bluuebunny/crossref_metadata_2025 huggingface dataset:
Network orientation via shortest paths
Authors: Silverbush Dana , Sharan Roded
Published: January 2014

The graph orientation problem calls for orienting the edges of a graph so as to maximize the number of pre-specified source–target vertex pairs that admit a directed path from the source to the target. Most algorithmic approaches to this problem share a common preprocessing step, in which the input graph is reduced to a tree by repeatedly contracting its cycles. Although this reduction is valid from an algorithmic perspective, the assignment of directions to the edges of the contracted cycles becomes arbitrary, and the connecting source–target paths may be arbitrarily long. In the context of biological networks, the connection of vertex pairs via shortest paths is highly motivated, leading to the following problem variant: given a graph and a collection of source–target vertex pairs, assign directions to the edges so as to maximize the number of pairs that are connected by a shortest (in the original graph) directed path. This problem is NP-complete and hard to approximate to within sub-polynomial factors. Here we provide a first polynomial-size integer linear program formulation for this problem, which allows its exact solution in seconds on current networks. We apply our algorithm to orient protein–protein interaction networks in yeast and compare it with two state-of-the-art algorithms. We find that our algorithm outperforms previous approaches and can orient considerable parts of the network, thus revealing its structure and function.

Availability and implementation: The source code is available at www.cs.tau.ac.il/∼roded/shortest.zip.

Contact:  roded@post.tau.ac.il
PGP: parallel prokaryotic proteogenomics pipeline for MPI clusters, high-throughput batch clusters and multicore workstations
Authors: Tovchigrechko Andrey , Venepally Pratap , Payne Samuel H.
Published: January 2014

Summary: We present the first public release of our proteogenomic annotation pipeline. We have previously used our original unreleased implementation to improve the annotation of 46 diverse prokaryotic genomes by discovering novel genes, post-translational modifications and correcting the erroneous annotations by analyzing proteomic mass-spectrometry data.

This public version has been redesigned to run in a wide range of parallel Linux computing environments and provided with the automated configuration, build and testing facilities for easy deployment and portability.

Availability and implementation: Source code is freely available from https://bitbucket.org/andreyto/proteogenomics under GPL license. It is implemented in Python and C++. It bundles the Makeflow engine to execute the workflows.

Contact:  atovtchi@jcvi.org
Trypanosome MKT1 and the RNA-binding protein ZC3H11: interactions and potential roles in post-transcriptional regulatory networks
Authors: Singh Aditi , Minia Igor , Droll Dorothea , Fadda Abeer , Clayton Christine , Erben Esteban
Published: January 2014

The trypanosome zinc finger protein ZC3H11 binds to AU-rich elements in mRNAs. It is essential for survival of the mammalian-infective bloodstream form, where it stabilizes several mRNAs including some encoding chaperones, and is also required for stabilization of chaperone mRNAs during the heat-shock response in the vector-infective procyclic form. When ZC3H11 was artificially ‘tethered’ to a reporter mRNA in bloodstream forms it increased reporter expression. We here show that ZC3H11 interacts with trypanosome MKT1 and PBP1, and that domains required for both interactions are necessary for function in the bloodstream-form tethering assay. PBP1 interacts with MKT1, LSM12 and poly(A) binding protein, and localizes to granules during parasite starvation. All of these proteins are essential for bloodstream-form trypanosome survival and increase gene expression in the tethering assay. MKT1 is cytosolic and polysome associated. Using a yeast two-hybrid screen and tandem affinity purification we found that trypanosome MKT1 interacts with multiple RNA-binding proteins and other potential RNA regulators, placing it at the centre of a post-transcriptional regulatory network. A consensus interaction sequence, H(E/D/N/Q)PY, was identified. Recruitment of MKT1-containing regulatory complexes to mRNAs via sequence-specific mRNA-binding proteins could thus control several different post-transcriptional regulons.
The influence of CpG and UpA dinucleotide frequencies on RNA virus replication and characterization of the innate cellular pathways underlying virus attenuation and enhanced replication
Authors: Atkinson Nicky J. , Witteveldt Jeroen , Evans David J. , Simmonds Peter
Published: January 2014

Most RNA viruses infecting mammals and other vertebrates show profound suppression of CpG and UpA dinucleotide frequencies. To investigate this functionally, mutants of the picornavirus, echovirus 7 (E7), were constructed with altered CpG and UpA compositions in two 1.1–1.3 Kbase regions. Those with increased frequencies of CpG and UpA showed impaired replication kinetics and higher RNA/infectivity ratios compared with wild-type virus. Remarkably, mutants with CpGs and UpAs removed showed enhanced replication, larger plaques and rapidly outcompeted wild-type virus on co-infections. Luciferase-expressing E7 sub-genomic replicons with CpGs and UpAs removed from the reporter gene showed 100-fold greater luminescence. E7 and mutants were equivalently sensitive to exogenously added interferon-β, showed no evidence for differential recognition by ADAR1 or pattern recognition receptors RIG-I, MDA5 or PKR. However, kinase inhibitors roscovitine and C16 partially or entirely reversed the attenuated phenotype of high CpG and UpA mutants, potentially through inhibition of currently uncharacterized pattern recognition receptors that respond to RNA composition. Generating viruses with enhanced replication kinetics has applications in vaccine production and reporter gene construction. More fundamentally, the findings introduce a new evolutionary paradigm where dinucleotide composition of viral genomes is subjected to selection pressures independently of coding capacity and profoundly influences host–pathogen interactions.
A phase demodulation method for two-dimensional grating-based X-ray interferometry
Authors: Nagai Kentaro
Published: January 2014

