31 research outputs found

    Review on Superconducting Materials

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    Short review of the topical comprehension of the superconductor materials classes Cuprate High-Temperature Superconductors, other oxide superconductors, Iron-based Superconductors, Heavy-Fermion Superconductors, Nitride Superconductors, Organic and other Carbon-based Superconductors and Boride and Borocarbide Superconductors, featuring their present theoretical understanding and their aspects with respect to technical applications.Comment: A previous version of this article has been published in \" Applied Superconductivity: Handbook on Devices and Applications \", Wiley-VCH ISBN: 978-3-527-41209-9. The new extended and updated version will be published in \" Encyclopedia of Applied Physics \", Wiley-VC

    Could conservative iron chelation lead to neuroprotection in amyotrophic lateral sclerosis?

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    Iron accumulation has been observed in mouse models and both sporadic and familial forms of Amyotrophic lateral sclerosis. Iron chelation could reduce iron accumulation and the related excess of oxidative stress in the motor pathways. However, classical iron chelation would induce systemic iron depletion. We assess the safety and efficacy of conservative iron chelation (i.e. chelation with low risk of iron depletion) in a murine preclinical model and pilot clinical trial. In Sod1G86R mice, deferiprone increased the mean life span as compared with placebo. The safety was good, without anemia after 12 months of deferiprone in the 23 ALS patients enrolled in the clinical trial. The decreases in the ALS Functional Rating Scale and the body mass index (BMI) were significantly smaller for the first 3 months of deferiprone treatment (30 mg/kg/day) than for the first treatment-free period. Iron levels in the cervical spinal cord, medulla oblongata and motor cortex (according to MRI), as well as cerebrospinal fluid levels of oxidative stress and neurofilament light chains were lower after deferiprone treatment. Our observation leads to the hypothesis that moderate iron chelation regimen that avoids changes in systemic iron levels may constitute a novel therapeutic modality of neuroprotection for ALS

    Heat transfer in a swirling fluidized bed with Geldart type-D particles

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    A relatively new variant in fluidized bed technology, designated as the swirling fluidized bed (SFB), was investigated for its heat transfer characteristics when operating with Geldart type D particles. Unlike conventional fluidized beds, the SFB imparts secondary swirling motion to the bed to enhance lateral mixing. Despite its excellent hydrodynamics, its heat transfer characteristics have not been reported in the published literature. Hence, two different sizes of spherical PVC particles (2.61mm and 3.65mm) with the presence of a center body in the bed have been studied at different velocities of the fluidizing gas. The wall-to-bed heat transfer coefficients were measured by affixing a thin constant foil heater on the bed wall. Thermocouples located at different heights on the foil show a decrease in the wall heat transfer coefficient with bed height. It was seen that only a discrete particle model which accounts for the conduction between the particle and the heat transfer surface and the gas-convective augmentation can adequately represent the mechanism of heat transfer in the swirling fluidized bed

    DMTs and Covid-19 severity in MS: a pooled analysis from Italy and France

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    We evaluated the effect of DMTs on Covid-19 severity in patients with MS, with a pooled-analysis of two large cohorts from Italy and France. The association of baseline characteristics and DMTs with Covid-19 severity was assessed by multivariate ordinal-logistic models and pooled by a fixed-effect meta-analysis. 1066 patients with MS from Italy and 721 from France were included. In the multivariate model, anti-CD20 therapies were significantly associated (OR = 2.05, 95%CI = 1.39–3.02, p < 0.001) with Covid-19 severity, whereas interferon indicated a decreased risk (OR = 0.42, 95%CI = 0.18–0.99, p = 0.047). This pooled-analysis confirms an increased risk of severe Covid-19 in patients on anti-CD20 therapies and supports the protective role of interferon

    Role of PRC1 chromatin factors in the robustness of neuronal differentiation programs in C. elegans

