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Campbell, A.

Publications and source records attributed to Campbell, A..

At least 55 records · Page 3Linked to original sources

A Deep Graph Neural Network Architecture for Modelling Spatio-temporal Dynamics in resting-stating functional MRI Data

Resting-state functional magnetic resonance imaging (rs-fMRI) has been successfully employed to understand the organisation of the human brain. For rs-fMRI analysis, the brain is typically parcellated into regions of interest (ROIs) and modelled as a graph where each ROI is a node and pairwise correlation between ROI blood-oxygen-level-dependent (BOLD) time series are edges. Recently, graph neural networks (GNNs) have seen a surge in popularity due to their successes in modelling unstructured relational data. The latest developments with GNNs, however, have not yet been fully exploited for the analysis of rs-fMRI data, particularly with regards to its spatio-temporal dynamics. Herein we present a novel deep neural network architecture, combining both GNNs and temporal convolutional networks (TCNs), which is able to learn from the spatial and temporal components of rs-fMRI data in an end-to-end fashion. In particular, this corresponds to intra-feature learning (i.e., learning temporal dynamics with TCNs) as well as inter-feature learning (i.e., leveraging spatial interactions between ROIs with GNNs). We evaluate our model with an ablation study using 35,159 samples from the UK Biobank rs-fMRI database. We also demonstrate explainability features of our architecture which map to realistic neurobiological insights. We hope our model could lay the groundwork for future deep learning architectures focused on leveraging the inherently and inextricably spatio-temporal nature of rs-fMRI data.

neuroscience↗

Omics versus Questionnaires: Using methylation data to assess the environmental impact of smoking on obesity-related traits

Variation in obesity-related traits has a genetic basis with heritabilities between 40 and 70%. While the global obesity pandemic is usually associated with environmental changes related to lifestyle and socioeconomic changes, most genetic studies do not include all relevant environmental covariates, so genetic contribution to variation in obesity-related traits cannot be accurately assessed. Some studies have described interactions between a few individual genes linked to obesity and environmental variables but there is no agreement on their total contribution to differences between individuals. Here we compared self-reported smoking data and a methylation-based proxy to explore the effect of smoking and genome-by-smoking interactions on obesity related traits from a genome-wide perspective to estimate the amount of variance they explain. Our results indicate that exploiting omic measures can improve models for complex traits such as obesity and can be used as a substitute for, or jointly with, environmental records to better understand causes of disease.

genomics↗

Mechanism of cell polarisation and first lineage segregation in the human embryo

The formation of differential cell lineages in the mammalian blastocyst from the totipotent zygote is crucial for implantation and the success of the whole pregnancy. The first lineage segregation generates the polarised trophectoderm (TE) tissue, which forms the placenta, and the apolar inner cell mass (ICM), which mainly gives rise to all foetal tissues and also the yolk sac1-3. The mechanism underlying this cell fate segregation has been extensively studied in the mouse embryo4,5. However, when and how it takes place in the human embryo remains unclear. Here, using time-lapse imaging and 325 surplus human embryos, we provide a detailed characterisation of morphological events and transcription factor expression and localisation to understand how they lead to the first lineage segregation in human embryogenesis. We show that the first lineage segregation of the human embryo is triggered by cell polarisation that occurs at the 8-cell stage in two sequential steps. In the first step, F-actin becomes apically polarised concomitantly with embryo compaction. In the second step, the Par complex becomes polarised to form the apical cellular domain. Mechanistically, we show that activation of Phospholipase C (PLC) triggers actin polarisation and is therefore essential for apical domain formation, as is the case in mouse embryos6. Finally, we show that, in contrast to the mouse embryo, the key extra-embryonic determinant GATA37,8 is expressed not only in extra-embryonic lineage precursors upon blastocyst formation. However, the cell polarity machinery enhances the expression and nuclear accumulation of GATA3. In summary, our results demonstrate for the first time that cell polarisation reinforces the first lineage segregation in the human embryo.

