Biology subjects

Drake, J.

Publications and source records attributed to Drake, J..

11 recordsLinked to original sources

bioRxiv2026

Novel insights into conserved biomineralization mechanisms revealed from a cold-water scleractinian coral skeletal proteome

Stony corals exhibit striking morphological plasticity across diverse environments and trophic strategies, raising fundamental questions about the conservation of their biomineralization machinery. Here, we characterize the skeletal organic matrix proteome of the cold-water, asymbiotic coral Desmophyllum pertusum and compare it with skeletal proteomes from a facultatively photosymbiotic temperate coral and an obligately photosymbiotic subtropical coral. Despite pronounced differences in habitat, symbiotic status, and skeletal micro-density, we observe convergence on a conserved "biomineralization toolkit". Comparative proteomics, genomics, and structural predictions reveal that this toolkit integrates diverse acidic matrix proteins, carbonic anhydrases, adhesion and structural proteins, and signaling components with multiple cellular export pathways. Together, these findings redefine coral biomineralization as a dynamic, coordinated network of cellular pathways rather than a static assemblage of matrix components. The symbiont-free model D. pertusum provides a mechanistic framework for dissecting coral calcification across environments and for assessing the resilience of this conserved machinery.

biochemistry↗

bioRxiv2025

Attributing the temperature response of tree seedling growth to underlying mechanisms

Studies of plant responses to temperature often focus on rates photosynthesis and respiration. However, within-plant utilisation and allocation of carbon are also strongly affected. It is unclear how much each of these processes contribute to determining the overall temperature response of growth. We applied a data assimilation framework to a glasshouse experiment with detailed physiological and growth measurements to investigate the relative contribution of different physiological processes to the overall temperature response of tree seedling growth. We found that both short-term effects of temperature and acclimatory responses of photosynthesis and respiration had a significant impact on the temperature response of growth. However, the effect of temperature on biomass allocation patterns to different tissues, non-structural carbohydrate utilisation and C losses to other unmeasured losses were also substantial in determining the temperature response of growth, particularly at sub-optimal temperatures. Our work demonstrates that the growth response to warming cannot be predicted using only the direct effect of temperature on photosynthesis and respiration and emphasizes the importance of temperature acclimation of photosynthesis, respiration and other C balance processes. Our results provide new guidance for process-based models to correctly describe the temperature effects on tree growth.

plant biology↗

bioRxiv2023

Saracatinib synergizes with enzalutamide to downregulate androgen receptor activity in castration resistant prostate cancer

Prostate cancer (PCa) remains the most diagnosed non-skin cancer amongst the American male population. Treatment for localized prostate cancer consists of androgen deprivation therapies (ADTs), which typically inhibit androgen production and the androgen receptor (AR). Though initially effective, a subset of patients will develop resistance to ADTs and the tumors will transition to castration-resistant prostate cancer (CRPC). Second generation hormonal therapies such as abiraterone acetate and enzalutamide are typically given to men with CRPC. However, these treatments are not curative and typically prolong survival only by a few months. Several resistance mechanisms contribute to this lack of efficacy such as the emergence of AR mutations, AR amplification, lineage plasticity, AR splice variants (AR-Vs) and increased kinase signaling. Having identified SRC kinase as a key tyrosine kinase enriched in CRPC patient tumors from our previous work, we evaluated whether inhibition of SRC kinase synergizes with enzalutamide or chemotherapy in several prostate cancer cell lines expressing variable AR isoforms. We observed robust synergy between the SRC kinase inhibitor, saracatinib, and enzalutamide, in the AR-FL+/AR-V+ CRPC cell lines, LNCaP95 and 22Rv1. We also observed that saracatinib significantly decreases AR Y534 phosphorylation, a key SRC kinase substrate residue, on AR-FL and AR-Vs, along with the AR regulome, supporting key mechanisms of synergy with enzalutamide. Lastly, we also found that the saracatinib-enzalutamide combination reduced DNA replication compared to the saracatinib-docetaxel combination, resulting in marked increased apoptosis. By elucidating this combination strategy, we provide pre-clinical data that suggests combining SRC kinase inhibitors with enzalutamide in select patients that express both AR-FL and AR-Vs.

