bluuebunny/crossref_metadata_2025 huggingface dataset:
Safe, accurate, prenatal diagnosis of thanatophoric dysplasia using ultrasound and free fetal DNA
Authors: Chitty Lyn S. , Khalil Asma , Barrett Angela N. , Pajkrt Eva , Griffin David R. , Cole Tim J.
Published: February 2013

Objective

To improve the prenatal diagnosis of thanatophoric dysplasia by defining the change in fetal size across gestation and the frequency of sonographic features, and developing non‐invasive molecular genetic diagnosis based on cell‐free fetal DNA (cffDNA) in maternal plasma.

Methods

Fetuses with a confirmed diagnosis of thanatophoric dysplasia were ascertained, records reviewed, sonographic features and measurements determined. Charts of fetal size were then constructed using the LMS (lambda‐mu‐sigma) method and compared with charts used in normal pregnancies and those complicated by achondroplasia. Cases in this cohort referred to our Regional Genetics Laboratory for molecular diagnosis using cffDNA were identified and results reviewed.

Results

Forty‐two cases were scanned in our units. Commonly reported sonographic features were very short and sometimes bowed femora, frontal bossing, cloverleaf skull, short fingers, a small chest and polyhydramnios. Limb shortening was obvious from as early as 13 weeks' gestation, with minimal growth after 20 weeks. Analysis of cffDNA in three of these pregnancies confirmed the presence of the c.742C>CT (p.Arg248Cys) or the c.1948A>AG (p.Lys650Glu) mutation in the fibroblast growth factor receptor 3 gene.

Conclusion

These data should improve the accuracy of the sonographic diagnosis of thanatophoric dysplasia and have implications for reliable and safe targeted molecular confirmation using cffDNA. © 2013 The Authors. Prenatal Diagnosis published by John Wiley & Sons Ltd.
Propoxyphene and the risk of out‐of‐hospital death
Authors: Ray Wayne A. , Murray Katherine T. , Kawai Vivian , Graham David J. , Cooper William O. , Hall Kathi , Michael Stein Charles
Published: February 2013

Purpose

The opioid analgesic propoxyphene was withdrawn from the US market in 2010, motivated by concerns regarding fatality in overdose and adverse cardiac effects, including prolongation of the QT interval. These concerns were based on case reports, summary vital statistics, and surrogate endpoint studies.

Methods

Using the linked Tennessee Medicaid database (1992–2007), we conducted a retrospective cohort study that compared risk of sudden cardiac, medication toxicity, and total out‐of‐hospital death for propoxyphene users with that for comparable nonusers of any prescribed opioid analgesic and users of hydrocodone, an opioid with similar indications. Cohort members had 1 873 500 propoxyphene prescriptions, 1 873 500 matched nonuser control periods, and 936 750 matched hydrocodone prescriptions.

Results

Current propoxyphene users had no increased risk for sudden cardiac death (versus nonusers: hazard ratio [HR] = 1.00 [0.81–1.23]; versus current hydrocodone users: HR = 0.91 [0.68–1.21]) but did have increased risk for medication toxicity deaths (versus nonusers: HR = 1.85 [1.07–3.19], p = 0.027; versus current hydrocodone users: HR = 2.10 [0.87–5.10], p = 0.100). Because toxicity deaths were a small proportion of study deaths, total out‐of‐hospital mortality differed by less than 10% between the study groups and was not significantly elevated for propoxyphene (versus nonusers: HR = 1.09 [0.95–1.25]; versus current hydrocodone users: HR = 1.06 [0.87–1.29] ).

Conclusions

Our findings support the concern that propoxyphene has greater toxicity in overdose but do not provide evidence that it increases the risk of sudden cardiac death. Copyright © 2013 John Wiley & Sons, Ltd.
Poly(ethylene glycol)‐modulated cellular biocompatibility of polyhydroxyalkanoate films
Authors: Chan Rodman TH , Marçal Helder , Ahmed Tania , Russell Robert A , Holden Peter J , Foster L John R
Published: February 2013

Polyhydroxybutyrate (PHB) and its copolymer with hydroxyvalerate, P(HB‐co‐HV), are widely used biomaterials. In this study, improvements of their biological properties of degradability and compatibility were achieved by blending with low‐molecular‐weight poly(ethylene glycol) (PEG106) approved for medical use. Surface morphology and chemistry are known to support cell attachment. Attachment and proliferation of neural olfactory ensheathing cells increased by 17.0 and 32.2% for PHB and P(HB‐co‐HV) composite films. Cell attachment was facilitated by increases in surface hydrophilicity, water contact angles decreased by 26 ± 2° and water uptake increased by 23.3% depending upon biopolymer and PEG loading. Cells maintained high viability (>95%) on the composite films with no evidence of cytotoxic effects. Assays of mitochondrial function and cell leakage showed improved cell health as a consequence of PEG loading. The PEG component was readily solubilised from composite films, allowing control of degradation profiles in the cell growth medium. Promotion of biopolymer compatibility and degradability was not at the expense of material properties, with the extension to break of the composites increasing by 5.83 ± 1.06%. Similarly, crystallinity decreased by 36%. The results show that blending of common polyhydroxyalkanoate biomaterials with low‐molecular‐weight PEG can be used to promote biocompatibility and manipulate physiochemical and material properties as well as degradation.© 2013 Society of Chemical Industry
GSAFold: A new application of GSA to protein structure prediction
Authors: Melo Marcelo C. R. , Bernardi Rafael C. , Fernandes Tácio V. A. , Pascutti Pedro G.
Published: February 2013

