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991.
Ga?l Manes Isabelle Meunier Almudena Avila-Fernández Sandro Banfi Guylène Le?Meur Xavier Zanlonghi Marta Corton Francesca Simonelli Philippe Brabet Gilles Labesse Isabelle Audo Saddek Mohand-Said Christina Zeitz José-Alain Sahel Michel Weber Hélène Dollfus Claire-Marie Dhaenens Delphine Allorge Elfride De?Baere Robert?K. Koenekoop Susanne Kohl Frans?P.M. Cremers Joe?G. Hollyfield Audrey Sénéchal Maxime Hebrard Béatrice Bocquet Carmen Ayuso García Christian?P. Hamel 《American journal of human genetics》2013,93(3):571-578
Vitelliform macular dystrophies (VMD) are inherited retinal dystrophies characterized by yellow, round deposits visible upon fundus examination and encountered in individuals with juvenile Best macular dystrophy (BMD) or adult-onset vitelliform macular dystrophy (AVMD). Although many BMD and some AVMD cases harbor mutations in BEST1 or PRPH2, the underlying genetic cause remains unknown for many affected individuals. In a large family with autosomal-dominant VMD, gene mapping and whole-exome sequencing led to the identification of a c.713T>G (p.Leu238Arg) IMPG1 mutation, which was subsequently found in two other families with autosomal-dominant VMD and the same phenotype. IMPG1 encodes the SPACR protein, a component of the rod and cone photoreceptor extracellular matrix domains. Structural modeling indicates that the p.Leu238Arg substitution destabilizes the conserved SEA1 domain of SPACR. Screening of 144 probands who had various forms of macular dystrophy revealed three other IMPG1 mutations. Two individuals from one family affected by autosomal-recessive VMD were homozygous for the splice-site mutation c.807+1G>T, and two from another family were compound heterozygous for the mutations c.461T>C (p.Leu154Pro) and c.1519C>T (p.Arg507∗). Most cases had a normal or moderately decreased electrooculogram Arden ratio. We conclude that IMPG1 mutations cause both autosomal-dominant and -recessive forms of VMD, thus indicating that impairment of the interphotoreceptor matrix might be a general cause of VMD. 相似文献
992.
Kathleen M. Meneely Qianyi Luo Prajnaparamita Dhar Audrey L. Lamb 《Archives of biochemistry and biophysics》2013
The isochorismate synthase from Pseudomonas aeruginosa (PchA) catalyzes the conversion of chorismate to isochorismate, which is subsequently converted by a second enzyme (PchB) to salicylate for incorporation into the salicylate-capped siderophore pyochelin. PchA is a member of the MST family of enzymes, which includes the structurally homologous isochorismate synthases from Escherichia coli (EntC and MenF) and salicylate synthases from Yersinia enterocolitica (Irp9) and Mycobacterium tuberculosis (MbtI). The latter enzymes generate isochorismate as an intermediate before generating salicylate and pyruvate. General acid–general base catalysis has been proposed for isochorismate synthesis in all five enzymes, but the residues required for the isomerization are a matter of debate, with both lysine221 and glutamate313 proposed as the general base (PchA numbering). This work includes a classical characterization of PchA with steady state kinetic analysis, solvent kinetic isotope effect analysis and by measuring the effect of viscosogens on catalysis. The results suggest that isochorismate production from chorismate by the MST enzymes is the result of general acid–general base catalysis with a lysine as the base and a glutamic acid as the acid, in reverse protonation states. Chemistry is determined to not be rate limiting, favoring the hypothesis of a conformational or binding step as the slow step. 相似文献
993.