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    L’acquisition et le maintien de l’identité d’un neurone sont assurés par des facteurs de transcription terminaux exprimés durant toute la vie du neurone. Cependant le processus d’expression génique peut être très bruité. L’objectif de mon projet de thèse est de déterminer comment un neurone peut acquérir et maintenir son identité de manière fiable malgré ce bruit intrinsèque, en utilisant le modèle C. elegans. En combinant des techniques récentes d’ingénierie du génome par CRISPR et des méthodes d’imagerie quantitative in vivo, j’ai observé que l’expression endogène des facteurs de transcription terminaux est fortement bruitée. J’ai également établi que des mutations dans le complexe chromatinien PRC1 induisent une perte stochastique de l’identité de certains neurones au cours du temps. Le complexe PRC1 agit directement au sein des neurones. Il affecte le niveau d’initiation de l’expression des facteurs de transcription terminaux durant l’embryogenèse ainsi que la fiabilité de la maintenance de leur expression aux stades larvaires et adultes. En conclusion, mon travail suggère que le complexe PRC1 joue un rôle important dans la protection des neurones contre le bruit génique, les aidant ainsi à acquérir et maintenir de manière fiable leur identité.The acquisition and maintenance of neuronal identity is driven by terminal transcription factors expressed throughout the life of the neuron. However, the gene expression process can be noisy. The aim of my PhD work is to determine how a neuron can acquire and maintain its identity in a reliable manner despite this intrinsic noise, using C. elegans as a model system. Combining recent techniques of genome engineering by CRISPR with in vivo quantitative imaging, I observed that the endogenous expression of terminal transcription factors is highly noisy. I also established that mutations in the chromatin complex PRC1 induce a stochastic loss of the identity of some neurons over time. The PRC1 complex directly acts in the neurons. It affects the levels of initiation of the terminal transcription factors during embryogenesis as well as the reliability of their maintenance at larval and adult stages. To conclude, my work suggests that the PRC1 complex plays an important role to protect neurons against gene expression noise, helping them to acquire and maintain their identity in a reliable manner

    Zic Genes in Nematodes: A Role in Nervous System Development and Wnt Signaling

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    International audienceTranscription factors of the Zic family play important roles during animal development, and their misregulation has been implicated in several human diseases. Zic proteins are present in nematodes, and their function has been mostly studied in the model organism C. elegans. C. elegans possesses only one Zic family member, REF-2. Functional studies have shown that this factor plays a key role during the development of the nervous system, epidermis, and excretory system. In addition, they have revealed that the C. elegans Zic protein acts as an atypical mediator of the Wnt/β-catenin pathway. In other animals including vertebrates, Zic factors are also regulators of nervous system development and modulators of Wnt signaling, suggesting that these are evolutionary ancient functions of Zic proteins

    Poly(ADP-ribosyl)ating enzymes coordinate changes in the expression of metabolic genes with developmental progression

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    Abstract Metabolism, known to be temporally regulated to meet evolving energy demands, plays a crucial role in shaping developmental pace. Recent studies have demonstrated that two key proteins PARP1 and PARG play a regulatory role in the transcription of both morphogenic and metabolic genes. Intriguingly, in Drosophila, the depletion of PARP1 or PARG proteins causes a developmental arrest before pupation, resulting in individuals unable to complete their development. This phenotype highlights the critical involvement of poly(ADP-ribosyl)ating enzymes in regulating the metamorphic process. In this study, we provide compelling evidence that these enzymes intricately coordinate transcriptional changes in both developmental and metabolic pathways during metamorphosis. Specifically, they promote the expression of genes crucial for pupation, while simultaneously negatively regulating the expression of metabolic genes before the transition to the pupal stage. Additionally, these enzymes suppress the expression of genes that are no longer required during this transformative period. Our findings shed light on the intricate interplay between poly(ADP-ribosyl)ating enzymes, developmental processes, and metabolic regulation before metamorphosis and highlight a new role of poly(ADP-ribosyl)ating enzymes in the global regulation of transcription

