Biology subjects

Thomas, A. E.

Publications and source records attributed to Thomas, A. E..

4 recordsLinked to original sources

bioRxiv2024

Retinal microglia-derived S100A9 incite NLRP3 inflammasome in a Western diet fed Ossabaw pig retina

PurposeWe established S100A9 as a myeloid-derived damage-associated molecular pattern (DAMPs) protein associated with increasing severity of diabetic retinopathy (DR) in type 2 diabetic subjects. The present study investigates the retinal localization, expression, and mechanisms of action for S100A9 in the young obese Ossabaw pig retina. MethodsRetinae from Ossabaw pigs fed a Western diet for 10 weeks were evaluated for S100 and inflammatory mediator expression using quantitative PCR and Western blot. Double immunohistochemistry was performed to identify the cellular sources of S100A9 in the pig retina. Primary pig retinal microglial cells (pMicroglia) were examined for S100A9 production. S100A9-induced responses were also investigated, and inhibitor studies elucidated the mechanism of action via the NLRP3 inflammasome. A specific inhibitor, Paquinimod (ABR-215757), was administered in vitro to assess the rescue of S100A9-induced NLRP3 inflammasome activation in pMicroglia. ResultsThe expression of the S100 family in the obese Ossabaw pig retina showed a significant elevation of S100A9, consistent with increased levels of circulating S100A9. Moreover, the retina had elevated levels of inflammatory mediators IL-6, IL-8, MCP-1, IL-1{beta} and NLRP3. Retinal microglia in obese Ossabaw were activated and accompanied by an increased expression of intracellular S100A9. pMicroglia isolated from pig retina transformed from ramified to amoeboid state when activated with LPS and produced high S100A9 transcript and protein levels. The S100A9 protein, in turn, further activated pMicroglia by heightened production of S100A9 transcripts and secretion of pro-inflammatory IL-1{beta} protein. Inhibition of TLR4 with TAK242 and NLRP3 with MCC950 attenuated the production of IL-1{beta} during S100A9 stimulus. Finally, pre-treatment with Paquinimod successfully reduced S100A9-driven increases of glycosylated-TLR4, NLRP3, ASC, Caspase-1, and IL-1{beta} production. ConclusionWe demonstrated that microglial-derived S100A9 perpetuates pro-inflammatory responses via the NLRP3 inflammasome in the retina of young Western-diet-fed Ossabaw pigs exhibiting diabetic retinopathy.

neuroscience↗

bioRxiv2024

Early transatlantic movement of horses and donkeys at Jamestown

Domestic horses and donkeys played a key role in the initial colonization of the Atlantic seaboard of the Americas, a process partially chronicled by historical records. While Spanish colonists brought horses to the Caribbean and southern latitudes earlier, the transport of domestic horses to the English colony at Jamestown, Virginia in 1606 was among the first dispersals to the eastern seaboard. Archaeozoological analysis, isotope analysis, and radiocarbon dating of identifiable domestic equid remains from two contexts associated with the initial occupation of Jamestown demonstrate intense processing and consumption of the first Jamestown horses during the "Starving Time" winter of 1609, while paleopathological data show evidence of their use in transport. Osteological, genetic, and isotopic study of these equid remains reveal the presence of at least one adult domestic donkey with mixed European and West African ancestry, possibly supplied through undocumented exchange during a trans-Atlantic stopover. These results reveal the importance of equids in the survival of early European settlers and the global connectivity of early trans-Atlantic exchange in horses and donkeys, showing Caribbean and African links in the founding livestock populations and pointing towards an important and ecologically-anchored role for donkeys in the early colonial lifeways along the Eastern seaboard.

genetics↗

bioRxiv2023

PBRM-1/PBAF-regulated genes in a multipotent progenitor

The Caenorhabditis elegans somatic gonadal precursors (SGPs) are multipotent progenitors that generate all somatic cells of the adult reproductive system. The two SGPs originate in the mesodermal layer and are born through a division that produces one SGP and one head mesodermal cell (hmc). One hmc terminally differentiates and the other dies by programmed cell death. The PBAF chromatin remodeling complex promotes the multipotent SGP fate. Complete loss of PBAF causes lethality, so we used a combination of Cre/lox recombination and GFP nanobody-directed protein degradation to eliminate PBRM-1, the signature subunit of the PBAF complex, from 83 mesodermal cells, including SGPs, body muscles, and the hmc. We used RNA sequencing to identify genes acting downstream of PBAF in these cells and identified 1955 transcripts that were significantly differentially expressed between pbrm-1(-) and pbrm-1(+) in the mesoderm of L1 larvae. We found that genes involved in muscle cell function were overrepresented; most of these genes had lower expression in the absence of PBRM-1, suggesting that PBAF promotes muscle differentiation. Among the differentially expressed genes were 125 genes that are normally expressed at higher levels in SGP vs. hmc and positively regulated by pbrm-1 and 53 that are normally expressed at higher levels in hmc vs. SGP and are negatively regulated by pbrm-1; these are candidate regulators of the SGP/hmc fate decision. We validated one candidate gene using a fluorescent reporter; the hsp-12.3 reporter was derepressed in SGPs in pbrm-1 mutants, suggesting that hsp-12.3 expression is normally repressed by pbrm-1 in SGPs.

developmental biology↗

bioRxiv2023

Winners and losers under past and future climate change

Understanding the historical and physiological context of species vulnerabilities to climate change is a crucial step in predicting "winners" and "losers" under climate change. However, few studies have compared the magnitude and mechanisms of extant species responses to climate change in both the past and the future. By combining temporally contrasting range and niche projections, we show that range shifts in the next 50 years will need to be more extreme than in the past 6000 years to track climate niches in a large plant radiation. A new subset of physiological niche traits, particularly temperature and radiation tolerance, will be strong filters of range occupancy under anthropogenic compared with Holocene climate change. In the absence of migration, temperature niche shifts tracking the magnitude of climate change will also be required for many species to maintain their present ranges. Where range shifts occur, our results suggest that communities will be restructured differently in different habitats, with widespread range contraction in the mountains and potential latitudinal range expansion in the lowlands. Our study adds to a growing body of evidence that despite the threats posed by climate change to many species, not all species will experience unmitigated loss, and that it may be possible to predict which species are most at risk based on physiological and geographical traits.

ecology↗