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71.
Simon C. Allen K. Ravi Acharya Kathleen A. Palmer Robert Shapiro Bert L. Vallee Harold A. Scheraga 《Journal of Protein Chemistry》1994,13(7):649-658
The three-dimensional structure of human angiogenin has been determined by X-ray crystallography and is compared here with an earlier model which predicted its structure, based on the homology of angiogenin with bovine pancreatic ribonuclease A. Comparison of the predicted model and crystal structure shows that the active-site histidine residues and the core of the angiogenin molecule, including most of the-strands and-helices, were predicted reasonably well. However, the structure of the surface loop regions and residues near the truncated C-terminus differs significantly. The C-terminal segment includes the active-site residues Asp-116, Gln-117, and Ser-118; Gln-117 in particular has been shown to be important in affecting the ribonucleolytic activity of angiogenin. Also, the orientation of one helix in the model differed from the orientation observed experimentally by about 20°, resulting in a large displacement of this chain segment. The difficulty encountered in predicting the surface loop regions has led to a new algorithm [Palmer and Scheraga (1991),J. Comput. Chem.,12, 505–526; (1992),J. Comput. Chem.,13, 329–350] for predicting the conformations of surface loops. 相似文献
72.
Chemical and biological behaviour of several Ni-forms was studied on different soil types with spinach as a test plant. For the positively charged forms, Ni-ions and Ni-TETREN-ions, extractability increased with decreasing pH and CEC values of the soil. On the other hand, Ni added as EDTA-complex resulted in an extremely high Ni mobility, enhancing extractable Ni in soils having higher pH and CEC values. Speciation of Ni in the saturation extracts of the soils revealed that the transformation of both added positive forms was dependent on the soil characteristics, while Ni added as EDTA-complex mainly remained in the negative form. This altered mobility, accompanied by variable modification of the original chemical form in the soil solution, affected plant uptake and appearance of phytotoxic effects. Speciation in the plant extracts indicated that regardless of the chemical form added to the soil, Ni was only found in neutral and negative complexes. Finally, using ion-pair reversed phase HPLC, Ni-EDTA-ions were quantified in both the soil solution and the plant extract. 相似文献
73.
Monica J. Justice Bebra J. Gilbert Kenneth W. Kinzler Bert Vogelstein Authur M. Buchberg Jeffrey D. Ceci Yoichi Matsuda Verne M. Chapman Christos Patriotis Antonios Makris Philip N. Tsichlis Nancy A. Jenkins Neal G. Copeland 《Genomics》1992,13(4):1281-1288
An interspecific backcross between C57BL/6J and Mus spretus was used to generate a molecular genetic linkage map of mouse chromosome 18 that includes 23 molecular markers and spans approximately 86% of the estimated length of the chromosome. The Apc, Camk2a, D18Fcr1, D18Fcr2, D18Leh1, D18Leh2, Dcc, Emb-rs3, Fgfa, Fim-2/Csfmr, Gnal, Grl-1, Grp, Hk-1rs1, Ii, Kns, Lmnb, Mbp, Mcc, Mtv-38, Palb, Pdgfrb, and Tpl-2 genes were mapped relative to each other in one interspecific backcross. A second interspecific backcross and a centromere-specific DNA satellite probe were used to determine the distance of the most proximal chromosome 18 marker to the centromere. The interspecific map extends the known regions of linkage homology between mouse chromosome 18 and human chromosomes 5 and 18 and identifies a new homology segment with human chromosome 10p. It also provides molecular access to many regions of mouse chromosome 18 for the first time. 相似文献
74.
Matthew P. Rubach Jackson Mukemba Salvatore Florence Bert K. Lopansri Keith Hyland Alicia D. Volkheimer Tsin W. Yeo Nicholas M. Anstey J. Brice Weinberg Esther D. Mwaikambo Donald L. Granger 《PLoS pathogens》2015,11(3)
Decreased bioavailability of nitric oxide (NO) is a major contributor to the pathophysiology of severe falciparum malaria. Tetrahydrobiopterin (BH4) is an enzyme cofactor required for NO synthesis from L-arginine. We hypothesized that systemic levels of BH4 would be decreased in children with cerebral malaria, contributing to low NO bioavailability. In an observational study in Tanzania, we measured urine levels of biopterin in its various redox states (fully reduced [BH4] and the oxidized metabolites, dihydrobiopterin [BH2] and biopterin [B0]) in children with uncomplicated malaria (UM, n = 55), cerebral malaria (CM, n = 45), non-malaria central nervous system conditions (NMC, n = 48), and in 111 healthy controls (HC). Median urine BH4 concentration in CM (1.10 [IQR:0.55–2.18] μmol/mmol creatinine) was significantly lower compared to each of the other three groups — UM (2.10 [IQR:1.32–3.14];p<0.001), NMC (1.52 [IQR:1.01–2.71];p = 0.002), and HC (1.60 [IQR:1.15–2.23];p = 0.005). Oxidized biopterins were increased, and the BH4:BH2 ratio markedly decreased in CM. In a multivariate logistic regression model, each Log10-unit decrease in urine BH4 was independently associated with a 3.85-fold (95% CI:1.89–7.61) increase in odds of CM (p<0.001). Low systemic BH4 levels and increased oxidized biopterins contribute to the low NO bioavailability observed in CM. Adjunctive therapy to regenerate BH4 may have a role in improving NO bioavailability and microvascular perfusion in severe falciparum malaria. 相似文献
75.
