bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mutations in KCND3 cause spinocerebellar ataxia type 22
Authors: Lee Yi‐Chung , Durr Alexandra , Majczenko Karen , Huang Yen‐Hua , Liu Yu‐Chao , Lien Cheng‐Chang , Tsai Pei‐Chien , Ichikawa Yaeko , Goto Jun , Monin Marie‐Lorraine , Li Jun Z. , Chung Ming‐Yi , Mundwiller Emeline , Shakkottai Vikram , Liu Tze‐Tze , Tesson Christelle , Lu Yi‐Chun , Brice Alexis , Tsuji Shoji , Burmeister Margit , Stevanin Giovanni , Soong Bing‐Wen 
Published: July 2012

AbstractObjective:To identify the causative gene in spinocerebellar ataxia (SCA) 22, an autosomal dominant cerebellar ataxia mapped to chromosome 1p21‐q23.Methods:We previously characterized a large Chinese family with progressive ataxia designated SCA22, which overlaps with the locus of SCA19. The disease locus in a French family and an Ashkenazi Jewish American family was also mapped to this region. Members from all 3 families were enrolled. Whole exome sequencing was performed to identify candidate mutations, which were narrowed by linkage analysis and confirmed by Sanger sequencing and cosegregation analyses. Mutational analyses were also performed in 105 Chinese and 55 Japanese families with cerebellar ataxia. Mutant gene products were examined in a heterologous expression system to address the changes in protein localization and electrophysiological functions.Results:We identified heterozygous mutations in the voltage‐gated potassium channel Kv4.3‐encoding gene KCND3: an in‐frame 3‐nucleotide deletion c.679_681delTTC p.F227del in both the Chinese and French pedigrees, and a missense mutation c.1034G>T p.G345V in the Ashkenazi Jewish family. Direct sequencing of KCND3 further identified 3 mutations, c.1034G>T p.G345V, c.1013T>C p.V338E, and c.1130C>T p.T377M, in 3 Japanese kindreds. Immunofluorescence analyses revealed that the mutant p.F227del Kv4.3 subunits were retained in the cytoplasm, consistent with the lack of A‐type K+ channel conductance in whole cell patch‐clamp recordings.Interpretation:Our data identify the cause of SCA19/22 in patients of diverse ethnic origins as mutations in KCND3. These findings further emphasize the important role of ion channels as key regulators of neuronal excitability in the pathogenesis of cerebellar degeneration. ANN NEUROL 2012;72:859–869.
Universality in heat conduction theory: weakly nonlocal thermodynamics
Authors: Ván P. , Fülöp T. 
Published: July 2012

AbstractA linear irreversible thermodynamic framework of heat conduction in rigid conductors is introduced. The deviation from local equilibrium is characterized by a single internal variable and a current multiplier. A general constitutive evolution equation of the current density of the internal energy is derived by introducing a linear relationship between the thermodynamic forces and fluxes. The well‐known Fourier, Maxwell–Cattaneo–Vernotte, Guyer–Krumhansl, Jeffreys‐type, and Green–Naghdi‐type equations of heat conduction are obtained as special cases. The universal character of the approach is demonstrated by two examples. Solutions illustrating the properties of the equation with jump boundary conditions are given.
Statistical characterization of the impact strengths of vapor‐grown carbon nanofiber/vinyl ester nanocomposites using a central composite design
Authors: Torres Glenn W. , Nouranian Sasan , Lacy Thomas E. , Toghiani Hossein , Pittman Charles U. , DuBien Janice L. 
Published: July 2012

AbstractThe effects of vapor‐grown carbon nanofiber (VGCNF) weight fraction, high‐shear mixing time, and ultrasonication time on the Izod impact strengths of VGCNF/vinyl ester (VE) nanocomposites were studied using a central composite design. A response surface model (RSM) for predicting impact strengths was developed using regression analysis. RSM predictions suggested that an 18% increase in impact strength was possible for nanocomposites containing only 0.170 parts per hundred parts resin (phr) of VGCNFs (∼0.1 v%) that were high‐shear mixed for 100 min when compared to that of neat VE. In general, the predicted impact strengths increased for high‐shear mixing times above 55 min and VGCNF weight fractions below 0.400 phr. The predicted strengths decreased as the VGCNF weight fraction was further increased. Scanning electron micrographs of the nanocomposite fracture surfaces showed that increased impact strength could be directly correlated to better nanofiber dispersion in the matrix. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013
Effect of the graphite nanoplatelet size on the mechanical, thermal, and electrical properties of polypropylene/exfoliated graphite nanocomposites
Authors: Kuvardina E. V. , Novokshonova L. A. , Lomakin S. M. , Timan S. A. , Tchmutin I. A. 
Published: July 2012

