42 research outputs found
LâintĂ©grine ÎČ1 et de son rĂ©gulateur ICAP-1α dans lâostĂ©ogenĂšse : rĂŽle dans la prolifĂ©ration, la diffĂ©renciation et la fonction ostĂ©oblastiques
Î1 integrins belong to a large family of receptors that have been shown to be of paramount importance for cell/extracellular matrix interactions. The ablation of the specific ÎČ1 integrin regulator ICAP-1α results in severe bone and mineralization defects. By combining mouse and cell biology we could demonstrate that loss of ICAP-1α was accompanied by an increase of ÎČ1 integrin activity that affects fibronectin and collagen deposition. Moreover, we could show that ICAP-1 is an important negative regulator of kindlin-2 recruitment on ÎČ1 integrin cytoplasmic domain (Brunner et al. JCB 2011). We then wanted to address the functional role of ÎČ1 integrin per se in osteogenesis and to understand how osteoblasts integrate environmental cues to coordinate bone formation and remodeling. For this we generated osteoblast specific ÎČ1 integrin deficient mice. These mice showed severe bone defects characterized by reduced bone mineralization and dynamic, as well as bending and fractures reminding human Juvenile Osteoporosis symptoms. In vitro analyses of ÎČ1 integrin deficient osteoblasts revealed proliferation defect which is not due to defective canonical MAPK/ERK pathway, but rather to defective activity of the co-transcription factor YAP. Then, we showed that ÎČ1 integrins are regulating cAMP level in osteoblasts and that the cAMP level correlates with YAP inactivation. We also linked YAP inactivation with raft endocytosis. Finally, in vivo and in vitro analyses revealed a functional incapacity of ÎČ1 integrin deficient osteoprecursors. We could show that the lazy phenotype of ÎČ1 integrin deficient osteoblasts is likely due to a reduced response to BMP signaling, a major osteoblast growth factor. Taken together, our findings demonstrate that ÎČ1 integrin is a key regulator of YAP-dependent osteoblast proliferation and BMP signaling allowing osteoblast functionality, mineralization and bone formation.L'intĂ©grine ÎČ1 appartient Ă une large famille de rĂ©cepteurs de premiĂšre importance pour les interactions cellule/matrice extracellulaire. La dĂ©lĂ©tion spĂ©cifique d'un rĂ©gulateur nĂ©gatif de l'intĂ©grine ÎČ1, ICAP-1α, induit de sĂ©vĂšres dĂ©fauts osseux. Nous avons pu montrer que la perte d'ICAP-1α est accompagnĂ©e d'une augmentation de l'activitĂ© de l'intĂ©grine ÎČ1, affectant le dĂ©pĂŽt des matrices de fibronectine et de collagĂšne de type I. De plus, nous avons pu montrer qu'ICAP-1α a une action antagoniste sur le recrutement de la kindline-2 au niveau du domaine cytoplasmique de l'intĂ©grine ÎČ1 (Brunner et al. JCB 2011). Nous nous sommes ensuite intĂ©ressĂ©s au rĂŽle de l'intĂ©grine ÎČ1 elle-mĂȘme dans l'ostĂ©ogenĂšse afin de comprendre comment les ostĂ©oblastes intĂšgrent les signaux du microenvironnement pour coordonner la formation et le remodelage osseux. Dans cette optique, nous avons gĂ©nĂ©rĂ© un modĂšle de souris dĂ©lĂ©tĂ©es pour l'intĂ©grine ÎČ1 spĂ©cifiquement dans les ostĂ©oblastes en cours de maturation. Ces souris prĂ©sentent un sĂ©vĂšre phĂ©notype osseux caractĂ©risĂ© par des rĂ©ductions importantes de la minĂ©ralisation et de la dynamique osseuse, ainsi que des dĂ©formations osseuses et des fractures rappelant le syndrome d'OstĂ©oporose JuvĂ©nile. L'analyse in vitro d'ostĂ©oblastes n'exprimant pas l'intĂ©grine ÎČ1 a rĂ©vĂ©lĂ© un dĂ©faut majeur de prolifĂ©ration impliquant non pas la voie canonique MAPK/ERK mais plutĂŽt un dĂ©faut d'activation du co-facteur de transcription YAP. De plus, nous avons pu montrer que les intĂ©grines ÎČ1 rĂ©gulaient le niveau d'AMP cyclique (AMPc) dans les ostĂ©oblastes et que ceci Ă©tait corrĂ©lĂ© Ă l'inactivation de YAP. De mĂȘme, nous avons pu relier l'inactivation de YAP Ă la dynamique d'endocytose des rafts. Finalement, des analyses in vivo et in vitro ont rĂ©vĂ©lĂ© un dĂ©faut fonctionnel des ostĂ©oblastes dĂ©pourvus d'intĂ©grine ÎČ1. Nous avons pu montrer que cette incapacitĂ© fonctionnelle Ă©tait due Ă une rĂ©duction de la rĂ©ponse au BMP-2, facteur de croissance ostĂ©oblastique majeur, non pas au niveau de son rĂ©cepteur mais probablement au niveau de l'activation des promoteurs BMP-dĂ©pendants. Nos rĂ©sultats montrent ainsi que l'intĂ©grine ÎČ1 est un rĂ©gulateur clĂ© de la prolifĂ©ration ostĂ©oblastique dĂ©pendante de YAP et de la signalisation BMP rĂ©gulant la fonction ostĂ©oblastique, la minĂ©ralisation et la formation osseuse
