Biology subjects

Hughes, A.

Publications and source records attributed to Hughes, A..

9 recordsLinked to original sources

bioRxiv2018

Biological control protects tropical forests

Biological control of invasive species can restore crop yields, and thus ease land pressure and contribute to forest conservation. In this study, we show how biological control against the mealybug Phenacoccus manihoti (Hemiptera) slowed deforestation across Southeast Asia. In Thailand, the newly-arrived mealybug caused an 18% decline in cassava yields over 2009-2010, a shortfall in national production and an escalation in the price of cassava products. This spurred an expansion of cassava cropping in neighboring countries from 713,000 ha in 2009 to >1 million ha by 2011: satellite imagery reveal 388%, 330%, 185% and 608% increases in peak deforestation rates in Cambodia, Lao PDR, Myanmar and Viet Nam focused in cassava crop expansion areas. Following release of the host-specific natural enemy Anagyrus lopezi (Hymenoptera) in 2010, mealybug outbreaks were reduced, cropping area contracted and associated deforestation slowed by 31-94% in individual countries. When used with due caution and according to current guidelines, biological control offers broad benefits for people and the environment.

ecology↗

bioRxiv2018

Properties of the epigenetic clock and age acceleration

BackgroundThe methylation status of numerous CpG sites in the human genome varies with age. The Horvath epigenetic clock used a wide variety of published DNA methylation data to produce an age prediction that has been widely used to, predict age in unknown samples, and draw conclusions about speed of ageing in various tissues, environments, and diseases. Despite its utility, there are a number of assumptions in the model that require examination. We explore the characteristics of the model in whole blood and multiple brain regions from older people, who are not well represented in the original training data, and in blood from a cross-sectional population study.\n\nResultsWe find that the model systematically underestimates age in tissues from older people. A decrease in slope of the predicted ages were observed at approximately 60 years, indicating that some loci in the model may change differently with age, and that age acceleration measures will themselves be age-dependent. This is seen most strongly in the cerebellum but is also present in other examined tissues, and is consistently observed in multiple datasets. An apparent association of Alzheimers disease with age acceleration disappears when age is used as a covariate. Association tests in the literature use a variety of methods for calculating age acceleration and often do not use age as a covariate. This is a potential cause of misleading findings.\n\nConclusionsAssociations of phenotypes with age acceleration should be evaluated cautiously, and chronological age should be included as a covariate in all analyses.

genomics↗

bioRxiv2018

Leveraging DNA methylation quantitative trait loci to characterize the relationship between methylomic variation, gene expression and complex traits.

Characterizing the complex relationship between genetic, epigenetic and transcriptomic variation has the potential to increase understanding about the mechanisms underpinning health and disease phenotypes. In this study, we describe the most comprehensive analysis of common genetic variation on DNA methylation (DNAm) to date, using the Illumina EPIC array to profile samples from the UK Household Longitudinal study. We identified 12,689,548 significant DNA methylation quantitative trait loci (mQTL) associations (P < 6.52x10-14) occurring between 2,907,234 genetic variants and 93,268 DNAm sites, including a large number not identified using previous DNAm-profiling methods. We demonstrate the utility of these data for interpreting the functional consequences of common genetic variation associated with > 60 human traits, using Summary data-based Mendelian Randomization (SMR) to identify 1,662 pleiotropic associations between 36 complex traits and 1,246 DNAm sites. We also use SMR to characterize the relationship between DNAm and gene expression, identifying 6,798 pleiotropic associations between 5,420 DNAm sites and the transcription of 1,702 genes. Our mQTL database and SMR results are available via a searchable online database (http://www.epigenomicslab.com/online-data-resources/) as a resource to the research community.

genetics↗

bioRxiv2018

Lipoprotein Signatures of Cholesteryl Ester Transfer Protein and HMG-CoA Reductase Inhibition

BackgroundCETP inhibition reduces vascular event rates but confusion surrounds its low-density lipoprotein (LDL)-cholesterol effects. We sought to clarify associations of genetic inhibition of CETP on detailed lipoproteins.\n\nMethods and ResultsWe used variants associated with CETP (rs247617) and HMGCR (rs12916) expression in 62,400 Europeans with detailed lipoprotein profiling from nuclear magnetic resonance spectroscopy. Genetic associations were scaled to 10% lower risk of coronary heart disease (CHD). Associations of lipoprotein measures with risk of incident CHD in three population-based cohorts (770 cases) were examined.\n\nCETP and HMGCR had near-identical associations with LDL-cholesterol concentration estimated by Friedewald-equation. HMGCR had a relatively consistent effect on cholesterol concentrations across all apolipoprotein B-containing lipoproteins. CETP had stronger effects on remnant and very-low-density lipoprotein cholesterol but no effect on cholesterol concentrations in LDL defined by particle size (diameter 18-26 nm) (-0.02SD 95%CI: -0.10, 0.05 for CETP versus -0.24SD, 95%CI -0.30, -0.18 for HMGCR). CETP had profound effects on lipid compositions of lipoproteins, with strong reductions in the triglyceride content of all highdensity lipoprotein (HDL) particles. These alterations in triglyceride composition within HDL subclasses were observationally associated with risk of CHD, independently of total cholesterol and triglycerides (strongest HR per 1-SD higher triglyceride composition in very-large HDL 1.35; 95%CI: 1.18, 1.54).\n\nConclusionCETP inhibition does not affect size-specific LDL cholesterol but may lower CHD risk by lowering cholesterol in other apolipoprotein-B containing lipoproteins and lowering triglyceride content of HDL particles. Conventional composite lipid assays may mask heterogeneous effects of lipid-altering therapies.

