Biology subjects

Robinson, N.

Publications and source records attributed to Robinson, N..

16 recordsLinked to original sources

bioRxiv2026

Patterns of association between mothers and offspring and their outcomes in a polygynous ungulate

Prolonged association between mothers and their offspring is common in ungulates, with the level of maternal investment likely to play a central role in shaping this trait. Here we examined patterns of association between mothers and offspring over time, the apparent benefits of association to offspring, and costs to mothers. We analyzed 40 years worth of census data from an individually-monitored, food-limited population of red deer (Cervus elaphus) on the Isle of Rum, Scotland. Starting from birth, female calves associated more frequently with their mothers than male calves in their first year. Calves also associated less with their mothers if the mother did not conceive a new calf. Association frequency decreased with mothers age and population density, and survival over the first year was not related to mother-calf association. Yearlings, now in their second year, were more often associated with their mothers if they were female, if there was no subsequent calf (or the subsequent calf died as a neonate), and if they were still being suckled. Increased association between mothers and yearlings was associated with increased survival to adulthood at 28 months, but suckling a yearling did not improve its probability of survival. For individuals that reached maturity, increased association in the yearling year was associated with slightly shorter adult life spans. The level of association between a calf and mother was not associated with the mothers immediate survival or fecundity. Our findings suggest that juveniles born to poor-condition mothers benefit from prolonged association through improved yearling survival.

animal behavior and cognition↗

bioRxiv2025

A modular method for rapidly prototyping targeted gas vesicle protein nanoparticles

Gas vesicles (GVs) are air-filled protein nanoparticles which are proving to be useful in a number of biomedical applications. We hypothesized that it could be possible to develop a modular method for creating rapidly prototyped GVs by modifying their surface chemistry to include targeting peptides in an orientation-specific manner. Here, we describe a modular method to create targeted GVs using His-tagged antibody fragments, ensuring that the antibody fragments are connected to the GV in an orientation-specific manner. This is achieved via the functionalization of the GVs with nickel-nitrilotriacetic acid (Ni-NTA) group. First, we validated that these functionalized GVs can bind His-tagged green fluorescent protein and characterized the particle size and surface charge of functionalized GVs. Then, GVs targeted to prostate-specific membrane antigen (PSMA) using a minibody were validated using a knockout validation in vitro.

bioengineering↗

bioRxiv2024

The diffusion of cooperative and solo bubble net feeding in Canadian Pacific humpback whales

Cooperative foraging, a mutualistic resource acquisition behaviour observed across diverse taxa, can drive social network structure, as it typically involves high rates of interactions between individuals. Understanding the mechanisms and distribution of such behaviours is important to elucidate the drivers of social organisation. Bubble net feeding ( bubble netting) is a specialised foraging technique practised by certain humpback whale (Megaptera novaeangliae) populations globally. Over 20 years of study in the northern Canadian Pacific, we observed the diffusion of two morphs of this behaviour: social cooperative and independent, or solo, bubble netting. Network-based diffusion analyses - a tool developed to test for social learning - find strong evidence for the social learning of bubble netting when a static social network is used, even after accounting for individual-level traits such as site fidelity and sex (10.6 x103 to 35.4x103 times more support for social versus asocial learning; p < 0.0001). However, we could not completely exclude homophily due to the inherent sociality of this cooperative foraging behaviour. Nonetheless, it is clear that the rapid diffusion of bubble netting throughout this population has significant consequences for its social structure, which should be information considered by those planning the conservation of this threatened population.

animal behavior and cognition↗

bioRxiv2024

Estimating the seroprevalence of tuberculosis (Mycobacterium bovis) infection in a wild deer population in southwest England