developmental biology↗

Whole genome CRISPR screens identify LRRK2-regulated endocytosis as a major mechanism for extracellular tau uptake by human neurons

Extracellular release and cellular uptake of pathogenic forms of the microtubule-associated protein tau contribute to the pathogenesis of several neurodegenerative diseases, including Alzheimers disease. Defining the cellular mechanisms and pathways for tau entry to human neurons is essential to understanding tauopathy pathogenesis and the rational design of disease-modifying therapeutics. Whole genome CRISPR loss-of-function screens in human iPSC-derived excitatory neurons, the major neuronal cell type affected in these diseases, enabled the delineation of the different cellular pathways for uptake of extracellular monomeric and fibrillar tau. Monomeric and fibrillar tau are both taken up by human neurons by receptor-mediated endocytosis, but involve different routes of entry at the neuronal surface: the low-density lipoprotein LRP1 is the primary receptor for monomeric tau, but contributes less to fibrillar tau entry. Similarly, endocytosis of monomeric tau is dependent on the familial Parkinsons disease gene LRRK2, but not required for endocytosis of fibrillar tau. These findings implicate LRP1 and LRRK2 in the pathogenesis of tauopathies and Parkinsons disease and identify LRRK2 as a potential therapeutic target for altering progression of these diseases.

neuroscience↗

Temporal modulation of the NF-κB RelA network in response to different types of DNA damage

Different types of DNA damage can initiate phosphorylation-mediated signalling cascades that result in stimulus specific pro- or anti-apoptotic cellular responses. Amongst its many roles, the NF-{kappa}B transcription factor RelA is central to these DNA damage response pathways. However, we still lack understanding of the co-ordinated signalling mechanisms that permit different DNA damaging agents to induce distinct cellular outcomes through RelA. Here, we use label-free quantitative phosphoproteomics to examine the temporal effects of exposure of U2OS cells to either etoposide (ETO) or hydroxyurea (HU) by monitoring the phosphorylation status of RelA and its protein binding partners. Although few stimulus-specific differences were identified in the constituents of phosphorylated RelA interactome after exposure to these DNA damaging agents, we observed subtle, but significant, changes in their phosphorylation states, as a function of both type and duration of treatment. The DNA double strand break (DSB)-inducing ETO invoked more rapid, sustained responses than HU, with regulated targets primarily involved in transcription, cell division and canonical DSB repair. Kinase substrate prediction of ETO-regulated phosphosites suggest abrogation of CDK1 and ERK1 signalling, in addition to the known induction of ATM/ATR. In contrast, HU-induced replicative stress mediated temporally dynamic regulation, with phosphorylated RelA binding partners having roles in rRNA/mRNA processing and translational initiation, many of which contained a 14-3-3{varepsilon} binding motif, and were putative substrates of the dual specificity kinase CLK1. Our data thus point to differential regulation of key cellular processes and the involvement of distinct signalling pathways in modulating DNA damage-specific functions of RelA.

biochemistry↗

DNA methylation signatures of aggression and closely related constructs: A meta-analysis of epigenome-wide studies across the lifespan

DNA methylation profiles of aggressive behavior may capture lifetime cumulative effects of genetic, stochastic, and environmental influences associated with aggression. Here, we report the first large meta-analysis of epigenome-wide association studies (EWAS) of aggressive behavior (N=15,324 participants). In peripheral blood samples of 14,434 participants from 18 cohorts with mean ages ranging from 7 to 68 years, 13 methylation sites were significantly associated with aggression (alpha=1.2x10-7; Bonferroni correction). In cord blood samples of 2,425 children from five cohorts with aggression assessed at mean ages ranging from 4 to 7 years, 83% of these sites showed the same direction of association with childhood aggression (r=0.74, p=0.006) but no epigenome-wide significant sites were found. Top-sites (48 at a false discovery rate of 5% in the peripherl blood meta-analysis or in a combined meta-analysis of peripheral blood and cord blood) have been associated with chemical exposures, smoking, cognition, metabolic traits, and genetic variation (mQTLs). Three genes whose expression levels were associated with top-sites were previously linked to schizophrenia and general risk tolerance. At six CpGs, DNA methylation variation in blood mirrors variation in the brain. On average 44% (range=3-82%) of the aggression-methylation association was explained by current and former smoking and BMI. These findings point at loci that are sensitive to chemical exposures with potential implications for neuronal functions. We hope these results to be a starting point for studies leading to applications as peripheral biomarkers and to reveal causal relationships with aggression and related traits.

