Biology subjects

Bell, S.

Publications and source records attributed to Bell, S..

28 records · Page 2Linked to original sources

bioRxiv2020

Forces experienced by instrumented animals depend on lifestyle

Animal-attached devices have transformed our understanding of vertebrate ecology. However, to be acceptable, researchers must minimize tag-related harm. The long-standing recommendation that tag masses should not exceed 3% of the animals body mass ignores tag forces generated by movement. We used collar-attached accelerometers on four free-ranging carnivores, spanning two orders of magnitude in mass, to reveal that during movement, forces exerted by 3% tags were generally equivalent to 4-19% of the animals masses, with a record of 54% in a hunting cheetah. Controlled studies on domestic dogs revealed how the tag forces are dictated by animal gait and speed but appear largely invariant of body mass. This fundamentally changes how acceptable tag mass limits should be determined, requiring cognizance of animal athleticism. One Sentence SummaryThere can be no universal rule for collar-tag masses as a percentage of carrier mass since tag forces depend on lifestyle.

ecology↗

bioRxiv2020

Signatures of selection in the coral holobiont reveal complex adaptations to inshore environments driven by Holocene climate change

Climate change at the Pleistocene/Holocene boundary reshaped many coastal landscapes, and provides an opportunity to study recent adaptive processes in marine species and ecosystems including coral reefs. On the Great Barrier Reef (GBR) sea level rise flooded a vast shelf creating a distinct inshore region which now harbours extensive coral assemblages despite being subject to relatively high turbidity, freshwater input and thermal fluctuations. To investigate how the coral holobiont has adapted to these conditions we first generated a highly contiguous genome assembly for Acropora tenuis based on long-read sequencing, and then used shallow whole-genome resequencing of 148 Acropora tenuis colonies from five inshore locations to model demographic history, identify signatures of selection and profile symbiont communities. We show that corals from Magnetic Island, located in the central inshore region of the GBR, are genetically distinct from those 50-500km further north, reflecting a Pleistocene (250-600Kya) split, whereas photosymbiont genotypes differ between reefs in a pattern more likely to reflect contemporary (Holocene) conditions. We also identified loci in the coral host genome with signatures of positive selection in the northern population and used coalescent simulations to show that these are unlikely to be accounted for by demographic history. Genes at these loci have roles in a diverse range of processes that includes heterotrophic nutrition, osmotic regulation, skeletal development and the establishment and maintenance of symbiosis. Our results show that, in the case of A. tenuis holobionts from the inshore GBR, the genomes of both the coral host and the primary photosymbiont of have been significantly shaped by their environment and illustrate the complexity of adaptations that have occurred in response to past climate change.

genomics↗

bioRxiv2020

Automated identification of multinucleated germ cells with U-Net

Phthalic acid esters (phthalates) are male reproductive toxicants, which exert their most potent toxicity during a critical window of sensitivity in fetal development. In the fetal rat, exposure to phthalates reduces testosterone biosynthesis, alters the development of seminiferous cords and other male reproductive tissues, and induces the formation of abnormal multinucleated germ cells (MNGs). Identification of MNGs is a time-intensive process, and it requires specialized training to identify MNGs in histological sections. As a result, MNGs are not routinely quantified in phthalate toxicity experiments. In order to speed up and standardize this process, we have developed an improved method for automated detection of MNGs. Using hand-labeled histological section images with human-identified MNGs, we trained a convolutional neural network with a U-Net architecture to identify MNGs on unlabeled images. With unseen hand-labeled images not used in model training, we assessed the performance of the model, using five different configurations of the data. On average, the model reached near human accuracy, and in the best model, it exceeded it. The use of automated image analysis will allow data on this histopathological endpoint to be more readily collected for analysis of phthalate toxicity. Our trained model application code is available for download at github.com/brown-ccv/mngcount.

pharmacology and toxicology↗

bioRxiv2019

Use of polygenic risk scores and other molecular markers to enhance cardiovascular risk prediction: Prospective cohort study and modelling analysis

BackgroundThere is debate about the value of adding information on genetic and other molecular markers to conventional cardiovascular disease (CVD) risk predictors.\n\nMethodsUsing data on 306,654 individuals without a history of CVD from UK Biobank, we calculated measures of risk-discrimination and reclassification upon addition of polygenic risk scores (PRS) and a panel of 27 clinical biochemistry markers to a conventional risk prediction model (i.e., including age, sex, systolic blood pressure, smoking status, history of diabetes, total cholesterol and HDL cholesterol). We then modelled implications of initiating guideline-recommended statin therapy after the assessment of molecular markers for a UK primary-care setting.\n\nFindingsThe C-index was 0.710 (95% CI, 0.703-0.717) for a CVD prediction model containing conventional risk predictors alone. The C-index increased by similar amounts when adding information on PRS or biochemistry markers (0.011 and 0.014, respectively; P<0.001), and it increased still further (0.022; P<0.001) when information on both was combined. Among cases and controls, continuous net reclassification improvements were about 12% and 19%, respectively, when both PRS and biochemistry markers were added. If PRS and biochemistry markers were to be assessed in the entire primary care population aged 40-75, then it could help prevent one additional CVD event for every 893 individuals screened. By contrast, targeted assessment only among people at intermediate (i.e., 5-10%) 10-year CVD risk could help prevent one additional CVD event for every 233 individuals screened. This targeted strategy could help reclassify 16% of the intermediate-risk group to the high-risk (i.e., [≥]10%) category, preventing 11% more CVD events than conventional risk prediction.\n\nInterpretationAdding information on both PRS and selected biochemistry markers moderately enhanced CVD predictive accuracy and could improve primary prevention of CVD. However, our modelling suggested that targeted assessment of molecular markers among individuals at intermediate-risk would be more efficient than blanket approaches.

