bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of IGPR-1 as a novel adhesion molecule involved in angiogenesis
Authors: Rahimi Nader , Rezazadeh Kobra , Mahoney John E. , Hartsough Edward , Meyer Rosana D.
Published: March 2012

Angiogenesis—the growth of new blood vessels from preexisting vessels—is an important physiological process and is considered to play a key role in tumor growth and metastasis. We identified the immunoglobulin-containing and proline-rich receptor-1 (IGPR-1, also called TMIGD2) gene as a novel cell adhesion receptor that is expressed in various human organs and tissues, mainly in cells with epithelium and endothelium origins. IGPR-1 regulates cellular morphology, homophilic cell aggregation, and cell–cell interaction. IGPR-1 activity also modulates actin stress fiber formation and focal adhesion and reduces cell migration. Silencing of expression of IGPR-1 by small interfering RNA (siRNA) and by ectopic overexpression in endothelial cells showed that IGPR-1 regulates capillary tube formation in vitro, and B16F melanoma cells engineered to express IGPR-1 displayed extensive angiogenesis in the mouse Matrigel angiogenesis model. Moreover, IGPR-1, through its proline-rich cytoplasmic domain, associates with multiple Src homology 3 (SH3)–containing signaling proteins, including SH3 protein interacting with Nck (SPIN90/WISH), bullous pemphigoid antigen-1, and calcium channel β2. Silencing of expression of SPIN90/WISH by siRNA in endothelial cells showed that SPIN90/WISH is required for capillary tube formation. These features of IGPR-1 suggest that IGPR-1 is a novel receptor that plays an important role in cell–cell interaction, cell migration, and angiogenesis.
Perispeckles are major assembly sites for the exon junction core complex
Authors: Daguenet Elisabeth , Baguet Aurélie , Degot Sébastien , Schmidt Ute , Alpy Fabien , Wendling Corinne , Spiegelhalter Coralie , Kessler Pascal , Rio Marie-Christine , Le Hir Hervé , Bertrand Edouard , Tomasetto Catherine
Published: March 2012

The exon junction complex (EJC) is loaded onto mRNAs as a consequence of splicing and regulates multiple posttranscriptional events. MLN51, Magoh, Y14, and eIF4A3 form a highly stable EJC core, but where this tetrameric complex is assembled in the cell remains unclear. Here we show that EJC factors are enriched in domains that we term perispeckles and are visible as doughnuts around nuclear speckles. Fluorescence resonance energy transfer analyses and EJC assembly mutants show that perispeckles do not store free subunits, but instead are enriched for assembled cores. At the ultrastructural level, perispeckles are distinct from interchromatin granule clusters that may function as storage sites for splicing factors and intermingle with perichromatin fibrils, where nascent RNAs and active RNA Pol II are present. These results support a model in which perispeckles are major assembly sites for the tetrameric EJC core. This subnuclear territory thus represents an intermediate region important for mRNA maturation, between transcription sites and splicing factor reservoirs and assembly sites.
SAMSCOPE: an OpenGL-based real-time interactive scale-free SAM viewer
Authors: Popendorf Kris , Sakakibara Yasubumi
Published: March 2012

Summary: Existing SAM visualization tools like ‘samtools tview’ (Li et al., 2009) are limited to a small region of the genome, and tools like Tablet (Milne et al., 2010) are limited to a relatively small number of reads and may fail outright on large datasets. We need to visualize complex ChIP-Seq and RNA-Seq features such as polarity as well as coverage across whole 3 Gbp genomes such as Human. We have addressed these problems in a lightweight visualization system called SAMSCOPE accelerated by OpenGL. The extensive pre-processing and fast OpenGL interface of SAMSCOPE provides instantaneous and intuitive browsing of complex data at all levels of detail across multiple experiments.

Availability and implementation: The SAMSCOPE software, implemented in C++ for Linux, with source code, binary packages and documentation are freely available from http://samscope.dna.bio.keio.ac.jp.

Contact:  yasu@bio.keio.ac.jp
Thermal windows supporting survival of the earliest life stages of Baltic herring (Clupea harengus)
Authors: Peck Myron A. , Kanstinger Philipp , Holste Linda , Martin Meike
Published: March 2012

Peck, M. A., Kanstinger, P., Holste, L., and Martin, M. 2012. Thermal windows supporting survival of the earliest life stages of Baltic herring (Clupea harengus). – ICES Journal of Marine Science, 69: 529–536. Projecting climate-driven changes in marine systems will require knowledge on how thermal windows affect the vital rates of key species. To examine the potential, direct effect of climate-driven warming on southwest Baltic herring, we quantified the survival, development, and biochemical condition of embryos (eggs and yolk-sac larvae) at ten temperatures between 2.9 and 21.7°C. Viable hatch was highest from 7 to 13°C, <20% at 2.9°C and 0% at 21.7°C. Between 5 and 19°C, increasing temperature (T) decreased the time to 50% hatch (Ht, h,): Ht = 4461.9 × T − 1.24 (r2 = 0.98, p < 0.0001). Using degree-days [°d = T (°C) × age (d)] could normalize some (but not all) thermal effects. Most hatching occurred 90–120°d post-fertilization, unfed larvae lost 0.33 µg dry mass (DM) °d−1, larvae did not survive >160°d post-hatch. RNA–DNA ratios rapidly decreased between 50 and 80°d post-hatch, whereas DNA ×DM−1 increased throughout the yolk-sac phase and likely provides a stronger indicator of irreversible starvation. The critical, “mixed feeding” stage is likely 60–100°d post-hatch. The broad thermal tolerance of herring embryos makes “direct”, negative effects of warming unlikely; however, a lack of common methods among studies makes it difficult to project how climate warming will affect embryos of different fish populations and species.
Marsden's Book of Movement Disorders
Authors: Donaldson Ivan , Marsden C. David , Schneider Susanne , Bhatia Kailash
Published: March 2012

