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Type I and II pyrethroid insecticides display different neurotoxicity. To investigate the long-term (60 days exposure) metabolic effect of the two types of pyrethroid insecticides deltamethrin and permethrin, 1H nuclear magnetic resonance (NMR) spectroscopy-based metabonomics was used to analyze the biochemical composition of urine and serum samples from rats administrated daily with deltamethrin or permethrin for 60 consecutive days, and principal component analysis used to visualize similarities and differences in the resultant biochemical profiles. Rats treated with either deltamethrin or permethrin displayed increased levels of urinary acetate, dimethylamine, dimethylglycine, trimethylamine and serum free amino acids, and decreased urinary 2-oxoglutarate, all of which are indicative of kidney lesions and nephrotoxicity. The reduced excretion of tricarboxylic acid cycle intermediates, together with increased 3-D-hydroxybutyrate, acetate, and lactate in treated rats could suggest disturbance of the energy metabolism, including an increased rate of anaerobic glycolysis, enhanced fatty acid β-oxidation and ketogenesis. These results show that these two types of insecticides have similarities in the urine and serum spectra, indicating that similar metabolic pathways are perturbed by the insecticides, which induced hepatotoxicity and nephrotoxicity. This approach may lead to the discovery of novel biomarkers of pyrethroids toxicity and thereby provide new insights into the toxicological mechanisms of pesticides pyrethroids. 相似文献
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David T. Parkin 《Bird Study》2013,60(3):223-242
Capsule Based on the 1999 Witherby Memorial Lecture – reviews how developments in molecular and population genetics have led to a reappraisal of species limits in birds. The taxonomy of birds of the West Palearctic has moved from the comparative stability of the ‘Voous List’ into a period of serious activity, with new data emerging in almost every issue of every evolutionary and avian journal! This activity comes from two directions. Firstly, developments in population genetics, molecular biology, acoustics, behaviour and distributional studies have opened new avenues to measuring differentiation among groups of birds. This, in turn, has led to the recognition that earlier views of what constitutes a ‘species’ are in need of modification (‘improvement’), and the emergence of the ‘lineage concept’ of species. I review some of the species concepts most relevant to avian studies, and attempt to show how and why this change has happened, and its consequences for taxonomy and species limits. Examples are given in the form of ‘case studies’, and include Carrion/Hooded Crows Corvus corone/cornix, Green-winged/Eurasian Teals Anas carolinensis/crecca and Phylloscopus warblers. 相似文献
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Yifeng Wu Yuanheng Cai Yi Sun Ruixue Xu Haina Yu Xiaojuan Han Hongxiang Lou Aixia Cheng 《FEBS letters》2013
Alkenal double bond reductases (DBRs) catalyze the NADPH-dependent reduction of the α,β-unsaturated double bond of many secondary metabolites. Two alkenal double bond reductase genes PaDBR1 and PaDBR2 were isolated from the liverwort species Plagiochasma appendiculatum. Recombinant PaDBR2 protein had a higher catalytic activity than PaDBR1 with respect to the reduction of the double bond present in hydroxycinnamyl aldehydes. The residue at position 56 appeared to be responsible for this difference in enzyme activity. The functionality of a C56 to Y56 mutation in PaDBR1 was similar to that of PaDBR2. Further site-directed mutagenesis and structural modeling suggested that the phenol ring stacking between this residue and the substrate was an important determinant of catalytic efficiency. 相似文献
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Pretreatment of rice straw by using renewable cholinium amino acids ionic liquids ([Ch][AA] ILs)‐water mixtures and the subsequent enzymatic hydrolysis of the residues were conducted in the present work. Of the eight mixtures composed of ILs and water, most were found to be effective for rice straw pretreatment. After pretreatment with 50% ILs‐water mixtures, the enzymatic digestion of the lignocellulosic biomass was enhanced significantly, thus leading to satisfactory sugar yields of >80% for glucose and approximately 50% for xylose. To better understand the ILs pretreatment mechanism, confocal laser scanning microscopy combined with immunolabeling and transmission electron microscopy were used to visualize changes in the contents and distribution of two major components—lignin and xylan. The results coupled with changes in chemical structures (infrared spectra) of the substrates indicated occurrence of extensive delignification, especially in cell corner and compound middle lumen of cell walls, which made polysaccharides more accessible to enzymes. This pretreatment process is promising for large‐scale application because of the high sugar yields, easy handling, being environmentally benign and highly tolerant to moisture, and significantly reduced cost and energy consumption. Biotechnol. Bioeng. 