bluuebunny/crossref_metadata_2025 huggingface dataset:
Hemin Exerts Multiple Protective Mechanisms and Attenuates Dextran Sulfate Sodium–induced Colitis
Authors: Zhong Wenwei , Xia Zhenwei , Hinrichs David , Rosenbaum James T , Wegmann Keith W , Meyrowitz Jeffery , Zhang Zili
Published: January 2010

Objective:

Inflammatory bowel disease (IBD) is characterized by recurrent and severe gastrointestinal inflammation. Activation of inflammatory cells, such as TH17 lymphocytes, and/or deficiency of regulatory T cells (Treg) are responsible for the pathogenesis of IBD. As an acute phase reactant, heme oxygenase‐1 (HO‐1) has been shown to play an anti‐inflammatory and immunomodulatory role in many disease processes. In this study, we used a dextran sulfate sodium (DSS)–induced murine colitis model to investigate the effect of upregulating HO‐1 by hemin on the development of colonic inflammation.

Materials and Methods:

The mice were enterically challenged with 4% DSS. In addition, some mice were intraperitoneally administered with hemin or Sn‐protoporphyrin (SnPP) on days 0, 1, and 6 after DSS treatment. The severity of colitis was evaluated by daily monitoring of weight change and diarrhea. At the end of the experiment, the colon, spleen, and mesenteric lymph nodes were harvested for histology and various immunological assays.

Results:

Compared to control groups, DSS challenge markedly induced HO‐1 expression in the colon epithelium. Upregulation of HO‐1 by hemin was further correlated with attenuation of DSS‐induced colitis. In contrast, inhibition of endogenous HO‐1 by SnPP aggravated the colitis. To further assess the anti‐inflammatory mechanisms, we examined whether hemin enhanced the proliferation of Treg cells and suppressed the production of interleukin (IL)‐17. Flow cytometry analysis revealed that hemin markedly expanded the CD4 + CD25 + Foxp3+ Treg population. Moreover, hemin attenuated IL‐17 and TH17‐related cytokines. This inhibition coincided with the attenuation of DSS‐induced colitis. Finally, terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end‐labeling assay showed that hemin treatment markedly reduced programmed cell death of colonic epithelium, indicating that hemin exerts a modulatory effect on the induction of Treg, IL‐17, and apoptosis.

Conclusions:

These results demonstrate that upregulation of HO‐1 by hemin ameliorated experimental colitis. Moreover, our study suggests a broader protective mechanism of hemin.
Numerical simulation of two-dimensional and three-dimensional axisymmetric advection–diffusion systems with complex geometries using finite-volume methods
Authors: Ashbourn J. M. A. , Geris L. , Gerisch A. , Young C. J. S.
Published: January 2010

A finite-volume method has been developed that can deal accurately with complicated, curved boundaries for both two-dimensional and three-dimensional axisymmetric advection–diffusion systems. The motivation behind this is threefold. Firstly, the ability to model the correct geometry of a situation yields more accurate results. Secondly, smooth geometries eliminate corner singularities in the calculation of, for example, mechanical variables and thirdly, different geometries can be tested for experimental applications. An example illustrating each of these is given: fluid carrying a dye and rotating in an annulus, bone fracture healing in mice, and using vessels of different geometry in an ultracentrifuge.
Azospirillum thiophilum sp. nov., a diazotrophic bacterium isolated from a sulfide spring
Authors: Lavrinenko Ksenia , Chernousova Elena , Gridneva Elena , Dubinina Galina , Akimov Vladimir , Kuever Jan , Lysenko Anatoly , Grabovich Margarita
Published: January 2010

A novel nitrogen-fixing strain, designated BV-ST, was isolated from a sulfur bacterial mat collected from a sulfide spring of the Stavropol Krai, North Caucasus, Russia. Strain BV-ST grew optimally at pH 7.5 and 37 °C. According to the results of phylogenetic analysis, strain BV-ST belonged to the genus Azospirillum within the family Rhodospirillaceae of the class Alphaproteobacteria. Within the genus Azospirillum, strain BV-ST was most closely related to Azospirillum doebereinerae GSF71T, A. picis IMMIB TAR-3T and A. lipoferum ATCC 29707T (97.7, 97.7 and 97.4 % 16S rRNA gene sequence similarity, respectively). DNA–DNA relatedness between strain BV-ST and A. doebereinerae DSM 13131T, A. picis DSM 19922T and A. lipoferum ATCC 29707T was 38, 55 and 42 %, respectively. Similarities between nifH sequences of strain BV-ST and members of the genus Azospirillum ranged from 94.5 to 96.8 %. Chemotaxonomic characteristics (quinone Q-10, major fatty acid C18 : 1
ω7c and G+C content 67 mol%) were similar to those of members of the genus Azospirillum. In contrast to known Azospirillum species, strain BV-ST was capable of mixotrophic growth under microaerobic conditions with simultaneous utilization of organic substrates and thiosulfate as electron donors for energy conservation. Oxidation of sulfide was accompanied by deposits of sulfur globules within the cells. Based on these observations, strain BV-ST is considered as a representative of a novel species of the genus Azospirillum, for which the name Azospirillum thiophilum sp. nov. is proposed. The type strain is BV-ST (=DSM 21654T =VKM B-2513T).
Pseudonocardia adelaidensis sp. nov., an endophytic actinobacterium isolated from the surface-sterilized stem of a grey box tree (Eucalyptus microcarpa)
Authors: Kaewkla Onuma , Franco Christopher M. M.
Published: January 2010

