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Under the selection pressure of drugs, mutations appear in HIV-1 protease even at the sites, which are conserved in the untreated individuals. Cysteine 95 is a highly conserved residue and is believed to be involved in regulation of HIV-1 protease. In some of the virus isolates from patients undergoing heavy treatment with anti-HIV protease drugs, C95F mutation has appeared. The present study reports 1.8A X-ray structure of C95M/C1095F double mutant of tethered HIV-1 protease dimer complexed with acetyl pepstatin. It is found that in this mutant, dimer interface has become more rigid and that the packing at the interface of terminal and core domains is altered. These alterations may be relevant to C95F mutation conferring drug resistance to HIV-1 protease. 相似文献
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García-Peñas A Gómez-Ruiz S Pérez-Quintanilla D Paschke R Sierra I Prashar S del Hierro I Kaluđerović GN 《Journal of inorganic biochemistry》2012,106(1):100-110
Titanocene dichloride [Ti(η5-C5H5)2Cl2] (1), has been grafted onto dehydrated hydroxyapatite (HAP), Al2O3 and two mesoporous silicas MSU-2 (Michigan State University Silica type 2) and HMS (Hexagonal Mesoporous Silica), to give the novel materials HAP/[Ti(η5-C5H5)2Cl2] (S1) (1.01 wt.% Ti), Al2O3/[Ti(η5-C5H5)2Cl2] (S2) (2.36 wt.% Ti), HMS/[Ti(η5-C5H5)2Cl2] (S3) (0.75 wt.% Ti) and MSU-2/[Ti(η5-C5H5)2Cl2] (S4) (0.74 wt.% Ti), which have been characterized by powder X-ray diffraction, X-ray fluorescence, nitrogen gas sorption, multinuclear magic angle spinning NMR spectroscopy, IR spectroscopy, thermogravimetry analysis, UV spectroscopy, scanning electronic microscopy and transmission electronic microscopy. The cytotoxicity of the titanocene-functionalized materials toward human cancer cell lines from five different histogenic origins: 8505 C (anaplastic thyroid cancer), A253 (head and neck cancer), A549 (lung carcinoma), A2780 (ovarian cancer) and DLD-1 (colon cancer) has been determined. M50 values (quantity of material needed to inhibit normal cell growth by 50%) and Ti-M50 values (quantity of anchored titanium needed to inhibit normal cell growth by 50%) indicate that the activity of S1-S4 against studied human cancer cells depended on the surface type as well as on the cell line. In addition, studies on the titanocene release and the interaction of the materials S1-S4 with DNA show that the cytotoxic activity may be due to particle action, because no release of titanium complexes has been observed in physiological conditions, while electrostatic interactions of titanocene-functionalized particles with DNA have been observed. 相似文献
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The rapid development of genomic technology has made high throughput genotyping widely accessible but the associated high throughput phenotyping is now the major limiting factor in genetic analysis of traits. This paper evaluates the use of thermal imaging for the high throughput field phenotyping of Solanum tuberosum for differences in stomatal behaviour. A large multi-replicated trial of a potato mapping population was used to investigate the consistency in genotypic rankings across different trials and across measurements made at different times of day and on different days. The results confirmed a high degree of consistency between the genotypic rankings based on relative canopy temperature on different occasions. Genotype discrimination was enhanced both through normalising data by expressing genotype temperatures as differences from image means and through the enhanced replication obtained by using overlapping images. A Monte Carlo simulation approach was used to confirm the magnitude of genotypic differences that it is possible to discriminate. The results showed a clear negative association between canopy temperature and final tuber yield for this population, when grown under ample moisture supply. We have therefore established infrared thermography as an easy, rapid and non-destructive screening method for evaluating large population trials for genetic analysis. We also envisage this approach as having great potential for evaluating plant response to stress under field conditions. 相似文献
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Matrix metalloproteinases‐2 (MMP‐2) and matrix metalloproteinases ‐9 (MMP‐9) are differentially expressed in different regions of normal and preeclampsia placentae 下载免费PDF全文
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Construction of a dense SNP map of a highly heterozygous diploid potato population and QTL analysis of tuber shape and eye depth 总被引:2,自引:0,他引:2
Ankush Prashar Csaba Hornyik Vanessa Young Karen McLean Sanjeev Kumar Sharma M. Finlay B. Dale Glenn J. Bryan 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2014,127(10):2159-2171
Key message
Generation of a dense SNP-based linkage map of a diploid potato population and identification of major QTLs for tuber shape and eye depth on chromosomes 2 and 10.Abstract
This paper reports the construction of a genetic map of a highly heterozygous full-sib diploid potato population (06H1) based on the use of a set of 8,303 single nucleotide polymorphism (SNP) markers. The map contains 1,355 distinct loci and 2,157 SNPs, 802 of which co-segregate with other markers. We find high levels of collinearity between the 12 chromosomal maps with a recently improved version of the potato genome assembly, with the expected genetic clustering in centromeric regions. The linkage maps are used in combination with highly detailed phenotypic assessments conducted over two growing seasons to perform quantitative trait loci analysis of two important potato traits, tuber shape and eye depth. The major loci segregating for tuber shape in 06H1 map to loci on chromosomes 2 and 10, with smaller effects mapping to three other chromosomes. A major locus for tuber eye depth co-locates with the tuber shape locus on chromosome 10. To assess when tuber shape is established in the developing tuber, we have performed staged observations of tuber formation. Our observations suggest that tuber shape is determined very early in tuber development. 相似文献10.
Jordan Woodrick Suhani Gupta Pooja Khatkar Sanchita Sarangi Ganga Narasimhan Akriti Trehan Sanjay Adhikari Rabindra Roy 《Nucleic acids research》2014,42(14):9033-9046
Repair of oxidative stress- and inflammation-induced DNA lesions by the base excision repair (BER) pathway prevents mutation, a form of genomic instability which is often observed in cancer as ‘mutation hotspots’. This suggests that some sequences have inherent mutability, possibly due to sequence-related differences in repair. This study has explored intrinsic mutability as a consequence of sequence-specific repair of lipid peroxidation-induced DNA adduct, 1, N6-ethenoadenine (εA). For the first time, we observed significant delay in repair of ϵA at mutation hotspots in the tumor suppressor gene p53 compared to non-hotspots in live human hepatocytes and endothelial cells using an in-cell real time PCR-based method. In-cell and in vitro mechanism studies revealed that this delay in repair was due to inefficient turnover of N-methylpurine-DNA glycosylase (MPG), which initiates BER of εA. We determined that the product dissociation rate of MPG at the hotspot codons was ≈5–12-fold lower than the non-hotspots, suggesting a previously unknown mechanism for slower repair at mutation hotspots and implicating sequence-related variability of DNA repair efficiency to be responsible for mutation hotspot signatures. 相似文献