Biology subjects

Walsh, M.

Publications and source records attributed to Walsh, M..

30 records · Page 2Linked to original sources

bioRxiv2022

Evolution of Daphnia population dynamics following invasion by a non-native predator

O_LIPredators are frequently observed to cause evolutionary responses in prey phenotypes, which may, in turn, translate into evolutionary shifts in prey population dynamics. Although a link between predation and population growth has been demonstrated in experimental evolution studies, insights from natural populations are lacking. C_LIO_LIHere we tested for evolutionary changes in the population dynamics of the herbivorous water flea Daphnia pulicaria in response to the invasion of the predatory spiny water flea (Bythotrephes longimanus) in the Great Lakes region, USA. Using a resurrection ecological approach and a 3-month population growth experiment (in the absence of predation) we compared population dynamics in daphnia from pre- and post-invasion time periods. C_LIO_LIPost-invasion daphnia were able to maintain an overall higher population abundance throughout the growth experiment, both in terms of the number of individuals (28% higher) and total population biomass (33% higher). Estimation of population dynamics parameters from a theta-logistic model suggested that this was achieved through an increase in intrinsic population growth rate as well as increased carrying capacity. C_LIO_LIThe observed difference in intrinsic rate of increase could not be predicted based on previous measurements of life-history traits in these clones. This indicates that care should be taken when extrapolating from a few life history traits measured in isolated individuals under controlled conditions to population dynamics. C_LIO_LIWhereas previous experimental evolution studies of predator-prey interactions have demonstrated that genotypes that have evolved under predation have inferior population growth when the predator is absent, this was not the case for the Daphnia. We suggest that complexities in ecological interactions of natural ecosystems, such as the potential for spatial and temporal avoidance of predation, makes it challenging to provide general predictions about evolutionary responses in population dynamics to predators. C_LI

evolutionary biology↗

bioRxiv2022

A preliminary description of the ecological characteristics of wild waterbird Japanese encephalitis virus hosts in high risk landscapes in India

Wild reservoirs of Japanese encephalitis virus are under-studied globally, which presents critical knowledge gaps for JEV infection ecology despite decades of received wisdom regarding this high-impact mosquito-borne virus. As a result, ardeid birds, generally understood to be the primary reservoirs for JEV, as well as other waterbirds occupying landscapes at high risk for spillover to humans, are frequently ignored by current surveillance mechanisms and infrastructure. This is particularly true in India, which experiences a high annual burden of human outbreaks. Incorporating wild reservoirs into surveillance of human and livestock populations is therefore essential but will first require a data-driven approach to target individual host species. The current study sought to define a preliminary ecological profile of JEV hosts based on 1) species ecological traits, and 2) species presence and abundance adjusted for the biotic constraints of sympatry. Optimal host species tended to be generalists and demonstrate regionally-increasing populations. While ardeid bird species richness, abundance, and relative abundance did demonstrate the strongest and most consistent associations with the distribution of human JEV outbreaks, this study also identified several individual species among two other bird families in these landscapes, the Anatidae and the Rallidae, which also exhibited an optimal host profile and were strongly associated with the distribution of outbreaks. The findings from this work provide the first data-driven evidence base to inform wildlife sampling for the monitoring of JEV circulation in outbreak hotspots in India and thus identify good preliminary targets for the development of One Health wildlife JEV surveillance.

ecology↗

bioRxiv2021

Sex-Related Neurocircuitry Supporting Camouflaging in Adults with Autism: Female Protection Insights

The male preponderance in autism led to the hypothesis that aspects of female biology are protective against autism. Females with autism report engaging in more compensatory behaviors (i.e., "camouflaging") to overcome autism-related social differences, which may be a downstream result of protective pathways. No studies have examined sex-related brain pathways supporting camouflaging in females with autism, despite its potential to inform mechanisms underlying the sex bias in autism. This case-control design included 45 non-intellectually-disabled adults with autism (male/female: 21/24) and 40 neurotypical adults (male/female: 19/21) ages 18-71. We used group multivariate voxel pattern analysis to conduct a data-driven, connectome-wide characterization of "sex-atypical" (sex-by-diagnosis) and "sex-typical" (sex) brain functional connectivity features linked to camouflaging, and validated findings in females with autism multi-modally via structural connectometry. Exploratory associations with cognitive control, memory, emotion recognition, and depression/anxiety examined the adaptive nature of functional connectivity patterns supporting camouflaging in females with autism. We found 1) "sex-atypical" functional connectivity patterns predicting camouflaging in the hypothalamus and precuneus and 2) "sex-typical" patterns in the anterior cingulate and right anterior parahippocampus. Higher hypothalamic functional connectivity with a limbic reward cluster was the strongest predictor of camouflaging in females with autism (a "sex-atypical" pattern), and also predicted better cognitive control/emotion recognition. Structural connectometry validated functional connectivity results with consistent brain pathways/effect patterns implicated across multi-modal findings in females with autism. This data-driven, connectome-wide characterization of "sex-atypical" and "sex-typical" brain connectivity features supporting compensatory social behavior in autism suggests hormones may play a role in the autism sex bias. Furthermore, both "male-typical" and "female-typical" brain connectivity patterns are implicated in camouflaging in females with autism in circuits associated with reward, emotion, and memory processing. "Sex-atypical" results are consistent with the fetal steroidogenic hypothesis, which would result in masculinized brain features in females with autism. However, female genetics/biology may contribute to "female-typical" patterns implicated in camouflaging.

