Biology subjects

Turner, H.

Publications and source records attributed to Turner, H..

6 recordsLinked to original sources

bioRxiv2025

Computational analysis of therapeutic potential for simplified Piper. spp- derived medicinal mixtures in anxiety, sleep, pain and seizure.

Phytomedicines have played a vital role in traditional medical systems globally, particularly in providing culturally relevant and accessible healthcare solutions. Piper methysticum, known as Kava, is a traditional Pacific Island phytomedicine with clinically validated anxiolytic properties, primarily attributed to its Kavalactones. However, the biogeographically restricted distribution of Piper methysticum and the ecological and cultural concerns surrounding its widespread adoption highlight the need to explore alternative sources within the Piper genus. This study investigates whether other species within the Piper genus, used phytomedically in non-Pacific contexts, exhibit similar therapeutic efficacy for anxiety, stress, and related disorders including Post-Traumatic Stress Disorder (PTSD). We employed a computational approach utilizing a novel data platform of non-Western phytomedical pharmacopeias to analyze the secondary metabolomes of various Piper species. Network analysis and multidimensional data projections were used to compare the chemical composition and therapeutic indications of these species with those of Piper methysticum. Our findings suggest that while Kavalactones are predominantly unique to Piper methysticum, other Piper species also contain bioactive compounds associated with anxiolytic and stress-relieving effects. These results provide insight into the potential for culturally and biogeographically contextualized approaches to PTSD treatment, beyond the exclusive use of Kava, and lay the groundwork for future research into alternative phytomedicinal therapies within the Piper genus.

pharmacology and toxicology↗

bioRxiv2025

A pathway to next-generation mast cell stabilizers identified through the novel Phytomedical Analytics for Research Optimization at Scale data platform.

Mast cell stabilizers (MCS) have the potential to address unmet therapeutic need in allergy and inflammation management. MCS chronically suppress all arms of the pro-inflammatory mast cell response to stimulation (e.g., histamine, protease, lipid mediators, cytokines, chemokines). They may therefore outperform approaches such as H1, H2 and H4 inhibitors (antihistamines) which block only the acute histamine release by mast cells and leave the rest of the functional response untouched. Despite their potential, current MCS (e.g., cromolyn sodium, Tranilast, nedocromil) in clinical use are hindered by poor bioavailability, frequent dosing, long lags to onset of relief, and enigmatic mechanisms of action. MCS have their origins in phytomedicine: cromolyn sodium is the longest standing drug in the class and is a derivatized form of Khellin from Ammi visnaga, used as an anti-inflammatory. Other phytopharmacopeias may offer candidate next generation MCS (ngMCS) and in this study we hypothesized that a coupled pharmacoanalytic and in vitro pharmacology approach could be used to identify, prioritize and derisk additional candidate MCS from phytomedical sources for later pre-clinical and clinical evaluation. Here, we report a novel data analytics workflow starting with a newly developed phytopharmacopeia data platform with >3.5B linkage pathways (country [->] medical system [->] formulation [->] indication [->] ingredient organism [->] chemical component [->] other parameters), covering 22 M sq. miles of biogeography and historical and contemporary timeframes. Additional data layers include druggability indices, target and pathway analyses. The current study validates a subset of candidate phytomedical ngMCS using in silico workflow and in vitro pharmacology, and develops a new harmonic mean-based MCS score for further streamlining of the candidate prioritization process. This proof-of-concept study may have particular relevance for complex presentations such as Mast Cell Activation Syndrome (MCAS) where ngMCS may outperform current management approaches.

immunology↗

bioRxiv2024

Multiwell-based G0-PCC assay for radiation biodosimetry

In cytogenetic biodosimetry, assessing radiation exposure typically requires over 48 hours for cells to reach mitosis, significantly delaying the administration of crucial radiation countermeasures needed within the first 24 hours post-exposure. To improve medical response times, we incorporated the G0-Premature Chromosome Condensation (G0-PCC) technique with the Rapid Automated Biodosimetry Tool-II (RABiT-II), creating a faster alternative for large-scale radiation emergencies. Our findings revealed that using a lower concentration of Calyculin A (Cal A) than recommended effectively increased the yield of highly-condensed G0-PCC cells (hPCC). However, integrating recombinant CDK1/Cyclin B kinase, vital for chromosome condensation, proved challenging due to the properties of these proteins affecting interactions with cellular membranes. Interestingly, Cal A alone was capable of inducing chromosome compaction in some G0 cells even in the absence of mitotic kinases, although these chromosomes displayed atypical morphologies. This suggests that Cal A mechanism for compacting G0 chromatin may differ from condensation driven by mitotic kinases. Additionally, we observed a correlation between radiation dose and extent of hPCC chromosome fragmentation, which allowed us to automate radiation damage quantification using a Convolutional Neural Network (CNN). Our method can address the need for a same-day cytogenetic biodosimetry test in radiation emergency situations.

