bluuebunny/crossref_metadata_2025 huggingface dataset:
Selective suppression of microglial activation by paeoniflorin attenuates morphine tolerance
Authors: Jiang C. , Xu L. , Chen L. , Han Y. , Tang J. , Yang Y. , Zhang G. , Liu W.
Published: November 2014

Background

The development of antinociceptive tolerance following repetitive administration of opioid analgesics significantly hinders their clinical use. Evidence has accumulated indicating that microglia within the spinal cord play a critical role in morphine tolerance. The present study investigated the effects and possible mechanisms of a natural compound, paeoniflorin, in morphine tolerance via its specific inhibition of microglial activation.

Methods

The microglia cell line BV‐2 was used. Cytokine expression was measured using quantitative polymerase chain reaction. Cell signalling was assayed by Western blot and immunohistochemistry. Nociception was assessed in Sprague‐Dawley rats and CD‐1 mice using Hargreaves’ methods or the hot‐plate test, respectively.

Results

(1) Morphine induces robust BV‐2 cell activation, as evidenced by increased p38 mitogen‐activated protein kinase (MAPK) phosphorylation, nuclear factor (NF)‐κB translocation and proinflammatory cytokine expression. These changes are inhibited by paeoniflorin. (2) Co‐administration of paeoniflorin with morphine potentiates morphine antinociception by inhibiting p38 MAPK/NF‐κB signalling in the spinal cord. (3) Co‐administration of paeoniflorin suppresses morphine‐increased expression of toll‐like receptor‐4 both in BV‐2 cells and within the spinal cord following chronic morphine treatment.

Conclusion

Paeoniflorin directly suppresses morphine‐induced microglial activation and thus results in potentiation of morphine acute analgesia and attenuation of morphine chronic antinociceptive tolerance.
Sensitive Phenol Detection Using Tyrosinase‐Based Phenol Oxidation Combined with Redox Cycling of Catechol
Authors: Noh Soodong , Yang Haesik
Published: November 2014

This paper reports sensitive phenol detection using (i) tyrosinase (Tyr)‐based oxidation of phenol to catechol, combined with (ii) electrochemical‐chemical‐chemical (ECC) redox cycling involving Ru(NH3)63+, catechol, and tris(2‐carboxyethyl)phosphine (TCEP). Phenol is converted into catechol by Tyr in the presence of dissolved O2. Catechol then reacts with Ru(NH3)63+, generating o‐benzoquinone and Ru(NH3)62+. o‐Benzoquinone is reduced back to catechol by TCEP, and Ru(NH3)62+ is accumulated over the course of the incubation. When Ru(NH3)62+ is electrochemically oxidized to Ru(NH3)63+, ECC redox cycling occurs. For simple phenol detection, bare ITO electrodes are used without modifying the electrodes with Tyr. The detection limit for phenol in tap water using Tyr‐based oxidation combined with ECC redox cycling is ca. 10−9 M, while that using only Tyr‐based oxidation is ca. 10−7 M.
Numerical assessment of a shock‐detecting sensor for low dissipative high‐order simulation of shock–vortex interactions
Authors: Khoshab Masih , Dehghan Ali Akbar , Esfahanian Vahid , Darian Hossein Mahmoodi
Published: November 2014

Considering the importance of high‐order schemes implementation for the simulation of shock‐containing turbulent flows, the present work involves the assessment of a shock‐detecting sensor for filtering of high‐order compact finite‐difference schemes for simulation of this type of flows. To accomplish this, a sensor that controls the amount of numerical dissipation is applied to a sixth‐order compact scheme as well as a fourth‐order two‐register Runge–Kutta method for numerical simulation of various cases including inviscid and viscous shock–vortex and shock–mixing‐layer interactions. Detailed study is performed to investigate the performance of the sensor, that is, the effect of control parameters employed in the sensor are investigated in the long‐time integration. In addition, the effects of nonlinear weighting factors controlling the value of the second‐order and high‐order filters in fine and coarse non‐uniform grids are investigated. The results indicate the accuracy of the nonlinear filter along with the promising performance of the shock‐detecting sensor, which would pave the way for future simulations of turbulent flows containing shocks. Copyright © 2014 John Wiley & Sons, Ltd.
Osteoinductive‐nanoscaled silk/HA composite scaffolds for bone tissue engineering application
Authors: Huang Xiaowei , Bai Shumeng , Lu Qiang , Liu Xi , Liu Shanshan , Zhu Hesun
Published: November 2014

