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排序方式: 共有192条查询结果,搜索用时 78 毫秒
61.
Riazi R Rafii M Clarke JT Wykes LJ Ball RO Pencharz PB 《American journal of physiology. Endocrinology and metabolism》2004,287(1):E142-E149
Maple syrup urine disease (MSUD) is an autosomal recessive disorder caused by defects in the mitochondrial multienzyme complex branched-chain alpha-keto acid dehydrogenase (BCKD; EC 1.2.4.4), responsible for the oxidative decarboxylation of the branched-chain ketoacids (BCKA) derived from the branched-chain amino acids (BCAA) leucine, valine, and isoleucine. Deficiency of the enzyme results in increased concentrations of the BCAA and BCKA in body cells and fluids. The treatment of the disease is aimed at keeping the concentration of BCAA below the toxic concentrations, primarily by dietary restriction of BCAA intake. The objective of this study was to determine the total BCAA requirements of patients with classical MSUD caused by marked deficiency of BCKD by use of the indicator amino acid oxidation (IAAO) technique. Five MSUD patients from the MSUD clinic of The Hospital for Sick Children participated in the study. Each was randomly assigned to different intakes of BCAA mixture (0, 20, 30, 50, 60, 70, 90, 110, and 130 mg.kg(-1).day(-1)), in which the relative proportion of BCAA was the same as that in egg protein. Total BCAA requirement was determined by measuring the oxidation of l-[1-(13)C]phenylalanine to (13)CO(2). The mean total BCAA requirement was estimated using a two-phase linear regression crossover analysis, which showed that the mean total BCAA requirement was 45 mg.kg(-1).day(-1), with the safe level of intake (upper 95% confidence interval) at 62 mg.kg(-1).day(-1). This is the first time BCAA requirements in patients with MSUD have been determined directly. 相似文献
62.
Gonzalez-Santos JM Cao H Wang A Koehler DR Martin B Navab R Hu J 《Nucleic acids research》2005,33(10):e94
Our progress in understanding mammalian gene function has lagged behind that of gene identification. New methods for mammalian gene functional analysis are needed to accelerate the process. In yeast, the powerful genetic shuffle system allows deletion of any chromosomal gene by homologous recombination and episomal expression of a mutant allele in the same cell. Here, we report a method for mammalian cells, which employs a helper-dependent adenoviral (HD-Ad) vector to synthesize small hairpin (sh) RNAs to knock-down the expression of an endogenous gene by targeting untranslated regions (UTRs). The vector simultaneously expresses an exogenous version of the same gene (wild-type or mutant allele) lacking the UTRs for functional analysis. We demonstrated the utility of the method by using PRPF3, which encodes the human RNA splicing factor Hprp3p. Recently, missense mutations in PRPF3 were found to cause autosomal-dominant Retinitis Pigmentosa, a form of genetic eye diseases affecting the retina. We knocked-down endogenous PRPF3 in multiple cell lines and rescued the phenotype (cell death) with exogenous PRPF3 cDNA, thereby creating a genetic complementation method. Because Ad vectors can efficiently transduce a wide variety of cell types, and many tissues in vivo, this method could have a wide application for gene function studies. 相似文献
63.
Roya Hooshmand-Rad Lena Claesson-Welsh Stefan Wennström Koutaro Yokote Agneta Siegbahn Carl-Henrik Heldin 《Experimental cell research》1997,234(2):434
Previous work has suggested a role for phosphatidylinositide 3′-kinase (PI3-kinase) in platelet-derived growth factor (PDGF)-induced actin reorganization and chemotaxis. In support of this notion, we show in this report that the PI3-kinase inhibitor wortmannin inhibits chemotaxis of PDGF β-receptor expressing porcine aortic endothelial (PAE/PDGFR-β) cells. Treatment with wortmannin resulted in a dose-dependent decrease in chemotaxis with an IC50value of about 15–20 nM.Higher concentrations of wortmannin also reduced basal random migration of transfected cells in the absence of PDGF. We also investigated the role of Rac in PDGF-induced actin reorganization and cell motility. Overexpression of wt Rac in PAE/PDGFR-β cells led to an increased cell motility and edge ruffling in response to PDGF-BB, compared to control cells. In PAE/PDGFR-β cells transfected with inducible V12Rac (a constitutively active Rac mutant), membrane ruffling occurred in the absence of PDGF stimulation and was independent of PI3-kinase activity. On the other hand, PAE/PDGFR-β cells transfected with inducible N17Rac (a dominant negative Rac mutant) failed to show membrane ruffling in response to PDGF stimulation. Together with previous observations, these data indicate that activation of PI3-kinase is crucial for initiation of PDGF-induced cell motility responses and that Rac has a major role downstream of PI3-kinase, in this pathway. 相似文献
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66.
