Biology subjects

Garland, G.

Publications and source records attributed to Garland, G..

6 recordsLinked to original sources

bioRxiv2026

APOE is a presynaptic protein that accumulates with age and modulates neurotransmitter release

The synaptic vesicle (SV) cycle is the fastest membrane trafficking and protein sorting process in biology. It underlies neuronal communication and cognition, yet synaptic function declines during normal aging, increasing vulnerability to neurologic disease. How the SV cycle is maintained across the lifespan of a complex organism remains unclear. Here, we used wild-type mice (C57BL/6J) to define the age- and sex-stratified molecular landscape of SVs and identified apolipoprotein E (APOE) as an abundant presynaptic protein further enriched in aged female samples. Super-resolution imaging, cell-type selective expression, and protease protection assays demonstrate that APOE originates from astroglia and associates with the cytosolic face of SVs. Using iGluSnFR and pHluorin optophysiology, we find that both decreased and increased APOE levels impair neurotransmission during stimulus trains. Together, these findings place APOE at the synapse and establish it as a cell-nonautonomous regulator of the SV cycle.

neuroscience↗

bioRxiv2025

Soil microbial and plant responses to increasing antibiotic concentration: a case study of five antibiotics

Antibiotic contamination from biogenic waste in agricultural soils poses a significant threat to soil health and crop productivity. We investigated the effect of antibiotics on the soil microbial community, antibiotic resistance genes (ARGs) and mobile genetic elements (MGEs) and plant productivity in a six week greenhouse trial. Here, Spinacia oleracea (spinach) and Raphanus sativus (radish) were grown from seed and a mix of five antibiotics, namely sulfamethoxazole, trimethoprim, enrofloxacin, clarithromycin and chlortetracycline, were added to the soil at concentrations 0, 0.1, 1 and 10 mg kg-1 soil dry weight (c0, c0.1, c1 and c10, respectively). Overall, we found that the antibiotic treatments significantly impacted prokaryotic -diversity and prokaryotic and fungal {beta}-diversity. Human and plant pathogen abundance did not increase under antibiotic exposure, but there was a significant reduction of plant growth-promoting bacteria. Moreover, the c10 treatment significantly increased the abundance of MGE intI1 indicative of horizontal gene transfer and ARG sul1 antibiotic resistance and significantly lowered radish biomass and nitrogen uptake, while spinach biomass and nitrogen uptake were unaffected. In summary, our study showed that antibiotic exposure significantly changed prokaryotic community diversity and taxonomy, while fungi remained largely unaffected. The reduction of plant growth-promoting bacteria may have a significant impact on soil nutrient cycling and crop productivity, but more research is needed to understand the long-term impact of these co-applied antibiotics on food production. Additionally, more studies are needed to understand the effect of antibiotics on realistic, field scale, conditions to fully understand the impact on environmental and human health. ImportanceAgricultural soils are increasingly contaminated with complex mixtures of antibiotics from various biogenic sources, yet we lack a clear understanding of their specific ecological impact. While many studies investigate antibiotics, they often are studied in pollution sources like manure which contain confounding factors like heavy metals. To provide clear mechanistic insight, we investigated the effects of a complex, five-antibiotic mixture on the soil-plant system, independent of other contaminants. This revealed that the effect of antibiotics extends beyond selecting for antibiotic resistance. Specifically, the reduction of prokaryotic diversity and plant growth-promoting bacteria under antibiotic exposure can have potential detrimental effects on plant and soil health. Moreover, we found that antibiotic exposure can reduce plant biomass and nitrogen uptake, but this is highly plant dependent. This research highlights the critical need to monitor antibiotic pollution due to its potential detrimental effect on plant health and alterations to the soil microbiome.

microbiology↗

bioRxiv2025

Diverse crop rotations off-set yield-scaled nitrogen losses via denitrification

Denitrification, a major source of gaseous nitrogen (N) emissions from agricultural soils, is influenced by management. Practices promoting belowground diversity are suggested to support sustainable agriculture, but their ability to modulate gaseous N-losses via denitrification remains inconclusive. To fill this knowledge gap, we sampled 106 cereal fields spanning a 3,000 km North-South gradient across Europe and compiled 56 associated climatic, soil, microbial and management variables. We found that increased denitrification was associated with higher proportion of time with crop cover over the last ten years. Denitrification rates were best predicted by microbial biomass and microbial functional guilds involved in N cycling, in particular denitrification. We also show that several diversification practices affect the variation in denitrification predictors, suggesting a trade-off between agricultural diversification and gaseous N-losses via denitrification. However, increased crop diversity in rotations improved yield-scaled denitrification, highlighting the potential of this practice to minimize N losses while contributing to sustainable food production.

