Biology subjects

Roitman, M.

Publications and source records attributed to Roitman, M..

3 recordsLinked to original sources

bioRxiv2025

Vacuolar invertase knockout enhances drought tolerance in potato plants

Drought stress is one of the most critical abiotic constraints limiting crop productivity worldwide, exacerbated by ongoing climate change and increasingly frequent extreme weather events. Stomatal regulation and osmoprotective sugar accumulation are critical adaptive mechanisms for plant survival under drought stress. Here, we characterize the enhanced drought resilience observed in CRISPR/Cas9-mediated potato, mutants in their vacuolar invertase gene (StVInv). Knockout plants exhibited improved performance under progressive drought stress and during rewatering drought, maintaining higher stomatal conductance, elevated transpiration rates, and superior photosynthetic efficiency compared to wild-type (WT) plants. These improved performance under similar transpiration rate led to higher agronomic water-use efficiency (AWUE) in stvinv plants resulting in greater biomass production despite reduced water availability. Metabolomic profiling revealed distinct adaptive strategies; stvinv plants preferentially accumulated galactinol and raffinose, indicating enhanced raffinose family oligosaccharide (RFO) metabolism. Furthermore, stvinv plants displayed lower levels of abscisic acid (ABA) and its catabolites under drought, suggesting a moderated ABA response facilitating a more risk-taking growth strategy that supports sustained growth and physiological stability. Our findings identify targeted metabolic and hormonal adjustments underlying drought resilience in potato plant, offering promising strategies for enhancing crop performance under water-limited conditions.

plant biology↗

bioRxiv2023

An Open-Source Platform for Head-Fixed Operant and Consummatory Behavior

Head-fixed behavioral experiments in rodents permit unparalleled experimental control, precise measurement of behavior, and concurrent modulation and measurement of neural activity. Here we present OHRBETS (Open-Source Head-fixed Rodent Behavioral Experimental Training System; pronounced Orbitz), a low-cost, open-source ecosystem of hardware and software to flexibly pursue the neural basis of a variety of motivated behaviors. Head-fixed mice tested with OHRBETS displayed operant conditioning for caloric reward that replicates core behavioral phenotypes observed during freely moving conditions. OHRBETS also permits for optogenetic intracranial self-stimulation under positive or negative operant conditioning procedures and real-time place preference behavior, like that observed in freely moving assays. In a multi-spout brief-access consumption task, mice displayed licking as a function of concentration of sucrose, quinine, and sodium chloride, with licking modulated by homeostatic or circadian influences. Finally, to highlight the functionality of OHRBETS, we measured mesolimbic dopamine signals during the multi-spout brief-access task that display strong correlations with relative solution value and magnitude of consumption. All designs, programs, and instructions are provided freely online. This customizable ecosystem enables replicable operant and consummatory behaviors and can be incorporated with methods to perturb and record neural dynamics in vivo. Impact StatementA customizable open-source hardware and software ecosystem for conducting diverse head-fixed behavioral experiments in mice.

neuroscience↗

bioRxiv2018

Epigenetic derepression of FKBP5 by aging and stress contributes to NF-kB-driven inflammation and cardiovascular risk

Aging and psychosocial stress are associated with increased inflammation and disease risk, but the underlying molecular mechanisms are poorly understood. Because both aging and stress are also associated with lasting epigenetic changes, a plausible hypothesis is that stress exposure along the lifespan could confer disease risk by epigenetically deregulating molecules involved in inflammatory processes. Here, by combining large-scale analyses in human cohorts with mechanistic in vitro investigations, we found that FKBP5, a protein implicated in stress physiology, contributes to these relations. Across independent human cohorts (total n=3,131), aging and stress-related phenotypes were synergistically associated with epigenetic derepression of FKBP5. These age/stress-related epigenetic effects were recapitulated in an in vitro model of replicative senescence, whereby we exposed replicating human fibroblasts to stress (glucocorticoid) hormones. Unbiased genome-wide analyses in human blood linked higher FKBP5 mRNA with a proinflammatory profile and altered NF-{kappa}B-related gene networks. Accordingly, experiments in immune cells showed that FKBP5 overexpression promotes inflammation by strengthening the interactions of NF-{kappa}B regulatory kinases, whereas opposing FKBP5 either by genetic deletion (CRISPR/Cas9-mediated) or selective pharmacological inhibition prevented the effects on NF-{kappa}B. Further, the age/stress-related epigenetic signature enhanced FKBP5 responsivity to NF-{kappa}B through a positive feedback loop and was present in individuals with a history of acute myocardial infarction, a disease state linked to peripheral inflammation. These findings suggest that FKBP5-NF-{kappa}B signaling mediates inflammation associated with aging and stress, potentially contributing to cardiovascular risk, and may thus point to novel biomarker and treatment possibilities.\n\nSignificanceDiseases of the aging are the leading cause of morbidity and mortality. Elucidating the molecular mechanisms through which modifiable factors, such as psychosocial stress, confer risk for aging-related disease can have profound implications. Here, by combining studies in humans with experiments in cells, we find that aging and stress synergize to epigenetically derepress FKBP5, a protein implicated in stress physiology. Higher FKBP5 promotes inflammation by activating the master immune regulator NF-{kappa}B, whereas opposing FKBP5 - either genetically or pharmacologically- prevents the effects on NF-{kappa}B. Further, the age/stress-related epigenetic signature of FKBP5 is associated with history of myocardial infarction, a disease state linked to inflammation. These findings provide molecular insights into stress-related disease and may point to novel biomarker and treatment possibilities.

genomics↗