AbstractPolypropylene (PP)/exfoliated graphite nanoplatelet (xGnP) nanocomposites with various intrinsic aspect ratios of graphite nanoplatelets (GnPs; large and small in diameter) were prepared by a melt‐mixing procedure. Transmission electron microscopy showed that all types of xGnP were well‐dispersed in the polymer matrix. The effects of the dimensions and loading of the xGnPs on the morphology, mechanical reinforcement, and electrical properties of PP/xGnP were studied. A differential scanning calorimetry study of the PP/xGnP morphology indicated that all types of xGnP additives were heterogeneous nucleation sites for PP crystallization. Tensile testing, DMA, and thermogravimetric analysis of PP/xGnPs with different types of GnP additives showed enhancements in their mechanical properties, heat resistance, and thermal stability compared to plain PP. We also found a significant increase in the conductivity of PP/xGnP. The PP/xGnP with a large diameter of GnPs demonstrated the lowest percolation threshold, equal to 4 vol % of the xGnP loading. The mechanical properties were estimated by means of micromechanical modeling. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013
Evaluation of the influence of polyoxide‐based surfactants on the separation process of model emulsions of asphaltenes using the FTIR‐ATR technique
Authors: Aguiar Janaina I. S. , Neto Jéssica S. G. , Almeida Sarah M. , Mansur Claudia R. E. 
Published: July 2012

AbstractDuring extraction of crude oil, water is generally present in the oil. This water‐in‐oil (w/o) mixture undergoes turbulent flow that promotes sheer forces, resulting in the appearance of emulsions. These emulsions can be highly stable due to the presence of compounds with polar characteristics such as asphaltenes, which act as natural emulsifiers and form resistant films at the oil–water interface. Nonionic surfactants based on polyoxides are widely used to prevent the formation or to break down w/o emulsions. To shed more light on the destabilization mechanism of w/o emulsions promoted by these surfactants, in this study the techniques of tensiometry and Fourier transform infrared spectroscopy with attenuated total reflectance (FTIR‐ATR) were applied to study the interface formed by poly(ethylene oxide)‐poly(propylene oxide) (PEO‐PPO) block copolymers and asphaltenic petroleum fractions. Initially, the critical micelle concentration of the copolymers in aqueous solution was determined. The results agreed with those found by tensiometry. The bottle test was used to evaluate the break‐down of the w/o emulsions in the presence of the PEO‐PPO block copolymers, and the results presented good agreement with those obtained by tensiometry and FTIR‐ATR. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013
Influence of gamma radiation on compatibilized LLDPE/magnesium hydroxide/sepiolite composites
Authors: Ahmad Ishaq , Shafiq Muhammad , Yasin Tariq 
Published: July 2012

AbstractThe influence of gamma irradiation on the properties of compatibilized linear low‐density polyethylene/magnesium hydroxide (MH)/sepiolite composites has been investigated. Vinyl triethoxy silane and maleated polyethylene have been used as compatibilizers. The compatibilizing effect in the composites is confirmed by the Fourier transform infrared spectra, which showed the presence of additional chemical bonds, which are responsible for the enhanced polymer‐filler interaction. As a result, the miscibility of the polar additives into the nonpolar polymer matrix is enhanced. The scanning electron micrographs revealed that the additives are well embedded and uniformly dispersed in the polymer matrix without any voids. The known thermal decomposition temperature of MH (∼ 350°C) is also increased in the compatibilized composites. In addition, 150 kGy irradiated composite showed a remarkable improvement of 37°C in the onset degradation temperature of unirradiated composite. Furthermore, the formation of radiation crosslinked structure in the composites also improved the mechanical properties of the composites. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013
Prescription stimulants in individuals with and without attention deficit hyperactivity disorder: misuse, cognitive impact, and adverse effects
Authors: Lakhan Shaheen E. , Kirchgessner Annette 
Published: July 2012

