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The FLASH effect is a radiobiological phenomenon that has garnered considerable interest in the clinical field. Pre-clinical experimental studies have highlighted its potential to reduce side effects on healthy tissues while maintaining isoeffectiveness on tumor tissues, thus widening the therapeutic window and enhancing the effectiveness of radiotherapy. The FLASH effect is achieved through the administration of the complete therapeutic radiation dose within a brief time frame, shorter than 200 milliseconds, and, therefore, utilizing remarkably high average dose rates above at least 40 Gy/s. Despite its potential in radiotherapy, the radiobiological mechanisms governing this effect and its quantitative relationship with temporal parameters of the radiation beam, such as dose-rate, dose-per-pulse, and average dose-rate within the pulse, remain inadequately elucidated. A more profound comprehension of these underlying mechanisms is imperative to optimize the clinical application and translation of the FLASH effect into routine practice. Due to the aforementioned factors, the undertaking of quantitative radiobiological investigations becomes imperative, necessitating the utilization of sophisticated and adaptable apparatus capable of generating radiation beams with exceedingly high dose-rates and dose-per-pulse characteristics. This study presents a comprehensive account of the design and operational capabilities of a Linear Accelerator (LINAC) explicitly tailored for FLASH radiotherapy research purposes. Termed the “ElectronFlash” (EF) LINAC, this specialized system employs a low-energy configuration (7 and 9 MeV) and incorporates a triode gun. The EF LINAC is currently operational at the Centro Pisano FLASH Radiotherapy (CPFR) facility located in Pisa, Italy. Lastly, this study presents specific instances exemplifying the LINAC’s adaptability, enabling the execution of hitherto unprecedented experiments. By enabling independent variations of the temporal parameters of the radiation beam implicated in the FLASH effect, these experiments facilitate the acquisition of quantitative data concerning the effect’s dependence on these specific parameters. This novel approach hopefully contributes to a more comprehensive understanding of the FLASH effect, shedding light on its intricate radiobiological behavior and offering valuable insights for optimizing its clinical implementation.

Background: Ephippidae fish are characterized by a discoid shape with a very small visceral cavity. Among them Platax orbicularis has a high economic potential due to its flesh quality and flesh to carcass ratio. Nonetheless, the development of its aquaculture is limited by high mortality rates, especially due to Tenacibaculum maritimum infection, occurring one to three weeks after the transfer of fishes from bio-secure land-based aquaculture system to the lagoon cages for growth. Among the lines of defense against this microbial infection, the gastrointestinal tract (GIT) is less studied. The knowledge about the morphofunctional anatomy of this organ in P. orbicularis is still scarce. Therefore, the aims of this study are to characterize the GIT in non-infected P. orbicularis juveniles to then investigate the impact of T. maritimum on this multifunctional organ., Methods: In the first place, the morpho-anatomy of the GIT in non-infected individuals was characterized using various histological techniques. Then, infected individuals, experimentally challenged by T. maritimum were analysed and compared to the previously established GIT reference., Results: The overlapped shape of the GIT of P. orbicularis is probably due to its constrained compaction in a narrow visceral cavity. Firstly, the GIT was divided into 10 sections, from the esophagus to the rectum. For each section, the structure of the walls was characterized, with a focus on mucus secretions and the presence of the Na + /K + ATPase pump. An identification key allowing the characterization of the GIT sections using in toto histology is given. Secondly, individuals challenged with T. maritimum exhibited differences in mucus type and proportion and, modifications in the mucosal and muscle layers. These changes could induce an imbalance in the trade-off between the GIT functions which may be in favour of protection and immunity to the disadvantage of nutrition capacities., Competing Interests: The authors declare there are no competing interests. Agnès Bardon-Albaret and Denis Saulnier are employed by Ifremer, UMR Ecosystèmes Insulaires Océaniens, UPF, ILM, IRD., (©2020 Alix et al.)

The posterior lateral line system (PLL) of teleost fish comprises a number of mechanosensory organs arranged in defined patterns on the body surface. Embryonic patterns are largely conserved among teleosts, yet adult patterns are highly diverse. Although changes in pattern modify the perceptual abilities of the system, their developmental origin remains unknown. Here we compare the processes that underlie the formation of the juvenile PLL pattern in Thunnus thynnus, the bluefin tuna, to the processes that were elucidated in Danio rerio, the zebrafish. In both cases, the embryonic PLL comprises five neuromasts regularly spaced along the horizontal myoseptum, but the juvenile PLL comprises four roughly parallel anteroposterior lines in zebrafish, whereas it is a simple dorsally arched line in tuna fish. We examined whether this difference involves evolutionary novelties, and show that the same mechanisms mediate the transition from embryonic to juvenile patterns in both species. We conclude that the marked difference in juveniles depends on a single change (dorsal vs. ventral migration of neuromasts) in the first days of larval life.

The lateral line system of amphibians and fish comprises a large number of individual mechanosensory organs, the neuromasts, and their sensory neurons. The pattern of neuromasts varies markedly between species, yet the embryonic pattern is highly conserved from the relatively basal zebrafish, Danio rerio, to more derived species. Here we examine in more detail the development of the posterior lateral line (PLL) in embryos and early larvae of one of the most derived fish species, the blue-fin tuna Thunnus thynnus, and of its close relative, the Atlantic bonito Sarda sarda. We show that the basic features of embryonic PLL development, including the migratory properties of the PLL primordium, the patterning of neuromasts and their innervation, are largely conserved between zebrafish and tuna. However, Thunnus and Sarda embryos differ from Danio in three respects: the larger size of the neuromast cupula, the capability of mature neuromasts to migrate dorsally, and the presence of a single, precisely located terminal neuromast.

All during fish postmortem evolution, structural muscle proteins are targets for various proteases. During the prerigor period (24 hours at 4 degrees C for sea bass), cytoskeletal proteins are affected by the first proteolytic events. These cleavages disrupt connections between myofibrils and the extracellular matrix, induce segmentation of myofibril cores, and modify the rheological properties of tissue. Dystrophin, a cytoskeletal actin-binding protein, is a relevant in situ marker for muscular proteolysis in the prerigor period. The immunodetection of dystrophin allowed the monitoring of early proteolysis during fish storage. Using antidystrophin antibodies directed toward the carboxy-terminal region, a highly sensitive domain exposed to calpain activity, we showed that proteolysis kinetics are strongly influenced by the muscular lipid content. In particular, comparison between low-fat diets (11.3% lipid) and high-fat diets (30% lipid), used during sea bass farming (90 days), revealed a faster proteolysis rate during the first 8 hours of storage at 0 degrees C with the high-fat diet. The origin of this faster proteolysis is discussed on the basis of a possible activation or translocation of calpains related to lipid accumulation in muscle fibers and cytoskeleton alterations.

In fish, dietary digestible energy (DE) content is a major factor controlling feed intake. It was therefore of interest to determine how circadian rhythm of feeding activity is influenced by the dietary DE levels. To that end, groups of European sea bass were fed on demand by means of self feeders, under light-dark and constant light conditions, with a fixed or an unlimited amount of feed with variable lipid contents. Daily total feed intake, but not the feeding rhythm, was adjusted in relation to the DE content of the diet regardless of the lighting conditions. We conclude that a satiation mechanism was likely responsible for the regulation of feed intake in relation to the dietary fat content but was not acting in itself on the mechanisms that drive the free-running rhythms of feeding activity. These results are giving additional evidence that a true endogenous clock is driving feeding activity rhythms in fish.