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排序方式: 共有921条查询结果,搜索用时 15 毫秒
71.
Erwin Knecht Carmen Aguado Sovan Sarkar Viktor I Korolchuk Olga Criado-García Santiago Vernia Patricia Boya Pascual Sanz Santiago Rodríguez de Córdoba David C Rubinsztein 《Autophagy》2010,6(7):991-993
Lafora disease (LD) is a progressive, lethal, autosomal recessive, neurodegenerative disorder that manifests with myoclonus epilepsy. LD is characterized by the presence of intracellular inclusion bodies called Lafora bodies (LB), in brain, spinal cord and other tissues. More than 50 percent of LD is caused by mutations in EPM2A that encodes laforin. Here we review our recent findings that revealed that laforin regulates autophagy. We consider how autophagy compromise may predispose to LB formation and neurodegeneration in LD, and discuss future investigations suggested by our data.Key words: autophagy, glycogen metabolism, Lafora disease, laforin, malin, neurodegeneration 相似文献
72.
Juan Jesús Molina-Rueda María Belén Pascual Francisco M. Cánovas Fernando Gallardo 《Planta》2010,232(6):1471-1483
Glutamate decarboxylase (GAD, EC 4.1.1.15) is a key enzyme in the synthesis of γ-aminobutyric acid (GABA) in higher plants.
A complete cDNA encoding glutamate decarboxylase (GAD, EC 4.1.1.15) was characterized from Pinus pinaster Ait, and its expression pattern was studied to gain insight into the role of GAD in the differentiation of the vascular system.
Pine GAD contained a C-terminal region with conserved residues and a predicted secondary structure similar to the calmodulin
(CaM)-binding domains of angiosperm GADs. The enzyme was able to bind to a bovine CaM-agarose column and GAD activity was
higher at acidic pH, suggesting that the pine GAD can be regulated in vivo by Ca2+/CaM and pH. A polyclonal antiserum was prepared against the pine protein. GAD expression was studied at activity, protein,
and mRNA level and was compared with the expression of other genes during the differentiation of the hypocotyl and induction
of reaction wood. In seedling organs, GABA levels closely matched GAD expression, with high levels in the root and during
lignification of the hypocotyl. GAD expression was also induced in response to the production of compression wood and its
expression matched the pattern of other genes involved in ethylene and 2-oxoglutarate synthesis. The results suggest of a
role of GAD in hypocotyl and stem development in pine. 相似文献
73.
Agnieszka Rynda Massimo Maddaloni Javier Ochoa-Repáraz Gayle Callis David W. Pascual 《PloS one》2010,5(1)
Conventional methods to induce tolerance in humans have met with limited success. Hence, efforts to redirect tolerogen uptake using reovirus adhesin, protein sigma 1 (pσ1), may circumvent these shortcomings based upon the recent finding that when reovirus pσ1 is engineered to deliver chicken ovalbumin (OVA) mucosally, tolerance is obtained, even with a single dose. To test whether single-dose tolerance can be induced to treat EAE, proteolipid protein (PLP130–151) was genetically fused to OVA to pσ1 (PLP:OVA-pσ1) and shown to significantly ameliorate EAE, suppressing proinflammatory cytokines by IL-10+ forkhead box P3 (FoxP3)+ CD25+CD4+ Treg and IL-4+CD25−CD4+ Th2 cells. IL-10R or IL-4 neutralization reversed protection to EAE conferred by PLP:OVA-pσ1, and adoptive transfer of Ag-specific Treg or Th2 cells restored protection against EAE in recipients. Upon assessment of each relative participant, functional inactivation of CD25 impaired PLP:OVA-pσ1''s protective capacity, triggering TGF-β-mediated inflammation; however, concomitant inactivation of TGF-β and CD25 reestablished PLP:OVA-pσ1-mediated protection by IL-28-producing FoxP3+CD25−CD4+ T cells. Thus, pσ1-based therapy can resolve EAE independently of or dependently upon CD25 and assigns IL-28 as an alternative therapy for autoimmunity. 相似文献
74.
A complex of catalytically inactive protein phosphatase-1 sandwiched between Sds22 and inhibitor-3 总被引:1,自引:0,他引:1
Lesage B Beullens M Pedelini L Garcia-Gimeno MA Waelkens E Sanz P Bollen M 《Biochemistry》2007,46(31):8909-8919
Protein Ser/Thr phosphatase-1 (PP1) associates with a host of proteins to form substrate-specific holoenzymes. Sds22 and Inhibitor-3 (I3) are two independently described ancient interactors of PP1. We show here by various approaches that Sds22 and I3 form a heterotrimeric complex with PP1, both in cell lysates and after purification. The stability of the complex depended on functional PP1 interaction sites in Sds22 and I3, indicating that PP1 is sandwiched between Sds22 and I3. Intriguingly, I3 could not be replaced in this complex by another PP1 interactor with the same PP1 binding motif. In vitro, Sds22 and I3 were potent inhibitors of PP1, but with only some substrates. The inhibition by Sds22 could be reproduced with synthetic Sds22 fragments comprising leucine-rich repeats (LRR) 2 and 5. Sds22 and LRR5 also slowly converted PP1 into a conformation that was inactive with all tested substrates. Cell lysates that were prepared under conditions that prevented the Sds22-induced inactivation of PP1 contained a catalytically inactive complex of Sds22, PP1, and I3, indicating that this complex exists in vivo. Therefore, our studies show that a pool of PP1 is complexly controlled by both Sds22 and I3. 相似文献
75.