This book represents the final work of the late Professor C. David Marsden, and serves as the 'clinical Bible' for the management of movement disorders. Extensively illustrated with many original photographs and diagrams of historical significance that have not been published previously, it is an essential reference not just for movement disorder specialists and researchers, but also for clinicians who care for patients with these disorders.
Structure and function of FusB: an elongation factor G-binding fusidic acid resistance protein active in ribosomal translocation and recycling
Authors: Guo Xiaohu , Peisker Kristin , Bäckbro Kristina , Chen Yang , Koripella Ravi Kiran , Mandava Chandra Sekhar , Sanyal Suparna , Selmer Maria
Published: March 2012

Fusidic acid (FA) is a bacteriostatic antibiotic that locks elongation factor G (EF-G) to the ribosome after GTP hydrolysis during elongation and ribosome recycling. The plasmid pUB101-encoded protein FusB causes FA resistance in clinical isolates of
Staphylococcus aureus
through an interaction with EF-G. Here, we report 1.6 and 2.3 Å crystal structures of FusB. We show that FusB is a two-domain protein lacking homology to known structures, where the N-terminal domain is a four-helix bundle and the C-terminal domain has an alpha/beta fold containing a C4 treble clef zinc finger motif and two loop regions with conserved basic residues. Using hybrid constructs between
S. aureus
EF-G that binds to FusB and
Escherichia coli
EF-G that does not, we show that the sequence determinants for FusB recognition reside in domain IV and involve the C-terminal helix of
S. aureus
EF-G. Further, using kinetic assays in a reconstituted translation system, we demonstrate that FusB can rescue FA inhibition of tRNA translocation as well as ribosome recycling. We propose that FusB rescues
S. aureus
from FA inhibition by preventing formation or facilitating dissociation of the FA-locked EF-G–ribosome complex.
Analytical stability conditions for elastic composite materials with a non-positive-definite phase
Authors: Kochmann D. M. , Drugan W. J.
Published: March 2012

Elastic multi-phase materials with a phase having appropriately tuned non-positive-definite elastic moduli have been shown theoretically to permit extreme increases in multiple desirable material properties. Stability analyses of such composites were only recently initiated. Here, we provide a thorough stability analysis for general composites when one phase violates positive-definiteness. We first investigate the dynamic deformation modes leading to instability in the fundamental two-phase solids of a coated cylinder (two dimensions) and a coated sphere (three dimensions), from which we derive
closed-form analytical
sufficient stability conditions for the full range of coating thicknesses. Next, we apply the energy method to derive a general correlation between composite stability limit and composite bulk modulus that enables determination of
closed-form analytical
sufficient stability conditions for arbitrary multi-phase materials by employing effective modulus formulas coupled with a numerical finite-element stability analysis. We demonstrate and confirm this new approach by applying it to (i) the two basic two-phase solids already analysed dynamically; and (ii) a more geometrically complex matrix/distributed-inclusions composite. The specific new analytical stability results, and new methods presented, provide a basis for creation of novel, stable composite materials.
Genetic and phylogenetic characterization of genome segments 2 and 6 of bluetongue virus isolates in Japan from 1985 to 2008
Authors: Shirafuji Hiroaki , Yanase Tohru , Kato Tomoko , Yamakawa Makoto
Published: March 2012

This study conducted genetic and phylogenetic analyses of genome segments 2 and 6 (Seg-2 and Seg-6), which encode serotype-specific structural proteins of the outer capsid, of bluetongue virus (BTV) isolated in Japan from 1985 to 2008. The Japanese strains of BTV were clearly sorted into six groups by several genetic characteristics of Seg-2, including segment length, ORF length and 5′- and 3′-terminal sequences, and were identified as serotypes 2, 3, 9, 12, 16 and 21 by phylogenetic comparisons with Seg-2 of reference and field strains of serotypes 1–24. In contrast, phylogenetic comparisons of Seg-6 also revealed some variations among the Japanese strains and partial correlations of the serotypes between the Japanese strains and the reference or field strains. Thus, the results revealed that at least six serotypes of BTV were isolated in Japan and that there were some variations in the genetic and phylogenetic characteristics of Seg-2 and Seg-6 among the Japanese strains, suggesting that BTV of several different origins has appeared sporadically in Japan. These data will be beneficial for understanding BTV epidemiology and taking better control measures against bluetongue in Japan and its neighbouring countries in the Asia-Pacific region.
Evidence for an endogenous papillomavirus-like element in the platypus genome
Authors: Cui Jie , Holmes Edward C.
Published: March 2012

