTSC (the transcripts of which are related to lysosomal biology), for the behavioural \{FTD\} subtype for which joint analyses showed suggestive association for rs302668 (p=2·44 Ă 10â7; 0·814 0·71â0·92). Analysis of expression and methylation quantitative trait loci data suggested that these loci might affect expression and methylation in cis. Interpretation Our findings suggest that immune system processes (link to 6p21.3) and possibly lysosomal and autophagy pathways (link to 11q14) are potentially involved in FTD. Our findings need to be replicated to better define the association of the newly identified loci with disease and to shed light on the pathomechanisms contributing to FTD. Funding The National Institute of Neurological Disorders and Stroke and National Institute on Aging, the Wellcome/MRC Centre on Parkinson's disease, Alzheimer's Research UK, and Texas Tech University Health Sciences Center
The Spectacle of Crime, Digitized
International audienceOne of the most significant features of the television series CSI: Crime Scene Investigationis its central preoccupation â forensic evidence â and the profession practised by its major characters â forensic science. Scientific inscriptions consistently allow the crime scene investigators (CSIs) to determine 'evidence' and 'truths' that otherwise elude them. At the same time, the dazzling digital effects used to punctuate key moments in each episode inevitably reference scientific technologies and the knowledge about reality that these promise. The success of the CSIs in every episode is premised upon knowledge guaranteed by scientific inscriptions and is itself an inscription of ways of seeing human bodies and the social body, represented by police scientists working to ensure public safety â a healthy social body. And it is also about how bodies, individual and social, are constituted as information, made knowable and validated by scientific instruments and procedures used to produce evidence
A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants.
This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ng.3448Advanced age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, with limited therapeutic options. Here we report on a study of >12 million variants, including 163,714 directly genotyped, mostly rare, protein-altering variants. Analyzing 16,144 patients and 17,832 controls, we identify 52 independently associated common and rare variants (P < 5 Ă 10(-8)) distributed across 34 loci. Although wet and dry AMD subtypes exhibit predominantly shared genetics, we identify the first genetic association signal specific to wet AMD, near MMP9 (difference P value = 4.1 Ă 10(-10)). Very rare coding variants (frequency <0.1%) in CFH, CFI and TIMP3 suggest causal roles for these genes, as does a splice variant in SLC16A8. Our results support the hypothesis that rare coding variants can pinpoint causal genes within known genetic loci and illustrate that applying the approach systematically to detect new loci requires extremely large sample sizes.We thank all participants of all the studies included for enabling this research by their participation in these studies. Computer resources for this project have been provided by the high-performance computing centers of the University of Michigan and the University of Regensburg. Group-specific acknowledgments can be found in the Supplementary Note. The Center for Inherited Diseases Research (CIDR) Program contract number is HHSN268201200008I. This and the main consortium work were predominantly funded by 1X01HG006934-01 to G.R.A. and R01 EY022310 to J.L.H
The impact of viral mutations on recognition by SARS-CoV-2 specific TÂ cells.
We identify amino acid variants within dominant SARS-CoV-2 TÂ cell epitopes by interrogating global sequence data. Several variants within nucleocapsid and ORF3a epitopes have arisen independently in multiple lineages and result in loss of recognition by epitope-specific TÂ cells assessed by IFN-Îł and cytotoxic killing assays. Complete loss of TÂ cell responsiveness was seen due to Q213K in the Aâ01:01-restricted CD8+ ORF3a epitope FTSDYYQLY207-215; due to P13L, P13S, and P13T in the Bâ27:05-restricted CD8+ nucleocapsid epitope QRNAPRITF9-17; and due to T362I and P365S in the Aâ03:01/Aâ11:01-restricted CD8+ nucleocapsid epitope KTFPPTEPK361-369. CD8+ TÂ cell lines unable to recognize variant epitopes have diverse TÂ cell receptor repertoires. These data demonstrate the potential for TÂ cell evasion and highlight the need for ongoing surveillance for variants capable of escaping TÂ cell as well as humoral immunity.This work is supported by the UK Medical Research Council (MRC); Chinese Academy of Medical Sciences(CAMS) Innovation Fund for Medical Sciences (CIFMS), China; National Institute for Health Research (NIHR)Oxford Biomedical Research Centre, and UK Researchand Innovation (UKRI)/NIHR through the UK Coro-navirus Immunology Consortium (UK-CIC). Sequencing of SARS-CoV-2 samples and collation of data wasundertaken by the COG-UK CONSORTIUM. COG-UK is supported by funding from the Medical ResearchCouncil (MRC) part of UK Research & Innovation (UKRI),the National Institute of Health Research (NIHR),and Genome Research Limited, operating as the Wellcome Sanger Institute. T.I.d.S. is supported by a Well-come Trust Intermediate Clinical Fellowship (110058/Z/15/Z). L.T. is supported by the Wellcome Trust(grant number 205228/Z/16/Z) and by theUniversity of Liverpool Centre for Excellence in Infectious DiseaseResearch (CEIDR). S.D. is funded by an NIHR GlobalResearch Professorship (NIHR300791). L.T. and S.C.M.are also supported by the U.S. Food and Drug Administration Medical Countermeasures Initiative contract75F40120C00085 and the National Institute for Health Research Health Protection Research Unit (HPRU) inEmerging and Zoonotic Infections (NIHR200907) at University of Liverpool inpartnership with Public HealthEngland (PHE), in collaboration with Liverpool School of Tropical Medicine and the University of Oxford.L.T. is based at the University of Liverpool. M.D.P. is funded by the NIHR Sheffield Biomedical ResearchCentre (BRC â IS-BRC-1215-20017). ISARIC4C is supported by the MRC (grant no MC_PC_19059). J.C.K.is a Wellcome Investigator (WT204969/Z/16/Z) and supported by NIHR Oxford Biomedical Research Centreand CIFMS. The views expressed are those of the authors and not necessarily those of the NIHR or MRC
The genetic architecture of the human cerebral cortex
The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder
Search for dark matter produced in association with bottom or top quarks in âs = 13 TeV pp collisions with the ATLAS detector
A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fbâ1 of protonâproton collision data recorded by the ATLAS experiment at âs = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements
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