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短暂性脱髓鞘导致长期认知障碍、髓鞘改变和神经网络同步缺陷

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神经损伤与功能重建 2024年第3期19卷 F0003-F0003页

作者： Océane Mercier Pascale P Quilichini Karine Magalon Florian Gil Antoine Ghestem Fabrice Richard Thomas Boudier Myriam Cayre Pascale Durbec 杜一星(编译) UMR7288 after IBDM Aix Marseille UnivCNRSIBDMMarseilleFrance U1106 after INS Aix Marseille UnivINSERMINSInst Neurosci SystMarseilleFrance aix marseille Univ Turing Centre for Living SystemsMarseilleFrance 不详

在成年大脑中,活动依赖性髓鞘可塑性是正确学习和记忆巩固所必需的。因此,髓鞘的丢失、改变,甚至细微的结构变更都会损害神经网络活动,导致功能障碍。在多发性硬化症中,虽然自发的髓鞘修复过程是可能的,但患者之间存在异质性。髓鞘修复... 详细信息

在成年大脑中,活动依赖性髓鞘可塑性是正确学习和记忆巩固所必需的。因此,髓鞘的丢失、改变,甚至细微的结构变更都会损害神经网络活动,导致功能障碍。在多发性硬化症中,虽然自发的髓鞘修复过程是可能的,但患者之间存在异质性。髓鞘修复有时会导致功能恢复,这通常在运动水平比在认知水平更明显。在铜宗处理的小鼠模型中,大量脑脱髓鞘随后发生自发且强烈的髓鞘再生。然而,重组髓鞘虽然具有功能,但可能不会表现出与发育髓鞘相同的形态特征,这可能会对神经网络的活动产生影响。基于此,本研究使用铜腙处理的小鼠模型来分析短暂性脱髓鞘对脑结构、功能和认知的长期影响。本研究结果表明,尽管脱鞘事件后存在髓鞘再生,但仍会导致长期认知障碍,例如空间工作记忆、社交记忆、认知灵活性和多动症的缺陷。这些缺陷与内侧前额叶皮质(m PFC)和海马体(HPC)髓鞘含量的减少以及结构髓鞘修饰有关,表明这些结构中的髓鞘再生过程可能不完善。在体电生理记录表明,脱髓鞘事件改变了HPC-mPFC活动的同步性,这对于记忆过程至关重要。总而言之,本研究数据表明,短暂脱髓鞘后的髓鞘修复过程不允许完全恢复皮质结构中的初始髓鞘特性。这些细微的变更改变了神经网络特征并导致小鼠长期认知缺陷。

关键词：认知多发性硬化症小鼠模型髓鞘再生神经网络活动

Reply to ‘Comment to: Single-cell profiling reveals the trajectories of natural killer cell differentiation in bone marrow and a stress signature induced by acute myeloid leukemia’

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Cellular & Molecular Immunology 2021年第5期18卷 1350-1352页

作者： Adeline Crinier Bertrand Escalière Emilie Narni-Mancinelli Eric Vivier aix marseille university CNRSINSERMCentre d’Immunologie de Marseille-LuminyMarseilleFrance APHM Hôpital de la TimoneMarseille-ImmunopôleMarseilleFrance Innate Pharma Research Laboratories Innate PharmaMarseilleFrance

We thank Melsen et *** their interest in our *** remarks allow us to clarify key aspects of our work on human bone marrow NK cell biology.1 Our study reports the unsupervised single-cell analysis of NK cells from eight healthy donors and eight acute myeloid leukemia(AML)patients.1 First,we detected an adaptive NK cell subset that correlated with the cytomegalovirus(CMV)positivity status of the donors.

