Efficient remote homology detection using local structure

MOTIVATION: The function of an unknown biological sequence can often be accurately inferred if we are able to map this unknown sequence to its corresponding homologous family. At present, discriminative methods such as SVM-Fisher and SVM-pairwise, which combine support vector machine (SVM) and sequence similarity, are recognized as the most accurate methods, with SVM-pairwise being the most accurate. However, these methods typically encode sequence information into their feature vectors and ignore the structure information. They are also computationally inefficient. Based on these observations, we present an alternative method for SVM-based protein classification. Our proposed method, SVM-I-sites, utilizes structure similarity for remote homology detection. RESULT: We run experiments on the Structural Classification of Proteins 1.53 data set. The results show that SVM-I-sites is more efficient than SVM-pairwise. Further, we find that SVM-I-sites outperforms sequence-based methods such as PSI-BLAST, SAM, and SVM-Fisher while achieving a comparable performance with SVM-pairwise. AVAILABILITY: I-sites server is accessible through the web at http://www.bioinfo.rpi.edu. Programs are available upon request for academics. Licensing agreements are available for commercial interests. The framework of encoding local structure into feature vector is available upon request.     

Crystallization and preliminary crystallographic analysis of human eukaryotic translation initiation factor 5A (eIF-5A)

Eukaryotic translation initiation factor 5A (eIF-5A) is universally found in all eukaryotic cells. It is the only protein in nature known to contain the unusual amino acid hypusine, a post-translationally modified lysine. Recombinant human eIF-5A was crystallized by the hanging-drop vapor diffusion method. Crystals were grown at 291 K using (NH4)2SO4 as precipitant. Diffraction data were obtained to a resolution of 2.7 A from a single frozen crystal belonging to space group C2, with unit-cell parameters a = 147.1 A, b = 60.4 A, c = 76.4 A, beta = 92.4 degrees. There are more than three molecules per asymmetric unit.     

A Possible Role of Glutathione as an Endogenous Agonist at the N-Methyl-d-Aspartate Recognition Domain in Rat Brain

Abstract: Glutathione, both reduced (GSH) and oxidized (GSSG), was effective in displacing binding of l -[³H]-glutamic acid (l -[³H]Glu) and dl -(E)-2-[³H]amino-4-propyl-5-phosphono-3-pentenoic acid ([³H]CGP-39653) in rat brain synaptic membranes, with less potent displacement of binding of dl -α-amino-3-hydroxy-5-[³H]-methylisoxazole-4-propionic and [³H]kainic acids. Liquid chromatographic analysis revealed that both GSH and GSSG were contaminated with l -Glu by <1%. Both GSH and GSSG potentiated (+)-5-[³H]methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine ([³H]MK-801) binding in a manner similar to that found with l -Glu. Pre-treatment with glutamate dehydrogenase (GDH) induced a marked rightward shift of the concentration-response curve for l -Glu in the presence of NAD without affecting that in its absence, whereas GDH was ineffective in affecting the potentiation by both GSH and GSSG even in the presence of NAD. In the presence of GSH at a maximally effective concentration, both glycine (Gly) and spermidine potentiated [³H]MK-801 binding to a somewhat smaller extent than that found in the presence of l -Glu at a maximally effective concentration. The potentiation of [³H]MK-801 binding by GSH was invariably attenuated by addition of CGP-39653, d -2-amino-5-phosphonovaleric acid (d -AP5), and 5,7-dichlorokynurenic acid (DCKA), whereas GSH was effective in diminishing potencies of CGP-39653, d -AP5, DCKA, and 6,7-dichloroquinoxaline-2,3-dione to inhibit [³H]MK-801 binding when determined in the presence of both l -Glu and Gly. These results suggest that glutathione may be an endogenous agonist selective for the N-methyl-d -aspartate (NMDA) recognition domain on the NMDA receptor ionophore complex.     

