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31.
Resta N Susca FC Di Giacomo MC Stella A Bukvic N Bagnulo R Simone C Guanti G 《Journal of cellular physiology》2006,209(1):67-73
Roberts syndrome (RS) is a rare disorder characterized by tetraphocomelia and several other clinical features. Cells from RS patients exhibit characteristic premature separation of heterochromatic region of many chromosomes and abnormalities in cell cycle. Mutations in the ESCO2 gene have recently been identified in 20 RS families. We performed mutational analysis of the ESCO2 gene in two fetuses diagnosed with RS and their normal parents. In both fetuses, we identified homozygosity for the c. 745_746delGT mutation, while the non-consanguineous parents were both heterozygous for the same mutation. Considering the position of the mutation identified, we carried out qualitative and quantitative real-time ESCO2 cDNA analysis on RNA isolated from CVS-stromal cells in one fetus, amniocytes in the second fetus, and lymphocytes from the heterozygous parents. The results of this analysis showed that despite the presence of a premature termination codon (PTC) 112 nucleotides upstream of the next exon3-exon4 junction, the mutant ESCO2 mRNA was present in both fetuses, albeit at low levels, indicating a partial resistance to nonsense mediated decay (NMD). Interestingly, when cells derived from the two fetuses were treated with an inhibitor of translation, they revealed the presence of tissue and individual variability in NMD efficiency, despite the identical mutational status. The existence of such a variation in the NMD efficiency could explain the broad intrafamilial and interfamilial variability in the clinical presentation of RS patients, and in other genetic diseases where nonsense mutations are responsible for most of the mutation load. Moreover, considering that a mutated full length mRNA was produced in both fetuses, we used Western blot analysis to demonstrate the absence of the ESCO2-truncated protein in cells derived from both fetuses and in a lymphoblastoid cell line derived from the parents. 相似文献
32.
Zorica Knezevic Nenad Milosavic Dejan Bezbradica Zivana Jakovljevic Radivoje Prodanovic 《Biochemical Engineering Journal》2006,30(3):269-278
The present study compares the results of three different covalent immobilization methods employed for immobilization of lipase from Candida rugosa on Eupergit® C supports with respect to enzyme loadings, activities and coupling yields. It seems that method yielding the highest activity retention of 43.3% is based on coupling lipase via its carbohydrate moiety previously modified by periodate oxidation. Study of thermal deactivation kinetics at three temperatures (37, 50 and 75 °C) revealed that the immobilization method also produces an appreciable stabilization of the biocatalyst, changing its thermal deactivation profile. By comparison of the t1/2 values obtained at 75 °C, it can be concluded that the lipase immobilized via carbohydrate moiety was almost 2-fold more stable than conventionally immobilized one and 18-fold than free lipase. The immobilization procedure developed is quite simple, and easily reproduced, and provides a promising solution for application of lipase in aqueous and microaqueous reaction system. 相似文献
33.
Prostate-specific membrane antigen regulates angiogenesis by modulating integrin signal transduction 下载免费PDF全文
Conway RE Petrovic N Li Z Heston W Wu D Shapiro LH 《Molecular and cellular biology》2006,26(14):5310-5324
The transmembrane peptidase prostate-specific membrane antigen (PSMA) is universally upregulated in the vasculature of solid tumors, but its functional role in tumor angiogenesis has not been investigated. Here we show that angiogenesis is severely impaired in PSMA-null animals and that this angiogenic defect occurs at the level of endothelial cell invasion through the extracellular matrix barrier. Because proteolytic degradation of the extracellular matrix is a critical component of endothelial invasion in angiogenesis, it is logical to assume that PSMA participates in matrix degradation. However, we demonstrate a novel and more complex role for PSMA in angiogenesis, where it is a principal component of a regulatory loop that is tightly modulating laminin-specific integrin signaling and GTPase-dependent, p21-activated kinase 1 (PAK-1) activity. We show that PSMA inhibition, knockdown, or deficiency decreases endothelial cell invasion in vitro via integrin and PAK, thus abrogating angiogenesis. Interestingly, the neutralization of beta(1) or the inactivation of PAK increases PSMA activity, suggesting that they negatively regulate PSMA. This negative regulation is mediated by the cytoskeleton as the disruption of interactions between the PSMA cytoplasmic tail and the anchor protein filamin A decreases PSMA activity, integrin function, and PAK activation. Finally, the inhibition of PAK activation enhances the PSMA/filamin A interaction and, thus, boosts PSMA activity. These data imply that PSMA participates in an autoregulatory loop, wherein active PSMA facilitates integrin signaling and PAK activation, leading to both productive invasion and downregulation of integrin beta(1) signaling via reduced PSMA activity. Therefore, we have identified a novel role for PSMA as a true molecular interface, integrating both extracellular and intracellular signals during angiogenesis. 相似文献
34.
