Biology subjects

Hill, N. J.

Publications and source records attributed to Hill, N. J..

6 recordsLinked to original sources

bioRxiv2026

Unlocking a flexible set of phylogenetic models for discrete and continuous trait evolution using discretized stochastic diffusion

The practical utility of many modern phylogenetic comparative methods can depend on how accurately mathematical models capture the evolutionary process of traits. Boucher and Demery (2016) described a new quantitative trait model for testing hypotheses about constraint on phenotypic character evolution: Brownian motion with reflective limits. Since their analytic solution for the probability function under this bounded scenario was intractable for reasonably-sized trees, Boucher and Demery (2016) also identified a creative technique for computing the likelihood of their model. The basis of this method derives from the convergence of an equal-rates, symmetric, ordered Markov chain and continuous stochastic diffusion in the limit as the number of lattice states in the chain goes to{infty} (or, alternatively, as their widths decrease towards zero). We realized that this general approach had the potential to unlock a surprisingly large number of additional models for the phylogenetic comparative analysis of discrete and continuous trait data, and we explore several of these in the present article. Specifically, we examine application of this discretized diffusion approximation to the threshold model from evolutionary quantitative genetics, to a new "semi-threshold" trait evolution model, to a joint model where the rate of evolution for a continuous trait depends on the value of a co-evolving discrete character, along with a separate model where precisely the converse is true, and to a discrete-character-dependent multi-trend trended continuous trait evolution model. We conclude with some context for the origins of our article and discussion of other possible applications of this powerful approach.

evolutionary biology↗

bioRxiv2026

A portable cortical evoked potential operant conditioning system (C-EPOCS): System development

This study presents customizations and evaluations aimed at adapting the Cortical-Evoked Potential Operant Conditioning System (C-EPOCS) into a portable, user-friendly platform for real-time neurofeedback applications. A primary goal was to simplify the component-heavy setup by integrating electroencephalography (EEG) and electromyography (EMG) data acquisition into a single system--while still supporting cortical and muscle response assessment and real-time feedback. One key limitation of portable biosignal acquisition systems is their typically lower sampling rates (e.g., 300-600 Hz) compared to high-resolution systems (e.g., 3200 Hz), which are commonly used for detecting transient responses such as the H-reflex and M-wave. In a C-EPOCS setup, these responses are useful for determining the target stimulation intensity and minimizing inter-session variability in effective afferent excitation. We evaluated whether lower-resolution EMG signals could still support the generation of H-reflex and M-wave recruitment curves for determining target stimulation intensity. Results showed that while EMG sampled at [~]600 Hz and [~]300 Hz produced greater dispersion in recruitment curve data--particularly at 300 Hz--they still yielded comparable estimates for stimulation intensities that elicit Hmax and Mthreshold, the key parameters for C-EPOCS. Additionally, we demonstrate the feasibility of using an automated response delineation algorithm under these conditions. Despite reduced signal clarity, the algorithm reliably identifies M-wave and H-reflex responses in real time. Overall, this study demonstrates the feasibility of a portable C-EPOCS system capable of providing immediate feedback based on both EMG and EEG signals. It also offers practical recommendations for selecting acquisition hardware to support reliable signal quality, real-time processing, and portability.

neuroscience↗

bioRxiv2025

Soleus H-reflex size versus stimulation rate in the presence of background muscle activity: A methodological study

IntroductionHoffmann reflex (HR) operant conditioning has emerged as an important intervention in neurorehabilitation. During conditioning, the HR is elicited at low rates ([~]0.2 Hz) to avoid the initial reduction in HR size that can occur over repeated stimulation, i.e., rate-dependent depression (RDD), thereby maintaining reflex size. This study investigated the impact of higher stimulation rates on HR size, where a stable, low-level, background electromyographic (EMG) signal is maintained over 225 conditioning trials in each of 30 sessions. A higher rate could shorten session length and/or number. MethodsFifteen healthy participants maintained low background soleus EMG (5-18 {micro}V, [~]1-3% of the maximum stimulation evoked direct muscle (M-wave) EMG response (Mmax) while standing. Soleus HR and M-wave recruitment curves were obtained at rates of 0.2, 1, and 2 Hz, from which Mmax and Hmax were calculated. Seventy-five HR trials (HRT) were collected for each stimulation rate at a target M-wave size ([~]10-20% of Mmax). ResultsThere was no evidence of RDD at higher stimulation rates. In addition, the mean HR over trials was reliable across participants and rates. The Intraclass Correlation Coefficient (ICC) was 0.965 (95%CI:0.915, 0.987). DiscussionThis study shows that H-reflex conditioning might be performed at rates up to 2 Hz with no RDD and with consistent HR values. A faster rate could increase the number of conditioning trials per session, reduce session duration, and/or reduce the number of sessions. It could thereby accelerate the conditioning process and make the process less demanding for participants. SupportNIH Grant P41 EB018783 (Wolpaw), NYS Spinal Cord Injury Research Board C37714GG (Gupta) and C38338GG (Wolpaw), VA SPiRE NCT05880251(Brangaccio), Stratton Veterans Affairs Medical Center.

