bluuebunny/crossref_metadata_2025 huggingface dataset:
Infection of influenza virus neuraminidase-vaccinated mice with homologous influenza virus leads to strong protection against heterologous influenza viruses
Authors: He Biao , Chang Haiyan , Liu Zhihua , Huang Chaoyang , Liu Xueying , Zheng Dan , Fang Fang , Sun Bing , Chen Ze
Published: August 2014

Vaccination is the best measure to prevent influenza pandemics. Here, we studied the protective effect against heterologous influenza viruses, including A/reassortant/NYMC X-179A (pH1N1), A/Chicken/Henan/12/2004 (H5N1), A/Chicken/Jiangsu/7/2002 (H9N2) and A/Guizhou/54/89×A/PR/8/34 (A/Guizhou-X) (H3N2), in mice first vaccinated with a DNA vaccine of haemagglutinin (HA) or neuraminidase (NA) of A/PR/8/34 (PR8) and then infected with the homologous virus. We showed that PR8 HA or NA vaccination both protected mice against a lethal dose of the homologous virus; PR8 HA or NA DNA vaccination and then PR8 infection in mice offered poor or excellent protection, respectively, against a second, heterologous influenza virus challenge. In addition, before the second heterologous influenza infection, the highest antibody level against nucleoprotein (NP) and matrix (M1 and M2) proteins was found in the PR8 NA-vaccinated and PR8-infected group. The level of induced cellular immunity against NP and M1 showed a trend consistent with that seen in antibody levels. However, PR8 HA+NA vaccination and then PR8 infection resulted in limited protection against heterologous influenza virus challenge. Results of the present study demonstrated that infection of the homologous influenza virus in mice already immunized with a NA vaccine could provide excellent protection against subsequent infection of a heterologous influenza virus. These findings suggested that NA, a major antigen of influenza virus, could be an important candidate antigen for universal influenza vaccines.
Analysis of new aphid lethal paralysis virus (ALPV) isolates suggests evolution of two ALPV species
Authors: Liu Sijun , Vijayendran Diveena , Carrillo-Tripp Jimena , Miller W. Allen , Bonning Bryony C.
Published: August 2014

Aphid lethal paralysis virus (ALPV; family Dicistroviridae) was first isolated from the bird cherry-oat aphid, Rhopalosiphum padi. ALPV-like virus sequences have been reported from many insects and insect predators. We identified a new isolate of ALPV (ALPV-AP) from the pea aphid, Acyrthosiphon pisum, and a new isolate (ALPV-DvV) from western corn rootworm, Diabrotica virgifera virgifera. ALPV-AP has an ssRNA genome of 9940 nt. Based on phylogenetic analysis, ALPV-AP was closely related to ALPV-AM, an ALPV isolate from honeybees, Apis mellifera, in Spain and Brookings, SD, USA. The distinct evolutionary branches suggested the existence of two lineages of the ALPV virus. One consisted of ALPV-AP and ALPV-AM, whilst all other isolates of ALPV grouped into the other lineage. The similarity of ALPV-AP and ALPV-AM was up to 88 % at the RNA level, compared with 78–79 % between ALPV-AP and other ALPV isolates. The sequence identity of proteins between ALPV-AP and ALPV-AM was 98–99 % for both ORF1 and ORF2, whilst only 85–87 % for ORF1 and 91–92 % for ORF2 between ALPV-AP and other ALPV isolates. Sequencing of RACE (rapid amplification of cDNA ends) products and cDNA clones of the virus genome revealed sequence variation in the 5′ UTRs and in ORF1, indicating that ALPV may be under strong selection pressure, which could have important biological implications for ALPV host range and infectivity. Our results indicated that ALPV-like viruses infect insects in the order Coleoptera, in addition to the orders Hemiptera and Hymenoptera, and we propose that ALPV isolates be classified as two separate viral species.
The Genetic Architecture of Gene Expression Levels in Wild Baboons
Authors: Tung Jenny , Zhou Xiang , Alberts Susan C , Stephens Matthew , Gilad Yoav
Published: August 2014

Gene expression variation is well documented in human populations and its genetic architecture has been extensively explored. However, we still know little about the genetic architecture of gene expression variation in other species, particularly our closest living relatives, the nonhuman primates. To address this gap, we performed an RNA sequencing (RNA-seq)-based study of 63 wild baboons, members of the intensively studied Amboseli baboon population in Kenya. Our study design allowed us to measure gene expression levels and identify genetic variants using the same data set, enabling us to perform complementary mapping of putativecis-acting expression quantitative trait loci (eQTL) and measurements of allele-specific expression (ASE) levels. We discovered substantial evidence for genetic effects on gene expression levels in this population. Surprisingly, we found more power to detect individual eQTL in the baboons relative to a HapMap human data set of comparable size, probably as a result of greater genetic variation, enrichment of SNPs with high minor allele frequencies, and longer-range linkage disequilibrium in the baboons. eQTL were most likely to be identified for lineage-specific, rapidly evolving genes. Interestingly, genes with eQTL significantly overlapped between the baboon and human data sets, suggesting that some genes may tolerate more genetic perturbation than others, and that this property may be conserved across species. Finally, we used a Bayesian sparse linear mixed model to partition genetic, demographic, and early environmental contributions to variation in gene expression levels. We found a strong genetic contribution to gene expression levels for almost all genes, while individual demographic and environmental effects tended to be more modest. Together, our results establish the feasibility of eQTL mapping using RNA-seq data alone, and act as an important first step towards understanding the genetic architecture of gene expression variation in nonhuman primates.
C. elegansharbors pervasive cryptic genetic variation for embryogenesis
Authors: Paaby Annalise B. , White Amelia G. , Riccardi David D. , Gunsalus Kristin C. , Piano Fabio , Rockman Matthew V.
Published: August 2014

