ORCID Profile
0000-0002-0668-7865
Current Organisations
University of Southampton
,
King's College London
,
King's College London - Guy's Campus
,
Keck School of Medicine of USC
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Publisher: Elsevier BV
Date: 02-2006
DOI: 10.1016/J.CUB.2006.01.017
Abstract: The central dogma of mammalian brain sexual differentiation has contended that sex steroids of gonadal origin organize the neural circuits of the developing brain. Recent evidence has begun to challenge this idea and has suggested that, independent of the masculinizing effects of gonadal secretions, XY and XX brain cells have different patterns of gene expression that influence their differentiation and function. We have previously shown that specific differences in gene expression exist between male and female developing brains and that these differences precede the influences of gonadal hormones. Here we demonstrate that the Y chromosome-linked, male-determining gene Sry is specifically expressed in the substantia nigra of the adult male rodent in tyrosine hydroxylase-expressing neurons. Furthermore, using antisense oligodeoxynucleotides, we show that Sry downregulation in the substantia nigra causes a statistically significant decrease in tyrosine hydroxylase expression with no overall effect on neuronal numbers and that this decrease leads to motor deficits in male rats. Our studies suggest that Sry directly affects the biochemical properties of the dopaminergic neurons of the nigrostriatal system and the specific motor behaviors they control. These results demonstrate a direct male-specific effect on the brain by a gene encoded only in the male genome, without any mediation by gonadal hormones.
Publisher: Elsevier BV
Date: 07-2023
Publisher: Canadian Science Publishing
Date: 09-2021
Abstract: Existing guidance on the installation of screw piles suggest that they should be installed in a pitch-matched manner to avoid disturbance to the soil that may have a detrimental effect on the in-service performance of the pile. Recent insights from centrifuge modelling have shown that installing screw piles in this way requires large vertical compressive (or crowd) forces, which is inconsistent with the common assumption that screw piles pull themselves into the ground requiring minimal vertical compressive force. In this paper, through the use of the discrete element method (DEM), the effects of advancement ratio, i.e., the ratio between the vertical displacement per rotation to the geometric pitch of the helix of the screw pile helix, on the installation resistance and in-service capacity of a screw pile is investigated. The findings are further used to assess the applicability of empirical torque capacity correlation factors for large diameter screw piles. The results of the investigation show that it is possible to reduce the required vertical compressive installation force by 96% by reducing the advancement ratio and that although over-flighting a screw pile can decrease the subsequent compressive capacity, it appears to increase the tensile capacity significantly.
Publisher: eLife Sciences Publications, Ltd
Date: 21-03-2019
DOI: 10.7554/ELIFE.39702
Abstract: Genetic predictions of height differ among human populations and these differences have been interpreted as evidence of polygenic adaptation. These differences were first detected using SNPs genome-wide significantly associated with height, and shown to grow stronger when large numbers of sub-significant SNPs were included, leading to excitement about the prospect of analyzing large fractions of the genome to detect polygenic adaptation for multiple traits. Previous studies of height have been based on SNP effect size measurements in the GIANT Consortium meta-analysis. Here we repeat the analyses in the UK Biobank, a much more homogeneously designed study. We show that polygenic adaptation signals based on large numbers of SNPs below genome-wide significance are extremely sensitive to biases due to uncorrected population stratification. More generally, our results imply that typical constructions of polygenic scores are sensitive to population stratification and that population-level differences should be interpreted with caution. Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed ( xref ref-type="decision-letter" rid="SA1" see decision letter /xref ).
Publisher: University of Dundee
Date: 27-05-2019
DOI: 10.20933/100001123
Publisher: Oxford University Press (OUP)
Date: 10-03-2018
DOI: 10.1093/MMY/MYX113
Abstract: Species of Scedosporium and Lomentospora are considered as emerging opportunists, affecting immunosuppressed and otherwise debilitated patients, although classically they are known from causing trauma-associated infections in healthy in iduals. Clinical manifestations range from local infection to pulmonary colonization and severe invasive disease, in which mortality rates may be over 80%. These unacceptably high rates are due to the clinical status of patients, diagnostic difficulties, and to intrinsic antifungal resistance of these fungi. In consequence, several consortia have been founded to increase research efforts on these orphan fungi. The current review presents recent findings and summarizes the most relevant points, including the Scedosporium/Lomentospora taxonomy, environmental distribution, epidemiology, pathology, virulence factors, immunology, diagnostic methods, and therapeutic strategies.
Publisher: Canadian Science Publishing
Date: 10-05-2023
Publisher: Springer Science and Business Media LLC
Date: 23-11-2016
DOI: 10.1038/NCOMMS13357
Abstract: Large consortia have revealed hundreds of genetic loci associated with anthropometric traits, one trait at a time. We examined whether genetic variants affect body shape as a composite phenotype that is represented by a combination of anthropometric traits. We developed an approach that calculates averaged PCs (AvPCs) representing body shape derived from six anthropometric traits (body mass index, height, weight, waist and hip circumference, waist-to-hip ratio). The first four AvPCs explain % of the variability, are heritable, and associate with cardiometabolic outcomes. We performed genome-wide association analyses for each body shape composite phenotype across 65 studies and meta-analysed summary statistics. We identify six novel loci: LEMD2 and CD47 for AvPC1, RPS6KA5 / C14orf159 and GANAB for AvPC3, and ARL15 and ANP32 for AvPC4. Our findings highlight the value of using multiple traits to define complex phenotypes for discovery, which are not captured by single-trait analyses, and may shed light onto new pathways.
Publisher: eLife Sciences Publications, Ltd
Date: 06-12-2018
Publisher: Public Library of Science (PLoS)
Date: 29-06-2016
Publisher: CRC Press
Date: 23-06-2022
Publisher: Public Library of Science (PLoS)
Date: 10-2015
Publisher: Springer Science and Business Media LLC
Date: 26-01-2014
DOI: 10.1038/NATURE12960
Publisher: Elsevier BV
Date: 09-2023
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United States of America
No related grants have been discovered for Charleston Chiang.