Amyotrophic Lateral Sclerosis: Role of the Canonical Wnt/Beta- Catenin Pathway and PPAR Gamma

Amyotrophic lateral sclerosis (ALS) is one of the most common adult-onset debilitating neurodegenerative diseases (NDs) which is characterized by a chronic progressive degeneration of upper and lower motor neurons, resulting in muscular atrophy, paralysis and ultimately death. It has been established that in ALS, the canonical Wnt/beta-catenin pathway is upregulated. Peroxisome proliferator-activated receptor gamma (PPAR gamma) generally varies in opposite way compared with the Wnt/beta-catenin signaling. Several studies carried out on ALS transgenic mice have shown the beneficial effects induced after treatment by PPAR agonists partly due to anti-inflammatory effects induced by PPAR gamma. The coupling between the Wnt/beta-catenin signaling and PPAR gamma has led to divide NDs into two classes: NDs in which the Wnt/beta-catenin pathway is upregulated whereas PPAR gamma is downregulated (ALS, Parkinson’s disease, Huntington’s disease and Friedreich’s ataxia); and NDs in which the Wnt-beta-catenin pathway is downregulated while PPAR gamma is upregulated (Alzheimer’s disease, bipolar disorder and schizophrenia)

Thermodynamics in Gliomas: Interactions between the Canonical WNT/Beta-Catenin Pathway and PPAR Gamma

Gliomas cells are the site of numerous metabolic and thermodynamics abnormalities with an increasing entropy rate which is characteristic of irreversible processes driven by changes in Gibbs energy, heat production, intracellular acidity, membrane potential gradient, and ionic conductance. We focus our review on the opposing interactions observed in glioma between the canonical WNT/beta-catenin pathway and PPAR gamma and their metabolic and thermodynamic implications. In gliomas, WNT/beta-catenin pathway is upregulated while PPAR gamma is downregulated. Upregulation of WNT/beta-catenin signaling induces changes in key metabolic enzyme that modify their thermodynamics behavior. This leads to activation pyruvate dehydrogenase kinase 1(PDK-1) and monocarboxylate lactate transporter 1 (MCT-1). Consequently, phosphorylation of PDK-1 inhibits pyruvate dehydrogenase complex (PDH). Thus, a large part of pyruvate cannot be converted into acetyl-CoA in mitochondria and in TCA (tricarboxylic acid) cycle. This leads to aerobic glycolysis despite the availability of oxygen, named Warburg effect. Cytoplasmic pyruvate is, in major part, converted into lactate. The WNT/beta-catenin pathway induces also the transcription of genes involved in cell proliferation, cell invasiveness, nucleotide synthesis, tumor growth, and angiogenesis, such as c-Myc, cyclin D1, PDK. In addition, in gliomas cells, PPAR gamma is downregulated, leading to a decrease in insulin sensitivity and an increase in neuroinflammation. Moreover, PPAR gamma contributes to regulate some key circadian genes. Abnormalities in the regulation of circadian rhythms and dysregulation in circadian clock genes are observed in gliomas. Circadian rhythms are dissipative structures, which play a key role in far-from-equilibrium thermodynamics through their interactions with WNT/beta-catenin pathway and PPAR gamma. In gliomas, metabolism, thermodynamics, and circadian rhythms are tightly interrelated

