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排序方式: 共有205条查询结果,搜索用时 165 毫秒
51.
52.
Abstract The B3LYP/6–311+G(d,p) method and three ONIOM extrapolation methods ONI-OM (B3LYP/6–311+G(d,p): AM1); ONIOM(B3LYP/6–311+G(d,p): MNDO); ONIOM (B3LYP/6–311+G(d,p): HF/3-21G(d)) were used to characterize the complexes of Zn2+ cation with anionic sulfonylated amino acid hydroxamates (RSO2NH-AA-CON(-)OH), possessing an unsubstituted RSO2NH—amino acyl moiety. According to the R moiety we distinguish between pentafluorophenyl and 4-methoxyphenyl derivates. The amino acid hydroxamates included in the study were the Gly, Ala, and Leu derivates. Of the inhibitors investigated, the weakest zinc affinity exhibits the pentafluorophenyl derivate with Gly amino acid and the strongest affinity the 4-methoxyphenyl derivate with Leu amino acid. The inhibitors form bidentate coordination bonds with the zinc cation by means of the sulfonyl oxygen and the ionized hydroxamate nitrogen atoms, respectively. The zinc affinities computed using the B3LYP/6–311 +G(d,p)//HF/6–31 +G(d,p) method are in very good agreement with the full density functional theory (DFT) B3LYP/6–311+G(d,p)//B3LYP/6- 311+G(d,p) method and this method can be adopted to model larger complexes of inhibitors with the active site of carbonic anhydrase. 相似文献
53.
Martin Sramko Martin Smiesko Milan Remko 《Journal of biomolecular structure & dynamics》2013,31(6):599-608
Abstract Studies that allow computing values of aqueous proton dissociation constants (pKa), gas phase proton affinities, and the free energy of solvation have been performed for six members of angiotensin-I-converting enzyme (ACE) inhibitor family (captopril, enalaprilat, imidaprilat, ramiprilat, perindoprilat, and spiraprilat). Density functional theory (DFT) calculations using PBE1PBE functional on optimized molecular geometries have been carried out to investigate the thermodynamics of gas-phase protonation. The conductor-like polarizable continuum model (CPCM) solvation method at various levels of theory was applied to calculate the free energy of solvation for the ACE inhibitors and their respective anions. The CPCM solvation calculations were performed on both gas-phase and solvent-phase optimized structures. The combination of gas-phase and solvation energies according to the thermodynamic cycle enabled us to compute accurate pKa values for the all studied molecules. 相似文献
54.
Bacterial surface display entails the presentation of recombinant proteins or peptides on the surface of bacterial cells. Escherichia coli is the most frequently used bacterial host for surface display and, as such, a variety of E. coli display systems have been described that primarily promote the surface exposure of peptides and small proteins. By contrast, display systems based on autotransporter proteins (ATs) and ice nucleation protein (INP) are excellent systems for the display of large and complex proteins, and are therefore of considerable biotechnological relevance. Here, we review recent advances in AT and INP-mediated display and their biotechnological applications. Additionally, we discuss several promising alternative display methods, as well as novel bacterial host organisms. 相似文献
55.
Kuipers RS Luxwolda MF Janneke Dijck-Brouwer DA Muskiet FA 《Prostaglandins, leukotrienes, and essential fatty acids》2011,85(5):245-252
Erythrocyte (RBC) fatty acid compositions from populations with stable dietary habits but large variations in RBC-arachidonic (AA) and RBC-docosahexaenoic acid (DHA) provided us with insight into relationships between DHA and AA. It also enabled us to estimate the maternal RBC-DHA (mRBC-DHA) status that corresponded with no decrease in mRBC-DHA during pregnancy, or in infant (i) RBC-DHA or mRBC-DHA during the first 3 months postpartum (DHA-equilibrium) while exclusively breastfeeding. At delivery, iRBC-AA is uniformly high and independent of mRBC-AA. Infants born to mothers with low RBC-DHA exhibit higher, but infants born to mothers with high RBC-DHA exhibit lower RBC-DHA than their mothers. This switch from ‘biomagnification’ into ‘bioattenuation’ occurs at 6 g% mRBC-DHA. At 6 g%, mRBC-DHA is stable throughout pregnancy, corresponds with postpartum infant DHA-equilibrium of 6 and 0.4 g% DHA in mature milk, but results in postpartum depletion of mRBC-DHA to 5 g%. Postpartum maternal DHA-equilibrium is reached at 8 g% mRBC-DHA, corresponding with 1 g% DHA in mature milk and 7 g% iRBC-DHA at delivery that increases to 8 g% during lactation. This 8 g% RBC-DHA concurs with the lowest risks of cardiovascular and psychiatric diseases in adults. RBC-data from 1866 infants, males and (non-)pregnant females indicated AA vs. DHA synergism at low RBC-DHA, but antagonism at high RBC-DHA. These data, together with high intakes of AA and DHA from our Paleolithic diet, suggest that bioattenuation of DHA during pregnancy and postnatal antagonism between AA and DHA are the physiological standard for humans across the life cycle. 相似文献
56.
