Biology subjects

Guillaume, M.

Publications and source records attributed to Guillaume, M..

6 recordsLinked to original sources

bioRxiv2025

Hepatocyte ERα orchestrates sex-specific liver adaptation to fasting and feeding states

Sex differences in hepatic physiology are thought to influence individual susceptibility to chronic liver diseases including Metabolic-Associated Steatotic Liver Disease (MALSD). Previous studies demonstrated the central contribution of estrogens which primarily influence liver biology through the activation of Estrogen Receptor alpha (ER). However, how ER signaling in hepatocyte modulates liver functions according to the nutritional status, a critical determinant of hepatic metabolism, remains to be characterized. The present study first reveals the nycthemeral expression profile of liver ER, which peaks during the feeding period (ZT16) in both male and female mice. ER expression is altered by reprogramming the hepatic circadian clock in response to inverted food intake, highlighting the influence of feeding on liver ER expression patterns. As ER is mainly expressed in hepatocytes both in human and mouse livers, the functional role of hepatocyte ER during fasting or feeding state was then delineated, using mice harboring ER hepatocyte-specific deletion (ERhep-/-) compared with their wild-type littermates (ERhep+/+). Transcriptomic analyses reveal significant sex differences in the adaptation of liver functions to this contrasted nutritional status, as well as the sex-specific regulatory effects of hepatocyte ER. In such physiological settings, hepatocyte ER deletion does not influence liver transcriptomic profiles in males but significantly alters gene expression in female livers, both fed and fasted conditions. Hepatocyte ER more specifically controls genes associated with inflammatory responses and fatty acid metabolic pathways in females, modulating the ChREBP and PPAR pathways in feeding or fasting states, respectively. Thus, hepatocyte ER is integral to liver metabolic adaptations to fasting and feeding in females but not in males, thus exhibiting both sex-specific and diet-dependent actions. Further characterizing sex differences in liver metabolic flexibility, these results provide new information to develop sex-based strategies for the prevention and management of MASLD.

physiology↗

bioRxiv2024

A family of lanthipeptides with anti-phage function

Bacteria synthesize natural products to adapt to their environment, where phage-bacteria interactions play a crucial role in bacterial ecology. Although a few natural products have been shown to protect bacteria from phage infection, the prevalence and diversity of chemical anti-phage defense remain largely unexplored. Here, we uncover a novel family of over 2000 lanthipeptide biosynthetic gene clusters from Actinobacteria that participate in anti-phage defense, which we named lanthiphages. Lanthiphages colocalize with other anti-phage systems in defense islands. We demonstrate that native lanthiphage expression protects the model strain Streptomyces coelicolor against diverse phages. Heterologous expression of four additional lanthiphage pathways shows that the anti-phage function is conserved across this family of biosynthetic gene clusters. Finally, we demonstrate that lanthiphage expression leads to the production of a novel compound and alters phage transcription. Our findings highlight that biosynthetic gene clusters with anti-phage functions can be successfully identified through genomic analysis. This work paves the way for the systematic mining of anti-phage natural products, which could constitute a novel reservoir of antiviral drugs.

microbiology↗

bioRxiv2024

Characterization of a major QTL for sodium accumulation in tomato shoot

Soil salinity is a serious concern for tomato culture, affecting both yield and quality parameters. Although some genes involved in tomato salt tolerance have been identified, their genetic diversity has been rarely studied. In the present study, we assessed salt tolerance-related traits at juvenile and adult stages in a large core collection and identified salt tolerance QTLs by genome-wide association study (GWAS). The results suggested that a major QTL is involved in leaf sodium accumulation at both physiological stages. We were able to identify the underlying candidate gene, a well-known sodium transporter, called SlHKT1.2. We showed that an eQTL for the expression of this gene colocalized with the sodium content QTL. A polymorphism putatively responsible for its variation was identified in the gene promoter. Finally, to extend the applicability of these results, we carried out the same analysis on a test-cross panel composed of the core collection crossed with a distant line. The results indicated that the identified QTL retained its functional impact even in a hybrid genetic context: this paves the way for its use in breeding programs aimed at improving salinity tolerance in tomato cultivars. Summary statementThe genetic diversity of sodium accumulation in tomato shoot under salt stress is associated with an expression QTL of SlHKT1.2. This gene, already identified as involved in tomato salinity tolerance, has been differentially selected during domestication and is of interest for the development of salinity-tolerant varieties.

plant biology↗

bioRxiv2020

Automatic processing of numerosity in human neocortex evidenced by occipital and parietal neuromagnetic responses