Bovine tuberculosis (bTB) is a major disease of cattle that is subject to an eradication strategy in England. To inform control policies and manage the epidemic, all potential sources of infection for cattle must be identified and understood. The causative agent of bTB, Mycobacterium bovis, has a wide host range including several deer species. While transmission between cattle and deer has been implicated in some localised endemic regions, the role of deer in the epidemiology of bTB in England is poorly understood. This paper presents the results of a serological survey to estimate the prevalence of M. bovis in a large wild deer population in the High bTB Risk Area of southwest England. Blood samples were collected post-mortem over a 12-month period from wild deer during annual deer management controls in the Exmoor area and tested for M. bovis serum antibodies. Overall, 432 samples were collected and 69 (16.0%) were seropositive. The true seroprevalence in our sample was estimated to be 29.2% (95% CrI 21.1-38.6%), using Bayesian Latent Class Analysis to account for imperfect diagnostic test accuracy. Prevalence did not appear to differ between sexes nor between species, although the sample was predominantly red deer. The lowest prevalence was observed in animals aged under 1-year. Whilst these results provide valuable insights into M. bovis seroprevalence in this wild deer population, they should be interpreted alongside other relevant information such as ecology, species-specific epidemiology and disease pathology, deer density and cattle management to inform potential transmission risks between cattle and wild deer.

zoology↗

bioRxiv2024

Characterisation of mesenchymal stromal cells in the skin of Atlantic salmon

BackgroundThe skin serves as the first line of defence for an organism against the external environment. Despite the global significance of salmon in aquaculture, a critical component of this first line of defence, mesenchymal stromal cells, remains unexplored. These pluripotent cells can differentiate into various tissues, including bone, cartilage, tendon, ligament, adipocytes, dermis, muscle and connective tissue within the skin. These cells are pivotal for preserving the integrity of skin tissue throughout an organisms lifespan and actively participate in wound healing processes. ResultsIn this study, we characterise mesenchymal stromal cells in detail for the first time in healthy Atlantic salmon tissue and during the wound healing process. Single-nucleus sequencing and spatial transcriptomics revealed the transcriptional dynamics of these cells, elucidating the differentiation pathways leading to osteogenic and fibroblast lineages in the skin of Atlantic salmon. We charted their activity during an in vivo wound healing time course, showing clear evidence of their active role during this process, as they become transcriptionally more active during the remodelling stage of wound healing. ConclusionsFor the first time, we chart the activity of sub-clusters of differentiating stromal cells during the process of wound healing, revealing different spatial niches of the various MSC subclusters, and setting the stage for investigations into the manipulation of MSCs to improve fish health.

genomics↗

bioRxiv2023

Keratinocytes Drive the Epithelial Hyperplasia Key to Sea Lice Resistance in Coho Salmon

BackgroundSalmonid species have followed markedly divergent evolutionary trajectories in their interactions with sea lice. While sea lice parasitism poses significant economic, environmental, and animal welfare challenges for Atlantic salmon (Salmo salar) aquaculture, coho salmon (Oncorhynchus kisutch) exhibit near-complete resistance to sea lice, achieved through a potent epithelial hyperplasia response leading to rapid louse detachment. The molecular mechanisms underlying these divergent responses to sea lice are unknown. ResultsWe characterised the cellular and molecular responses of Atlantic salmon and coho salmon to sea lice using single-nuclei RNA sequencing. Juvenile fish were exposed to copepodid sea lice (Lepeophtheirus salmonis), and lice-attached pelvic fin and skin samples were collected 12h, 24h, 36h, 48h, and 60h after exposure, along with control samples. Comparative analysis of control and treatment samples revealed an immune and wound-healing response that was common to both species, but attenuated in Atlantic salmon, potentially reflecting greater sea louse immunomodulation. Our results revealed unique but complementary roles of three layers of keratinocytes in the epithelial hyperplasia response leading to rapid sea lice rejection in coho salmon. Our results suggest that basal keratinocytes direct the expansion and mobility of intermediate and, especially, superficial keratinocytes, which eventually encapsulate the parasite. ConclusionOur results highlight the key role of keratinocytes to coho salmons sea lice resistance, and the diverged biological response of the two salmonid host species when interacting with this parasite. This study has identified key pathways and candidate genes that could be manipulated using various biotechnological solutions to improve Atlantic salmon sea lice resistance.