Papillomaviruses (PVs) infect a wide range of vertebrates and have diversified into multiple genetic types, some of which have serious consequences for human health. Although PVs have to date only been characterized as exogenous viral forms, here we report the observation of an endogenous viral element (EPVLoa) in the genome of the platypus (Ornithorhynchus anatinus) that is related to PVs. Further data mining for endogenous PV-like elements is therefore warranted.
A third gyrovirus species in human faeces
Authors: Phan Tung G. , Li Linlin , O’Ryan Miguel G. , Cortes Hector , Mamani Nora , Bonkoungou Isidore J. O. , Wang Chunling , Leutenegger Christian M. , Delwart Eric
Published: March 2012

Until 2011 the genus Gyrovirus in the family Circoviridae consisted of a single virus (Chicken anemia virus or CAV) causing a common immunosuppressive disease in chickens when a second gyrovirus (HGyV) was reported on the skin of 4 % of healthy humans. HGyV is very closely related to a recently described chicken gyrovirus, AGV2, suggesting that they belong to the same viral species. During a viral metagenomic analysis of 100 human faeces from children with diarrhoea in Chile we identified multiple known human pathogens (adenoviruses, enteroviruses, astroviruses, sapoviruses, noroviruses, parechoviruses and rotaviruses) and a novel gyrovirus species we named GyV3 sharing <63 % similarity with other gyrovirus proteins with evidence of recombination with CAV in its UTR. Gyroviridae consensus PCR revealed a high prevalence of CAV DNA in diarrhoea and normal faeces from Chilean children and faeces of USA cats and dogs, which may reflect consumption of CAV-infected/vaccinated chickens. Whether GyV3 can infect humans and/or chickens requires further studies.
Primate segmental duplication creates novel promoters for theLRRC37gene family within the 17q21.31 inversion polymorphism region
Authors: Bekpen Cemalettin , Tastekin Ibrahim , Siswara Priscillia , Akdis Cezmi A. , Eichler Evan E.
Published: March 2012

TheLRRC37gene family maps to a complex region of the human genome and has been subjected to multiple rounds of segmental duplication. We investigate the expression and regulation of this gene family in multiple tissues and organisms and show a testis-specific expression of this gene family in mouse but a more ubiquitous pattern of expression among primates. Evolutionary and phylogenetic analyses support a model in which new alternative promoters have been acquired during primate evolution. We identify two promoters, Cl8 and particularly Cl3, both of which are highly active in the cerebellum and fetal brain in human and have been duplicated from a promoter region of two unrelated genes,BPTFandDND1, respectively. Two of these more broadly expressed gene family members,LRRC37A1andA4, define the boundary of a common human inversion polymorphism mapping to chromosome 17q21.31 (theMAPTlocus)—a region associated with risk for frontal temporal dementia, Parkinsonism, and intellectual disability. We propose that the regulation of theLRRC37family occurred in a stepwise manner, acquiring foreign promoters fromBPTFandDND1via segmental duplication. This unusual evolutionary trajectory altered the regulation of theLRRC37family, leading to increased expression in the fetal brain and cerebellum.
The evolution of African great ape subtelomeric heterochromatin and the fusion of human chromosome 2
Authors: Ventura Mario , Catacchio Claudia R. , Sajjadian Saba , Vives Laura , Sudmant Peter H. , Marques-Bonet Tomas , Graves Tina A. , Wilson Richard K. , Eichler Evan E.
Published: March 2012

Chimpanzee and gorilla chromosomes differ from human chromosomes by the presence of large blocks of subterminal heterochromatin thought to be composed primarily of arrays of tandem satellite sequence. We explore their sequence composition and organization and show a complex organization composed of specific sets of segmental duplications that have hyperexpanded in concert with the formation of subterminal satellites. These regions are highly copy number polymorphic between and within species, and copy number differences involving hundreds of copies can be accurately estimated by assaying read-depth of next-generation sequencing data sets. Phylogenetic and comparative genomic analyses suggest that the structures have arisen largely independently in the two lineages with the exception of a few seed sequences present in the common ancestor of humans and African apes. We propose a model where an ancestral human-chimpanzee pericentric inversion and the ancestral chromosome 2 fusion both predisposed and protected the chimpanzee and human genomes, respectively, to the formation of subtelomeric heterochromatin. Our findings highlight the complex interplay between duplicated sequences and chromosomal rearrangements that rapidly alter the cytogenetic landscape in a short period of evolutionary time.
Reactive Oxygen Species-Driven Transcription in Arabidopsis under Oxygen Deprivation
Authors: Pucciariello Chiara , Parlanti Sandro , Banti Valeria , Novi Giacomo , Perata Pierdomenico
Published: March 2012