This paper presents a novel approach to achieving high spatial resolution in the demodulation of images produced by a two-dimensional X-ray Talbot interferometry (XTI) system. Currently, demodulation of XTI images is mainly performed by either phase-stepping (PS) or Fourier transform (FT) methods. However, the PS method for two-dimensional XTI demodulation requires a larger number of exposures and a more complex grating control process than that of one-dimensional XTI. On the other hand, although the FT method uses only a single-fringe image, it gives lower spatial resolution than the PS method. For practical application of two-dimensional XTI, a simpler exposure process with high spatial resolution is required. In this paper, we introduce a hybrid method combining the PS and FT methods. This method simplifies the exposure process in comparison with the PS method required in two-dimensional XTI while achieving higher spatial resolution than the FT method in the demodulation of images. The method works by using additional exposures to eliminate unnecessary spectral components that appear in the FT method. Furthermore, the proposed method is demonstrated by using actual two-dimensional XTI data and shown to achieve high spatial resolution in the demodulation of images for both the
x
- and
y
-differential phase components.
Synchrotron- and laboratory-based X-ray phase-contrast imaging for imaging mouse articular cartilage in the absence of radiopaque contrast agents
Authors: Marenzana Massimo , Hagen Charlotte K. , Borges Patricia Das Neves , Endrizzi Marco , Szafraniec Magdalena B. , Vincent Tonia L. , Rigon Luigi , Arfelli Fulvia , Menk Ralf-Hendrik , Olivo Alessandro
Published: January 2014

The mouse model of osteoarthritis (OA) has been recognized as the most promising research tool for the identification of new OA therapeutic targets. However, this model is currently limited by poor throughput, dependent on the extremely time-consuming histopathology assessment of the articular cartilage (AC). We have recently shown that AC in the rat tibia can be imaged both in air and in saline solution using a laboratory system based on coded-aperture X-ray phase-contrast imaging (CAXPCi). Here, we explore ways to extend the methodology for imaging the much thinner AC of the mouse, by means of gold-standard synchrotron-based phase-contrast methods. Specifically, we have used analyser-based phase-contrast micro-computed tomography (micro-CT) for its high sensitivity to faint phase changes, coupled with a high-resolution (4.5 μm pixel) detector. Healthy, diseased (four weeks post induction of OA) and artificially damaged mouse AC was imaged at the Elettra synchrotron in Trieste, Italy, using the above method. For validation, we used conventional micro-CT combined with radiopaque soft-tissue staining and standard histomorphometry. We show that mouse cartilage can be visualized correctly by means of the synchrotron method. This suggests that: (i) further developments of the laboratory-based CAXPCi system, especially in terms of pushing the resolution limits, might have the potential to resolve mouse AC
ex vivo
and (ii) additional improvements may lead to a new generation of CAXPCi micro-CT scanners which could be used for
in vivo
longitudinal pre-clinical imaging of soft tissue at resolutions impossible to achieve by current MRI technology.
‘Taking X-ray phase contrast imaging into mainstream applications’ and its satellite workshop ‘Real and reciprocal space X-ray imaging’
Authors: Olivo Alessandro , Robinson Ian
Published: January 2014

A double event, supported as part of the Royal Society scientific meetings, was organized in February 2013 in London and at Chicheley Hall in Buckinghamshire by Dr A. Olivo and Prof. I. Robinson. The theme that joined the two events was the use of X-ray phase in novel imaging approaches, as opposed to conventional methods based on X-ray attenuation. The event in London, led by Olivo, addressed the main roadblocks that X-ray phase contrast imaging (XPCI) is encountering in terms of commercial translation, for clinical and industrial applications. The main driver behind this is the development of new approaches that enable XPCI, traditionally a synchrotron method, to be performed with conventional laboratory sources, thus opening the way to its deployment in clinics and industrial settings. The satellite meeting at Chicheley Hall, led by Robinson, focused on the new scientific developments that have recently emerged at specialized facilities such as third-generation synchrotrons and free-electron lasers, which enable the direct measurement of the phase shift induced by a sample from intensity measurements, typically in the far field. The two events were therefore highly complementary, in terms of covering both the more applied/translational and the blue-sky aspects of the use of phase in X-ray research. optics, image processing
Burkholderia dolosa phenotypic variation during the decline in lung function of a cystic fibrosis patient during 5.5 years of chronic colonization
Authors: Moreira Ana Sílvia , Coutinho Carla P. , Azevedo Pilar , Lito Luís , Melo-Cristino José , Sá-Correia Isabel
Published: January 2014

Although rarely isolated from cystic fibrosis (CF) patients, Burkholderia dolosa is associated with accelerated lung function decline. During 18 years of epidemiological surveillance in the major Portuguese CF centre in Lisbon, only one patient was infected with B. dolosa. Pulmonary deterioration, associated with the evolution of forced expiratory volume in 1 s, occurred during 5.5 years of colonization with this B. dolosa clone (with the new sequence type ST-668). Transient co-colonization with Burkholderia cenocepacia and other bacterial and fungal pathogens occurred, but B. dolosa prevailed until the patient’s death. The systematic assessment of relevant phenotypes for the sequential clonal isolates examined in this retrospective study (14 of B. dolosa and four of B. cenocepacia) showed that they were variants, although in general no isolation time-dependent pattern of alteration was identified. However, the first B. dolosa isolate retrieved was more susceptible to gentamicin, imipenem and tobramycin, and exhibited a higher swarming motility compared with most of the isolates obtained during the later stages of disease progression and antimicrobial therapy.
Golgi- and Trans-Golgi Network-Mediated Vesicle Trafficking Is Required for Wax Secretion from Epidermal Cells
Authors: McFarlane Heather E. , Watanabe Yoichiro , Yang Weili , Huang Yan , Ohlrogge John , Samuels A. Lacey
Published: January 2014