Sexual behaviors, cannabis, alcohol and monkeypox infection

The emergence of the monkeypox virus (MPXV) outbreak in 2022 is a worldwide health issue. The rapid increase of monkeypox cases caused the WHO to designate the escalating global monkeypox outbreak a Public Health Emergency of International Concern on July 23, 2022. The WHO has called on the group currently most affected by the virus, men who have sex with men (MSM), to limit their sexual partners. The diminution in number of sexual partners not only decreases the proportion of infected MSM but could also increases the number of days needed to reach a given infection level among the general population. Several behavioral factors could be associated with high levels of different sexual partners, such as cannabis use and alcohol consumption. Firstly, this review focuses on the association between cannabis and alcohol consumption and the number of sexual partners, and their possible impact on the current MPXV outbreak by impairing the immune responses. Secondly, this review investigated in the UK Biobank cohort the relationship between alcohol and cannabis use and the number of sexual partners. Among the 115,604 participants, 1.8% declared to be MSM, 1.9% to be WSW (women having sex with women), 43.3% men heterosexuals and 53.0% women heterosexuals. MSM and WSW showed higher lifetime sexual partners (N = 17.4 (SD:17.52) and N = 13.65 (SD: 13.21), respectively) compared to heterosexual men (N = 6.89 (SD: 9.47) and women (N = 5.19 (SD:6.56), p < 0.001. After adjustment for age, body mass index, lifetime sexual activity, educational and income levels, tobacco and cardiovascular diseases, cannabis use and alcohol consumption remained significantly associated with increase in the number of different sexual partners in all four subgroups. Thus, cannabis use and alcohol consumption may have two detrimental effects on the MPXV outbreak: by participating in the increase of the number of sexual partners which are mainly responsible for the augmentation of the number of new MPXV infected cases and by impairing the immune response to a viral infection. Health and safety policies should address the factors and practices, including chemsex, leading to an increase in risk of sexual behaviors responsible for MPXV dissemination in the worldwide population

Construction dynamique de fragments par minimisation de l'énergie libre lors de collisions d'ions lourds

La recherche théorique en physique des ions lourds se fait essentiellement avec des simulations numériques de leurs collisions. Cependant, pour que la description soit fondamentale, les calculs doivent se dérouler sur les constituants élémentaires des noyaux: les nucléons. Ces réactions produisent des sources excitées qui ne sont que des nuages de nucléons à la sortie de la simulation dynamique. Pour pouvoir procéder à la désexcitation de ces sources et ensuite à la comparaison expérimentale, une importante étape doit être franchie en construisant des fragments depuis la distribution des nucléons dans l'espace des phases. Appelée "clusterisation", cette reconnaissance peut être faite selon diverses approches, toutes devant produire un portrait statique très similaire sur une distribution de nucléons en fin de réaction dite de "freeze-out". Aussi, il est aussi très intéressant d'étudier la formation de ces fragments avant le freeze-out, i.e. dans la phase d'expansion. Des modèles existent déjà, utilisant un critère énergétique en recherchant la partition la plus liée (minimisation de l'énergie totale). Ce projet propose un critère entropique, soit la maximisation de l'entropie sous contraintes. Parmi les contraintes envisagées, l'énergie des partitions sera retenue en première approximation. Dans ce contexte, la clusterisation se fera donc par minimisation de l'énergie libre d'Helmoltz. L'étude des différentes façons de regrouper les nucléons en fragments et ainsi former des configurations pose un important problème de combinatoire. L'exploration de ces partitions sera faite à l'aide d'un calcul Monte Carlo (algorithme de Metropolis). Etant donné la contrainte utilisée dans la maximisation de l'entropie, le seul paramètre intensif associé devant être déterminé dans le calcul Monte Carlo est la température. Cette dernière sera extraite selon des règles de "correspondance", qui seront établies entre des ensembles statistiques à l'équilibre thermodynamique, dont les propriétés sont bien connues, et un ensemble hors équilibre constitué des différentes voies de la réaction sous clusterisation. Ces différentes voies sont produites par la dynamique qui est, dans ce projet, décrite par la Dynamique Moléculaire Antisymétrisée (AMD). L'étude de la clusterisation dynamique se fera sur des événements centraux de la réaction ⁴⁰Ca -I- ⁴⁰Ca à 35AMeV. Elle permettra d'évaluer le temps de formation des fragments puis mesurera l'effet de la température des sources sur leur formation

Digital twin for healthcare systems

Digital twin technology is revolutionizing healthcare systems by leveraging real-time data integration, advanced analytics, and virtual simulations to enhance patient care, enable predictive analytics, optimize clinical operations, and facilitate training and simulation. With the ability to gather and analyze a wealth of patient data from various sources, digital twins can offer personalized treatment plans based on individual characteristics, medical history, and real-time physiological data. Predictive analytics and preventive interventions are made possible by machine learning algorithms, allowing for early detection of health risks and proactive interventions. Digital twins can optimize clinical operations by analyzing workflows and resource allocation, leading to streamlined processes and improved patient care. Moreover, digital twins can provide a safe and realistic environment for healthcare professionals to enhance their skills and practice complex procedures. The implementation of digital twin technology in healthcare has the potential to significantly improve patient outcomes, enhance patient safety, and drive innovation in the healthcare industry