Viana R Towler MC Pan DA Carling D Viollet B Hardie DG Sanz P 《The Journal of biological chemistry》2007,282(22):16117-16125
Mammalian AMP-activated protein kinase is a serine/threonine protein kinase that acts as a sensor of cellular energy status. AMP-activated protein kinase is a heterotrimer of three different subunits, i.e. alpha, beta, and gamma, with alpha being the catalytic subunit and beta and gamma having regulatory roles. Although several studies have defined different domains in alpha and beta involved in the interaction with the other subunits of the complex, little is known about the regions of the gamma subunits involved in these interactions. To study this, we have made sequential deletions from the N termini of the gamma subunit isoforms and studied the interactions with alpha and beta subunits, both by two-hybrid analysis and by co-immunoprecipitation. Our results suggest that a conserved region of 20-25 amino acids in gamma1, gamma2, and gamma3, immediately N-terminal to the Bateman domains, is required for the formation of a functional, active alphabetagamma complex. This region is required for the interaction with the beta subunits. The interaction between the alpha and gamma subunits does not require this region and occurs instead within the Bateman domains of the gamma subunit, although the alpha-gamma interaction does appear to stabilize the beta-gamma interaction. In addition, sequential deletions from the C termini of the gamma subunits indicate that deletion of any of the CBS (cystathionine beta-synthase) motifs prevents the formation of a functional complex with the alpha and beta subunits. 相似文献
76.
Pascual López-López Clara García-Ripollés Álvaro Soutullo Luis Cadahía Vicente Urios 《Biodiversity and Conservation》2007,16(13):3755-3780
The Bonelli’s eagle (BE) is considered by the European Union as a high-priority species for conservation in the Valencian
Community (East of Spain). However, in 2006 the European Union opened a legal procedure against the Spanish Kingdom, accused
of lacking of an adequate network of special protected areas (SPAs) to preserve the BE in the region. Here we evaluate whether
important bird areas (IBAs) and SPAs network is enough to preserve this species, on the basis of a thorough analysis of habitat
preferences. A GAP analysis is performed to conduct a revision of current SPAs and BirdLife proposed IBAs. Our results suggest
that the current network of SPAs becomes insufficient to protect the BE. The IBAs network, although improves the current network
of SPAs, increasing the percentage of BE potential habitat included, also results inadequate. We propose a new SPAs network
according to the potential suitable habitat for the species. Given the trade-off between financial investment and the conservation
of biodiversity, we propose to maximize the surface of potential habitat included in the protected network minimizing the
surface of the region that would be necessary to protect, thus avoiding an unnecessary expense and otherwise unrealistic results. 相似文献
77.
Tasler S Kraus J Wuzik A Müller O Aschenbrenner A Cubero E Pascual R Quintana-Ruiz JR Dordal A Mercè R Codony X 《Bioorganic & medicinal chemistry letters》2007,17(22):6224-6229
Based on a pharmacophore alignment on a 5-HT(6) ligand applying 4SCan technology, a new lead series was identified and further structurally investigated. K(i)s down to 8 nM were achieved. 相似文献
78.
79.
Orlandi-Pradines E Almeras L Denis de Senneville L Barbe S Remoué F Villard C Cornelie S Penhoat K Pascual A Bourgouin C Fontenille D Bonnet J Corre-Catelin N Reiter P Pagés F Laffite D Boulanger D Simondon F Pradines B Fusaï T Rogier C 《Microbes and infection / Institut Pasteur》2007,9(12-13):1454-1462
Exposure to vectors of infectious diseases has been associated with antibody responses against salivary antigens of arthropods among people living in endemic areas. This immune response has been proposed as a surrogate marker of exposure to vectors appropriate for evaluating the protective efficacy of antivectorial devices. The existence and potential use of such antibody responses in travellers transiently exposed to Plasmodium or arbovirus vectors in tropical areas has never been investigated. The IgM and IgG antibody responses of 88 French soldiers against the saliva of Anopheles gambiae and Aedes aegypti were evaluated before and after a 5-month journey in tropical Africa. Antibody responses against Anopheles and Aedes saliva increased significantly in 41% and 15% of the individuals, respectively, and appeared to be specific to the mosquito genus. A proteomic and immunoproteomic analysis of anopheles and Aedes saliva allowed for the identification of some antigens that were recognized by most of the exposed individuals. These results suggest that antibody responses to the saliva of mosquitoes could be considered as specific surrogate markers of exposure of travellers to mosquito vectors that transmit arthropod borne infections. 相似文献
80.