An aerobic, actinobacterial strain with rod-shaped spores, EUM 221T, which was isolated from the surface-sterilized stem of a grey box tree (Eucalyptus microcarpa), is described. Phylogenetic evaluation based on 16S rRNA gene sequence similarity showed that this isolate belongs to the family Pseudonocardiaceae, with the closest neighbour being Pseudonocardia zijingensis 6330T (98.7 %). The level of 16S rRNA gene sequence similarity between the isolate and species of the genus Pseudonocardia with validly published names ranged from 95 to 98 %. Chemotaxonomic data (meso-diaminopimelic acid; major menaquinone MK-8(H4); major fatty acid iso-C16 : 0) confirmed the affiliation of strain EUM 221T to the genus Pseudonocardia. The results of the phylogenetic analysis, including physiological and biochemical studies in combination with DNA–DNA hybridization, allowed the genotypic and phenotypic differentiation of strain EUM 221T from the closest described species. Therefore, this strain represented a novel species and the name proposed is Pseudonocardia adelaidensis sp. nov. The type strain is EUM 221T (=DSM 45352T =ACM 5286T).
Euzebyella saccharophila gen. nov., sp. nov., a marine bacterium of the family Flavobacteriaceae
Authors: Lucena Teresa , Pascual Javier , Giordano Assunta , Gambacorta Agata , Garay Esperanza , Arahal David R. , Macián M. Carmen , Pujalte María J.
Published: January 2010

Strain 7SM30T
, an aerobic marine, Gram-negative, heterotrophic and yellow- to orange-pigmented bacterium isolated from seawater from Castellón, Spain, was characterized using a polyphasic approach. Analysis of the 16S rRNA gene sequence showed that the isolate represented a novel lineage within the family Flavobacteriaceae. The most closely related genera were Pseudozobellia, Zobellia and Kriegella. Cells of strain 7SM30T were non-motile rods that required sea salts for growth, used a wide variety of carbohydrates as sole carbon and energy sources and, unlike species of the genera Pseudozobellia and Zobellia, did not possess flexirubin-type pigment or hydrolyse agar. Strain 7SM30T contained MK6 as the sole respiratory quinone. Phosphatidylethanolamine (PE) was the only identifiable polar lipid, although other lipids were also detected. The predominant cellular fatty acids were saturated C15 and monounsaturated C15. The DNA G+C content was around 40 mol%. On the basis of extensive phenotypic and phylogenetic comparative analysis, it is concluded that the new strain represents a novel genus and species, for which the name Euzebyella saccharophila gen. nov., sp. nov., is proposed. The type strain of the type species is 7SM30T (=CECT 7477T=KCTC 22655T).
ZFP191 is required by oligodendrocytes for CNS myelination
Authors: Howng Shen Yi B. , Avila Robin L. , Emery Ben , Traka Maria , Lin Wensheng , Watkins Trent , Cook Susan , Bronson Roderick , Davisson Muriel , Barres Ben A. , Popko Brian
Published: January 2010

The controlling factors that prompt mature oligodendrocytes to myelinate axons are largely undetermined. In this study, we used a forward genetics approach to identify a mutant mouse strain characterized by the absence of CNS myelin despite the presence of abundant numbers of late-stage, process-extending oligodendrocytes. Through linkage mapping and complementation testing, we identified the mutation as a single nucleotide insertion in the gene encoding zinc finger protein 191 (Zfp191), which is a widely expressed, nuclear-localized protein that belongs to a family whose members contain both DNA-binding zinc finger domains and protein–protein-interacting SCAN domains. Zfp191 mutants express an array of myelin-related genes at significantly reduced levels, and our in vitro and in vivo data indicate that mutant ZFP191 acts in a cell-autonomous fashion to disrupt oligodendrocyte function. Therefore, this study demonstrates that ZFP191 is required for the myelinating function of differentiated oligodendrocytes.
Role of the hypothalamic–pituitary–thyroid axis in metabolic regulation by JNK1
Authors: Sabio Guadalupe , Cavanagh-Kyros Julie , Barrett Tamera , Jung Dae Young , Ko Hwi Jin , Ong Helena , Morel Caroline , Mora Alfonso , Reilly Judith , Kim Jason K. , Davis Roger J.
Published: January 2010

The cJun N-terminal kinase 1 (JNK1) is implicated in diet-induced obesity. Indeed, germline ablation of the murine Jnk1 gene prevents diet-induced obesity. Here we demonstrate that selective deficiency of JNK1 in the murine nervous system is sufficient to suppress diet-induced obesity. The failure to increase body mass is mediated, in part, by increased energy expenditure that is associated with activation of the hypothalamic–pituitary–thyroid axis. Disruption of thyroid hormone function prevents the effects of nervous system JNK1 deficiency on body mass. These data demonstrate that the hypothalamic–pituitary–thyroid axis represents an important target of metabolic signaling by JNK1.
The Heat-Inducible Transcription Factor HsfA2 Enhances Anoxia Tolerance in Arabidopsis
Authors: Banti Valeria , Mafessoni Fabrizio , Loreti Elena , Alpi Amedeo , Perata Pierdomenico
Published: January 2010