cell biology↗

bioRxiv2021

Requirement for an Otopetrin-Like protein for acid taste in Drosophila

Many of the Drosophila receptors required for bitter, sugar and other tastes have been identified. However, the receptor required for the taste of acid has been elusive. In Drosophila, the major families of taste receptors, such as "Gustatory Receptors" and "Ionotropic Receptors" are unrelated to taste receptors in mammals. Previous work indicated that members of these major families do not appear to be broadly required acid sensors. Here, to identify the enigmatic acid taste receptor, we interrogated three genes encoding proteins distantly related the mammalian Otopertrin1 proton channel. We found that RNAi knockdown or mutation of Otopetrin-Like A (OtopLA) by CRISPR/Cas9, severely impairs the behavioral rejection of sugary foods laced with HCl or carboxylic acids. Mutation of OtopLA also greatly reduces acid-induced action potentials. We identified an isoform of OtopLA that was expressed in the proboscis and was sufficient to restore acid sensitivity to OtopLA mutant flies. OtopLA functioned in acid taste in a subset of bitter-activated gustatory receptor neurons that senses protons. This work highlights an unusual functional conservation of a receptor required for a taste modality in flies and mammals.

neuroscience↗

bioRxiv2021

A Non-redundant Role for T cell-derived IL-22 in Antibacterial Defense of Colonic Crypts

IL-22 is a key cytokine in immune defense against pathogens at barrier sites. In response to enteric attaching and effacing bacteria, IL-22 produced by type 3 innate lymphoid cells (ILC3s) is thought to be important early for induction of antimicrobial peptides (AMPs) that protect intestinal epithelial cells (IECs) in advance of T cell-derived IL-22 that arises later. Yet, the basis for a requirement for both innate and adaptive IL-22-producing immune cells in protecting the intestinal mucosa is unknown. Here, using novel mice that both report IL-22 expression and can be targeted for its lineage-specific deletion, we show that mice with deficiency of IL-22 targeted to innate immune cells, including ILC3s, have impaired STAT3 activation of surface colonic IECs colonized by bacteria early in infection. In contrast, mice with IL-22 deficiency limited to T cells have complete loss of STAT3 activation in IECs lining colonic crypts and fail to protect the crypts from bacterial invasion late despite ongoing production of IL-22 from ILC3s. T cell-derived IL-22 is required for upregulation of many host-protective genes by crypt IECs, including those encoding AMPs, neutrophil-recruiting chemokines, and mucins and mucin-related molecules, while also restricting pro-inflammatory genes downstream of IFN{gamma} and TNF signals. Thus, T cell-derived IL-22 is indispensable for antibacterial defense and damage control of intestinal crypts.

immunology↗

bioRxiv2021

A de novo paradigm for male infertility

IntroductionDe novo mutations (DNMs) are known to play a prominent role in sporadic disorders with reduced fitness1. We hypothesize that DNMs play an important role in male infertility and explain a significant fraction of the genetic causes of this understudied disorder. To test this hypothesis, we performed trio-based exome-sequencing in a unique cohort of 185 infertile males and their unaffected parents. Following a systematic analysis, 29 of 145 rare protein altering DNMs were classified as possibly causative of the male infertility phenotype. We observed a significant enrichment of Loss-of-Function (LoF) DNMs in LoF-intolerant genes (p-value=1.00x10-5) as well as predicted pathogenic missense DNMs in missense-intolerant genes (p-value=5.01x10-4). One DNM gene identified, RBM5, is an essential regulator of male germ cell pre-mRNA splicing2. In a follow-up study, 5 rare pathogenic missense mutations affecting this gene were observed in a cohort of 2,279 infertile patients, with no such mutations found in a cohort of 5,784 fertile men (p-value=0.009). Our results provide the first evidence for the role of DNMs in severe male infertility and point to many new candidate genes affecting fertility.

genetics↗