neuroscience↗

bioRxiv2021

Low mammalian species richness increases Kyasanur Forest Disease outbreak risk in deforested landscapes in the Western Ghats, India

Kyasanur forest disease virus (KFDV) is a rapidly expanding tick-borne zoonotic virus with natural foci in the forested region of the Western Ghats of South India. The Western Ghats is one of the worlds most important biodiversity hotspots and, like many such areas of high biodiversity, is under significant pressure from anthropogenic landscape change. The current study sought to quantify mammalian species richness using ensemble models of the distributions of a sample of species extant in the Western Ghats and to explore its association with KFDV outbreaks, as well as the modifying effects of deforestation on this association. Species richness was quantified as a composite of individual species distributions, as derived from ensembles of boosted regression tree, random forest, and generalised additive models. Species richness was further adjusted for the potential biotic constraints of sympatric species. Both species richness and forest loss demonstrated strong positive associations with KFDV outbreaks, however forest loss substantially modified the association between species richness and outbreaks. High species richness was associated with increased KFDV risk but only in areas of low forest loss. In contrast, lower species richness was associated with increased KFDV risk in areas of greater forest loss. This relationship persisted when species richness was adjusted for biotic constraints at the taluk-level. In addition, the taluk-level species abundances of three monkey species (Macaca radiata, Semnopithecus hypoleucus, and Semnopithecus priam) were also associated with outbreaks. These results suggest that increased monitoring of wildlife in areas of significant habitat fragmentation may add considerably to critical knowledge gaps in KFDV epidemiology and infection ecology and should be incorporated into novel One Health surveillance development for the region. In addition, the inclusion of some primate species as sentinels of KFDV circulation into general wildlife surveillance architecture may add further value. HighlightsO_LILocal mammalian species richness is estimated across the entire Western Ghats region C_LIO_LILow species richness is associated with high KFDV risk in deforested landscapes C_LIO_LIThis work identifies key landscapes for wildlife disease surveillance development C_LI

ecology↗

bioRxiv2021

12-Lipoxygenase Governs the Innate Immune Pathogenesis of Islet Inflammation and Autoimmune Diabetes

Macrophages and related myeloid cells are innate immune cells that participate in the early islet inflammation of type 1 diabetes (T1D). The inflammatory signals and antigen presentation by these cells may be inducers of the adaptive immune response that is the hallmark of T1D. The enzyme 12-lipoxygenase (12-LOX) catalyzes the formation of pro-inflammatory eicosanoids from membrane-derived phospholipids, but its role and mechanisms in the pathogenesis of islet inflammation have not been elucidated. Leveraging a model of T1D-like islet inflammation in zebrafish, we show here that macrophages contribute significantly to the loss of {beta}-cells and the subsequent development of hyperglycemia. Depletion or inhibition of 12-LOX in this model resulted in significantly reduced macrophage infiltration into islets with preservation of {beta}-cell mass. In mice, we deleted the gene encoding 12-LOX (Alox15) in the myeloid lineage in the non-obese diabetic (NOD) model of T1D. Myeloid cell-specific Alox15 knockout NOD mice demonstrated reduced insulitis and T-cell responses, preserved {beta} cell mass, and almost complete protection from the development of T1D. A critical effect of 12-LOX depletion appeared secondary to a defect in myeloid cell migration, a function required for immune surveillance and tissue injury responses. This effect on migration appeared to be secondary to the loss of the chemokine receptor CXCR3. Transgenic expression of the gene encoding CXCR3 rescued the migrator defect in zebrafish 12-LOX morphants. Taken together, our results reveal a formative role for innate immune myeloid cells in the early pathogenesis of T1D and identify 12-LOX as a necessary enzyme to promote their pro-diabetogenic phenotype in the context of autoimmunity.

immunology↗

bioRxiv2020

A preliminary ecological profile of Kyasanur Forest disease virus hosts among the mammalian wildlife of the Western Ghats, India