Humans and other animal species are endowed with the ability to sense, represent, and mentally manipulate the number of items in a set without needing to count them. One central hypothesis is that this ability relies on an automated functional system dedicated to numerosity, the perception of the discrete numerical magnitude of a set of items. This system has classically been associated with intraparietal regions, however accumulating evidence in favor of an early visual number sense calls into question the functional role of parietal regions in numerosity processing. Targeting specifically numerosity among other visual features in the earliest stages of processing requires high temporal and spatial resolution. We used frequency-tagged magnetoencephalography (MEG) to investigate the early automatic processing of numerical magnitudes and measured the steady-state brain responses specifically evoked by numerical and other visual changes in the visual scene. The neuromagnetic responses showed implicit discrimination of numerosity, total occupied area, and convex hull. The source reconstruction corresponding to the implicit discrimination responses showed common and separate sources along the ventral and dorsal visual pathways. Occipital sources attested the perceptual salience of numerosity similarly to both other implicitly discriminable visual features. Crucially, we found parietal responses uniquely associated with numerosity discrimination, showing automatic processing of numerosity in the parietal cortex, even when not relevant to the task. Taken together, these results provide further insights into the functional roles of parietal and occipital regions in numerosity encoding along the visual hierarchy. Significance StatementApproximating the number of items in a set has been identified as a building block of mathematical cognition but the processing of numerosity is not fully understood. The natural correlation between numerosity and other visual features makes it difficult to test whether the number of items is a perceptual primitive or whether it needs to be recombined at a higher level. We used frequency-tagged magnetoencephalography to localize the implicit discrimination of numerosity within the visual hierarchy. We found that numerosity yielded occipital responses, supporting that the human visual system can grasp it at a single glance. Crucially, numerosity also yielded specific parietal responses, showing that numerosity is a perceptual primitive with a unique automatic involvement of parietal cortex.

neuroscience↗

bioRxiv2019

Spontaneous and automatic processing of magnitude and parity information of Arabic digits: A frequency-tagging EEG study.

Arabic digits (1-9) are everywhere in our daily lives. These symbols convey various semantic information, and numerate adults can easily extract from them several numerical features such as magnitude and parity. Nonetheless, since most studies used active processing tasks to assess these properties, it remains unclear whether and to what degree the access to magnitude and especially to parity is automatic. Here we investigated with EEG whether spontaneous processing of magnitude or parity can be recorded in a frequency-tagging approach, in which participants are passively stimulated by fast visual sequences of Arabic digits. We assessed automatic magnitude processing by presenting a stream of frequent small digit numbers mixed with deviant large digits (and the reverse) with a sinusoidal contrast modulation at the frequency of 10 Hz. We used the same paradigm to investigate numerical parity processing, contrasting odd digits to even digits. We found significant brain responses at the frequency of the fluctuating change and its harmonics, recorded on electrodes encompassing right occipitoparietal regions, in both conditions. Our findings indicate that both magnitude and parity are spontaneously and unintentionally extracted from Arabic digits, which supports that they are salient semantic features deeply associated to digit symbols in long-term memory.

neuroscience↗

bioRxiv2019

The neural signature of numerosity: Separating numerical and continuous magnitude extraction in early visual cortex with frequency-tagged EEG

The ability to handle approximate quantities, or number sense, has been recurrently linked to mathematical skills, though the nature of the mechanism allowing to extract numerical information (i.e., numerosity) from environmental stimuli is still debated. A set of objects is indeed not only characterized by its numerosity but also by other features, such as the summed area occupied by the elements, which often covary with numerosity. These intrinsic relations between numerosity and non-numerical magnitudes led some authors to argue that numerosity is not independently processed but extracted through a weighting of continuous magnitudes. This view cannot be properly tested through classic behavioral and neuroimaging approaches due to these intrinsic correlations. The current study used a frequency-tagging EEG approach to separately measure responses to numerosity as well as to continuous magnitudes. We recorded occipital responses to numerosity, total area, and convex hull changes but not to density and dot size. We additionally applied a model predicting primary visual cortex responses to the set of stimuli. The model output was closely aligned with our electrophysiological data, since it predicted discrimination only for numerosity, total area, and convex hull. Our findings thus demonstrate that numerosity can be independently processed at an early stage in the visual cortex, even when completely isolated from other magnitude changes. The similar implicit discrimination for numerosity as for some continuous magnitudes, which correspond to basic visual percepts, shows that both can be extracted independently, hence substantiating the nature of numerosity as a primary feature of the visual scene.

neuroscience↗