Lipid secretion from epidermal cells to the plant surface is essential to create the protective plant cuticle. Cuticular waxes are unusual secretory products, consisting of a variety of highly hydrophobic compounds including saturated very-long-chain alkanes, ketones, and alcohols. These compounds are synthesized in the endoplasmic reticulum (ER) but must be trafficked to the plasma membrane for export by ATP-binding cassette transporters. To test the hypothesis that wax components are trafficked via the endomembrane system and packaged in Golgi-derived secretory vesicles, Arabidopsis (Arabidopsis thaliana) stem wax secretion was assayed in a series of vesicle-trafficking mutants, including gnom like1-1 (gnl1-1), transport particle protein subunit120-4, and echidna (ech). Wax secretion was dependent upon GNL1 and ECH. Independent of secretion phenotypes, mutants with altered ER morphology also had decreased wax biosynthesis phenotypes, implying that the biosynthetic capacity of the ER is closely related to its structure. These results provide genetic evidence that wax export requires GNL1- and ECH-dependent endomembrane vesicle trafficking to deliver cargo to plasma membrane-localized ATP-binding cassette transporters.
Structural basis for DNA recognition and nuclease processing by the Mre11 homologue SbcD in double-strand breaks repair
Authors: Liu Shun , Tian Li-fei , Liu Yan-ping , An Xiao-min , Tang Qun , Yan Xiao-xue , Liang Dong-cai
Published: January 2014

The Mre11 complex comprising meiotic recombination 11 (Mre11), Rad50 and Nijmegen breakage syndrome 1 (Nbs1) plays multiple important roles in the sensing, processing and repair of DNA double-strand breaks (DSBs). Here, crystal structures of theEscherichia coliMre11 homologue SbcD and its Mn2+complex are reported. Dimerization of SbcD depends on a four-helix bundle consisting of helices α2, α3, α2′ and α3′ of the two monomers, and the irregular and bent conformation of helices α3 and α3′ in the SbcD dimer results in a dimeric arrangement that differs from those of previously reported Mre11 dimers. This finding indicates a distinct selectivity in DNA substrate recognition. The biochemical data combined with the crystal structures revealed that the SbcD monomer exhibits single-stranded DNA (ssDNA) endonuclease activity and double-stranded DNA (dsDNA) exonuclease activity on the addition of a high concentration of Mn2+. For the first time, atomic force microscopy analysis has been used to demonstrate that the SbcD monomer also possesses Mn2+-dependent dsDNA endonuclease activity. Loop β7–α6 of SbcD is likely to be a molecular switch and plays an important role in the regulation of substrate binding, catalytic reaction and state transitions. Based on structural and mutational analyses, a novel ssDNA-binding model of SbcD is proposed, providing insight into the catalytic mechanism of DSBs repair by the Mre11 complex.
The family-wide structure and function of human dual-specificity protein phosphatases
Authors: Jeong Dae Gwin , Wei Chun Hua , Ku Bonsu , Jeon Tae Jin , Chien Pham Ngoc , Kim Jae Kwan , Park So Ya , Hwang Hyun Sook , Ryu Sun Young , Park Hwangseo , Kim Deok-Soo , Kim Seung Jun , Ryu Seong Eon
Published: January 2014

Dual-specificity protein phosphatases (DUSPs), which dephosphorylate both phosphoserine/threonine and phosphotyrosine, play vital roles in immune activation, brain function and cell-growth signalling. A family-wide structural library of human DUSPs was constructed based on experimental structure determination supplemented with homology modelling. The catalytic domain of each individual DUSP has characteristic features in the active site and in surface-charge distribution, indicating substrate-interaction specificity. The active-site loop-to-strand switch occurs in a subtype-specific manner, indicating that the switch process is necessary for characteristic substrate interactions in the corresponding DUSPs. A comprehensive analysis of the activity–inhibition profile and active-site geometry of DUSPs revealed a novel role of the active-pocket structure in the substrate specificity of DUSPs. A structure-based analysis of redox responses indicated that the additional cysteine residues are important for the protection of enzyme activity. The family-wide structures of DUSPs form a basis for the understanding of phosphorylation-mediated signal transduction and the development of therapeutics.
Structure of the N-terminal domain of the effector protein LegC3 fromLegionella pneumophila
Authors: Yao Deqiang , Cherney Maia , Cygler Miroslaw
Published: January 2014

Legionella pneumophilasecretes over 300 effectors during the invasion of human cells. The functions of only a small number of them have been identified. LegC3 is one of the identified effectors, which is believed to act by inhibiting vacuolar fusion. It contains two predicted transmembrane helices that divide the protein into a larger N-terminal domain and a smaller C-terminal domain. The function of LegC3 has been shown to be associated primarily with the N-terminal domain, which contains coiled-coil sequence motifs. The structure of the N-terminal domain has been determined and it is shown that it is highly α-helical and contains a helical bundle followed by a long antiparallel coiled-coil. No similar protein fold has been observed in the PDB. A long loop at the tip of the coiled-coil distal from the membrane is disordered and may be important for interaction with an as yet unidentified protein.
Identification of the first small-molecule ligand of the neuronal receptor sortilin and structure determination of the receptor–ligand complex
Authors: Andersen Jacob Lauwring , Schrøder Tenna Juul , Christensen Søren , Strandbygård Dorthe , Pallesen Lone Tjener , García-Alai Maria Marta , Lindberg Samsa , Langgård Morten , Eskildsen Jørgen Calí , David Laurent , Tagmose Lena , Simonsen Klaus Baek , Maltas Philip James , Rønn Lars Christian Biilmann , de Jong Inge E. M. , Malik Ibrahim John , Egebjerg Jan , Karlsson Jens-Jacob , Uppalanchi Srinivas , Sakumudi Durga Rao , Eradi Pradheep , Watson Steven P. , Thirup Søren
Published: January 2014