ecology↗

bioRxiv2024

Longitudinal Fragility phenotyping predicts lifespan and age-associated morbidity in C57BL/6 and Diversity Outbred mice

Aging studies in mammalian models often depend on natural lifespan data as a primary outcome. Tools for lifespan prediction could accelerate these studies and reduce the need for veterinary intervention. Here, we leveraged large-scale longitudinal frailty and lifespan data on two genetically distinct mouse cohorts to evaluate noninvasive strategies to predict life expectancy in mice. We applied a modified frailty assessment, the Fragility Index, derived from existing frailty indices with additional deficits selected by veterinarians. We developed an ensemble machine learning classifier to predict imminent mortality (95% proportion of life lived [95PLL]). Our algorithm represented improvement over previous predictive criteria but fell short of the level of reliability that would be needed to make advanced prediction of lifespan and thus accelerate lifespan studies. Highly sensitive and specific frailty-based predictive endpoint criteria for aged mice remain elusive. While frailty-based prediction falls short as a surrogate for lifespan, it did demonstrate significant predictive power and as such must contain information that could be used to inform the conclusion of aging experiments. We propose a frailty-based measure of healthspan as an alternative target for aging research and demonstrate that lifespan and healthspan criteria reveal distinct aspects of aging in mice.

bioinformatics↗

bioRxiv2023

Regulators of health and lifespan extension in genetically diverse mice on dietary restriction

Caloric restriction (CR) delays aging and extends healthy lifespan in multiple species. Alternative forms of dietary restriction (DR) such as intermittent fasting (IF) have drawn significant interest as a more sustainable regimen, but the landscape of longevity-promoting dietary interventions remains largely unexplored. Identifying the most robust, efficacious, and experimentally tractable modes of DR is key to better understanding and implementing effective longevity interventions for human healthspan. To that end, we have performed an extensive assessment of DR interventions, investigating the effects of graded levels of CR (20% and 40%) and IF (1 day and 2 days of fasting per week) on the health and survival of 960 genetically diverse female mice. All interventions extended lifespan, although only CR significantly reduced the mortality doubling time. Notably, IF did not extend lifespan in mice with high pre-intervention bodyweight. We carried out extensive phenotyping to determine the health effects of long-term DR and to better understand the mechanisms driving within-diet heterogeneity in lifespan. The top within-diet predictor of lifespan was the ability of mice to maintain bodyweight through periods of handling, an indicator of stress resilience. Additional predictors of long lifespan include specific changes in immune cells, red blood cell distribution width (RDW), and retention of adiposity in late life. We found that lifespan is heritable (h2 = 0.24), and that genetic background has a larger influence on lifespan than dietary interventions. We identified a significant association for lifespan and RDW on chromosome 18 that explained 4.3% of the diet-adjusted variation in lifespan. Diet-induced changes on metabolic traits, although beneficial, were relatively poor predictors of lifespan, arguing against the long-standing notion that DR works by counteracting the negative effects of obesity. These findings indicate that improving health and extending lifespan are not synonymous and that metabolic parameters may be inappropriate endpoints for evaluating aging interventions in preclinical models and clinical trials.

genetics↗

bioRxiv2021

Intermittent fasting and caloric restriction interact with genetics to shape physiological health in mice

Dietary interventions can dramatically affect physiological health and organismal lifespan. The degree to which organismal health is improved depends upon genotype and the severity of dietary intervention, but neither the effects of these factors, nor their interaction, have been quantified in an outbred population. Moreover, it is not well understood what physiological changes occur shortly after dietary change and how these may affect the health of early adulthood population. In this article, we investigated the effect of six month exposure of either caloric restriction or intermittent fasting on a broad range of physiological traits in 960 one year old Diversity Outbred mice. We found caloric restriction and intermittent fasting affected distinct aspects of physiology and neither the magnitude nor the direction (beneficial or detrimental) of effects were concordant with the severity of the intervention. In addition to the effects of diet, genetic variation significantly affected 31 of 36 traits (heritabilties ranged from 0.04-0.65). We observed significant covariation between many traits that was due to both diet and genetics and quantified these effects with phenotypic and genetic correlations. We genetically mapped 16 diet-independent and 2 diet-dependent significant quantitative trait loci, both of which were associated with cardiac physiology. Collectively, these results demonstrate the degree to which diet and genetics interact to shape the physiological health of early adult-hood mice following six months of dietary intervention.

genetics↗