Biology subjects

Jimenez, G. A.

Publications and source records attributed to Jimenez, G. A..

3 recordsLinked to original sources

bioRxiv2026

The TREM2 targeting small molecule Sob-AM2 improves cognition independent of Aβ plaque alteration in 5xFAD mice

BackgroundInflammation is an early event that substantially influences Alzheimers disease (AD) pathogenesis, making it a compelling target for therapeutic intervention. Sob-AM2 is a brain-penetrating thyromimetic drug capable of inducing the expression of microglial cell surface receptor TREM2, which mediates the switch from pro-inflammatory to a more restorative microglial state. ObjectiveEvaluate the effects of Sob-AM2 on cognition, AD pathology and microglial activity in the 5xFAD mouse model of amyloid-beta (A{beta}) accumulation. MethodsSeven-month-old 5xFAD mice and their wild-type littermates were administered Sob-AM2 subcutaneously three times per week for 12 weeks. In the last two weeks of treatment mice underwent behavioral tests to assess cognition and monitor for off-target mobility effects. At the end of treatment, brain tissue was harvested for gene and protein expression analyses. ResultsSob-AM2 treatment increased TREM2 expression in the brains of 5xFAD mice. This was accompanied by an improvement in both spatial and associative memory as well as an increase in the expression of synaptic genes synaptophysin and PSD-95. No significant changes were detected in A{beta} plaque burden or the expression of microglial activation marker Iba1 in Sob-AM2 treated animals, however, the expression of the phagocytic marker CD68 was significantly increased in the hippocampus, but not the cortex, in Sob-AM2 treated 5xFAD mice. ConclusionThese results suggest that the cognitive-enhancing effects of Sob-AM2 are not the result of reduced overall plaque burden. Future work is needed to further investigate the neuroprotective mechanism of Sob-AM2 and how it may be affecting microglial phenotypes.

neuroscience↗

bioRxiv2026

Body size, wing area, and wing loading follow a pattern of trait conservatism in Drosophila

Wing loading is a metric of flight performance that captures the relationship between body mass and wing area and reflects how much weight each unit of wing surface supports during flight. Comparative studies have documented substantial differences in wing loading among individuals and across species. However, no study has evaluated the extent of this variation when species are reared under identical, controlled conditions. Here, we address that gap by measuring wing loading in 30 species of drosophilids raised in a common lab environment. We applied comparative phylogenetic methods to assess the extent to which the evolution of body mass, wing area, and wing loading is structured by shared ancestry. We find that wing area and body mass exhibit moderate phylogenetic signal, but wing loading does not. In addition, all three traits are best explained by a model of evolution in which most trait divergence occurs during speciation events. More conservative analyses provide no support for adaptive peaks in wing loading within drosophilids. Together, our results indicate that the evolutionary dynamics of wing loading in Drosophila differ from those described in birds and bats, and raise the question of whether similar patterns characterize other insect lineages.

evolutionary biology↗

bioRxiv2025

Exploring the Evolution of the Cariogenic Oral Pathobiont Streptococcus mutans Using Ancient DNA

The oral pathobiont Streptococcus mutans can contribute to dental caries development through metabolism of dietary carbohydrates. Adoption of carbohydrate-rich agricultural diets is associated with increased prevalence of dental caries in archaeological populations; however, the evolutionary impact of changing subsistence strategies on cariogenic microbes like S. mutans remains to be explored. Here, we use a novel hybridization capture reagent to generate genome-wide ancient DNA data from a global set of 75 S. mutans strains spanning the last 8,000 years. Most virulence-associated genes predate the origins of agriculture; however, we highlight loci regulating genetic competence, bacteriocin production, and biofilm formation which are absent in 5 strains from pre-agricultural ancient hunter-gatherers, suggesting that their acquisition may have been associated with adaptation to carbohydrate-rich agricultural diets. Together, our study highlights ancient DNA as a promising tool for exploring the dynamic interplay between subsistence strategy, microbes, and dental pathology in human populations through time.

evolutionary biology↗