genomics↗

bioRxiv2023

Mitochondrial translocation of TFEB regulates complex I and inflammation

TFEB is a master regulator of autophagy, lysosome biogenesis and mitochondrial metabolism that works, and immunity, primarily through transcription controlled by cytosol-to-nuclear translocation. Emerging data indicate additional regulatory interactions at the surface of organelles such as lysosomes. Here we show that TFEB has a non-transcriptional role in mitochondria, regulating the electron transport chain complex I to down-modulate inflammation. Proteomic analysis revealed extensive TFEB co-precipitation with several mitochondrial proteins, whose interactions are disrupted upon infection with S. Typhimurium. Localization of TFEB in the mitochondrial matrix was confirmed by high resolution confocal microscopy and biochemistry with translocation dependent on a conserved N-terminal TOMM20-binding motif enhanced by mTOR inhibition. Within the mitochondria, TFEB and protease LONP1 antagonistically co-regulate complex I, reactive oxygen species and the inflammatory response. Consequently, during infection, lack of TFEB specifically in the mitochondria exacerbates the expression of pro-inflammatory cytokines, contributing to innate immune pathogenesis.

cell biology↗

bioRxiv2021

Characterisation of the Ubiquitin-ESCRT pathway in Asgard archaea sheds new light on origins of membrane trafficking in eukaryotes

The ESCRT machinery performs a critical role in membrane remodelling events in all eukaryotic cells, including in membrane trafficking, membrane repair, cytokinetic abscission, in viral egress, and in the generation of extracellular vesicles. While the machinery is complex in modern day eukaryotes, where it comprises dozens of proteins, the system has simpler and more ancient origins. Indeed, homologues of ESCRT-III and the Vps4 ATPase, the proteins that execute the final membrane scission reaction, play analogous roles in cytokinesis and potentially in extracellular vesicle formation in TACK archaea where ESCRT-I and II homologues seem to be absent. Here, we explore the phylogeny, structure, and biochemistry of homologues of the ESCRT machinery and the associated ubiquitylation system found in genome assemblies of the recently discovered Asgard archaea. In these closest living prokaryotic relatives of eukaryotes, we provide evidence for the ESCRT-I and II sub-complexes being involved in the ubiquitin-directed recruitment of ESCRT-III,_as it is in eukaryotes. This analysis suggests a pre-eukaryotic origin for the Ub-coupled ESCRT system and a likely path of ESCRT evolution via a series of gene duplication and diversification events.

cell biology↗

bioRxiv2021

Cancer cells adapt FAM134B-BiP complex mediated ER-phagy to survive hypoxic stress

In a tumor microenvironment cancer cells experience hypoxia resulting in the accumulation of misfolded/unfolded proteins in the endoplasmic reticulum (ER) which elicit unfolded protein response (UPR) as an adaptive mechanism. UPR activates autophagy enabling the degradation of misfolded/unfolded proteins. More recently, ER-specific autophagy has been implicated in the removal of damaged ER and restoration of ER-homeostasis. Our investigations reveal that during hypoxia induced ER-stress, the ER-phagy receptor FAM134B targets damaged portions of ER into autophagosomes to restore ER-homeostasis in cancer cells. Loss of FAM134B in breast cancer cells results in increased ER-stress and reduced cell proliferation. Mechanistically, upon sensing hypoxia activated proteotoxic stress, the ER chaperone BiP forms a complex with FAM134B and promotes ER-phagy. Our studies have further led to the identification of a pharmacological agent vitexin that disrupts FAM134B-BiP complex thereby inhibits ER-phagy and suppresses breast cancer progression in vivo.

cancer biology↗

bioRxiv2021

S. Typhimurium impairs glycolysis-mediated acidification of phagosomes to evade macrophage defense

Regulation of the cellular metabolism is now recognized as a crucial mechanism for the homeostasis of innate and adaptive immune cells upon diverse extracellular stimuli. Macrophages, for instance, increase glycolysis upon stimulation with pathogen-associated molecular patterns (PAMPs). Conceivably, pathogens also counteract these metabolic changes for their own survival in the host. However, despite this dynamic interplay in host-pathogen interactions, the role of immunometabolism in the context of intracellular bacterial infections is still unclear. Here, employing unbiased metabolomic and transcriptomic approaches, we investigated the role of metabolic adaptations of macrophages upon Salmonella enterica serovar Typhimurium (S. Typhimurium) infections. Importantly, our results suggested that S. Typhimurium abrogates glycolysis and its modulators such as insulin-signaling to impair macrophage defense. Mechanistically, glycolytic enzyme aldolase A is critical for v-ATPase assembly and the acidification of phagosomes upon S. Typhimurium infection, and impairment in the glycolytic machinery eventually leads to decreased bacterial clearance and antigen presentation in macrophages. Collectively, our results highlight a vital molecular link between metabolic adaptation and phagosome maturation in macrophages, which is targeted by S. Typhimurium to evade cell-autonomous defense.