The folding process defines three‐dimensional protein structures from their amino acid chains. A protein's structure determines its activity and properties; thus knowing such conformation on an atomic level is essential for both basic and applied studies of protein function and dynamics. However, the acquisition of such structures by experimental methods is slow and expensive, and current computational methods mostly depend on previously known structures to determine new ones. Here we present a new software called GSAFold that applies the generalized simulated annealing (GSA) algorithm on ab initio protein structure prediction. The GSA is a stochastic search algorithm employed in energy minimization and used in global optimization problems, especially those that depend on long‐range interactions, such as gravity models and conformation optimization of small molecules. This new implementation applies, for the first time in ab initio protein structure prediction, an analytical inverse for the Visitation function of GSA. It also employs the broadly used NAMD Molecular Dynamics package to carry out energy calculations, allowing the user to select different force fields and parameterizations. Moreover, the software also allows the execution of several simulations simultaneously. Applications that depend on protein structures include rational drug design and structure‐based protein function prediction. Applying GSAFold in a test peptide, it was possible to predict the structure of mastoparan‐X to a root mean square deviation of 3.00 Å. Proteins 2012; © 2012 Wiley Periodicals, Inc.
Peptide binding to the PDZ3 domain by conformational selection
Authors: Steiner Sandra , Caflisch Amedeo
Published: February 2013

The PDZ domains, a large family of peptide recognition proteins, bind to the C‐terminal segment of membrane ion channels and receptors thereby mediating their localization. The peptide binding process is not known in detail and seems to differ among different PDZ domains. For the third PDZ domain of the synaptic protein PSD‐95 (PDZ3), a lock‐and‐key mechanism was postulated on the basis of the almost perfect overlap of the crystal structures in the presence and absence of its peptide ligand. Here, peptide binding to PDZ3 is investigated by explicit solvent molecular dynamics (MD) simulations (for a total of 1.3 μs) and the cut‐based free energy profile method for determining free energy barriers and basins. The free energy landscape of apo PDZ3 indicates that there are multiple basins within the native state. These basins differ by the relative orientation of the α2 helix and β2 strand, the two secondary structure elements that make up the peptide binding site. Only the structure with the smallest aperture of the binding site is populated in the MD simulations of the complex whose analysis reveals that the peptide ligand binds to PDZ3 by selecting one of three conformations. Thus, the dynamical information obtained by the atomistic simulations increment the static, that is, partial, picture of the PDZ3 binding mechanism based on the X‐ray crystallography data. Importantly, the simulation results show for the first time that conformational selection is a possible mechanism of peptide binding by PDZ domains in general. Proteins 2012. © 2012 Wiley Periodicals, Inc.
Identification, structural, and biochemical characterization of a group of large Csn2 proteins involved in CRISPR‐mediated bacterial immunity
Authors: Lee Kwang‐Hoon , Lee Seong‐Gyu , Eun Lee Kyung , Jeon Hyesung , Robinson Howard , Oh Byung‐Ha
Published: February 2013

Many prokaryotic organisms acquire immunity against foreign genetic material by incorporating a short segment of foreign DNA called spacer into chromosomal loci, termed clustered regularly interspaced short palindromic repeats (CRISPRs). The encoded RNAs are processed into small fragments that guide the silencing of the invading genetic elements. The CRISPR‐associated (Cas) proteins are the main executioners of these processes. Herein, we report the crystal structure of Stu0660 of Streptococcus thermophilus, a Cas protein involved in the acquisition of new spacers. By homotetramerization, Stu0660 forms a central channel which is decorated with basic amino acids and binds linear double‐stranded DNA (dsDNA), but not circular dsDNA. Despite undetectably low sequence similarity, two N‐terminal domains of Stu0660 are similar to the entire structure of an Enterococcus faecalis Csn2 protein, which also forms a homotetramer and binds dsDNA. Thus, this work identifies a previously unknown group of Stu0660‐like Csn2 proteins (∼350 residues), which are larger than the known canonical Csn2 proteins (∼220 residues) by containing an extra C‐terminal domain. The commonly present central channel in the two subgroups appears as a design to selectively interact with linear dsDNA. Proteins 2012. © 2012 Wiley Periodicals, Inc.
The catalytic domain of the germination‐specific lytic transglycosylase SleB from Bacillus anthracis displays a unique active site topology
Authors: Jing Xing , Robinson Howard R. , Heffron Jared D. , Popham David L. , Schubot Florian D.
Published: February 2013

Bacillus anthracis produces metabolically inactive spores. Germination of these spores requires germination‐specific lytic enzymes (GSLEs) that degrade the unique cortex peptidoglycan to permit resumption of metabolic activity and outgrowth. We report the first crystal structure of the catalytic domain of a GSLE, SleB. The structure revealed a transglycosylase fold with unique active site topology and permitted identification of the catalytic glutamate residue. Moreover, the structure provided insights into the molecular basis for the specificity of the enzyme for muramic‐δ‐lactam‐containing cortex peptidoglycan. The protein also contains a metal‐binding site that is positioned directly at the entrance of the substrate‐binding cleft. Proteins 2012;. © 2012 Wiley Periodicals, Inc.
Analysis of the movements of helices in EF‐hands
Authors: Kawasaki Hiroshi , Kretsinger Robert H.
Published: February 2013