cancer biology↗

bioRxiv2022

Modelling human endurance: Power laws vs critical power

The power-duration relationship describes the time to exhaustion for exercise at different intensities. It is generally believed to be a "fundamental bioenergetic property of living systems" that this relationship is hyperbolic. Indeed, the hyperbolic (a.k.a. critical-power) model which formalises this belief is the dominant tool for describing and predicting high-intensity exercise performance, e.g. in cycling, running, rowing, or swimming. However, the hyperbolic model is now the focus of two heated debates in the literature because: (a) it unrealistically represents efforts that are short (< 2 minutes) or long (> 15 minutes); (b) it contradicts widely-used performance predictors such as the so-called functional threshold power (FTP) in cycling. We contribute to both debates by demonstrating that the power-duration relationship is more adequately represented by an alternative, power-law model. In particular, we show that the often observed good fit of the hyperbolic model between 2 and 15 minutes should not be taken as proof that the power-duration relationship is hyperbolic. Rather, in this range, a hyperbolic function just happens to approximate a power law fairly well. We also prove mathematical results which suggest that the power-law model is a safer tool for pace selection than the hyperbolic model and that the former better models fatigue than the latter. Finally, we use the power-law model to shed light on popular performance predictors in cycling, running and rowing such as FTP and Jack Daniels "VDOT" calculator.

physiology↗

bioRxiv2022

S100a9 Attenuates Inflammation during Repeated Social Defeat Stress

Post-traumatic stress disorder (PTSD), a consequence of psychological trauma, is associated with increased inflammation and an elevated risk of developing comorbid inflammatory diseases. However, the mechanistic link between this mental health disorder and inflammation remains elusive. Using a pre-clinical model of PTSD known as repeated social defeat stress (RSDS), we previously identified that S100a8 and S100a9 mRNA, genes that encode the protein calprotectin, were significantly upregulated in T-lymphocytes after psychological trauma. Calprotectin expression positively correlated with inflammatory gene expression and the mitochondrial redox environment in T-lymphocytes, therefore, we hypothesized that genetic deletion of calprotectin would attenuate the inflammatory and redox phenotype displayed after RSDS. Using pharmacological and genetic manipulation of S100a9 (which functionally eliminates calprotectin) in mice, we unexpectedly observed worsening of behavioral pathology, inflammation, and the mitochondrial redox environment in mice after RSDS compared to wild-type (WT) animals. Furthermore, loss of calprotectin significantly enhanced the metabolic demand on T-lymphocytes suggesting this protein may play an undescribed role in mitochondrial regulation. This was further supported by single-cell RNA sequencing analysis demonstrating that RSDS and loss of S100a9 primarily altered genes associated with mitochondrial function and oxidative phosphorylation. Taken together, these data demonstrate the loss of calprotectin potentiates the RSDS-induced phenotype, which suggests its observed upregulation after psychological trauma may provide previously unexplored protective functions.

immunology↗

bioRxiv2021

Improving long-read consensus sequencing accuracy with deep learning

The PacBio HiFi sequencing technology combines less accurate, multi-read passes from the same molecule (subreads) to yield consensus sequencing reads that are both long (averaging 10-25 kb) and highly accurate. However, these reads can retain residual sequencing error, predominantly insertions or deletions at homopolymeric regions. Here, we train deep learning models to polish HiFi reads by recognizing and correcting sequencing errors. We show that our models are effective at reducing these errors by 25-40% in HiFi reads from human as well as E. coli genomes.

genomics↗

bioRxiv2021

Physiological and transcriptomic variability indicative of differences in key functions within a single coral colony