Comparative analysis of avian influenza virus diversity in poultry and humans during a highly pathogenic avian influenza A (H7N7) virus outbreak 总被引:1,自引:0,他引:1
Jonges M Bataille A Enserink R Meijer A Fouchier RA Stegeman A Koch G Koopmans M 《Journal of virology》2011,85(20):10598-10604
Although increasing data have become available that link human adaptation with specific molecular changes in nonhuman influenza viruses, the molecular changes of these viruses during a large highly pathogenic avian influenza virus (HPAI) outbreak in poultry along with avian-to-human transmission have never been documented. By comprehensive virologic analysis of combined veterinary and human samples obtained during a large HPAI A (H7N7) outbreak in the Netherlands in 2003, we mapped the acquisition of human adaptation markers to identify the public health risk associated with an HPAI outbreak in poultry. Full-length hemagglutinin (HA), neuraminidase (NA), and PB2 sequencing of A (H7N7) viruses obtained from 45 human cases showed amino acid variations at different codons in HA (n=20), NA (n=23), and PB2 (n=23). Identification of the avian sources of human virus infections based on 232 farm sequences demonstrated that for each gene about 50% of the variation was already present in poultry. Polygenic accumulation and farm-to-farm spread of known virulence and human adaptation markers in A (H7N7) virus-infected poultry occurred prior to farm-to-human transmission. These include the independent emergence of HA A143T mutants, accumulation of four NA mutations, and farm-to-farm spread of virus variants harboring mammalian host determinants D701N and S714I in PB2. This implies that HPAI viruses with pandemic potential can emerge directly from poultry. Since the public health risk of an avian influenza virus outbreak in poultry can rapidly change, we recommend virologic monitoring for human adaptation markers among poultry as well as among humans during the course of an outbreak in poultry. 相似文献
57.
Bijker MS van den Eeden SJ Franken KL Melief CJ Offringa R van der Burg SH 《Journal of immunology (Baltimore, Md. : 1950)》2007,179(8):5033-5040
Therapeutic vaccination trials, in which patients with cancer were vaccinated with minimal CTL peptide in oil-in-water formulations, have met with limited success. Many of these studies were based on the promising data of mice studies, showing that vaccination with a short synthetic peptide in IFA results in protective CD8(+) T cell immunity. By use of the highly immunogenic OVA CTL peptide in IFA as a model peptide-based vaccine, we investigated why minimal CTL peptide vaccines in IFA performed so inadequately to allow full optimization of peptide vaccination. Injection of the minimal MHC class I-binding OVA(257-264) peptide in IFA transiently activated CD8(+) effector T cells, which eventually failed to undergo secondary expansion or to kill target cells, as a result of a sustained and systemic presentation of the CTL peptides gradually leaking out of the IFA depot without systemic danger signals. Complementation of this vaccine with the MHC class II-binding Th peptide (OVA(323-339)) restored both secondary expansion and in vivo effector functions of CD8(+) T cells. Simply extending the CTL peptide to a length of 30 aa also preserved these CD8(+) T cell functions, independent of T cell help, because the longer CTL peptide was predominantly presented in the locally inflamed draining lymph node. Importantly, these functional differences were reproduced in two additional model Ag systems. Our data clearly show why priming of CTL with minimal peptide epitopes in IFA is suboptimal, and demonstrate that the use of longer versions of these CTL peptide epitopes ensures the induction of sustained effector CD8(+) T cell reactivity in vivo. 相似文献
58.