Juan Pablo Muñoz Saška Ivanova Jana Sánchez‐Wandelmer Paula Martínez‐Cristóbal Eduard Noguera Ana Sancho Angels Díaz‐Ramos María Isabel Hernández‐Alvarez David Sebastián Caroline Mauvezin Manuel Palacín Antonio Zorzano 《The EMBO journal》2013,32(17):2348-2361
Mitofusin 2 (Mfn2) is a key protein in mitochondrial fusion and it participates in the bridging of mitochondria to the endoplasmic reticulum (ER). Recent data indicate that Mfn2 ablation leads to ER stress. Here we report on the mechanisms by which Mfn2 modulates cellular responses to ER stress. Induction of ER stress in Mfn2‐deficient cells caused massive ER expansion and excessive activation of all three Unfolded Protein Response (UPR) branches (PERK, XBP‐1, and ATF6). In spite of an enhanced UPR, these cells showed reduced activation of apoptosis and autophagy during ER stress. Silencing of PERK increased the apoptosis of Mfn2‐ablated cells in response to ER stress. XBP‐1 loss‐of‐function ameliorated autophagic activity of these cells upon ER stress. Mfn2 physically interacts with PERK, and Mfn2‐ablated cells showed sustained activation of this protein kinase under basal conditions. Unexpectedly, PERK silencing in these cells reduced ROS production, normalized mitochondrial calcium, and improved mitochondrial morphology. In summary, our data indicate that Mfn2 is an upstream modulator of PERK. Furthermore, Mfn2 loss‐of‐function reveals that PERK is a key regulator of mitochondrial morphology and function. 相似文献
994.
Abstract The aim of this study was to assess the respective impacts of the surface energy and surface roughness of bare and coated steels on biofouling and sanitisation. Bioadhesion of Staphylococcus aureus CIP 53.154 was studied on two stainless steel surfaces with smooth or specific micro-topography. Two coatings were also studied: silicon oxide (hydrophilic) and polysiloxane (hydrophobic). On smooth surfaces, adhesion was reduced on an apolar coating and cell viability increased with the surface polarity. A specific micro-topography decreased the level of bacterial adhesion on bare surfaces by a factor ten. On this surface, only single adherent cells were observed, contrasting with cells in clusters on smoother surfaces. As a consequence, cell repartition influenced bacterial viability. Most isolated adherent cells were dead whereas cells in clusters were still alive. In addition, the quaternary ammonium chloride used in sanitisation, acted at once both as a tensio-active molecule and a biocide. It only displaced adherent cells but did not remove them. 相似文献
995.
Pedro Tauler Antoni Aguiló Isabel Gimeno Aina Noguera Alvar Agustí Josep A. Tur 《Free radical research》2013,47(9):931-938
We have determined the effects of chronic vitamin C intake on neutrophil and lymphocyte antioxidant defences during the acute phase immune response induced by intense exercise. Blood samples were taken from 16 voluntary athletes in basal conditions, both immediately after and 1 h after a duathlon competition. Sportsmen's nutrient intakes were determined before the competition. After determining the basal plasmatic ascorbate levels, the results were analysed taking into account the vitamin C intake and their plasmatic levels. Two groups were constituted, the vitamin C supplemented group and the control group, with the dietary vitamin C intake as the only statistical difference between groups. The duathlon competition induced a significant neutrophilia, which was higher in the supplemented group. Lymphocyte antioxidant enzyme activities increased after the competition, with a higher increase in SOD activity in the control group than in the supplemented one. The competition decreased neutrophil antioxidant enzyme activities and neutrophil ascorbate concentration. The decrease in the SOD activity in the supplemented group was higher than in the control group. Finally, the duathlon competition increased the expression of MAC-1 neutrophil adhesion molecule in the supplemented group. High vitamin C intake influenced the response of neutrophils and lymphocytes to oxidative stress induced by exercise, increasing the neutrophil activation. 相似文献
996.
Rousseau M Gaugler MH Rodallec A Bonnaud S Paris F Corre I 《Biochemical and biophysical research communications》2011,(4):750-755
Endothelial cells of the microvasculature are major target of ionizing radiation, responsible of the radiation-induced vascular early dysfunctions. Molecular signaling pathways involved in endothelial responses to ionizing radiation, despite being increasingly investigated, still need precise characterization. Small GTPase RhoA and its effector ROCK are crucial signaling molecules involved in many endothelial cellular functions. Recent studies identified implication of RhoA/ROCK in radiation-induced increase in endothelial permeability but other endothelial functions altered by radiation might also require RhoA proteins. Human microvascular endothelial cells HMEC-1, either treated with Y-27632 (inhibitor of ROCK) or invalidated for RhoA by RNA interference were exposed to 15 Gy. We showed a rapid radiation-induced activation of RhoA, leading to a deep reorganisation of actin cytoskeleton with rapid formation of stress fibers. Endothelial early apoptosis induced by ionizing radiation was not affected by Y-27632 pre-treatment or RhoA depletion. Endothelial adhesion to fibronectin and formation of focal adhesions increased in response to radiation in a RhoA/ROCK-dependent manner. Consistent with its pro-adhesive role, ionizing radiation also decreased endothelial cells migration and RhoA was required for this inhibition. These results highlight the role of RhoA GTPase in ionizing radiation-induced deregulation of essential endothelial functions linked to actin cytoskeleton. 相似文献
997.
