排序方式: 共有237条查询结果,搜索用时 93 毫秒
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Jean-Jacques Legrand Cecile Fisch Pierre-Olivier Guillaumat Jean-Marc Pavard Mahmoud Attia Stephane De Jouffrey 《Biomarkers》2013,18(1):63-77
The ovariectomized old cynomolgus monkey is a recognized model of human osteoporosis, and the same species can be used for the assessment of the efficacy and potential toxicity of agents intended to prevent or treat osteoporosis. Several assays have been developed that can measure the same biochemical markers of bone turnover as are used in human patients for the diagnosis and treatment follow-up of bone-related diseases, including osteoporosis. The aim of the present study was to describe the results obtained with these assays in normal control monkeys, their variations with age and sex, and their sensitivity in monitoring the bone turnover induced by ovariectomy in old skeletally mature cynomolgus monkeys. Seven old cynomolgus monkeys were bilaterally ovariectomized and 13 age-matched monkeys were sham-operated. Bone mineral density and biochemical markers were measured before and at regular intervals after surgery for up to 20 months. Total alkaline phosphatase (total ALP), bone-specific alkaline phosphatase isoenzyme (bone ALP) and osteocalcin (OC) were highly correlated to the decrease in bone mineral density (BMD) induced by ovariectomy. Deoxypyridinoline (DPD) measured by enzyme-linked immunoassay was insensitive to the bone resorption induced by ovariectomy, but cross-linked N-telopeptide (NTX-I) was higher in ovariectomized monkeys than in control monkeys. These results demonstrate that reliable biochemical parameters are available to adequately monitor and provide insight into osteoclastic bone resorption and osteoblastic bone formation, the two components of bone turnover in this animal model, and can thus be used to assess the efficacy and toxicity of potential therapeutic agents. 相似文献
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Fran?ois Téoulé Cynthia Brisac Isabelle Pelletier Pierre-Olivier Vidalain Sophie Jégouic Carmen Mirabelli Ma?l Bessaud Nicolas Combelas Arnaud Autret Frédéric Tangy Francis Delpeyroux Bruno Blondel 《Journal of virology》2013,87(20):11031-11046
We have shown that the circulating vaccine-derived polioviruses responsible for poliomyelitis outbreaks in Madagascar have recombinant genomes composed of sequences encoding capsid proteins derived from poliovaccine Sabin, mostly type 2 (PVS2), and sequences encoding nonstructural proteins derived from other human enteroviruses. Interestingly, almost all of these recombinant genomes encode a nonstructural 3A protein related to that of field coxsackievirus A17 (CV-A17) strains. Here, we investigated the repercussions of this exchange, by assessing the role of the 3A proteins of PVS2 and CV-A17 and their putative cellular partners in viral replication. We found that the Golgi protein acyl-coenzyme A binding domain-containing 3 (ACBD3), recently identified as an interactor for the 3A proteins of several picornaviruses, interacts with the 3A proteins of PVS2 and CV-A17 at viral RNA replication sites, in human neuroblastoma cells infected with either PVS2 or a PVS2 recombinant encoding a 3A protein from CV-A17 [PVS2-3A(CV-A17)]. The small interfering RNA-mediated downregulation of ACBD3 significantly increased the growth of both viruses, suggesting that ACBD3 slowed viral replication. This was confirmed with replicons. Furthermore, PVS2-3A(CV-A17) was more resistant to the replication-inhibiting effect of ACBD3 than the PVS2 strain, and the amino acid in position 12 of 3A was involved in modulating the sensitivity of viral replication to ACBD3. Overall, our results indicate that exchanges of nonstructural proteins can modify the relationships between enterovirus recombinants and cellular interactors and may thus be one of the factors favoring their emergence. 相似文献
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Bulle Cécile Margni Manuele Patouillard Laure Boulay Anne-Marie Bourgault Guillaume De Bruille Vincent Cao Viêt Hauschild Michael Henderson Andrew Humbert Sebastien Kashef-Haghighi Sormeh Kounina Anna Laurent Alexis Levasseur Annie Liard Gladys Rosenbaum Ralph K. Roy Pierre-Olivier Shaked Shanna Fantke Peter Jolliet Olivier 《The International Journal of Life Cycle Assessment》2019,24(9):1653-1674
The International Journal of Life Cycle Assessment - This paper addresses the need for a globally regionalized method for life cycle impact assessment (LCIA), integrating multiple state-of-the-art... 相似文献
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Kotzki PO 《Journal de la Société de Biologie》2004,198(2):163-168
