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排序方式: 共有279条查询结果,搜索用时 930 毫秒
191.
Jonathan CM Clark Toru Akiyama Crispin R Dass Peter FM Choong 《Cancer cell international》2010,10(1):20
Background
Chondrosarcoma responds poorly to adjuvant therapy and new, clinically relevant animal models are required to test targeted therapy. 相似文献192.
Hanna-Kirsti S. Leiros Bjørn Olav Brandsdal Seán M. McSweeney 《Biochimica et Biophysica Acta - Proteins and Proteomics》2010,1804(4):967-976
Metronidazole (MTZ) is an antibiotic commonly used to treat anaerobic bacterial infections in humans and animals. Antibiotic resistance toward this class of 5-nitroimidazole (5-Ni) drug derivatives has been related to the Nim genes thought to encode a reductase. Here we report the biophysical characteristics of the NimA protein from Deinococcus radiodurans (DrNimA) binding to MTZ and three other 5-Ni drugs. The interaction energies of the protein and antibiotic are studied by isothermal titration calorimetry (ITC) and with free energy and linear interaction energy (LIE) calculations, where the latter method revealed that the antibiotic binding is mainly of hydrophobic character. ITC measurements further found that one DrNimA dimer has two antibiotic binding sites which were not affected by mutation of the reactive His71. The observed association constants (Ka) were in the range of 5.1–49 ? 104 M− 1 and the enthalpy release upon binding to DrNimA for the four drugs studied was relatively low (∼ − 1 kJ/mol) but still measurable. The drug binding is mainly entropy driven and along with the hydrophobic drug binding site found by crystallography, this possibly explains the low observed enthalpy values. The effect of the His71 mutation and the presence of MTZ were studied by differential scanning calorimetry (DSC). Native DrNimA is a yellow colored protein where the interaction from His71 to the cofactor is thought to be responsible for the coloring. Mutations of His71 to Ala, Ser, Leu or Asp all gave transparent, colorless protein solutions, and the two mutant crystal structures of DrNimA-H71A and DrNimA-H71S presented revealed no cofactor binding. 相似文献
193.
A mathematical approach was developed to model and optimize selection on multiple known quantitative trait loci (QTL) and polygenic estimated breeding values in order to maximize a weighted sum of responses to selection over multiple generations. The model allows for linkage between QTL with multiple alleles and arbitrary genetic effects, including dominance, epistasis, and gametic imprinting. Gametic phase disequilibrium between the QTL and between the QTL and polygenes is modeled but polygenic variance is assumed constant. Breeding programs with discrete generations, differential selection of males and females and random mating of selected parents are modeled. Polygenic EBV obtained from best linear unbiased prediction models can be accommodated. The problem was formulated as a multiple-stage optimal control problem and an iterative approach was developed for its solution. The method can be used to develop and evaluate optimal strategies for selection on multiple QTL for a wide range of situations and genetic models. 相似文献
194.
Fioravanti E Durá MA Lascoux D Micossi E Franzetti B McSweeney S 《Biochemistry》2008,47(44):11581-11589
The expression level of protein DR1199 is observed to increase considerably in the radio-resistant bacterium Deinococcus radiodurans following irradiation. This protein belongs to the DJ-1 superfamily, which includes proteins with diverse functions, such as the archaeal proteases PhpI and PfpI, the bacterial chaperone Hsp31 and hyperosmotic stress protein YhbO, and the human Parkinson's disease-related protein DJ-1. All members of the superfamily are oligomeric, and the oligomerization interface varies from protein to protein. Although for many of these proteins, their function remains obscure, most of them are involved in cellular protection against environmental stresses. We have determined the structure of DR1199 to a resolution of 2.15 A, and we have tested its function and studied its role in the response to irradiation and more generally to oxidative stress in D. radiodurans. The protein is a dimer displaying an oligomerization interface similar to that observed for the YhbO and PhpI proteins. The cysteine in the catalytic triad (Cys 115) is oxidized in our structure, similar to modifications seen in the corresponding cysteine of the DJ-1 protein. The oxidation occurs spontaneously in DR1199 crystals. In solution, no proteolytic or chaperone activity was detected. On the basis of our results, we suggest that DR1199 might work as a general stress protein involved in the detoxification of the cell from oxygen reactive species, rather than as a peptidase in D. radiodurans. 相似文献
195.