Reactive oxygen species (ROS) play an important role as triggers of gene expression during biotic and abiotic stresses, among which is low oxygen (O2). Previous studies have shown that ROS regulation under low O2 is driven by a RHO-like GTPase that allows tight control of hydrogen peroxide (H2O2) production. H2O2 is thought to regulate the expression of heat shock proteins, in a mechanism that is common to both O2 deprivation and to heat stress. In this work, we used publicly available Arabidopsis (Arabidopsis thaliana) microarray datasets related to ROS and O2 deprivation to define transcriptome convergence pattern. Our results show that although Arabidopsis response to anoxic and hypoxic treatments share a common core of genes related to the anaerobic metabolism, they differ in terms of ROS-related gene response. We propose that H2O2 production under O2 deprivation is a trait present in a very early phase of anoxia, and that ROS are needed for the regulation of a set of genes belonging to the heat shock protein and ROS-mediated groups. This mechanism, likely not regulated via the N-end rule pathway for O2 sensing, is probably mediated by a NADPH oxidase and it is involved in plant tolerance to the stress.
Single-pass flow-through reaction cell for high-temperature and high-pressurein situneutron diffraction studies of hydrothermal crystallization processes
Authors: Xia Fang , Brugger Joël , Qian Gujie , Ngothai Yung , O'Neill Brian , Zhao Jing , Pullen Stewart , Olsen Scott , Pring Allan
Published: March 2012

A large-volume single-pass flow-through cell forin situneutron diffraction investigation of hydrothermal crystallization processes is reported. The cell is much more versatile than previous designs owing to the ability to control independently and precisely temperature (up to 673 K), pressure (up to 46 MPa), flow rate (0.01–10 ml min−1) and reaction-fluid volume (≥65 ml). Such versatility is realized by an innovative design consisting of a room-temperature and ambient-pressure external fluid supply module, a high-pressure reaction module which includes a high-temperature sample compartment enclosed in a vacuum furnace, and a room-temperature and high-pressure backpressure regulation module for pressure control. The cell provides a new avenue for studying various parameters of hydrothermal crystallizations independently,in situand in real time at extreme hydrothermal conditions (e.g.supercritical). The cell was successfully commissioned on the high-intensity powder diffractometer beamline, Wombat, at the Australian Nuclear Science and Technology Organisation by investigating the effect of pressure on the hydrothermal pseudomorphic conversion from SrSO4(celestine) to SrCO3(strontianite) at a constant temperature of 473 K and flow rate of 5 ml min−1. The results show that the increase of pressure exerts a nonlinear effect on the conversion rate, which first increases with increasing pressure from 14 to 20 MPa, and then decreases when pressure further increases to 24 MPa.
Modulation of quartz-like GeO2structure by Si substitution: an X-ray diffraction study of Ge1−xSixO2(0 ≤x< 0.2) flux-grown single crystals
Authors: Lignie Adrien , Granier Dominique , Armand Pascale , Haines Julien , Papet Philippe
Published: March 2012

The spontaneous nucleation by the high-temperature flux method of GeO2and SiO2-substituted GeO2(Ge1−xSixO2) compounds was improved to give single crystals free of hydroxy groups. The crystal structure and quality of these α-quartz-like piezoelectric materials were studied by single-crystal X-ray diffraction at room temperature. The refinements gave excellent final reliability factors, which are an indication of single crystals with a low level of defects. A good correlation was found between the silicon content in Ge1−xSixO2crystals determined through extrapolation from the inter-tetrahedral bridging angle and that found from energy-dispersive X-ray spectroscopy. The effect of germanium replacement by silicon on the distortion of the α-quartz-type GeO2structure was followed by the evolution of the intra-tetrahedral angle and other structural parameters. TheTO4(T= Si, Ge) distortion was found to be larger in α-GeO2than in α-SiO2and, as expected, the irregularity of theTO4tetrahedra decreased linearly as the substitution of Si for Ge increased.
Automated determination of the extinction symbolviaelectron diffraction data
Authors: Camalli Mercedes , Carrozzini Benedetta , Cascarano Giovanni Luca , Giacovazzo Carmelo
Published: March 2012

The identification of the extinction symbol is routine for single-crystal X-ray data. Because of peak overlap and possible preferred orientation the task is more difficult for powder diffraction data, but recent computer programs based on probabilistic approaches have made it more automatic. This paper describes a new algorithm for the automatic identification of the Laue group and of the extinction symbol from electron diffraction intensities. The algorithm has a statistical basis and tries to deal with the severe problems arising from the often nonkinematical nature of the diffraction intensities and from the limited accuracy of the lattice parameters determinedviaelectron diffraction. The approach has been checked using a wide set of test structures.
Upgrade of automated sample exchanger SPACE
Authors: Murakami Hironori , Ueno Go , Shimizu Nobutaka , Kumasaka Takashi , Yamamoto Masaki
Published: March 2012

SPACE (SPring-8 precise automatic cryo-sample exchanger) is an automated sample exchanger for cryo-cooled protein crystals, developed at SPring-8. Since the start of its operation, SPACE has been continuously improved and upgraded to cope with the requirements of new beamlines and users. One important upgrade of SPACE provides support for conventional metal-base pins, which are attached to the goniometer head magnetically. Other hardware improvements include increasing the sample storage capacity. The upgraded version of SPACE, as reported here, is continuously operated and is an essential component of beamline operation at SPring-8.
Application of matrix decomposition algorithms for singular matrices to the Pawley method inZ-Rietveld
Authors: Oishi-Tomiyasu R. , Yonemura M. , Morishima T. , Hoshikawa A. , Torii S. , Ishigaki T. , Kamiyama T.
Published: March 2012