Medical and biological imaging has undergone a revolution in the past decade. Positron emission tomography (PET) has been developed to visualize biochemical and physiological phenomena in living humans and animals. For instance, blood flow, blood volume, glucose metabolism, amino acid metabolism, can be quantitatively estimated by means of PET with various radioactive tracers. This functional and molecular imaging technique has progressed rapidly from being a research technique in laboratories to a routine clinical imaging modality. The most widely used radiotracer in routine is 18F-fluorodeoxyglucose (18FDG), which is an analogue of glucose. Since glucose metabolism is increased many fold in malignant tumors, PET has a major role in the field of clinical oncology and recently in cardiology and neurology. PET is also a valuable tool to study cerebral or cardiac binding sites and to image the expression of reporter genes in small animals. In this review, we summarize the most recent developments in PET imaging with particular reference to the radiotracers available and their application. 相似文献
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The human maintenance DNA (cytosine-5) methyltransferase (hDNMT1) consists of a large N-terminal regulatory domain fused to a catalytic C-terminal domain by randomly repeated Gly-Lys dipeptides. Several N-terminal deletion mutants of hDNMT1 were made, purified, and tested for substrate specificity. Deletion mutants lacking 121, 501, 540, or 580 amino acids from the N-terminus still functioned as DNA methyltransferases, methylated CG sequences, and preferred hemimethylated to unmethylated DNA, as did the full-length hDNMT1. Methylated DNA stimulated methylation spreading on unmethylated CpG sequences for the full-length and the 121 amino acid deletion hDNMT1 equally well but not for the mutants lacking 501, 540, or 580 amino acids, indicating the presence of an allosteric activation determinant between amino acids 121 and 501. Peptides from the N- and C-termini bound methylated DNA independently. Point mutation analysis within the allosteric region revealed that amino acids 284-287 (KKHR) were involved in methylated DNA-mediated allosteric activation. Allosteric activation was reduced in the double point mutant enzymes D25 (K284A and K285A) and D12 (H286A and R287A). Retinoblastoma gene product (Rb), a negative regulator of DNA methylation, bound to the allosteric site of hDNMT1 and inhibited methylation, suggesting Rb may regulate methylation spreading. 相似文献
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Vidalain PO Laine D Zaffran Y Azocar O Servet-Delprat C Wild TF Rabourdin-Combe C Valentin H 《Journal of virology》2002,76(13):6415-6424
In the thymus, epithelial cells comprise a heterogeneous population required for the generation of functional T lymphocytes, suggesting that thymic epithelium disruption by viruses may compromise T-cell lymphopoiesis in this organ. In a previous report, we demonstrated that in vitro, measles virus induced differentiation of cortical thymic epithelial cells as characterized by (i) cell growth arrest, (ii) morphological and phenotypic changes, and (iii) apoptotis as a final step of this process. In the present report, we have analyzed the mechanisms involved. First, measles virus-induced differentiation of thymic epithelial cells is shown to be strictly dependent on beta interferon (IFN-beta) secretion. In addition, transfection with double-stranded RNA, a common intermediate of replication for a broad spectrum of viruses, is reported to similarly mediate thymic epithelial cell differentiation through IFN-beta induction. Finally, we demonstrated that recombinant IFN-alpha, IFN-beta, or IFN-gamma was sufficient to induce differentiation and apoptosis of uninfected thymic epithelial cells. These observations suggested that interferon secretion by either infected cells or activated leukocytes, such as plasmacytoid dendritic cells or lymphocytes, may induce thymic epithelium disruption in a pathological context. Thus, we have identified a new mechanism that may contribute to thymic atrophy and altered T-cell lymphopoiesis associated with many infections. 相似文献
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Le Crom S Kapsimali M Barôme PO Vernier P 《Journal of structural and functional genomics》2003,3(1-4):161-176
The neuromodulatory effects of dopamine on the central nervous system of craniates are mediated by two classes of G protein-coupled receptors (D1 and D2), each comprising several subtypes. A systematic isolation and characterization of the D1 and D2-like receptors was carried out in most of the Craniate groups. It revealed that two events of gene duplications took place during vertebrate evolution, before or simultaneously to the emergence of Gnathostomes. It led to the conservation of two-to-four paralogous receptors (subtypes), depending on the species. Additional duplication of dopamine receptor gene occurred independently in the teleost fish lineage. Duplicated genes were maintained in most of the vertebrate groups, certainly by the acquisition of a few functional characters, specific of each subtypes, as well as by discrete changes in their expression territories in the brain. The evolutionary scenario elaborated from these data suggests that receptor gene duplications were the necessary conditions for the expansion of vertebrate forebrain to occur, allowing dopamine systems to exert their fundamental role as modulator of the adaptive capabilities acquired by vertebrate species. 相似文献