Biology subjects

Woods, P.

Publications and source records attributed to Woods, P..

5 recordsLinked to original sources

bioRxiv2026

Basal forebrain projections to the lateral habenula sex-dependently regulate ethanol and sucrose consumption

BackgroundCompulsive alcohol use despite negative outcomes is a defining characteristic of alcohol use disorder. Rats exposed to long-term intermittent alcohol access (IAA) demonstrate sustained motivation for ethanol despite presence of the bitter additive quinine, offering a useful preclinical model of compulsive alcohol use. However, little is known about the role of habenular circuitry in the development of this phenotype. Here, we employed chemogenetic techniques targeting basal forebrain (BF) input to the lateral habenula (LHb) to probe the involvement of this neural circuitry in aversion-resistant alcohol consumption. MethodsFollowing long-term IAA or control conditions, male and female Long-Evans rats underwent surgery for the expression of designer receptors in BF-to-LHb projections. We then excited this pathway in rats with IAA history, or inhibited this pathway in rats with more limited ethanol history, before testing consumption of unadulterated and quinine-adulterated ethanol as well as unadulterated and quinine-adulterated sucrose. ResultsLong-term IAA elevated ethanol drinking in all rats and aversion-resistant ethanol preference in males. Chemogenetic activation of BF-to-LHb neurons in rats with IAA history produced different effects in males and females: excitation enhanced ethanol intake in females, but reduced ethanol preference in males, regardless of quinine adulteration. Activation also led to a relative insensitivity to quinine-adulteration of sucrose when compared to controls, particularly in females. Chemogenetic inhibition in rats with limited prior ethanol exposure did not alter either ethanol or sucrose consumption with or without quinine. ConclusionsOur results suggest a differential role for BF-to-LHb circuitry in ethanol drinking based on sex, and a potential role for this circuitry in the sensitivity to quinine in the context of natural reward consumption.

neuroscience↗

bioRxiv2025

A panel of near-isogenic lines derived from locally adapted populations of a wild plant: A powerful tool for dissecting additive and non-additive effects on ecologically important traits

Identifying and estimating the effects of loci contributing to natural variation in ecologically important traits can be hampered by quantitative inheritance, dominance, epistasis, and environmentally dependent trait expression. Here we announce the availability of germplasm and sequence data for a reciprocal panel of near-isogenic lines (NILs) derived from locally adapted natural populations of Arabidopsis thaliana, for investigating the genetic basis of ecologically important traits. We created a panel of 54 NILs and performed whole genome sequencing to precisely locate introgression segments(s) in each NIL. Deep sequencing largely confirmed prior knowledge of NIL genotypes but also identified multiple novel small introgressions and regions of residual heterozygosity. To illustrate the utility of this panel, we identified genomic regions underlying ecotypic differences in flowering time in a laboratory common garden experiment. We detected strong additive effects on flowering time in multiple NILs with segments at the top of chromosome 5 implicating the floral regulator FLC, as expected based on previous quantitative trait locus studies. We also detected novel and complex contributions to ecotypic differences in flowering time, only visible in the NILs, suggesting the possibility of epistasis. Our results highlight the utility of this panel for dissecting the genetic architecture of ecologically important traits, including the future potential for fine mapping of additive effects and testing for epistasis and linkage using NILs derived from the panel. This panel can be used by any member of the research community to investigate any of a broad suite of traits for which the parents differ.

evolutionary biology↗

bioRxiv2025

The Ambiguous Genetic Code of Methanogenic Archaea that Grow on Methylamines

Natural genetic code expansion is a phenomenon wherein an additional amino acid is encoded by a stop codon. These non-standard amino acids are beneficial as they facilitate novel biochemical reactions. However, code expansion leads to ambiguity at the recoded stop codon, which can either be read through or terminated. Pyrrolysine (Pyl) is encoded by the amber codon (TAG/UAG) and is widespread in archaea, where it is required for methylamine-mediated methanogenesis, an environmentally important metabolism. Mechanisms to conditionally suppress the amber stop codon for Pyl installation during protein synthesis have not been identified. Using the model methanogen, Methanosarcina acetivorans, we demonstrate that Pyl-encoding archaea maintain an ambiguous genetic code wherein UAG encodes dual meaning as stop and Pyl. Our data suggest that expression of Pyl biosynthesis and incorporation genes is tuned to the cellular demand for Pyl, which allows these archaea to navigate ambiguous stop decoding in response to environmental cues.

microbiology↗

bioRxiv2025

Museum genomics reveals temporal genetic stasis and global genetic diversity in Arabidopsis thaliana

Global patterns of population genetic variation through time offer a window into evolutionary processes that maintain diversity. Over time, lineages may expand or contract their distribution, causing turnover in population genetic composition. At individual loci, migration, drift, and selection (among other processes) may affect allele frequencies. Museum specimens of widely distributed species offer a unique window into the genetics of understudied populations and changes over time. Here, we sequenced genomes of 130 herbarium specimens and 91 new field collections of Arabidopsis thaliana and combined these with published genomes. We sought a broader view of genomic diversity across the species, and to test if population genomic composition is changing through time. We documented extensive and previously uncharacterized diversity in a range of populations in Africa, populations that are under threat from anthropogenic climate change. Through time, we did not find dramatic changes in genomic composition of populations. Instead, we found a pattern of genetic change every 100 years of the same magnitude seen when comparing Eurasian populations that are 185 km apart, potentially due to a combination of drift and changing selection. We found only mixed signals of polygenic adaptation at phenology and physiology QTL. We did find that genes conserved across eudicots show altered levels of directional allele frequency change, potentially due to variable purifying and background selection. Our study highlights how museum specimens can reveal new dimensions of population diversity and show how wild populations are evolving in recent history.

evolutionary biology↗

bioRxiv2020

Proteoglycan 4 (PRG4) expression and functionin dry eye associated inflammation

PurposeDry eye disease (DED) affects hundreds of millions worldwide. Proteoglycan 4 (PRG4) has been shown to improve signs and symptoms of DED in humans. The objectives of this study were to characterize endogenous PRG4 expression by telomerase-immortalized human corneal epithelial (hTCEpi) cells, examine how exogenous recombinant human PRG4 (rhPRG4) modulates cytokine and chemokine secretion in response to TNF and IL-1{beta}, explore rhPRG4 as a potential substrate and/or inhibitor of MMP-9, and to understand how experimental dry (EDE) in mice affects PRG4 expression. MethodsPRG4 secretion was quantified by Western blotting and PRG4 expression by immunocytochemistry. Cytokine/chemokine release was measured by ELISA, and MMP-9 inhibition was quantified using an MMP-9 inhibitor kit. EDE was induced in mice, and PRG4 was visualized by immunohistochemistry in the cornea and Western blotting in lacrimal gland lysate. ResultshTCEpi cells synthesize and secrete PRG4 in vitro, which is inhibited by TNF and IL-1{beta}. TNF and IL-1{beta} significantly increased secretion of cytokine IL-6 and chemokines IL-8, IP-10, RANTES, and ENA-78, and several of these chemokines were downregulated after cotreatment with rhPRG4. Fluorescently-labelled rhPRG4 was internalized by hTCEpi cells. rhPRG4 was not digested by MMP-9 and inhibited in vitro activity of exogenous MMP-9 both in solution and in the presence of human tears. Finally, EDE decreased corneal and lacrimal gland expression of PRG4. ConclusionsThese results demonstrate rhPRG4s anti-inflammatory properties in the corneal epithelium and its contribution to ocular surface homeostasis, furthering our understanding of PRG4s immunomodulatory properties in the context of DED inflammation.

biochemistry↗