Study of surface treated historical materials
Import 05/08/2014DiplomovĂĄ prĂĄce se zabĂœvĂĄ obecnĂœm studiem povrchovĂœch Ășprav technikou plĂĄtkovĂ©ho zlacenĂ na historickĂœch pĆedmÄtech, zejmĂ©na obrazovĂœch rĂĄmech. V teoretickĂ© ÄĂĄsti prĂĄce pojednĂĄvĂĄ o historii a principech zhotovovĂĄnĂ technologiĂ zlacenĂ povrchu rĆŻznĂœch materiĂĄlĆŻ od minulosti k souÄasnosti. ZĆetel je kladen na dĆevÄnĂ© obrazovĂ© rĂĄmy a jejich ÄĂĄsti. CĂlem prĂĄce je prĆŻzkum sloĆŸenĂ povrchovĂœch Ășprav a to jak sloĆŸenĂ slitiny pouĆŸitĂ©ho plĂĄtkovĂ©ho kovu, tak sloĆŸenĂ pojiv a podkladovĂ© vrstvy. ExperimentĂĄlnĂ ÄĂĄst je zamÄĆena na prĆŻzkum povrchu historickĂœch pĆedmÄtĆŻ pomocĂ skenovacĂ elektronovĂ© mikroskopie a analĂœzu typu syntetickĂœch pryskyĆic rĂĄmĆŻ pomocĂ spektroskopickĂœch a chromatografickĂœch metod.This thesis deals with the general study of finishes leaf gilding technique on historical subjects, especially picture frames. The theoretical part deals with the history and principles of making technology gilding the surface of various materials from past to present. Consideration shall be given to the wooden picture frames and parts. The aim of the work is investigation of the finishes in both the composition of the alloy used leaf metal and binder composition and the underlying layer. The experimental part will focus on exploration of historical objects surface using scanning electron microscopy and analysis of the type of synthetic resin frames using chromatographic methods.636 - Katedra materiĂĄlovĂ©ho inĆŸenĂœrstvĂvĂœborn
Osteoblast mineralization requires ÎČ1 integrin/ICAP-1âdependent fibronectin deposition
ICAP-1 prevents recruitment of kindlin-2 to ÎČ1 integrin to control dynamics of fibrillar adhesion sites, fibronectin deposition, and osteoblast mineralization during bone formation
Afadin controls cell polarization and mitotic spindle orientation in developing cortical radial glia
In Vitro Models for Studying Secondary Plant Metabolite Digestion and Bioaccessibility
There is an increased interest in secondary plant metabolites, such as polyphenols and carotenoids, due to their proposed health benefits. Much attention has focused on their bioavailability, a prerequisite for further physiological functions. As human studies are time consuming, costly, and restricted by ethical concerns, in vitro models for investigating the effects of digestion on these compounds have been developed and employed to predict their release from the food matrix, bioaccessibility, and assess changes in their profiles prior to absorption. Most typically, models simulate digestion in the oral cavity, the stomach, the small intestine, and, occasionally, the large intestine. A plethora of models have been reported, the choice mostly driven by the type of phytochemical studied, whether the purpose is screening or studying under close physiological conditions, and the availability of the model systems. Unfortunately, the diversity of model conditions has hampered the ability to compare results across different studies. For example, there is substantial variability in the time of digestion, concentrations of salts, enzymes, and bile acids used, pH, the inclusion of various digestion stages; and whether chosen conditions are static (with fixed concentrations of enzymes, bile salts, digesta, and so on) or dynamic (varying concentrations of these constituents). This review presents an overview of models that have been employed to study the digestion of both lipophilic and hydrophilic phytochemicals, comparing digestive conditions in vitro and in vivo and, finally, suggests a set of parameters for static models that resemble physiological conditions
The Dark Energy Survey : more than dark energy â an overview
