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101.
Tropomyosin (Tm) is a dimer made of two alpha helical chains associated into a parallel coiled-coil. In mammalian skeletal and cardiac muscle, the Tm is expressed from two separate genes to give the α- and β-Tm isoforms. These associate in vivo to form homo- (α(2)) and heterodimers (α·β) with little β(2) normally observed. The proportion of α(2) vs α·β varies across species and across muscle types from almost 100% α(2)- to 50% α·β-Tm. The ratio can also vary during development and in disease. The functional significance of the presence of these two isoforms has not been defined because it is difficult to isolate or purify the α·β dimer for functional studies. Here we report an effective method for purifying bacterially expressed Tm as α·β dimers using a cleavable N-terminal tag on one of the two chains. The same method can be used to isolate Tm dimers in which one chain carries a mutation. We go on to show that the α·β dimers differ in key properties (actin affinity, thermal stability) from either the α(2)- or β(2)-Tm. However, the ability to regulate myosin binding when combined with cardiac troponin appears unaffected. 相似文献
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103.
Stavropoulou C Zachaki S Alexoudi A Chatzi I Georgakakos VN Terzoudi GI Pantelias GE Karageorgiou CE Sambani C 《Free radical biology & medicine》2011,51(3):713-718
Oxidative stress plays a pivotal role in the pathogenesis of multiple sclerosis (MS). Inactivating polymorphisms of genes encoding detoxification enzymes, such as NAD(P)H:quinone oxidoreductase 1 (NQO1), could influence susceptibility to MS. To test this hypothesis we performed a case-control study in which we compared the distribution of NQO1 genotypes between 231 MS patients and 380 controls, using both PCR-RFLP and real-time PCR assays. Correlations with MS clinical subtype classification and gender were also evaluated. A significantly higher frequency of the homozygous (T/T) and heterozygous (C/T) NQO1 C609T variant genotypes was observed among MS patients compared to controls (P = 0.01), with MS patients showing a 1.5-fold increased risk of carrying at least one variant T allele (P = 0.009). Interestingly, patients belonging to the primary progressive subgroup exhibited a significantly higher incidence of the heterozygous C/T variant genotype, compared to the other forms of MS (P = 0.019). There was no correlation of the NQO1 polymorphism with gender. These results provide the first evidence for a pathogenetic role for the NQO1 C609T polymorphism in MS susceptibility and suggest a possible role for the NQO1 genetic background in the development of primary progressive MS. 相似文献
104.
Odett Kaiser Pooyan Aliuos Kirsten Wissel Thomas Lenarz Darja Werner Günter Reuter Andrej Kral Athanasia Warnecke 《PloS one》2013,8(12)
The formation of gliosis around implant electrodes for deep brain stimulation impairs electrode–tissue interaction. Unspecific growth of glial tissue around the electrodes can be hindered by altering physicochemical material properties. However, in vitro screening of neural tissue–material interaction requires an adequate cell culture system. No adequate model for cells dissociated from the inferior colliculus (IC) has been described and was thus the aim of this study. Therefore, IC were isolated from neonatal rats (P3_5) and a dissociated cell culture was established. In screening experiments using four dissociation methods (Neural Tissue Dissociation Kit [NTDK] T, NTDK P; NTDK PN, and a validated protocol for the dissociation of spiral ganglion neurons [SGN]), the optimal media, and seeding densities were identified. Thereafter, a dissociation protocol containing only the proteolytic enzymes of interest (trypsin or papain) was tested. For analysis, cells were fixed and immunolabeled using glial- and neuron-specific antibodies. Adhesion and survival of dissociated neurons and glial cells isolated from the IC were demonstrated in all experimental settings. Hence, preservation of type-specific cytoarchitecture with sufficient neuronal networks only occurred in cultures dissociated with NTDK P, NTDK PN, and fresh prepared papain solution. However, cultures obtained after dissociation with papain, seeded at a density of 2×104 cells/well and cultivated with Neuro Medium for 6 days reliably revealed the highest neuronal yield with excellent cytoarchitecture of neurons and glial cells. The herein described dissociated culture can be utilized as in vitro model to screen interactions between cells of the IC and surface modifications of the electrode. 相似文献
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106.
Ciofi C Tzika AC Natali C Watts PC Sulandari S Zein MS Milinkovitch MC 《Molecular ecology resources》2011,11(3):550-556
Multiplex PCR assays for the coamplification of microsatellite loci allow rapid and cost-effective genetic analyses and the production of efficient screening protocols for international breeding programs. We constructed a partial genomic library enriched for di-nucleotide repeats and characterized 14 new microsatellite loci for the Komodo monitor (or Komodo dragon, Varanus komodoensis). Using these novel microsatellites and four previously described loci, we developed multiplex PCR assays that may be loaded on a genetic analyser in three separate panels. We tested the novel set of microsatellites for polymorphism using 69 individuals from three island populations and evaluated the resolving power of the entire panel of 18 loci by conducting (i) a preliminary assignment test to determine population(s) of origin and (ii) a parentage analysis for 43 captive Komodo monitors. This panel of polymorphic loci proved useful for both purposes and thus can be exploited for fine-scale population genetic analyses and as part of international captive breeding programs directed at maintaining genetically viable ex situ populations and reintroductions. 相似文献
107.