Marzieh Naseri Margot Zöller Jamshid Hadjati Roya Ghods Ehsan Ranaei Pirmardan Jafar Kiani Leila Eini Mahmood Bozorgmehr Zahra Madjd 《Journal of cellular and molecular medicine》2021,25(7):3312-3326
Cancer stem cells (CSCs) are responsible for therapeutic resistance and recurrence in colorectal cancer. Despite advances in immunotherapy, the inability to specifically eradicate CSCs has led to treatment failure. Hence, identification of appropriate antigen sources is a major challenge in designing dendritic cell (DC)-based therapeutic strategies against CSCs. Here, in an in vitro model using the HT-29 colon cancer cell line, we explored the efficacy of DCs loaded with exosomes derived from CSC-enriched colonospheres (CSCenr-EXOs) as an antigen source in activating CSC-specific T-cell responses. HT-29 lysate, HT-29-EXOs and CSCenr lysate were independently assessed as separate antigen sources. Having confirmed CSCs enrichment in spheroids, CSCenr-EXOs were purified and characterized, and their impact on DC maturation was investigated. Finally, the impact of the antigen-pulsed DCs on the proliferation rate and also spheroid destructive capacity of autologous T cells was assessed. CSCenr-EXOs similar to other antigen groups had no suppressive/negative impacts on phenotypic maturation of DCs as judged by the expression level of costimulatory molecules. Notably, similar to CSCenr lysate, CSCenr-EXOs significantly increased the IL-12/IL-10 ratio in supernatants of mature DCs. CSCenr-EXO-loaded DCs effectively promoted T-cell proliferation. Importantly, T cells stimulated with CSCenr-EXOs disrupted spheroids' structure. Thus, CSCenr-EXOs present a novel and promising antigen source that in combination with conventional tumour bulk-derived antigens should be further explored in pre-clinical immunotherapeutic settings for the efficacy in hampering recurrence and metastatic spread. 相似文献
67.
Mohammad Fereidouni Roya Mahdavi Sarah Mahmoudzade Hadis Rezapoor Alireza Fereidouni Afsane Bahrami 《Reports of Biochemistry & Molecular Biology》2021,10(2):257
Background:Allergic disorders are common health problems worldwide with significant socio-economic impacts. The best diagnostic method using allergenic extract is the skin prick test. Regarding the effects of geo-climatic factors and allergenic extract source material quality, the aim of study was to determine the safety and efficacy of some in-house-developed allergenic extracts.Methods:Forty-five different allergenic extracts, including common regional pollen, foods, and dog and cat hair, as well as positive and negative extracts, were prepared from domestic sources using optimum extraction methods. All extracts passed stability and sterility testing, and sterile final products containing 50% glycerin in 10 and 20 w/v concentrations were used. Skin prick testing was performed on volunteers and immediate or late side effects were recorded. Results:In total, 56 students (mean age: 21.2±2.3y, M/F ratio: 1.07) participated in this study. For inhalant allergens, all extracts except dog hair extract caused positive responses. Salsola kali (Russian thistle) and Fraxinus velutina (ash tree) were the most common grass and tree pollen extracts, respectively. Of 18 different food extracts, five, including egg white, tomato, fig, melon, and green pepper caused skin reactivity in only one person. No participant reported any immediate or late side effects, including large local reaction or systemic response.Conclusion:The result of the current study confirmed the safety of all our in-house-developed allergenic extracts. Regarding efficacy, almost all inhalant and five food allergens caused positive skin responses.Key Words: Allergenic extract, In-house extract, Skin prick test 相似文献
68.