Sortilin is a type I membrane glycoprotein belonging to the vacuolar protein sorting 10 protein (Vps10p) family of sorting receptors and is most abundantly expressed in the central nervous system. Sortilin has emerged as a key player in the regulation of neuronal viability and has been implicated as a possible therapeutic target in a range of disorders. Here, the identification of AF40431, the first reported small-molecule ligand of sortilin, is reported. Crystals of the sortilin–AF40431 complex were obtained by co-crystallization and the structure of the complex was solved to 2.7 Å resolution. AF40431 is bound in the neurotensin-binding site of sortilin, with the leucine moiety of AF40431 mimicking the binding mode of the C-terminal leucine of neurotensin and the 4-methylumbelliferone moiety of AF40431 forming π-stacking with a phenylalanine.
Structure of an unusualS-adenosylmethionine synthetase fromCampylobacter jejuni
Authors: Zano Stephen P. , Pavlovsky Alexander G. , Viola Ronald E.
Published: January 2014

S-Adenosylmethionine (AdoMet) participates in a wide range of methylation and other group-transfer reactions and also serves as the precursor for two groups of quorum-sensing molecules that function as regulators of the production of virulence factors in Gram-negative bacteria. The synthesis of AdoMet is catalyzed by AdoMet synthetases (MATs), a ubiquitous family of enzymes found in species ranging from microorganisms to mammals. The AdoMet synthetase from the bacteriumCampylobacter jejuni(cjMAT) is an outlier among this homologous enzyme family, with lower sequence identity, numerous insertions and substitutions, and higher catalytic activity compared with other bacterial MATs. Alterations in the structure of this enzyme provide an explanation for its unusual dimeric quaternary structure relative to the other MATs. Taken together with several active-site substitutions, this new structure provides insights into its improved kinetic properties with alternative substrates.
1-Azaniumylcyclobutane-1-carboxylate monohydrate
Authors: Butcher Ray J. , Brewer Greg , Burton Aaron S. , Dworkin Jason P.
Published: January 2014

In the title compound, C5H9NO2·H2O, the amino acid is in the usual zwitterionic form involving the α-carboxylate group. The cyclobutane backbone of the amino acid is disordered over two conformations, with occupancies of 0.882 (7) and 0.118 (7). In the crystal, N—H...O and O—H...O hydrogen bonds link the zwitterions [with the water molecule involved as both acceptor (with the NH3+) and donor (through a single carboxylate O from two different aminocyclobutane carboxylate moities)], resulting in a two-dimensional layered structure lying parallel to (100).
Methyl 4-(4-bromoanilino)-2′,5-dioxo-5H-spiro[furan-2,3′-indoline]-3-carboxylate
Authors: Gangadharan Rajeswari , Kiruthika Selvarangam E. , Sethusankar K. , Perumal P. T.
Published: January 2014

In the title compound, C19H13BrN2O5, the spiro furan ring is almost planar with a maximum deviation of 0.034 (2) Å. The indole unit and the furan ring are normal to each other, making a dihedral angle of 87.82 (8) °. The molecular structure is stabilized by an intramolecular N—H...O hydrogen bond, which generates anS(6) ring motif. In the crystal, molecules are linkedviapairs of N—H...O hydrogen bonds, forming inversion dimers enclosingR22(8) ring motifs.
2-(4,5-Dichloro-2-nitrophenyl)-4-methoxy-3-methyl-9-phenylsulfonyl-9H-carbazole
Authors: Narayanan P. , Sethusankar K. , Saravanan Velu , Mohanakrishnan Arasambattu K.
Published: January 2014

In the title compound, C26H18Cl2N2O5S, the carbazole ring system is essentially planar with a maximum deviation of 0.0498 (16) Å for the N atom. The carbazole ring system is almost orthogonal to the phenylsulfonyl and dichloro-substituted nitrophenyl rings, making dihedral angles of 84.23 (7) and 85.46 (12)°, respectively. The molecular structure features intramolecular C—H...O interactions, which generate twoS(6) ring motifs. In the crystal, molecules are linked by C—Cl...O halogen bonds [3.016 (3) Å, 166.63 (5)°], which generate infiniteC(8) chains running parallel to [010].
1-[2-(Dimethylazaniumyl)ethyl]-1H-1,2,3,4-tetrazole-5-thiolate
Authors: Tagore Sadasivam Sharmila , Krishna Sivaraman , Gomathi Sundaramoorthy , Sethuraman Velusamy
Published: January 2014

In the crystal structure of the title zwitterion, C5H11N5S, molecules are linkedviaN—H...N hydrogen bonds, forming zigzag chains propagating along [010]. The chains are linked by C—H...S hydrogen bonds, forming two dimensional networks lying parallel to (001).
5-Amino-1H-pyrazol-2-ium hydrogen succinate
Authors: Yamuna Thammarse S. , Kaur Manpreet , Anderson Brian J. , Jasinski Jerry P. , Yathirajan H. S.
Published: January 2014

In the cation of the title salt, C3H6N3+·C4H5O4−, the protonated pyrazolium ring is planar (r.m.s. deviation = 0.012 Å). An intramolecular C—H...O hydrogen bond occurs in the anion. In the crystal, N—H...O hydrogen bonds and a weak C—H...O interaction between the cations and anions form two sets ofR22(8) graph-set ring motifs. Intermolecular O—H...O hydrogen bonds between these lead to a criss-cross pattern along thebaxis. In addition to the classical hydrogen bonds, a weak C—H...π(pyrazolium) interaction is observed and contributes to crystal packing. All of these interactions link the molecules into a two-dimensional supramolecular framework parallel to (10-1).
N1,N2-Dimethylethane-1,2-diaminium dichloride
Authors: Merola Joseph S.
Published: January 2014