genomics↗

bioRxiv2019

Automated data extraction from historical city directories the rise and fall of mid-century gas stations in Providence, RI

The location of defunct environmentally hazardous businesses like gas stations has many implications for modern American cities. To track down these locations, we present the directoreadr code (github.com/brown-ccv/directoreadr). Using scans of Polk city directories from Providence, RI, directoreadr extracts and parses business location data with a high degree of accuracy. The image processing pipeline ran without any human input for 94.4% of the pages we examined. For the remaining 5.6%, we processed them with some human input. Through hand-checking a sample of three years, we estimate that ~94.6% of historical gas stations are correctly identified and located, with historical street changes and non-standard address formats being the main drivers of errors. As an example use, we look at gas stations, finding that gas stations were most common early in the study period in 1936, beginning a sharp and steady decline around 1950. We are making the dataset produced by directoreadr publicly available. We hope it will be used to explore a range of important questions about socioeconomic patterns in Providence and cities like it during the transformations of the mid-1900s.

ecology↗

bioRxiv2019

Neurology-related protein biomarkers are associated with general fluid cognitive ability and brain volume in older age

Identifying the biological correlates of late life cognitive function is important if we are to ascertain biomarkers for, and develop treatments to help reduce, age-related cognitive decline. This study investigated the associations between plasma levels of 91 neurology-related proteins (Olink(R) Proteomics) and general fluid cognitive ability in the Lothian Birth Cohort 1936 (LBC1936, N=798), the Lothian Birth Cohort 1921 (LBC1921, N=165), and the INTERVAL BioResource, (N=4,451). In LBC1936, we also examined mediation of protein-cognitive ability associations by MRI-derived indices of brain structure. In the LBC1936, 22 of the proteins and the first principal component (PC) created from a PC analysis of the 91 proteins, were associated with general fluid cognitive ability ({beta} between -0.11 and -0.17, p<0.0029). Total brain volume partially mediated the association between 10 of these proteins and general fluid cognitive ability. Effect sizes for the 22 proteins, although smaller, were all in the same direction as in LBC1936 in an age-matched subsample of INTERVAL. Similar effect sizes were found for the majority of these 22 proteins in the older LBC1921. The associations were not replicated in a younger subset of INTERVAL. In conclusion, we identified plasma levels of a number of neurology-related proteins that were associated with general fluid cognitive ability in later life, some of which were mediated by brain volume.

neuroscience↗

bioRxiv2019

Genetic determinants of lipids and cardiovascular disease outcomes: a wide-angled Mendelian randomization investigation

AimsTo systematically investigate causal relationships between circulating lipids and cardiovascular outcomes, using a Mendelian randomization approach.\n\nMethods and ResultsIn the primary analysis, we performed two-sample multivariable Mendelian randomization using data from participants of European ancestry. We also conducted univariable analyses using inverse-variance weighted and robust methods, and gene-specific analyses using variants that can be considered as proxies for specific lipid-lowering medications. We obtained associations with lipid fractions from the Global Lipids Genetics Consortium, a meta-analysis of 188,577 participants, and genetic associations with cardiovascular outcomes from 367,703 participants in UK Biobank.\n\nFor LDL-cholesterol, in addition to the expected positive associations with coronary artery disease (CAD) risk (odds ratio per 1 standard deviation increase [OR], 1.45; 95% confidence interval [95%CI] 1.35-1.57) and other atheromatous outcomes (ischemic cerebrovascular disease and peripheral vascular disease), we found independent associations of genetically-predicted LDL-cholesterol with abdominal aortic aneurysm (OR 1.75; 95%CI 1.40-2.17), and aortic valve stenosis (OR 1.46; 95%CI 1.25-1.70). Genetically-predicted triglyceride levels were positively associated with CAD (OR 1.25; 95%CI 1.12-1.40), aortic valve stenosis (OR 1.29; 95%CI 1.04-1.61), and hypertension (OR 1.17; 95%CI 1.07-1.27), but inversely associated with venous thromboembolism (OR 0.79; 95%CI 0.67-0.93). The positive associations of genetically-predicted LDL-cholesterol and triglycerides with heart failure and aortic stenosis appeared to be mediated by CAD.\n\nConclusionLowering LDL-cholesterol is likely to prevent abdominal aortic aneurysm and aortic stenosis, in addition to CAD and other atheromatous cardiovascular outcomes. Lowering triglycerides is likely to prevent CAD and aortic valve stenosis, but may increase risk of thromboembolism.

