Biology subjects

Ross, N.

Publications and source records attributed to Ross, N..

9 recordsLinked to original sources

bioRxiv2025

Neuropeptidergic transmission shapes emergent properties of prefrontal cortical circuits underlying learning

The prefrontal cortex (PFC) is essential for top-down control of affect and its dysfunction is implicated in many psychiatric disorders. Inhibitory interneurons expressing somatostatin have been implicated in cognition, affect, and disease. However, somatostatins function as a neuropeptide transmitter remains unclear. Here, we investigated the contribution of somatostatin neurotransmission in differentiating between salient (rewarding or aversive) and neutral outcomes. Monitoring somatostatin release and somatostatin receptor antagonism revealed time-dependent regulation of outcome-specific associative learning during acquisition. We found that somatostatin transmission enables configural representations incorporating a salient, aversive outcome in prefrontal cortical neurons, and a threat-driven shift in population-level network activity in-vivo. These findings show a novel role for somatostatin, an interneuron "cellular marker", signaling in shaping learning and emergent network dynamics. Further this framework revealed that reduced somatostatin neuropeptidergic transmission may impair top-down control of affective behaviors observed in mental health disorders, suggesting potential new avenues for therapeutic intervention.

neuroscience↗

bioRxiv2023

Localized Rift Valley Fever Virus Persistence Depends on a High Transovarial Transmission Fraction

Rift Valley fever virus (RVFV) has spread beyond continental Africa and threatens to follow West Nile, chikungunya and Zika viruses into the Americas. Its impact in new localities and the capacity to control future outbreaks, depends on whether and how RVFV persists at small spatial scales. Transovarial transmission (TOT) is hypothesized as an important mechanism for local persistence, yet its role in RVFV ecology remains poorly understood. We examine whether RVFV can persist locally via TOT while maintaining a realistic seroprevalence pattern of interepidemic and epidemic transmission. We developed a mechanistic, compartmental model of RVFV dynamics within a single host (sheep) and two vector (mosquito) populations, driven by temperate climatic factors. Decades-long persistence was possible in our simulations, which generally captured the observed outbreak patterns in central South Africa with a mean annual seroprevalence ([~]23%) within the range reported during interepidemic periods (5-40%). Persistence was only possible with a substantial TOT fraction and over a narrow range of parameters. The basic reproduction number (R0) was close to one at mean vector population sizes, suggesting a relatively limited expansion of the infected vector population during outbreaks. This limited expansion provides the system with the flexibility to support both low-level transmission and large outbreaks and, counterintuitively, large outbreaks resulted in smaller infected Aedes egg populations. This has important consequences for control: low-level vaccination may prevent large outbreaks without eliminating RVFV and local control efforts may be most effective immediately following an outbreak, suggesting elimination may be possible after emergence in temperate regions.

ecology↗

bioRxiv2023

Ongoing amphibian trade into the United States threatens salamander biodiversity

The fungal pathogen Batrachochytrium salamandrivorans (Bsal) is a major potential threat to salamander biodiversity in North America, where it is not yet known to occur. In the United States, a 2016 policy restricted the trade in 20 salamander genera in attempts to prevent Bsal introduction. However, little comprehensive data is available to evaluate the impact of this policy action. Here, we collated a dataset of United States amphibian imports from 1999 to 2021 and show that reported legal trade in the targeted taxa was effectively reduced by the ban. Unfortunately, amphibian trade into the United States continues to risk Bsal introduction given that other species and genera now known to carry Bsal are still traded in large quantities (millions of live individuals annually). Additional policy responses focused on Bsal carrier taxa, especially frogs in the genus Rana, could help mitigate the impact of Bsal on North American salamanders.

ecology↗

bioRxiv2020

CCP1, a tubulin deglutamylase, increases survival of rodent spinal cord neurons following glutamate-induced excitotoxicity