We have developed a method to place an EF‐lobe in a coordinate system that recognizes the similarity of its two EF‐hand domains as well as their relationship by a pseudo‐two fold axis, z. The x‐axis connects the center of mass, calculated from α‐carbons of helices E1 and F1, with the center of mass of E2 and F2. The resulting coordinate system is intrinsic to each EF‐lobe and requires no comparison with other EF‐lobes. It has provided an intuitive and informative way to compare EF‐lobes and especially those changes associated with calcium and/or target binding. We analyzed the EF‐lobes of calmodulin and of other subfamilies with four EF‐hands. We have rationalized a complex pattern of changes of conformation associated with calcium coordination and effector binding as observed in different subfamilies of EF‐hand proteins. Proteins 2012. © 2012 Wiley Periodicals, Inc.
Characterizing the morphology of protein binding patches
Authors: Malod‐Dognin Noël , Bansal Achin , Cazals Frédéric
Published: February 2013

Let the patch of a partner in a protein complex be the collection of atoms accounting for the interaction. To improve our understanding of the structure–function relationship, we present a patch model decoupling the topological and geometric properties. While the geometry is classically encoded by the atomic positions, the topology is recorded in a graph encoding the relative position of concentric shells partitioning the interface atoms. The topological–geometric duality provides the basis of a generic dynamic programming‐based algorithm comparing patches at the shell level, which may favor topological or geometric features. On the biological side, we address four questions, using 249 cocrystallized heterodimers organized in biological families. First, we dissect the morphology of binding patches and show that Nature enjoyed the topological and geometric degrees of freedom independently while retaining a finite set of qualitatively distinct topological signatures. Second, we argue that our shell‐based comparison is effective to perform atomic‐level comparisons and show that topological similarity is a less stringent than geometric similarity. We also use the topological versus geometric duality to exhibit topo‐rigid patches, whose topology (but not geometry) remains stable upon docking. Third, we use our comparison algorithms to infer specificity‐related information amidst a database of complexes. Finally, we exhibit a descriptor outperforming its contenders to predict the binding affinities of the affinity benchmark. The softwares developed with this article are available from http://team.inria.fr/abs/vorpatch_compatch/. Proteins 2012; © 2012 Wiley Periodicals, Inc.
Solution structure and siRNA‐mediated knockdown analysis of the mitochondrial disease‐related protein C12orf65
Authors: Kogure Hiroyuki , Hikawa Yusuke , Hagihara Mamoru , Tochio Naoya , Koshiba Seizo , Inoue Yusuke , Güntert Peter , Kigawa Takanori , Yokoyama Shigeyuki , Nameki Nobukazu
Published: February 2013

Loss of function of the c12orf65 gene causes a mitochondrial translation defect, leading to encephalomyopathy. The C12orf65 protein is thought to play a role similar to that of ICT1 in rescuing stalled mitoribosomes during translation. Both proteins belong to a family of Class I peptide release factors (RFs), all characterized by the presence of a GGQ motif. Here, we determined the solution structure of the GGQ‐containing domain (GGQ domain) of C12orf65 from mouse by NMR spectroscopy, and examined the effect of siRNA‐mediated knockdown of C12orf65 on mitochondria in HeLa cells using flow cytometry. The GGQ domain, comprising residues 60–124 of the 184‐residue full‐length protein, forms a structure with a 310‐β1‐β2‐β3‐α1 topology that resembles the GGQ domain structure of RF more closely than that of ICT1. Thus, the GGQ domain structures of this protein family can be divided into two types, depending on the region linking β2 and β3; the C12orf65/RF type having a 6‐residue π‐HB turn and the ICT1 type having an α‐helix. Knockdown of C12orf65 resulted in increased ROS production and apoptosis, leading to inhibition of cell proliferation. Substantial changes in mitochondrial membrane potential and mass in the C12orf65‐knockdown cells were observed compared with the control cells. These results indicate that the function of C12orf65 is essential for cell vitality and mitochondrial function. Although similar effects were observed in ICT1‐downregulated cells, there were significant differences in the range and pattern of the effects between C12orf65‐ and ICT1‐knockdown cells, suggesting different roles of C12orf65 and ICT1 in rescuing stalled mitoribosomes. Proteins 2012. © 2012 Wiley Periodicals, Inc.
Comparing aminoglycoside binding sites in bacterial ribosomal RNA and aminoglycoside modifying enzymes
Authors: Romanowska Julia , Reuter Nathalie , Trylska Joanna
Published: February 2013