microbiology↗

bioRxiv2020

Expression of type I interferon-associated genes at antiretroviral therapy interruption predicts HIV virological rebound

Although certain individuals with HIV infection can stop antiretroviral therapy (ART) without evidence of viral load rebound, the mechanisms under-pinning post-treatment control remain unclear. Twelve individuals who had received 12 months of ART from primary HIV infection and then undertook a TI were sampled at the time of stopping therapy. Using RNA-Seq we explored gene expression in CD4 T cells to look for evidence of a mechanism that might underpin virological rebound and lead to discovery of an associated biomarker. Using independent analysis tools, genes associated with the type I interferon response were strongly associated with a delayed time to viral rebound following TI. These are the first data we are aware of that link transcriptomic signatures associated with innate immunity with control following TI. While these results need to be confirmed in larger trials, they could help define a strategy for new therapies and identify new biomarkers for remission.

microbiology↗

bioRxiv2020

Ranking the direct threats to biodiversity in sub-Saharan Africa

Sub-Saharan Africa benefits from large investments in biodiversity conservation, yet there is no prioritization of the many direct threats to biodiversity available to inform organizations developing sub-Saharan or sub-regional conservation strategies. Consequently, regional investments by funders of biodiversity conservation such as international conservation organizations, foundations, and bilateral and multilateral donors may be suboptimal. To identify the priority threats to biodiversity in sub-Saharan Africa, we classified the direct threats to biodiversity using standardized threats categories and triangulated data from a Delphi consensus of sub-Saharan Africa biodiversity experts, known threats to IUCN Red-listed sub-Saharan African species, and National Biodiversity Strategy and Action Plans from 47 sub-Saharan African countries. After ranking the threats from each source and averaging the rankings, we find that the highest threats are: annual and perennial crops (non-timber); logging and wood harvesting (natural forests); fishing and harvesting aquatic resources (marine and freshwater); and hunting and collecting terrestrial animals. Within the sub-regions of sub-Saharan Africa there is considerable variation. The highest ranked threat in Central Africa is hunting. In East Africa, it is agriculture. In Southern Africa, it is invasive non-native/alien species, and in West Africa, agriculture and logging are tied as the highest threats. There are known ways to address all of these threats, and concentrating investments on these threats while accounting for unique socio-ecological contexts across sub-Saharan Africa is essential for the sustained conservation of biodiversity.

ecology↗

bioRxiv2019

Proteasome-mediated protein degradation resets the cell division cycle and triggers ESCRT-III-mediated cytokinesis in an archaeon

The archaeon Sulfolobus acidocaldarius is a relative of eukaryotes known to progress orderly through its cell division cycle despite lacking obvious CDK/cyclin homologues. Here, in exploring the mechanisms underpinning archaeal cell division cycle control, we show that the proteasome of S. acidocaldarius, like its eukaryotic counterpart, regulates the transition from the end of one cell division cycle to the beginning of the next. Further, we identify the archaeal ESCRT-III homologue CdvB as a key target of the proteasome, and show that state-dependent degradation of CdvB triggers archaeal cell division by allowing constriction of a CdvB1:CdvB2 ESCRT-III division ring. These findings suggest an ancient role for proteasome-mediated degradation in resetting the cell division cycle in both archaea and eukaryotes.

cell biology↗

bioRxiv2019

Prevalence estimate of blood doping in elite track and field at the introduction of the Athlete Biological Passport