epidemiology↗

bioRxiv2019

Genetic analysis identifies molecular systems and biological pathways associated with household income

Socio-economic position (SEP) is a multi-dimensional construct reflecting (and influencing) multiple socio-cultural, physical, and environmental factors. Previous genome-wide association studies (GWAS) using household income as a marker of SEP have shown that common genetic variants account for 11% of its variation. Here, in a sample of 286,301 participants from UK Biobank, we identified 30 independent genome-wide significant loci, 29 novel, that are associated with household income. Using a recently-developed method to meta-analyze data that leverages power from genetically-correlated traits, we identified an additional 120 income-associated loci. These loci showed clear evidence of functional enrichment, with transcriptional differences identified across multiple cortical tissues, in addition to links with GABAergic and serotonergic neurotransmission. We identified neurogenesis and the components of the synapse as candidate biological systems that are linked with income. By combining our GWAS on income with data from eQTL studies and chromatin interactions, 24 genes were prioritized for follow up, 18 of which were previously associated with cognitive ability. Using Mendelian Randomization, we identified cognitive ability as one of the causal, partly-heritable phenotypes that bridges the gap between molecular genetic inheritance and phenotypic consequence in terms of income differences. Significant differences between genetic correlations indicated that, the genetic variants associated with income are related to better mental health than those linked to educational attainment (another commonly-used marker of SEP). Finally, we were able to predict 2.5% of income differences using genetic data alone in an independent sample. These results are important for understanding the observed socioeconomic inequalities in Great Britain today.

genetics↗

bioRxiv2018

High Genetic Potential for Proteolytic Decomposition in Northern Peatland Ecosystems

AbstractNitrogen (N) is a scarce nutrient commonly limiting primary productivity. Microbial decomposition of complex carbon (C) into small organic molecules (e.g., free amino acids) has been suggested to supplement biologically-fixed N in high latitude peatlands. We evaluated the microbial (fungal, bacterial, and archaeal) genetic potential for organic N depolymerization in peatlands at Marcell Experimental Forest (MEF) in northern Minnesota. We used guided gene assembly to examine the abundance and diversity of protease genes; and further compared to those of N-fixing (nifH) genes in shotgun metagenomic data collected across depth at two distinct peatland environments (bogs and fens). Microbial proteases greatly outnumbered nifH genes with the most abundant gene families (archaeal M1 and bacterial Trypsin) each containing more sequences than all sequences attributed to nifH. Bacterial protease gene assemblies were diverse and abundant across depth profiles, indicating a role for bacteria in releasing free amino acids from peptides through depolymerization of older organic material and contrasting the paradigm of fungal dominance in depolymerization in forest soils. Although protease gene assemblies for fungi were much less abundant overall than for bacteria, fungi were prevalent in surface samples and therefore may be vital in degrading large soil polymers from fresh plant inputs during early stage of depolymerization. In total, we demonstrate that depolymerization enzymes from a diverse suite of microorganisms, including understudied bacterial and archaeal lineages, are likely to play a substantial role in C and N cycling within northern peatlands.\n\nImportanceNitrogen (N) is a common limitation on primary productivity, and its source remains unresolved in northern peatlands that are vulnerable to environmental change. Decompositionof complex organic matter into free amino acids has been proposed as an important N source, but the genetic potential of microorganisms mediating this process has not been examined. Such information can elucidate possible responses of northern peatlands to environmental change. We show high genetic potential for microbial production of free amino acids across a range of microbial guilds. In particular, the abundance and diversity of bacterial genes encoding proteolytic activity suggests a predominant role for bacteria in regulating productivity and contrasts a paradigm of fungal dominance of organic N decomposition. Our results expand our current understanding of coupled carbon and nitrogen cycles in north peatlands and indicate that understudied bacterial and archaeal lineages may be central in this ecosystems response to environmental change.

ecology↗

bioRxiv2018

Universal kinetics for engagement of mechanosensing pathways in cell adhesion

When plated onto substrates, cell morphology and even stem cell differentiation are influenced by the stiffness of their environment. Stiffer substrates give strongly spread (eventually polarized) cells with strong focal adhesions, and stress fibers; very soft substrates give a less developed cytoskeleton, and much lower cell spreading. The kinetics of this process of cell spreading is studied extensively, and important universal relationships are established on how the cell area grows with time. Here we study the population dynamics of spreading cells, investigating the characteristic processes involved in cell response to the substrate. We show that unlike the individual cell morphology, this population dynamics does not depend on the substrate stiffness. Instead, a strong activation temperature dependence is observed. Different cell lines on different substrates all have long-time statistics controlled by the thermal activation over a single energy barrier {triangleup}G {approx} 19 kcal/mol, while the early-time kinetics follows a power law ~ t5. This implies that the rate of spreading depends on an internal process of adhesion-mechanosensing complex assembly and activation: the operational complex must have 5 component proteins, and the last process in the sequence (which we believe is the activation of focal adhesion kinase) is controlled by the binding energy {triangleup}G.

biophysics↗