Polyps in different locations on individual stony coral colonies experience variation in numerous environmental conditions including flow and light, potentially leading to transcriptional and physiological differences across the colony. Here, we describe high-resolution physiological measurements and differential gene expression from multiple locations within a single colony of Stylophora pistillata, aiming to relate these to environmental gradients across the coral colony. We observed broad transcriptional responses in both the host and photosymbiont in response to height above the substrate, cardinal direction, and, most strongly, location along the branch axis. Specifically, several key physiological processes in the host appear more active toward branch tips including several metabolic pathways, toxin production for prey capture or defense, and biomolecular mechanisms of biomineralization. Further, the increase in gene expression related to these processes toward branch tips is conserved between S. pistillata and Acropora spp. The photosymbiont appears to respond transcriptionally to relative light intensity along the branch and due to cardinal direction. These differential responses were observed across the colony despite its genetic homogeneity and likely inter-polyp communication. While not a classical division of labor, each part of the colony appears to have distinct functional roles related to polyps differential exposure to environmental conditions.

genomics↗

bioRxiv2020

Network Preservation Reveals Shared and Unique Biological Processes Associated with Chronic Alcohol Abuse in NAc and PFC.

BackgroundExcessive alcohol consumption has become a growing public health concern worldwide due to the potential development of alcohol dependence (AD). Prolonged alcohol abuse leads to dysregulation of the mesocorticolimbic pathway (MCL), effectively disrupting executive functioning and the allostatic conditioning of reward response. MethodsWe utilized weighted gene co-expressed network analysis (WGCNA) and network preservation using a case/control study design (n=35) to identify unique and shared biological processes dysregulated in AD in the prefrontal cortex (PFC) and nucleus accumbens (NAc). We used correlation and regression analyses to identify mRNA/miRNA interactions and local expression quantitative trait loci (cis-eQTL) to identify genetic regulatory mechanisms for networks significantly associated with AD. ResultsNetwork analyses revealed 6 and 3 significant mRNA modules from the NAc and PFC, respectively. Network preservation revealed immune response upregulation in both regions, whereas cellular morphogenesis/localization and cilia-based cell projection processes were upregulated only in the NAc. We observed 4 significantly correlated module eigengenes (ME) between the significant mRNA and miRNA modules in PFC, and 6 significant miRNA/mRNA ME correlations in NAc, with the mir-449a/b cluster emerging as a potential regulator for cellular morphogenesis/localization dysregulation in this brain region. Finally, we identified cis-eQTLs (37 mRNA and 9 miRNA in NAc, and 17 mRNA and 16 miRNA in PFC) which potentially mediate alcohols effect in a brain region-specific manner. ConclusionIn agreement with previous reports, we observed a generalized upregulation of immune response processes in subjects with AD, that highlights alcohols neurotoxic properties, while simultaneously demonstrating distinct molecular changes in subcortical brain regions as a result of chronic alcohol abuse. Such changes further support previous neuroimaging and physiological studies that emphasize the distinct roles PFC and NAc play in the development of addictive behaviors.

genomics↗

bioRxiv2019

Fishing for mammals: landscape-level monitoring of terrestrial and semi-aquatic communities using eDNA from lotic ecosystems