Conditionally functional mutations are an important class of natural genetic variation, yet little is known about their prevalence in natural populations or their contribution to disease risk. Here, we describe a vast reserve of cryptic genetic variation, alleles that are normally silent but which affect phenotype when the function of other genes is perturbed, in the gene networks ofC. elegansembryogenesis. We find evidence that cryptic-effect loci are ubiquitous and segregate at intermediate frequencies in the wild. The cryptic alleles demonstrate low developmental pleiotropy, in that specific, rather than general, perturbations are required to reveal them. Our findings underscore the importance of genetic background in characterizing gene function and provide a model for the expression of conditionally functional effects that may be fundamental in basic mechanisms of trait evolution and the genetic basis of disease susceptibility.
Latent and activeabPPO4 mushroom tyrosinase cocrystallized with hexatungstotellurate(VI) in a single crystal
Authors: Mauracher Stephan Gerhard , Molitor Christian , Al-Oweini Rami , Kortz Ulrich , Rompel Annette
Published: August 2014

Tyrosinases, bifunctional metalloenzymes, catalyze the oxidation of monophenols ando-diphenols too-quinones, the precursor compounds of the brown-coloured pigment melanin. In eukaryotic organisms, tyrosinases are expressed as latent zymogens that have to be proteolytically cleaved in order to form highly active enzymes. This activation mechanism, known as the tyrosinase maturation process, has scientific and industrial significance with respect to biochemical and technical applications of the enzyme. Here, not only the first crystal structure of the mushroom tyrosinaseabPPO4 is presented in its active form (Ser2–Ser383) and in its 21 kDa heavier latent form (Ser2–Thr545), but furthermore the simultaneous presence of both forms within one single-crystal structure is shown. This allows for a simple approach to investigate the transition between these two forms. IsoformabPPO4 was isolated and extensively purified from the natural source (Agaricus bisporus), which contains a total of six polyphenol oxidases (PPOs). The enzyme formed crystals (diffracting to a resolution of 2.76 Å) owing to the employment of the 6-tungstotellurate(VI) salt (Na6[TeW6O24]·22H2O) as a cocrystallization agent. Two of these disc-shaped Anderson-type polyoxoanions [TeW6O24]6−separate two asymmetric units comprising one crystallographic heterodimer ofabPPO4, thus resulting in very interesting crystal packing.
A high-throughput colourimetric method for the determination of pH in crystallization screens
Authors: Kirkwood Jobie , Wilson Julie , O'Keefe Simon , Hargreaves David
Published: August 2014

The crystallization of proteins is dependent on the careful control of numerous parameters, one of these being pH. The pH of crystallization is generally reported as that of the buffer; however, the true pH has been found to be as many as four pH units away. Measurement of pH with a meter is time-consuming and requires the reformatting of the crystallization solution. To overcome this, a high-throughput method for pH determination of buffered solutions has been developed with results comparable to those of a pH meter.
The structure of the C-terminal domain of theZaire ebolavirusnucleoprotein
Authors: Dziubańska Paulina J. , Derewenda Urszula , Ellena Jeffrey F. , Engel Daniel A. , Derewenda Zygmunt S.
Published: August 2014

Ebolavirus(EBOV) causes severe hemorrhagic fever with a mortality rate of up to 90%. EBOV is a member of the orderMononegaviralesand, like other viruses in this taxonomic group, contains a negative-sense single-stranded (ss) RNA. The EBOV ssRNA encodes seven distinct proteins. One of them, the nucleoprotein (NP), is the most abundant viral protein in the infected cell and within the viral nucleocapsid. Like other EBOV proteins, NP is multifunctional. It is tightly associated with the viral genome and is essential for viral transcription, RNA replication, genome packaging and nucleocapsid assembly prior to membrane encapsulation. NP is unusual among theMononegaviralesin that it contains two distinct regions, or putative domains, the C-terminal of which shows no homology to any known proteins and is purported to be a hub for protein–protein interactions within the nucleocapsid. The atomic structure of NP remains unknown. Here, the boundaries of the N- and C-terminal domains of NP from Zaire EBOV are defined, it is shown that they can be expressed as highly stable recombinant proteins inEscherichia coli, and the atomic structure of the C-terminal domain (residues 641–739) derived from analysis of two distinct crystal forms at 1.98 and 1.75 Å resolution is described. The structure reveals a novel tertiary fold that is distantly reminiscent of the β-grasp architecture.
Space-group and origin ambiguity in macromolecular structures with pseudo-symmetry and its treatment with the programZanuda
Authors: Lebedev Andrey A. , Isupov Michail N.
Published: August 2014