Kyasanur Forest disease (KFD) is one of Indias severe arboviruses capable of causing prolonged debilitating disease. It has been expanding beyond its historical endemic locus at an alarming rate over the last two decades. The natural nidus of this zoonosis is located in the monsoon rainforest of the Western Ghats, India, which is one of the worlds most important biodiversity hotspots. Definitive reservoir hosts for KFD virus (KFDV) have yet to be delineated, and thus much of the infection ecology of this virus, and its consequent transmission dynamics, remains uncertain. Given its unique biogeographical context, identifying ecological parameters of KFDV relevant to the virus epidemiology has been complex and challenging. The challenge has been exacerbated by diminished research efforts in wildlife surveillance over the last two decades, coinciding with the expansion of the range of KFD across the region. The current investigation sought to define a preliminary ecological profile of KFDV hosts based on their life history and feeding traits to aid in re-establishing targeted wildlife surveillance and to discern those ecological traits of wildlife hosts that may improve our understanding of KFD epidemiology. The importance of fast-living among KFDV hosts was of special interest with respect to the latter aim. We compared mammalian traits between host and non-host species using general additive models and phylogenetic generalised linear models. This study found that both body mass and forest forage were strongly associated with mammalian host infection status, but that reproductive life history traits were not. These findings will help in structuring ecologically based wildlife surveillance and field investigations, while also helping to parameterise novel epidemiological models of zoonotic infection risk that incorporate species functional traits in a region where biogeography, landscape ecology, and community ecology manifest extraordinary complexity, particularly under growing anthropogenic pressure.

ecology↗

bioRxiv2019

Oncologic Therapy Shapes the Fitness Landscape of ClonalHematopoiesis

Clonal hematopoiesis (CH) is frequent in cancer patients and associated with increased risk of therapy related myeloid neoplasms (tMN). To define the relationship between CH, oncologic therapy, and tMN progression, we studied 24,439 cancer patients. We show that previously treated patients have increased rates of CH, with enrichment of mutations in DNA Damage Response (DDR) genes (TP53, PPM1D, CHEK2). Exposure to radiation, platinum and topoisomerase II inhibitors have the strongest association with CH with evidence of dose-dependence and gene-treatment interactions. We validate these associations in serial sampling from 525 patients and show that exposure to cytotoxic and radiation therapy imparts a selective advantage specifically in hematopoietic cells with DDR mutations. In patients who progressed to tMN, the clone at CH demarcated the dominant clone at tMN diagnosis. CH mutational features predict risk of therapy-related myeloid neoplasm in solid tumor patients with clinical implications for early detection and treatment decisions.

genetics↗

bioRxiv2019

Insights into an alternative pathway for glycerol metabolism in a glycerol kinase deficient Pseudomonas putida KT2440

Pseudomonas putida KT2440 is known to metabolise glycerol via glycerol-3-phosphate using glycerol kinase an enzyme previously described as critical for glycerol metabolism (1). However, when glycerol kinase was knocked out in P. putida KT2440 it retained the ability to use glycerol as the sole carbon source, albeit with a much-extended lag period and 2 fold lower final biomass compared to the wild type strain. A metabolomic study identified glycerate as a major and the most abundant intermediate in glycerol metabolism in this mutated strain with levels 21-fold higher than wild type. Erythrose-4-phosphate was detected in the mutant strain, but not in the wild type strain. Glyceraldehyde and glycraldehyde-3-phosphate were detected at similar levels in the mutant strain and the wild type. Transcriptomic studies identified 191 genes that were more than 2-fold upregulated in the mutant compared to the wild type and 175 that were down regulated. The genes involved in short chain length fatty acid metabolism were highly upregulated in the mutant strain. The genes encoding 3-hydroxybutyrate dehydrogenase were 5.8-fold upregulated and thus the gene was cloned, expressed and purified to reveal it can act on glyceraldehyde but not glycerol as a substrate.\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=128 SRC=\"FIGDIR/small/567230_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (21K):\norg.highwire.dtl.DTLVardef@1b5298eorg.highwire.dtl.DTLVardef@bb4841org.highwire.dtl.DTLVardef@184de3forg.highwire.dtl.DTLVardef@1b2e2a_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2018

Ecological and life history traits are associated with Ross River virus infection among sylvatic mammals in Australia