genetics↗

Drosophila USP22/non-stop regulates the Hippo pathway to polarise the actin cytoskeleton during collective border cell migration

Polarisation of the actin cytoskeleton is vital for the collective migration of cells in vivo. During invasive border cell migration in Drosophila, actin polarisation is directly controlled by Hippo pathway components, which reside at contacts between border cells in the cluster. Here we identify, in a genetic screen for deubiquitinating enzymes involved in border cell migration, an essential role for non-stop/USP22 in the expression of Hippo pathway components expanded and merlin; loss of non-stop function consequently leads to a redistribution of F-actin and the polarity determinant Crumbs, loss of polarised actin protrusions and premature tumbling of the border cell cluster. Non-stop is a component of the Spt-Ada-Gcn5-acetyltransferase (SAGA) transcriptional coactivator complex, but SAGA’s histone acetyltransferase module, which does not bind to expanded or merlin, is dispensable for migration. Taken together, our results uncover novel roles for SAGA-independent non-stop/USP22 in Hippo-mediated collective cell migration, which may help guide studies in other systems where USP22 is necessary for cell motility and invasion.Competing Interest StatementThe authors have declared no competing interest.View Full Text

cell biology↗

A High Content Screen for Mucin-1-Reducing Compounds Identifies Fostamatinib as a Candidate for Rapid Repurposing for Acute Lung Injury during the COVID-19 pandemic

Drug repurposing is the only method capable of delivering treatments on the shortened time-scale required for patients afflicted with lung disease arising from SARS-CoV-2 infection. Mucin-1 (MUC1), a membrane-bound molecule expressed on the apical surfaces of most mucosal epithelial cells, is a biochemical marker whose elevated levels predict the development of acute lung injury (ALI) and respiratory distress syndrome (ARDS), and correlate with poor clinical outcomes. In response to the pandemic spread of SARS-CoV-2, we took advantage of a high content screen of 3,713 compounds at different stages of clinical development to identify FDA-approved compounds that reduce MUC1 protein abundance. Our screen identified Fostamatinib (R788), an inhibitor of spleen tyrosine kinase (SYK) approved for the treatment of chronic immune thrombocytopenia, as a repurposing candidate for the treatment of ALI. In vivo, Fostamatinib reduced MUC1 abundance in lung epithelial cells in a mouse model of ALI. In vitro, SYK inhibition by Fostamatinib promoted MUC1 removal from the cell surface. Our work reveals Fostamatinib as a repurposing drug candidate for ALI and provides the rationale for rapidly standing up clinical trials to test Fostamatinib efficacy in patients with COVID-19 lung injury.

cell biology↗

Population GNNs for Brain Age Prediction

Many common neurological and neurodegenerative disorders, such as Alzheimers disease, dementia and multiple sclerosis, have been associated with abnormal patterns of apparent ageing of the brain. Discrepancies between the estimated brain age and the actual chronological age (brain age gaps) can be used to understand the biological pathways behind the ageing process, assess an individuals risk for various brain disorders and identify new personalised treatment strategies. By flexibly integrating minimally preprocessed neuroimaging and non-imaging modalities into a population graph data structure, we train two types of graph neural network (GNN) architectures to predict brain age in a clinically relevant fashion as well as investigate their robustness to noisy inputs and graph sparsity. The multimodal population graph approach has the potential to learn from the entire cohort of healthy and affected subjects of both sexes at once, capturing a wide range of con-founding effects and detecting variations in brain age trends between different sub-populations of subjects.