Anoxia induces several heat shock proteins, and a mild heat pretreatment can acclimatize Arabidopsis (Arabidopsis thaliana) seedlings to subsequent anoxic treatment. In this study, we analyzed the response of Arabidopsis seedlings to anoxia, heat, and combined heat + anoxia stress. A significant overlap between the anoxic and the heat responses was observed by whole-genome microarray analysis. Among the transcription factors induced by both heat and anoxia, the heat shock factor A2 (HsfA2), known to be involved in Arabidopsis acclimation to heat and to other abiotic stresses, was strongly induced by anoxia. Heat-dependent acclimation to anoxia is lost in an HsfA2 knockout mutant (hsfa2) as well as in a double mutant for the constitutively expressed HsfA1a/HsfA1b (hsfA1a/1b), indicating that these three heat shock factors cooperate to confer anoxia tolerance. Arabidopsis seedlings that overexpress HsfA2 showed an increased expression of several known targets of this transcription factor and were markedly more tolerant to anoxia as well as to submergence. Anoxia failed to induce HsfA2 target proteins in wild-type seedlings, while overexpression of HsfA2 resulted in the production of HsfA2 targets under anoxia, correlating well with the low anoxia tolerance experiments. These results indicate that there is a considerable overlap between the molecular mechanisms of heat and anoxia tolerance and that HsfA2 is a player in these mechanisms.
Glycolysis and the Tricarboxylic Acid Cycle Are Linked by Alanine Aminotransferase during Hypoxia Induced by Waterlogging of Lotus japonicus
Authors: Rocha Marcio , Licausi Francesco , Araújo Wagner L. , Nunes-Nesi Adriano , Sodek Ladaslav , Fernie Alisdair R. , van Dongen Joost T.
Published: January 2010

The role of nitrogen metabolism in the survival of prolonged periods of waterlogging was investigated in highly flood-tolerant, nodulated Lotus japonicus plants. Alanine production revealed to be a critical hypoxic pathway. Alanine is the only amino acid whose biosynthesis is not inhibited by nitrogen deficiency resulting from RNA interference silencing of nodular leghemoglobin. The metabolic changes that were induced following waterlogging can be best explained by the activation of alanine metabolism in combination with the modular operation of a split tricarboxylic acid pathway. The sum result of this metabolic scenario is the accumulation of alanine and succinate and the production of extra ATP under hypoxia. The importance of alanine metabolism is discussed with respect to its ability to regulate the level of pyruvate, and this and all other changes are discussed in the context of current models concerning the regulation of plant metabolism.
Actin-Binding Proteins Implicated in the Formation of the Punctate Actin Foci Stimulated by the Self-Incompatibility Response inPapaver
Authors: Poulter Natalie S. , Staiger Christopher J. , Rappoport Joshua Z. , Franklin-Tong Vernonica E.
Published: January 2010

The actin cytoskeleton is a key target for signaling networks and plays a central role in translating signals into cellular responses in eukaryotic cells. Self-incompatibility (SI) is an important mechanism responsible for preventing self-fertilization. The SI system of Papaver rhoeas pollen involves a Ca2+-dependent signaling network, including massive actin depolymerization as one of the earliest cellular responses, followed by the formation of large actin foci. However, no analysis of these structures, which appear to be aggregates of filamentous (F-)actin based on phalloidin staining, has been carried out to date. Here, we characterize and quantify the formation of F-actin foci in incompatible Papaver pollen tubes over time. The F-actin foci increase in size over time, and we provide evidence that their formation requires actin polymerization. Once formed, these SI-induced structures are unusually stable, being resistant to treatments with latrunculin B. Furthermore, their formation is associated with changes in the intracellular localization of two actin-binding proteins, cyclase-associated protein and actin-depolymerizing factor. Two other regulators of actin dynamics, profilin and fimbrin, do not associate with the F-actin foci. This study provides, to our knowledge, the first insights into the actin-binding proteins and mechanisms involved in the formation of these intriguing structures, which appear to be actively formed during the SI response.
Reconstruction of Metabolic Pathways, Protein Expression, and Homeostasis Machineries across Maize Bundle Sheath and Mesophyll Chloroplasts: Large-Scale Quantitative Proteomics Using the First Maize Genome Assembly
Authors: Friso Giulia , Majeran Wojciech , Huang Mingshu , Sun Qi , van Wijk Klaas J.
Published: January 2010

Chloroplasts in differentiated bundle sheath (BS) and mesophyll (M) cells of maize (Zea mays) leaves are specialized to accommodate C4 photosynthesis. This study provides a reconstruction of how metabolic pathways, protein expression, and homeostasis functions are quantitatively distributed across BS and M chloroplasts. This yielded new insights into cellular specialization. The experimental analysis was based on high-accuracy mass spectrometry, protein quantification by spectral counting, and the first maize genome assembly. A bioinformatics workflow was developed to deal with gene models, protein families, and gene duplications related to the polyploidy of maize; this avoided overidentification of proteins and resulted in more accurate protein quantification. A total of 1,105 proteins were assigned as potential chloroplast proteins, annotated for function, and quantified. Nearly complete coverage of primary carbon, starch, and tetrapyrole metabolism, as well as excellent coverage for fatty acid synthesis, isoprenoid, sulfur, nitrogen, and amino acid metabolism, was obtained. This showed, for example, quantitative and qualitative cell type-specific specialization in starch biosynthesis, arginine synthesis, nitrogen assimilation, and initial steps in sulfur assimilation. An extensive overview of BS and M chloroplast protein expression and homeostasis machineries (more than 200 proteins) demonstrated qualitative and quantitative differences between M and BS chloroplasts and BS-enhanced levels of the specialized chaperones ClpB3 and HSP90 that suggest active remodeling of the BS proteome. The reconstructed pathways are presented as detailed flow diagrams including annotation, relative protein abundance, and cell-specific expression pattern. Protein annotation and identification data, and projection of matched peptides on the protein models, are available online through the Plant Proteome Database.
An Arabidopsis Mutant with High Cyclic Electron Flow around Photosystem I (hcef) Involving the NADPH Dehydrogenase Complex
Authors: Livingston Aaron K. , Cruz Jeffrey A. , Kohzuma Kaori , Dhingra Amit , Kramer David M.
Published: January 2010