The presence of pseudo-symmetry in a macromolecular crystal and its interplay with twinning may lead to an incorrect space-group (SG) assignment. Moreover, if the pseudo-symmetry is very close to an exact crystallographic symmetry, the structure can be solved and partially refined in the wrong SG. Typically, in such incorrectly determined structures all or some of the pseudo-symmetry operations are, in effect, taken for crystallographic symmetry operations andvice versa. A mistake only becomes apparent when theRfreeceases to decrease below 0.39 and further model rebuilding and refinement cannot improve the refinement statistics. If pseudo-symmetry includes pseudo-translation, the uncertainty in SG assignment may be associated with an incorrect choice of origin, as demonstrated by the series of examples provided here. The programZanudapresented in this article was developed for the automation of SG validation.Zanudaruns a series of refinements in SGs compatible with the observed unit-cell parameters and chooses the model with the highest symmetry SG from a subset of models that have the best refinement statistics.
Conformation-independent structural comparison of macromolecules withProSMART
Authors: Nicholls Robert A. , Fischer Marcus , McNicholas Stuart , Murshudov Garib N.
Published: August 2014

The identification and exploration of (dis)similarities between macromolecular structures can help to gain biological insight, for instance when visualizing or quantifying the response of a protein to ligand binding. Obtaining a residue alignment between compared structures is often a prerequisite for such comparative analysis. If the conformational change of the protein is dramatic, conventional alignment methods may struggle to provide an intuitive solution for straightforward analysis. To make such analyses more accessible, theProcrustes Structural Matching Alignment and Restraints Tool(ProSMART) has been developed, which achieves a conformation-independent structural alignment, as well as providing such additional functionalities as the generation of restraints for use in the refinement of macromolecular models. Sensible comparison of protein (or DNA/RNA) structures in the presence of conformational changes is achieved by enforcing neither chain nor domain rigidity. The visualization of results is facilitated by popular molecular-graphics software such asCCP4mgandPyMOL, providing intuitive feedback regarding structural conservation and subtle dissimilarities between close homologues that can otherwise be hard to identify. Automatically generated colour schemes corresponding to various residue-based scores are provided, which allow the assessment of the conservation of backbone and side-chain conformations relative to the local coordinate frame. Structural comparison tools such asProSMARTcan help to break the complexity that accompanies the constantly growing pool of structural data into a more readily accessible form, potentially offering biological insight or influencing subsequent experiments.
Deformable elastic network refinement for low-resolution macromolecular crystallography
Authors: Schröder Gunnar F. , Levitt Michael , Brunger Axel T.
Published: August 2014

Crystals of membrane proteins and protein complexes often diffract to low resolution owing to their intrinsic molecular flexibility, heterogeneity or the mosaic spread of micro-domains. At low resolution, the building and refinement of atomic models is a more challenging task. The deformable elastic network (DEN) refinement method developed previously has been instrumental in the determinion of several structures at low resolution. Here, DEN refinement is reviewed, recommendations for its optimal usage are provided and its limitations are discussed. Representative examples of the application of DEN refinement to challenging cases of refinement at low resolution are presented. These cases include soluble as well as membrane proteins determined at limiting resolutions ranging from 3 to 7 Å. Potential extensions of the DEN refinement technique and future perspectives for the interpretation of low-resolution crystal structures are also discussed.
Crystal structure of 4,4′-(disulfanediyl)dibutanoic acid–4,4′-bipyridine (1/1)
Authors: Atria Ana María , Garland Maria Teresa , Baggio Ricardo
Published: August 2014

4,4′-(Disulfanediyl)dibutanoic acid (dtba) and 4,4′-bipyridine (4,4′-bpy) crystallize in an 1:1 ratio, leading to the title co-crystal with composition C8H14O4S2·C10H8N2. A distinctive feature of the crystal structure is the geometry of the dtba moiety, which appears to be stretched [with a 9.98 (1) Å span between outermost carbons] and acts as an hydrogen-bonding connector, forming linear chains along [-211] with the 4,4′-bpy moiety by way of O—H...N hydrogen bonds and C—H...O interactions. The influence of the molecular shape on the hydrogen-bonding pattern is analysed by comparing the title compound and two other 4,4′-bpy co-crystals with closely related molecules of similar formulation but different geometry, showing the way in which this correlates with the packing arrangement.
Crystal structure of 3-methyl-2,6-bis(4-methyl-1,3-thiazol-5-yl)piperidin-4-one
Authors: Manimaran A. , Sethusankar K. , Ganesan S. , Ananthan S.
Published: August 2014

In the title compound, C14H17N3OS2, the central piperidinone ring adopts a chair conformation and the thiazole rings are inclined to its mean plane by 80.16 (12) and 67.15 (12)°. The O atom and methyl group C atom deviate significantly from the mean plane of the central piperidinone ring, by 0.8138 (2) and 0.3175 (2) Å, respectively. The dihedral angle between the thiazole rings is 51.88 (13)°. In the crystal, molecules are linkedviaC—H...O hydrogen bonds, forming zigzagC(10) chains running parallel to [001].
Crystal structure of 4-acetylphenyl 3-methylbenzoate
Authors: Mani Karthik Ananth , Viswanathan Vijayan , Narasimhan S. , Velmurugan Devadasan
Published: August 2014

The planes of the aromatic rings of the title compound, C16H14O3, make a dihedral angle of 82.52 (8)°. The acetyl group and the phenyl ring make a dihedral angle of 1.65 (1)°. In the crystal, the molecules are linked by C—H...O interactions, generatingC(7) chains along thea-axis direction.
Crystal structure of methyl 2-[2,4-bis(4-fluorophenyl)-3-azabicyclo[3.3.1]nonan-9-ylidene]hydrazinecarboxylate
Authors: Kamaraj A. , Rajkumar R. , Krishnasamy K. , Murugavel S.
Published: August 2014

