Biology subjects

Anis, E.

Publications and source records attributed to Anis, E..

6 recordsLinked to original sources

bioRxiv2026

Within- and between-host dynamics of highly pathogenic avian influenza in domestic birds from Pennsylvania farms and live bird markets

Since late 2021, highly pathogenic avian influenza viruses (HPAI) of the H5 subtype clade 2.3.4.4b have spread across the Americas, devastating wildlife, agricultural animals, and resulting in dozens of human spillovers. National surveillance strategies generally provide only a single representative sequence per poultry outbreak, precluding fine-scale geographic transmission inference or studies of within-outbreak evolution. We produced high-quality deep sequence data from 46 infected Galliformes and Anseriformes sampled from commercial farm and live bird market (LBM) outbreaks in Pennsylvania from 2023-2025. We found that H5N1 viruses were introduced into Pennsylvania at least 68 independent times. We recover independent origins of live bird market outbreaks within the same county 3 weeks apart, and transmission between Pennsylvania LBM and New York commercial birds, suggesting high transmission risk within the Northeast live bird market distribution system. Analyses of within-farm variant populations show frequent variant sharing between samples from the same outbreak, suggesting that variants are propagated among epidemiologically linked infections. We identified 9 known adaptive mutations in these samples, including one instance of PB2 D701N in a LBM chicken sample, suggesting that while rare, concerning mammalian adaptive mutations can be present within these domestic outbreaks. Our data suggest that domestic bird outbreaks support high circulating diversity and wide transmission bottlenecks, increasing the risk of minority variants arising and propagating between infections. These data can help inform targeted biosecurity measures and better quantify the risk of viral adaptation during agricultural outbreaks.

genomics↗

bioRxiv2025

Aggregation-prone alpha-synuclein proteoforms and dysregulated molecular signatures in the vermiform appendix of synucleinopathy patients

Synucleinopathies, including Parkinsons disease, are neurodegenerative diseases characterized by intracellular inclusions containing the amyloidogenic protein alpha-synuclein. While classically considered to be brain disorders, increasing evidence suggests involvement of the gut, with alpha-synuclein aggregates potentially propagating to the brain via the vagus nerve. Evidence also suggests that the vermiform appendix is particularly susceptible to alpha-synuclein aggregation, and appendectomy impacts the onset of Parkinsons disease. However, the mechanisms underlying the aggregation of alpha-synuclein in the vermiform appendix remains poorly understood. To explore this, we assessed aggregation properties in postmortem appendix tissues from healthy controls and synucleinopathy patients using the alpha-synuclein seed amplification assay (alpha-synuclein-SAA) and performed total RNA sequencing alongside differential bisulfite-hybridization-based DNA methylation analysis in the same tissues to investigate the molecular underpinnings. Moreover, we determined alpha-synuclein cleavage patterns by cataloging soluble alpha-synuclein proteoforms from postmortem substantia nigra and post-surgical appendix tissues using top-down mass spectrometry (TD-MS). Alpha-synuclein-SAA was positive in appendix samples for 68.75% of synucleinopathy patients and 6.6% of controls. Genomic profiling revealed dysregulated expression of genes linked to protein folding/degradation, immune/inflammatory responses, and ciliary dynamics in synucleinopathy appendix tissues. TD-MS identified 65 distinct alpha-synuclein proteoforms in the substantia nigra and appendix, with 9 unique to the appendix. Further, in silico modeling revealed higher aggregation propensity of alpha-synuclein proteoforms in the appendix versus substantia nigra. Together, our findings suggest that a tissue environment of alpha-synuclein dysproteostasis in the appendix has the potential to contribute to the development of synucleinopathies. One Sentence SummaryAppendixes from synucleinopathy patients show altered gene expression, unique -syn proteoforms, and higher aggregation propensity than substantia nigra.

neuroscience↗

bioRxiv2025

Whole-genome DNA methylation profiling in COVID-19 positive patients reveals alterations in pathways linked to neurological dysfunction

BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmissible RNA betacoronavirus, causing coronavirus disease-19 (COVID-19). Infection with SARS-CoV-2 can result in a broad spectrum of clinical outcomes, ranging from asymptomatic or mild to a severe, deadly illness. Emerging evidence suggests SARS-CoV-2 affects host gene regulation through epigenetic mechanisms, such as DNA methylation, potentially contributing to immune dysregulation and post-acute sequelae, including neurological and psychiatric disorders. However, the extent and functional relevance of these epigenetic changes remain uncertain. Methods and resultsWe employed whole-genome bisulfite sequencing to profile DNA methylation in peripheral blood from SARS-CoV-2-positive patients across a spectrum of symptom severity, ranging from asymptomatic to severe (n=101), in comparison to SARS-CoV-2-negative individuals (n=105). We observed a widespread hypomethylation in the genomes of infected individuals, which was more pronounced in severe cases. Notably, we identified differentially methylated genes in patients with mild (19 genes), moderate (19 genes), and severe (35 genes) symptoms. These genes included those involved in canonical immune responses as well as known to be linked to neurodegenerative diseases. Subsequent pathway enrichment analysis further supported the significant association between the differentially methylated genes and those implicated in Alzheimers and Parkinsons disease, as well as neuropsychiatric conditions, suggesting potential epigenetic links between acute SARS-CoV-2 infection and long-term neurological outcomes. This is one of the first studies to comprehensively map severity-stratified genome-wide DNA methylation changes in COVID-19 patients. ConclusionOur findings underscore the potential importance of epigenetic regulation in the acute responses to SARS-CoV-2 infection and highlight an overlap with epigenetic mechanisms relevant for neuropsychiatric disease processes.

neuroscience↗

bioRxiv2025

A Wildlife Health Outbreak Response Table-top Exercise for Pandemic Preparedness Planning

Zoonotic diseases have received significantly more attention over the last few decades, emerging with increasing frequency and causing the majority of notable disease outbreaks in this century, including the COVID-19 pandemic. As human activities and shifting climate patterns induce changes in the environment that alter habitat and range of reservoir species, the potential for human and animal interactions will increase and enhance the opportunity for spillover. Thus, any emergency response preparedness planning must take into account the function and coordination of agencies across the sectors of human, animal and environmental health. Within the Commonwealth of Pennsylvania a table-top exercise was performed to evaluate a multi-agency response during a hypothetical zoonotic disease investigation. The exercise was evaluated by the participants to gain feedback on the overall process and lessons learned. Here, we describe the tabletop exercise scenario and the insights gained. We found that differences in operational structure create challenges for interdepartmental communication and in the ability to resource a coordinated response, highlighting opportunities to develop infrastructure that will facilitate future actions. A set of recommendations are outlined that may enhance cross-agency activities and promote more effective and efficient emergency response.

scientific communication and education↗

bioRxiv2023

Metagenomics for pathogen detection during a wildlife mortality event in songbirds

Mass mortality events in wildlife can be indications of an emerging infectious disease. During the spring and summer of 2021, hundreds of dead passerines were reported across the eastern US. Birds exhibited a range of clinical signs including swollen conjunctiva, ocular discharge, ataxia, and nystagmus. As part of the diagnostic investigation, high-throughput metagenomic next-generation sequencing was performed across three molecular laboratories on samples from affected birds. Many potentially pathogenic microbes were detected, with bacteria comprising the largest proportion; however, no singular agent was consistently identified, with many of the detected microbes also found in unaffected (control) birds, and thus considered to be subclinical infections. Congruent results across laboratories have helped drive further investigation into alternative causes including environmental contaminants and nutritional deficiencies. This work highlights the utility of metagenomic approaches in investigations of emerging diseases and provides a framework for future wildlife mortality events. Article Summary LineThe causative agent of a mass mortality event in passerines remains inconclusive after metagenomic high-throughput sequencing with results prompting further investigation into non-pathogenic causes.

genomics↗

bioRxiv2022

Bat Red Blood Cells express Nucleic Acid Sensing Receptors and bind RNA and DNA

Red blood cells (RBCs) demonstrate immunomodulatory capabilities through the expression of nucleic acid sensors. However, little is known about bat RBCs, and no studies have examined the immune function of bat erythrocytes. Here we show that bat RBCs express the nucleic acid-sensing Toll-like receptors TLR7 and TLR9 and bind the nucleic acid ligands, single-stranded RNA, and CpG DNA. Collectively, these data suggest that, like human RBCs, bat erythrocytes possess immune function and may be reservoirs for nucleic acids. These findings provide unique insight into bat immunity and may uncover potential mechanisms by which virulent pathogens in humans are concealed in bats.

immunology↗