Biology subjects

Aguilar, E. A.

Publications and source records attributed to Aguilar, E. A..

4 recordsLinked to original sources

bioRxiv2026

Long-term Musculoskeletal and Marrow Sparing with Proton FLASH in Juvenile Mice: Implications for Pediatric Osteosarcoma

PurposeOsteosarcoma is the most common primary bone malignancy in children and adolescents. Radiotherapy is limited by intrinsic radioresistance and the risk of severe long-term musculoskeletal toxicities. FLASH radiotherapy, delivered at ultra-high dose rates (>40 Gy/s), has demonstrated normal tissue sparing in preclinical models, but its effects on the developing skeleton and marrow remain poorly defined. This study evaluated the chronic normal tissue effects of proton FLASH in juvenile mice, modeling the pediatric context. Methods and MaterialsJuvenile C57BL/6 mice (3-4 weeks old) were randomized to receive 11 Gy FLASH ({approx}200 Gy/s) or conventional proton irradiation (0.2 Gy/s average), or sham treatment to the left hind leg using a synchrotron-based proton beamline. Mice were followed for 10 weeks post-treatment. Bone toxicity was assessed with microCT (bone mineral density, bone volume fractions, trabecular indices) and histology. Bone marrow cellularity was quantified on H&E-stained sections, and muscle fibrosis was assessed using Massons trichrome. ResultsFLASH-treated mice exhibited significant preservation of bone microarchitecture compared with conventional treated mice, with higher bone mineral density and bone volume fractions (p < 0.05). Trabecular numbers were maintained, while structure model index indicates a mechanically favorable trabecular structures in the FLASH group. Bone marrow cellularity was preserved in FLASH mice (5.3% reduction vs. sham) compared with conventional (11.3 % reduction, p < 0.05). Muscle fibrosis was significantly lower in FLASH group (fibrosis positivity 2.6 % vs. 3.0% for FLASH vs. conventional CONV, p < 0.05). No severe immobility or weight loss was observed across groups. ConclusionsProton FLASH significantly reduces long-term bone, marrow, and muscle toxicities in juvenile mice. These findings provide the first demonstration of musculoskeletal sparing in a synchrotron proton FLASH platform and highlight its translational potential for pediatric osteosarcoma.

cancer biology↗

bioRxiv2022

Phyllochron duration and changes through rice development shape the vertical leaf size profile

O_LIWell-irrigated aerobic rice (Oryza sativa L.) plants are often shorter with smaller leaves, and the leaf appearance rate is slower in well-irrigated than in flooded environments. This observation questions the functional relationship between the leaf appearance rate, which is correlated with the apical cell production rate, and leaf length that is in turn correlated with the leaf division zone length. C_LIO_LIMeristem size, blade size, and appearance were monitored for all leaves from leaf 6 on the main stem of rice plants in field experiments using two varieties, two watering systems, and three sowing dates. C_LIO_LILeaf blade and division zone lengths were correlated in all leaves of the main stem of rice plants. New stable linear relationships were found between the leaf division zone growth duration and internal cell production rate, which changed after leaf 11. These stable relationships imply a stable link between the rates of cell production in the stem apex and leaf meristem, explaining the vertical leaf size profile. C_LIO_LIOverall, faster leaf appearance leads to shorter leaves and organs in rice because of a functional link, which is counterbalanced by additional acclimation in transplanted plants. C_LI

plant biology↗

bioRxiv2021

The vagus nerve is critical for regulation of hypothalamic-pituitary-adrenal axis responses to acute stress

The hypothalamic pituitary adrenal (HPA) axis is a critical regulator of physiologic and psychological responses to acute and chronic stressors. HPA axis function is control by numerous feedback inhibitory mechanisms, disruptions of which can lead to various psychiatric conditions, such as depression, posttraumatic stress disorder, and schizophrenia. Vagus nerve stimulation has been shown to be efficacious in the treatment of in these various mental health issues potentially via modulation of HPA axis function, but the mechanisms by which the vagus nerve may regulate HPA function has not been fully elucidated. In the present studies, we sought to test the hypothesis that the vagus nerve is a critical regulator of HPA function. Neuroendocrine function and neurocircuit changes in corticotropin releasing factor (CRF) neurons in the paraventricular nucleus of the hypothalamus (PVN) were examined following acute stress after subdiaphragmatic left vagotomy (VX) in adult male Sprague-Dawley rats. We found that VX mimics HPA activation seen in sham surgery animals exposed to acute restraint stress, particularly increased plasma corticosterone levels, elevated PVN CRF mRNA, and increased action potential firing of putative CRF neurons in PVN brain slices. Furthermore, VX animals exposed to acute restraint stress showed increased elevations of plasma corticosterone and PVN CRF mRNA which may be due to lack of compensatory PVN GABAergic signaling in response to acute stress. Both Sham/Stress and VX/no stress conditions increased action potential firing in putative PVN CRF neurons, but this effect was not seen in the VX/stress condition, suggesting that not all forms of stress compensation are lost following VX. Overall, these findings suggest that the vagus nerve may play a critical role in regulating HPA axis function via modulation of local PVN neurocircuit activity.

neuroscience↗

bioRxiv2018

Access schedules mediate the impact of high fat diet on ethanol intake in mice.

Alcoholism and high fat diet (HFD)-induced obesity individually promote insulin resistance and glucose intolerance in clinical populations, increasing risk for metabolic diseases. Conversely, animal studies, typically utilizing forced/continuous alcohol (EtOH) access, tend to show that EtOH intake mitigates HFD-induced effects on insulin and glucose function, while HFD decreases voluntary EtOH intake in continuous access models. However, the impact of HFD on intermittent EtOH intake and resultant changes to metabolic function are not well characterized. The present studies sought to determine if HFD alters EtOH intake in male C57Bl/6J mice given differing two-bottle choice EtOH access schedules, and to assess resultant impact on insulin sensitivity and glucose tolerance. In the first experiment, mice had Unlimited Access EtOH (UAE)+HFD (n=15; HFD=60% calories from fat, 10% EtOH v/v, ad libitum) or UAE+Chow (n=15; control diet=16% calories from fat, ad libitum) for 6 weeks. UAE+HFD mice had lower EtOH preference, consumed significantly less EtOH, and were insulin resistant and hyperglycemic compared with UAE+Chow mice. In the second experiment, mice had Limited Access EtOH (LAE, 4 hrs/d; 3 d/wk)+HFD (n=15) or LAE+Chow (n=15) with increasing EtOH concentrations (10%, 15%, 20%). LAE+HFD mice had no difference in total EtOH consumption compared to LAE+Chow mice, but exhibited hyperglycemia, insulin resistance, and glucose intolerance. In the third experiment, mice had intermittent HFD access (single 24 hr session/week) with limited access to EtOH (iHFD-E, 4hrs/d; 4 d/wk) (n=10). iHFD-E mice displayed binge eating behaviors and consumed significantly more EtOH than mice given ad libitum chow or HFD, suggesting transfer of binge eating to binge drinking behaviors. Although iHFD-E mice did not have significantly altered body composition, they developed insulin insensitivity and glucose intolerance. These results suggest that access schedules determine the impact of HFD on EtOH consumption and resultant metabolic dysfunction.

animal behavior and cognition↗