In the title compound, C22H23F2N3O2, the bicyclic ring system exists in a twin-chair conformation with an equatorial disposition of the 4-fluorophenyl groups on the heterocycle. These aromatic rings are inclined to one another by 19.4 (1)°. In the crystal, molecules are linked by pairs of N—H...O and C—H...O hydrogen bonds into inversion dimers, incorporatingR12(7) andR22(8) ring motifs; the same O atom accepts both hydrogen bonds. These dimers are further linked by a pair of C—H...F hydrogen bonds, enclosingR22(28) ring motifs, forming supramolecular chains along [010]. The NH group of the pyridine ring is not involved in hydrogen bonding, probably due to the steric hindrance of the fluorophenyl groups.
Crystal structure of 5-[bis(4-ethoxyphenyl)amino]thiophene-2-carbaldehyde
Authors: Tan Jing-Yun , Kong Ming , Wu Jie-Ying
Published: August 2014

In the title compound, C21H21NO3S, the planes of the two benzene rings are nearly perpendicular to one another [dihedral angle = 84.50 (10)°] and they are oriented with respect to the plane of the thiophene ring at dihedral angles of 59.15 (9) and 66.61 (9)°. In the crystal, molecules are linked by weak C—H...O hydrogen bonds, forming supramolecular chains propagating along theb-axis direction.
Crystal structure of (E)-N′-benzylidene-2-methoxybenzohydrazide
Authors: Taha Muhammad , Baharudin M. Syukri , Zaki Hamizah Mohd , Yamin Bohari M. , Naz Humera
Published: August 2014

In the title benzoylhydrazide derivative, C15H14N2O2, the dihedral angle between the planes of the two phenyl rings is 12.56 (9)°. The azomethine double bond adopts anEconfiguration stabilized by an N—H...O hydrogen bond. In the crystal, the components are linked by C—H...O interactions to form chains along thebaxis.
Crystal structure of (1,3-dimethylthiourea-κS)tris(triphenylphosphane-κP)silver(I) acetate
Authors: Wattanakanjana Yupa , Nimthong Arunpatcha , Darasuriyong Chanokphat
Published: August 2014

In the mononuclear title salt, [Ag(C3H8N2S)(C18H15P)3](CH3COO), the AgIion exhibits a distorted tetrahedral coordination sphere defined by three P atoms from three triphenylphosphane ligands and one S atom from a 1,3-dimethylthiourea ligand. In the crystal, the acetate anion is linked with the complex cationviaduplex N—H...O hydrogen bonds [graph-set motifR22(8)].
Crystal structures of two cross-bridged chromium(III) tetraazamacrocycles
Authors: Prior Timothy J. , Maples Danny L. , Maples Randall D. , Hoffert Wesley A. , Parsell Trenton H. , Silversides Jon D. , Archibald Stephen J. , Hubin Timothy J.
Published: August 2014

The crystal structure of dichlorido(4,10-dimethyl-1,4,7,10-tetraazabicyclo[5.5.2]tetradecane)chromium(III) hexafluoridophosphate, [CrCl2(C12H26N4)]PF6, (I), has monoclinic symmetry (space groupP21/n) at 150 K. The structure of the related dichlorido(4,11-dimethyl-1,4,8,11-tetraazabicyclo[6.6.2]hexadecane)chromium(III) hexafluoridophosphate, [CrCl2(C14H30N4)]PF6, (II), also displays monoclinic symmetry (space groupP21/c) at 150 K. In each case, the CrIIIion is hexacoordinate with twocischloride ions and two non-adjacent N atoms boundcisequatorially and the other two non-adjacent N atoms boundtransaxially in acis-V conformation of the macrocycle. The extent of the distortion from the preferred octahedral coordination geometry of the CrIIIion is determined by the parent macrocycle ring size, with the larger cross-bridged cyclam ring in (II) better able to accommodate this preference and the smaller cross-bridged cyclen ring in (I) requiring more distortion away from octahedral geometry.
Crystal structure of 5-chloro-3-cyclohexylsulfinyl-2,4,6-trimethyl-1-benzofuran
Authors: Choi Hong Dae , Lee Uk
Published: August 2014

In the title compound, C17H21ClO2S, the cyclohexyl ring adopts a chair conformation with the C—S bond in an equatorial orientation. In the crystal, molecules are linked by C—H...O and C—H...π hydrogen bonds and a Cl...π [3.594 (2) Å] contact into chains along thea-axis direction.
Crystal structure of 1-[(2S*,4R*)-6-fluoro-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl]pyrrolidin-2-one
Authors: Pradeep P. S. , Naveen S. , Kumara M. N. , Mahadevan K. M. , Lokanath N. K.
Published: August 2014