The cation of the title salt, C4H14N22+·2Cl−, is located on a crystallographic inversion center and is bisected by a mirror plane, with one quarter of the C4H14N22+·2Cl−formula unit being crystallographically unique. he chloride ions also sit on a mirror plane. The conformation of the cation is a regular straight-chain conformation with all non-H atoms inantipositions. In the crystal, hydrogen bonding between N—H groups and chloride anions yields a zigzag ladder-type structure along [010].
catena-Poly[[(N,N-dimethylcyanamide-κN)lithium]-μ3-bromido]
Authors: Xie Qianwen , Tong Hongbo , Zhou Meisu
Published: January 2014

The title complex, [LiBr(C3H6N2)]n, is the unexpected product of a reaction beteween (Dipp)N(Li)SiMe3(Dipp = 2,6-diisopropylphenyl), Me2NCN and CuBr. The compound is a one-dimensional polymer with a step structure derived from the association of inversion dimers, formed by bromido ligands bridging two Li+cations, each of which carries a dimethylcyanamide ligand. The planar (LiBr)2unit of the polymer core has a regular rhombic shape [Li—Br—Li 77.55 (16)° and Br—Li—Br 102.45 (16)°]. These (LiBr·NCNMe2)2dimers represent the repeat unit of a polymer system propagated by additional Br—Li and Li—Br bonds generating an infinite step structure along thea-axis direction.
Tris(2,6-dibenzoyl-4-methylphenolato-κ2O1,O2)cobalt(III)
Authors: Gupta Abhishek K. , Srivastava Sanjay , Butcher Ray J.
Published: January 2014

In the title compound, [Co(C21H15O3)3], the CoIIIion is coordinated in a slightly distorted octahedral environment by three phenolate O and three benzoyl O atoms from three monoanionic bidentate 2,6-dibenzoyl-4-methylphenolate ligands. The dihedral angles between the mean planes of the central phenolate rings and the peripheral phenyl rings are 46.62 (10)/87.06 (9), 60.44 (8)/23.13 (8) and 46.49 (6)/65.29 (6)°. The crystal packing is stabilized by weak intermolecular C—H...O interactions. Molecules are further linked by two π–π [centroid–centroid distances = 3.8612 (14) and 3.9479 (14) Å] and four C—H...π interactions, forming a three-dimensional network.
1-[(E)-2-(5-tert-Butyl-2-hydroxyphenyl)diazen-1-yl]naphthalen-2-ol
Authors: Bougueria Hassiba , Mili Assia , Benosmane Ali , Bouchoul Abd el kader , Bouaoud Salaheddine
Published: January 2014

The non-H atoms of the title compound, C20H20N2O2, is located on a mirror plane except two methyl groups of thetert-butyl group. Intramolecular N—H...O hydrogen bonds exist between the hydroxy and diazenyl groups. In the crystal, molecules are linked by weak C—H...O hydrogen bonds into supramolecular chains running along thea-axis direction.
Inhibition of soluble epoxide hydrolase is renoprotective in 5/6 nephrectomized Ren‐2 transgenic hypertensive rats
Authors: Kujal Petr , Čertíková Chábová Vera , Škaroupková Petra , Husková Zuzana , Vernerová Zdena , Kramer Herbert J , Walkowska Agnieszka , Kompanowska‐Jezierska Elzbieta , Sadowski Janusz , Kitada Kento , Nishiyama Akira , Hwang Sung H , Hammock Bruce D , Imig John D , Červenka Ludek
Published: January 2014

The aim of the present study was to test the hypothesis that increasing kidney tissue concentrations of epoxyeicosatrienoic acids (EETs) by preventing their degradation to the biologically inactive dihydroxyeicosatrienoic acids (DHETEs) using blockade of soluble epoxide hydrolase (sEH) would attenuate the progression of chronic kidney disease (CKD).

Ren‐2 transgenic rats (TGR) after 5/6 renal mass reduction (5/6 NX) served as a model of CKD associated with angiotensin (Ang) II‐dependent hypertension. Soluble epoxide hydrolase was inhibited using cis‐4‐[4‐(3‐adamantan‐1‐yl‐ureido)cyclohexyloxy]benzoic acid (c‐AUCB; 3 mg/L drinking water) for 20 weeks after 5/6 NX. Sham‐operated normotensive transgene‐negative Hannover Sprague‐Dawley (HanSD) rats served as controls.

When applied in TGR subjected to 5/6 NX, c‐AUCB treatment improved survival rate, prevented the increase in blood pressure, retarded the progression of cardiac hypertrophy, reduced proteinuria and the degree of glomerular and tubulointerstitial injury and reduced glomerular volume. All these organ‐protective actions were associated with normalization of the intrarenal EETs : DHETEs ratio, an index of the availability of biologically active EETs, to levels observed in sham‐operated HanSD rats. There were no significant concurrent changes of increased intrarenal AngII content.

Together, these results show that 5/6 NX TGR exhibit a profound deficiency of intrarenal availability of active epoxygenase metabolites (EETs), which probably contributes to the progression of CKD in this model of AngII‐dependent hypertension, and that restoration of intrarenal availability of EETs using long‐term c‐AUCB treatment exhibits substantial renoprotective actions.
Resveratrol and vitamin E rescue valproic acid‐induced teratogenicity: The mechanism of action
Authors: Hsieh Chiu‐Lan , Chen Kuan‐Chou , Lin Ping‐Xiao , Peng Chiung‐Chi , Peng Robert Y
Published: January 2014

Valproic acid (VPA) induces haemorrhagic liposis of the cervical muscles in the chicken embryo model (CEM). Vitamin E and resveratrol (RV) exhibit prominent anti‐oxidative and glutathione (GSH)‐protecting effects.

In the present study we hypothesized that vitamin E and RV would ameliorate VPA induced haemorrhagic liposis in chick embryos. To this end, 120 Day 0 fertilized eggs were divided into 10 groups (n = 12 in each). The effects of different combinations of VPA (60 mmol/L), RV (0.2 and 2.0 mmol/L) and vitamin E (0.2 and 2.0 mmol/L) applied to Hamburger and Hamilton (HH) Stage 10 (Day 1.5) embryos were tested in the CEM using established methods.

