Biology subjects

George, J. G.

Publications and source records attributed to George, J. G..

3 recordsLinked to original sources

bioRxiv2026

ATF4 Coordinates Transcriptomic and Structural Adaptations in Aging Muscle

Aging is associated with a progressive loss of skeletal muscle function, known as sarcopenia; however, the molecular mechanisms coordinating cellular stress responses and structural adaptations permissive of sarcopenia remain incompletely understood. In our previous studies, we found aging differentially impacted mitochondrial networks by muscle, suggesting unique stress thresholds and response activation. Here, we investigate the role of activating transcription factor 4 (ATF4), a master regulator of the integrated stress response (ISR), in aged quadriceps muscle using complementary patient and aging mouse models. Older adults exhibited a marked decrease in aerobic capacity, muscle strength, and endurance when compared with young participants. These results paralleled findings in aged mice, with significant loss of muscle mass across multiple hindlimb muscles. Ultrastructural analysis revealed substantial age-related changes in mitochondrial morphology, including increased volume, surface area, and branching index, as well as a shift toward larger, more complex mitochondria. Our data indicate that ATF4 binds directly to the promoter region of the gene encoding TFAM, suggesting a transcriptional regulatory relationship to support DNA stability. These structural and transcriptional changes likely impair oxidative capacity and drive a feed-forward cycle of mitochondrial dysfunction and ISR activation. Our findings indicate that ATF4 coordinates transcriptomic and structural adaptations in aging muscle, identifying the ISR pathway as a potential therapeutic target for preserving muscle function in older adults.

cell biology↗

bioRxiv2025

Free-living food intake and repopulation of the gut microbiota after a health-screening colonoscopy

ObjectiveRole of microbiome has been highly studied for its association with various medical conditions. After a colonoscopy, repopulation of colonic microbial load is known to occur, however the quality and timing of natural repopulation has not been investigated after a bowel preparation. Further, no study has documented detailed free-living dietary intakes concurrently with gut microbiome repopulation post-colonoscopy. Here we sought to determine the early pattern of repopulation relative to dietary intake. MethodsHealthy adults (n=15 [4 female/11 male], BMI=27.2{+/-}3.9 kg/m2, age 51.4{+/-}7.2 y) who were scheduled to undergo a screening colonoscopy were recruited from the Gastroenterology Clinic at the University of Missouri. Within two weeks before the colonoscopy (baseline), subjects completed detailed food records for 3 days. Post-colonoscopy, subjects ate their free-living diets and detailed food records were collected on Days 0, 1, 2, 4, 7, 10, and 13. Fecal samples were obtained pre-colonoscopy and on post-colonoscopy Days 3, 5, 8, 11, and 14. Gut microbiome composition was assessed by 16S rRNA amplicon sequencing. ResultsWithin 5 days after the procedure, subjects reported consuming more total daily energy relative to baseline, presumably to make up for the low energy intake that occurred during the bowel-prep. At baseline, fiber intake (21.0{+/-}9.1 g/d) was higher than on the day of the colonoscopy, Day 0 (16.1{+/-}11.2, P=0.0159). Thereafter, daily fiber intake was the same as baseline. Marked intersubject microbiome beta diversity was observed by principal coordinate analysis using weighted and unweighted dissimilarities (P=0.0001, F=15.23, one-way PERMANOVA). Select taxa were depleted acutely post-colonoscopy (e.g., within the phylum Bacillota). Specifically, significant effects of time were observed between baseline and Day 3 fecal samples (pairwise P=0.0013, F=2.9). These changes trended to return to baseline by Day 5 and with subsequent samples, taxa remained similar to baseline when tested using a weighted dissimilarity analysis (Bray-Curtis). ConclusionsThese results quantitatively demonstrate the magnitude of the significant changes in microbial relative abundance and diversity immediately post-colonoscopy. The timing of repopulation aligned with changes in fiber intake after the procedure. These data highlight the importance of nutrition after a screening colonoscopy in reestablishing a healthy microbiome.

microbiology↗

bioRxiv2024

Sidelobe suppressed Bessel beams for one-photon light-sheet microscopy

Bessel beams (BB) have found widespread adoption in various forms of light-sheet microscopy. However, for one-photon fluorescence, the transverse profile of the beam poses challenges due to the detrimental effect of the sidelobes. Here, we mitigate this issue by using a computer generated phase element for generating a sidelobe suppressed Bessel beam (SSBB). We then progress to perform a comparison of biological imaging using SSBB to standard BB in a light-sheet geometry. The SSBB peak intensity is more than an order of magnitude higher than the first sidelobe. In contrast to a standard BB light-sheet, SSBB does not need deconvolution and propagates to depths exceeding 400m in phantom samples maintaining a transverse size of 5 m. Finally, we demonstrate the advantage of using a SSBB light-sheet for biological applications by imaging fixed early-stage zebrafish larvae. In comparison to the standard BB, we observe a two-fold increase in contrast-to-noise ratio (CNR) when imaging the labelled cellular eye structures and the notochords. Our results provide an effective approach to generating and using SSBB light-sheets to enhance contrast for one-photon light-sheet microscopy.

biophysics↗