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The passage of a natural substrate, L-arabinose (L-ARA) through Escherichia coli porin embedded in an artificial bilayer, is studied by equilibrium molecular dynamics simulations. We investigate the early stage of translocation process of L-ARA from intra-cellular to extra-cellular side (Int-to-Ext) across the bilayer. The average trajectory path over all L-ARA molecules along with quantum-mechanical configuration-optimizations at PM3 level predict the existence of at least three trapping zones. The common feature within all these zones is that L-ARA remains perpendicular to the channel axis. It is remarkable how the orientation and translational-rotational motion of L-ARA molecule play a role in its transport through OmpF channel. These simulations are important for better understanding of permeation process in OmpF channel. They also provide an insight into the chiral recognition of translocation process in protein nanochannels from substrate and protein prospects and help interpret experiments on permeation process of small dipolar molecules across biological membranes. 相似文献
53.
Jonathan M. Flowers Khaled M. Hazzouri Gina M. Pham Ulises Rosas Tayebeh Bahmani Basel Khraiwesh David R. Nelson Kenan Jijakli Rasha Abdrabu Elizabeth H. Harris Paul A. Lefebvre Erik F.Y. Hom Kourosh Salehi-Ashtiani Michael D. Purugganan 《The Plant cell》2015,27(9):2353-2369
We performed whole-genome resequencing of 12 field isolates and eight commonly studied laboratory strains of the model organism Chlamydomonas reinhardtii to characterize genomic diversity and provide a resource for studies of natural variation. Our data support previous observations that Chlamydomonas is among the most diverse eukaryotic species. Nucleotide diversity is ∼3% and is geographically structured in North America with some evidence of admixture among sampling locales. Examination of predicted loss-of-function mutations in field isolates indicates conservation of genes associated with core cellular functions, while genes in large gene families and poorly characterized genes show a greater incidence of major effect mutations. De novo assembly of unmapped reads recovered genes in the field isolates that are absent from the CC-503 assembly. The laboratory reference strains show a genomic pattern of polymorphism consistent with their origin as the recombinant progeny of a diploid zygospore. Large duplications or amplifications are a prominent feature of laboratory strains and appear to have originated under laboratory culture. Extensive natural variation offers a new source of genetic diversity for studies of Chlamydomonas, including naturally occurring alleles that may prove useful in studies of gene function and the dissection of quantitative genetic traits. 相似文献
54.
Kourosh Honarmand Ebrahimi Peter-Leon Hagedoorn Jaap A. Jongejan Wilfred R. Hagen 《Journal of biological inorganic chemistry》2009,14(8):1265-1274
The hollow sphere-shaped 24-meric ferritin can store large amounts of iron as a ferrihydrite-like mineral core. In all subunits
of homomeric ferritins and in catalytically active subunits of heteromeric ferritins a diiron binding site is found that is
commonly addressed as the ferroxidase center (FC). The FC is involved in the catalytic Fe(II) oxidation by the protein; however,
structural differences among different ferritins may be linked to different mechanisms of iron oxidation. Non-heme ferritins
are generally believed to operate by the so-called substrate FC model in which the FC cycles by filling with Fe(II), oxidizing
the iron, and donating labile Fe(III)–O–Fe(III) units to the cavity. In contrast, the heme-containing bacterial ferritin from
Escherichia coli has been proposed to carry a stable FC that indirectly catalyzes Fe(II) oxidation by electron transfer from a core that oxidizes
Fe(II). Here, we put forth yet another mechanism for the non-heme archaeal 24-meric ferritin from Pyrococcus furiosus in which a stable iron-containing FC acts as a catalytic center for the oxidation of Fe(II), which is subsequently transferred
to a core that is not involved in Fe(II)-oxidation catalysis. The proposal is based on optical spectroscopy and steady-state
kinetic measurements of iron oxidation and dioxygen consumption by apoferritin and by ferritin preloaded with different amounts
of iron. Oxidation of the first 48 Fe(II) added to apoferritin is spectrally and kinetically different from subsequent iron
oxidation and this is interpreted to reflect FC building followed by FC-catalyzed core formation. 相似文献
55.
Preparation of FMD type A87/IRN inactivated vaccine by gamma irradiation and the immune response on guinea pig 总被引:1,自引:0,他引:1
Farahnaz Motamedi Sedeh Akbar Khorasani Kamal Shafaee Hadi Fatolahi Kourosh Arbabi 《Indian journal of microbiology》2008,48(3):326-330
FMD is one of the most economically damaging diseases that affect livestock animals. In this study FMD Virus type A87/IRN
was multiplied on BHK21 cells. The virus was titrated by TCID50 method, it was 107.5/ml. The FMD virus samples were inactivated by gamma ray from 60Co source at −20°C. Safety test was done by IBRS2 monolayer
cell culture method, also antigenicity of irradiated and un-irradiated virus samples were studied by Complement Fixation Test.
The Dose/Survival curve for irradiated FMD Virus was drawn, the optimum dose range for inactivation of FMDV type A87/IRN and
unaltered antigenicity was obtained 40–44 kGy. The inactivated virus samples by irradiation and ethyleneimine (EI) were formulated
respectively as vaccine with Al(OH)3 gel and other substances. The vaccines were inoculated to Guinea pigs and the results
of Serum Neutralization Test for the normal vaccine and radio-vaccine showed protective titer after 8 months. The potency
test of the inactivated vaccines was done, PD50 Value of the vaccines were calculated 7.06 and 5.6 for inactivated vaccine
by EI and gamma irradiation respectively. 相似文献
56.