关键词： myeloid acute

Systemic treatment for metastatic prostate cancer

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Asian Journal of Urology 2019年第2期6卷 162-168页

作者： Gwenaelle Gravis Centre de Recherche en Cancerologie de marseille(CRCM) Institut Paoli-CalmettesAix-Marseille UniversityMarseilleFrance

The management of metastatic prostate cancer(mPCa)has changed over the past ten *** new drugs have been approved with significant overall survival benefits in metastatic castration resistant prostate cancer(PCa)including chemotherapy(docetaxel,cabazitaxel),new hormonal therapies(abiraterone,enzalutamide),Radium-223 and *** addition of docetaxel to androgen deprivation therapy(ADT)versus ADT alone in the castration sensitive metastatic setting has gained significant overall survival benefit particularly for high volume *** recently two phase III trials have assessed the efficacy of abiraterone plus prednisone plus ADT over ADT alone in newly high risk castrate sensitive *** of the appropriate treatment sequence using these therapies is important for maximizing the clinical benefit in castration sensitive and castration resistant PCa *** fields are the identification of new subtypes with molecular characterization and new therapeutic targets.

关键词： Prostate cancer Metastatic prostate cancer Castrate sensitive metastatic prostate cancer Abiraterone Docetaxel

Molecular engineering of dendrimer nanovectors for siRNA delivery and gene silencing

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Frontiers of Chemical Science and Engineering 2017年第4期11卷 663-675页

作者： Yu Cao Xiaoxuan Liu Ling Peng . aix-marseille université CNRS Centre Interdisciplinaire de Nanoscience de Marseille UMR 7325 Equipe Labellisée Ligue Contre le Caner 13288 Marseille France.. State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases Center of Drug Discovery Center of Advanced Pharmaceuticals and Biomaterials China Pharmaceutical University Nanjing 210009 China

Small interfering RNA （siRNA） therapeutics hold great promise to treat a variety of diseases, as long as they can be delivered safely and effectively into cells. Dendrimers are appealing vectors for siRNA delivery by virtue of their well-defined molecular architecture and multivalent cooperativity. However, the clinical translation of RNA therapeutics mediated by dendrimer delivery is hampered by the lack of dendrimers that are of high quality to meet good manufacturing practice standard. In this context, we have developed small amphiphilic dendrimers that self-assemble into supramolecular structures, which mimic high-generation dendrimers synthesized with cova- lent construction, yet are easy to produce in large amount and superior quality. Indeed, the concept of supramolecular dendrimers has proved to be very promising, and has opened up a new avenue for dendrimer-mediated siRNA delivery. A series of self-assembling supramolecular dendrimers have consequently been established, some of them out-performing the currently available nonviral vectors in delivering siRNA to various cell types in vitro and in vivo, including human primary cells and stem cells. This short review presents a brief introduction to RNAi therapeutics, the obstacles to their delivery and the advantages of dendrimer delivery vectors as well as our bio-inspired struc^rally flexible dendrimers for siRNA delivery. We then highlight our efforts in creating self- assembling amphiphilic dendrimers to construct supramo- lecular dendrimer nanosystems for effective siRNA delivery as well as the related structural alterations to enhance delivery efficiency. The advent of self-assembling supramolecular dendrimer nanovectors holds great pro- mise and heralds a new era of dendrimer-mediated delivery of RNA therapeutics in biomedical applications.

关键词： gene therapy RNAi therapeutics dendrimer,nanovectors gene silencing

Two is better than one: combinatorial receptor targeting enhances hepatocellular carcinoma (HCC) therapeutic response

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Hepatobiliary Surgery and Nutrition 2022年第1期11卷 139-142页

作者： Celia Sequera Flavio Maina aix marseille Univ CNRSDevelopmental Biology Institute of Marseille(IBDM)Turing Center for Living SystemsParc Scientifique de LuminyMarseilleFrance