genetics↗

bioRxiv2018

Structure of the chromatin remodelling enzyme Chd1 bound to a ubiquitinylated nucleosome

ATP-dependent chromatin remodelling proteins represent a diverse family of proteins that share ATPase domains that are adapted to regulate protein-DNA interactions. Here we present structures of the yeast Chd1 protein engaged with nucleosomes in the presence of the transition state mimic ADP-beryllium fluoride. The path of DNA strands through the ATPase domains indicates the presence of contacts conserved with single strand translocases and additional contacts with both strands that are unique to Snf2 related proteins. The structure provides connectivity between rearrangement of ATPase lobes to a closed, nucleotide bound state and the sensing of linker DNA. Two turns of linker DNA are prised off the surface of the histone octamer as a result of Chd1 binding, and both the histone H3 tail and ubiquitin conjugated to lysine 120 are re-orientated towards the unravelled DNA. This indicates how changes to nucleosome structure can alter the way in which histone epitopes are presented.

molecular biology↗

bioRxiv2018

"Light-box" accelerated growth of poinsettias: LED-only Illumination

For the current commercialized agricultural industry which requires a reduced product lead time to customer and supply all year round, an artificial light emitting diode (LED)-based illumination has high potential due to high efficiency of electrical-to-light conversion. The main advantage of the deployed Red Green Blue Amber LED lighting system is colour mixing capability, which means the ability to generate all the colours in the spectrum by using three or four primary colour LEDs. The accelerated plant growth was carried out in a \"light-box\" which was made to generate an artificial day/night cycle and had a capability to tune the colour mixing ratio along the colour temperature curve of the chromaticity diagram. The control group of plants form the same initial batch was grown on the same shelf in a greenhouse at the same conditions with addition of artificial illumination by incandescent lamps for few hours. More dense and better quality (hence, commercial value) plants were grown in the light-box. Costs and efficiency projections of LED lamps for horticultural applications is discussed together with required capital investment. The total cost of the \"light-box\" including LED lamps and electronics was 850 AUD.

plant biology↗

bioRxiv2018

Signaling pathway screening platforms are an efficient approach toidentify therapeutic targets in precision-medicine oriented early phaseclinical trials

Precision medicine aims to tailor cancer therapies to target specific tumorpromoting aberrations. For tumors that lack actionable drivers, extensive molecular characterization and pre-clinical drug efficacy studies will be required to match patients with the appropriate targeted therapy. A cell line maintained at low passage and a patient-derived xenograft model (PDX) were generated using a fresh biopsy from a patient with a poorly-differentiated neuroendocrine tumor of unknown primary origin. Next-generation sequencing, high throughput signaling network analysis, and drug efficacy trials were then conducted to identify actionable targets for therapeutic intervention. No actionable mutations were identified after whole exome sequencing of the patients DNA; however, whole genome sequencing revealed amplification of the 3q and 5p chromosomal arms, that include the PIK3CA and RICTOR genes, respectively. Consistent with amplification of these genes, pathway analysis revealed activation of the AKT pathway. Based on this analysis, efficacy of PIK3CA and AKT inhibitors were evaluated in the tumor biopsy-derived cell culture and PDX, and response to the AKT inhibitor AZD5363 was observed both in vitro and in vivo indicating the patient would benefit from targeted therapies directed against the serine/threonine kinase AKT. In conclusion, our study demonstrates that high throughput signaling pathway analysis complements next-generation sequencing approaches for detection of actionable alterations and will aid in patient stratification into early-phase clinical trials.

clinical trials↗

bioRxiv2018

The Delirium and Population Health Informatics Cohort study protocol: ascertaining the determinants and outcomes from delirium in a whole population.

BackgroundDelirium affects 25% of older inpatients and is associated with long-term cognitive impairment and future dementia. However, no population studies have systematically ascertained cognitive function before, cognitive deficits during, and cognitive impairment after delirium. Therefore, there is a need to address the following question: does delirium, and its features (including severity, duration, and presumed aetiologies), predict long-term cognitive impairment, independent of cognitive impairment at baseline?\n\nMethodsThe Delirium and Population Health Informatics Cohort (DELPHIC) study is an observational population-based cohort study based in the London Borough of Camden. It is recruiting 2000 individuals aged [≥]70 years and prospectively following them for two years, including daily ascertainment of all inpatient episodes for delirium. Daily inpatient assessments include the Memorial Delirium Assessment Scale, the Observational Scale for Level of Arousal, and the Hierarchical Assessment of Balance and Mobility. Data on delirium aetiology is also collected. The primary outcome is the change in the modified Telephone Interview for Cognitive Status at two years.\n\nDiscussionDELPHIC is the first population sample to assess older persons before, during and after hospitalisation. The cumulative incidence of delirium in the general population aged [≥]70 will be described. DELPHIC offers the opportunity to quantify the impact of delirium on cognitive and functional outcomes. Overall, DELPHIC will provide a real-time public health observatory whereby information from primary, secondary, intermediate and social care can be integrated to understand how acute illness is linked to health and social care outcomes.

epidemiology↗

bioRxiv2017

Quantius: Generic, high-fidelity human annotation of scientific images at 105-clicks-per-hour

We describe Quantius, a crowd-based image annotation platform that provides an accurate alternative to task-specific computational algorithms for difficult image analysis problems. We use Quantius to quantify a variety of computationally challenging medium-throughput tasks with ~50x and 30x savings in analysis time and cost respectively, relative to a single expert annotator. We show equivalent deep learning performance for Quantius- and expert-derived annotations, bridging towards scalable integration with tailored machine-learning algorithms.

bioinformatics↗