Z-Rietveldis a program suite for Rietveld analysis and the Pawley method; it was developed for analyses of powder diffraction data in the Materials and Life Science Facility of the Japan Proton Accelerator Research Complex. Improvements have been made to the nonlinear least-squares algorithms ofZ-Rietveldso that it can deal with singular matrices and intensity non-negativity constraints. Owing to these improvements,Z-Rietveldsuccessfully executes the Pawley method without requiring any constraints on the integrated intensities, even in the case of severely or exactly overlapping peaks. In this paper, details of these improvements are presented and their advantages discussed. A new approach to estimate the number of independent reflections contained in a powder pattern is introduced, and the concept of good reflections proposed by Sivia [J. Appl. Cryst.(2000),33, 1295–1301] is shown to be explained by the presence of intensity non-negativity constraints, not the intensity linear constraints.
In situquantitative analysis of stress and texture development in forsterite aggregates deformed at 6 GPa and 1373 K
Authors: Bollinger Caroline , Merkel Sébastien , Raterron Paul
Published: March 2012

The investigation of materials plastic properties at high pressure is a fast-growing field, owing to the coupling of high-pressure deformation apparatuses with X-ray synchrotron radiation. In such devices, materials strain and strain rate are measured by time-resolved radiography, while differential stress is deduced from the elastic response of thedspacing of the crystallographic planes as measured by X-ray diffraction. Here a new protocol is presented, which allows thein situmeasurement of stress and texture development in aggregates deformed at high pressure for experiments carried out with the recently installed ten-element energy-dispersive detector at the X17B2 beamline of the National Synchrotron Light Source (Brookhaven National Laboratory, Upton, NY, USA). Cycling deformation of a forsterite specimen was carried out at a pressure of ∼6 GPa and a temperature of ∼1373 K, using a deformation-DIA apparatus. Diffraction peak energies are analysed in terms of differential stress and principal stress direction, while the intensities of peaks obtained at different azimuths are analysed in terms of lattice preferred orientation (LPO). The development and evolution of a marked LPO, with the (010) plane perpendicular to the compression axis, is observedin situduring the run and is confirmed by electron backscatter diffraction measurements on the run product.
CrystalEye: automated aggregation, semantification and dissemination of the world's open crystallographic data
Authors: Day Nick , Downing Jim , Adams Sam , England N. W. , Murray-Rust Peter
Published: March 2012

CrystalEyeautomatically aggregates crystallographic data from web resources (the supplementary data to articles on publishers' web sites) into a structured XML-based repository, and then adds value to that open data by providing methods to easily browse, search and to keep up-to-date with the latest published information.
Application of constrained real-space refinement of flexible molecular fragments to automatic model building of RNA structures
Authors: Pavelcik Frantisek
Published: March 2012

New methods have been developed for locating phosphate groups and nucleic acid bases in the electron density of RNA structures. These methods utilize a constrained real-space refinement of molecular fragments and a phased rotation–conformation–translation function. Real-space refinement has also contributed to the improvement of the bone/base method of RNA model building and to redesigning the method of building double helices in nucleic acid structures. This improvement is reflected in the increased accuracy of the model building and the ability to better distinguish between correct and false solutions. A program,RSR, was created, and the programsNUT,HELandDHLwere upgraded and organized into a program system, which is CCP4 oriented. Source codes will also be released.
New developments in theATSASprogram package for small-angle scattering data analysis
Authors: Petoukhov Maxim V. , Franke Daniel , Shkumatov Alexander V. , Tria Giancarlo , Kikhney Alexey G. , Gajda Michal , Gorba Christian , Mertens Haydyn D. T. , Konarev Petr V. , Svergun Dmitri I.
Published: March 2012

New developments in the program packageATSAS(version 2.4) for the processing and analysis of isotropic small-angle X-ray and neutron scattering data are described. They include (i) multiplatform data manipulation and display tools, (ii) programs for automated data processing and calculation of overall parameters, (iii) improved usage of high- and low-resolution models from other structural methods, (iv) new algorithms to build three-dimensional models from weakly interacting oligomeric systems and complexes, and (v) enhanced tools to analyse data from mixtures and flexible systems. The newATSASrelease includes installers for current major platforms (Windows, Linux and Mac OSX) and provides improved indexed user documentation. The web-related developments, including a user discussion forum and a widened online access to runATSASprograms, are also presented.
PDB_REDO: constructive validation, more than just looking for errors
Authors: Joosten Robbie P. , Joosten Krista , Murshudov Garib N. , Perrakis Anastassis
Published: March 2012