Gijsen HJ Berthelot D De Cleyn MA Geuens I Brône B Mercken M 《Bioorganic & medicinal chemistry letters》2012,22(2):797-800
The transient receptor potential A1 (TRPA1) channel has been implicated in a number of inflammatory and nociceptive processes, and antagonists of the TRPA1 receptor could offer a potential treatment for conditions such as inflammatory or neuropathic pain, airway disorders, and itch. In a high throughput screen aimed at the identification of TRPA1 antagonists, 4-phenyl-2-thioxo-1,2,3,4-tetrahydro-indeno[1,2-d]pyrimidin-5-one (1) was identified as a potent TRPA1 receptor antagonist. A series of analogous tricyclic 3,4-dihydropyrimidine-2-thiones has been prepared via the multi-component Biginelli reaction and subsequent derivatization. This has led to TRPA1 antagonists with potencies around 10nM for both rat and human derived TRPA1 receptors. The activity was shown to reside exclusively in the 4R-enantiomers. 相似文献
76.
Heart-type fatty acid-binding protein (H-FABP) is a major fatty acid-binding factor in skeletal muscles. Genetic lack of H-FABP
severely impairs the esterification and oxidation of exogenous fatty acids in soleus muscles isolated from chow-fed mice (CHOW-solei)
and high fat diet-fed mice (HFD-solei), and prevents the HFD-induced accumulation of muscle triacylglycerols (TAGs). Here,
we examined the impact of H-FABP deficiency on the relationship between fatty acid utilization and glucose oxidation. Glucose
oxidation was measured in isolated soleus muscles in the presence or absence of 1 mM palmitate (simple protocol) or in the
absence of fatty acid after preincubation with 1 mM palmitate (complex protocol). With the simple protocol, the mutation slightly
reduced glucose oxidation in CHOW-muscles, but markedly increased it in HFD-muscles; unexpectedly, this pattern was not altered
by the addition of palmitate, which reduced glucose oxidation in both CHOW- and HFD-solei irrespective of the mutation. In
the complex protocol, the mutation first inhibited the synthesis and accumulation of TAGs and then their mobilization; with
this protocol, the mutation increased glucose oxidation in both CHOW- and HFD-solei. We conclude: (i) H-FABP mediates a non-acute
inhibition of muscle glucose oxidation by fatty acids, likely by enabling both the accumulation and mobilization of a critical
mass of muscle TAGs; (ii) H-FABP does not mediate the acute inhibitory effect of extracellular fatty acids on muscle glucose
oxidation; (iii) H-FABP affects muscle glucose oxidation in opposing ways, with inhibition prevailing at high muscle TAG contents. 相似文献
77.
Murphy EJ Barcelo-Coblijn G Binas B Glatz JF 《The Journal of biological chemistry》2004,279(33):34481-34488
Cell culture systems have demonstrated a role for cytoplasmic fatty acid-binding proteins (FABP) in lipid metabolism, although a similar function in intact animals is unknown. We addressed this issue using heart fatty acid-binding protein (H-FABP) gene-ablated mice. H-FABP gene ablation reduced total heart fatty acid uptake 40 and 52% for [1-(14)C]16:0 and [1-(14)C]20:4n-6 compared with controls, respectively. Similarly, the amount of fatty acid found in the aqueous fraction was reduced 40 and 52% for [1-(14)C]16:0 and [1-(14)C]20:4n-6, respectively. Less [1-(14)C]16:0 entered the triacylglycerol pool, with significant redistribution of fatty acid between the triacylglycerol pool and the total phospholipid pool. Less [1-(14)C]20:4n-6 entered each lipid pool measured, but these changes did not alter the distribution of tracer among these pools. In gene-ablated mice, significantly more [1-(14)C]16:0 was targeted to choline and ethanolamine glycerophospholipids, whereas more [1-(14)C]20:4n-6 was targeted to the phosphatidylinositol (PtdIns) pool. H-FABP gene ablation significantly increased PtdIns mass 1.4-fold but reduced PtdIns 20:4n-6 mass 30%. Consistent with a reported effect of FABP on plasmalogen mass, ethanolamine plasmalogen mass was reduced 30% in gene-ablated mice. Further, 20:4n-6 mass was reduced in each of the three other major phospholipid classes, suggesting H-FABP has a role in maintaining steady-state 20:4n-6 mass in heart. In summary, H-FABP was important for heart fatty acid uptake and targeting of fatty acids to specific heart lipid pools as well as for maintenance of phospholipid pool mass and acyl chain composition. 相似文献
78.