Domestic Yttrium Consumption Trends in Japan

Yttrium tends to occur in the same ore deposits as the lanthanides and exhibits similar chemical properties as rare earth elements. Yttrium sources are typically concentrated in China, and there are concerns about supply security. Yttrium is used in small, but essential, quantities in a variety of advanced industrial sectors, for example, in phosphors, advanced ceramics, optical glasses, and batteries. In terms of resource security, it is important to verify the domestic yttrium consumption trends. In order to characterize the domestic yttrium consumption trends in Japan, we tracked the historical yttrium consumption patterns from 2001 to 2011 by applying the bottom‐up approach and illustrated the recent domestic yttrium flow by using a substance flow analysis. The results showed that the total yttrium consumption has remained steady over 10 years, from 1,124 tonnes (t) in 2001 to 967 t in 2011. Recent consumption in 2011 was driven primarily by the use of yttrium in fluorescent lamps (462 t), nickel metal hydride batteries (185 t), and optic glasses (149 t).     

Effects of synbiotic on growth,digestibility, immune and antioxidant performance in broilers

The overuse of in-feed antibiotics has been associated with serious issues, including the developing of antibiotic-resistant pathogens and causing drug residues in poultry products. To date, many countries have restricted the use of growth-promoting antibiotics in food animals, resulting in the increased need for effective alternatives to in-feed antibiotic. Synbiotics, which are composed of probiotics and prebiotics, have been shown to act synergistically when applied simultaneously. Thus, this study investigated the effects of a synbiotic, composed of microencapsulated Lactobacillus plantarum (MLP) and fructooligosaccharide (FOS), on growth, immune and antioxidant parameters, and digestibility of calcium and phosphorus in broilers. A total of 168 newly hatched male broilers were randomly allotted to three dietary groups (n = 7): (1) a corn-soybean meal basal diet (CON); (2) basal diet + synbiotic (SYN); and (3) basal diet + aureomycin (ANT). Compared with the CON, chickens had greater average daily gain and digestibility of calcium and phosphorus in the SYN group (P < 0.05). In the SYN and ANT group, serum IgA, IgG, and IL-10 levels were higher, while the serum TNF-α, IL-2, and IL-6 levels were reduced (P < 0.05) compared to CON. Compared with CON, the level of serum malondialdehyde was lower (P < 0.05) and SOD level was higher (P < 0.05) in either SYN or ANT group. No significant differences in populations of Escherichia coli were seen in chickens among the three groups, whereas, the populations of Lactobacillus were higher (P < 0.05) in chickens in the SYN group compared with those in CON and ANT groups. Taken together, the addition of SYN, consisting of MLP and FOS, had benefits on growth, immune and antioxidant parameters, and digestibility of calcium and phosphorus, indicating its potential to serve as a substitute for antibiotics in broiler feeding.     

酶解乳蛋白对初生仔猪小肠组织学结构及隐窝细胞增殖的影响(英文)

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A structural view of the antibiotic degradation enzyme NDM-1 from a superbug

Gram-negative Enterobacteriaceae with resistance to carbapenem conferred by New Delhi metallo-β-lactamase 1 (NDM-1) are a type of newly discovered antibiotic-resistant bacteria. The rapid pandemic spread of NDM-1 bacteria worldwide (spreading to India, Pakistan, Europe, America, and Chinese Taiwan) in less than 2 months characterizes these microbes as a potentially major global health problem. The drug resistance of NDM-1 bacteria is largely due to plasmids containing the blaNDM-1 gene shuttling through bacterial populations. The NDM-1 enzyme encoded by the blaNDM-1 gene hydrolyzes β-lactam antibiotics, allowing the bacteria to escape the action of antibiotics. Although the biological functions and structural features of NDM-1 have been proposed according to results from functional and structural investigation of its homologues, the precise molecular characteristics and mechanism of action of NDM-1 have not been clarified. Here, we report the three-dimensional structure of NDM-1 with two catalytic zinc ions in its active site. Biological and mass spectroscopy results revealed that D-captopril can effectively inhibit the enzymatic activity of NDM-1 by binding to its active site with high binding affinity. The unique features concerning the primary sequence and structural conformation of the active site distinguish NDM-1 from other reported metallo-β-lactamases (MBLs) and implicate its role in wide spectrum drug resistance. We also discuss the molecular mechanism of NDM-1 action and its essential role in the pandemic of drug-resistant NDM-1 bacteria. Our results will provide helpful information for future drug discovery targeting drug resistance caused by NDM-1 and related metallo-β-lactamases.