Developments of the PDB_REDO procedure that combine re-refinement and rebuilding within a unique decision-making framework to improve structures in the PDB are presented. PDB_REDO uses a variety of existing and custom-built software modules to choose an optimal refinement protocol (e.g. anisotropic, isotropic or overall B-factor refinement, TLS model) and to optimize the geometry versus data-refinement weights. Next, it proceeds to rebuild side chains and peptide planes before a final optimization round. PDB_REDO works fully automatically without the need for intervention by a crystallographic expert. The pipeline was tested on 12 000 PDB entries and the great majority of the test cases improved both in terms of crystallographic criteria such as R
free and in terms of widely accepted geometric validation criteria. It is concluded that PDB_REDO is useful to update the otherwise `static' structures in the PDB to modern crystallographic standards. The publically available PDB_REDO database provides better model statistics and contributes to better refinement and validation targets.
Practical structure solution with
ARCIMBOLDO
Authors: Rodríguez Dayté , Sammito Massimo , Meindl Kathrin , de Ilarduya Iñaki M. , Potratz Marianus , Sheldrick George M. , Usón Isabel
Published: March 2012

Since its release in September 2009, the structure-solution program ARCIMBOLDO, based on the combination of locating small model fragments such as polyalanine α-helices with density modification with the program SHELXE in a multisolution frame, has evolved to incorporate other sources of stereochemical or experimental information. Fragments that are more sophisticated than the ubiquitous main-chain α-helix can be proposed by modelling side chains onto the main chain or extracted from low-homology models, as locally their structure may be similar enough to the unknown one even if the conventional molecular-replacement approach has been unsuccessful. In such cases, the program may test a set of alternative models in parallel against a specified figure of merit and proceed with the selected one(s). Experimental information can be incorporated in three ways: searching within ARCIMBOLDO for an anomalous fragment against anomalous differences or MAD data or finding model fragments when an anomalous substructure has been determined with another program such as SHELXD or is subsequently located in the anomalous Fourier map calculated from the partial fragment phases. Both sources of information may be combined in the expansion process. In all these cases the key is to control the workflow to maximize the chances of success whilst avoiding the creation of an intractable number of parallel processes. A GUI has been implemented to aid the setup of suitable strategies within the various typical scenarios. In the present work, the practical application of ARCIMBOLDO within each of these scenarios is described through the distributed test cases.
Handling ligands with Coot
Authors: Debreczeni Judit É. , Emsley Paul
Published: March 2012

Coot is a molecular-graphics application primarily aimed to assist in model building and validation of biological macromolecules. Recently, tools have been added to work with small molecules. The newly incorporated tools for the manipulation and validation of ligands include interaction with PRODRG, subgraph isomorphism-based tools, representation of ligand chemistry, ligand fitting and analysis, and are described here.
Formation and regulation of the cancer stem cell niche
Authors: Takakura Nobuyuki
Published: March 2012

It is widely accepted that tumors contain cancer stem cells (CSC) possessing self‐renewal potential as well as the ability to generate numerous cancer cells. Cancer stem cells are resistant to conventional cancer therapy and have greater invasive and metastatic behavior. It has been suggested that blood vessels provide a niche that maintains stemness in normal organs. This role also extends to the field of cancer biology. Cancer stem cells have been isolated from leukemias and solid cancers. Identification of these cells and their niche is critical for identifying molecular targets in order to inhibit their growth and to destroy their niche. For this purpose, sorting of living CSC is required to monitor their presence in the presumptive niche to establish whether a CSC candidate actually shows malignant features. Based on and referring to analyses in normal tissues, molecules including nitric oxide, Wnt, neuropilin‐1, hepatocyte growth factor and others involved in the maintenance of CSC have been isolated. Stem cells might affect niche cells and niche cells produce stemness factors on such stimulation. Therefore, the niche might be flexible to support self‐renewal or differentiation of stem cells even in the same niche cells. (Cancer Sci 2012; 103: 1177–1181)
Combined spinal epidural vs epidural labour analgesia: does initial intrathecal analgesia reduce the subsequent minimum local analgesic concentration of epidural bupivacaine?
Authors: Patel N. P. , Armstrong S. L. , Fernando R. , Columb M. O. , Bray J. K. , Sodhi V. , Lyons G. R.
Published: March 2012

Labour analgesia initiated using a combined spinal‐epidural (CSE) technique may reduce subsequent epidural bupivacaine requirements compared with an epidural‐only technique. We compared the minimum local analgesic concentrations (MLAC) of epidural bupivacaine following initial intrathecal or epidural injection. In a prospective, double‐blind study, 115 women requesting epidural analgesia were randomly assigned to receive either an epidural with bupivacaine 20 mg and fentanyl 40 μg or a CSE with intrathecal bupivacaine 2.5 mg and fentanyl 5 μg. Analgesia was assessed using a visual analogue pain score. When further analgesia was requested, bupivacaine 20 ml was given, and the concentration was determined using the technique of up‐down sequential allocation. The MLAC of bupivacaine in the epidural group was 0.032% wt/vol (95% CI 0.020–0.044) compared with 0.047% wt/vol (95% CI 0.042–0.052) in the CSE group. Bupivacaine requirements for the second injection were increased following intrathecal analgesia by a factor of 1.45 (p = 0.026) compared with epidural analgesia.
Acute pulmonary oedema in pregnant women
Authors: Dennis A. T. , Solnordal C. B.
Published: March 2012