AbstractPrescription stimulants are often used to treat attention deficit hyperactivity disorder (ADHD). Drugs like methylphenidate (Ritalin, Concerta), dextroamphetamine (Dexedrine), and dextroamphetamine‐amphetamine (Adderall) help people with ADHD feel more focused. However, misuse of stimulants by ADHD and nonaffected individuals has dramatically increased over recent years based on students' misconceptions or simple lack of knowledge of associated risks. In this review, we discuss recent advances in the use and increasing misuse of prescription stimulants among high school and college students and athletes. Given the widespread belief that stimulants enhance performance, there are in fact only a few studies reporting the cognitive enhancing effects of stimulants in ADHD and nonaffected individuals. Student athletes should be apprised of the very serious consequences that can emerge when stimulants are used to improve sports performance. Moreover, misuse of stimulants is associated with dangers including psychosis, myocardial infarction, cardiomyopathy, and even sudden death. As ADHD medications are prescribed for long‐term treatment, there is a need for long‐term safety studies and education on the health risks associated with misuse is imperative.
Enzyme‐Specific Activation versus Leaving Group Ability
Authors: de Beer Roseri J. A. C. , Bögels Berry , Schaftenaar Gijs , Zarzycka Barbara , Quaedflieg Peter J. L. M. , van Delft Floris L. , Nabuurs Sander B. , Rutjes Floris P. J. T. 
Published: July 2012

AbstractEnzyme‐specific activation and the substrate mimetics strategy are effective ways to circumvent the limited substrate recognition often encountered in protease‐catalyzed peptide synthesis. A key structural element in both approaches is the guanidinophenyl (OGp) ester, which enables important interactions for affinity and recognition by the enzyme—at least, this is usually the explanation given for its successful application. In this study we show that leaving group ability is of equal or even greater importance. To this end we used both experimental and computational methods: 1) synthesis of close analogues of OGp, and their evaluation in a dipeptide synthesis assay with trypsin, 2) molecular docking studies to provide insights into the binding mode, and 3) ab initio calculations to evaluate their electronic properties.
Enhancement of the Substrate Scope of Transketolase
Authors: Ranoux Adeline , Karmee Sanjib K. , Jin Jianfeng , Bhaduri Anirban , Caiazzo Aldo , Arends Isabel W. C. E. , Hanefeld Ulf 
Published: July 2012

AbstractTo enhance the activity of transketolase towards nonphosphorylated substrates and enlarge the scope of its substrates, notably to long polyol aldehyde acceptors (D‐ribose or D‐glucose), a rational design‐supported evolution strategy was applied. By using docking experiments, an in silico library, and iterative mutagenesis, libraries of single‐ and double‐point mutants were designed and generated. A double‐screening approach was implemented, coupling a preselection activity assay (HPLC method) and a selective assay (GC method) to find the best enzymes. Several mutants (R526N, R526Q, R526Q/S525T, R526K/S525T) showed improved activities towards nonphosphorylated substrates as the coupled products of lithium hydroxypyruvate (HPA) with glycolaldehyde (GO), D‐ribose or D‐glucose. These mutated enzymes were further characterised. They were shown to be up to four times more active than the wild‐type (mutant R526Q/S525T) for nonphosphorylated substrates LiHPA/GO (Vm/Km for LiHPA = 92.4 instead of 28.8×10−3 min−1 for the wild‐type) and 2.6 times more active for substrates LiHPA/rib.
A smart 19F and 1H MRI probe with self‐immolative linker as a versatile tool for detection of enzymes
Authors: Keliris Aneta , Mamedov Ilgar , Hagberg Gisela E. , Logothetis Nikos K. , Scheffler Klaus , Engelmann Jörn 
Published: July 2012

ABSTRACTHere we report on a dual‐modal 19F and 1H MRI paramagnetic probe with a self‐immolative linker, Gd–DOMF–Gal. The enzymatic conversion of this probe by β‐galactosidase resulted in a simultaneous turning on of the fluorine signal and changed ability of the Gd3+ complex to modulate the 1H MR signal intensity of the surrounding water molecules. A versatile imaging platform for monitoring a variety of enzymes by 19F and 1H MRI using this molecular design is proposed. Copyright © 2012 John Wiley & Sons, Ltd.
In vivo monitoring of antiangiogenic therapy by magnetic resonance and bioluminescence imaging in an M21 tumor model through activation of an hsp70 promoter–luciferase reporter construct
Authors: Hundt Walter , Steinbach Silke , O'Connell‐Rodwell Caitlin E. , Mayer Dirk , Burbelko Mykhaylo , Guccione Samira 
Published: July 2012