Développement d'une méthodologie extensible pour la détection de charges électriques uniques dans une boîte quantique par un pont capacitif cryogénique

Dans ce travail, une approche alternative à la détection de charge dans les boîtes quantiques ayant pour but d'améliorer l'extensibilité de ces dispositifs est examinée. Cette méthode alternative est basée sur l'utilisation d'un pont capacitif. Un tel circuit intégrant un transistor à effet de champ fonctionnel à température cryogénique a été caractérisé. Les étapes d'optimisation des différents paramètres de fonctionnement du circuit, comme sa capacité totale ou le gain du transistor, sont présentées. Les expériences de détection de charge effectuées sur un transistor monoélectronique à l'aide du circuit ont mené à la détection de signaux correspondant à des transitions de charge, même en l'absence de transport électrique dans le dispositif. Le signal observé diffère légèrement du signal attendu pour des raisons encore incertaines, mais ses dépendances envers les paramètres expérimentaux sont celles qui sont attendues. La sensibilité à la charge du dispositif est encore trop basse pour réaliser des mesures en un coup (single-shot). Toutefois, des améliorations subséquentes pourraient aller jusqu'à permettre le remplacement des détecteurs de charge actuels, ce qui aurait des impacts positifs sur l'extensibilité des dispositifs de boîte quantique. La capacité additionnelle du circuit à tracer des courbes de caractérisation capacité-tension cryogéniques est aussi démontrée, ce qui est intéressant pour la caractérisation détaillée de toute composante semi-conductrice cryogénique étant donné que les appareils de caractérisation habituels ne peuvent pas être utilisés dans ces conditions

Interactions between PPAR Gamma and the Canonical Wnt/Beta-Catenin Pathway in Type 2 Diabetes and Colon Cancer

In both colon cancer and type 2 diabetes, metabolic changes induced by upregulation of the Wnt/beta-catenin signaling and downregulation of peroxisome proliferator-activated receptor gamma (PPAR gamma) may help account for the frequent association of these two diseases. In both diseases, PPAR gamma is downregulated while the canonical Wnt/beta-catenin pathway is upregulated. In colon cancer, upregulation of the canonical Wnt system induces activation of pyruvate dehydrogenase kinase and deactivation of the pyruvate dehydrogenase complex. As a result, a large part of cytosolic pyruvate is converted into lactate through activation of lactate dehydrogenase. Lactate is extruded out of the cell by means of activation of monocarboxylate lactate transporter-1. This phenomenon is called Warburg effect. PPAR gamma agonists induce beta-catenin inhibition, while inhibition of the canonical Wnt/beta-catenin pathway activates PPAR gamma

Modeling the 3-micron Class Er-Doped Fluoride Fiber Laser with a Cubic Energy Transfer Rate Dependence

We propose an energy transfer model with a cubic atomic population dependence to accurately model the behavior of various reported high-power erbium-doped fluoride fiber lasers operating near 2.8 microns. We first show that the previously introduced weakly interacting (WI) and strongly interacting (SI) models are not adequate for precisely modeling such high-power erbium-doped fluoride fiber lasers. We compare results obtained with the WI and SI models to the proposed model by simulating 4 different highly doped (7 mol.%) fiber lasers previously reported in the literature. Laser efficiencies and powers are reproduced with great accuracy. In addition, four other independent fiber laser systems based on erbium doping concentrations varying from 1-6 mol.% are also simulated with good accuracy using the proposed model with the exact same set of spectroscopic parameters, which confirms its validity for various erbium doping concentrations. Redshifting of laser wavelength is also taken into account by considering the full cross section spectra and computing signal powers over several wavelength channels.Comment: 9 pages, 18 figures, submitted to IEEE Journal of Quantum Electronic