2013; 110: 1895–1902. © 2013 Wiley Periodicals, Inc. 相似文献
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Svetla Stoilova‐McPhie Gillian C. Lynch Steven Ludtke B. Montgomery Pettitt 《Biopolymers》2013,99(7):448-459
Factor VIII (FVIII) is the blood coagulation protein which when defective or deficient causes for hemophilia A, a severe hereditary bleeding disorder. Activated FVIII (FVIIIa) is the cofactor to the serine protease factor IXa (FIXa) within the membrane‐bound Tenase complex, responsible for amplifying its proteolytic activity more than 100,000 times, necessary for normal clot formation. FVIII is composed of two noncovalently linked peptide chains: a light chain (LC) holding the membrane interaction sites and a heavy chain (HC) holding the main FIXa interaction sites. The interplay between the light and heavy chains (HCs) in the membrane‐bound state is critical for the biological efficiency of FVIII. Here, we present our cryo‐electron microscopy (EM) and structure analysis studies of human FVIII‐LC, when helically assembled onto negatively charged single lipid bilayer nanotubes. The resolved FVIII‐LC membrane‐bound structure supports aspects of our previously proposed FVIII structure from membrane‐bound two‐dimensional (2D) crystals, such as only the C2 domain interacts directly with the membrane. The LC is oriented differently in the FVIII membrane‐bound helical and 2D crystal structures based on EM data, and the existing X‐ray structures. This flexibility of the FVIII‐LC domain organization in different states is discussed in the light of the FVIIIa–FIXa complex assembly and function. © 2013 Wiley Periodicals, Inc. Biopolymers 99: 448–459, 2013. 相似文献
959.
Kok Hong Lim Heng Huang Arnd Pralle Sheldon Park 《Biotechnology and bioengineering》2013,110(1):57-67
The coupling between the quaternary structure, stability and function of streptavidin makes it difficult to engineer a stable, high affinity monomer for biotechnology applications. For example, the binding pocket of streptavidin tetramer is comprised of residues from multiple subunits, which cannot be replicated in a single domain protein. However, rhizavidin from Rhizobium etli was recently shown to bind biotin with high affinity as a dimer without the hydrophobic tryptophan lid donated by an adjacent subunit. In particular, the binding site of rhizavidin uses residues from a single subunit to interact with bound biotin. We therefore postulated that replacing the binding site residues of streptavidin monomer with corresponding rhizavidin residues would lead to the design of a high affinity monomer useful for biotechnology applications. Here, we report the construction and characterization of a structural monomer, mSA, which combines the streptavidin and rhizavidin sequences to achieve optimized biophysical properties. First, the biotin affinity of mSA (Kd = 2.8 nM) is the highest among nontetrameric streptavidin, allowing sensitive monovalent detection of biotinylated ligands. The monomer also has significantly higher stability (Tm = 59.8°C) and solubility than all other previously engineered monomers to ensure the molecule remains folded and functional during its application. Using fluorescence correlation spectroscopy, we show that mSA binds biotinylated targets as a monomer. We also show that the molecule can be used as a genetic tag to introduce biotin binding capability to a heterologous protein. For example, recombinantly fusing the monomer to a cell surface receptor allows direct labeling and imaging of transfected cells using biotinylated fluorophores. A stable and functional streptavidin monomer, such as mSA, should be a useful reagent for designing novel detection systems based on monovalent biotin interaction. Biotechnol. Bioeng. 2013; 110: 57–67. © 2012 Wiley Periodicals, Inc. 相似文献
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