David Ando Roya Zandi Yong?Woon Kim Michael Colvin Michael Rexach Ajay Gopinathan 《Biophysical journal》2014,106(9):1997-2007
The transport of cargo across the nuclear membrane is highly selective and accomplished by a poorly understood mechanism involving hundreds of nucleoporins lining the inside of the nuclear pore complex (NPC). Currently, there is no clear picture of the overall structure formed by this collection of proteins within the pore, primarily due to their disordered nature. We perform coarse-grained simulations of both individual nucleoporins and grafted rings of nups mimicking the in vivo geometry of the NPC and supplement this with polymer brush modeling. Our results indicate that different regions or blocks of an individual NPC protein can have distinctly different forms of disorder and that this property appears to be a conserved functional feature. Furthermore, this block structure at the individual protein level is critical to the formation of a unique higher-order polymer brush architecture that can exist in distinct morphologies depending on the effective interaction energy between the phenylalanine glycine (FG) domains of different nups. Because the interactions between FG domains may be modulated by certain forms of transport factors, our results indicate that transitions between brush morphologies could play an important role in regulating transport across the NPC, suggesting novel forms of gated transport across membrane pores with wide biomimetic applicability. 相似文献
69.
Ebrahim Mostafavi Arash Aghajani Nargesi Zaniar Ghazizadeh Mehrdad Larry Roya Horabad Farahani Afsaneh Morteza Alireza Esteghamati Claude Vigneron Manouchehr Nakhjavani 《The Journal of membrane biology》2014,247(8):695-701
Calcium is a key regulator of cell dynamics. Dysregulation of its cytosolic concentration is implicated in the pathophysiology of several diseases. This study aimed to assess the effects of calcium on the network of membrane cytoskeletal proteins. Erythrocyte membranes were obtained from eight healthy donors and incubated with 250 µM and 1.25 mM calcium solutions. Membrane cytoskeletal proteins were quantified using SDS-PAGE at baseline and after 3 and 5 days of incubation. Supra-physiologic concentrations of calcium (1.25 mM) induced a significant proteolysis in membrane cytoskeletal proteins, compared with magnesium (p < 0.001). Actin exhibited the highest sensitivity to calcium-induced proteolysis (6.8 ± 0.3 vs. 5.3 ± 0.6, p < 0.001), while spectrin (39.9 ± 1.0 vs. 40.3 ± 2.0, p = 0.393) and band-6 (6.3 ± 0.3 vs. 6.8 ± 0.8, p = 0.191) were more resistant to proteolysis after incubation with calcium in the range of endoplasmic reticulum concentrations (250 µM). Aggregation of membrane cytoskeletal proteins was determined after centrifugation and was significantly higher after incubation with calcium ions compared with control, EDTA and magnesium solutions (p < 0.001). In a supra-physiologic range of 1.25–10 mM of calcium ions, there was a nearly perfect linear relationship between calcium concentration and aggregation of erythrocyte membrane cytoskeletal proteins (R 2 = 0.971, p < 0.001). Our observation suggests a strong interaction between calcium ions and membrane cytoskeletal network. Cumulative effects of disrupted calcium homeostasis on cytoskeletal proteins need to be further investigated at extended periods of time in disease states. 相似文献
70.
Conor Rossi Gabriela Ruß-Popa Valeria Mattiangeli Fionnuala McDaid Andrew J. Hare Hossein Davoudi Haeedeh Laleh Zahra Lorzadeh Roya Khazaeli Homa Fathi Matthew D. Teasdale Abolfazl A'ali Thomas Stllner Marjan Mashkour Kevin G. Daly 《Biology letters》2021,17(7)
Mummified remains have long attracted interest as a potential source of ancient DNA. However, mummification is a rare process that requires an anhydrous environment to rapidly dehydrate and preserve tissue before complete decomposition occurs. We present the whole-genome sequences (3.94 X) of an approximately 1600-year-old naturally mummified sheep recovered from Chehrābād, a salt mine in northwestern Iran. Comparative analyses of published ancient sequences revealed the remarkable DNA integrity of this mummy. Hallmarks of postmortem damage, fragmentation and hydrolytic deamination are substantially reduced, likely owing to the high salinity of this taphonomic environment. Metagenomic analyses reflect the profound influence of high-salt content on decomposition; its microbial profile is predominated by halophilic archaea and bacteria, possibly contributing to the remarkable preservation of the sample. Applying population genomic analyses, we find clustering of this sheep with Southwest Asian modern breeds, suggesting ancestry continuity. Genotyping of a locus influencing the woolly phenotype showed the presence of an ancestral ‘hairy’ allele, consistent with hair fibre imaging. This, along with derived alleles associated with the fat-tail phenotype, provides genetic evidence that Sasanian-period Iranians maintained specialized sheep flocks for different uses, with the ‘hairy’, ‘fat-tailed’-genotyped sheep likely kept by the rural community of Chehrābād''s miners. 相似文献