In the title compound, C14H17FN2O, the 1,2,3,4-tetrahydropyridine ring of the quinoline moiety adopts a half-chair conformation, while the pyrrolidine ring has an envelope conformation with the central methylene C atom as the flap. The pyrrolidine ring lies in the equatorial plane and its mean plane is normal to the mean plane of the quinoline ring system, with a dihedral angle value of 88.37 (9)°. The bridging N—C bond distance [1.349 (3) Å] is substantially shorter than the sum of the covalent radii (dcov: C—N = 1.47 Å and C=N = 1.27 Å), which indicates partial double-bond character for this bond, resulting in a certain degree of charge delocalization. In the crystal, molecules are linked by N—H...O and C—H...O hydrogen bonds, forming sheets lying parallel to (10-1). These two-dimensional networks are linkedviaC—H...F hydrogen bonds and C—H...π interactions, forming a three-dimensional structure.
Crystal structure of 2,5-dimethyl-3-(3-methylphenylsulfonyl)-1-benzofuran
Authors: Choi Hong Dae , Lee Uk
Published: August 2014

In the title compound, C17H16O3S, the dihedral angle between the plane of the benzofuran ring system [r.m.s. deviation = 0.010 (1) Å] and that of the 3-methylphenyl ring is 79.09 (5)°. Intramolecular C—H...O hydrogen bonds are observed. In the crystal, molecules are connected into a chain along thec-axis direction by two different pairs of inversion-generated interactions: C—H...π hydrogen bonds between the methyl groups and the benzene rings of the 3-methylphenyl fragments and π–π interactions between the benzene and furan rings of neighbouring molecules [centroid–centroid distance = 3.673 (2) Å].
Chemical conversion of cisplatin and carboplatin with histidine in a model protein crystallized under sodium iodide conditions
Authors: Tanley Simon W. M. , Helliwell John R.
Published: August 2014

Cisplatin and carboplatin are platinum anticancer agents that are used to treat a variety of cancers. Previous X-ray crystallographic studies of carboplatin binding to histidine in hen egg-white lysozyme (HEWL) showed a partial chemical conversion of carboplatin to cisplatin owing to the high sodium chloride concentration used in the crystallization conditions. Also, the co-crystallization of HEWL with carboplatin in sodium bromide conditions resulted in the partial conversion of carboplatin to the transbromoplatin form, with a portion of the cyclobutanedicarboxylate (CBDC) moiety still present. The results of the co-crystallization of HEWL with cisplatin or carboplatin in sodium iodide conditions are now reported in order to determine whether the cisplatin and carboplatin converted to the iodo form, and whether this took place in a similar way to the partial conversion of carboplatin to cisplatin in NaCl conditions or to transbromoplatin in NaBr conditions as seen previously. It is reported here that a partial chemical transformation has taken place to a transplatin form for both ligands. The NaI-grown crystals belonged to the monoclinic space groupP21with two molecules in the asymmetric unit. The chemically transformed cisplatin and carboplatin bind to both His15 residues,i.e.in each asymmetric unit. The binding is only at the Nδatom of His15. A third platinum species is also seen in both conditions bound in a crevice between symmetry-related molecules. Here, the platinum is bound to three I atoms identified based on their anomalous difference electron densities and their refined occupancies, with the fourth bound atom being a Cl atom (in the cisplatin case) or a portion of the CBDC moiety (in the carboplatin case).
High-resolution crystal structures of alternate forms of the human CD44 hyaluronan-binding domain reveal a site for protein interaction
Authors: Liu Li-Kai , Finzel Barry
Published: August 2014

Two new crystal structures of the extracellular hyaluronan-binding domain of human CD44 are described at high resolution. A hexagonal crystal form at 1.60 Å resolution and a monoclinic form at 1.08 Å resolution both have two molecules in the asymmetric unit arranged about a similar noncrystallographic twofold axis of symmetry. These structures are compared with those previously reported at 2.20 Å resolution to show that the fold is quite resistant to structural deformation in different crystal environments. Unexpectedly, a short peptide is found in the monoclinic crystals at a site remote from the known hyaluronan-binding groove. The peptide with a valine at the carboxy-terminus must have co-purified from the bacterial expression host and binds on the opposite side of the domain from the known hyaluronan-binding groove. This opportunistic binding may identify a site of interaction used as CD44 assembles with other proteins to accomplish effective signaling regarding changes to the extracellular environment.
Structure of nucleoside diphosphate kinase from pacific shrimp (Litopenaeus vannamei) in binary complexes with purine and pyrimidine nucleoside diphosphates
Authors: López-Zavala Alonso A. , Quintero-Reyes Idania E. , Carrasco-Miranda Jesús S. , Stojanoff Vivian , Weichsel Andrzej , Rudiño-Piñera Enrique , Sotelo-Mundo Rogerio R.
Published: August 2014

Nucleoside diphosphate kinase (NDK; EC 2.7.4.6) is an enzyme that catalyzes the third phosphorylation of nucleoside diphosphates, leading to nucleoside triphosphates for DNA replication. Expression of the NDK fromLitopenaeus vannamei(LvNDK) is known to be regulated under viral infection. Also, as determined by isothermal titration calorimetry,LvNDK binds both purine and pyrimidine deoxynucleoside diphosphates with high binding affinity for dGDP and dADP and with no heat of binding interaction for dCDP [Quintero-Reyeset al.(2012),J. Bioenerg. Biomembr.44, 325–331]. In order to investigate the differences in selectivity,LvNDK was crystallized as binary complexes with both acceptor (dADP and dCDP) and donor (ADP) phosphate-group nucleoside diphosphate substrates and their structures were determined. The three structures with purine or pyrimidine nucleotide ligands are all hexameric. Also, the binding of deoxy or ribonucleotides is similar, as in the former a water molecule replaces the hydrogen bond made by Lys11 to the 2′-hydroxyl group of the ribose moiety. This allows Lys11 to maintain a catalytically favourable conformation independently of the kind of sugar found in the nucleotide. Because of this, shrimp NDK may phosphorylate nucleotide analogues to inhibit the viral infections that attack this organism.
Carboplatin binding to histidine
Authors: Tanley Simon W. M. , Diederichs Kay , Kroon-Batenburg Loes M. J. , Levy Colin , Schreurs Antoine M. M. , Helliwell John R.
Published: August 2014

