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Ashraf, R.

Publications and source records attributed to Ashraf, R..

2 recordsLinked to original sources

Hormonal control of postmitotic neuronal identity

Developmental transcriptional programs establish neuronal diversity and circuit assembly, but how these regulators continue to shape and preserve neuronal identity remains unresolved. The Drosophila central complex comprises precisely wired circuits of diverse neuronal types that coordinate complex behaviors. Within this structure, dorsal fan-shaped body (dFB) neurons integrate internal-state signals to regulate sleep, feeding, and energy homeostasis, yet how distinct dFB subtypes are specified and maintained remains unknown. More broadly, whether developmental transcription factors continue to act in mature neurons to preserve neuronal identity is poorly understood. Here, we define the developmental origin and molecular regulation of neuronal identity in 84C10-labelled dFB neurons that innervate layers 6-7 of the FB and contribute to nutrient sensing and metabolic adaptation. Using lineage tracing, clonal analysis, and birth dating, we show that dFB neurons are generated late in development and arise from two distinct type II neural stem cell lineages, dorsolateral 1 and dorsomedial 4. These dFB neurons continue to express the late temporal transcription factor, ecdysone-induced protein 93 (E93), in adulthood. Post-mitotic depletion of E93 results in progressive neuronal loss and ectopic expansion of axonal arborizations across FB layers and, notably, a marked reduction in vesicular glutamate transporter (vGLUT) expression. These defects are accompanied by impaired increases in fat-to-lean mass ratios in response to high-sugar feeding. Together, our findings identify E93 as a post-mitotically retained temporal transcription factor that maintains neuronal survival, laminar connectivity, and neurotransmitter identity, revealing that developmental temporal programs are redeployed in adulthood to sustain neuronal identity and function.

neuroscience↗

A multi-institutional study to investigate the sparing effect after whole brain electron FLASH in mice: Reproducibility and temporal evolution of functional, electrophysiological, and neurogenic endpoints

PurposeUltra-high dose-rate radiotherapy (FLASH) has been shown to mitigate normal tissue toxicities associated with conventional dose rate radiotherapy (CONV) without compromising tumor killing in preclinical models. A prominent challenge in preclinical radiation research, including FLASH, is validating both the physical dosimetry and the biological effects across multiple institutions. MethodsWe previously demonstrated dosimetric reproducibility of two different electron FLASH devices at separate institutions using standardized phantoms and dosimeters. In this study, we compared the outcome of FLASH and CONV 10 Gy whole brain irradiation on female adult mice at both institutions to evaluate the reproducibility and temporal evolution of multiple endpoints. ResultsFLASH sparing of behavioral performance on novel object recognition (4 months post-irradiation) and electrophysiologic long-term potentiation (LTP, 5-months post-irradiation) was reproduced between institutions. Interestingly, differences between FLASH and CONV on the endpoints of hippocampal neurogenesis (Sox2, doublecortin), neuroinflammation (microglial activation), and electrophysiology (LTP) at late times were not observed at early times. ConclusionsIn summary, we demonstrated reproducible FLASH sparing effects between two beams and two institutions with validated dosimetry. FLASH sparing effects on the endpoints evaluated manifested at late but not early time points.

cancer biology↗