Microtubules (MTs) are cytoskeletal elements that provide structural support, establish morphology, and act as roadways for intracellular transport in cells. Neurons extend and must maintain long axons and dendrites to transmit information through the nervous system. Therefore, in neurons, the ability to independently regulate cytoskeletal stability and MT-based transport in different cellular compartments is essential. Post-translational modification of MTs is one mechanism by which neurons can regulate the cytoskeleton. The carboxypeptidase CCP1 negatively regulates post-translational glutamylation of MTs. We previously demonstrated that the CCP1 homolog in C. elegans is important for maintenance of cilia. In mammals, loss of CCP1, and the resulting hyperglutamylation of MTs, causes neurodegeneration. It has long been known that CCP1 expression is activated by neuronal injury; however, whether CCP1 plays a neuroprotective role after injury is unknown. Furthermore, it not yet clear whether CCP1 acts on ciliary MTs in spinal cord neurons. Using an in vitro model of excitotoxic neuronal injury coupled with shRNA-mediated knockdown of CCP1, we demonstrate that CCP1 protects neurons from excitotoxic death. Unexpectedly, excitotoxic injury reduced CCP1 expression in our system, and knockdown of CCP1 did not result in loss or shortening of cilia in cultured spinal cord neurons. Our results suggest that CCP1 acts on axonal and dendritic MTs to promote cytoskeletal rearrangements that support neuroregeneration and that enzymes responsible for glutamylation of MTs might be therapeutically targeted to prevent excitotoxic death after spinal cord injuries.

cell biology↗

bioRxiv2020

Mutation of NEKL-4/NEK10 and TTLL genes opposes loss of the CCPP-1 deglutamylase and prevents neuronal ciliary degeneration

Ciliary microtubules are subject to post-translational modifications that act as a "Tubulin Code" to regulate motor traffic, binding proteins and stability. In humans, loss of CCP1, a cytosolic carboxypeptidase and tubulin deglutamylating enzyme, causes infantile-onset neurodegeneration. In C. elegans, mutations in ccpp-1, the homolog of CCP1, result in progressive degeneration of neuronal cilia and loss of neuronal function. To identify genes that regulate microtubule glutamylation and ciliary integrity, we performed a forward genetic screen for suppressors of ciliary degeneration in ccpp-1 mutants. We isolated the ttll-5(my38) suppressor, a mutation in the tubulin tyrosine ligase-like glutamylase gene. We show that mutation in ttll-4, ttll-5, or ttll-11 gene suppressed the hyperglutamylation-induced loss of microtubules and kinesin-2 mislocalization in ccpp-1 cilia. We also identified the nekl-4(my31) suppressor, an allele affecting the NIMA (Never in Mitosis A)-related kinase NEKL-4/NEK10. In humans, NEK10 mutation causes bronchiectasis, an airway and mucociliary transport disorder caused by defective motile cilia. C. elegans NEKL-4 does not localize to cilia yet plays a role in regulating axonemal microtubule stability. This work defines a pathway in which glutamylation, a component of the Tubulin Code, is written by TTLL-4, TTLL-5, and TTLL-11; is erased by CCPP-1; is read by ciliary kinesins; and its downstream effects are modulated by NEKL-4 activity. Identification of regulators of microtubule glutamylation in diverse cellular contexts is important to the development of effective therapies for disorders characterized by changes in microtubule glutamylation. By identifying C. elegans genes important for neuronal and ciliary stability, our work may inform research into human ciliopathies and neurodegenerative diseases.

genetics↗

bioRxiv2020

Climate change will drive novel cross-species viral transmission

At least 10,000 species of mammal virus are estimated to have the potential to spread in human populations, but the vast majority are currently circulating in wildlife, largely undescribed and undetected by disease outbreak surveillance 1-3 . In addition, changing climate and land use are already driving geographic range shifts in wildlife, producing novel species assemblages and opportunities for viral sharing between previously isolated species 4, 5 . In some cases, this will inevitably facilitate spillover into humans 6, 7 --a possible mechanistic link between global environmental change and emerging zoonotic disease 8 . Here, we map potential hotspots of viral sharing, using a phylogeographic model of the mammal-virus network, and projections of potential geographic range shifts for 3,139 mammal species under climate change and land use scenarios for the year 2070. Range-shifting mammal species are predicted to aggregate at high elevations, in biodiversity hotspots, and in areas of high human population density in Asia and Africa, driving the novel cross-species transmission of their viruses an estimated 4,000 times. Counter to expectations, holding warming under 2{degrees}C within the century does not reduce new viral sharing, due to greater potential range expansions-- highlighting the need to invest in surveillance even in a low-warming future. Most projected viral sharing is driven by diverse hyperreservoirs (rodents and bats) and large-bodied predators (carnivores). Because of their unique dispersal capacity, bats account for the majority of novel viral sharing, and are likely to share viruses along evolutionary pathways that could facilitate future emergence in humans. Our findings highlight the urgent need to pair viral surveillance and discovery efforts with biodiversity surveys tracking species range shifts, especially in tropical countries that harbor the most emerging zoonoses.