Cyclic electron flow (CEFI) has been proposed to balance the chloroplast energy budget, but the pathway, mechanism, and physiological role remain unclear. We isolated a new class of mutant in Arabidopsis thaliana, hcef for high CEF1, which shows constitutively elevated CEF1. The first of these, hcef1, was mapped to chloroplast fructose-1,6-bisphosphatase. Crossing hcef1 with pgr5, which is deficient in the antimycin A–sensitive pathway for plastoquinone reduction, resulted in a double mutant that maintained the high CEF1 phenotype, implying that the PGR5-dependent pathway is not involved. By contrast, crossing hcef1 with crr2-2, deficient in thylakoid NADPH dehydrogenase (NDH) complex, results in a double mutant that is highly light sensitive and lacks elevated CEF1, suggesting that NDH plays a direct role in catalyzing or regulating CEF1. Additionally, the NdhI component of the NDH complex was highly expressed in hcef1, whereas other photosynthetic complexes, as well as PGR5, decreased. We propose that (1) NDH is specifically upregulated in hcef1, allowing for increased CEF1; (2) the hcef1 mutation imposes an elevated ATP demand that may trigger CEF1; and (3) alternative mechanisms for augmenting ATP cannot compensate for the loss of CEF1 through NDH.
XDS
Authors: Kabsch Wolfgang
Published: January 2010

The usage and control of recent modifications of the program packageXDSfor the processing of rotation images are described in the context of previous versions. New features include automatic determination of spot size and reflecting range and recognition and assignment of crystal symmetry. Moreover, the limitations of earlier package versions on the number of correction/scaling factors and the representation of pixel contents have been removed. Large program parts have been restructured for parallel processing so that the quality and completeness of collected data can be assessed soon after measurement.
Integration, scaling, space-group assignment and post-refinement
Authors: Kabsch Wolfgang
Published: January 2010

Important steps in the processing of rotation data are described that are common to most software packages. These programs differ in the details and in the methods implemented to carry out the tasks. Here, the working principles underlying the data-reduction packageXDSare explained, including the new features of automatic determination of spot size and reflecting range, recognition and assignment of crystal symmetry and a highly efficient algorithm for the determination of correction/scaling factors.
Structures of human MST3 kinase in complex with adenine, ADP and Mn2+
Authors: Ko Tzu-Ping , Jeng Wen-Yih , Liu Chia-I , Lai Ming-Derg , Wu Chun-Lan , Chang Wei-Jung , Shr Hui-Lin , Lu Te-Jung , Wang Andrew H.-J.
Published: January 2010

The MST family is a subclass of mammalian serine/threonine kinases that are related to the yeast sterile-20 protein and are implicated in regulating cell growth and transformation. The MST3 protein contains a 300-residue catalytic domain and a 130-residue regulatory domain, which can be cleaved by caspase and activated by autophosphorylation, promoting apoptosis. Here, five crystal structures of the catalytic domain of MST3 are presented, including a complex with ADP and manganese, a unique cofactor preferred by the enzyme, and a complex with adenine. Similar to other protein kinases, the catalytic domain of MST3 folds into two lobes: the smaller N lobe forms the nucleotide-binding site and the larger C lobe recognizes the polypeptide substrate. The bound ADP and Mn2+ions are covered by a glycine-rich loop and held in place by Asn149 and Asp162. A different orientation was observed for the ligand in the MST3–adenine complex. In the activation loop, the side chain of Thr178 is phosphorylated and is sandwiched by Arg143 and Arg176. Comparison of this structure with other similar kinase structures shows a 180° rotation of the loop, leading to activation of the enzyme. The well defined protein–ligand interactions also provide useful information for the design of potent inhibitors.
Structure of grouper iridovirus purine nucleoside phosphorylase
Authors: Kang You-Na , Zhang Yang , Allan Paula W. , Parker William B. , Ting Jing-Wen , Chang Chi-Yao , Ealick Steven E.
Published: January 2010

