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Compound screening platform using human induced pluripotent stem cells to identify small molecules that promote chondrogenesis

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Protein & Cell 2012年第12期3卷 934-942页

作者： Sheng-Lian Yang Erica Harnish Thomas Leeuw Uwe Dietz Erika Batchelder Paul SWright Jane Peppard Paul August Cecile Volle-Challier Francoise Bono jean-marc Herbert Juan Carlos Izpisua Belmonte Gene Expression Laboratories The Salk Institute for Biological Studies10010 N.Torrey Pines Rd.La JollaCA 92037USA Sanofi US R&DEarly to Candidate UnitTucson Research Center2090 E.Innovation Park DriveTucsonAZ 85755USA Sanofi Deutschland GmbH R&DTSU Aging Quality of LifeIndustriepark HoechstFrankfurt am Main 65926Germany Sanofi R&D Early to Candidate Unit195Route d'Espagne-BP 13669ToulouseFrance Center of Regeneration Medicine Dr.Aiguader 88Barcelona 08003Spain

Articular cartilage,which is mainly composed of collagen Ⅱ,enables smooth skeletal *** of collagen Ⅱ can be caused by various events,such as injury,but degeneration especially increases over the course of normal ***,the body does not fully repair itself from this type of degeneration,resulting in impaired ***,an articular cartilage repair surgical technique,has been commonly used in the clinic to induce the repair of tissue at damage *** stem cells(MSC)have also been used as cell therapy to repair degenerated ***,the therapeutic outcomes of all these techniques vary in different patients depending on their age,health,lesion size and the extent of damage to the *** repairing tissues either form fibrocartilage or go into a hypertrophic stage,both of which do not reproduce the equivalent functionality of endogenous hyaline *** of the reasons for this is inefficient chondrogenesis by endogenous and exogenous *** that promote chondrogenesis could be used to induce self-repair of damaged cartilage as a non-invasive approach alone,or combined with other techniques to greatly assist the therapeutic *** recent development of human induced pluripotent stem cell(iPSCs),which are able to self-renew and differentiate into multiple cell types,provides a potentially valuable cell resource for drug screening in a“more relevant”cell *** we report a screening platform using human iPSCs in a multi-well plate format to identify compounds that could promote chondrogenesis.

关键词： hESC hiPSC chondrogenesis compound screening platform

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走出荒野

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2015年

作者： directed by jean-marc Vallee eng

影片改编自美国作家谢莉尔·斯瑞德2012年的同名自传，讲述婚姻触礁，母亲去世，自己在绝望中生活多年之后，虽然毫无徒步经验，却独自一人踏上PacificCrestTrail远足之路，通过长途步行找回自我的故事。

ISBN: (纸本)9787799149929

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A Potential Flow Based Flight Simulator for an Underwater Glider

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Journal of Marine Science and Application 2013年第1期12卷 112-121页

作者： Surasak Phoemsapthawee marc Le Boulluec jean-marc Laurens Fran ois Deniset International Maritime College Kasetsart University-Si Racha Campus Si Racha 20230 Thailand Ifremer RDT/HOBP-70 Plouzané 29280 France Ensta-Bretagne 2 rue Fran ois VernyBrest cedex9 29806France IRENav Ecole NavaleLanveoc CC-600Brest cedex9 29240France

Underwater gliders are recent innovative types of autonomous underwater vehicles （AUVs） used in ocean exploration and observation. They adjust their buoyancy to dive and to return to the ocean surface. During the change of altitude, they use the hydrodynamic forces developed by their wings to move forward. Their flights are controlled by changing the position of their centers of gravity and their buoyancy to adjust their trim and heel angles. For better flight control, the understanding of the hydrodynamic behavior and the flight mechanics of the underwater glider is necessary. A 6-DOF motion simulator is coupled with an unsteady potential flow model for this purpose. In some specific cases, the numerical study demonstrates that an inappropriate stabilizer dimension can cause counter-steering behavior. The simulator can be used to improve the automatic flight control. It can also be used for the hydrodynamic design optimization of the devices.