Eric A Gaucher Logan G Graddy Tang Li Rosalia CM Simmen Frank A Simmen David R Schreiber David A Liberles Christine M Janis Steven A Benner 《BMC biology》2004,2(1):19
Background
Joining a model for the molecular evolution of a protein family to the paleontological and geological records (geobiology), and then to the chemical structures of substrates, products, and protein folds, is emerging as a broad strategy for generating hypotheses concerning function in a post-genomic world. This strategy expands systems biology to a planetary context, necessary for a notion of fitness to underlie (as it must) any discussion of function within a biomolecular system. 相似文献196.
197.
Diel variation in beaked whale diving behavior 总被引:2,自引:0,他引:2
Robin W. Baird Daniel L. Webster † Gregory S. Schorr ‡ Daniel J. McSweeney § Jay Barlow ¶ 《Marine Mammal Science》2008,24(3):630-642
We investigate diel variation in beaked whale diving behavior using data from time–depth recorders deployed on six Blainville's ( Mesoplodon densirostris) (255 h) and two Cuvier's ( Ziphius cavirostris ) (34 h) beaked whales. Deep foraging dives (>800 m) occurred at similar rates during the day and night for Blainville's beaked whales, and there were no significant diel differences in ascent rates, descent rates, or mean or maximum depths or durations for deep dives. Dive to mid-water depths (100–600 m) occurred significantly more often during the day (mean = 1.59 h−1 ) than at night (mean = 0.26 h−1 ). Series of progressively shallower "bounce" dives were only documented to follow the deep, long dives made during the day; at night whales spent more time in shallow (<100 m) depths. Significantly slower ascent rates than descent rates were found following deep foraging dives both during the day and night. Similar patterns were found for the Cuvier's beaked whales. Our results suggest that so-called "bounce" dives do not serve a physiological function, although the slow ascents may. This diel variation in behavior suggests that beaked whales may spend less time in surface waters during the day to avoid near-surface, visually oriented predators such as large sharks or killer whales ( Orcinus orca ). 相似文献
198.
Meunier-Jamin C Kapp U Leonard GA McSweeney S 《The Journal of biological chemistry》2004,279(24):25830-25837
The three-dimensional structure of the organic hydroperoxide resistance protein (OHRP) from Deinococcus radiodurans as determined using single crystal xray diffraction techniques is reported. Comparison of the structure with that obtained for OHRP from Pseudomonas aeruginosa reveals that the polypeptide chain of OHRPs can adopt two significantly different conformations ("in" and "out") in the region of the active site disulfide moiety. It is postulated that the closed configuration is consistent with efficient catalysis of the reduction of organic hydroperoxides, whereas the open form is required for enzyme recycling. Comparison of the structures of OHRP and that of the osmotically induced protein C (OsmC) from Mycoplasma pneumoniae shows that OHRPs and OsmCs are structurally homologous, perhaps indicating related functions for the two families of proteins. 相似文献
199.
200.
Relapsing polychondritis (RP) is an autoimmune disease that affects extra-articular cartilage. Matrilin-1-induced relapsing
polychondritis (MIRP) is a model for RP and is useful for studies of the pathogenic mechanisms in this disease. There are
indications that the major histocompatibility complex (MHC) class II plays a major role in RP, since DR4+ patients are more commonly affected than controls. We have now addressed the role of the MHC region, as well as the non-MHC
contribution, using congenic mouse strains. Of the MHC congenic strains, B10.Q (H2
q
) was the most susceptible, the B10.P (H2
p
) and B10.R (H2
r
) strains developed mild disease, while B10 strains carrying the v, b, f, or u H2 haplotypes were resistant. A slight variation
of susceptibility of H2
q
strains (B10.Q> C3H.Q> DBA/1) was observed and the (B10.Q × DBA/1)F1 was the most susceptible of all strains. Furthermore, macrophages and CD4+ T cells were the most prominent cell types in inflammatory infiltrates of the tracheal cartilage. Macrophages are the major
source of many cytokines, such as interleukin-10 (IL-10), which is currently being tested as a therapeutic agent in several
autoimmune diseases. We therefore investigated B10.Q mice devoid of IL-10 through gene deletion and found that they developed
a significantly more severe disease, with an earlier onset, than their heterozygous littermates. In conclusion, MHC genes,
as well as non-MHC genes, are important for MIRP induction, and IL-10 plays a major suppressive role in cartilage inflammation
of the respiratory tract. 相似文献