Purine nucleoside phosphorylase (PNP) catalyzes the reversible phosphorolysis of purine ribonucleosides to the corresponding free bases and ribose 1-phosphate. The crystal structure of grouper iridovirus PNP (givPNP), corresponding to the first PNP gene to be found in a virus, was determined at 2.4 Å resolution. The crystals belonged to space groupR3, with unit-cell parametersa= 193.0,c= 105.6 Å, and contained four protomers per asymmetric unit. The overall structure of givPNP shows high similarity to mammalian PNPs, having an α/β structure with a nine-stranded mixed β-barrel flanked by a total of nine α-helices. The predicted phosphate-binding and ribose-binding sites are occupied by a phosphate ion and a Tris molecule, respectively. The geometrical arrangement and hydrogen-bonding patterns of the phosphate-binding site are similar to those found in the human and bovine PNP structures. The enzymatic activity assay of givPNP on various substrates revealed that givPNP can only accept 6-oxopurine nucleosides as substrates, which is also suggested by its amino-acid composition and active-site architecture. All these results suggest that givPNP is a homologue of mammalian PNPs in terms of amino-acid sequence, molecular mass, substrate specificity and overall structure, as well as in the composition of the active site.
Complexes ofThermotoga maritimaS-adenosylmethionine decarboxylase provide insights into substrate specificity
Authors: Bale Shridhar , Baba Kavita , McCloskey Diane E. , Pegg Anthony E. , Ealick Steven E.
Published: January 2010

The polyamines putrescine, spermidine and spermine are ubiquitous aliphatic cations and are essential for cellular growth and differentiation.S-Adenosylmethionine decarboxylase (AdoMetDC) is a critical pyruvoyl-dependent enzyme in the polyamine-biosynthetic pathway. The crystal structures of AdoMetDC from humans and plants and of the AdoMetDC proenzyme fromThermotoga maritimahave been obtained previously. Here, the crystal structures of activatedT. maritimaAdoMetDC (TmAdoMetDC) and of its complexes withS-adenosylmethionine methyl ester and 5′-deoxy-5′-dimethylthioadenosine are reported. The results demonstrate for the first time that TmAdoMetDC autoprocesses without the need for additional factors and that the enzyme contains two complete active sites, both of which use residues from both chains of the homodimer. The complexes provide insights into the substrate specificity and ligand binding of AdoMetDC in prokaryotes. The conservation of the ligand-binding mode and the active-site residues between human andT. maritimaAdoMetDC provides insight into the evolution of AdoMetDC.
Pseudo-merohedral twinning and noncrystallographic symmetry in orthorhombic crystals of SIVmac239 Nef core domain bound to different-length TCRζ fragments
Authors: Kim Walter M. , Sigalov Alexander B. , Stern Lawrence J.
Published: January 2010

HIV/SIV Nef mediates many cellular processes through interactions with various cytoplasmic and membrane-associated host proteins, including the signalling ζ subunit of the T-cell receptor (TCRζ). Here, the crystallization strategy, methods and refinement procedures used to solve the structures of the core domain of the SIVmac239 isolate of Nef (Nefcore) in complex with two different TCRζ fragments are described. The structure of SIVmac239 Nefcorebound to the longer TCRζ polypeptide (Leu51–Asp93) was determined to 3.7 Å resolution (Rwork= 28.7%) in the tetragonal space groupP43212. The structure of SIVmac239 Nefcorein complex with the shorter TCRζ polypeptide (Ala63–Arg80) was determined to 2.05 Å resolution (Rwork = 17.0%), but only after the detection of nearly perfect pseudo-merohedral crystal twinning and proper assignment of the orthorhombic space groupP212121. The reduction in crystal space-group symmetry induced by the truncated TCRζ polypeptide appears to be caused by the rearrangement of crystal-contact hydrogen-bonding networks and the substitution of crystallographic symmetry operations by similar noncrystallographic symmetry (NCS) operations. The combination of NCS rotations that were nearly parallel to the twin operation (k, h, −l) andaandbunit-cell parameters that were nearly identical predisposed theP212121crystal form to pseudo-merohedral twinning.
Structure of human desArg-C5a
Authors: Cook William J. , Galakatos Nicholas , Boyar William C. , Walter Richard L. , Ealick Steven E.
Published: January 2010

The anaphylatoxin C5a is derived from the complement component C5 during activation of the complement cascade. It is an important component in the pathogenesis of a number of inflammatory diseases. NMR structures of human and porcine C5a have been reported; these revealed a four-helix bundle stabilized by three disulfide bonds. The crystal structure of human desArg-C5a has now been determined in two crystal forms. Surprisingly, the protein crystallizes as a dimer and each monomer in the dimer has a three-helix core instead of the four-helix bundle noted in the NMR structure determinations. Furthermore, the N-terminal helices of the two monomers occupy different positions relative to the three-helix core and are completely different from the NMR structures. The physiological significance of these structural differences is unknown.
PHENIX: a comprehensive Python-based system for macromolecular structure solution
Authors: Adams Paul D. , Afonine Pavel V. , Bunkóczi Gábor , Chen Vincent B. , Davis Ian W. , Echols Nathaniel , Headd Jeffrey J. , Hung Li-Wei , Kapral Gary J. , Grosse-Kunstleve Ralf W. , McCoy Airlie J. , Moriarty Nigel W. , Oeffner Robert , Read Randy J. , Richardson David C. , Richardson Jane S. , Terwilliger Thomas C. , Zwart Peter H.
Published: January 2010

Macromolecular X-ray crystallography is routinely applied to understand biological processes at a molecular level. However, significant time and effort are still required to solve and complete many of these structures because of the need for manual interpretation of complex numerical data using many software packages and the repeated use of interactive three-dimensional graphics.PHENIXhas been developed to provide a comprehensive system for macromolecular crystallographic structure solution with an emphasis on the automation of all procedures. This has relied on the development of algorithms that minimize or eliminate subjective input, the development of algorithms that automate procedures that are traditionally performed by hand and, finally, the development of a framework that allows a tight integration between the algorithms.
Managing product variety in emerging markets
Authors: Felipe Scavarda Luiz , Reichhart Andreas , Hamacher Silvio , Holweg Matthias
Published: January 2010

Purpose

The need for an efficient provision of product variety has been widely established as a means of competing in the marketplace, yet previous studies into the management of product variety have commonly analysed products in isolated developed markets. The purpose of this paper is to investigate how firms manage their product variety in emerging markets. This paper aims to investigate the rationale underlying the restriction of variety in such settings, and define general mechanisms by which firms can adapt their product variety when operating in both emerging and developed markets simultaneously.

