Biology subjects

Fort, P.

Publications and source records attributed to Fort, P..

7 recordsLinked to original sources

bioRxiv2026

Schizosaccharomyces orthogroup (SOG) resource: a web platform for exploring gene conservation in fission yeasts

The fission yeast Schizosaccharomyces pombe is a prominent model organism widely used to investigate fundamental cellular mechanisms. In addition to S. pombe, the genus Schizosaccharomyces includes six other species--S. octosporus, S. japonicus, S. cryophilus, S. osmophilus, S. lindneri, and S. versatilis. These fission yeast species share a common ancestor from which the genus diversified over more than 200 million years. This extensive evolutionary divergence provides opportunities for comparative genomics. Here, we present the Schizosaccharomyces orthogroup (SOG) resource, a web platform developed from our high-quality genome assemblies, gene annotations, and orthology assignments. Most fission yeast genes are assigned to one of over 5,000 orthogroups. The platform enables users to visualize orthogroup sequence alignments and phylogenetic trees, retrieve coding and flanking sequences, and explore the conservation of local synteny. This resource will benefit researchers focusing on individual genes as well as those investigating gene evolution at broader scales. It is freely accessible at https://www.sogweb.org. TAKE AWAYO_LIThe SOG resource covers all known species of Schizosaccharomyces. C_LIO_LIThe platform is built on high-quality genome assemblies and annotations. C_LIO_LIMost genes are assigned to one of over 5,000 orthogroups. C_LIO_LIUsers can view and explore alignments, phylogenetic trees, and local synteny. C_LIO_LIThis free resource aids functional and evolutionary research. C_LI

genomics↗

bioRxiv2025

Comparative distribution of the hypothalamic neurons activated during Wakefulness and Paradoxical (REM) sleep using TRAP2-red mice: contribution of Orexin, MCH, Lhx6 and a new marker Meis2

Study objectivesParadoxical sleep (PS) is a state involving numerous hypothalamic neuronal subpopulations, many remaining neurochemically uncharacterized. Our goal was to compare hypothalamic neurons active during Wakefulness or PS rebound (PSR) and explore their potential overlap, with a focus on melanin-concentrating-hormone (MCH), Orexin (Orx), Lhx6 and a new contingent of Meis2- expressing neurons. MethodIn the same TRAP2-red mouse, neurons activated during Wakefulness (4h) and PSR (2h) express TdTomato and c-Fos, respectively. Double-labelling and triple immunofluorescence with neurochemical markers were performed to characterize and quantify cell populations in hypothalamic structures. ResultsTwelve hypothalamic structures showed distinct activation patterns. The anterior hypothalamic area (AHA), zona incerta (ZI) and tuberal nucleus contained more activated neurons during PSR than Wakefulness, whereas the paraventricular hypothalamic (PVN) and supraoptic (SO) nuclei were predominantly activated during Wakefulness. MCH and Lhx6 neurons were mainly recruited during PSR, whereas Orx neurons were activated during both. A ventral subpopulation of MCH neurons showed higher activation during PSR than the dorsal subpopulation. Additionally, [~]30% of the c-Fos+ neurons in ZI and AHA express Meis2. A similar proportion of TdTomato+ neurons positive for Meis2 were encountered in PVN and SO. Overall, [~]20% of all hypothalamic neurons activated during PSR are now neurochemically identified. ConclusionOur study identifies new neuronal populations activated during PSR in AHA and tuberal nucleus. We further get evidence that Meis2 delineates novel neuronal populations activated during PSR. In summary, our results using TRAP2-red mice characterize new cell populations activated during Wakefulness or PSR, opening experimental paths for determining their function regarding vigilance states. Statement of significanceWakefulness and paradoxical sleep are very similar at the electroencephalographic level. It remains relevant to determine the potential overlap of the neurons active during each vigilance state. We here took advantage of the powerful transgenic TRAP2-red mice to directly compare in the same animal the brain cell activation during both states, with a focus on the hypothalamus. A deeper knowledge of each individual subpopulation of hypothalamic neurons within complex brain circuits underlying the sleep-waking cycle will help the understanding and validation of treatments of sleep disorders, at least those directly linked to demonstrated hypothalamic dysfunction as Narcolepsy (Orx neurons), Amyotrophic Lateral Sclerosis (MCH and Orx signaling) or neurodegenerative diseases (Parkinsons and Alzheimer diseases).

neuroscience↗

bioRxiv2025

Drug-induced versus non-pharmacological wakefulness: similar or different states? A whole brain analysis in TRAP2 transgenic mice

A large body of data indicate that the aminergic, cholinergic and hypocretin/orexin neurons are responsible for inducing wakefulness. However, recent data showed that other systems might also play a key role. Further, wakefulness induced by different drugs versus non-pharmacological means could be generated by different populations of neurons. To address these questions, we evaluated at the whole brain level in the same mice using TRAP2 model whether the same neurons were activated by the wake-inducing drugs modafinil and solriamfetol versus non-pharmacological wake. Our results show that several subcortical structures such as the bed nucleus of the stria terminalis, central amygdalar nucleus, paraventricular hypothalamic and thalamic and supraoptic nuclei, lateral parabrachial nucleus and lateral reticular area (including its noradrenergic neurons) are significantly more activated by solriamfetol than modafinil and non-pharmacological wakefulness. In contrast, a second category of structures including the orexin neurons, the parasubthalamic and laterodorsal tegmental nucleus are strongly activated in all types of induced wake. Further, some classical wake systems like the dopaminergic neurons of the ventral tegmental area or the dorsal raphe nucleus and the noradrenergic neurons of the locus coeruleus are either very poorly or not strongly activated. These results reveal that many structures not previously involved in wakefulness might play a key role in regulating the state and that some structures might be more recruited by solriamfetol than modafinil or non-pharmacological wakefulness. Our results are particularly relevant for pathologies such as hypersomnia. They open a new era in the study of the mechanisms responsible for inducing wakefulness.

