Biology subjects

Gerard, N.

Publications and source records attributed to Gerard, N..

3 recordsLinked to original sources

bioRxiv2025

FLASH or flare: variable intestinal toxicity results in a mouse model following proton pencil beam scanning irradiation on a clinical superconducting synchrocyclotron

Background and aimsUltra-high dose rate (FLASH) irradiation is a promising technique to reduce radiation-induced normal tissue toxicities while preserving antitumor efficacy. We evaluated the feasibility and intestinal sparing potential of FLASH irradiation using a clinical synchrocyclotron-based proton therapy system generating a pulsed beam. Material and methodsC57BL/6J mice received abdominal irradiation (2x2 cm) in transmission mode at FLASH (>60 Gy/s) or conventional (CONV, 0.5 Gy/s) dose rates using a 230 MeV superconducting synchrocyclotron proton pencil beam scanning (PBS) system. Two independent irradiation rounds were performed. Endpoints included 75-day survival, regenerating crypt counts, whole blood counts at day 4, and intestinal wall thickness, cyst-like structures, and cytokine levels at day 75. ResultsIn the first irradiation round, survival after 14.5 Gy FLASH was markedly improved (5/8 survivors) compared to CONV (0/8), whereas in the second round, survival rates were identical (2/7 per group). Overall, pooled data indicated improved survival with 14.5 Gy FLASH. The LD50 was 13.74 Gy in CONV and 14.48 Gy in FLASH mode, corresponding to a FLASH modifying factor of 0.95. FLASH at 14.5 Gy increased regenerating crypt numbers compared to CONV, but only in the first round, supporting survival outcomes. No significant differences were observed in whole blood counts, cytokine profiles, or long-term intestinal structural changes between groups. ConclusionFLASH proton therapy delivered with a clinical synchrocyclotron PBS system can reduce short-term gastrointestinal toxicity in mice. However, inconsistent results across irradiation rounds highlight limitations of this model for reliable FLASH studies.

cancer biology↗

bioRxiv2021

Detection of antimicrobial resistance, pathogenicity, and virulence potentials of non-typhoidal Salmonella isolates at the Yaounde abattoir using whole genome sequencing technique

One of the crucial public health problems today is emerging and re-emerging of multidrug-resistant bacterial pathogens coupled with a decline in the development of new antimicrobials. Non-typhoidal Salmonella is classified among the multidrug-resistant bacterial pathogens of international concern. To predict their multidrug resistance potentials, 19 assembled genomes (partial genomes) of 23 non-typhoidal Salmonella isolated at the Yaounde abattoir between December 2014 and November 2015 from live cattle (n=1), beef carcass (n=19), butchers hands (n=1) and the beef processing environments (n=2) were explored using whole-genome sequencing. Phenotypically, while approximately 22% (n=5) of Salmonella isolates showed moderate resistance to streptomycin, 13.04 % (n=3) were multidrug-resistant. Genotypically, all the Salmonella isolates possessed high multidrug resistance potentials against several classes of antibiotics (third-generation cephalosporin and fluoroquinolone), which are assigned highest priority drugs by the World Health Organization. Moreover, more than 31% of the isolates exhibited resistance potentials to polymyxin, considered as the last resort drug with both clinical and veterinary relevance. Additionally, close to 80% of non-typhoidal Salmonella isolates in this study harboured silent resistant genes and thus constituted potential reservoirs of antibiotic resistance to other foodborne bacteria. Plasmids also appear to play a critical role in the horizontal transfer of antibiotic resistance genes of some isolates. The isolates showed a high degree of pathogenicity and possessed key effector proteins to establish infection in their hosts, including humans. The overall results demand prudent use of antibiotics and constant monitoring of antimicrobial resistance of non-typhoidal Salmonella in the Cameroonian abattoirs. Author summaryNon-typhoidal Salmonella has been classified among the multidrug resistant bacterial pathogens of international concern. A growing resistance to a broad range of antibacterial compounds in animals and clinical settings has been reported in Non-Typhoidal Salmonella. Current knowledge of their antibiotic resistance profile is essential to inform policy decisions for the choice of appropriate management of invasive salmonellosis. The significance of our research consists in predicting the multidrug resistance, pathogenicity and virulence potentials of Salmonella organisms using whole genome sequencing. This unveils the need for the development of a diagnostic model that takes into account the genotype-phenotype antibacterial resistance profile of Salmonella, which is of both clinical and veterinary relevance.

microbiology↗

bioRxiv2019

Satellite glial cells modulate cholinergic transmission between sympathetic neurons

Postganglionic sympathetic neurons and satellite glial cells are the two major cell types of the peripheral sympathetic ganglia. Sympathetic neurons project to and provide neural control of peripheral organs and have been implicated in human disorders ranging from cardiovascular disease to peripheral neuropathies. Here we show that satellite glia regulate postnatal development and activity of sympathetic neurons, providing evidence for local ganglionic control of sympathetic drive. We show changes in the cellular architecture of the rat sympathetic ganglia during the postnatal period, with satellite glia enwrapping sympathetic neuronal somata during a period of neuronal hypertrophy. In culture, satellite glia contribute to neuronal survival, promote synapse formation and play a modulatory role in neuron-to-neuron cholinergic neurotransmission, consistent with the close contact seen within the ganglia. Cultured satellite glia make and release neurotrophins, which can partially rescue the neurons from nerve growth factor deprivation. Electrophysiological recordings and immunocytochemical analysis on cultured sympathetic neurons show that satellite glial cells influence synapse number and total neuronal activity with little effect on neuronal intrinsic excitability. Thus, satellite glia play an early and ongoing role within the postnatal sympathetic ganglia, expanding our understanding of the contributions of local and target-derived factors in the regulation of sympathetic neuron function.

neuroscience↗