Acute pulmonary oedema in pregnant women is an uncommon but life‐threatening event. The aims of this review are to address why pulmonary oedema occurs in pregnant women and to discuss immediate management. We performed a systematic literature search of electronic databases including MEDLINE, EMBASE and the Cochrane Library, using the key words obstetrics, pregnancy, acute pulmonary oedema, pregnancy complications, maternal, cardiac function and haemodynamics. We present a simple clinical classification of acute pulmonary oedema in pregnancy into pulmonary oedema occurring in normotensive or hypotensive women (i.e. without hypertension), and acute pulmonary oedema occurring in hypertensive women, which allows focused management. Pre‐eclampsia remains an important cause of hypertensive acute pulmonary oedema in pregnancy and preventive strategies include close clinical monitoring and restricted fluid administration. Immediate management of acute pulmonary oedema includes oxygenation, ventilation and circulation control with venodilators. Pregnancy‐specific issues include consideration of the physiological changes of pregnancy, the risk of aspiration and difficult airway, reduced respiratory and metabolic reserve, avoidance of aortocaval compression and delivery of the fetus.
A randomised comparison of the LMA Supreme™ and LMA ProSeal™ in children
Authors: Jagannathan N. , Sohn L. E. , Sawardekar A. , Gordon J. , Langen K. E. , Anderson K.
Published: March 2012

We conducted a randomised trial comparing the size‐2 LMA Supreme™ with the LMA ProSeal™ in 60 children undergoing surgery. The outcomes measured were airway leak pressure, ease and time for insertion, fibreoptic examination, incidence of gastric insufflation, ease of gastric tube placement, quality of the airway during anaesthetic maintenance and complications. There were no statistically significant differences between the LMA Supreme and LMA ProSeal in median (IQR [range]) insertion time (12 (10–15 [7–18]) s vs 12 (10–13 [8–25]) s; p = 0.90), airway leak pressures (19 (16–21 [12–30]) cmH2O vs 18 (16–24 [10–34]) cmH2O; p = 0.55), fibreoptic position of the airway or drain tube, ease of gastric access and complications. Both devices provided effective ventilation requiring minimal airway manipulation. The LMA Supreme can be a useful alternative to the LMA ProSeal when single‐use supraglottic devices with gastric access capabilities are required.
Combining quantitative trait loci and heterogeneous microarray data analyses reveals putative candidate pathways affecting mastitis in cattle
Authors: Lewandowska‐Sabat A. M. , Günther J. , Seyfert H. M. , Olsaker I.
Published: March 2012

Mastitis is a frequent disease and considerable problem for the global dairy industry. Identification of solutions leading to the development of new control strategies is therefore of high importance. In this study, we have integrated genomic data from genome‐wide association mapping in cattle with transcriptomic data from microarray studies of several mastitis pathogens and host species in vitro and in vivo. To identify significant candidate pathways directly and indirectly involved in the immune response to mastitis, ingenuity pathway analysis (ipa) and database for annotation, visualization and integrated discovery bioinformatic (david) were applied. Several candidate pathways were found. Of great interest are IL‐17 and IL‐8 signalling pathways, responsible for the recruitment and migration of inflammatory cells into tissue during inflammation and infection. These results may emphasize further functional studies for identification of factors contributing to resistance to mastitis pathogens in cattle.
Children's and parents' thoughts and feelings about adoption, birth culture identity and discrimination in families with internationally adopted children
Authors: Reinoso Marta , Juffer Femmie , Tieman Wendy
Published: March 2012

We examined the perceptions of adoption and related issues in 68 families with internationally adopted children in Spain (48 transracial and 20 same‐race adoptions). The adopted children, between the ages of 8 and 12 years, and their parents answered questions about the children's thoughts and feelings about adoption. Descriptive data and scores on four scales – family, adoption, birth culture identity and discrimination – were obtained. Compared with same‐race adoptees, transracial adoptees scored significantly higher on birth culture identity and perceived discrimination. High levels of convergence between the children's and parents' viewpoints on the experiences of adoption and related issues were found. Nevertheless, the adopted children scored higher than their parents on birth culture identity, suggesting that at this age adoptive parents may underestimate their children's connection to their cultural origins. In contrast, the same‐race adoptees scored significantly lower on perceived discrimination than their mothers. We conclude that at this age adoptive parents should acknowledge their adopted child's daily‐life experiences regarding cultural identity with the birth country and discrimination.
The 2011 submarine volcanic eruption in El Hierro (Canary Islands)
Authors: Carracedo Juan Carlos , Torrado Francisco Pérez , González Alejandro Rodríguez , Soler Vicente , Turiel José Luis Fernández , Troll Valentin R. , Wiesmaier Sebastian
Published: March 2012

Forty years after the Teneguía Volcano (La Palma, 1971), a submarine eruption took place off the town of La Restinga, south of El Hierro, the smallest and youngest island of the Canarian Archipelago. Precursors allowed an early detection of the event and its approximate location, suggesting it was submarine. Uncertainties derived from insufficient scientific information available to the authorities during the eruption, leading to disproportionate civil protection measures, which had an impact on the island's economy—based primarily on tourism—while residents experienced extra fear and distress.
Relationship between conventional sperm parameters and motile sperm organelle morphology examination (MSOME)
Authors: Perdrix A. , Saïdi R. , Ménard J. F. , Gruel E. , Milazzo J. P. , Macé B. , Rives N.
Published: March 2012