neuroscience↗

bioRxiv2024

Induction of a Muller glial-specific protective pathway safeguards the retina from diabetes induced damage

Diabetes can lead to cell-type-specific responses in the retina, including vascular lesions, glial dysfunction and neurodegeneration, all of which contribute to retinopathy. However, the molecular mechanisms underlying these cell type-specific responses, and the cell types that are sensitive to diabetes have not been fully elucidated. Employing single cell transcriptomic analyses, we profiled the transcriptional changes induced by diabetes in different retinal cell types in diabetic rat models as the disease progressed. Rod photoreceptors, a subtype of amacrine interneurons, and Muller glial cells exhibited rapid responses to diabetes at the transcript levels. Genes associated with ion regulation were upregulated in all three cell types, suggesting a common response to diabetes. Furthermore, focused studies revealed that while Muller glial cells initially increased the expression of genes playing protective roles, they cannot sustain this beneficial effect as the disease progressed. We explored one of the candidate protective genes, Zinc finger protein 36 homolog (Zfp36), and observed that depleting Zfp36 in rat Muller glial cells in vivo using AAV-based tools exacerbated early diabetes-induced phenotypes, including gliosis, neurodegeneration, and vascular defects. Notably, the over-expression of Zfp36 slowed the development of phenotypes associated with diabetic retinopathy. In summary, this work unveiled retinal cell types that are sensitive to diabetes and demonstrated that Muller glial cells can mount protective responses through Zfp36. The failure to maintain Zfp36 levels contributes to the development of diabetic retinopathy.

neuroscience↗

bioRxiv2023

Modelling human brain-wide pigmentation in rodents recapitulates age-related multisystem neurodegenerative deficits

One key limitation in developing effective treatments for neurodegenerative diseases is the lack of models accurately mimicking the complex physiopathology of the human disease. Humans accumulate with age the pigment neuromelanin inside neurons that synthesize catecholamines. Neurons reaching the highest neuromelanin levels preferentially degenerate in Parkinsons, Alzheimers and apparently healthy aging individuals. However, this brain pigment is not taken into consideration in current animal models because common laboratory species, such as rodents, do not produce neuromelanin. Here we generate a tissue-specific transgenic mouse, termed tgNM, that mimics the human age-dependent brain-wide distribution of neuromelanin within catecholaminergic regions, based on the constitutive catecholamine-specific expression of human melanin-producing enzyme tyrosinase. We show that, in parallel to progressive human-like neuromelanin pigmentation, these animals display age-related neuronal dysfunction and degeneration affecting numerous brain circuits and body tissues, linked to motor and non-motor deficits, reminiscent of early neurodegenerative stages. This model may open new research avenues in brain aging and neurodegeneration.

neuroscience↗

bioRxiv2021

Ras/MAPK signalling intensity defines subclonal fitness in a mouse model of primary and metastatic hepatocellular carcinoma

Quantitative differences in signal transduction are to date an understudied feature of tumour heterogeneity. The MAPK Erk pathway, which is activated in a large proportion of human tumours, is a prototypic example of distinct cell fates being driven by signal intensity. We have used primary hepatocyte precursors transformed with different dosages of an oncogenic form of Ras to model subclonal variations in MAPK signalling. Orthotopic allografts of Ras-transformed cells in immunocompromised mice gave rise to fast-growing aggressive tumours, both at the primary location and in the peritoneal cavity. Fluorescent labelling of cells expressing different oncogene levels, and consequently varying levels of MAPK Erk activation, highlighted the selection processes operating at the two sites of tumour growth. Indeed, significantly higher Ras expression was observed in primary as compared to metastatic tumours, despite the evolutionary trade-off of increased apoptotic death in the liver that correlated with high Ras dosage. Analysis of the immune tumoral microenvironment at the two locations suggests that fast metastatic growth in the immunocompromised setting is abrogated in immunocompetent animals due to efficient antigen presentation by peritoneal dendritic cells. Furthermore, our data indicate that, in contrast to the metastatic outgrowth, strong MAPK signalling is required in the primary liver tumours to resist elimination by NK cells. Overall, this study describes a quantitative aspect of tumour heterogeneity and highlights potential vulnerability of a subtype of hepatocellular carcinoma as a function of MAPK Erk signalling intensity.

cancer biology↗

bioRxiv2020

Aspartate-phobia of thermophiles as a reaction to deleterious chemical transformations

Prokaryotes growing at high temperatures have a high proportion of charged residues in their proteins to stabilize their 3D structure. By mining 175 disparate bacterial and archaeal proteomes we found that, against the general trend for charged residues, the frequency of aspartic acid residues decreases strongly as natural growth temperature increases. In search of the explanation, we hypothesized that the reason for such unusual correlation is the deleterious consequences of spontaneous chemical transformations of aspartate at high temperatures. Our subsequent statistical analysis supported this hypothesis. First, knowing that these chemical modifications are higher in the unfolded polypeptide chains, we observed the most pronounced decrease of Asp frequency with temperature within intrinsically disordered regions. Second, it is known that the reaction rate of the chemical transformations of Asp is highest with the smallest downstream residue Gly and noticeably reduced for bulky residues. In agreement with this, the frequency of Gly residues downstream of Asp decreases with optimal growth temperature, while the frequency of bulky residues significantly increases. Thus, our analysis suggests that organisms have likely adapted to high temperatures by minimizing the harmful consequences of spontaneous chemical transformations of Asp residues.

evolutionary biology↗