Biology subjects

Walker, T. D.

Publications and source records attributed to Walker, T. D..

6 recordsLinked to original sources

bioRxiv2026

Genomic selection validated across two generations of loblolly pine breeding

This study evaluated the effectiveness of genomic selection (GS) in loblolly pine (Pinus taeda) using a two-generation closed breeding population and a genetically diverse Mainline population. Single-step genomic best linear unbiased prediction (ssGBLUP) models were used to include all phenotypic, genotypic, and pedigree information. Prediction accuracies of genomic estimated breeding values reached up to 0.70 for stem volume and stem straightness. Prediction accuracy showed a strong linear relationship with mean relatedness between training and validation populations (r > 0.92). Adjusting the scaling between genomic and pedigree relationship matrices improved model stability, increased prediction accuracy, and reduced bias in genomic estimated breeding values. Estimates of heritability and variance components from ssGBLUP were consistent with pedigree-based models, particularly when genomic relationships were properly scaled. Genomic selection had approximately 50% more genetic gain per year relative to conventional selection. Overall, these results demonstrate that GS can be effectively integrated into operational conifer breeding programs, given sustained investment in large, well-connected training populations with high-quality phenotypic data. We also outline the planned implementation of GS in the North Carolina State University Cooperative Tree Improvement Program to increase genetic gain.

genetics↗

bioRxiv2025

IFI16 senses and protects stalled replication forks

Replication stress is a key driver of DNA damage and genome instability. Replication stress-induced fork remodelling generates a new DNA end that is vulnerable to the action of nucleases, and which is protected by a range of factors including the canonical tumour suppressors BRCA1 and BRCA2. Here we report that replication stress drives elevated production of cytokines and chemokines in the absence of DNA damage. The DNA sensor IFI16 binds nascent DNA at stalled replication forks and signals via the DNA sensing adaptor STING, to induce the activation of NF-{kappa}B and the production of pro-inflammatory cytokines in response to replication stress. IFI16 also acts directly at stalled replication forks to protect nascent DNA from degradation by the nucleases MRE11 and DNA2. Furthermore, IFI16 is required for the interferon-mediated rescue of fork protection in BRCA-deficient cells, highlighting the critical role of IFI16 in the cross-talk between innate immunity and fork protection during replication stress. HighlightsO_LIReplication stress induces an early innate immune response, which is dependent on the DNA sensing factors IFI16 and STING, but not cGAS C_LIO_LIIFI16 binds directly to nascent DNA at stalled replication forks C_LIO_LIIFI16 prevents nucleolytic degradation of reversed forks C_LIO_LIIFI16 is required for interferon-mediated fork protection in BRCA-deficient cells C_LI

cancer biology↗

bioRxiv2025

Microbial metabolism of food allergens determines the severity of IgE-mediated anaphylaxis

Anaphylaxis is an acute, potentially life-threatening reaction, often triggered by foods and largely mediated by IgE. Critically important to anaphylaxis are the factors that modulate its severity. The human microbiota is known to influence oral tolerance, but the microbial mechanisms directly involved in IgE-mediated anaphylaxis remain unknown. Here, we demonstrate that human saliva and jejunum harbor peanut-degrading bacteria that metabolize immunodominant allergens (Ara h 1 and 2) and alter IgE-binding. Additionally, we provide in vivo evidence that oral bacteria metabolize peanut allergens, influencing systemic allergen exposure and anaphylaxis severity. Finally, in clinical studies, we observe that common peanut-degrading bacteria, such as Rothia, from the oral cavity, are more abundant in peanut-allergic patients who exhibit better tolerance to allergen exposure. Altogether, these results demonstrate that human microbiota modulates IgE-mediated reactions through allergen metabolism. We reveal a novel microbial mechanism with potential to prevent, or reduce, the severity of IgE-mediated anaphylaxis.

immunology↗

bioRxiv2023

A Distinct Phenotype of Polarized Memory B cell holds IgE Memory

Allergen-specific IgE antibodies mediate allergic pathology in diseases such as allergic rhinitis and food allergy. Memory B cells (MBCs) contribute to circulating IgE by regenerating IgE-producing plasma cells upon allergen encounter. We report a population of type 2 polarized MBCs defined as CD23hi, IL-4Rhi, CD32low at the transcriptional and surface protein levels. These "MBC2s" are enriched in IgG1 and IgG4-expressing cells, while constitutively expressing germline transcripts for IgE. Allergen-specific B cells from patients with allergic rhinitis and food allergy were enriched in MBC2s. MBC2s generated allergen specific-IgE during sublingual immunotherapy, thereby identifying these cells as the primary reservoir of IgE. The identification of MBC2s provides insights into the maintenance of IgE memory, which is detrimental in allergic diseases, but which could be beneficial in protection against venoms and helminths. One-Sentence SummaryIdentification of a novel memory B cell subset which holds allergen specific IgE memory.

immunology↗

bioRxiv2020

Interrupting reactivation of immunological memory reprograms allergy and averts anaphylaxis

IgE production against innocuous antigens can lead to life-threatening reactions such as anaphylaxis. While IgE levels drastically decline with strict allergen avoidance, the ability to regenerate IgE can persist for a lifetime, as is the case for peanut allergy. The mechanism by which IgE regenerates remains unresolved. A novel culture system and application of single-cell RNA-sequencing, elucidated the transcriptomic signature of human peanut-reactive B and T cells and revealed IL-4/IL-13 as a signaling pathway critical for the IgE recall response. Indeed, interruption of this pathway not only prevented IgE production and anaphylaxis, but also reprogrammed the pathogenic response against peanut. This investigation advances our understanding of the mechanism that regenerates IgE in food allergy and spotlights IL-4/IL-13 blockade as a therapeutic with disease-transforming potential. One Sentence SummarySingle-cell transcriptomics of allergic memory responses reveals how to teach the immune system to forget.

immunology↗

bioRxiv2019

Microbial regulation of enteric eosinophils and its impact on tissue remodeling and Th2 immunity

Eosinophils have emerged as multifaceted cells that contribute to tissue homeostasis. However, the factors that control their frequency and function at mucosal sites remain unclear. Here, we investigated the role of the microbiota in regulating enteric eosinophils. We found that small intestinal (SI) eosinophilia was significantly greater in germ-free (GF) mice compared to specific pathogen free (SPF) controls. This phenomenon was associated with enteric overexpression of signals that mediate attraction, retention and survival of eosinophils, and was reversed by colonization. Additionally, we generated a novel strain of eosinophil-deficient GF mice. These mice displayed intestinal fibrosis and were less prone to allergic sensitization as compared to GF controls. Overall, our study demonstrates that commensal microbes regulate intestinal eosinophil frequency and function, which impacts tissue repair and allergic sensitization to food antigens. These data support a critical interplay between the commensal microbiota and intestinal eosinophils in shaping homeostatic, innate and adaptive immune processes in health and disease.

immunology↗