Finding effective therapies for hepatocellular carcinoma(HCC)is an ongoing challenge for both researchers and *** for new treatment options emerging from in vitro,preclinical,and clinical studies is often tempered by limited patient benefits and associated side effects,tolerated in some cases due to the lack of *** complexity of identifying effective treatment options resides in several features of HCC,notably the extraordinary heterogeneity in molecular alterations among different patients(1-3),the lack of consistent alterations associated with oncogene addictions(4),and a so-called“non-oncogene addiction”by which tumorigenicity results from the action of non-mutated genes(5,6).This complex configuration also prevents identification of unequivocal alterations used to design therapies,as for some other cancer *** HCC treatments are based on the Barcelona Clinic Liver Cancer(BCLC)guidelines according to the stage of lesions among other *** HCC at early stages(30-40%of HCC patients),treatments include lesion resection,liver transplantation,radiofrequency ablation(RFA)and microwave ablation(MWA),achieving a median overall survival(OS)of more than 60 *** HCC at intermediate stages(~20%of HCC patients),the advised treatment is generally transarterial chemoembolization(TACE),achieving an OS of 20 *** HCC at advanced stages(~40%of HCC patients),targeted therapies are the most frequent treatments,leading to an OS of 11 months with most targeted *** HCC at terminal stages,only palliative care is provided(~10%of HCC patients),with less than 3 months OS(7,8).

关键词： alterations hepatocellular treatment

Bio-inspired Topological Skeleton for the Analysis of Quadruped Kinematic Gait

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Journal of Bionic Engineering 2018年第5期15卷 839-850页

作者： Benjamin Boudon Jean-Marc Linares Anick Abourachid Arthur Vauquelin Emmanuel Mermoz aix marseille university CNRS ISM Marseille 13009 France Museum National d'Histoire Naturelle Pavillon d'Anatomie Comparbe 57 rue Cuvier F-75231 Paris Cedex 05 France Airbus Helicopters Abroport de Marseille Provence Marignane 13700 France

In bio-inspired design activities, nature is a basis of knowledge. Over the last twenty years, many solutions to measure and analyze human or animal gaits have been developed （VICON system, X-ray radiography...）. Although, these methods are becoming more and more accurate, they are quite expensive, long to set up and not easily portable. In this paper, a method called the bio-inspired topological skeleton is proposed in order to complement the classic videography process and to enable animal gait analysis. A new predictive kinematic model with closed-loops of an unguligrade quadruped is suggested. This kinematic model includes three segments per leg and takes into account the scapula movements. The proposed method allows us to improve the accuracy of the kinematic input data measured from a single video including an additional artefact. To show the benefits of this method, joint parameters that are difficult to measure are derived symbolically from the kinematic model and compared with experimental data.

关键词： quadruped locomotion motion analysis topological skeleton closed-form solutions Multibody Systems (MBS)

Conversion of the refractory ammonia and acetic acid in catalytic wet air oxidation of animal byproducts

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Journal of Environmental Sciences 2011年第3期23卷 520-528页

作者： Virginie Fontanier Sofiane Zalouk Stéphane Barbati aix-marseille universite's-CNRS (UMR 6264)-Laboratoire de Chimie Provence:quipe Chimie de l'Environnement Continental-3 Place Victor Hugo (case 29)-13331 Marseille cedex 3France

Wet air oxidation （WAO） and catalytic wet air oxidation （CWAO） of slaughtered animal byproducts （ABPs） were investigated. Two step experiment was carried out consisting of a non-catalysed WAO run followed by a CWAO run at 170-275 ℃, 20 MPa, and reaction time 180 min. The WAO （lst step） of sample （5 g/L total organic carbon （TOC）） yielded （82.0 ±4）% TOC removal and （78.4 ± 13.2）% conversion of the initial organic-N into NH4＋-N. Four metal catalysts （Pd, Pt, Rh, Ru） supported over alumina have been tested in catalytic WAO （2nd step） at elevated pH to enhance ammonia conversion and organic matter removal, particularly acetic acid. It was found that the catalysts Ru, Pt, and Rh had significant effects on the TOC removal （95.1%, 99.5% and 96.7%, respectively） and on the abatement of ammonia （93.4%, 96.7% and 96.3%, respectively） with high nitrogen selectivity. The catalyst Pd was found to have the less activity while Pt had the best performance. The X-Ray diffraction analysis showed that the support of catalyst was not stable under the experimental conditions since it reacted with phosphate present in solution. Nitrite and nitrate ions were monitored during the oxidation reaction and it was concluded that CWAO of ammonia in real waste treatment framework was in good agreement with the results obtained from the literature for ideal solutions of ammonia.