This overview paper describes the legacy prospect and discovery potential of the Dark Energy Survey (DES) beyond cosmological studies, illustrating it with examples from the DES early data. DES is using a wide-field camera (DECam) on the 4 m Blanco Telescope in Chile to image 5000 sq deg of the sky in five filters (grizY). By its completion, the survey is expected to have generated a catalogue of 300 million galaxies with photometric redshifts and 100 million stars. In addition, a time-domain survey search over 27 sq deg is expected to yield a sample of thousands of Type Ia supernovae and other transients. The main goals of DES are to characterize dark energy and dark matter, and to test alternative models of gravity; these goals will be pursued by studying large-scale structure, cluster counts, weak gravitational lensing and Type Ia supernovae. However, DES also provides a rich data set which allows us to study many other aspects of astrophysics. In this paper, we focus on additional science with DES, emphasizing areas where the survey makes a difference with respect to other current surveys. The paper illustrates, using early data (from âScience Verificationâ, and from the first, second and third seasons of observations), what DES can tell us about the Solar system, the Milky Way, galaxy evolution, quasars and other topics. In addition, we show that if the cosmological model is assumed to be +cold dark matter, then important astrophysics can be deduced from the primary DES probes. Highlights from DES early data include the discovery of 34 trans-Neptunian objects, 17 dwarf satellites of the Milky Way, one published z > 6 quasar (and more confirmed) and two published superluminous supernovae (and more confirmed)
ÎČ1 integrin and its regulator ICAP-1α functions during osteogenesis : implication for osteoblast proliferation, differentiation and function
L'intĂ©grine ÎČ1 appartient Ă une large famille de rĂ©cepteurs de premiĂšre importance pour les interactions cellule/matrice extracellulaire. La dĂ©lĂ©tion spĂ©cifique d'un rĂ©gulateur nĂ©gatif de l'intĂ©grine ÎČ1, ICAP-1α, induit de sĂ©vĂšres dĂ©fauts osseux. Nous avons pu montrer que la perte d'ICAP-1α est accompagnĂ©e d'une augmentation de l'activitĂ© de l'intĂ©grine ÎČ1, affectant le dĂ©pĂŽt des matrices de fibronectine et de collagĂšne de type I. De plus, nous avons pu montrer qu'ICAP-1α a une action antagoniste sur le recrutement de la kindline-2 au niveau du domaine cytoplasmique de l'intĂ©grine ÎČ1 (Brunner et al. JCB 2011). Nous nous sommes ensuite intĂ©ressĂ©s au rĂŽle de l'intĂ©grine ÎČ1 elle-mĂȘme dans l'ostĂ©ogenĂšse afin de comprendre comment les ostĂ©oblastes intĂšgrent les signaux du microenvironnement pour coordonner la formation et le remodelage osseux. Dans cette optique, nous avons gĂ©nĂ©rĂ© un modĂšle de souris dĂ©lĂ©tĂ©es pour l'intĂ©grine ÎČ1 spĂ©cifiquement dans les ostĂ©oblastes en cours de maturation. Ces souris prĂ©sentent un sĂ©vĂšre phĂ©notype osseux caractĂ©risĂ© par des rĂ©ductions importantes de la minĂ©ralisation et de la dynamique osseuse, ainsi que des dĂ©formations osseuses et des fractures rappelant le syndrome d'OstĂ©oporose JuvĂ©nile. L'analyse in vitro d'ostĂ©oblastes n'exprimant pas l'intĂ©grine ÎČ1 a rĂ©vĂ©lĂ© un dĂ©faut majeur de prolifĂ©ration impliquant non pas la voie canonique MAPK/ERK mais plutĂŽt un dĂ©faut d'activation du co-facteur de transcription YAP. De plus, nous avons pu montrer que les intĂ©grines ÎČ1 rĂ©gulaient le niveau d'AMP cyclique (AMPc) dans les ostĂ©oblastes et que ceci Ă©tait corrĂ©lĂ© Ă l'inactivation de YAP. De mĂȘme, nous avons pu relier l'inactivation de YAP Ă la dynamique d'endocytose des rafts. Finalement, des analyses in vivo et in vitro ont rĂ©vĂ©lĂ© un dĂ©faut fonctionnel des ostĂ©oblastes dĂ©pourvus d'intĂ©grine ÎČ1. Nous avons pu montrer que cette incapacitĂ© fonctionnelle Ă©tait due Ă une rĂ©duction de la rĂ©ponse au BMP-2, facteur de croissance ostĂ©oblastique majeur, non pas au niveau de son rĂ©cepteur mais probablement au niveau de l'activation des promoteurs BMP-dĂ©pendants. Nos rĂ©sultats montrent ainsi que l'intĂ©grine ÎČ1 est un rĂ©gulateur clĂ© de la prolifĂ©ration ostĂ©oblastique dĂ©pendante de YAP et de la signalisation BMP rĂ©gulant la fonction ostĂ©oblastique, la minĂ©ralisation et la formation osseuse.