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O'Connor, B.

Publications and source records attributed to O'Connor, B..

7 recordsLinked to original sources

Parental age at reproduction accelerates offspring pace of life in Gryllus bimaculatus

Across invertebrates, it is widely known that older parents produce offspring with abbreviated lifespans (i.e., the Lansing effect). Yet the ecological and evolutionary ramifications of such nongenetic parental age effects remain unclear. Two demographic processes could culminate in a Lansing effect, with different fitness implications: (i) Later-conceived offspring may display greater mortality from conception, constraining fitness from birth. (ii) Alternatively, they may exhibit an increased age-specific mortality (i.e., accelerated senescence), with negative effects that manifest after maturity. If parental age accelerates offspring senescence without affecting initial mortality rate, then later-conceived offspring may maintain fitness by shifting to a faster pace-of-life. We exposed Gryllus bimaculatus parents to one of three experimental temperatures to generate environmental variation in parent mortality. Using a longitudinal within-parent study, we tested whether parental age influenced offspring longevity via increased initial mortality or accelerated senescence, and whether these effects depended on the parents thermal environment. Contrary to our predictions, we found no evidence that parental age reduced offspring longevity. Instead, parental age mediated offspring pace-of-life. Irrespective of the parents thermal environment, the earliest- and latest-conceived offspring were demographically distinct. Later-conceived offspring exhibited accelerated development, a smaller adult mass, and improved reproductive success. Unexpectedly, they also showed extended adult lifespans. This increased adult lifespan did not arise from reduced initial mortality, but from a delayed onset and slower progression of actuarial senescence. The slowed senescence in later-conceived offspring is unlikely to reflect a direct parental age effect, potentially arising indirectly through causal effects on adult size. Our results challenge the universality of the Lansing effect and contribute to a growing recognition that parental age has important life-history consequences. Accelerated life-histories in later-conceived offspring may be adaptive, enabling these individuals to compete over dwindling seasonal resources or overcome seasonal time constraints. Determining whether these demographic parental age effects accumulate across generations, or persist under natural environments, will be essential for establishing their ecological consequences and proximate role in the evolution of ageing. Open research statementData and code are not yet provided but will be made openly and freely available on request during the review process. Data will be uploaded to the Dryad data repository and code will be uploaded to Zenodo open repository on acceptance of the manuscript.

evolutionary biology↗

Rapid GeneXpert surveillance of influenza A virus in seabirds and the environment provides early warning for wildlife health in Aotearoa New Zealand

The global expansion of highly pathogenic avian influenza (HPAI) virus A(H5N1) underscores the need for rapid surveillance at high-risk wildlife interfaces. Taiaroa Head (45.7828{degrees} S, 170.7333{degrees} E) in the South Island of Aotearoa New Zealand hosts a plethora of aquatic wildlife including a large red-billed gull (Chroicocephalus novaehollandiae scopulinus) colony as well as the only mainland breeding colony of northern royal albatross (Diomedea sanfordi). The Royal Albatross Centre is also a major nature tourism destination, attracting tens of thousands of visitors annually, thereby creating a dense ecological and human-wildlife interface vulnerable to viral incursion. We evaluated the GeneXpert II platform using the Xpert(R) Xpress Flu/RSV cartridge as a field-deployable tool for avian influenza virus detection in environmental and wildlife-associated samples. The assay detected synthetic influenza A viral RNA and multiple endemic low pathogenic avian influenza virus subtypes (A(H3N8), A(H1N9), A(H5N2) and A(H7N7)) circulating in New Zealand birds. Influenza A virus was reliably identified in spiked environmental water samples with no consistent PCR inhibition as well as naturally occurring avian influenza virus in duck pond water. Field deployment demonstrated that the system could be operated by non-laboratory personnel with minimal training in a non-clinical setting. This study establishes the feasibility of near-real-time environmental monitoring. Repurposing clinical cartridge-based point-of-care diagnostics offers a practical early warning approach for avian influenza virus surveillance at ecologically and economically significant locations.

microbiology↗

Gabapentinoids promote striatal dopamine release and rescue multiple deficits of a mouse model of early Parkinson's

Neuronal entry and handling of intracellular calcium have long-been hypothesised to burden vulnerable dopamine neurons in Parkinsons disease. However, no treatments for Parkinsons target calcium biology. Gabapentinoid drugs bind to 2{delta} subunits of voltage-gated calcium channels (VGCCs) and are licensed for neurological disorders including dopamine-dysregulated restless leg syndrome, suggesting their potential utility to modify both calcium biology and dopamine signalling. We therefore tested whether gabapentinoids modulate dopamine signalling, underlying VGCC-dependence, and potential for treating Parkinsons. In mouse striatum, we reveal that gabapentinoids ex vivo promote dopamine release, via sex-specific dependence on 2{delta}1/2 subunits and alterations to the calcium- and VGCC-subtype-dependence of dopamine release or its tonic inhibition by striatal GABA. In vivo administration of gabapentinoids to a mouse model of early Parkinsons rescued deficits in dopamine release, dysregulation of GABAergic inhibition and dopamine content, and abolished parkinsonian deficits in movement transitions. Thus, gabapentinoids urgently deserve attention for repurposing for Parkinsons disease. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=184 SRC="FIGDIR/small/675586v1_ufig1.gif" ALT="Figure 1"> View larger version (51K): org.highwire.dtl.DTLVardef@16cd7e1org.highwire.dtl.DTLVardef@d104e5org.highwire.dtl.DTLVardef@98683eorg.highwire.dtl.DTLVardef@1e3e3ae_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

Linking acoustic telemetry data to spatial covariates in river networks with spatially explicit capture-recapture models