Blomqvist ME Reynolds C Katzov H Feuk L Andreasen N Bogdanovic N Blennow K Brookes AJ Prince JA 《Human genetics》2006,119(1-2):29-37
Most genetic sequence variants that contribute to variability in complex human traits will have small effects that are not
readily detectable with population samples typically used in genetic association studies. A potentially valuable tool in the
gene discovery process is meta-analysis of the accumulated published data, but in order to be valid these require a sample
of studies representative of the true genetic effect and thus hypothetically should include some positive and an abundance
of negative reports. A survey of the literature on association studies for Alzheimer disease (AD) from January 2004–April
2005, identified 138 studies, 86 of which reported positive findings other than for apolipoprotein E (APOE), strongly indicative of publication bias. We report here an analysis of 62 genetic markers, tested for association with
AD risk as well as for possible effects upon quantitative indices of AD severity (mini-mental state examination scores, age-at-onset,
and cerebrospinal fluid (CSF) β-amyloid (Aβ) and CSF tau proteins). Within this set, only modest signals were present that,
with the exception of APOE are easily lost when corrections for multiple hypotheses are applied. In isolation, results are thus broadly negative. Genes
studied encompass both novel candidates as well as several recently claimed to be associated with AD (e.g. urokinase plasminogen
activator (PLAU) and acetyl-coenzyme A acetyltransferase 1 (ACAT1)). By reporting these data we hope to encourage the publication of gene compendia to guide further studies and aid future
meta-analyses aimed at resolving the involvement of genes in complex human traits. 相似文献
35.
Jovanović S Jovanović N Jovanović A 《Biochemical and biophysical research communications》2006,341(1):57-66
In the heart, the opening of sarcolemmal ATP-sensitive K(+) (K(ATP)) channels seems to be crucial for the cardiac protection against hypoxia/ischaemia. In the present study, we have exposed cardiomyocytes under hypoxia to high extracellular glucose (30 mM). Under these conditions, intracellular concentration of 1,3-bisphosphoglycerate has increased confirming stimulation of glycolysis. Perforated patch-clamp electrophysiology revealed that hypoxia induces whole-cell K(+) current in cardiomyocytes more efficiently in the presence than in the absence of high glucose. Glucose significantly promoted survival of cardiomyocytes exposed to hypoxia. HMR 1098, an antagonist of sarcolemmal K(ATP) channels, inhibited glucose-induced activation of whole-cell K(+) current during hypoxia as well as glucose-mediated cytoprotection. An inhibitor of glyceraldehyde 3-phosphate dehydrogenase, iodoacetate, inhibited glycolysis in hypoxia and blocked the activation of sarcolemmal K(ATP) channels. Based on the obtained results, we conclude that the activation of sarcolemmal K(ATP) channels is involved in glucose-mediated cardioprotection. 相似文献
36.
Analysis of single Alzheimer solid plaque cores by laser capture microscopy and nanoelectrospray/tandem mass spectrometry 总被引:2,自引:0,他引:2
Söderberg L Bogdanovic N Axelsson B Winblad B Näslund J Tjernberg LO 《Biochemistry》2006,45(32):9849-9856
Aggregation of the 40-42 residue amyloid beta-peptide (Abeta) into amyloid plaques is a central event in Alzheimer's disease (AD) pathogenesis. Many proteins have by immunohistochemical techniques been shown to codeposit with Abeta in AD plaques. It is possible that some of these could seed Abeta aggregation and therefore be found in the actual core of the plaque. Here, we present a highly sensitive method for unbiased biochemical analysis of plaque cores. A mild purification protocol based on centrifugation and filtration was used to purify intact plaque cores from human AD brain. The purified plaques were dispensed on a glass slide and viewed in a laser capture microscope, and plaque cores were catapulted into a tube cap by a laser beam. After dissolution in formic acid, plaques were digested and analyzed by liquid chromatography coupled online to electrospray/tandem mass spectrometry. One single plaque was found to be sufficient for positive identification of the main amyloid component. Remarkably, Abeta was the only protein identified when 200 plaques were isolated and analyzed with the present method. Thus, it is possible that no proteins copolymerize with Abeta in the plaque cores and that Abeta alone is sufficient for formation of plaque cores. In support of this notion, core-like structures were observed after incubation of synthetic Abeta for 2 weeks. We suggest that the method described here could be used for the general analysis of amyloid aggregates and inclusion bodies found in other neurodegenerative disorders and that plaque cores in AD brain are molecularly homogeneous structures. 相似文献
37.