Aminoglycoside antibiotics are used against severe bacterial infections. They bind to the bacterial ribosomal RNA and interfere with the translation process. However, bacteria produce aminoglycoside modifying enzymes (AME) to resist aminoglycoside actions. AMEs form a variable group and yet they specifically recognize and efficiently bind aminoglycosides, which are also diverse in terms of total net charge and the number of pseudo‐sugar rings. Here, we present the results of 25 molecular dynamics simulations of three AME representatives and aminoglycoside ribosomal RNA binding site, unliganded and complexed with an aminoglycoside, kanamycin A. A comparison of the aminoglycoside binding sites in these different receptors revealed that the enzymes efficiently mimic the nucleic acid environment of the ribosomal RNA binding cleft. Although internal dynamics of AMEs and their interaction patterns with aminoglycosides differ, the energetical analysis showed that the most favorable sites are virtually the same in the enzymes and RNA. The most copied interactions were of electrostatic nature, but stacking was also replicated in one AME:kanamycin complex. In addition, we found that some water‐mediated interactions were very stable in the simulations of the complexes. We show that our simulations reproduce well findings from NMR or X‐ray structural studies, as well as results from directed mutagenesis. The outcomes of our analyses provide new insight into aminoglycoside resistance mechanism that is related to the enzymatic modification of these drugs. Proteins 2013. © 2012 Wiley Periodicals, Inc.
Combining coarse‐grained nonbonded and atomistic bonded interactions for protein modeling
Authors: Zacharias Martin
Published: February 2013

A hybrid coarse‐grained (CG) and atomistic (AT) model for protein simulations and rapid searching and refinement of peptide–protein complexes has been developed. In contrast to other hybrid models that typically represent spatially separate parts of a protein by either a CG or an AT force field model, the present approach simultaneously represents the protein by an AT (united atom) and a CG model. The interactions of the protein main chain are described based on the united atom force field allowing a realistic representation of protein secondary structures. In addition, the AT description of all other bonded interactions keeps the protein compatible with a realistic bonded geometry. Nonbonded interactions between side chains and side chains and main chain are calculated at the level of a CG model using a knowledge‐based potential. Unrestrained molecular dynamics simulations on several test proteins resulted in trajectories in reasonable agreement with the corresponding experimental structures. Applications to the refinement of docked peptide–protein complexes resulted in improved complex structures. Application to the rapid refinement of docked protein–protein complex is also possible but requires further optimization of force field parameters. Proteins 2013. © 2012 Wiley Periodicals, Inc.
Critical analysis of the successes and failures of homology models of G protein‐coupled receptors
Authors: Bhattacharya Supriyo , Lam Alfonso Ramon , Li Hubert , Balaraman Gouthaman , Niesen Michiel Jacobus Maria , Vaidehi Nagarajan
Published: February 2013

We present a critical assessment of the performance of our homology model refinement method for G protein‐coupled receptors (GPCRs), called LITICon that led to top ranking structures in a recent structure prediction assessment GPCRDOCK2010. GPCRs form the largest class of drug targets for which only a few crystal structures are currently available. Therefore, accurate homology models are essential for drug design in these receptors. We submitted five models each for human chemokine CXCR4 (bound to small molecule IT1t and peptide CVX15) and dopamine D3DR (bound to small molecule eticlopride) before the crystal structures were published. Our models in both CXCR4/IT1t and D3/eticlopride assessments were ranked first and second, respectively, by ligand RMSD to the crystal structures. For both receptors, we developed two types of protein models: homology models based on known GPCR crystal structures, and ab initio models based on the prediction method MembStruk. The homology‐based models compared better to the crystal structures than the ab initio models. However, a robust refinement procedure for obtaining high accuracy structures is needed. We demonstrate that optimization of the helical tilt, rotation, and translation is vital for GPCR homology model refinement. As a proof of concept, our in‐house refinement program LITiCon captured the distinct orientation of TM2 in CXCR4, which differs from that of adrenoreceptors. These findings would be critical for refining GPCR homology models in future. Proteins 2013. © 2012 Wiley Periodicals, Inc.
High resolution crystal structure of Sco5413, a widespread actinomycete MarR family transcriptional regulator of unknown function
Authors: Holley Tracey A. , Stevenson Clare E. M. , Bibb Mervyn J. , Lawson David M.
Published: February 2013

The crystal structure of Sco5413 from Streptomyces coelicolor A3(2) has been determined at 1.25 Å resolution, the highest resolution reported for a MarR family transcriptional regulator. Putative orthologs are encoded by the majority of sequenced actinomycete genomes, and may play roles in regulating growth and antibiotic production, but they have yet to be assigned a precise function. Sco5413 forms a homodimer and, through comparisons with other MarR family protein structures, we postulate that it adopts a conformation compatible with DNA binding, and that a channel at the dimer interface, lined by well‐conserved residues, is the binding site of an unidentified effector ligand. Proteins 2013. © 2012 Wiley Periodicals, Inc.
Structure and activity of the NAD(P)+‐dependent succinate semialdehyde dehydrogenase YneI from Salmonella typhimurium
Authors: Zheng Hongyan , Beliavsky Alina , Tchigvintsev Anatoli , Brunzelle Joseph S. , Brown Greg , Flick Robert , Evdokimova Elena , Wawrzak Zdzislaw , Mahadevan Radhakrishnan , Anderson Wayne F. , Savchenko Alexei , Yakunin Alexander F.
Published: February 2013