ecology↗

bioRxiv2019

United States wildlife and wildlife product imports from 2000-2014

The global wildlife trade network is a massive system that has been shown to threaten biodiversity conservation, introduce non-native species and pathogens, and cause chronic animal welfare concerns. Despite its scale and impact, comprehensive characterization of the global wildlife trade is hampered by data that are limited in their temporal or taxonomic scope and detail. To help fill this gap, we present data on 15 years of the importation of wildlife and their derived products into the United States (2000-2014), originally collected by the United States Fish and Wildlife Service. We curated and cleaned the data and added taxonomic information to improve data usability. These data include > 2 million wildlife or wildlife product shipments, representing > 60 biological classes and > 3.2 billion live organisms. These data will be broadly useful to both scientists and policymakers seeking to better understand the volume, sources, biological composition, and potential risks of the global wildlife trade.

ecology↗

bioRxiv2019

Predicting the global mammalian viral sharing network using phylogeography

Understanding interspecific viral transmission is key to understanding viral ecology and evolution, disease spillover into humans, and the consequences of global change. Prior work has demonstrated that macroecological factors drive viral sharing in some mammalian groups, but analyses have never attempted to predict viral sharing in a pan-mammalian context. Here we show that host phylogenetic similarity and geographic range overlap are strong, nonlinear predictors of viral sharing among species across the entire mammal class. Using these traits, we predict global viral sharing patterns across 4196 mammal species and show that our simulated network successfully predicts viral sharing and reservoir host status using internal validation and an external dataset. We predict high rates of mammalian viral sharing in the tropics, particularly among rodents and bats, and that within- and between-order sharing differs geographically and taxonomically. Our results emphasize the importance of macroecological factors in shaping mammalian viral communities, and provide a robust, general model to predict viral host range and guide pathogen surveillance and conservation efforts.

ecology↗

bioRxiv2018

The global distribution of Bacillus anthracis and associated anthrax risk to humans, livestock, and wildlife

Bacillus anthracis is a spore-forming, Gram-positive bacterium responsible for anthrax, an acute and commonly lethal infection that most significantly affects grazing livestock, wild ungulates and other herbivorous mammals, but also poses a serious threat to human health1, 2. The geographic extent of B. anthracis endemism is still poorly understood, despite multi-decade research on anthrax epizootic and epidemic dynamics around the world3, 4. Several biogeographic studies have focused on modeling environmental suitability for anthrax at local or national scales5-9, but many countries have limited or inadequate surveillance systems, even within known endemic regions. Here we compile an extensive global occurrence dataset for B. anthracis, drawing on confirmed human, livestock, and wildlife anthrax outbreaks. With these records, we use boosted regression trees10, 11 to produce the first map of the global distribution of B. anthracis as a proxy for anthrax risk. Variable contributions to the model support pre-existing hypotheses that environmental suitability for B. anthracis depends most strongly on soil characteristics such as pH that affect spore persistence, and the extent of seasonal fluctuations in vegetation, which plays a key role in transmission for herbivores12, 13. We apply the global model to estimate that 1.83 billion people (95% credible interval: 0.59--4.16 billion) live within regions of anthrax risk, but most of that population faces little occupational exposure to anthrax. More informatively, a global total of 63.8 million rural poor livestock keepers (95% CI: 17.5--168.6 million) and 1.1 billion livestock (95% CI: 0.4--2.3 billion) live within vulnerable regions. Human risk is concentrated in rural areas, and human and livestock vulnerability are both concentrated in rainfed systems throughout arid and temperate land across Eurasia, Africa, and North America. We conclude by mapping where anthrax risk overlaps with vulnerable wild ungulate populations, and therefore could disrupt sensitive conservation efforts for species like bison, pronghorn, and saiga that coincide with anthrax-prone, mixed-agricultural landscapes. Anthrax is a zoonotic disease caused by the Gram-positive bacterium Bacillus anthracis, a generalist soil-transmitted pathogen found on every inhabited continent14, and several islands including Haiti and parts of the Philippines and Indonesia. Worldwide, an estimated 20,000 to 100,000 cases of anthrax occur annually, mostly in poor rural areas15. In clinical presentations of anthrax, case fatality rates are a function of exposure pathway. Respiratory exposure from spore inhalation is important the context of bioterrorism, but is highly uncommon, and accounts for a negligible fraction of the global burden of anthrax cases. Cutaneous exposure to B. anthracis accounts for the majority of human cases worldwide, and typically presents with low mortality; gastrointestinal exposure accounts for the remainder and presents with intermediate to high fatality rates. Cutaneous and gastrointestinal cases of anthrax are most commonly caused by handling and slaughtering infected livestock, or butchering and eating contaminated meat; untreated gastrointestinal cases likely account for most human mortality from anthrax.14-16

epidemiology↗