Siau Jia Wei Thomas Joseph Sharon Chee Ling Li Larisa Yurlova Kourosh Zolghadr Christopher Brown David Lane Chandra Verma Farid Ghadessy 《PloS one》2013,8(11)
Pharmacological modulation of p53 activity is an attractive therapeutic strategy in cancers with wild-type p53. Presently in clinical trials, the small molecule Nutlin-3A competitively binds to HDM2, a key negative regulator of p53 and blocks its activity. We have described resistance mutations in HDM2 that selectively reduce affinity for Nutlin but not p53. In the present communication, we show that stapled peptides targeting the same region of HDM2 as Nutlin are refractory to these mutations, and display reduced discrimination between the wild-type and mutant HDM2s with regards to functional abrogation of interaction with p53. The larger interaction footprint afforded by stapled peptides suggests that this class of ligands may prove comparatively more resilient to acquired resistance in a clinical setting. 相似文献
57.
Kourosh Vahdati Shima Bayat Hassan Ebrahimzadeh Maryam Jariteh Masoud Mirmasoumi 《Plant Cell, Tissue and Organ Culture》2008,93(2):163-171
Low efficiency of embryo maturation, germination and conversion to plantlets is a major problem in many species including
Persian walnut. We studied the effects of abscisic acid (ABA) and sucrose, on the maturation and germination of Persian walnut
(Juglans regia) somatic embryos. Individual globular somatic embryos were grown on a maturation medium supplemented with different combinations
of ABA and sucrose for ca. 1 month, until shoot meristems and radicles had developed. White and opaque embryos in late cotyledonary
stage were subjected to desiccation after the culture period on maturation media. The number of germinated somatic embryos
was influenced by the concentrations of ABA in the maturation medium. The best treatment for germination, in which both shoot
and root were developed contained 2 mg l−1 ABA and resulted in 41% conversion of embryos into plantlets. Regeneration was reduced at higher levels of ABA. While ABA
always reduced the rate of secondary embryogenesis, treatments containing 4.0% sucrose significantly increased the number
of secondary embryos. On the other hand, sucrose had little influence on maturation. Normal and abnormal embryos were verified
anatomically. 相似文献
58.
Anna Fyrberg Freidoun Albertioni Kourosh Lotfi 《Nucleosides, nucleotides & nucleic acids》2013,32(6-7):712-719
Resistance toward nucleoside analogues is often due to decreased activities of the activating enzymes deoxycytidine kinase (dCK) and/or deoxyguanosine kinase (dGK). With small interfering RNA (siRNA), dCK and dGK were downregulated by approximately 70% in CEM cells and tested against six nucleoside analogues using the methyl thiazol tetrazolium assay. SiRNA-transfected cells reduced in dCK activity were 3- to 6-fold less sensitive to CdA, AraC, and CAFdA. The sensitivity to AraG and FaraA was unchanged, while the sensitivity toward gemcitabine was significantly increased. dGK depletion in cells resulted in lower sensitivity to FaraA, dFdC, CAFdA, and AraG, but slightly higher sensitivity to CdA and AraC. 相似文献
59.
A Synthetic Peptide with the Putative Iron Binding Motif of Amyloid Precursor Protein (APP) Does Not Catalytically Oxidize Iron 总被引:1,自引:0,他引:1
The β-amyloid precursor protein (APP), which is a key player in Alzheimer's disease, was recently reported to possess an Fe(II) binding site within its E2 domain which exhibits ferroxidase activity [Duce et al. 2010, Cell 142: 857]. The putative ligands of this site were compared to those in the ferroxidase site of ferritin. The activity was indirectly measured using transferrin, which scavenges the Fe(III) product of the reaction. A 22-residue synthetic peptide, named FD1, with the putative ferroxidase site of APP, and the E2 domain of APP were each reported to exhibit 40% of the ferroxidase activity of APP and of ceruloplasmin. It was also claimed that the ferroxidase activity of APP is inhibited by Zn(II) just as in ferritin. We measured the ferroxidase activity indirectly (i) by the incorporation of the Fe(III) product of the ferroxidase reaction into transferrin and directly (ii) by monitoring consumption of the substrate molecular oxygen. The results with the FD1 peptide were compared to the established ferroxidase activities of human H-chain ferritin and of ceruloplasmin. For FD1 we observed no activity above the background of non-enzymatic Fe(II) oxidation by molecular oxygen. Zn(II) binds to transferrin and diminishes its Fe(III) incorporation capacity and rate but it does not specifically bind to a putative ferroxidase site of FD1. Based on these results, and on comparison of the putative ligands of the ferroxidase site of APP with those of ferritin, we conclude that the previously reported results for ferroxidase activity of FD1 and - by implication - of APP should be re-evaluated. 相似文献
60.
Glioblastoma multiform (GBM) is a highly malignant brain tumor. Bevacizumab is a recent therapy for stopping tumor growth and even shrinking tumor through inhibition of vascular development (angiogenesis). This paper presents a non-invasive approach based on image analysis of multi-parametric magnetic resonance images (MRI) to predict response of GBM to this treatment. The resulting prediction system has potential to be used by physicians to optimize treatment plans of the GBM patients. The proposed method applies signal decomposition and histogram analysis methods to extract statistical features from Gd-enhanced regions of tumor that quantify its microstructural characteristics. MRI studies of 12 patients at multiple time points before and up to four months after treatment are used in this work. Changes in the Gd-enhancement as well as necrosis and edema after treatment are used to evaluate the response. Leave-one-out cross validation method is applied to evaluate prediction quality of the models. Predictive models developed in this work have large regression coefficients (maximum R
2 = 0.95) indicating their capability to predict response to therapy. 相似文献