Biology subjects

Morales, A. L.

Publications and source records attributed to Morales, A. L..

3 recordsLinked to original sources

bioRxiv2026

Telomeric heterochromatin acts in trans to promote meiotic centromere assembly via Aurora B kinase recruitment

During meiosis, chromosomes face a paradox: the machinery that ensures reductional chromosome segregation also destabilizes centromeres by dismantling kinetochores, risking chromosome missegregation. Here we show how cells resolve this crisis through an unexpected activity of the telomere bouquet. We demonstrate that the bouquet transfers heterochromatin components to pericentromeres, which in turn recruit the Aurora B kinase to direct centromere reassembly. The heterochromatin protein Swi6HP1 relocates from telomeres to centromeres, enabling Haspin kinase-dependent phosphorylation of histone H3 and consequent enrichment of the chromosomal passenger complex, which includes the Aurora B kinase. Aurora B then phosphorylates core centromere proteins, including CenpA and CenpC, to promote kinetochore reassembly. Phosphomimetic mutants of CenpA or CenpC bypass the telomere-heterochromatin-Haspin pathway, demonstrating that Aurora B-mediated phosphorylation is sufficient for reassembly. This function is conserved in mitotically proliferating cells subjected to centromere dismantlement. Our findings establish a safeguarded system that couples meiotic nuclear architecture to centromere identity and reveal a fundamental role for the Aurora B kinase in centromere assembly, beyond its canonical function in correcting kinetochore-spindle attachment errors.

cell biology↗

bioRxiv2025

Commensal taxa in gut microbiota limit antibiotic resistance during extended oral antibiotic use

Certain bacterial infections, such as those involving prosthetics, can require antimicrobial therapy over months to years, potentially increasing the burden of antimicrobial resistance. Here we longitudinally track the antimicrobial resistome in mice during continuous antibiotic dosing over 21 months. The burden of antibiotic resistance genes (ARGs) initially increases, but, surprisingly, declines in later months, approaching levels observed in untreated animals. ARG burden is regulated by taxonomy and declines as ARG-harboring taxa that initially bloom are replaced by commensals. Furthermore, we find that the dynamics of antibiotic-induced ARG burden are influenced by age-related differences in microbial taxonomy and can be removed by fecal microbiota transplantation. We show that commensals may regulate the resistome by limiting the growth of ARG-harboring taxa, thereby providing antimicrobial expansion resistance.

microbiology↗

bioRxiv2024

Effects of long-term high dose aspartame on body mass, bone strength, femoral geometry, and microbiota composition in a young and aged cohort of male and female mice

BackgroundRecent reassessment of the safety of aspartame has prompted increased evaluation of its effect on the health of a range of tissues. The gut microbiome is altered by oral aspartame. One prior study suggested that changes in the microbiome caused by aspartame could influence the strength of bone in young skeletally developing mice. Here we ask how aspartame influences bone in mice of different age and sex. ObjectiveThe objective of this study was to determine the effect of aspartame on the bone strength and gut microbiota of young and aged mice. MethodsMale and female C57Bl/6J mice were untreated or treated with a high dose of aspartame in their drinking water from 1 month of age until 4 (young cohort; n = 80) or 22 months (aged cohort; n = 52). ResultsIn aged males, mice treated with aspartame had greater body mass, whole bone strength, and femoral geometry relative to untreated. Specifically, in aged males, aspartame led to 9% increase in body mass (p < 0.001), 22% increase in whole bone strength (p = 0.006), and 17% increase in section modulus (p < 0.001) relative to untreated mice. Aged males and females receiving aspartame had a different microbiota than untreated mice and a decreased abundance of Odoribacter. No differences in body mass, whole bone strength, or femoral geometry were associated with aspartame dosing in young males or young or aged females. ConclusionsAspartame treated aged males had greater whole bone strength and the effect appeared to be explained by greater body mass. Aspartame treatment did not alter whole bone strength in young males or young or aged females despite the aspartame having a similar effect on the microbiota of both aged males and females.

bioengineering↗