Aldehyde dehydrogenases are found in all organisms and play an important role in the metabolic conversion and detoxification of endogenous and exogenous aldehydes. Genomes of many organisms including Escherichia coli and Salmonella typhimurium encode two succinate semialdehyde dehydrogenases with low sequence similarity and different cofactor preference (YneI and GabD). Here, we present the crystal structure and biochemical characterization of the NAD(P)+‐dependent succinate semialdehyde dehydrogenase YneI from S. typhimurium. This enzyme shows high activity and affinity toward succinate semialdehyde and exhibits substrate inhibition at concentrations of SSA higher than 0.1 mM. YneI can use both NAD+ and NADP+ as cofactors, although affinity to NAD+ is 10 times higher. High resolution crystal structures of YneI were solved in a free state (1.85 Å) and in complex with NAD+ (1.90 Å) revealing a two domain protein with the active site located in the interdomain interface. The NAD+ molecule is bound in the long channel with its nicotinamide ring positioned close to the side chain of the catalytic Cys268. Site‐directed mutagenesis demonstrated that this residue, as well as the conserved Trp136, Glu365, and Asp426 are important for activity of YneI, and that the conserved Lys160 contributes to the enzyme preference to NAD+. Our work has provided further insight into the molecular mechanisms of substrate selectivity and activity of succinate semialdehyde dehydrogenases. © 2012 Wiley Periodicals, Inc.
On the relationship between the sequence conservation and the packing density profiles of the protein complexes
Authors: Chang Chih‐Min , Huang Yu‐Wen , Shih Chien‐Hua , Hwang Jenn‐Kang
Published: February 2013

We have recently showed that the weighted contact number profiles (or the packing density profiles) of proteins are well correlated with those of the corresponding sequence conservation profiles. The results suggest that a protein structure may contain sufficient information about sequence conservation comparable to that derived from multiple homologous sequences. However, there are ambiguities concerning how to compute the packing density of the subunit of a protein complex. For the subunits of a complex, there are different ways to compute its packing density – one including the packing contributions of the other subunits and the other one excluding their contributions. Here we selected two sets of enzyme complexes. Set A contains complexes with the active sites comprising residues from multiple subunits, while set B contains those with the active sites residing on single subunits. In Set A, if the packing density profile of a subunit is computed considering the contributions of the other subunits of the complex, it will agree better with the sequence conservation profile. But in Set B the situations are reversed. The results may be due to the stronger functional and structural constraints on the evolution processes on the complexes of Set A than those of Set B to maintain the enzymatic functions of the complexes. The comparison of the packing density and the sequence conservation profiles may provide a simple yet potentially useful way to understanding the structural and evolutionary couplings between the subunits of protein complexes. Proteins 2013; 81:1192–1199. © 2013 Wiley Periodicals, Inc.
Erratum: Characterisation of multiple carrier transport in indium nitride grown by molecular beam epitaxy [Phys. Status Solidi C 4, 2423–2427 (2007)]
Authors: Fehlberg Tamara B. , Umana‐Membreno Gilberto A. , Gallinat Chad S. , Koblmüller Gregor , Bernardis Sarah , Nener Brett D. , Parish Giacinta , Speck James S.
Published: February 2013

This paper erroneously neglected to reference an earlier paper, an oversight which the authors wish to correct to improve the overall contribution of both papers. (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Microstructural corrosion of aluminium alloys: a predictive finite element model based on corrosion–mimicking experiments
Authors: Sorriano Claire , Oltra Roland , Zimmer Alexandre , Vuillemin Bruno , Vuillemin Bruno , Borkowski Celine
Published: February 2013

The purpose of this study is to implement the basis of a finite element model (FEM) based on the resolution of the Nernst–Planck equation in order to progress in the predictive simulation of microstructural corrosion on aluminium alloys. Certain constituent intermetallic particles at the surface of aluminium alloys are considered as preferential sites for the initiation of structural corrosion resulting in localised trenching around the particles and the surrounding Al matrix. In this work, a modified scanning electrochemical microscope (SECM) experiment was used to induce such phenomena via a local alkalinization on 200 nm thick aluminium coatings, promoting their local dissolution in an aerated 0.1 M NaCl electrolyte. Using a 2D finite element modelling to simulate the SECM experiments, the role of the local alkalinization was validated and the calculated Al dissolution rate was found in agreement with the experimental evaluation. The same FEM model was then successfully applied to simulate the damage formed around a micrometric copper particle embedded in pure aluminium. Copyright © 2013 John Wiley & Sons, Ltd.
Theoretical models of DNA flexibility
Authors: Dršata Tomáš , Lankaš Filip
Published: February 2013

DNA sequence‐dependent three‐dimensional structure and mechanical deformability play a large role in biological processes such as protein–DNA interactions, nucleosome positioning, promoter identification, and drug–DNA recognition. On the important scale of 10–100 base pairs, models where DNA bases are represented by interacting rigid bodies have proved useful. We focus on a recently proposed rigid base model with nonlocal, harmonic interaction energy. We discuss the choice of internal coordinates and a method to obtain model parameters from coordinate fluctuations. Parameter transformation upon change of reference strand, coordinate constraints, and models with reduced number of degrees of freedom are described. Relation to traditional local harmonic models is clarified. We outline recent attempts to include anharmonic effects. A rigid base model of a DNA oligomer containing A‐tract is presented as an example. Perspectives of model development and application are discussed.