neuroscience↗

Extensive transfer of genes for edible seaweed digestion from marine to human gut bacteria

Humans harbor numerous species of colonic bacteria that digest the fiber polysaccharides in commonly consumed terrestrial plants. More recently in history, regional populations have consumed edible macroalgae seaweeds containing unique polysaccharides. It remains unclear how extensively gut bacteria have adapted to digest these nutrients and use these abilities to colonize microbiomes around the world, especially outside Asia. Here, we show that the ability of gut bacteria to digest seaweed polysaccharides is more pervasive than previously appreciated. Using culture-based approaches, we show that known Bacteroides genes involved in seaweed degradation have mobilized into many members of this genus. We also identify several previously unknown examples of marine bacteria-derived genes, and their corresponding mobile DNA elements, that are involved in degrading seaweed polysaccharides. Some of these genes reside in gut-resident, Gram-positive Firmicutes, for which phylogenetic analysis suggests an origin in the Epulopiscium gut symbionts of marine fishes. Our results are important for understanding the metabolic plasticity of the human gut microbiome, the global exchange of genes in the context of dietary selective pressures and identifying new functions that can be introduced or engineered to design and fill orthogonal niches for a future generation of engineered probiotics.

microbiology↗

Use of the Polo-like kinase 4 (PLK4) inhibitor centrinone to investigate intracellular signaling networks using SILAC-based phosphoproteomics

Polo-like kinase 4 (PLK4) is the master regulator of centriole duplication in metazoan organisms. Catalytic activity and protein turnover of PLK4 are tightly coupled in human cells, since changes in PLK4 concentration and catalysis have profound effects on centriole duplication and supernumerary centrosomes, which are associated with aneuploidy and cancer. Recently, PLK4 has been targeted with a variety of small molecule kinase inhibitors exemplified by centrinone, which rapidly induces inhibitory effects on PLK4 and leads to on-target centrosome depletion. Despite this, relatively few PLK4 substrates have been identified unequivocally in human cells, and PLK4 signaling outside centriolar networks remains poorly characterised. We report an unbiased mass spectrometry (MS)-based quantitative analysis of cellular protein phosphorylation in stable PLK4-expressing U2OS human cells exposed to centrinone. PLK4 phosphorylation was itself sensitive to brief exposure to the compound, resulting in PLK4 stabilization. Analysing asynchronous cell populations, we report hundreds of centrinone-regulated cellular phosphoproteins, including centrosomal and cell cycle proteins and a variety of likely non-canonical substrates. Surprisingly, sequence interrogation of ~300 significantly down-regulated phosphoproteins reveals an extensive network of centrinone-sensitive [Ser/Thr]Pro phosphorylation sequence motifs, which based on our analysis might be either direct or indirect targets of PLK4. In addition, we confirm that NMYC and PTPN12 are PLK4 substrates, both in vitro and in human cells. Our findings suggest that PLK4 catalytic output directly controls the phosphorylation of a diverse set of cellular proteins, including Pro-directed targets that are likely to be important in PLK4-mediated cell signaling.

biochemistry↗

Epigenetic clocks predict prevalence and incidence of leading causes of death and disease burden