In elite sport, the Athlete Biological Passport (ABP) was invented to tackle cheaters by monitoring closely changes in biological parameters, flagging atypical variations. The haematological module of the ABP was indeed adopted in 2011 by the International Association of Athletics Federations (IAAF). This study estimates the prevalence of blood doping based on haematological parameters in a large cohort of track & field athletes measured at two international major events (2011 & 2013 IAAF World Championships) with a hypothesized decrease in prevalence due to the ABP introduction.\n\nA total of 3683 blood samples were collected and analysed from all participating athletes originating from 209 countries. The estimate of doping prevalence was obtained by using a Bayesian network with seven variables, as well as \"doping\" as a variable mimicking doping with low-doses of recombinant human erythropoietin (rhEPO), to generate reference cumulative distribution functions (CDFs) for the Abnormal Blood Profile Score (ABPS) from the ABP.\n\nOur results from robust haematological parameters indicate an estimation of an overall blood doping prevalence of 18% in average in endurance athletes (95% Confidence Interval (C.I.) 14-22%). A higher prevalence was observed in female athletes (22%, C.I. 16-28%) than in male athletes (15%, C.I. 9-20%). In conclusion, this study presents the first comparison of blood doping prevalence in elite athletes based on biological measurements from major international events that may help scientists and experts to use the ABP in a more efficient and deterrent way.\n\nWhat are the new findings ?O_LIThis study presents the first comparison of blood doping prevalence in elite track & field athletes based on biological measurements from major international events\nC_LIO_LIOur results from robust haematological parameters indicate an estimation of an overall blood doping prevalence of 18% in average in endurance athletes.\nC_LIO_LIThe confidence intervals for blood doping prevalence range from 9-28% with wide discrepancies between certain countries.\nC_LI\n\nHow might it impact on clinical practice in the near futureO_LIThe further development of the Athlete Biological Passport with a careful monitoring of biological parameters still represents the most consistent approach to thwart athletes using undetectable prohibited substances or methods.\nC_LIO_LIThis study describes a method to define blood doping prevalence with the analysis of robust haematological parameters\nC_LIO_LIEstimates of doping prevalence in subpopulations of athletes may represent a valuable tool for the antidoping authorities to perform a risk assessment in their sport.\nC_LI

physiology↗

bioRxiv2019

HIV reservoir size is determined prior to ART initiation and linked to CD8 T cell activation and memory expansion

Initiation of antiretroviral therapy (ART) in early compared with chronic HIV infection is associated with a smaller HIV reservoir. This longitudinal analysis of 63 individuals who commenced ART during primary HIV infection (PHI) investigates which pre-and post-therapy factors associate most closely with reservoir size (HIV DNA) following treatment initiation during PHI. The best predictor of reservoir size at one-year was pre-ART HIV DNA which was in turn significantly associated with CD8 memory differentiation (effector memory, naive and T-betnegEomesneg subsets), CD8 T cell activation (CD38 expression) and PD-1 and Tim-3 expression on memory CD4 T cells. No associations were found for any immunological variables following one-year of ART. HIV reservoir size is determined around the time of ART initiation in individuals treated during PHI. CD8 T cell activation and memory expansion are linked to HIV reservoir size, suggesting the importance of the initial host-viral interplay in eventual reservoir size.

immunology↗

bioRxiv2017

Enrichment of the HIV reservoir in CD32+ CD4 T cells occurs early in blood and tissue

The Fc receptor CD32 has been proposed as a marker for CD4 T cells latently infected with HIV. We demonstrate that enrichment for HIV DNA in CD32+ CD4 T cells can be found early in infection in both tissue and blood. However, we find no evidence for a correlation between CD32 expression on CD4 T cells and either HIV DNA levels or time to rebound viraemia following treatment interruption. CD32+ CD4 T cells have a more differentiated memory phenotype, and high levels of expression of immune checkpoint receptors PD-1, Tim-3 and TIGIT as well as the activation marker, HLA DR. There was no difference in the phenotype or frequency of CD32 expressing cells prior to or after the initiation of antiretroviral therapy, or compared with healthy controls, suggesting that preferential infection or survival, rather than up-regulation, may be responsible for the observed enrichment of proviral HIV DNA in CD32+ CD4 T cells.

immunology↗