Neural agrin plays a pleiotropic role in skeletal muscle innervation and maturation, but its specific effects on the contractile function of aneural engineered muscle remain unknown. In this study, neonatal rat skeletal myoblasts cultured within 3-dimensional engineered muscle tissue constructs were treated with 10 nM soluble recombinant miniagrin and assessed using histological, biochemical, and functional assays. Depending on the treatment duration and onset time relative to the stage of myogenic differentiation, miniagrin was found to induce up to 1.7-fold increase in twitch and tetanus force amplitude. This effect was associated with the 2.3-fold up-regulation of dystrophin gene expression at 6 d after agrin removal and enhanced ACh receptor (AChR) cluster formation, but no change in cell number, expression of muscle myosin, or important aspects of intracellular Ca(2+) handling. In muscle constructs with endogenous ACh levels suppressed by the application of α-NETA, miniagrin increased AChR clustering and twitch force amplitude but failed to improve intracellular Ca(2+) handling and increase tetanus-to-twitch ratio. Overall, our studies suggest that besides its synaptogenic function that could promote integration of engineered muscle constructs in vivo, neural agrin can directly promote the contractile function of aneural engineered muscle via mechanisms distinct from those involving endogenous ACh. 相似文献
38.
Vukelic MÐ Mitic ZJ Miljkovic MS Zivkovic JM Ignjatovic NL Uskokovic DP Zivanov-Curlis JŽ Vasiljevic PJ Najman SJ 《Journal of applied biomaterials & functional materials》2012,10(1):e43-e48
Simulated body fluid (SBF) is an artificial fluid which has ionic composition and ionic concentration similar to human blood plasma. Purpose: This paper compares the interaction between the nanomaterial containing calcium phosphate/poly-dl-lactide-co-glycolide (N-CP/PLGA) and SBF, in order to investigate whether and to what extent inorganic ionic composition of human blood plasma leads to the aforementioned changes in the material. Methods: N-CP/PLGA was incubated for 1, 2, 3, and 5 weeks in SBF. The surface of the material was analyzed on SEM-EDS and FTIR spectrometer, while SBF was subjected to pH and electrical conductivity measurement. Results: Our results indicate that dissolution of the polymer component of the material N-CP/PLGA and precipitation of the material similar to hydroxyapatite on its surface are based on the morphologic changes seen in this material. Conclusions: The mechanism of the apatite formation on the bioceramic surface was intensively studied and was considered crucial in designing the new biomaterials. The results obtained in this work indicate that N-CP/PLGA may be a good candidate for application to bone regeneration. 相似文献
39.
Tanasic I Milic-Lemic A Tihacek-Sojic L Stancic I Mitrovic N 《Biomechanics and modeling in mechanobiology》2012,11(6):751-758
It was the purpose of this study to determine and analyse strains in the bone of posterior mandible below the removable and fixed partial dentures using Digital Image Correlation Method. Dried mandible with shortened dental arch (Kennedy Class 1) was used in the experiment. The mandible model was prepared for accepting two types of restorations for bilaterally missing molars conventional therapy, and removable and fixed partial dentures were manufactured following standard prosthetic protocol. The models with prosthetic restorations placed in situ were subjected to loading of 50-300 N, and photographed using two digital cameras as part of the digital image correlation method equipment. Afterwards, the obtained data for strains within restored mandible during loading ciclus were analysed in the software Aramis and graphically presented. Percentage size of the mandible strains within the line section are from 0.14 to 0.19% for the removable partial denture experimental model and 0-0.14% for the fixed partial denture experimental model. The study has demonstrated that Digital Image Correlation method can be used to measure strain on the mandible surface and replacements during loading and that from biomechanical perspective both therapeutic modalities can be equally useful for the restoration of the mandible with bilaterally distal edentulous spaces. 相似文献
40.
Parts L Hedman ÅK Keildson S Knights AJ Abreu-Goodger C van de Bunt M Guerra-Assunção JA Bartonicek N van Dongen S Mägi R Nisbet J Barrett A Rantalainen M Nica AC Quail MA Small KS Glass D Enright AJ Winn J;MuTHER Consortium Deloukas P Dermitzakis ET McCarthy MI Spector TD Durbin R Lindgren CM 《PLoS genetics》2012,8(5):e1002704