关键词： underwater glider potential flow Newton-Euler equation autonomous underwater vehicles (AUVs) flight simulator

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Dynamics of hepatic and intestinal cholesterol and bile acid pathways: The impact of the animal model of estrogen deficiency and exercise training

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World Journal of Hepatology 2016年第23期8卷 961-975页

作者： jean-marc Lavoie Department of Kinesiology University of Montreal

Plasma cholesterol level is determined by a complex dynamics that involves transport lipoproteins which levels are tightly dependent on how the liver and the intestine regulate cholesterol and biliary acid metabolism. Regulation of cholesterol and biliary acids by the liver and the intestine is in turn coupled to a large array of enzymes and transporters that largely influence the inflow and the outflow of cholesterol and biliary acids through these organs. The activity of the key regulators of cholesterol and biliary acids may be influenced by several external factors such as pharmacological drugs and the nutritional status. In recent years, more information has been gathered about the impact of estrogens on regulation of cholesterol in the body. Exposure to high levels of estrogens has been reported to promote cholesterol gallstone formation and women are twice as likely as men to develop cholesterol gallstones. The impact of estrogen withdrawal, such as experienced by menopausal women, is therefore of importance and more information on how the absence of estrogens influence cholesterol regulation is started to come out, especially through the use of animal models. An interesting alternative to metabolic deterioration due to estrogen deficiency is exercise training. The present review is intended to summarize the present information that links key regulators of cholesterol and biliary acid pathways in liver and intestine to the absence of estrogens in an animal model and to discuss the potential role of exercise training as an alternative.

关键词： PSCK9 Low-density Lipoprotein receptor Very low-density Lipoprotein Sterol regulatory element binding proteins Ovariectomy High-density Lipoprotein Lipoproteins

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一种源自北非蝎的抗昆虫毒素Am IT的结构与功能鉴定(英文)

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生理学报 2015年第3期67卷 295-304页

作者： Naoual Oukkache Rachid ElJaoudi Fatima Chgoury Marisa Teixeira Rocha jean-marc Sabatie 摩洛哥巴斯德研究所毒液和毒素实验室摩洛哥卡萨布兰卡20360 布坦坦研究所毒液学实验室爬虫学部巴西圣保罗05503-900 拉巴特研究所医学和药学系药理毒理实验室摩洛哥拉巴特艾克斯-马赛大学全国保健与医学研究所(INSERM) 法国马赛13288

本研究主要分离和鉴定了一种源自北非蝎被称为Am IT的新毒素。详细分析了Am IT对昆虫神经索钠电流的调节效应。Am IT经凝胶过滤纯化后通过C18反相高效液相色谱法纯化。采用雄性德国蟑螂(德国小蠊)的幼虫和C57/BL6小鼠进行Am IT体内毒性... 详细信息

本研究主要分离和鉴定了一种源自北非蝎被称为Am IT的新毒素。详细分析了Am IT对昆虫神经索钠电流的调节效应。Am IT经凝胶过滤纯化后通过C18反相高效液相色谱法纯化。采用雄性德国蟑螂(德国小蠊)的幼虫和C57/BL6小鼠进行Am IT体内毒性分析。Am IT与两种β毒素的竞争实验则采用125I修饰的毒素通过与大鼠脑突触体膜的放射免疫法测定。Am IT的氨基酸序列通过Edman降解法测定。在结合实验中,Am IT被观察到与另一种源自北非蝎的毒素AaH IT4存在竞争效应。而且它可以被β型毒素的抗体识别,由此说明它与β型毒素(或相关毒素家族)的结构相似。新毒素显示了双重的活性,它既能与抗哺乳动物毒素在结合实验中竞争,又能促使昆虫躯体产生收缩反应。该毒素能够竞争携带放射标记的β毒素Css IV与大鼠突触体膜钠通道的结合。通过氨基酸序列分析,Am IT显示出与AaH IT4有92%的同源性。以上结果说明,Am IT不但显示了隶属于旧大陆的抗昆虫毒素的性质,表现为结合于昆虫的钠通道;而且它与隶属于新大陆的抗哺乳动物毒素类似,表现为对小鼠的毒性。因此,Am IT与AaH IT4在结构与功能上是极为类似的。

关键词：北非蝎毒蝎毒素 Am IT β毒素抗哺乳动物毒素抗昆虫毒素钠通道毒性从头测序 Edman降解法

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Normalized intervertebral disc MRI signal as a biomarker of pain

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Journal of Biomedical Science and Engineering 2013年第3期6卷 372-380页