Design/methodology/approach

The paper uses the case of a global vehicle manufacturer that offers common products across developed and emerging markets to illustrate the difference between them in terms of product variety, and examine the process that underlies its management. The paper utilises a combination of data collection techniques.

Findings

The paper shows empirically how product variety (in particular ex factory variety) is restricted in emerging markets, as one would expect, and it identifies the mechanisms by which product variety is managed across different markets. The paper further illustrates how emerging markets have developed secondary coping mechanisms to deliver additional variety through late configuration in the distribution system.

Originality/value

By examining the differential management of product variety in emerging and developed markets, the findings yield several novel aspects by providing both empirical evidence and explanations for the restriction of product variety in emerging markets.
Radical economics and our current predicament
Authors: Armour Leslie
Published: January 2010

Purpose

The purpose of this paper is to introduce the “Radical economics” issue in International Journal of Social Economics.

Design/methodology/approach

“Radical economics” has two basic meanings. One employs the basic sense of “radical”, whatever goes to the roots of the matter. The other common meaning of radical has to do with whatever diverges from the orthodoxy of the time. This issue examines radical economics in both senses.

Findings

The recent world economic crisis raises basic questions about economic thought. Complex mathematical formulae led banks to take what proved to be unwarranted risks. Behind them is a tendency to regard economics as a self‐contained discipline. Complexities which sociologists, social psychologists, anthropologists and historians have done something to unravel are sometimes simply ignored. The philosophical bases of the economic theories in circulation are often more than two centuries old. But some important ideas from the past have been forgotten, the distinction between wealth and riches is one. Social change also plays a part in the problems. Community friendly capitalism, ridiculed and attacked by some economists, has faded. At a deeper level the tendency for the rich to get much richer while the poorest people in the world are only slightly better off has produced more instability and uncertainty, which economists have not successfully addressed.

Practical implications

It is hoped readers will join in these ongoing explorations.

Social implications

The recent economic crisis has been importantly a crisis of confidence. Economic studies, which offer hope for change, can be an element in increasing confidence.

Originality/value

The problem posed by the constant expansion necessitated in the ordinary way the need to invest profits may threaten the sustainability of life on our planet and no immediately available economic theory seems to address this. This issue begins to raise the essential questions, with hopes of continuing the discussion.
Applying western organization development in China: lessons from a case of success
Authors: Wang Jia
Published: January 2010

Purpose

The purpose of this paper is to explore a successful case of a Chinese state‐owned enterprise (SOE) as it applied western organization development (OD) approaches. Specifically, this study seeks to answer two questions: How has western organization development and change (OD/C) been applied in one Chinese SOE? and What lessons can be learned from this successful case?

Design/methodology/approach

The paper employs a single case design to gain an in‐depth understanding. The case study is the methodology when the focus is on a contemporary phenomenon within a real‐life context.

Findings

The findings reveal that the organization successfully uses a number of western OD techniques in creating a shared vision, establishing a performance‐based human resource management system, and standardizing budgetary and cost control procedures. The success of the company's change effort is largely attributed to leadership, standardization of management systems, commitment to learning and training, and partnership with an OD expert.

Research limitations/implications

Findings of this paper are limited by the single case study design. Future research is needed to study more cases of success where western OD techniques have been applied. Further research is also warranted to identify indigenous OD approaches used by Chinese organizations. Current research also needs to be expanded to study regions or countries that are undergoing similar economic transitions and have adopted western‐based OD techniques.

Originality/value

By focusing on an under‐explored research territory – China – the paper expands the current knowledge of OD into the international domain and fills in the gap of OD/C research which is lacking in China.
Phylogeny of the millipede order Spirobolida (Arthropoda: Diplopoda: Helminthomorpha)
Authors: Pitz Kevin M. , Sierwald Petra
Published: January 2010

This study examines relationships within the millipede order Spirobolida using an exemplar approach, sampling within families to maximize geographical and morphological diversity; due to lack of available material, Allopocockiidae and Hoffmanobolidae were not included in analyses. The focus of this study was to test monophyly of the order, the suborders, and the families of Spirobolida and to propose interfamilial relationships using morphological and molecular data in a total‐evidence approach. Both maximum‐parsimony analyses and Bayesian inference were employed to analyse two datasets consisting of combined morphological and molecular data, one aligned using progressive alignment methods and the second aligned by secondary structure models. Rhinocricidae was recovered sister to all remaining spirobolidan millipedes and is elevated to suborder status as suborder Rhinocricidea. Trigoniulidea was recovered as monophyletic as was Spirobolidea excluding Rhinocricidae; Spirobolidea is redefined to reflect this change. All previously recognized families were recovered, with the exception of Spirobolidae; in all instances, this family was paraphyletic or part of a polytomy that lacked sufficient resolution to assess its monophyly. The results reaffirm much of the existing taxonomic foundation within Spirobolida. This study provides the first phylogenetic test of higher‐level relationships within Spirobolida and will serve as a foundation for future work in this group at finer levels. © The Willi Hennig Society 2010.
A genome‐wide scan for signatures of recent selection in Holstein cattle
Authors: Qanbari S. , Pimentel E. C. G. , Tetens J. , Thaller G. , Lichtner P. , Sharifi A. R. , Simianer H.
Published: January 2010