Both RV and vitamin E (both at 2.0 mmol/L) effectively rescued neural tube defects in the early stage CEM and inhibited the malformation rate compared with that in the control group (8.4% and 5.0% vs 36.5 ± 3.0%, respectively; P < 0.05) and suppressed serum homocysteine and S‐adenosylhomocysteine concentrations, downregulated cervical muscular carnitine, triglycerides, H2O2, malondialdehyde, interleukin‐6 and ACC expression (P < 0.05 for all) and upregulated CPT1 expression and GSH (P < 0.05 for both).

The haemorrhagic liposis of cervical muscles can be alleviated by RV and vitamin E. It appears that the main mechanism of action of RV and vitamin E in rescuing VPA‐induced teratogenicity is through the suppression of reactive oxygen species and upregulation of GSH.
Endothelial and neuronal nitric oxide synthases variably modulate the oestrogen‐mediated control of blood pressure and cardiovascular autonomic control
Authors: El‐Mas Mahmoud M , Abdel‐Rahman Abdel A
Published: January 2014

We have shown previously that long‐term oestrogen (E2) replacement lowers blood pressure (BP) and improves cardiovascular autonomic control in ovariectomized (OVX) rats. In the present study, we investigated whether constitutive and/or inducible (i) nitric oxide synthase (NOS) modulate these E2 effects.

We evaluated changes in BP, myocardial contractility index (dP/dtmax) and power spectral indices of haemodynamic variability following selective inhibition of endothelial (e) NOS with N5‐(1‐iminoethyl)‐ l‐ornithine (l‐NIO), neuronal (n) NOS with Nω‐propyl‐l‐arginine (NPLA) or iNOS with 1400W in telemetered OVX rats treated for 16 weeks with (OVXE2) or without (control; OVXC) E2.

The OVXE2 rats exhibited: (i) reduced BP and increased dP/dtmax; (ii) cardiac parasympathetic dominance, as reflected by the reduced low‐frequency (LF; 0.25–0.75 Hz)/high‐frequency (HF; 0.75–3 Hz) ratio of interbeat intervals (IBILF/HF); and (iii) reduced LF oscillations of systolic BP, suggesting a reduced vasomotor sympathetic tone. Inhibition of eNOS (l‐NIO; 20 mg/kg, i.p.) elicited a shorter‐lived pressor response in OVXE2 than OVXC, rats along with reductions in dP/dtmax and increases in the spectral index of spontaneous baroreflex sensitivity (index α). Treatment with 1 mg/kg, i.p., NPLA reduced BP and increased the IBILF/HF ratio in OVXE2 but not OVXC rats. The iNOS inhibitor 1400W (5 mg/kg, i.p.) caused no haemodynamic changes in OVXC or OVXE2 rats.

Overall, constitutive NOS isoforms exert restraining tonic modulatory BP effects that encompass eNOS‐mediated reductions and nNOS‐mediated elevations in BP in OVXE2 rats. Baroreflex facilitation and dP/dtmax reductions may account for the shorter pressor action of l‐NIO in E2‐treated, compared with untreated, OVX rats.
Mathematical modelling of enteric neural motor patterns
Authors: Chambers Jordan D , Thomas Evan A , Bornstein Joel C
Published: January 2014

The enteric nervous system modulates intestinal behaviours, such as motor patterns and secretion. Although much is known about different types of neurons and simple reflexes in the intestine, it remains unclear how complex behaviours are generated.

Mathematical modelling is an important tool for assisting the understanding of how the neurons and reflexes can be pieced together to generate intestinal behaviours.

Models have identified a functional role for slow excitatory post‐synaptic potentials (EPSPs) by distinguishing between fast and slow EPSPs in the ascending excitation reflex. These models also discovered coordinated firing of similarly located neurons as emergent properties of feed‐forward networks of interneurons in the intestine. A model of the recurrent network of intrinsic sensory neurons identified important control mechanisms to prevent uncontrolled firing due to positive feedback and that the interaction between these control mechanisms and slow EPSPs is necessary for the networks to encode ongoing sensory stimuli. This model also showed that such networks may mediate migrating motor complexes.

A network model of vasoactive intestinal peptide neurons in the submucosal plexus found this relatively sparse recurrent network could produce uncontrolled firing under conditions that appear to be related to cholera toxin‐induced hypersecretion.

Abstract modelling of the intestinal fed‐state motor patterns has identified how stationary contractions can arise from a polarized network.

These models have also helped predict and/or explained pharmacological evidence for two rhythm generators and the requirement of feedback from contractions in the circular muscle.
Exogenous L‐arginine attenuates the effects of angiotensin II on renal hemodynamics and the pressure natriuresis–diuresis relationship
Authors: Das Satarupa , Mattson David L
Published: January 2014

Administration of exogenous L‐arginine (L‐Arg) attenuates angiotensin‐II (AngII)‐mediated hypertension and kidney disease in rats.

The present study assessed renal hemodynamics and pressure diuresis–natriuresis in anaesthetized rats infused with vehicle, AngII (20 ng/kg per min i.v.) or AngII + L‐Arg (300 μg/kg per min i.v.). Experiments in isolated aortic rings were carried out to assess L‐Arg effects on the vasculature.

Increasing renal perfusion pressure (RPP) from ˜100 to 140 mmHg resulted in a nine‐ to tenfold increase in urine flow and sodium excretion rate in control animals. In comparison, AngII infusion significantly reduced renal blood flow (RBF) and glomerular filtration rate (GFR) by 40–42%, and blunted the pressure‐dependent increase in urine flow and sodium excretion rate by 54–58% at elevated RPP. Supplementation of L‐Arg reversed the vasoconstrictor effects of AngII and restored pressure‐dependent diuresis to levels not significantly different from control rats.