Mou C Pitel F Gourichon D Vignoles F Tzika A Tato P Yu L Burt DW Bed'hom B Tixier-Boichard M Painter KJ Headon DJ 《PLoS biology》2011,9(3):e1001028
Vertebrate skin is characterized by its patterned array of appendages, whether feathers, hairs, or scales. In avian skin the distribution of feathers occurs on two distinct spatial levels. Grouping of feathers within discrete tracts, with bare skin lying between the tracts, is termed the macropattern, while the smaller scale periodic spacing between individual feathers is referred to as the micropattern. The degree of integration between the patterning mechanisms that operate on these two scales during development and the mechanisms underlying the remarkable evolvability of skin macropatterns are unknown. A striking example of macropattern variation is the convergent loss of neck feathering in multiple species, a trait associated with heat tolerance in both wild and domestic birds. In chicken, a mutation called Naked neck is characterized by a reduction of body feathering and completely bare neck. Here we perform genetic fine mapping of the causative region and identify a large insertion associated with the Naked neck trait. A strong candidate gene in the critical interval, BMP12/GDF7, displays markedly elevated expression in Naked neck embryonic skin due to a cis-regulatory effect of the causative mutation. BMP family members inhibit embryonic feather formation by acting in a reaction-diffusion mechanism, and we find that selective production of retinoic acid by neck skin potentiates BMP signaling, making neck skin more sensitive than body skin to suppression of feather development. This selective production of retinoic acid by neck skin constitutes a cryptic pattern as its effects on feathering are not revealed until gross BMP levels are altered. This developmental modularity of neck and body skin allows simple quantitative changes in BMP levels to produce a sparsely feathered or bare neck while maintaining robust feather patterning on the body. 相似文献
108.
Rachid Z Katsoulas A Williams C Larroque AL McNamee J Jean-Claude BJ 《Bioorganic & medicinal chemistry letters》2007,17(15):4248-4253
Steps toward the identification of combi-molecules with strong abl tyrosine kinase (TK) inhibitory property and significant DNA damaging potential are described. The optimized combi-molecule 13a was shown to induce approximately twofold stronger abl TK inhibitory activity than Gleevec and high levels of DNA damage in chronic myelogenous leukemic cells. 相似文献
109.
Simian virus 40 large T antigen is a J-domain-containing protein with multiple functions. Among its numerous activities, T antigen can bind heat shock cognate 70 (hsc70) but the biological significance of this interaction has not been fully understood. Here, we show that T antigen can act as an hsc70 co-chaperone enhancing the protein-folding ability of the hsc70 chaperone machine. We also show that T antigen exerts its function in collaboration with the mammalian homologue of DnaJ. Moreover, we show that the participation of T antigen in the hsc70 chaperone machine has cell-type-specific characteristics. 相似文献
110.
Athanasia Sepsa Georgia Levidou Antonis Gargalionis Christos Adamopoulos Anastasia Spyropoulou Georgia Dalagiorgou Irene Thymara Efstathios Boviatsis Marios S. Themistocleous Kalliopi Petraki George Vrettakos Vassilis Samaras Athanassios Zisakis Efstratios Patsouris Christina Piperi Penelope Korkolopoulou 《PloS one》2015,10(1)
Although epigenetic alterations play an essential role in gliomagenesis, the relevance of aberrant histone modifications and the respective enzymes has not been clarified. Experimental data implicates histone H3 lysine (K) methyltransferases SETDB1 and SUV39H1 into glioma pathobiology, whereas linker histone variant H1.0 and H4K20me3 reportedly affect prognosis. We investigated the expression of H3K9me3 and its methyltransferases along with H4K20me3 and H1x in 101 astrocytic tumors with regard to clinicopathological characteristics and survival. The effect of SUV39H1 inhibition by chaetocin on the proliferation, colony formation and migration of T98G cells was also examined. SETDB1 and cytoplasmic SUV39H1 levels increased from normal brain through low-grade to high-grade tumors, nuclear SUV39H1 correlating inversely with grade. H3K9me3 immunoreactivity was higher in normal brain showing no association with grade, whereas H1x and H4K20me3 expression was higher in grade 2 than in normal brain or high grades. These expression patterns of H1x, H4K20me3 and H3K9me3 were verified by Western immunoblotting. Chaetocin treatment significantly reduced proliferation, clonogenic potential and migratory ability of T98G cells. H1x was an independent favorable prognosticator in glioblastomas, this effect being validated in an independent set of 66 patients. Diminished nuclear SUV39H1 expression adversely affected survival in univariate analysis. In conclusion, H4K20me3 and H3K9 methyltransferases are differentially implicated in astroglial tumor progression. Deregulation of H1x emerges as a prognostic biomarker. 相似文献