The data from the newly available 50 K SNP chip was used for tagging the genome‐wide footprints of positive selection in Holstein–Friesian cattle. For this purpose, we employed the recently described Extended Haplotype Homozygosity test, which detects selection by measuring the characteristics of haplotypes within a single population. To assess formally the significance of these results, we compared the combination of frequency and the Relative Extended Haplotype Homozygosity value of each core haplotype with equally frequent haplotypes across the genome. A subset of the putative regions showing the highest significance in the genome‐wide EHH tests was mapped. We annotated genes to identify possible influence they have in beneficial traits by using the Gene Ontology database. A panel of genes, including FABP3, CLPN3, SPERT, HTR2A5, ABCE1, BMP4 and PTGER2, was detected, which overlapped with the most extreme P‐values. This panel comprises some interesting candidate genes and QTL, representing a broad range of economically important traits such as milk yield and composition, as well as reproductive and behavioural traits. We also report high values of linkage disequilibrium and a slower decay of haplotype homozygosity for some candidate regions harbouring major genes related to dairy quality. The results of this study provide a genome‐wide map of selection footprints in the Holstein genome, and can be used to better understand the mechanisms of selection in dairy cattle breeding.
Cost‐effectiveness analysis and efficient use of the pharmaceutical budget: the key role of clinical pharmacologists
Authors: Edlin Richard , Round Jeff , Hulme Claire , McCabe Christopher
Published: January 2010

The purpose of this paper is to provide information about cost‐effectiveness analysis and the roles of clinical pharmacologists generally in providing efficient health care. The paper highlights the potential consequences of ‘off‐label prescribing’ and ‘indication creep’ behaviour given slower growth (or potential cuts) in the NHS budget. This paper highlights the key roles of clinical pharmacologists in delivering an efficient health care system when resources are allocated using cost‐effectiveness analyses. It describes what cost‐effectiveness analysis (CEA) is and how incremental cost‐effectiveness ratios (ICERs) are used to identify efficient options. After outlining the theoretical framework within which using CEA can promote the efficient allocation of the health care budget, it considers the place of disinvestment within achieving efficient resource allocation. Clinical pharmacologists are argued to be critical to providing improved population health under CEA‐based resource allocation processes because of their roles in implementation and disinvestment. Given that the challenges facing the United Kingdom National Health Service (NHS) are likely to increase, this paper sets out the stark choices facing clinical pharmacologists.
Comparison of intravenous immune globulin and high dose anti‐D immune globulin as initial therapy for childhood immune thrombocytopenic purpura
Authors: Kane Ian , Ragucci Dominic , Shatat Ibrahim F. , Bussel James , Kalpatthi Ram
Published: January 2010

This report documents our experience with intravenous immune globulin (IVIG) (1 g/kg, iv) and high‐dose, anti‐D immune globulin (anti‐D) (75 μg/kg) as initial treatment for childhood immune thrombocytopenic purpura (ITP). The medical records of children diagnosed with ITP at a single institution between January 2003 and May 2008 were retrospectively reviewed. Participants received either IVIG or high‐dose anti‐D immune globulin as their initial treatment for ITP. For the 53 patients included for analysis, there was no statistical difference in efficacy between each group; however, patients who received anti‐D experienced a higher rate of adverse drug reactions (ADRs), particularly chills and rigours, and 2 of 24 patients in the anti‐D group developed severe anaemia requiring medical intervention. Patients who presented with mucosal bleeding had higher rates of treatment failure (32%) compared to those who presented with dry purpura (6%), regardless of treatment. Both IVIG and high‐dose anti‐D are effective first‐line therapies for childhood ITP. However, we observed increased ADRs in the high‐dose anti‐D group in contrast to previously published reports. Further studies are needed to evaluate safety and premedications for high‐dose anti‐D and to determine the utility of using the presence of mucosal bleeding to predict treatment failure.
Behaviour and attitudes among Spanish general dentists towards the anticoagulated patient: a pilot study
Authors: López‐Jornet Pia , Camacho‐Alonso Fabio , Escribano Myriam Gonzalez , Martinez‐Beneyto Yolanda
Published: January 2010

Aim  To determine the attitude of Spanish general dentists in relation to dental extraction in patients with heart valve prostheses subjected to acenocoumarol anticoagulation.

Material and methods  A telephone survey was made of Spanish general dentists, asking about the indicated approach in the case of performing dental extractions in patients with heart valve prostheses subjected to acenocoumarol (Sintrom®) anticoagulation.