Individuals of the same chronological age display different rates of biological ageing. A number of measures of biological age have been proposed which harness age-related changes in DNA methylation profiles. These include methylation-based predictors of chronological age (HorvathAge, HannumAge), all-cause mortality (DNAm PhenoAge, DNAm GrimAge) and telomere length (DNAm Telomere Length). In this study, we test the association between these epigenetic markers of ageing and the prevalence and incidence of the leading causes of disease burden and mortality in high-income countries. Furthermore, we test the clocks relationships with phenotypic measures associated with these conditions, including spirometric and biochemical traits. We carry out these analyses in 9,537 individuals from the Generation Scotland: Scottish Family Health Study. We find that DNAm GrimAge outperforms other epigenetic clocks in its associations with self-report disease prevalence and related clinical traits. DNAm GrimAge associates with chronic obstructive pulmonary disease (COPD) prevalence (Odds Ratio = 3.29, P = 3.0 x 10-4) and pulmonary spirometry tests ({beta} = [-0.10 to -0.15], P = [1.4 x 10-4 to 1.4 x 10-6]) at study baseline after adjusting for possibly confounding risk factors including alcohol, body mass index, deprivation, education and smoking. After adjusting for these confounding risk factors, DNAm GrimAge, DNAm PhenoAge and DNAm Telomere Length, measured at study baseline, predict incidence of ICD-10-coded disease states including COPD, type 2 diabetes and cardiovascular disease after thirteen years of follow-up (Hazard Ratios = [0.80 (telomere length) to 2.19 (GrimAge)], P = [9.9 x 10-4, 1.9 x 10-14]). Our data show that despite accounting for several possible confounding variables, epigenetic markers of ageing predict incidence of common disease. This may have significant implications for their potential utility in clinical settings to complement gold-standard methods of clinical assessment and management.

genomics↗

A genome-wide association study finds genetic variants associated with neck or shoulder pain in UK Biobank

BackgroundCommon types of musculoskeletal conditions include pain in the neck and shoulder areas. This study seeks to identify the genetic variants associated with neck or shoulder pain based on a genome-wide association approach using 203,309 subjects from the UK Biobank cohort and look for replication evidence from the Generation Scotland: Scottish Family Health Study (GS:SFHS) and TwinsUK. MethodsCases in the UK Biobank were determined by a question which asked the participants if they had experienced pain in the neck or shoulder in the previous month influencing daily activities. Controls were the UK Biobank participants who reported no pain anywhere in the last month. A genome-wide association study was performed adjusting for age, sex, BMI and 9 population principal components. Significant and independent genetic variants were then sent to GS:SFHS and TwinsUK for replication. ResultsWe identified 3 genetic loci that were associated with neck or shoulder pain in the UK Biobank samples. The most significant locus was in an intergenic region in chromosome 17, rs12453010, having P = 1.66 x 10-11. The second most significant locus was located in the FOXP2 gene in chromosome 7 with P = 2.38 x 10-10 for rs34291892. The third locus was located in the LINC01572 gene in chromosome 16 with P = 4.50 x 10-8 for rs62053992. In the replication stage, among 4 significant and independent genetic variants, rs2049604 in the FOXP2 gene and rs62053992 in the LINC01572 gene were weakly replicated in GS:SFHS (P = 0.0240 and P = 0.0202, respectively). None of the single nucleotide polymorphisms (SNPs) were replicated in the TwinsUK cohort (P > 0.05). ConclusionsWe have identified 3 loci associated with neck or shoulder pain in the UK Biobank cohort, two of which were weakly supported in a replication cohort. Further evidence is needed to confirm their roles in neck or shoulder pain. SignificanceThis is the first genome-wide association study on neck or shoulder pain. We have identified 3 genetic loci (an intergenic region in chromosome 17, the FOXP2 gene in chromosome 7, and the LINC01572 gene in chromosome 16) that are associated with neck or shoulder pain using the UK Biobank cohort, among which the FOXP2 gene and the LINC01572 gene were weakly replicated by the Generation Scotland: Scottish Family Health Study (P < 0.05). The SNP heritability was 0.11, indicating neck or shoulder pain is a heritable trait. The tissue expression analysis suggested that neck or shoulder pain was related to multiple brain tissues, indicating the involvement of neuron function. The results will inform further research in the characterisation of the mechanisms of neck or shoulder pain.

genetics↗

Subthreshold psychosis symptoms associated with molecular genetic risk in a population-based cohort: Findings from Generation Scotland