Dose‐dependent contraction to AngII (10−10 mol/L to 10−7 mol/L) was observed with a maximal force equal to 27 ± 3% of the response to 10−5 mol/L phenylephrine. Contraction to 10−7 mol/L AngII was blunted by 75 ± 3% with 10−4 mol/L L‐Arg. The influence of L‐Arg to blunt AngII‐mediated contraction was eliminated by endothelial denudation or incubation with nitric oxide synthase inhibitors. Furthermore, the addition of 10−3 mol/L cationic or neutral amino acids, which compete with L‐Arg for cellular uptake, blocked the effect of L‐Arg. Anionic amino acids did not influence the effects of L‐Arg on AngII‐mediated contraction.

These studies show that L‐Arg blunts AngII‐mediated vascular contraction by an endothelial‐ and nitric oxide synthase‐dependent mechanism involving cellular uptake of L‐Arg.
An anthropologist among the film‐makers: A cautionary tale: Part 2. The politics of circulation (Respond to this article at http://www.therai.org.uk/at/debate)
Authors: Caplan Pat
Published: January 2014

In this second part, Pat Caplan continues her account of the production of one episode in the Face values ethnographic film series, an early example of the efforts the Royal Anthropological Institute made to popularize anthropology under royal patronage in the 1970s. Part one, as published in the previous issue, sought to cover the aims of the series, and in this second part she considers the extent to which the original aims were realized.
Confucius institutes (Respond to this article at http://www.therai.org.uk/at/debate)
Authors: Sahlins Marshall , Turk James L.
Published: January 2014

Many hundreds Confucius Institutes have mushroomed in higher education centres all over the world. In this comment, Marshall Sahlins continues his analysis of troublesome aspects of these institutions and considers what anthropologists have come up with in terms of research on these so far. He also touches on the Canadian campaign for university teachers to boycott these.

James Turk commends Marshall Sahlins for looking into the issue of academic freedom in relation to Confucius Institutes. This is part of a campaign by the Canadian Association of University Teachers to secure academic freedom where universities enter into collaboration with third parties.
What do popular Spanish women's magazines say about caesarean section? A 21‐year survey
Authors: Torloni MR , Campos Mansilla B , Merialdi M , Betrán AP
Published: January 2014

Objectives

Caesarean section (CS) rates are increasing worldwide and maternal request is cited as one of the main reasons for this trend. Women's preferences for route of delivery are influenced by popular media, including magazines. We assessed the information on CS presented in Spanish women's magazines.

Design

Systematic review.

Setting

Women's magazines printed from 1989 to 2009 with the largest national distribution.

Sample

Articles with any information on CS.

Methods

Articles were selected, read and abstracted in duplicate. Sources of information, scientific accuracy, comprehensiveness and women's testimonials were objectively extracted using a content analysis form designed for this study.

Main outcome measures

Accuracy, comprehensiveness and sources of information.

Results

Most (67%) of the 1223 selected articles presented exclusively personal opinion/birth stories, 12% reported the potential benefits of CS, 26% mentioned the short‐term and 10% mentioned the long‐term maternal risks, and 6% highlighted the perinatal risks of CS. The most frequent short‐term risks were the increased time for maternal recovery (n = 86), frustration/feelings of failure (n = 83) and increased post‐surgical pain (n = 71). The most frequently cited long‐term risks were uterine rupture (n = 57) and the need for another CS in any subsequent pregnancy (n = 42). Less than 5% of the selected articles reported that CS could increase the risks of infection (n = 53), haemorrhage (n = 31) or placenta praevia/accreta in future pregnancies (n = 6). The sources of information were not reported by 68% of the articles.

Conclusions

The portrayal of CS in Spanish women's magazines is not sufficiently comprehensive and does not provide adequate important information to help the readership to understand the real benefits and risks of this route of delivery.
In Vitro Anti‐Inflammatory Activity of Selected Oxalate‐Degrading Probiotic Bacteria: Potential Applications in the Prevention and Treatment of Hyperoxaluria
Authors: Giardina Silvana , Scilironi Cristina , Michelotti Angela , Samuele Alberta , Borella Fabio , Daglia Maria , Marzatico Fulvio
Published: January 2014

Oxalate (Ox) is a very common component of the human diet, capable to collect in the renal tissue and bind calcium to form calcium oxalate (CaOx) crystals. A supersaturation of CaOx crystal may cause nephrocalcinosis and nephrolithiasis. The inflammation derived from the CaOx crystal accumulation, together with innate or secondary renal alterations, could strongly affect the renal function. In this case a consumption of probiotics with either oxalate‐degrading activity at intestinal level and systemic anti‐inflammatory activity could be an alternative approach to treat the subjects with excess of urinary oxalate excretion. 11 strains of lactic acid bacteria (Lactobacilli and Bifidobacteria), already included in the list of bacteria safe for the human use, were investigated for their capability to degrade oxalate by mean of RP‐HPLC‐UV method and modulate inflammation in an in vitro model system based on peripheral blood mononuclear cells. Four promising bacterial strains (Lactobacillus plantarum PBS067, Lactobacillus acidophilus LA‐14, Bifidobacterium breve PBS077, Bifidobacterium longum PBS078) were identified as innovative biological tools for the prevention and the therapeutic treatment of hyperoxaluria and the inflammatory events associated to the Ox accumulation.