Results  Of the 271 dentists answered, 175 were male (64.6%) and 96 were female (35.4%), with a mean professional experience of 20.17 ± 9.3 years. A total of 228 dentists (84.1%) indicated the need to refer the patient to a specialist for establishing the required approach, while 43 dentists (15.9%) did not consider such a measure to be necessary. Among this latter group of 43 dentists, 26 (60.5%) considered that acenocoumarol should be withdrawn or replaced by low‐molecular weight heparin, while 17 (39.5%) were of the opinion that the anticoagulation regimen should not be modified. In relation to the international normalized ratio, 36 (83.7%) did not consider it necessary to request this parameter. As regards the prevention of endocarditis, 11 (25.6%) specified the need for prophylaxis, although only eight (72.7%) did so correctly. There were no statistically significant differences in behaviour in relation to either gender or years of professional experience.

Conclusions  This study identifies a lack of knowledge on the part of the dentists regarding the approach to dental extraction in patients with heart valve prostheses subjected to anticoagulation. Due educational measures therefore should be reinforced among these professionals.
Genetic analysis of petrobactin transport in Bacillus anthracis
Authors: Carlson Jr Paul E. , Dixon Shandee D. , Janes Brian K. , Carr Katherine A. , Nusca Tyler D. , Anderson Erica C. , Keene Sarra E. , Sherman David H. , Hanna Philip C.
Published: January 2010

Iron acquisition mechanisms play an important role in the pathogenesis of many infectious microbes. In Bacillus anthracis, the siderophore petrobactin is required for both growth in iron‐depleted conditions and for full virulence of the bacterium. Here we demonstrate the roles of two putative petrobactin binding proteins FatB and FpuA (encoded by GBAA5330 and GBAA4766 respectively) in B. anthracis iron acquisition and pathogenesis. Markerless deletion mutants were created using allelic exchange. The ΔfatB strain was capable of wild‐type levels of growth in iron‐depleted conditions, indicating that FatB does not play an essential role in petrobactin uptake. In contrast, ΔfpuA bacteria exhibited a significant decrease in growth under low‐iron conditions when compared with wild‐type bacteria. This mutant could not be rescued by the addition of exogenous purified petrobactin. Further examination of this strain demonstrated increased levels of petrobactin accumulation in the culture supernatants, suggesting no defect in siderophore synthesis or export but, instead, an inability of ΔfpuA to import this siderophore. ΔfpuA spores were also significantly attenuated in a murine model of inhalational anthrax. These results provide the first genetic evidence demonstrating the role of FpuA in petrobactin uptake.
Comprehensive understanding of idiopathic guttate hypomelanosis: clinical and histopathological correlation
Authors: Kim Sue Kyung , Kim En Hyung , Kang Hee Young , Lee Eun‐So , Sohn Seonghyang , Kim You Chan
Published: January 2010

Background  The histological findings associated with idiopathic guttate hypomelanosis (IGH) are hyperkeratosis, an atrophic epidermis, and flattened rete ridges. In addition, a decreased melanin content and reduced numbers of melanocytes are reported features. However, there are few recent studies that have been published on the histopathology of IGH and no comparative studies are available on the skin lesions and perilesional skin of patients with IGH.

Objectives  The goals of this study were to identify the clinical and histopathological features of IGH and determine their correlation. We evaluated the clinical features and the histopathological differences between the skin lesions and the perilesional skin in patients with IGH.

Methods  A clinical survey was carried out on 47 patients with IGH. Specimens from skin lesions and perilesional skin were stained with hematoxylin‐eosin, Fontana–Masson, MART‐1, and NKI/beteb. We also studied the ultrastructure of four cases.

Results  About 30% of the patients had their initial lesions prior to 20 years of age. The arm was the most commonly affected site (53%). Histologically, we found hyperkeratosis in 18 cases (38.3%), but epidermal atrophy was present in only five cases (10.6%), and flattened rete ridges in seven cases (14.9%) compared to the normal skin. Epidermal atrophy was more frequently found at nonsun‐exposed areas. The IGH lesions demonstrated decreased melanin pigment and reduced numbers of melanocytes by NKI/beteb and MART‐1. The ultrastructural evaluation showed degenerative melanocytes and decreased melanosomes. One specimen had normal melanocytes with decreased melanosomes.

Conclusions  Idiopathic guttate hypomelanosis is a disorder with multifactorial etiology; its pathogenesis may depend on various factors such as patient age and sun‐exposure. Histopathologically, hyperkeratosis was frequently found; however, the other characteristic findings such as epidermal atrophy and flattened rete ridges were relatively rare.
Nicotine induces the expression of early growth response‐1 in human skin dermal fibroblasts
Authors: Choi Jae Eun , Kim Ji Na , Jeong Sang Hoon , Son Sang Wook
Published: January 2010

Background  Egr‐1 is known to play an important role in cell growth, differentiation, and cell survival. Human skin dermal fibroblasts (HSDF) may be an important target for adverse effects of tobacco components. However, nicotinic effect for early growth response‐1 (Egr‐1) expression is unknown in HSDF.

Methods  Cytotoxicity of nicotine was assessed by cell viability test in HSDF. The expression of Egr‐1 protein and mRNA after nicotine treatment was evaluated by Western blotting and real‐time reverse transcription–polymerase chain reaction. We also measured the promoter activity of Egr‐1 in HSDF after nicotine exposure.

Results  Early growth response‐1 protein and mRNA levels were increased in dermal fibroblasts exposed to nicotine. Nicotine treatment stimulated the promoter activity of Egr‐1 in cultured human fibroblasts.

Conclusion  In this study, we demonstrate that Egr‐1 expression is markedly induced in HSDF after exposure to nicotine.