ImportanceSubthreshold psychosis symptoms in the general population may be associated with genetic risk for schizophrenia. In this analysis, empirically-derived symptom factor scores led to a detection of significant and robust polygenic signal.\n\nObjectiveThis study sought to optimize genetic association with data-driven symptom factor scores, accounting for cohort factor structure and sex differences.\n\nDesignEFA-derived symptom factor scores were regressed onto PRS for schizophrenia in models accounting for age and genetic ancestry principal components. Follow-up examination of symptom factor score associations with other related genetic risks included ADHD, autism, bipolar disorder, major depression, and neuroticism.\n\nParticipantsThis study examined the newly expanded symptom dataset from the Northern European ancestry cohort, Generation Scotland: Scottish Family Health Study (N = 9,105 individuals 18-65 years of age) comprising common variant and subthreshold psychosis symptom data. A total of 5,391 females and 3,713 males with age M[SD] = 45.2 [13] were included in the final analyses.\n\nMain Outcome and MeasureSubthreshold psychosis symptoms were measured using the Schizotypal Personality Questionnaire-Brief (SPQ-B). Primary phenotypic factor scores and genome-wide polygenic risk scores (PRS) reflected weighted sum scores and were examined as continuous measures. Polygenic risk scores were calculated from genome-wide association summary statistics using 7,358,674 imputed common genetic variants passing quality control.\n\nResultsIn males, symptom factor scores were positively associated with polygenic risk for schizophrenia alone and implicated primarily interpersonal/negative symptoms. In females, symptom factor scores were positively associated with polygenic risks for ADHD and autism but not schizophrenia. Scores were robustly associated with genetic risk for neuroticism across both males and females.\n\nConclusions and RelevanceThis study detected a significant association of subthreshold psychosis symptoms with genetic risk for schizophrenia and neuroticism in a population-based sample. Furthermore, important sex differences suggest a need for better understanding of schizophrenia risk assessment in females.\n\nKey PointsO_ST_ABSQuestionC_ST_ABSWhat molecular genetic risks are associated with subthreshold psychosis symptoms in the general population?\n\nFindingsIn a large population-based cohort (N = 9,084), significant associations of polygenic risks with symptoms were observed. Symptoms were associated with genetic risk for schizophrenia in males, for ADHD and autism spectrum disorder in females, and for neuroticism across both males and females.\n\nMeaningAssociations of genetic risk with symptoms in the general population are highly significant and suggest important sex differences.

genetics↗

Assessment of DNA methylation differences between carriers of APOE ε4 and APOE ε2

BACKGROUNDThe Apolipoprotein E (APOE) {varepsilon}4 allele is the strongest genetic risk factor for late onset Alzheimers disease, while the {varepsilon}2 allele confers protection. Previous studies report differential DNA methylation of APOE between {varepsilon}4 and {varepsilon}2 carriers, but associations with epigenome-wide methylation have not previously been characterised. METHODSUsing the EPIC array, we investigated epigenome-wide differences in whole blood DNA methylation patterns between Alzheimers disease-free APOE {varepsilon}4 (n=2469) and {varepsilon}2 (n=1118) carriers from the two largest single-cohort DNA methylation samples profiled to date. Using a discovery, replication and meta-analysis study design, methylation differences were identified using epigenome-wide association analysis and differentially methylated region (DMR) approaches. Results were explored using pathway and methylation quantitative trait loci (meQTL) analyses. RESULTSWe obtained replicated evidence for DNA methylation differences in a ~169kb region, which encompasses part of APOE and several upstream genes. Meta-analytic approaches identified DNA methylation differences outside of APOE: differentially methylated positions were identified in DHCR24, LDLR and ABCG1 (2.59 x 10-100[&le;]P[&le;]2.44 x 10-8) and DMRs were identified in SREBF2 and LDLR (1.63 x 10-4[&le;]P[&le;]3.01 x 10-2). Pathway and meQTL analyses implicated lipid-related processes and high density lipoprotein cholesterol was identified as a partial mediator of the methylation differences in ABCG1 and DHCR24. CONCLUSIONSAPOE {varepsilon}4 vs. {varepsilon}2 carrier status is associated with epigenome-wide methylation differences in the blood. The loci identified are located in trans as well as cis to APOE and implicate genes involved in lipid homeostasis.