Î1 integrins belong to a large family of receptors that have been shown to be of paramount importance for cell/extracellular matrix interactions. The ablation of the specific ÎČ1 integrin regulator ICAP-1α results in severe bone and mineralization defects. By combining mouse and cell biology we could demonstrate that loss of ICAP-1α was accompanied by an increase of ÎČ1 integrin activity that affects fibronectin and collagen deposition. Moreover, we could show that ICAP-1 is an important negative regulator of kindlin-2 recruitment on ÎČ1 integrin cytoplasmic domain (Brunner et al. JCB 2011). We then wanted to address the functional role of ÎČ1 integrin per se in osteogenesis and to understand how osteoblasts integrate environmental cues to coordinate bone formation and remodeling. For this we generated osteoblast specific ÎČ1 integrin deficient mice. These mice showed severe bone defects characterized by reduced bone mineralization and dynamic, as well as bending and fractures reminding human Juvenile Osteoporosis symptoms. In vitro analyses of ÎČ1 integrin deficient osteoblasts revealed proliferation defect which is not due to defective canonical MAPK/ERK pathway, but rather to defective activity of the co-transcription factor YAP. Then, we showed that ÎČ1 integrins are regulating cAMP level in osteoblasts and that the cAMP level correlates with YAP inactivation. We also linked YAP inactivation with raft endocytosis. Finally, in vivo and in vitro analyses revealed a functional incapacity of ÎČ1 integrin deficient osteoprecursors. We could show that the lazy phenotype of ÎČ1 integrin deficient osteoblasts is likely due to a reduced response to BMP signaling, a major osteoblast growth factor. Taken together, our findings demonstrate that ÎČ1 integrin is a key regulator of YAP-dependent osteoblast proliferation and BMP signaling allowing osteoblast functionality, mineralization and bone formation
Afadin controls cell polarization and mitotic spindle orientation in developing cortical radial glia.
BackgroundIn developing tissues, cell polarity and tissue architecture play essential roles in the regulation of proliferation and differentiation. During cerebral cortical development, adherens junctions link highly polarized radial glial cells in a neurogenic niche that controls their behavior. How adherens junctions regulate radial glial cell polarity and/or differentiation in mammalian cortical development is poorly understood.ResultsConditional deletion of Afadin, a protein required for formation and maintenance of epithelial tissues, leads to abnormalities in radial glial cell polarity and subsequent loss of adherens junctions. We observed increased numbers of obliquely-oriented progenitor cell divisions, increased exit from the ventricular zone neuroepithelium, and increased production of intermediate progenitors.ConclusionsTogether, these findings indicate that Afadin plays an essential role in regulating apical-basal polarity and adherens junction integrity of radial glial cells, and suggest that epithelial architecture plays an important role in radial glial identity by regulating mitotic orientation and preventing premature exit from the neurogenic niche
Specificities of ÎČ1 integrin signaling in the control of cell adhesion and adhesive strength.
International audienceCells exert actomyosin contractility and cytoskeleton-dependent force in response to matrix stiffness cues. Cells dynamically adapt to force by modifying their behavior and remodeling their microenvironment. This adaptation is favored by integrin activation switch and their ability to modulate their clustering and the assembly of an intracellular hub in response to force. Indeed integrins are mechanoreceptors and mediate mechanotransduction by transferring forces to specific adhesion proteins into focal adhesions which are sensitive to tension and activate intracellular signals. α(5)ÎČ(1) integrin is considered of major importance for the formation of an elaborate meshwork of fibronectin fibrils and for the extracellular matrix deposition and remodeling. Here we summarize recent progress in the study of mechanisms regulating the activation cycle of ÎČ(1) integrin and the specificity of α(5)ÎČ(1) integrin in mechanotransduction