ABSTRACTWe have investigated the effect of targeted gene therapy on the melanoma cell line M21, using a combination of bioluminescence imaging (BLI) and magnetic resonance imaging (MRI). M21 cells transfected with a plasmid containing either an hsp70 (Hspa1b) or a CMV promoter fragment, along with the luciferase reporter gene, were grown to a tumor size of 900 mm3. Five mice in each group were intravenously treated every 72 h with a complex consisting of a nanoparticle, an Arg–Gly–Asp–peptide, and a dominant negative mutant protein kinase inhibitor gene. BLI and MRI were performed at specific time intervals. The MRI scan protocol included T1‐weighted‐spin‐echo ± contrast medium, T2‐weighted‐fast‐spin‐echo, dynamic contrast‐enhanced MRI (DCE‐MRI), and diffusion‐weighted‐stimulated‐echo‐acquisition‐mode‐sequence. The T2 times were obtained using a 1.5 T GE MRI scanner. The size of the treated M21 tumors remained almost constant during the treatment phase (837.8 ± 133.4 vs 914.8 ± 134.4 mm3). BLI showed that, if transcription was controlled by the CMV promoter, the luciferase activity decreased to 51.1 ± 8.3%. After transcription was controlled by the hsp70 promoter, the highest luciferase activity (4.4 ± 0.3 fold) was seen after 24 h. The signal‐to‐noise ratio (SNR; T2‐weighted images) of the tumors was 36.7 ± 0.6 and subsequently dropped to 31.2 ± 4.4 (p = 0.004). DCE‐MRI showed a reduction of the slope and the Akep of 67.8% ± 4.3 and 64.8% ± 3.3%, respectively, compared with the baseline. The SNR value (T1‐weighted images) of the tumors was 42.3 ± 1.9 immediately following contrast medium application and subsequently dropped to 28.5 ± 3.0 (p < 0.001). In the treatment group, the diffusion coefficient increased significantly under therapy (0.66 ± 0.05 vs the pretreatment value of 0.54 ± 0.009 p < 0.01). Thus, we observed that targeted antiangiogenic therapy can induce activation of the hsp70 promoter through a heat shock/luciferase reporter system. Moreover, MRI showed a significant reduction of the contrast medium uptake parameters and an increase in the diffusion coefficient of the tumors. Copyright © 2012 John Wiley & Sons, Ltd.
Uniform mesoporous silica coated iron oxide nanoparticles as a highly efficient, nontoxic MRI T2 contrast agent with tunable proton relaxivities
Authors: Ye Fei , Laurent Sophie , Fornara Andrea , Astolfi Laura , Qin Jian , Roch Alain , Martini Alessandro , Toprak Muhammet S. , Muller Robert N. , Muhammed Mamoun 
Published: July 2012

ABSTRACTMonodisperse mesoporous silica (mSiO2) coated superparamagnetic iron oxide (Fe3O4@mSiO2) nanoparticles (NPs) have been developed as a potential magnetic resonance imaging (MRI) T2 contrast agent. To evaluate the effect of surface coating on MRI contrast efficiency, we examined the proton relaxivities of Fe3O4@mSiO2 NPs with different coating thicknesses. It was found that the mSiO2 coating has a significant impact on the efficiency of Fe3O4 NPs for MRI contrast enhancement. The efficiency increases with the thickness of mSiO2 coating and is much higher than that of the commercial contrast agents. Nuclear magnetic resonance (NMR) relaxometry of Fe3O4@mSiO2 further revealed that mSiO2 coating is partially permeable to water molecules and therefore induces the decrease of longitudinal relaxivity, r1. Biocompatibility evaluation of various sized (ca. 35–95 nm) Fe3O4@mSiO2 NPs was tested on OC‐k3 cells and the result showed that these particles have no negative impact on cell viability. The enhanced MRI efficiency of Fe3O4@mSiO2 highlights these core–shell particles as highly efficient T2 contrast agents with high biocompatibility. Copyright © 2012 John Wiley & Sons, Ltd.
Role of EphA/ephrin‐A signaling in the development of topographic maps in mouse corticothalamic projections
Authors: Torii Masaaki , Rakic Pasko , Levitt Pat 
Published: July 2012

AbstractCorticothalamic (CT) feedback outnumbers thalamocortical projections and regulates sensory information processing at the level of the thalamus. It is well established that EphA7, a member of EphA receptor family, is involved in the topographic mapping of CT projections. The aim of the present study was to dissect the precise impact of EphA7 on each step of CT growth. We used in utero electroporation‐mediated EphA7 overexpression in developing somatosensory CT axons to dissect EphA7/ephrin‐A‐dependent mechanisms involved in regulating both initial targeting and postnatal growth of the CT projections. Our data revealed that topographic maps of cortical afferents in the ventrobasal complex and medial part of the posterior complex in the thalamus become discernible shortly after birth and are fully established by the second postnatal week. This process starts with the direct ingrowth of the CT axons to the designated areas within target thalamic nuclei and by progressive increase of axonal processes in the terminal zones. Large‐scale overproduction and elimination of exuberant widespread axonal branches outside the target zone was not observed. Each developmental event was coordinated by spatially and temporally different responsiveness of CT axons to the ephrin‐A gradient in thalamic nuclei, as well as by the matching levels of EphA7 in CT axons and ephrin‐As in thalamic nuclei. These results support the concept that the topographic connections between the maps in the cerebral cortex and corresponding thalamic nuclei are genetically prespecified to a large extent, and established by precise spatiotemporal molecular mechanisms that involve the Eph family of genes. J. Comp. Neurol. 521:626–637, 2013.
WDR1 expression in normal and noise‐damaged Sprague‐Dawley rat cochleae
Authors: Song Jae‐Jin , Adler Henry J. , Lee Ho Sun , Jang Jeong Hun , Park Min‐Hyun , Lee Jun Ho , Chang Sun O , Oh Seung Ha 
Published: July 2012