Practical Application

The oxalate‐degrading activity of some probiotics and their capability to modulate the release of inflammation mediators could be exploited as a new nutraceutical and therapeutic approach for the treatment of oxalate accumulation and the related inflammatory state.
Initiation of the flexirubin biosynthesis in Chitinophaga pinensis
Authors: Schöner Tim A. , Fuchs Sebastian W. , Schönau Christian , Bode Helge B.
Published: January 2014

Bacteria from the Bacteroidetes phylum are known producers of the chemotaxonomic relevant flexirubins. These orange pigments comprise a non‐isoprenoid aryl‐polyene carboxylic acid esterified with a dialkylresorcinol. Herein, we report a gene cluster from Chitinophaga pinensis encoding the biosynthesis of the polyene moiety and the biochemical characterization of a tyrosine ammonia‐lyase and a 4‐coumarate‐CoA ligase responsible for the initiation of the polyene biosynthesis. Additionally, the flexirubin of C. pinensis was characterized by a combination of feeding experiments, high‐performance liquid chromatography tandem mass spectrometry and matrix‐assisted laser desorption/ionization mass spectrometry.
Association between urinary adiponectin level and renal involvement in systemic lupus erythematous
Authors: Loghman Maryam , Haghighi Anousheh , Broumand Behrooz , Ataipour Yousef , Tohidi Maryam , Marzbani Caroline , Fakharran Mehdi
Published: January 2014

Aim

To assess association between urinary levels of adiponectin and severity of renal involvement in SLE patients. Also, this study aims to determine the value of urinary adiponectin levels to discriminate renal involvement in these patients.

Methods

In a multi‐center cross‐sectional survey, 50 consecutive patients diagnosed as having systemic lupus erythematosus (SLE) according to American College of Rheumatology criteria were classified into two groups with or without renal involvement (microscopic hematuria, reduced glomerular filtration rate < 25% of normal value, and proteinuria > 500 mg/24 h) which was confirmed by renal biopsy. Urinary adiponectin was measured by enzyme‐linked immunosorbent assay. SLE disease activity levels were assessed by SLE Disease Activity Index (SLEDAI) score.

Results

Comparing urinary levels of adiponectin between the two groups indicated considerable discrepancy in this index between the groups with and without renal involvement (146.33 ± 258.83 ng/mL vs. 22.96 ± 44.33 ng/mL, P = 0.023). Also, urinary adiponectin/creatinine ratio was significantly higher in the former group (221.72 ± 414.58 vs. 19.99 ± 41.19, P = 0.019). Our study showed a higher mean SLEDAI score in those with renal involvement than others (23.60 ± 2.53 vs. 9.12 ± 3.03, P < 0.001). Multivariable linear regression analysis with the presence of potential confounders showed that the level of urinary adiponectin was significantly higher in those with renal involvement than other patients (β = 0.470, P = 0.023). The optimal cut‐off point for urinary adiponectin levels to discriminate renal involvement from normal renal state was 7.5 ng/mL, yielding a sensitivity of 80% and specificity of 52%.

Conclusion

Urinary levels of adiponectin are significantly elevated in SLE patients with renal involvement. The measurement of this biomarker can be helpful to discriminate impaired from normal renal function in SLE patients.
Symbiont‐driven sulfur crystal formation in a thiotrophic symbiosis from deep‐sea hydrocarbon seeps
Authors: Eichinger Irmgard , Schmitz‐Esser Stephan , Schmid Markus , Fisher Charles R. , Bright Monika
Published: January 2014

The siboglinid tubewormSclerolinum contortumsymbiosis inhabits sulfidic sediments at deep‐sea hydrocarbon seeps in theGulf ofMexico. A single symbiont phylotype in the symbiont‐housing organ is inferred from phylogenetic analyses of the 16Sribosomal ribonucleic acid (16S rRNA) gene and fluorescent in situ hybridization. The phylotype we studied here, and a previous study from an arctic hydrocarbon seep population, reveal identical 16S rRNAsymbiont gene sequences. While sulfide is apparently the energy source for the symbionts (and ultimately the gutless host), both partners also have to cope with its toxicity. This study demonstrates abundant large sulfur crystals restricted to the trophosome area. Based onRaman microspectroscopy and energy dispersiveX‐ray analysis, these crystals have the sameS8 sulfur configuration as the recently described small sulfur vesicles formed in the symbionts. The crystals reside adjacent to the symbionts in the trophosome. This suggests that their formation is either extra‐ or intracellular in symbionts. We propose that formation of these crystals provides both energy‐storage compounds for the symbionts and serves the symbiosis by removing excess toxic sulfide from host tissues. This symbiont‐mediated sulfide detoxification may have been crucial for the establishment of thiotrophic symbiosis and continues to remain an important function of the symbionts.
Vascular endothelial growth factor C is an indicator of lymph node metastasis in thoracic esophageal squamous cell carcinomas and its role in long‐term survival after surgery
Authors: Pan Xufeng , Mao Teng , Fang Wentao , Chen Wenhu
Published: January 2014

Background

To define the role of vascular endothelial growth factor C (VEGF‐C) on lymph node (LN) metastasis of human esophageal squamous cell carcinoma (ESCC), and to investigate its impact on overall survival.

Methods

Real‐time polymerase chain reaction was introduced to quantify the expression of VEGF‐CmRNA. One hundred and eight samples (59 tumor tissue and 59 paired normal tissue) were analyzed.

Results

VEGF‐CmRNA expression was significantly higher in tumor tissues than in normal mucosa (P = 0.02). VEGF‐CmRNA expression was significantly higher in LN (+) patients than in LN (‐) patients (P = 0.04). VEGF‐CmRNA expression was related to a positive LN number (P = 0.06) and a positive LN station number (P = 0.04). VEGF‐CmRNA expression was significantly higher in stage III and IV patients than in stage I and II patients (P = 0.03). A logistic regression model showed that VEGF‐CmRNA and T status were independent risk factors for LN metastasis(P < 0.05). In univariate analysis, survival tended to be poorer in the VEGF‐CmRNA high expression group (22.0 months vs. 44.0 months, P = 0.08). A Cox regression model revealed that a positive LN station number was the only independent risk factor for overall survival (P < 0.01).

Conclusion

VEGF‐C was a useful indicator for LN metastasis in human ESCC, and it might have some influence on long‐term survival by affecting LN metastasis.