作者： Mohamed Aissiou Delphine Périé jean-marc Mac-Thiong Department of Surgery Faculty of Medicine Université de Montréal Montreal Canada Mechanical Engineering Department Ecole Polytechnique de Montréal Montreal Canada Research Center Sainte-Justine University Hospital Montreal Canada

The drop in the MRI signal intensity, analysed without any normalisation, was found related to the intervertebral disc degeneration, but its association with low back pain remains controversial. The authors developed the analysis of MR signal intensity distribution (AMRSID) method that analyzes the 3D distribution of the normalized T2-weighted MR signal intensity within the intervertebral disc using descriptive statistics of histograms and weighted centers. In this study, we hypothesized that the distribution of the normalized MRI signal intensity within T2- weighted images of the intervertebral disc is a bio-marker of low back pain (LBP) independently of age and disc degenerescence. The aims were to: 1) characterize intervertebral disc degeneration in vertebral fracture from MR T1-weighted and T2-weighted images;2) evaluate the sensitivity of the normalized MRI signal distribution to the presence of LBP, discs height loss and aging. We prospectively studied 22 patients who underwent an MRI acquisition within 48h after an accidental lumbar vertebral fracture. The presence of prefracture low back pain, spinal stenosis, annular disruption, intervertebral disc height loss was noted from each patient’s medical record. The presence of Modic changes, High-Intensity Zones (HIZs) and vertebral endplate perforations was recorded from MRI. The descriptive statistics of the normalized T2-weighted signal were compared using one-way ANOVAs and a principal component analysis was proposed. MRI, associated to normalisation of the signal intensity and principal component analysis, offers a remarkable potential for in-vivo imaging and analysis of vertebral fractures and adjacent tissues for the patient’s follow-up. The mean normalized MRI signal intensity of the adjacent intervertebral disc to the vertebral fracture was found to be a bio-marker of pain, independently of age and disc degeneration. However, the parameters describing the distribution of the normalized signal intensity w

关键词： MRI Intervertebral Disc Normalized Signal Intensity Low Back Pain Vertebral Fractures

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Ultrastructure and Analytical Features of the Sinus Floor Augmentation with Osteograph^(█) and PepGen P-15^(█)

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Journal of Biomaterials and Nanobiotechnology 2013年第1期4卷 64-73页

作者： jean-Christophe Dahlet Abdessamad Boukari marc Collavini Joseph Hemmerle Dental Faculty University of Strasbourg1 Place de l’HopitalStrasbourgFrance National Institute for Health and Medical Research(INSERM)UMR 977 11 Rue HumannStrasbourgFrance

The aim of the present study was to investigate an inorganic bovine-derived hydroxyapatite bone substitute (Osteograph?) mixed with the same biomaterial coated with a synthetic peptide (P-15) analogue of collagen (PepGen P-15?). This blend of bone replacement materials was used for sinus floor augmentation. Assessments were carried out by using histology methods, transmission electron microscopy (TEM) and microanalysis (EDX). Ultrastructural and analytical features of the interfaces between the graft material and the peri-biomaterial tissues were evaluated six months after implantation. Our findings clearly show that newly-formed crystallites first develop at the surface of implanted crystals. Histological investigations revealed new bone tissue linking biomaterial particles together. TEM assessments pointed out that lamellar bone was generally separated from the graft material by a layer of woven bone measuring between 1 and 1.5 μm in thickness. Although calcified bone tissue was observed in direct contact with bone filling particles, the presence of mineralized granular material around implanted particles was also noticed. No characteristic periodic striation of mineralized collagen was evident within that mineralized structure. Chemical analyses (TEM-EDX) realized at different locations of newly formed mineralized granular substance along the interface revealed average Ca/P ratios ranging between 1.02 and 1.63. The different, concomitantly occurring, aforementioned structural features of the interfaces strongly suggested that the host responses to the used biomaterial blend resulted from dynamic osseointegration phenomena related to various interfacial mechanisms. Nevertheless, the biological response to the bone graft material appeared clinically and histologically satisfactory.