Carboplatin is a second-generation platinum anticancer agent used for the treatment of a variety of cancers. Previous X-ray crystallographic studies of carboplatin binding to histidine (in hen egg-white lysozyme; HEWL) showed the partial conversion of carboplatin to cisplatin owing to the high NaCl concentration used in the crystallization conditions. HEWL co-crystallizations with carboplatin in NaBr conditions have now been carried out to confirm whether carboplatin converts to the bromine form and whether this takes place in a similar way to the partial conversion of carboplatin to cisplatin observed previously in NaCl conditions. Here, it is reported that a partial chemical transformation takes place but to a transplatin form. Thus, to attempt to resolve purely carboplatin binding at histidine, this study utilized co-crystallization of HEWL with carboplatin without NaCl to eliminate the partial chemical conversion of carboplatin. Tetragonal HEWL crystals co-crystallized with carboplatin were successfully obtained in four different conditions, each at a different pH value. The structural results obtained show carboplatin bound to either one or both of the N atoms of His15 of HEWL, and this particular variation was dependent on the concentration of anions in the crystallization mixture and the elapsed time, as well as the pH used. The structural details of the bound carboplatin molecule also differed between them. Overall, the most detailed crystal structure showed the majority of the carboplatin atoms bound to the platinum centre; however, the four-carbon ring structure of the cyclobutanedicarboxylate moiety (CBDC) remained elusive. The potential impact of the results for the administration of carboplatin as an anticancer agent are described.
Structure of a DsbF homologue fromCorynebacterium diphtheriae
Authors: Um Si-Hyeon , Kim Jin-Sik , Lee Kangseok , Ha Nam-Chul
Published: August 2014

Disulfide-bond formation, mediated by the Dsb family of proteins, is important in the correct folding of secreted or extracellular proteins in bacteria. In Gram-negative bacteria, disulfide bonds are introduced into the folding proteins in the periplasm by DsbA. DsbE fromEscherichia colihas been implicated in the reduction of disulfide bonds in the maturation of cytochromec. The Gram-positive bacteriumMycobacterium tuberculosisencodes DsbE and its homologue DsbF, the structures of which have been determined. However, the two mycobacterial proteins are able to oxidatively fold a proteinin vitro, unlike DsbE fromE. coli. In this study, the crystal structure of a DsbE or DsbF homologue protein fromCorynebacterium diphtheriaehas been determined, which revealed a thioredoxin-like domain with a typical CXXC active site. Structural comparison withM. tuberculosisDsbF would help in understanding the function of theC. diphtheriaeprotein.
Structure of glutathioneS-transferase 1 from the major human hookworm parasiteNecator americanus(Na-GST-1) in complex with glutathione
Authors: Asojo Oluwatoyin A. , Ceccarelli Christopher
Published: August 2014

GlutathioneS-transferase 1 fromNecator americanus(Na-GST-1) is a vaccine candidate for hookworm infection that has a high affinity for heme and metal porphyrins. As part of attempts to clarify the mechanism of heme detoxification by hookworm GSTs, co-crystallization and soaking studies ofNa-GST-1 with the heme-like molecules protoporphyrin IX disodium salt, hematin and zinc protoporphyrin were undertaken. While these studies did not yield the structure of the complex ofNa-GST-1 with any of these molecules, co-crystallization experiments resulted in the first structures of the complex ofNa-GST-1 with the substrate glutathione. The structures of the complex ofNa-GST-1 with glutathione were solved from pathological crystalline aggregates comprising more than one crystal form. These first structures of the complex ofNa-GST-1 with the substrate glutathione were solved by molecular replacement from data collected with a sealed-tube home source using the previously reported apo structure as the search model.
Structure ofMycobacterium smegmatisEis in complex with paromomycin
Authors: Kim Kyoung Hoon , An Doo Ri , Yoon Hye Jin , Yang Jin Kuk , Suh Se Won
Published: August 2014

TheRv2416cgene ofMycobacterium tuberculosis(Mtb) encodes the enhanced intracellular survival (Eis) protein that enhances intracellular survival of the pathogen in host macrophages during infection. TheMtbEis protein is released into the cytoplasm of the phagocyte during intracellular infection and modulates the host immune response. It also contributes to drug resistance by acetylating multiple amine groups of aminoglycosides. Interestingly, the nonpathogenicM. smegmatis(Msm) contains a homologouseisgene (MSMEG_3513). The overall structures ofMtbEis andMsmEis are highly similar to each other, reflecting the high level (58%) of amino-acid sequence identity between them. BothMtbEis andMsmEis are active as aminoglycoside acetyltransferases, while onlyMtbEis functions as anN∊-acetyltransferase to acetylate Lys55 of dual-specificity protein phosphatase 16 (DUSP16)/mitogen-activated protein kinase phosphatase 7 (MKP-7), leading to the suppression of host immune responses. Here, the crystal structure ofMsmEis in the paromomycin-bound form is reported, revealing detailed interactions between an aminoglycoside antibiotic andMsmEis. The crystal structure ofMsmEis in the paromomycin-bound form has been determined at 3.3 Å resolution. This work provides potentially useful information for structure-guided discovery of Eis inhibitors as a novel antituberculosis drug against drug-resistantMtb.
The structure of alanine racemase fromAcinetobacter baumannii
Authors: Davis Emily , Scaletti-Hutchinson Emma , Opel-Reading Helen , Nakatani Yoshio , Krause Kurt L.
Published: August 2014