BackgroundRoss River virus (RRV) is Australias most important arbovirus given its annual burden of disease and the relatively large number of Australians at risk for infection. This mosquito-borne arbovirus is also a zoonosis, making its epidemiology and infection ecology complex and cryptic. Our grasp of enzootic, epizootic, and zoonotic RRV transmission dynamics is imprecise largely due to a poor understanding of the role of wild mammalian hosts in the RRV system.\n\nMethodsThe current study applied a piecewise structural equation model (PSEM) toward an interspecific comparison of sylvatic Australian mammals to characterize the ecological and life history profile of species with a history of RRV infection relative to those species with no such history among all wild mammalian species surveyed for RRV infection. The effects of species traits were assessed through multiple causal pathways within the PSEM framework.\n\nResultsSylvatic mammalian species with a history of RRV infection tended to express dietary specialization and smaller population density. These species were also characterized by a longer gestation length.\n\nConclusionsThis study provides the first interspecific comparison of wild mammals for RRV infection and identifies some potential targets for future wildlife surveys into the infection ecology of this important arbovirus. An applied RRV macroecology may prove invaluable to the epidemiological modeling of RRV epidemics across diverse sylvatic landscapes, as well as to the development of human and animal health surveillance systems.

ecology↗

bioRxiv2018

Genetic mechanisms of primary chemotherapy resistance in pediatric acute myeloid leukemia: A report from the TARGET initiative

Acute myeloid leukemias (AML) are characterized by mutations of tumor suppressor and oncogenes, involving distinct genes in adults and children. While certain mutations have been associated with the increased risk of AML relapse, the genomic landscape of primary chemotherapy resistant AML is not well defined. As part of the TARGET initiative, we performed whole-genome DNA and transcriptome (RNA and miRNA) sequencing analysis of pediatric AML with failure of induction chemotherapy. We identified at least three genetic groups of patients with induction failure, including those with NUP98 rearrangements, somatic mutations of WT1 in the absence of NUP98 mutations, and additional recurrent variants including those in KMT2C and MLLT10. Comparison of specimens before and after chemotherapy revealed distinct and invariant gene expression programs. While exhibiting overt therapy resistance, these leukemias nonetheless showed diverse forms of clonal evolution upon chemotherapy exposure. This included selection for mutant alleles of FRMD8, DHX32, PIK3R1, SHANK3, MKLN1, as well as persistence of WT1 and TP53 mutant clones, and elimination or contraction of FLT3, PTPN11, and NRAS mutant clones. These findings delineate genetic mechanisms of primary chemotherapy resistance in pediatric AML, which should inform improved approaches for its diagnosis and therapy.

cancer biology↗

bioRxiv2018

The wildlife-livestock interface modulates anthrax suitability in India

Anthrax is a potentially life-threatening bacterial disease that can circulate in wild and domestic animals and subsequently spillover to human contacts with devastating consequences for human and animal health, as well as livestock economies and ecosystem conservation. India has a high annual occurrence of anthrax in some regions, but a country-wide delineation of risk has not yet been undertaken. The current study modeled the geographic suitability of anthrax across India and its associated environmental features using a biogeographical application of machine learning. Both biotic and abiotic features contributed to risk across multiple scales of influence and the wildlife-livestock interface, using elephants as a wildlife sentinel species, was the dominant feature in delineating anthrax suitability. In addition, water-soil balance, soil chemistry, and historical forest loss were also influential. These findings suggest that the wildlife-livestock interface plays an important role in the cycling of anthrax in India. Prevention efforts targeted toward this interface, particularly within anthropogenic ecotones, may yield successes in reducing ongoing transmission between animal hosts and subsequent zoonotic transmission to humans.

epidemiology↗

bioRxiv2018

Towards automation of germline variant curation inclinical cancer genetics

Cancer care professionals are confronted with interpreting results from multiplexed gene sequencing of patients at hereditary risk for cancer. Assessments for variant classification now require orthogonal data searches, requiring aggregation of multiple lines of evidence from diverse resources. The burden of evidence for each variant to meet thresholds for pathogenicity or actionability now poses a growing challenge for those seeking to counsel patients and families following germline genetic testing. A computational algorithm that automates, provides uniformity and significantly accelerates this interpretive process is needed. The tool described here, Pathogenicity of Mutation Analyzer (PathoMAN) automates germline genomic variant curation from clinical sequencing based on ACMG guidelines. PathoMAN aggregates multiple tracks of genomic, protein and disease specific information from public sources. We compared expert manually curated variant data from studies on (i) prostate cancer (ii) breast cancer and (iii) ClinVar to assess performance. PathoMAN achieves high concordance (83.1% pathogenic, 75.5% benign) and negligible discordance (0.04% pathogenic, 0.9% benign) when contrasted against expert curation. Some loss of resolution (8.6% pathogenic, 23.64% benign) and gain of resolution (6.6% pathogenic, 1.6% benign) was also observed. We highlight the advantages and weaknesses related to the programmable automation of variant classification. We also propose a new nosology for the five ACMG classes to facilitate more accurate reporting to ClinVar. The proposed refinements will enhance utility of ClinVar to allow further automation in cancer genetics. PathoMAN will reduce the manual workload of domain level experts. It provides a substantial advance in rapid classification of genetic variants by generating robust models using a knowledge-base of diverse genetic data https://pathoman.mskcc.org.

genetics↗