关键词： Sinus Floor Augmentation Bone Grafting Osteograph^(█) PepGen P-15^9█) Ultrastructure Microanalysis

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Automatic Optimization of Chirp Setting Parameters in Medical Ultrasound Contrast Imaging

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Journal of Life Sciences 2013年第6期7卷 592-598页

作者： Amira Zaylaa Sebastien Menigot Jamal Charara jean-marc Girault Department of Medical Biophysics and Imaging Universite Franqois Rabelais de Tours UMR-S930 and ERL3106 B.P 3223Tours France INSERM U930 Tours France Department of Physics and Electronics Lebanese University Hadath Campus B.P. 5 Beirut Lebanon IUT Ville d'Avray Universite Paris Ouest Nanterre La Defense B.P. 105 Avray France

Medical ultrasound contrast imaging is a powerful modality undergoing successive developments in the last decade to date Lately, pulse inversion has been used in both ultrasound tissue harmonic and contrast imaging. However, there was a tradeoff between resolution and penetration. Chirp excitations partially solved the tradeoff, but the chirp setting parameters were not optimized. The present work proposes for the first time combining chirp inversion with ultrasound contrast imaging, with the motivation to improve the contrast, by automatically optimizing the setting parameters of chirp excitation, it is thus an optimal command problem. Linear chirps, 5 μm diameter microbubbles and gradient ascent algorithm were simulated to optimize the chirp setting parameters. Simulations exhibited a gain of 5 dB by automatic optimization of chirp inversion relative to pulse inversion. The automatic optimization process was quite fast. Combining chirp inversion with ultrasound contrast imaging led to a maximum backscattered power permitting high contrast outcomes and optimum parameters.

关键词： Medical ultrasound contrast imaging chirp inversion chirp setting parameters automatic technique optimal command.

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Ab Initio Study of the Electronic and Vibrational Properties of 1-nm-Diameter Single-Walled Nanotubes

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Advances in Materials Physics and Chemistry 2013年第2期3卷 178-184页

作者： Jesus Marquina Chrystian Power Jesus Gonzalez jean-marc Broto Centro de Estudios Avanzado en Optica Facultad de CienciasUniversidad de los AndesMeridaVenezuela Centro de Estudios de Semiconductores Facultad de CienciasUniversidad de los AndesMeridaVenezuela Malta Consolider Team CITIMACFacultad de CienciasUniversidad de CantabriaSantanderEspana LNCMI Paul Sabatier UniversityToulouseFrance

The electronic structure, band gap, density of states of the (8,8), (14,0) and (12,3) single-walled carbon nanotubes by the SIESTA (Spanish Initiative for Electronic Simulations with Thousands of Atoms) method in the framework density-functional theory (DFT) with the generalized gradients approximation (GGA) were studied. Also, we studied the vibrational properties of the (8,8) and (14,0) nanotubes. Only the calculated relaxed geometry for (12,3) nanotube show significant deviations from the ideal rolled graphene sheet configuration. The electronic transition energies of van Hove singularities were studied and compared with previous results. The calculated band structures, density of states and dispersion curves for all tubes were in good agreement with theoretical and experimental results.

关键词： Carbon Nanotubes Electronic Structure Dispersion Curve

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sTREM-1 is a specific biomarker of TREM-1 pathway activation

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Cellular & Molecular Immunology 2021年第8期18卷 2054-2056页

作者： Lucie Jolly Kévin Carrasco Margarita Salcedo-Magguilli jean-Jacques Garaud Simon Lambden Tom van der Poll Alexandre Mebazaa Pierre-François Laterre Sebastien Gibot Amir Boufenzer marc Derive Inotrem Vandœuvre-lès-NancyFrance Division of Infectious Diseases Amsterdam University Medical CentersUniversity of AmsterdamAmsterdamThe Netherlands Intensive Care Unit Saint Louis-Lariboisière-Fernand Widal University HospitalAssistance Publique Hôpitaux de Parisand Universitéde ParisInserm MASCOTParisFrance Intensive Care Unit UniversitéCatholique de LouvainLouvain-la-NeuveBelgium Intensive Care Unit CHRU de Nancyand Universitéde LorraineNancyFrance

TREM-1(triggering receptor expressed on myeloid cells-1)is a transmembrane receptor expressed by innate immune cells,including endothelial cells and ***-1 is a crucial mediator of septic shock that acts by synergizing with Toll-like receptors(TLRs)to amplify the inflammatory responses to pathogens,thus promoting sepsis-induced immune dysregulation and organ dysfunction[1,2,3].

关键词： immune myeloid activation

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