Acinetobacter baumanniiis an opportunistic Gram-negative bacterium which is a common cause of hospital-acquired infections. Numerous antibiotic-resistant strains exist, emphasizing the need for the development of new antimicrobials. Alanine racemase (Alr) is a pyridoxal 5′-phosphate dependent enzyme that is responsible for racemization between enantiomers of alanine. As D-alanine is an essential component of the bacterial cell wall, its inhibition is lethal to prokaryotes, making it an excellent antibiotic drug target. The crystal structure ofA. baumanniialanine racemase (AlrAba) from the highly antibiotic-resistant NCTC13302 strain has been solved to 1.9 Å resolution. Comparison of AlrAbawith alanine racemases from closely related bacteria demonstrates a conserved overall fold. The substrate entryway and active site of the enzymes were shown to be highly conserved. The structure of AlrAbawill provide the template required for future structure-based drug-design studies.
More about systematic errors in charge-density studies
Authors: Henn Julian , Meindl Kathrin
Published: August 2014

In order to detect and graphically visualize the absence or presence of systematic errors in fit data, conditional probabilities are employed to analyze the statistical independence or dependence of fit residuals. This concept is completely general and applicable to all scientific fields in which model parameters are fitted to experimental data. The applications presented in this work refer to published charge-density data.
Easy access: a case study on rural marketing
Authors: Ranjan Parida Rashmi , Sahney Sangeeta
Published: August 2014

Subject area

Marketing management and marketing strategy, rural marketing, sales and distribution.

Study level/applicability

Students of business schools specialising in the area of marketing or rural marketing.

Case overview

The case focuses on the rural market. It deals with the alternative distribution channels adopted for last mile distribution among rural consumers of underdeveloped Odisha (India). The case discusses key issues pertaining to rural marketing, business viability, social issues and public sentiment.Easy access is an entrepreneurial venture by an erstwhile intellectual marketing professor of a premier B-school. The objective behind this initiative is multiple, viz., rural marketing, developing alternative distribution networks, women empowerment, etc. The case highlights that the business of Easy Access started with noble social objectives like women empowerment and developing a cost effective distribution network so that rural customers would be benefited. The case also highlights that the practices adopted by Easy access was not good enough to track & forecast demand effectively as well as the supply chain to replenish stock was not proper.Since the particular market is a backward region and there are number of Govt. schemes and people are given many things for free. People thought Easy Access is result of one of such schemes. Also there were social issues of improper address and mismatch identity (as mentioned in the case) etc.So the issues of demand forecasting and supply chain management along with social issues resulted in financial loss and thus the viability of business venture (Easy Access) is a concern. The social objectives associated with this venture are also at stake or at danger because of financial loss.

Expected learning outcomes

The case provides insights into the marketing concepts like rural marketing, marketing strategy in emerging markets and sales and distribution.

Supplementary materials

Teaching notes are available for educators only. Please contact your library to gain login details or email support@emeraldinsight.com to request teaching notes.
Motives for reading and articulating user-generated restaurant reviews on Yelp.com
Authors: Parikh Anish , Behnke Carl , Vorvoreanu Mihaela , Almanza Barbara , Nelson Doug
Published: August 2014

Purpose

– The purpose of this research is to examine why and when restaurant consumers use and contribute user-generated reviews. This research is needed to determine the relevance of user-generated restaurant reviews in the current marketplace.

Design/methodology/approach

– The research methodology is based on a quantitative approach, and focused on current Yelp.com users as its population. Questions focused on the amount of usage, motives for usage, level of trust, users’ tendencies to seek novelty in restaurants and motives for contribution.

Findings

– Users tend to trust the reviews on Yelp.com and engage in the community aspects of the platform. Yelp.com users also are altruistic in their motivation for contributing reviews to Yelp.com. Yelp.com users who access it tend to act on the information found within the reviews.

Originality/value

– Research articles have focused on user-generated reviews in the past; however, few have examined motivations of using and posting restaurant reviews. The value of conducting research comes from being able to understand the importance of user-generated restaurant reviews for customers in a comprehensive manner.
Factors influencing hotel customers’ intention to use a fingerprint system
Authors: (Sunny) Kim Jungsun , Bernhard Bo
Published: August 2014

Purpose

– This paper aims to extend the technology acceptance model (TAM) to explore the factors influencing a hotel customer’s intention to use a fingerprint system instead of a traditional keycard system and the moderating factors (i.e. gender and age) on the relationships between the proposed factors and the customer’s intention to use fingerprint technology. When hotels add new technologies, the potential vulnerability of their systems also increases. Underestimating such risks can possibly result in massive losses from identity theft and related fraud for hoteliers. Customers who are aware of these risks may become more open to innovative methods of identification or verification, such as biometrics.