With the motile sperm organelle morphology examination (MSOME), spermatozoa morphology may be assessed directly on motile spermatozoa at high magnification (up to 6600×). This procedure describes more precisely spermatozoa abnormalities, especially head vacuoles. However, no consensus has been established concerning normal or abnormal MSOME criteria. The aim of our study was to define MSOME vacuole criteria assessed objectively with a digital imaging system software to establish a potential relationship between conventional semen parameters. A total of 440 semen samples were obtained from males consulting in Rouen University Hospital Reproductive Biology Laboratory. Conventional semen analysis (volume, sperm concentration, progressive motility, vitality and morphology) and MSOME assessment {sperm head length, width and area as well as vacuole number, vacuole area and relative vacuole area to sperm head [RVA (%) = [vacuole area (μm2)/head area (μm2)] × 100)]} were performed for each semen sample. Among our 440 males, 109 presented normal conventional semen parameters and 331 abnormal ones. Sperm head vacuoles were significantly larger in abnormal semen samples (p < 0.0001). RVA was the most discriminative MSOME criterion between normal and abnormal semen samples according to ROC curves analysis, and was negatively correlated with poor sperm morphology (r = −0.53, p < 0.0001). We concluded to (i) the normal occurrence of vacuoles in sperm head whatever the normality or abnormality of semen parameters, (ii) the discriminative function of the RVA to distinguish semen samples with normal and abnormal parameters, and (iii) the strong correlation between high RVA and poor sperm morphology.
Effects of inducible nitric oxide synthase (iNOS) deficiency in mice on Sertoli cell proliferation and perinatal testis development
Authors: Auharek S. A. , Lara N. L. M. , Avelar G. F. , Sharpe R. M. , França L. R.
Published: March 2012

Nitric oxide (NO) plays crucial roles in several physiological and pathological conditions. The iNOS isoform produces high levels of NO independent of intracellular calcium and, in the testis, which is expressed in Sertoli (SC), Leydig (LC) and germ cells. The testicular roles of NO are unclear, but it can inhibit LC testosterone production. Our aim was to evaluate the effects of iNOS deficiency on testis development in mice from late fetal life through early puberty. Therefore, testes from wild type (C57BCL/6) and iNOS−/− mice (B6.129P2‐ Nos2tm1Lau/J) were sampled at various ages between e18.5 and Pnd20 and evaluated by histological and stereological analyses; proliferating cells were labelled with 3H‐thymidine. At all ages, testis weight and anogenital index, a measure of fetal androgen exposure, were greater in iNOS‐deficient mice than in wild type mice. At all ages after birth, iNOS‐deficient mice exhibited increased (p < 0.05) SC number per testis, and this was accounted for by a higher SC proliferation index (p < 0.05) in iNOS‐deficient mice, especially on Pnd1 and Pnd5. Similarly, LC number per testis was higher (p < 0.05) in iNOS−/− mice than in wild type at all post‐natal ages. Highly positive and significant correlations were observed between the proliferation index for SC, LC and peritubular myoid cells on e18.5 and post‐natally. Although lumen formation was slightly advanced in iNOS−/− mice, no obvious other effects on pubertal testis development were observed. These results imply that NO may normally constrain testis somatic cell development, especially SC, perhaps by limiting testosterone production. Removal of this constraint results in normal, but larger, testes with greater sperm production. Our data pinpoint the window of iNOS (NO) action on SC proliferation and raise the possibility that experimental manipulation of NO in early post‐natal life could be used to enhance SC proliferation if this was deficient for any reason.
External validity of physical activity interventions for community‐dwelling older adults with fall risk: a quantitative systematic literature review
Authors: McMahon Siobhan , Fleury Julie
Published: March 2012

mcmahon s. & fleury j. (2012) External validity of physical activity interventions for community‐dwelling older adults with fall risk: a quantitative systematic literature review. Journal of Advanced Nursing68(10), 2140–2154.

Aim.  To appraise the external validity of physical activity interventions designed to reduce falls among community‐dwelling older adults, using the reach, efficacy/effectiveness, adoption, implementation, and maintenance framework.

Background.  Falls are a globally common, important, and a preventable problem. The efficacy of physical activity interventions to reduce falls among older adults is well established. Translation of this research into practice is slow as evidenced by persistently low proportions of older adults who engage in physical activities and the rising incidence of falls.

Data sources.  Four electronic databases were searched for relevant studies published between 2000–2010. Studies that examined the effects of physical activity interventions designed to reduce falls among community‐dwelling older adults were included in this review (n = 46).

Design.  This was a quantitative systematic review with narrative synthesis. The reach, efficacy/effectiveness, adoption, implementation, and maintenance framework guided the identification, appraisal, and synthesis of indicators representing study validity.

Results.  The majority of studies in this review described indicators representing internal validity. Details about indicators representing external validity were reported infrequently, limiting the generalizability of fall‐preventive physical activity interventions in diverse cultures and social contexts over time.

Conclusions.  To foster translational research in real world settings, additional programmatic intervention research is needed that: (i) targets diverse populations; (ii) incorporates theories of behavioural change; (iii) describes and operationalizes critical content that enables replication and translation; (iv) tests innovative measures of fall risk and physical activity; and (v) evaluates feasibility and acceptability.