Favrelle A Boyère C Laurent P Broze G Blecker C Paquot M Jérôme C Debuigne A 《Carbohydrate research》2011,(9):8727-1164
The lipase-catalysed esterification of sugars with hemifluorinated acid derivatives is reported for the first time. A series of mannose modified derivatives having fluorinated chains with different length have been prepared accordingly in moderate yield. A preliminary evaluation of the surface active properties of these hemifluorinated mannose esters revealed their ability to reduce the surface tension of water much more efficiently than their aliphatic counterparts. 相似文献
998.
Bergouignan A Rudwill F Simon C Blanc S 《Journal of applied physiology (Bethesda, Md. : 1985)》2011,111(4):1201-1210
Although it is no longer debatable that sedentary behaviors are an actual cause of many metabolic diseases, the physiology of physical inactivity has been poorly investigated for this purpose. Along with microgravity, the physiological adaptations to spaceflights require metabolic adaptations to physical inactivity, and that is exceedingly well-simulated during the ground-based microgravity bed-rest analogs. Bed rest thus represents a unique model to investigate the mechanisms by which physical inactivity leads to the development of current societal chronic diseases. For decades, however, clinicians and physiologists working in space research have worked separately without taking full awareness of potential strong mutual questioning. This review summarizes the data collected over the last 60 years on metabolic adaptations to bed rest in healthy subjects. Our aim is to provide evidence that supports the hypothesis that physical inactivity per se is one of the primary causes in the development of metabolic inflexibility. This evidence will focus on four main tenants of metabolic inflexiblity: 1) insulin resistance, 2) impaired lipid trafficking and hyperlipidemia, 3) a shift in substrate use toward glucose, and 4) a shift in muscle fiber type and ectopic fat storage. Altogether, this hypothesis places sedentary behaviors upstream on the list of factors involved in metabolic inflexibility, which is considered to be a primary impairment in several metabolic disorders such as obesity, insulin resistance, and type 2 diabetes mellitus. 相似文献
999.
Guillon-Munos A Oikonomopoulou K Michel N Smith CR Petit-Courty A Canepa S Reverdiau P Heuzé-Vourc'h N Diamandis EP Courty Y 《The Journal of biological chemistry》2011,286(29):25505-25518
Kallikrein-related peptidases (KLKs) are an emerging group of secreted serine proteases involved in several physiological and pathological processes. We used a degradomic approach to identify potential substrates of KLK12. MDA-MB-231 cells were treated either with KLK12 or vehicle control, and the proteome of the overlying medium was analyzed by mass spectrometry. CCN1 (cyr61, ctgf, nov) was among the proteins released by the KLK12-treated cells, suggesting that KLK12 might be responsible for the shedding of this protein from the cell surface. Fragmentation of CCN1 by KLK12 was further confirmed in vitro, and the main cleavage site was localized in the hinge region between the first and second half of the recombinant protein. KLK12 can target all six members of the CCN family at different proteolytic sites. Limited proteolysis of CCNs (cyr61, ctgf, nov) was also observed in the presence of other members of the KLK family, such as KLK1, KLK5, and KLK14, whereas KLK6, KLK11, and KLK13 were unable to fragment CCNs. Because KLK12 seems to have a role in angiogenesis, we investigated the relations between KLK12, CCNs, and several factors known to be involved in angiogenesis. Solid phase binding assays showed that fragmentation of CCN1 or CCN5 by KLK12 prevents VEGF(165) binding, whereas it also triggers the release of intact VEGF and BMP2 from the CCN complexes. The KLK12-mediated release of TGF-β1 and FGF-2, either as intact or truncated forms, was found to be concentration-dependent. These findings suggest that KLK12 may indirectly regulate the bioavailability and activity of several growth factors through processing of their CCN binding partners. 相似文献
1000.