Design/methodology/approach

– The online survey instrument was developed based on TAMs. The authors collected complete 526 responses from hotel customers and tested the hypotheses using structural equation modeling.

Findings

– This study found seven factors (i.e. perceived usefulness, perceived ease of use, subjective norm, perceived convenience, perceived data security, perceived property security and personal concerns) which significantly influence a hotel customer’s intention to use fingerprint technology. Gender and age played important moderating roles in the relationships between some of these factors and the intention to use.

Practical implications

– Recommendations are made as to how hotels can benefit from the implementation of biometrics, particularly fingerprint systems. For example, a hotel’s marketing campaign can be more effective by emphasizing the advantages of fingerprint technology related to “data security and convenience” for younger consumers (i.e. Gen X and Gen Y).

Originality/value

– Both educators and practitioners will benefit from the findings of this empirical study, as there are very few published studies on a customer’s fingerprint technology acceptance in the hotel context.
Shaping travelers’ attitude toward travel mobile applications
Authors: Young Im Jin , Hancer Murat
Published: August 2014

Purpose

– This study aimed to investigate the direct and indirect relationship of utilitarian motivation, hedonic motivation and self-identity to travelers’ attitude toward travel mobile application usage using the technology acceptance model (TAM). In addition, this study identified the differences in these relationships according to users’ level of experience in general mobile application usage.

Design/methodology/approach

– This study used a causal research design. Online survey was conducted with a self-administered questionnaire.

Findings

– Utilitarian motivation is the most important factor in shaping the attitude in using travel mobile applications. However, hedonic motivation plays a role as an important catalyst for utilitarian motivation. Self-identity has a positive direct effect on attitude and an indirect effect through perceived enjoyment. There were differences in these relationships by the years of using similar technologies, general mobile application.

Practical implications

– This study provided meaningful implications for practitioners who utilize mobile applications as their communication channel with customers in the hospitality and tourism industry. For example, using graphic and simple icons helps users make free of efforts from reading and writing in text.

Originality/value

– This paper presented an important and needed research for the area of hospitality information technology. This study enhances the understanding of travel mobile application usage behavior by investigating interrelationship of utilitarian/hedonic motivation and self-identity on attitude toward using travel mobile application.
Stylized patterns of implied volatility in India: a case study of NSE Nifty options
Authors: Shaikh Imlak , Padhi Puja
Published: August 2014

Purpose

– The aim of this study is to examine the “volatility smile” or/and “skew”, term structure and implied volatility surfaces based on those European options written in the standard and poor (S&P) Nifty equity index. The stochastic nature of implied volatility across strike price, time-to-expiration and moneyness violates the core assumption of the Black–Scholes option pricing model.

Design/methodology/approach

– The potential determinants of implied volatility are the degree of moneyness, time-to-expiration and the liquidity of the strikes. The empirical work has been expressed by means of a simple ordinary least squares (OLS) framework and presents the estimation results according to moneyness, time-to-expiration and liquidity of options.

Findings

– The options data give evidence of the existence of a classical U-shaped volatility smile for the Indian options market. Indeed, there is some evidence that the “volatility smirk” which pertains to 30-day options and also implied volatility remain higher for the shorter maturity options and decrease as the time-to-expiration increases. The results lead us to believe that in-the-money calls and out-of-the-money puts are of higher volatility than at-the-money options. Conclusion was drawn due to the persistence of the smile in the options market.

Practical implications

– The practical implication of studying stylized patterns of implied volatility is that it educates the volatility traders about how in-the-money and out-of-the-money options are priced in the options market, and provides an estimate of volatility for the pricing of future options.

Originality/value

– This study is an extension of previous work. The undertaking has been to examine the case of a more liquid and transparent options market, which is missing from the earlier work. The current study is more relevant because, since 2008, significant changes have been observed in the futures and options market in India.
Organizational structure and knowledge-practice diffusion in the MNC
Authors: Lupton Nathaniel , Beamish Paul
Published: August 2014

Purpose

– This study aims to examine the interaction of formal and informal cross-border knowledge-sharing practices of four large multinational corporations (MNCs) in aerospace, software, IT services and telecommunications industries. The goal was to determine the manner in which coordination and control mechanisms facilitated knowledge transfer.

Design/methodology/approach

– Case studies comprised secondary data and semi-structured interviews with corporate headquarters and subsidiary managers in large MNCs conducted in the USA, Canada, Mexico, China, India and Eastern Europe.

Findings

– The primary finding of this study is that knowledge transfer mechanisms arise as a result of both formal and informal structures of the MNC. Formal structures which create either mutual dependencies or occasions for knowledge exchange facilitate transfer. Formal structure which inhibits knowledge transfer can be overcome by knowledge brokers and evaluation metrics.

Research limitations/implications

– These findings suggest that knowledge transfer is more informal than formal, but that MNC headquarters does play a role, intended or not, through shaping the interdependencies among geographically distributed units. Managers should be mindful of both the manner in which tasks and the organization are structured, as these have an indirect impact on the development of knowledge channels.

Originality/value

– This paper investigates the role of organizational structure and its effect, both intended and unintended, on the transfer of knowledge-based practices. While knowledge transfer has been heavily researched, this study examines the phenomenon at a finer-grained level of analysis.