O_LIEnvironmental DNA (eDNA) metabarcoding has revolutionised biomonitoring in both marine and freshwater ecosystems. However, for semi-aquatic and terrestrial animals, the application of this technique remains relatively untested.\nC_LIO_LIWe first assess the efficiency of eDNA metabarcoding in detecting semi-aquatic and terrestrial mammals in natural lotic ecosystems in the UK by comparing sequence data recovered from water and sediment samples to the mammalian communities expected from historical data. Secondly, we evaluate the detection efficiency of eDNA samples compared to multiple conventional non-invasive survey methods (latrine surveys and camera trapping) using occupancy modelling.\nC_LIO_LIeDNA metabarcoding detected a large proportion of the expected mammalian community within each area. Common species in the areas were detected at the majority of sites. Several key species of conservation concern in the UK were detected by eDNA in areas where authenticated records do not currently exist, but potential false positives were also identified for several non-native species.\nC_LIO_LIWater-based eDNA samples provided comparable results to conventional survey methods in per unit of survey effort for three species (water vole, field vole, and red deer) using occupancy models. The comparison between survey effort to reach a detection probability of [≥]0.95 revealed that 3-6 water replicates would be equivalent to 3-5 latrine surveys and 5-30 weeks of single camera deployment, depending on the species.\nC_LIO_LISynthesis and Applications. eDNA metabarcoding represents an extremely promising tool for monitoring mammals, allowing for the detection of multiple species simultaneously, and provides comparable results to widely-used conventional survey methods. eDNA from freshwater systems delivers a terrestrial dividend by detecting both semi-aquatic and terrestrial mammalian communities, and provides a basis for future monitoring at a landscape level over larger spatial and temporal scales (i.e. long-term monitoring at national levels).\nC_LI

ecology↗

bioRxiv2019

Assessing the role of long-noncoding RNA in nucleus accumbens in subjects with alcohol dependence

Recently, long noncoding RNA (lncRNA) were implicated in the etiology of alcohol dependence (AD). As lncRNA provide another layer of complexity to the transcriptome, assessing their expression in the brain is the first critical step towards understanding lncRNA functions in AD. To that end, we profiled the expression of lncRNA and protein coding genes (PCG) in nucleus accumbens (NAc) from 41 subjects with AD and 41 controls. At false discovery rate (FDR) of 5%, we identified 69 and 309 differentially expressed lncRNA and PCG genes, respectively. Using co-expression network analyses, we identified three lncRNA and five PCG modules significantly correlated with AD at Bonferroni adj. p[≤]0.05. To better understand lncRNA functions, we integrated the lncRNA and PCG hubs from the significant AD modules; at FDR of 5%, we identified 3 151 positive and 2 255 negative correlations supporting the functional role of lncRNA in the development of AD. Gene enrichment analysis revealed that PCG significantly correlated with lncRNA are, among others, enriched for neuronal and immune related processes. To highlight the mechanisms, by which genetic variants contribute to AD, we integrated lncRNA and PCG hubs with genome-wide SNP data. At FDR[≤]0.3, we identified 276 expression quantitative trait loci (eQTL), affecting the expression of 20 and 256 lncRNA and PCG hubs, respectively. Our study is the first to profile lncRNA expression in nucleus accumbens in a large postmortem alcohol brain sample and our results may provide novel insights into the regulation of the brain transcriptome across disease.

neuroscience↗

bioRxiv2017

Estimating environmental suitability

Author statementJD proposed the model, JD and RR wrote the code and performed the analysis, JD wrote the first draft of the manuscript, and all authors contributed substantially to revisions.\n\nAbstractMethods for modeling species, distributions in nature are typically evaluated empirically with respect to data from observations of species occurrence and, occasionally, absence at surveyed locations. Such models are relatively \"theory-free\". In contrast, theories for explaining species, distributions draw on concepts like fitness, niche, and environmental suitability. This paper proposes that environmental suitability be defined as the conditional probability of occurrence of a species given the state of the environment at a location. Any quantity that is proportional to this probability is a measure of relative suitability and the support of this probability is the niche. This formulation suggests new methods for presence-background modeling of species distributions that unify statistical methodology with the conceptual framework of niche theory. One method, the plug-and-play approach, is introduced for the first time. Variations on the plug-and-play approach were studied with respect to their numerical performance on 106 species from an exhaustively sampled presence/absence survey of vegetation in the Canton of Vaud, Switzerland. Additionally, we looked at the robustness of these methods to the presence of irrelevant information and sample size. Although irrelevant variables eroded the predictive performance of all methods, these methods were found to be both numerically and statistically robust.

ecology↗