关键词： wet oxidation, heterogeneous catalysis animal byproducts acetic acid ammonia, nitrite nitrate

Lagrangian model of zooplankton dispersion:numerical schemes comparisons and parameter sensitivity tests

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Chinese Journal of Oceanology and Limnology 2011年第2期29卷 438-445页

作者：丘仲锋 Andrea M.DOGLIOLI 何宜军 Francois CARLOTTI Key Laboratory of Ocean Circulation and Waves Institute of Oceanology CAS Laboratoire d'Ocanographie Physique et Biogochimie Aix Marseille UniversiteCNRSUMR 6535MarseilleFrance

This paper presents two comparisons or tests for a Lagrangian model of zooplankton dispersion:numerical schemes and time ***,we compared three numerical schemes using idealized *** show that the precisions of the advanced Adams-Bashfold-Moulton(ABM) method and the Runge-Kutta(RK) method were in the same order and both were much higher than that of the Euler ***,the advanced ABM method is more efficient than the RK method in computational memory requirements and time *** therefore chose the advanced ABM method as the Lagrangian particle-tracking ***,we performed a sensitivity test for time steps,using outputs of the hydrodynamic model,*** show that the time step choices depend on the fluid response time that is related to the spatial resolution of velocity *** method introduced by Oliveira et *** 2002 is suitable for choosing time steps of Lagrangian particle-tracking models,at least when only considering advection.

关键词： Lagrangian numerical scheme time steps zooplankton

In vitro gastrointestinal digestion study of two wheat cultivars and evaluation of xylanase supplementation

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Journal of Animal Science and Biotechnology 2015年第3期6卷 355-368页

作者： Mickael Lafond Bernard Bouza Sandrine Eyrichine Friedrich Rouffineau Luc Saulnier Thierry Giardina Estelle Bonnin Aurélie Preynat iSm2-BiosCiences UMR 7313 Aix Marseille Université Adisseo France S.A.S. Centre d'Expertise et de Recherche en Nutrition INRA UR 1268-BiopolymeresInteractions-Assemblages

Background： The filamentous fungus Talaromyces versatifis is known to improve the metabolizable energy of wheat- based poultry diets thanks to its ability to produce a pool of CAZymes and particularly endo-β（1,4）-xylanases. In order to appreciate their in vivo mode of action, the supplementation effect of two of its xylanases, XynD and XynB from families GH10 and GHll respectively, have been evaluated on two different wheat cultivars Caphorn and Isengrain, which were chosen amongst 6 varieties for their difference in non starch polysaccharides content and arabinoxylan composition. Results： Polysaccharides digestion was followed during 6 h along the digestive tract using the TNO gastrointestinal model-1, to mimic monogastric metabolism. Polysaccharide degradation appeared to occur mainly at the jejunal level and was higher with Isengrain than with Caphorn. For both cultivars, XynD and XynB supplementation increased notably the amount of reducing end sugars into the jejuno-ileal dialysates, which has been confirmed by a valuable increase of the soluble glucose into the jejunal dialysates. Conclusions： The amounts of arabinose and xylose into the dialysates and ileal deliveries increased consequently mainly for Caphorn, suggesting that XynD and XynB supplementation in wheat-based diet could alleviate the anti-nutritional effects of arabinoxylans by limiting the physical entrapment of starch and could increase the available metabolizable energy.

关键词： in vitro TNO gastrointestinal model-1 Talaromyces versatilis Wheat cultivars XynB XynD