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排序方式: 共有226条查询结果,搜索用时 160 毫秒
101.
102.
Banka S Blom HJ Walter J Aziz M Urquhart J Clouthier CM Rice GI de Brouwer AP Hilton E Vassallo G Will A Smith DE Smulders YM Wevers RA Steinfeld R Heales S Crow YJ Pelletier JN Jones S Newman WG 《American journal of human genetics》2011,(2):214-225
Dihydrofolate reductase (DHFR) is a critical enzyme in folate metabolism and an important target of antineoplastic, antimicrobial, and antiinflammatory drugs. We describe three individuals from two families with a recessive inborn error of metabolism, characterized by megaloblastic anemia and/or pancytopenia, severe cerebral folate deficiency, and cerebral tetrahydrobiopterin deficiency due to a germline missense mutation in DHFR, resulting in profound enzyme deficiency. We show that cerebral folate levels, anemia, and pancytopenia of DHFR deficiency can be corrected by treatment with folinic acid. The characterization of this disorder provides evidence for the link between DHFR and metabolism of cerebral tetrahydrobiopterin, which is required for the formation of dopamine, serotonin, and norepinephrine and for the hydroxylation of aromatic amino acids. Moreover, this relationship provides insight into the role of folates in neurological conditions, including depression, Alzheimer disease, and Parkinson disease. 相似文献
103.
M19 modulates skeletal muscle differentiation and insulin secretion in pancreatic β-cells through modulation of respiratory chain activity 总被引:1,自引:0,他引:1
Cambier L Rassam P Chabi B Mezghenna K Gross R Eveno E Auffray C Wrutniak-Cabello C Lajoix AD Pomiès P 《PloS one》2012,7(2):e31815
Mitochondrial dysfunction due to nuclear or mitochondrial DNA alterations contributes to multiple diseases such as metabolic myopathies, neurodegenerative disorders, diabetes and cancer. Nevertheless, to date, only half of the estimated 1,500 mitochondrial proteins has been identified, and the function of most of these proteins remains to be determined. Here, we characterize the function of M19, a novel mitochondrial nucleoid protein, in muscle and pancreatic β-cells. We have identified a 13-long amino acid sequence located at the N-terminus of M19 that targets the protein to mitochondria. Furthermore, using RNA interference and over-expression strategies, we demonstrate that M19 modulates mitochondrial oxygen consumption and ATP production, and could therefore regulate the respiratory chain activity. In an effort to determine whether M19 could play a role in the regulation of various cell activities, we show that this nucleoid protein, probably through its modulation of mitochondrial ATP production, acts on late muscle differentiation in myogenic C2C12 cells, and plays a permissive role on insulin secretion under basal glucose conditions in INS-1 pancreatic β-cells. Our results are therefore establishing a functional link between a mitochondrial nucleoid protein and the modulation of respiratory chain activities leading to the regulation of major cellular processes such as myogenesis and insulin secretion. 相似文献
104.
This special issue on "Systems biology and personalized medicine" includes five complementary articles that highlight how functional genomics and computational physiology can contribute to the development of predictive, preventive, personalized and participatory (P4) medicine. Edited by Prof. Leroy Hood and Prof. Charles Auffray. 相似文献
105.
106.
Mark S. Brown Stefan Gundacker Alaric Taylor Clemens Tummeltshammer Etiennette Auffray Paul Lecoq Ioannis Papakonstantinou 《PloS one》2014,9(5)
The uncertainty in time of particle detection within a scintillator detector, characterised by the coinci- dence time resolution (CTR), is explored with respect to the interaction position within the scintillator crystal itself. Electronic collimation between two scintillator detectors is utilised to determine the CTR with depth of interaction (DOI) for different materials, geometries and wrappings. Significantly, no rela- tionship between the CTR and DOI is observed within experimental error. Confinement of the interaction position is seen to degrade the CTR in long scintillator crystals by 10%. 相似文献
107.
108.
C Auffray 《Comptes rendus de l'Académie des sciences. Série III, Sciences de la vie》1986,302(8):287-292
HLA class II beta chains contain in their aminoterminal polymorphic domain a highly conserved tetrapeptide (RFDS) also present in protein F encoded by the LAV virus. Homology between this tetrapeptide and the fibronectin cell-attachment site (RGDS) has suggested a role in cell adhesion processes. I propose here that such a structure, that I call adhesiotope, would allow stabilization of intermolecular contacts between molecules present at the surface of interacting cells or viruses. Analysis of a three dimensional model of the T4 antigen suggests that the tetrapeptide RADS is located at the surface of the aminoterminal, immunoglobulin-like domain. A model is proposed in which interaction between the adhesiotopes present in class II antigens (RFDS) and T4 (RADS) is the molecular basis of conjugate formation between antigen presenting cells and T helper lymphocytes. The LAV virus, having the RFDS adhesiotope on its surface, would mimic class II antigens in their interaction with T4 and infect selectively T4 positive cells, resulting in the acquired immune deficiency syndrome. 相似文献
109.
The chicken nerve growth factor (beta NGF) gene has been mapped by fluorescent in situ hybridization to a pair of microchromosomes, confirming previous reports of the existence of a single gene locus. A 39-kb genomic fragment cloned in a cosmid vector and including the 5' end of the beta NGF locus was biotinylated for nonradioactive detection of the gene. This report adds to the increasing evidence proving microchromosomal localization of highly conserved and biologically fundamental genes. The implications of such genes belonging to very small linkage groups for the transmission of alleles from generation to generation together with the relevance of nonisotopic in situ hybridization for avian gene mapping are considered. 相似文献
110.
Involvement of the low-density lipoprotein receptor-related protein in the transcytosis of the brain delivery vector angiopep-2 总被引:1,自引:0,他引:1
Demeule M Currie JC Bertrand Y Ché C Nguyen T Régina A Gabathuler R Castaigne JP Béliveau R 《Journal of neurochemistry》2008,106(4):1534-1544
The blood–brain barrier (BBB) restricts the entry of proteins as well as potential drugs to cerebral tissues. We previously reported that a family of Kunitz domain-derived peptides called Angiopeps can be used as a drug delivery system for the brain. Here, we further characterize the transcytosis ability of these peptides using an in vitro model of the BBB and in situ brain perfusion. These peptides, and in particular Angiopep-2, exhibited higher transcytosis capacity and parenchymal accumulation than do transferrin, lactoferrin, and avidin. Angiopep-2 transport and accumulation in brain endothelial cells were unaffected by the P-glycoprotein inhibitor, cyclosporin A, indicating that this peptide is not a substrate for the efflux pump P-glycoprotein. However, competition studies show that activated α2 -macroglobulin, a specific ligand for the low-density lipoprotein receptor-related protein-1 (LRP1) and Angiopep-2 can share the same receptor. In addition, LRP1 was detected in glioblastomas and brain metastases from lung and skin cancers. Fluorescent microscopy also revealed that Alexa488-Angiopep-2 co-localized with LRP1 in brain endothelial cell monolayers. Overall, these results suggest that Angiopep-2 transport across the BBB is, in part, mediated by LRP1. 相似文献