genetics↗

DNA methylation in the APOE gene: its link with Alzheimer’s and cardiovascular health

Genetic variation in the apolipoprotein E (APOE) gene is associated with Alzheimers disease (AD) and risk factors for cardiovascular disease (CVD). DNA methylation at APOE has been linked to altered cognition and AD. It is unclear if epigenetic marks could be used for predicting future disease. We assessed blood-based DNA methylation at 13 CpGs in the APOE gene in 5828 participants from the Generation Scotland (GS) cohort. Using linear regression, we examined the relationship between APOE methylation, cognition, cholesterol, and the risks for AD and CVD. DNA methylation at two CpGs was associated with the ratio of total-to-HDL cholesterol, but not with cognition, or the risks of AD or CVD. APOE methylation could be involved in the levels of blood cholesterol, but there is no evidence for the utility of APOE methylation as a biomarker for predicting AD or CVD.

neuroscience↗

Characterisation of an inflammation-related epigenetic score and its association with cognitive ability

Results from large cohort studies investigating the association between inflammation and cognition have been mixed, possibly due to methodological disparities. However, a key issue in research utilising inflammatory biomarkers is their typically phasic responses. C-reactive protein (CRP) is widely used to investigate the association between chronic inflammation and cognition, but its plasma concentrations can markedly deviate in response to acute infection. Recently a large-scale epigenome-wide association study identified DNA methylation correlates of CRP. DNA methylation is thought to be relatively stable in the short term, marking it as a potentially useful signature of exposure. Here, we generate an epigenetic CRP score and investigate its trajectories with age, and associations with cognitive ability, in comparison to serum CRP in two cohorts: a longitudinal study of older adults (the Lothian Birth Cohort 1936, n=889) and a large, cross-sectional cohort (Generation Scotland, n=7,028).\n\nWe identified differing trajectories of serum CRP across the cohorts, with no homogeneous trends seen with age. Conversely, the epigenetic score was consistently found to increase with age, and to do so more rapidly in males compared to females. Higher levels of serum CRP were found to associate with poorer cognition in Lothian Birth Cohort 1936, but not in Generation Scotland. However, a consistent negative association was identified between cognition and the epigenetic score in both cohorts. Furthermore, the epigenetic score accounted for a greater proportion of variance in cognitive ability.\n\nOur results suggest that epigenetic signatures of acute inflammatory markers may provide an enhanced signature of chronic inflammation, allowing for more reliable stratification of individuals, and thus clearer inference of associations with incident health outcomes.

genomics↗

LeafByte: A mobile application that measures leaf area and herbivory quickly and accurately

O_LIIn both basic and applied studies, quantification of herbivory on foliage is a key metric in characterizing plant-herbivore interactions, which underpin many ecological, evolutionary, and agricultural processes. Current methods of quantifying herbivory are slow or inaccurate. We present LeafByte, a free iOS application for measuring leaf area and herbivory. LeafByte can save data automatically, read and record barcodes, handle both light and dark colored plant tissue, and be used non-destructively.\nC_LIO_LIWe evaluate its accuracy and efficiency relative to existing herbivory assessment tools.\nC_LIO_LILeafByte has the same accuracy as ImageJ, the field standard, but is 50% faster. Other tools, such as BioLeaf and grid quantification, are quick and accurate, but limited in the information they can provide. Visual estimation is quickest, but it only provides a coarse measure of leaf damage and tends to overestimate herbivory.\nC_LIO_LILeafByte is a quick and accurate means of measuring leaf area and herbivory, making it a useful tool for research in fields such as ecology, entomology, agronomy, and plant science.\nC_LI

ecology↗