Biology subjects

Giraud, S.

Publications and source records attributed to Giraud, S..

4 recordsLinked to original sources

bioRxiv2026

Combined lactate and hypothermia therapy enhances neuroprotection following neonatal hypoxic-ischemic brain injury

Background and Purpose: Neonatal hypoxia-ischemia (NHI) is a leading cause of mortality and long-term neurodevelopmental disability. Therapeutic hypothermia (TH) is currently the only established treatment for NHI; however, its efficacy remains limited, underscoring the need for adjunctive neuroprotective strategies. Lactate is now regarded as a major metabolic substrate of the brain and has previously been shown to exert neuroprotective effects following experimental NHI. We investigated whether lactate enhances hypothermia-induced neuroprotection and evaluated the optimal timing of administration and potential underlying mechanisms. Methods: Postnatal day 7 Wistar rats were subjected to NHI using the Rice-Vannucci model and treated with TH alone (2h at 32{degrees}C), sodium L-lactate alone, or combined L-lactate-TH. Animals underwent longitudinal magnetic resonance imaging (MRI) and behavioral assessments, complemented by histological, immunohistochemical, and Western blot analyses, including assessment of protein lactylation. The effect of sodium L-lactate administration timing relative to TH was also evaluated. Results: Lactate significantly enhanced the neuroprotective effects of TH, particularly when administered before hypothermia, resulting in greater lesion recovery, reduced neuroinflammation and apoptotic cell death, preserved neuronal integrity, and improved long-term motor and cognitive outcomes. Combined treatment preserved neuronal lactate transporter, prevented NHI-induced astrocytic glutamate transporter upregulation, modulated lactylation markers, supporting coordinated metabolic and epigenetic adaptations following NHI. Conclusions: Early lactate administration enhances the neuroprotective efficacy of TH following NHI. These findings identify lactate as a promising adjunct to TH and support its translational potential as a metabolic strategy to improve outcomes following NHI brain injury.

neuroscience↗

bioRxiv2025

Fibrillarin-mediated ribosomal RNA maturation is a novel therapeutic vulnerability in triple-negative breast cancer

Triple-negative breast cancer (TNBC) remains one of the most challenging breast cancer subtypes to treat due to the lack of effective therapeutic options. Ribosome biogenesis has recently emerged as a promising therapeutic target across various cancers. Despite the current targeting of ribosome biogenesis through RNA polymerase I (RNA Pol I) inhibition, we speculated that other factors essential for ribosome assembly, such as rRNA maturation factors, may also represent therapeutic targets in TNBC. Here, we demonstrate that ribosome biogenesis-related genes are notably overexpressed in TNBC compared to other breast cancer subtypes, highlighting its critical role in TNBC progression. Accordingly, we show that RNA Pol I inhibition exerts potent anti-proliferative effects in pre-clinical models of TNBC, both in vitro and in vivo. However, the DNA-damaging activity of RNA Pol I inhibitors raises safety concerns, highlighting the need for alternative strategies to inhibit ribosome biogenesis. To this end, we show that targeting a downstream rRNA maturation step, specifically pre-rRNA cleavage, by inhibiting the maturation factor Fibrillarin, also inhibits tumor growth in TNBC models. Notably, ribosome biogenesis inhibition, through either RNA Pol I or Fibrillarin targeting, induces cell cycle arrest without triggering significant cell death. These findings establish ribosome biogenesis as a therapeutic vulnerability in TNBC and identify rRNA maturation, and Fibrillarin in particular, as novel targets for potential therapeutic intervention. SignificanceTargeting ribosome biogenesis, through inhibition of either rRNA synthesis or maturation, induces anti-tumoral effects in TNBC, representing a novel therapeutic vulnerability with potential to improve patient outcomes.

cancer biology↗

bioRxiv2023

Challenging popular belief, mosquito larvae breathe underwater

It is taken for granted that immature mosquito only breathe atmospheric air through their siphons. However, there is no quantitative study that demonstrated it. We analysed the survival of the last instar larvae of Aedes aegypti fully submerged at different temperatures, and measured oxygen consumption from air and dissolved in water, of larvae and pupae of this species under different conditions. Results revealed that under water, larvae survived much longer than expected, reaching 50% mortality only after 58, 10, and 5 days at 15{degrees}, 25{degrees} and 35{degrees}C, respectively. Interestingly, whereas we registered moults to pupae in larvae with access to air, individuals kept submerged never moulted. When remaining at the water surface, larvae obtained 12.72% of O2 from the water, while pupae only 5.32%. When completely submerged, larvae consumed less oxygen than in contact with the surface, but enough for surviving, while pupae did not. At both media, temperature affected larvae respiration rate, with relatively close Q10 values. In the related species, Ae. albopictus, a similar pattern of O2 consumption were observed. Larvae got 12.14% of their oxygen from the water. Interestingly, no significant differences in total O2 consumption were found between water O2 consumption, when Ae. albopictus larvae were submerged, or when they also have access to air (dual O2 consumption). Our findings not only challenge the classical idea that mosquito larvae only breathe atmospheric O2, but also force us to reconsider the potential effectiveness of control methods based on asphyxiating larvae by detaching from water surface. Summary statementWe present the first quantitative analysis of mosquito larvae respiration in air and water, unravelling the unknown capacity of larvae of the most cosmopolitan disease vector of breathing underwater.

zoology↗

bioRxiv2018

WASABI: a dynamic iterative framework for gene regulatory network inference

Inference of gene regulatory networks from gene expression data has been a long-standing and notoriously difficult task in systems biology. Recently, single-cell transcriptomic data have been massively used for gene regulatory network inference, with both successes and limitations. In the present work we propose an iterative algorithm called WASABI, dedicated to inferring a causal dynamical network from time-stamped single-cell data, which tackles some of the limitations associated with current approaches. We first introduce the concept of waves, which posits that the information provided by an external stimulus will affect genes one-by-one through a cascade, like waves spreading through a network. This concept allows us to infer the network one gene at a time, after genes have been ordered regarding their time of regulation. We then demonstrate the ability of WASABI to correctly infer small networks, which have been simulated in silico using a mechanistic model consisting of coupled piecewise-deterministic Markov processes for the proper description of gene expression at the single-cell level. We finally apply WASABI on in vitro generated data on an avian model of erythroid differentiation. The structure of the resulting gene regulatory network sheds a fascinating new light on the molecular mechanisms controlling this process. In particular, we find no evidence for hub genes and a much more distributed network structure than expected. Interestingly, we find that a majority of genes are under the direct control of the differentiation-inducing stimulus. In conclusion, WASABI is a versatile algorithm which should help biologists to fully exploit the power of time-stamped single-cell data.

systems biology↗