This article is categorized under:

Electronic Structure Theory > Density Functional Theory
Perceived Ubiquity in Mobile Services
Authors: Okazaki Shintaro , Mendez Felipe
Published: February 2013

Ubiquity has been referred to as one of the most important characteristics of mobile services. In this study, an instrument for the measurement of perceived ubiquity reflecting the benefits derived from continuity, immediacy, portability, and searchability is developed using a multiple-stage approach. In the initial stage, perceived ubiquity is conceptualized through interdisciplinary perspectives as a multidimensional, 32-item eight-factor construct. In the second stage, the original measurement is pretested on a student sample and recalibrated into a 16-item four-factor instrument. In the third stage, general consumers are invited to complete a task in which they are asked to perform a search with a mobile device before rating the measurement items. A confirmatory factor analysis produces a 12-item four-factor instrument. Furthermore, a second-order structure results from a statistical comparison of alternative models through a competing model strategy. In the final stage, we use a scenario method to validate the measurement tool while establishing discriminant, nomological, and known-group validities. The thorough validation results demonstrate the value of our instrument as a measurement tool of perceived ubiquity that is useful in describing the unique nature of mobile devices and predicting differences in user perceptions of mobile services and desktop PC services. Theoretical and managerial implications are discussed, important limitations are recognized and future research directions are suggested.
Effect of laminin 332 on motility and invasion in bladder cancer
Authors: Kang Sung‐Gu , Ha Young‐Ran , Ko Young‐Hwii , Kang Seok‐Ho , Joo Kwan‐Joong , Cho Hyun‐Yee , Park Hong‐Seok , Kim Chul‐Hwan , Kwon Soon‐Young , Kim Je‐Jong , Cheon Jun , Lee Jeong‐Gu
Published: February 2013

We examined the correlation between laminin 332 and malignancy in bladder cancer patients, and, using a strain of invasive bladder cancer cells, determined whether laminin 332 causes bladder cancer motility and invasion. To investigate the correlation between laminin 332 g2 distribution and patient outcome, we performed a semiquantitative immunohistochemical analysis of 35 paraffin‐embedded samples using the antibody D4B5, which is specific for the laminin 5 γ2 chain. To evaluate the role of laminin 332 in NBT‐II cell motility and invasion, we used a scratch assay and the Boyden chamber chemoinvasion system. Tumor stage and grade were significantly correlated with a loss of laminin 332 γ2 chain from the basement membrane (p = 0.001) and its retention in the cytoplasm (p = 0.001) (Kruskal–Wallis test). Kaplan–Meier survival curves revealed an association between the risk of progression and cytoplasmic retention of the laminin 332 γ2 chain. In addition, an in vitro scratch assay showed an increase in the migration of cells treated with laminin 332 from their cluster. The Boyden chamber assay showed that laminin 332 potentiated NBT‐II cell invasion. Immunohistochemistry results showed that bladder cancer patients with a higher malignancy expressed more laminin 332. The in vitro scratch and invasion assay showed that laminin 332 stimulated the motility and invasion of bladder cancer cells. The invasion assay explains the correlation between laminin 332 expression and bladder cancer malignancy.
Genetically engineered mouse models of prostate cancer
Authors: Parisotto Maxime , Metzger Daniel
Published: February 2013

Despite major improvement in treatment of early stage localised prostate cancer, the distinction between indolent tumors and those that will become aggressive, as well as the lack of efficient therapies of advanced prostate cancer, remain major health problems. Genetically engineered mice (GEM) have been extensively used to investigate the molecular and cellular mechanisms underlying prostate tumor initiation and progression, and to evaluate new therapies. Moreover, the recent development of conditional somatic mutagenesis in the mouse prostate offers the possibility to generate new models that more faithfully reproduce the human disease, and thus should contribute to improve diagnosis and treatments. The strengths and weaknesses of various models will be discussed, as well as future opportunities.
Soil–landscape response to mid and late Quaternary climate fluctuations based on numerical simulations
Authors: Cohen Sagy , Willgoose Garry , Hancock Greg
Published: February 2013

We use a numerical dynamic soil–landscape model to study one aspect of the spatio-temporal soil–landscape evolution process, the effect of climatic fluctuations on soil grading distribution in space and time in response to the interplay between physical weathering and surface erosion (soil mineralogical fluxes). We simulate a synthetic soil–landscape system over the middle and late Quaternary (last 400 ka). The results show that (1) soil–landscape response to climate change is non-linear and highly spatially variable, even at hillslope scale; and (2) soil–landscape adjustment to climate change can lag tens of thousands of years and is both spatially and temporally variable. We propose that the legacy of past climatic condition (i.e. last glacial maximum) in modern soil–landscape systems vary considerably in space. This implies that the spatiotemporal uniformity in which soil is typically described in Earth system modeling and analysis (e.g. carbon cycle) grossly underestimates their actual complexity.
Inertial collapse of liquid rings
Authors: Darbois Texier Baptiste , Piroird Keyvan , Quéré David , Clanet Christophe
Published: February 2013

Liquid rings can be generated in the Leidenfrost state using liquid oxygen of low boiling point ($- 183~\textdegree \mathrm{C} $) and high magnetic susceptibility, allowing one to ‘sculpt’ the liquid into a ring shape using an annular magnet. When the magnetic field is turned off, the ring shrinks back into a puddle with a constant acceleration. A potential flow approach accurately describes the dynamics of closure with an equation reminiscent of the Rayleigh–Plesset equation for the collapse of transient cavities.
A Terminal Prognosis? The Study of US Politics in Europe
Authors: ASHBEE EDWARD
Published: February 2013