Kuipers RS Smit EN van der Meulen J Janneke Dijck-Brouwer DA Rudy Boersma E Muskiet FA 《Prostaglandins, leukotrienes, and essential fatty acids》2007,76(4):221-233
BACKGROUND: We need information on the diet on which our genes evolved. OBJECTIVE: We studied the milk fatty acid [FA] composition of mothers living in the island of Chole [Tanzania, Indian Ocean]. These mothers have high intakes of boiled marine fish and coconut, and consume plenty amount of fruits and vegetables. DESIGN: The outcome was compared with three fish-eating tribes living along Tanzanian freshwater lakes [Kerewe, Nyakius, Nyiramba], four tribes living in the Tanzanian inland [Hadzabe, Maasai, Sonjo, Iraqw] and our milk FA database. RESULTS: Milk from Chole contained high levels of 12:0 [20.17 g%], 14:0 [21.19], 12:0/14:0 ratio [0.92 g/g], arachidonic acid [AA, 0.50 g%] and docosahexaenoic acid [DHA, 0.73], but low levels of linoleic acid [LA, 4.23]. The combination of a high medium chain fatty acid [MCFA; 相似文献
59.
Subterranean archipelago in the Australian arid zone: mitochondrial DNA phylogeography of amphipods from central Western Australia 总被引:1,自引:0,他引:1
Cooper SJ Bradbury JH Saint KM Leys R Austin AD Humphreys WF 《Molecular ecology》2007,16(7):1533-1544
In 1998, a unique subterranean ecosystem was discovered in numerous isolated calcrete (carbonate) aquifers in the arid Yilgarn region of Western Australia. Previous morphological and genetic analyses of a subterranean water beetle fauna suggest that calcrete aquifers are equivalent to closed island habitats that have been isolated for millions of years. We tested this hypothesis further by phylogeographic analyses of subterranean amphipods (Crangonyctoidea: Paramelitidae and Hyalidae) using mitochondrial DNA sequence data derived from the cytochrome oxidase I gene. Phylogenetic analyses and population genetic analyses (samova) provided strong evidence for the existence of at least 16 crangonyctoid and six hyalid divergent mitochondrial lineages, each restricted in their distribution to a single calcrete aquifer, in support of the 'subterranean island (archipelago) hypothesis' and extending its scope to include entirely water respiring invertebrates. Sequence divergence estimates between proximate calcrete populations suggest that calcretes have been isolated at least since the Pliocene, coinciding with a major aridity phase that led to the intermittent drying of surface water. The distribution of calcretes along palaeodrainage channels and on either side of drainage divides, have had less influence on the overall phylogeographic structure of populations, with evidence that ancestral crangonyctoid and hyalid species moved between catchments multiple times prior to their isolation within calcretes. At least two potential modes of evolution may account for the diversity of subterranean amphipod populations: dispersal/vicariance of stygobitic species or colonization of calcretes by surface species and independent evolution of stygobitic characteristics. 相似文献
60.
Mercedes Soriano Hui Li Cédric Jacquard Gerco C. Angenent Joan Krochko Remko Offringa Kim Boutilier 《The Plant cell》2014,26(6):2568-2581
In Arabidopsis thaliana, zygotic embryo divisions are highly regular, but it is not clear how embryo patterning is established in species or culture systems with irregular cell divisions. We investigated this using the Brassica napus microspore embryogenesis system, where the male gametophyte is reprogrammed in vitro to form haploid embryos in the absence of exogenous growth regulators. Microspore embryos are formed via two pathways: a zygotic-like pathway, characterized by initial suspensor formation followed by embryo proper formation from the distal cell of the suspensor, and a pathway characterized by initially unorganized embryos lacking a suspensor. Using embryo fate and auxin markers, we show that the zygotic-like pathway requires polar auxin transport for embryo proper specification from the suspensor, while the suspensorless pathway is polar auxin transport independent and marked by an initial auxin maximum, suggesting early embryo proper establishment in the absence of a basal suspensor. Polarity establishment in this suspensorless pathway was triggered and guided by rupture of the pollen exine. Irregular division patterns did not affect cell fate establishment in either pathway. These results confirm the importance of the suspensor and suspensor-driven auxin transport in patterning, but also uncover a mechanism where cell patterning is less regular and independent of auxin transport. 相似文献