Search results for "Wild type"
showing 10 items of 181 documents
6-mercaptopurine and 9-(2-phosphonyl-methoxyethyl) adenine (PMEA) transport altered by two missense mutations in the drug transporter gene ABCC4
2008
Multiple drug resistance protein 4 (MRP4, ABCC4) belongs to the C subfamily of the ATP-binding cassette (ABC) transporter superfamily and participates in the transport of diverse antiviral and chemotherapeutic agents such as 6-mercaptopurine (6-MP) and 9-(2-phosphonyl methoxyethyl) adenine (PMEA). We have undertaken a comprehensive functional characterization of protein variants of MRP4 found in Caucasians and other ethnicities. A total of 11 MRP4 missense genetic variants (nonsynonymous SNPs), fused to green fluorescent protein (GFP), were examined in Xenopus laevis oocytes for their effect on expression, localization, and function of the transporter. Radiolabeled 6-MP and PMEA were chosen…
Nitric oxide synthesis is related to astroglial cell cycle in the mouse retina via p53 gene regulation
2009
Purpose To analyze the influence of p53 gene in retinal astrocytes morphology and function. Methods Adult mice of the strain C57BL/6 were distributed into two groups: 1) wild type TP53, as the controls (cp53; n=20) and 2) mice with an extra copy of p53 (sp53; n=22). Both eyeballs were enucleated, after death by ether narcosis, to obtain the retinas. Right retinas were frozen (-85oC) until processing to assess nitric oxide (NO) synthesis. Left retinas were obtained and proccesed to perform immunohistochemical localization of the glial fibrillary acidic protein (GFAP). Data are expressed as the mean ± SD. Statistical analysis was carried out using Student’s t-test. Confidence interval was tak…
Phase III study of regorafenib versus placebo as maintenance therapy in RAS wild type metastatic colorectal cancer (RAVELLO trial)
2015
TPS789 Background: Treatment of metastatic colorectal cancer (mCRC) has improved due to the introduction of more active chemotherapies (CT) and novel targeted agents that have significantly increased response rate (RR), progression free survival (PFS) and overall survival (OS). Recently, CORRECT and CONCUR trials have demonstrated both activity and efficacy of regorafenib, a small multi-kinase inhibitor, as monotherapy in pretreated mCRC. The wide range of action of regorafenib makes it an ideal candidate for monotherapy in earlier disease treatment lines in which different pathways could be involved in the acquisition of resistance. To improve long term efficacy of first line therapy seve…
Direct Identification of Each Specific Mutation in Codon 12 and 13 of ci-ki-ras2 by SSCP Analysis
1998
We compared the SSCP behaviour of the DNA fragments containing c-ki-ras 2 wild type 12 and 13 codons or each of the 12 possible point mutated sequences in these two codons. We found that a single electrophoresis condition was sufficient to distinguish each specific mutation from the other 11 and from the wild type sequence. This observation makes it possible to identify each specific mutation directly by SSCP without any need for reamplification and sequencing.
A Multivariate Analysis of HIV-1 Protease Inhibitors and Resistance Induced by Mutation
2005
This paper describes the use of the multivariate statistical procedure principal component analysis as a tool to explore the inhibitory activity of classes of protease inhibitors (PIs) against HIV-1 viruses (wild type and more-frequent single mutants, V82A, V82F, and I84V) and against protease enzymes. The analysis of correlations between biological activity and molecular descriptors or similarity indexes allowed a reliable classification of the 51 derivatives considered in this study. The best results were obtained in the case of the I84V mutant for which a high number of predictions was achieved. On this basis, this statistical approach is proposed as a reliable method for the prediction …
Performance of industrial strains of Saccharomyces cerevisae during wine fermentation is affected by manipulation strategies based on sporulation.
2002
Genetic manipulation of industrial wine yeast strains has become an essential tool for both the study of the molecular mechanisms underlaying their physiology and the improvement of their fermentative properties. The construction of null mutants for any gene in these usually diploid strains, by using a procedure based on sporulation of a heterozygote lacking one copy of the gene of interest, has been tested as an alternative to the tedious work of sequential disruption of the complete set of copies. Our results indicate that most of the homozygotes resulting from sporulation of wine yeast strains are defective in glucose consumption under microvinification conditions in synthetic must and p…
A short-range gradient of histone H3 acetylation and Tup1p redistribution at the promoter of the Saccharomyces cerevisiae SUC2 gene.
2003
Chromatin immunoprecipitation assays are used to map H3 and H4 acetylation over the promoter nucleosomes and the coding region of the Saccharomyces cerevisiae SUC2 gene, under repressed and derepressed conditions, using wild type and mutant strains. In wild type cells, a high level of H3 acetylation at the distal end of the promoter drops sharply toward the proximal nucleosome that covers the TATA box, a gradient that become even steeper on derepression. In contrast, substantial H4 acetylation shows no such gradient and extends into the coding region. Overall levels of both H3 and H4 acetylation rise on derepression. Mutation of GCN5 or SNF2 lead to substantially reduced SUC2 expression; in…
Yeast HAT1 and HAT2 deletions have different life-span and transcriptome phenotypes
2005
AbstractHAT-B is a yeast histone acetyltransferase composed of Hat1, Hat2 and Hif1 proteins. We demonstrate that a hat2 mutant or a hat1hat2 double mutant, but not a hat1 mutant, have an extended life-span. Transcriptome analysis shows that the single hat mutants are not very different from wild type. However, the comparison of the hat1 and hat2 transcriptomes shows that they are different. The hat1hat2 double mutant shows a transcriptional phenotype similar to that of the hat1 mutant but strongly enhanced. These results indicate that Hat2p could have additional functions in the cell to those of Hat1p.
Expression of the gene encoding secretor type galactoside 2 ? fucosyltransferase (FUT2) and ABH antigens in patients with oral lesions
2010
Objective: The aim of this work was to evaluate the expression of FUT2 gene in saliva and histo ABH antigens of patients with oral lesions. Study Design: In total 178 subjects were examined, half of whom suffered from oral pre-cancerous and cancerous lesions, while the other half were the healthy control group We analyzed the FUT 2 polymorphism by ASO-PCR (allele specific oligonucleotid – polymerase chain reaction) with specific primers for G428 allele and the wild type allele of FUT2 gene. To reveal A, B and H antigens in tissue sections of the patients (n= 89) we used a modified specific red cell adherence technique. Results: We found a high intensity of oral disease in the non-secretor g…
Two changes of the same nucleotide confer resistance to diuron and antimycin in the mitochondrial cytochrome b gene of Schizosaccharomyces pombe
1988
AbstractDiuron (3-(3,4-dichlorophenyl)-1,1-dimethylurea) and antimycin, both inhibitors of mitochondrial respiration, block electron flow between cytochromes b and c1. Mutants resistant to either drug have been selected using Schizosaccharomyces pombe strains with an extrachromosomally inherited mutator. In analogy to Saccharomyces cerevisiae these mutational sites were assumed to map in the cytochrome b gene. DNA sequence analysis showed that two changes in the same nucleotide are responsible for resistance to antimycin and diuron. Analysis of resistant and sensitive progeny of crosses between the mutants and the wild type confirmed the correlation between mutational alteration and resista…