The study of US politics in Europe has always been small-scale. In the UK, it is often tied to contemporary history. In much of continental Europe, it is distanced from political science (which largely eschews area studies) and is instead, intellectually and institutionally, an adjunct to American studies. Whereas many other fields within political science have been compelled to consider the methodological underpinnings of their work, US politics has yet to do this. In contrast, within the US, political science has, since the behaviouralist revolution, been largely structured around quantitative forms of analysis. There is therefore a significant gulf between the study of US politics in Europe and political science in both Europe and the US. Furthermore, American studies is itself under long-term threat in some European countries because, forecasters suggest, the demand for English-language teaching (to which American studies is generally tied) will decline in the long term. As a consequence of these developments, those who study US politics at university level are not being replaced as they retire and there are few new entrants into the profession. The article suggests that US politics should, as a subdiscipline, seek out openings that might bring the subject back towards political science. In particular, it argues that US politics researchers in Europe should look more closely at developments within historical institutionalism, American political development (APD) and comparative politics.
Postauricular hypodermic injection to treat inner ear disorders: experimental feasibility study using magnetic resonance imaging and pharmacokinetic comparison
Authors: Li J , Yu L , Xia R , Gao F , Luo W , Jing Y
Published: February 2013

Background:

To investigate the feasibility of postauricular hypodermic injection for treating inner ear disorders, we compared perilymph pharmacokinetics for postauricular versus intravenous injection, using magnetic resonance imaging, in an animal model.

Methods:

Twelve albino guinea pigs were divided randomly into two groups and administered gadopentetate dimeglumine via either a postauricular or an intravenous bolus injection. A 7.0 Tesla magnetic resonance imaging system was used to assess the signal intensities of gadolinium-enhanced images of the cochlea, as a biomarker for changes in gadopentetate dimeglumine concentration in the perilymph. Pharmacokinetic parameters were calculated based on these signal intensity values.

Results:

Guinea pigs receiving postauricular injection showed longer times to peak signal intensity, longer elimination half-life, longer mean residence time and a greater area under the signal–time curve (from pre-injection to the last time point) (p < 0.05).

Conclusion:

Postauricular injection shows potential as an efficient drug delivery route for the treatment of inner ear disorders.
Seasonal fruiting and seed dispersal by the brown lemur in a tropical dry forest, north-western Madagascar
Authors: Sato Hiroki
Published: February 2013

Community-wide seasonal fruiting and seed dispersal by the common brown lemur (Eulemur fulvus fulvus) was investigated in a tropical dry forest, north-western Madagascar. The brown lemur is the sole disperser of large seeds > 10 mm in diameter. Considering the limited assemblage of dispersers, large-seeded plants should display distinctive fruiting patterns to acquire dispersers. To compare fruiting patterns and seed dispersal by the brown lemur between small-seeded and large-seeded plants, fruiting conditions for 432 trees on a transect, feeding activity over 1212 h of observation, and the composition of 1126 dung samples were recorded for 1 y. Seeds of a total of 52 species were identified through both observations and faecal analysis. As rainfall increased, larger numbers of species and individuals of small-seeded plants fruited. Among the 52 species, the brown lemur dispersed 29 and 13 species with small and large seeds, respectively, during the rainy season. High moisture levels probably favoured seed germination and seedling establishment in various species. During the dry season, although small-seeded species rarely fruited, a few large-seeded species, particularly Vitex beraviensis, formed a long-term fruiting peak and provided essential food resources for the brown lemur. Because seeds of these large-seeded plants were frequently dispersed by the brown lemur, dry-season fruiting seemed to be favourable to avoid competition for dispersers with other plant species.
Contemporary Just War Thinking: Which Is Worse, to Have Friends or Critics?
Authors: Johnson James Turner
Published: February 2013

The increasingly widespread and energetic engagement with the idea of just war over the last fifty years of thinking on morality and armed conflict—especially in English-speaking countries—presents a striking contrast to the previous several centuries, going back to the early 1600s, in which thinkers addressing moral issues related to war did so without reference to the just war idea.
Update on diversity and distribution of HIV-1 subtypes in Yunnan province
Authors: SU Y.-Z. , MA Y.-L. , JIA M.-H. , HE X. , YANG L. , CHENG C.-L. , CHEN M. , SHI Y.-H. , CHEN L. , CHEN H.-C. , YANG C.-J. , YU S.-Y. , LU L.
Published: February 2013

The aim of this study was to characterize updated HIV subtypes in Yunnan to determine their origins and distribution within the population. RT–PCR of both thegagandenvgenes were sequenced from Yunnan province inhabitants newly diagnosed with HIV-1. Sequence data from 290 samples were used for statistical analysis of subtype distribution and phylogenetic tree construction. Distribution data were adjusted to account for different geographical distributions of HIV-1 subtypes in the population. Phylogenetic analysis revealed six HIV-1 subtypes in Yunnan, including eight types of unique recombination forms (URFs). The most prevalent subtypes in this province, CRF07_BC (18·9%), CRF08_BC (39·1%), CRF01_AE (22·4%), and URFs (subtype C, 5·9% and subtype B, 4·5%), were all recombinants. We found significant differences in the distribution of these HIV-1 subtypes not only geographically, but also between various ethnic groups and with respect to transmission routes. Our findings indicate a complex population of HIV-1 subtypes, URFs, and recombinant subtypes in Yunnan province. This diversity could make the prevention and control of HIV infection in Yunnan more difficult due to the possibility of virus recombination or infection by multiple subtypes.
Stress Levels in EMS Personnel: A National Survey
Authors: Cydulka Rita K. , Emerman Charles L. , Shade Bruce , Kubincanek John
Published: February 2013

Objective:

The purpose of this study was to evaluate stress levels in emergency medical services personnel across the United States.