O_LISpatially explicit capture-recapture (SECR) models extend classical capture-recapture models to include spatially-explicit animal locations and environmental covariates. SECR models have been widely employed in terrestrial studies to predict the population size and densities of animals assuming a closed population over a defined area. In this work, we extend and apply SECR models to a novel use-case that both uses a relative density formulation and accounts for biased tagging distributions to estimate parameters of habitat use from acoustic telemetry data in a branching river network. C_LIO_LIUsing SECR models, we predict how temperature distributions during the summer feeding season influenced how tagged Arctic grayling (Thymallus arcticus) distributed themselves through the Parsnip watershed in northcentral British Columbia, Canada. We found that the relative density of tagged Arctic grayling peaked at water temperatures of 12.4 {degrees}C. In warm years, relative densities were constricted as parts of the watershed became unfavorably warm. In cool years, fish were distributed widely throughout the watershed. C_LIO_LIIn acoustic telemetry, only the tagged population is available for detection. We highlight several specific considerations and assumptions for using this approach: i.e. (a) activity centres are assumed to remain in the same location throughout the study period, thus the time window of the study should be selected accordingly (e.g., exclude migratory periods); (b) inferences from acoustic telemetry data depict relative (not absolute) densities; and (c) spatial tagging effort must be defined in the model to ensure that predictions are not merely an artefact of tagging effort across space and time. When applied following these assumptions, this method is broadly useful for ecologists as it presents a quantitative way to merge automated telemetry datasets with discrete habitat parameters that drive population distributions through time and are relevant to managers and conservation professionals. Further, this method can be applied to branching river networks in which topological challenges have hindered other statistical approaches. C_LI

ecology↗

N-Glycans on the extracellular domain of the Notch1 receptor control Jagged-1 induced Notch signalling and myogenic differentiation of S100β resident vascular stem cells

Notch signalling, critical for development and postnatal homeostasis of the vascular system, is highly regulated by several mechanisms including glycosylation. While the importance of O-linked glycosylation is widely accepted, the structure and function of N-glycans has yet to be defined. Here, we take advantage of lectin binding assays in combination with pharmacological, molecular, and site-directed mutagenetic approaches to study N-glycosylation of the Notch1 receptor. We find that several key oligosaccharides containing bisecting or core fucosylated structures decorate the receptor, control expression and receptor trafficking, and dictate Jagged-1 activation of Notch target genes and myogenic differentiation of multipotent S100{beta} vascular stem cells. N-glycans at asparagine (N) 1241 and 1587 protect the receptor from accelerated degradation, while the oligosaccharide at N888 directly affects signal transduction. Conversely, N-linked glycans at N959, N1179, N1489 do not impact canonical signalling but inhibit differentiation. Our work highlights a novel functional role for N-glycans in controlling Notch1 signalling and differentiation of vascular stem cells. TeaserA sweet development in Notch regulation of vascular smooth muscle cell differentiation

cell biology↗

Concerning the eXclusion in human genomics: The choice of sex chromosome representation in the human genome drastically affects number of identified variants

Over the past 30 years, a community of scientists have pieced together every base pair of the human reference genome from telomere-to-telomere. Interestingly, most human genomics studies omit more than 5% of the genome from their analyses. Under normal circumstances, omitting any chromosome(s) from analysis of the human genome would be reason for concern--the exception being the sex chromosomes. Sex chromosomes in eutherians share an evolutionary origin as an ancestral pair of autosomes. In humans, they share three regions of high sequence identity (~98-100%), which--along with the unique transmission patterns of the sex chromosomes--introduce technical artifacts into genomic analyses. However, the human X chromosome bears numerous important genes--including more "immune response" genes than any other chromosome--which makes its exclusion irresponsible when sex differences across human diseases are widespread. To better characterize the effect that including/excluding the X chromosome may have on variants called, we conducted a pilot study on the Terra cloud platform to replicate a subset of standard genomic practices using both the CHM13 reference genome and sex chromosome complement-aware (SCC-aware) reference genome. We compared quality of variant calling, expression quantification, and allele-specific expression using these two reference genome versions across 50 human samples from the Genotype-Tissue-Expression consortium annotated as females. We found that after correction, the whole X chromosome (100%) can generate reliable variant calls--allowing for the inclusion of the whole genome in human genomics analyses as a departure from the status quo of omitting the sex chromosomes from empirical and clinical genomics studies.

genomics↗

A robotic platform for fluidically-linked human body-on-chips experimentation

Here we describe of an Interrogator instrument that uses liquid-handling robotics, a custom software package, and an integrated mobile microscope to enable automated culture, perfusion, medium addition, fluidic linking, sample collection, and in situ microscopic imaging of up to 10 Organ Chips inside a standard tissue culture incubator. The automated Interrogator platform maintained the viability and organ-specific functions of 8 different vascularized, 2-channel, Organ Chips (intestine, liver, kidney, heart, lung, skin, blood-brain barrier (BBB), and brain) for 3 weeks in culture when fluidically coupled through their endothelium-lined vascular channels using a common blood substitute medium. When an inulin tracer was perfused through the multi-organ Human Body-on-Chips (HuBoC) fluidic network, quantitative distributions of this tracer could be accurately predicted using a physiologically-based multi-compartmental reduced order (MCRO) in silico model of the experimental system derived from first principles. This automated culture platform enables non-invasive imaging of cells within human Organ Chips and repeated sampling of both the vascular and interstitial compartments without compromising fluidic coupling, which should facilitate future HuBoc studies and pharmacokinetics (PK) analysis in vitro.

bioengineering↗