    Age-Related Changes of Gene Expression Profiles in Drosophila

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    An individual’s gene expression profile changes throughout their life. This change in gene expression is shaped by differences in physiological needs and functions between the younger and older organism. Despite intensive studies, the aging process is not fully understood, and several genes involved in this process may remain to be identified. Here we report a transcriptomic analysis of Drosophila melanogaster using microarrays. We compared the expression profiles of two-day-old female adult flies with those of 45-day-old flies. We identified 1184 genes with pronounced differences in expression level between young and old age groups. Most genes involved in muscle development/maintenance that display different levels of expression with age were downregulated in older flies. Many of these genes contributed to sarcomere formation and function. Several of these genes were functionally related to direct and indirect flight muscles; some of them were exclusively expressed in these muscles. Conversely, several genes involved in apoptosis processes were upregulated in aging flies. In addition, several genes involved in resistance to toxic chemicals were upregulated in aging flies, which is consistent with a global upregulation of the defense response system in aging flies. Finally, we randomly selected 12 genes among 232 genes with unknown function and generated transgenic flies expressing recombinant proteins fused with GFP protein to determine their subcellular expression. We also found that the knockdown of some of those 12 genes can affect the lifespan of flies

    PRC1 chromatin factors strengthen the consistency of neuronal cell fate specification and maintenance in C. elegans

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    International audienceIn the nervous system, the specific identity of a neuron is established and maintained by terminal selector transcription factors that directly activate large batteries of terminal differentiation genes and positively regulate their own expression via feedback loops. However, how this is achieved in a reliable manner despite noise in gene expression, genetic variability or environmental perturbations remains poorly understood. We addressed this question using the AIY cholinergic interneurons of C. elegans, whose specification and differentiation network is well characterized. Via a genetic screen, we found that a loss of function of PRC1 chromatin factors induces a stochastic loss of AIY differentiated state in a small proportion of the population. PRC1 factors act directly in the AIY neuron and independently of PRC2 factors. By quantifying mRNA and protein levels of terminal selector transcription factors in single neurons, using smFISH and CRISPR tagging, we observed that, in PRC1 mutants, terminal selector expression is still initiated during embryonic development but the level is reduced, and expression is subsequently lost in a stochastic manner during maintenance phase in part of the population. We also observed variability in the level of expression of terminal selectors in wild type animals and, using correlation analysis, established that this noise comes from both intrinsic and extrinsic sources. Finally, we found that PRC1 factors increase the resistance of AIY neuron fate to environmental stress, and also secure the terminal differentiation of other neuron types. We propose that PRC1 factors contribute to the consistency of neuronal cell fate specification and maintenance by protecting neurons against noise and perturbations in their differentiation program

    Wnt ligands regulate the asymmetric divisions of neuronal progenitors in C. elegans embryos

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    International audienceWnt/β-catenin signalling has been implicated in the terminal asymmetric divisions of neuronal progenitors in vertebrates and invertebrates. However, the role of Wnt ligands in this process remains poorly characterized. Here, we used the terminal divisions of the embryonic neuronal progenitors in C. elegans to characterize the role of Wnt ligands during this process, focusing on a lineage that produces the cholinergic interneuron AIY. We observed that, during interphase, the neuronal progenitor is elongated along the anteroposterior axis, then divides along its major axis, generating an anterior and a posterior daughter with different fates. Using time-controlled perturbations, we show that three Wnt ligands, which are transcribed at higher levels at the posterior of the embryo, regulate the orientation of the neuronal progenitor and its asymmetric division. We also identify a role for a Wnt receptor (MOM-5) and a cortical transducer APC (APR-1), which are, respectively, enriched at the posterior and anterior poles of the neuronal progenitor. Our study establishes a role for Wnt ligands in the regulation of the shape and terminal asymmetric divisions of neuronal progenitors, and identifies downstream components
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