neuroscience↗

bioRxiv2024

Host population structure and rare dispersal events drive leptospirosis transmission patterns among Rattus norvegicus in Boston, Massachusetts, US

Leptospirosis (caused by pathogenic bacteria in the genus Leptospira) is prevalent worldwide but more common in tropical and subtropical regions. Transmission can occur following direct exposure to infected urine from reservoir hosts, such as rats, or a urine-contaminated environment, which then can serve as an infection source for additional rats and other mammals, including humans. The brown rat, Rattus norvegicus, is an important reservoir of leptospirosis in urban settings. We investigated leptospirosis among brown rats in Boston, Massachusetts and hypothesized that rat dispersal in this urban setting influences the movement, persistence, and diversity of Leptospira. We analyzed DNA from 328 rat kidney samples collected from 17 sites in Boston over a seven-year period (2016-2022); 59 rats representing 12 of 17 sites were positive for Leptospira. We used 21 neutral microsatellite loci to genotype 311 rats and utilized the resulting data to investigate genetic connectivity among sampling sites. We generated whole genome sequences for 28 Leptospira isolates obtained from frozen and fresh tissue from some of the 59 Leptospira-positive rat kidneys. When isolates were not obtained, we attempted Leptospira genomic DNA capture and enrichment, which yielded 14 additional Leptospira genomes from rats. We also generated an enriched Leptospira genome from a 2018 human case in Boston. We found evidence of high genetic structure and limited dispersal among rat populations that is likely influenced by major roads and/or other unknown dispersal barriers, resulting in distinct rat population groups within the city; at certain sites these groups persisted for multiple years. We identified multiple distinct phylogenetic clades of L. interrogans among rats, with specific clades tightly linked to distinct rat populations. This pattern suggests L. interrogans persists in local rat populations and movement of leptospirosis in this urban rat community is driven by rat dispersal. Finally, our genomic analyses of the 2018 human leptospirosis case in Boston suggests a link to rats as the source. These findings will be useful for guiding rat control and human leptospirosis mitigation efforts in this and other urban settings.

molecular biology↗

bioRxiv2022

Outbreak of Highly Pathogenic Avian Influenza H5N1 in New England Seals

The recent incursion of Highly Pathogenic Avian Influenza A (H5N1) virus into North America and subsequent dissemination of virus across the continent, has had significant adverse impacts on domestic poultry, and has led to widespread mortality in many wild bird species. Here we report the recent spillover of H5N1 into marine mammals in the northeastern United States, with associated mortality on a regional scale. This spillover is coincident with a second wave of H5N1 in sympatric wild birds also experiencing regional mortality events. Viral sequences derived from both seal and avian hosts reveal distinct viral genetic differences between the two waves of infection. Spillover into seals was closely related to virus from the second wave, and one of eight seal-derived sequences had the mammalian adaptation PB2 E627K. One-Sentence SummaryAn outbreak of H5N1 in New England seals is the first known population-scale mammalian mortality event associated with the emerging highly pathogenic avian influenza clade 2.3.4.4b.

molecular biology↗

bioRxiv2020

Ferrets not infected by SARS-CoV-2 in a high-exposure domestic setting

Ferrets (Mustela putorius furo) are mustelids of special relevance to laboratory studies of respiratory viruses and have been shown to be susceptible to SARS-CoV-2 infection and onward transmission. Here, we report the results of a natural experiment where 29 ferrets in one home had prolonged, direct contact and constant environmental exposure to two humans with symptomatic COVID-19. We observed no evidence of SARS-CoV-2 transmission from humans to ferrets based on RT-PCR and ELISA. To better understand this discrepancy in experimental and natural infection in ferrets, we compared SARS-CoV-2 sequences from natural and experimental mustelid infections and identified two surface glycoprotein (Spike) mutations associated with mustelids. While we found evidence that ACE2 provides a weak host barrier, one mutation only seen in ferrets is located in the novel S1/S2 cleavage site and is computationally predicted to decrease furin activity. These data support that host factors interacting with the novel S1/S2 cleavage site may be a barrier in ferret SARS-CoV-2 susceptibility and that domestic ferrets are at low risk of natural infection from currently circulating SARS-CoV-2. This may be overcome in laboratory settings using concentrated viral inoculum, but the effects of ferret host-adaptations require additional investigation.

molecular biology↗