Biology subjects

Rich, C.

Publications and source records attributed to Rich, C..

4 recordsLinked to original sources

bioRxiv2024

Effects of Inosine-5'-Monophosphate Dehydrogenase (IMPDH/GuaB) Inhibitors on Borrelia burgdorferi Growth in Standard and Modified Culture Conditions

Borrelia burgdorferis Inosine-5-Monophosphate dehydrogenase (IMPDH, GuaB) is a potential therapeutic target. GuaB is not needed for B. burgdorferi survival and replication in standard growth media, therefore our ability to test novel drugs against the whole organism is limited to tests using mammalian hosts. Modifications to standard culture conditions that can induce borreliastatic effects of GuaB inhibitors will enhance our ability to evaluate these inhibitors. This study aimed to evaluate basic modifications to standard growth media that can achieve this objective. Effects of GuaB inhibitors (mycophenolic acid, 6-Chloropurine) were compared in standard Barbour-Stoenner-Kelly-II (BSK-II) medium with BSK-II modified to 60% concentration rabbit serum, using B. burgdorferi 5A1. Effects were also evaluated with another BSK-II modification with the direct supplementation of hypoxanthine, adenine, and nicotinamide (75 M each). In standard BSK-II, neither mycophenolic acid nor 6-Chloropurine riboside affected B. burgdorferi growth. An ANOVA showed significant, dose-dependent interactions between culture condition and treatment considering modified growth conditions (F = 4.471, P = 0.001). Mycophenolic acid at 250 M reduced replication by 48 and 50% (P < 0.001 each). 6-Chloropurine riboside was more effective in both conditions at 250 M, reducing growth by 64 and 65% (P < 0.001 each). Effects of GuaB inhibitors were shown against whole organism Borrelia burgdorferi for the first time. Modification of BSK-II medium with physiologically relevant levels of mammalian serum supports replication and induces GuaB inhibitor-mediated suppression of replication. Effects of 6-Chloropurine riboside were demonstrated for the first time, indicating that B. burgdorferi can salvage and phosphorylate these analogue purine derivatives. These molecules can be manipulated to better inhibit replication. Optimisation will allow the assessment of novel Borrelia-specific IMPDH inhibitor molecules in culture for Lyme disease interventions. HighlightsO_LIEffects of IMPDH inhibitors are shown against whole organism Borrelia burgdorferi for the first time. C_LIO_LIModification of BSK-II medium with physiologically relevant levels of mammalian serum supports replication and induces IMPDH inhibitor-mediated suppression of replication. C_LIO_LIEffects of 6-Chloropurine riboside are demonstrated for the first time, indicating that B. burgdorferi can salvage and phosphorylate these analogue purine derivatives. These molecules can be manipulated to better inhibit replication. C_LIO_LIOptimisation of modified BSK-II will allow the assessment of novel Borrelia-specific IMPDH inhibitor molecules in culture for Lyme disease interventions. C_LI

microbiology↗

bioRxiv2021

Diversity and evolution of amphibian pupil shapes

Pupil constriction has important functional consequences for animal vision, yet the evolutionary mechanisms underlying diverse pupil sizes and shapes, often among animals that occupy optically similar environments, are poorly understood. We aimed to quantify the diversity and evolution of pupil shapes among amphibians and test for potential correlations to ecology based on functional hypotheses. Using photographs, we surveyed pupil shape and the orientation of the constricted pupil across adults of 1293 amphibian species, 72 families, and 3 orders, and additionally for larval life stages for all families of frogs and salamanders with a biphasic ontogeny. Pupil shape is exceptionally diverse in amphibians with evolutionary transitions throughout the amphibian tree of life. For amphibians with a biphasic life history, we found that pupils change in many species that occupy distinct habitats before and after metamorphosis. Finally, we found that non-elongated (round or diamond) constricted pupils were correlated with species inhabiting consistently dim light environments (burrowing and aquatic species) and that elongated pupils (vertical and horizontal) were more common in species with larger absolute eye sizes. We propose that amphibians provide a valuable group within which to explore the anatomical, physiological, optical, and ecological mechanisms underlying the evolution of pupil shape.

evolutionary biology↗

bioRxiv2018

Discordant perturbations of transcriptome and epigenome landscapes highlight dual roles of proinflammatory players in normal and IL1B-compromised OPC maturation trajectory in a prenatal model of diffuse white matter injury

Inflammatory insults accompanying prematurity provokes diffuse white matter injury (DWMI) which is associated with increased risk of neurodevelopmental disorders: pre-term infants have a 10 to 18-fold increased risk of developing autism spectrum disorders, compared to term infants. DWMI is due to maturation arrest in oligodendrocyte precursor cells (OPCs). Using integrated genome-wide approaches in a validated mouse perinatal model of DWMI, induced by systemic- and neuro-inflammation based on repeated interleukin-1B administrations, we show that neuroinflammation induces limited epigenomic disturbances in OPCs. In contrast, we unravel marked transcriptomic alterations of genes of the immune/inflammatory pathways, which are expressed in unstressed OPCs and physiologically downregulated along OPC maturation. Consistently, we observe that transcription factors of the inflammatory pathways occupy DNA both in unstressed and inflamed OPCs. Thus, rather than altering genome-wide chromatin accessibility, neuroinflammation takes advantage of open chromatin regions and deeply counteracts the stage-dependent downregulation of these active transcriptional programs. Therefore, our study opens new avenues for the future development of targeted approaches to protect preterm brains. Highlights{circ} Limited epigenomic impact of inflammation on OPC maturation blockade {circ}Major transcriptomic disturbances take advantage of a primed epigenetic landscape {circ}Proinflammatory genes are active in OPCs and downregulated upon maturation {circ}Neuroinflammation counteracts both this downregulation and maturation in OPCs

developmental biology↗

bioRxiv2018

Cell type identity determines transcriptomic immune responses in Arabidopsis thaliana roots.

Root pathogens are a major threat in global crop production and protection strategies are required to sustainably enhance the efficiency of root immunity. Our understanding of root immunity is still limited relative to our knowledge of immune responses in leaves. In an effort to reveal the organisation of immunity in roots, we undertook a cell type-specific transcriptome analysis to identify gene networks activated in epidermis, cortex and pericycle cells of Arabidopsis roots upon treatment with two immunity elicitors, the bacterial microbe-associated molecular pattern flagellin, and the endogenous damage-associated molecular pattern Pep1. Our analyses revealed that both elicitors induced immunity gene networks in a cell type-specific manner. Interestingly, both elicitors did not alter cell identity-determining gene networks. Using sophisticated paired motif promoter analyses, we identified key transcription factor pairs involved in the regulation of cell type-specific immunity networks. In addition, our data show that cell identity networks integrate with cell immunity networks to activate cell type-specific immune response according to the functional capabilities of each cell type.\n\nMaterial Distribution FootnoteThe author responsible for distribution of materials integral to the findings presented in this article in accordance with the policy described in the Instructions for Authors (www.plantcell.org) is: Patrick Schafer (p.schafer@warwick.ac.uk).

plant biology↗