A new computational efficient approach for trabecular bone analysis using beam models generated with skeletonized graph technique 总被引:1,自引:0,他引:1
Pothuaud L Van Rietbergen B Charlot C Ozhinsky E Majumdar S 《Computer methods in biomechanics and biomedical engineering》2004,7(4):205-213
Micro-finite element (FE) analysis is a well established technique for the evaluation of the elastic properties of trabecular bone, but is limited in its application due to the large number of elements that it requires to represent the complex internal structure of the bone. In this paper, we present an alternative FE approach that makes use of a recently developed 3D-Line Skeleton Graph Analysis (LSGA) technique to represent the complex internal structure of trabecular bone as a network of simple straight beam elements in which the beams are assigned geometrical properties of the trabeculae that they represent. Since an enormous reduction of cputime can be obtained with this beam modeling approach, ranging from approximately 1,200 to 3,600 for the problems investigated here, we think that the FE modeling technique that we introduced could potentially constitute an interesting alternative for the evaluation of the elastic mechanical properties of trabecular bone. 相似文献
79.
A standardized method for the sampling of rhizosphere and rhizoplan soil bacteria associated to a herbaceous root system 总被引:3,自引:0,他引:3
Cindy D. C. Barillot Claude-Olivier Sarde Valerie Bert Eric Tarnaud Nelly Cochet 《Annals of microbiology》2013,63(2):471-476
Plants-microorganisms interactions play a fundamental role in terrestrial ecosystems and various methods have been reported for plant-associated bacteria extraction. However, these methods exhibit notable variations and lack of some procedural details that may impact the interpretations of results. We propose here a standardized and detailed protocol for the independent extraction of bulk, rhizosphere and rhizoplan soil fractions. This protocol was applied to the sampling of different polluted soil fractions collected in the vicinity of Arabidopsis halleri dense root system. It allowed us to determine the cultivable bacterial densities in each fraction and to confirm the existence of a bacterial gradient linked to roots distance, with a higher amount of bacteria in the rhizospheric area. We suggest to use this unified procedure as a common basis for soil sampling and bacterial communities analysis from other roots systems. 相似文献
80.
Evelyn Ploetz Gea K. Schuurman-Wolters Niels Zijlstra Amarins W. Jager Douglas A. Griffith Albert Guskov Giorgos Gouridis Bert Poolman Thorben Cordes 《Open biology》2021,11(4)
The ATP-binding cassette transporter GlnPQ is an essential uptake system that transports glutamine, glutamic acid and asparagine in Gram-positive bacteria. It features two extra-cytoplasmic substrate-binding domains (SBDs) that are linked in tandem to the transmembrane domain of the transporter. The two SBDs differ in their ligand specificities, binding affinities and their distance to the transmembrane domain. Here, we elucidate the effects of the tandem arrangement of the domains on the biochemical, biophysical and structural properties of the protein. For this, we determined the crystal structure of the ligand-free tandem SBD1-2 protein from Lactococcus lactis in the absence of the transporter and compared the tandem to the isolated SBDs. We also used isothermal titration calorimetry to determine the ligand-binding affinity of the SBDs and single-molecule Förster resonance energy transfer (smFRET) to relate ligand binding to conformational changes in each of the domains of the tandem. We show that substrate binding and conformational changes are not notably affected by the presence of the adjoining domain in the wild-type protein, and changes only occur when the linker between the domains is shortened. In a proof-of-concept experiment, we combine smFRET with protein-induced fluorescence enhancement (PIFE–FRET) and show that a decrease in SBD linker length is observed as a linear increase in donor-brightness for SBD2 while we can still monitor the conformational states (open/closed) of SBD1. These results demonstrate the feasibility of PIFE–FRET to monitor protein–protein interactions and conformational states simultaneously. 相似文献