AbstractWD40 repeat protein 1 (WDR1) has been suggested as a protective mechanism or a sign of regeneration in avian cochlea. However, its role in mammalian cochlea has yet to be determined. Hence, we investigated WDR1 expression in sound‐overstimulated Sprague‐Dawley rats. Rats were divided into three groups (the permanent and temporary threshold shift [PTS and TTS] groups and the control group) according to the extent of noise exposure and euthanized immediately, 3, or 7 days after noise exposure for cochlear harvest. Immunocytochemistry localized WDR1 to outer hair cells, Deiter's cells, outer sulcus cells, and Reissner's membrane in the control group, and the PTS and TTS groups exhibited stronger WDR1 expression in the same cochlear regions than the controls. Moreover, WDR1 expression in these noise‐exposed groups was extended to inner hair cells and basal cells of the stria vascularis. The expression of WDR1 in the PTS and TTS groups showed differences in intensity and shifts of localization, based on exposure length and recovery duration. Contrary to the avian cochlea, hair cell regeneration does not naturally occur in the acoustically damaged mammalian cochlea. Therefore, elevated WDR1 expression after acoustic overstimulation in the current experiments may provide a mechanism for protection against noise exposure. J. Comp. Neurol. 521:1470–1481, 2013. © 2012 Wiley Periodicals, Inc.
Mutation of the BiP/GRP78 gene causes axon outgrowth and fasciculation defects in the thalamocortical connections of the mammalian forebrain
Authors: Favero Carlita B. , Henshaw Rasha N. , Grimsley‐Myers Cynthia M. , Shrestha Ayushma , Beier David R. , Dwyer Noelle D. 
Published: July 2012

AbstractProper development of axonal connections is essential for brain function. A forward genetic screen for mice with defects in thalamocortical development previously isolated a mutant called baffled. Here we describe the axonal defects of baffled in further detail and identify a point mutation in the Hspa5 gene, encoding the endoplasmic reticulum chaperone BiP/GRP78. This hypomorphic mutation of BiP disrupts proper development of the thalamocortical axon projection and other forebrain axon tracts, as well as cortical lamination. In baffled mutant brains, a reduced number of thalamic axons innervate the cortex by the time of birth. Thalamocortical and corticothalamic axons are delayed, overfasciculated, and disorganized along their pathway through the ventral telencephalon. Furthermore, dissociated mutant neurons show reduced axon extension in vitro. Together, these findings demonstrate a sensitive requirement for the endoplasmic reticulum chaperone BiP/GRP78 during axon outgrowth and pathfinding in the developing mammalian brain. J. Comp. Neurol. 521:677–696, 2013. © 2012 Wiley Priodcals, Inc.
Practice note: Responding to civic conflict: Developing intergroup dialogue co‐facilitators
Authors: Chung‐mei Lensen Kristin , Chesler Mark , Brown Nancy 
Published: July 2012

AbstractA large U.S. city (called here, Coastal City), with a liberal milieu and a history of racial and ethnic conflict, was elected several years ago to increase its ability to deal with racial conflict. The city chose the intergroup dialogue (IGD) method. Here we examine IGD and how it differs from some other conflict response approaches—including the program's purpose, design, initial implementation, and lessons learned in this enterprise. This article describes a program to train intergroup dialogue co‐facilitators, engaging a civic process to improve race relations in a large urban setting.
Use of peace circles in large‐scale community conflict: A case study
Authors: Hamlin Jack B. , Darling Justine 
Published: July 2012

AbstractThis article presents a case study that addresses a community conflict surrounding the issues of homelessness. The decision to use a Peace Circle format, the manner in which it was implemented, including the preparation and controls put in place, the actual process, the manner in which local media was handled to the advantage of the process, and the results and follow‐up of the peace circle process when used in a large scale forum are discussed.