Design:

Confidential, 20-question survey tool, Medical Personnel Stress Survey-Abbreviated (MPSS-R). A total score of 50 indicates average stress levels. A score of 12.5 on the subset measurements of somatic distress, job dissatisfaction, organizational stress, and negative attitudes towards patients indicates average levels of stress. Data were analyzed using ANOVA and t-test.

Interventions:

None.

Results:

A total of 658 of 3,000 emergency medical technicians (EMTs) (22%) completed the survey. The mean value of 69.3±6.3 for the total stress scores was very high Mean values for the subset scores were: somatic distress = 19.6±3.3; organizational stress = 17.3±2.4; job dissatisfaction = 17.0±2.6; negative attitudes towards patients = 15.5±2.3. Characteristics predicting higher stress were EMT-basic (A) licensure, basic life support (BLS) only service provider, volunteer status, new employee working in a small EMS organization, and providing service to a small town.

Conclusion:

Stress levels in EMS personnel were very high, were manifested primarily as somatic distress, secondarily as organizational stress and job dissatisfaction, and lastly as negative patient attitudes. Stress levels and subset manifestations of occupational stress among EMS personnel varied depending on gender, marital status, age, level of training and function, on salaried or volunteer status, length of time as an EMT, and size of the organization, city, and population served. Care should be taken to address stresses peculiar to individual EMS system needs.
God Save This “Broken” Land: The Efficacy of Closed-Circuit Voter Targeting in a U.K. Election
Authors: Calfano Brian Robert , Djupe Paul A. , Wilson Angelia R.
Published: February 2013

Recent research in the United States has found candidates for elected office are able to use a rhetorical form of closed-circuit communication with evangelical Protestants — “God Talk” — that communicates valuable political information without alerting other constituencies. Close observation of the 2010 parliamentary elections in the United Kingdom (U.K.) uncovered what appeared to be a form of God Talk in use by David Cameron and the Conservative Party, especially the use of “broken” to describe the state of Britain. Thus, we assess whether God Talk is an efficacious communication strategy in the U.K. using an experiment that selectively exposes participants to God Talk statements. The mixed results suggest that some forms of God Talk are better than others in conveying to U.K. evangelicals that a candidate is conservative and religious without triggering the same associations by non-evangelical voters. We close with a discussion of the normative impact of such communication strategies.
Robust estimation of microbial diversity in theory and in practice
Authors: Haegeman Bart , Hamelin Jérôme , Moriarty John , Neal Peter , Dushoff Jonathan , Weitz Joshua S
Published: February 2013

Quantifying diversity is of central importance for the study of structure, function and evolution of microbial communities. The estimation of microbial diversity has received renewed attention with the advent of large-scale metagenomic studies. Here, we consider what the diversity observed in a sample tells us about the diversity of the community being sampled. First, we argue that one cannot reliably estimate the absolute and relative number of microbial species present in a community without making unsupported assumptions about species abundance distributions. The reason for this is that sample data do not contain information about the number of rare species in the tail of species abundance distributions. We illustrate the difficulty in comparing species richness estimates by applying Chao’s estimator of species richness to a set of in silico communities: they are ranked incorrectly in the presence of large numbers of rare species. Next, we extend our analysis to a general family of diversity metrics (‘Hill diversities’), and construct lower and upper estimates of diversity values consistent with the sample data. The theory generalizes Chao’s estimator, which we retrieve as the lower estimate of species richness. We show that Shannon and Simpson diversity can be robustly estimated for the in silico communities. We analyze nine metagenomic data sets from a wide range of environments, and show that our findings are relevant for empirically-sampled communities. Hence, we recommend the use of Shannon and Simpson diversity rather than species richness in efforts to quantify and compare microbial diversity.
Changes in assembly processes in soil bacterial communities following a wildfire disturbance
Authors: Ferrenberg Scott , O’Neill Sean P , Knelman Joseph E , Todd Bryan , Duggan Sam , Bradley Daniel , Robinson Taylor , Schmidt Steven K , Townsend Alan R , Williams Mark W , Cleveland Cory C , Melbourne Brett A , Jiang Lin , Nemergut Diana R
Published: February 2013

Although recent work has shown that both deterministic and stochastic processes are important in structuring microbial communities, the factors that affect the relative contributions of niche and neutral processes are poorly understood. The macrobiological literature indicates that ecological disturbances can influence assembly processes. Thus, we sampled bacterial communities at 4 and 16 weeks following a wildfire and used null deviation analysis to examine the role that time since disturbance has in community assembly. Fire dramatically altered bacterial community structure and diversity as well as soil chemistry for both time-points. Community structure shifted between 4 and 16 weeks for both burned and unburned communities. Community assembly in burned sites 4 weeks after fire was significantly more stochastic than in unburned sites. After 16 weeks, however, burned communities were significantly less stochastic than unburned communities. Thus, we propose a three-phase model featuring shifts in the relative importance of niche and neutral processes as a function of time since disturbance. Because neutral processes are characterized by a decoupling between environmental parameters and community structure, we hypothesize that a better understanding of community assembly may be important in determining where and when detailed studies of community composition are valuable for predicting ecosystem function.