Osteoinductive silk/hydroxyapatite (HA) composite scaffolds for bone regeneration were prepared by combining silk with HA/silk core–shell nanoparticles. The HA/silk nanoparticles were directly dispersed in silk solution to form uniform silk/HA blend and then composite scaffolds after a freeze‐drying process. The HA/silk nanoparticles uniformly distributed in silk scaffolds at nanometer scale at varying HA content up to 40%, and substantially improved the compressive strength of the scaffolds produced. Rat bone mesenchymal stem cells (rBMSCs) were cultured in these scaffolds and cell proliferation was analyzed by confocal microscopy and DNA assay. Gene expression and biochemical assays were employed to study the influence of increasing HA/silk nanoparticles on in vitro osteogenic differentiation of rBMSCs. Increasing HA/silk nanoparticles inside silk scaffolds improved the growth and osteogenic capability of rBMSCs in the absence of osteogenic growth factors, and also significantly increased the calcium and collagen I deposition. In addition, compared to silk/HA composite scaffolds containing HA aggregates, the scaffolds loaded with HA/silk nanoparticles showed remarkably higher stiffness and better osteogenic property at same HA content, implying a preferable microenvironment for rBMSCs. These results suggest that the osteogenic property as well as mechanical property of silk/HA scaffolds could be further improved through fabricating their structure and topography at nanometer scale, providing more suitable systems for bone regeneration. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 103B: 1402–1414, 2015.
Mesenchymal Stem Cells Promote Epithelial to Mesenchymal Transition and Metastasis in Gastric Cancer Though Paracrine Cues and Close Physical Contact
Authors: Xue Zengfu , Wu Xiumin , Chen Xiong , Liu Yali , Wang Xin , Wu Kaichun , Nie Yongzhan , Fan Daiming
Published: November 2014

Mesenchymal stem cells (MSCs) have been shown to integrate into the tumor stroma; however, the precise mechanisms of this process are still elusive. In this study, the EMT phenotype and the enhanced metastatic ability of tumor cells were observed using transwell and trans‐endothelial migration assays, respectively, as well as by using electron and laser confocal microscopy. Critical genes were screened and validated using gene arrays and clinical samples, and the changes at the protein level were examined both in vitro and in vivo. Cancer cells acquired an “activated” carcinoma‐associated fibroblasts (CAFs) phenotype after being in close contact with MSCs and enhancing tumor metastasis and growth in vivo. Paracrine signals also induced EMT and promoted transwell and trans‐endothelial migration, the changes were dependent on β‐catenin, MMP‐16, snail and twist. Notably, the higher expression levels of β‐catenin and MMP‐16 were correlated with tumor invasion and distant organ and lymph node metastases in intestinal type gastric cancer. MSCs within the tumor niche significantly facilitated tumor growth and metastasis by paracrine cues and close physical connection. This occurred partly through snail, twist and its downstream targets, specifically β‐catenin/MMP‐16. J. Cell. Biochem. 116: 618–627, 2015. © 2014 Wiley Periodicals, Inc.
Mutation of Spry2 Induces Proliferation and Differentiation of Osteoblasts but Inhibits Proliferation of Gingival Epithelial Cells
Authors: Sanui Terukazu , Tanaka Urara , Fukuda Takao , Toyoda Kyosuke , Taketomi Takaharu , Atomura Ryo , Yamamichi Kensuke , Nishimura Fusanori
Published: November 2014

Sprouty was identified as an inhibitor of the fibroblast growth factor (FGF) receptor, and Sprouty2 (Spry2) functions as a negative regulator of receptor tyrosine kinase signaling. In this study, we investigated how inhibition of Spry2 affects osteoblasts and gingival epithelial cells in periodontal tissue regeneration in vitro. Transduction of a dominant‐negative mutant of Spry2 (Y55A‐Spry2) enhanced basic fibroblast growth factor (bFGF)‐ and epidermal growth factor (EGF)‐induced ERK activation in MC3T3‐E1 osteoblastic cells. In contrast, it decreased their activation in GE1 cells. Consistent with these observations, Y55A‐Spry2 increased osteoblast proliferation with bFGF and EGF stimulation, whereas the proliferation of Y55A‐Spry2‐introduced GE1 cells was decreased via the ubiquitination and degradation of EGF receptors (EGFRs). In addition, Y55A‐Spry2 caused upregulation of Runx2 expression and downregulation of Twist, a negative regulator of Runx2, with treatment of bFGF and EGF, resulting in enhanced osteoblastogenesis accompanied by alkaline phosphatase activation and osteocalcin expression in MC3T3‐E1 cells. These data suggest that suppression of Spry2 expression induces proliferation and differentiation of osteoblastic cells after the addition of a bFGF and EGF cocktail but inhibits proliferation in gingival epithelial cells. These in vitro experiments may provide a molecular basis for novel therapeutic approaches in periodontal tissue regeneration. Taken together, our study proposes that combined application of an inhibitor for tyrosine 55 of Spry2, bFGF, and EGF may effectively allow alveolar bone growth and block the ingrowth of gingival epithelial cells toward bony defects, biologically mimicking a barrier effect in guided tissue regeneration, with in vivo investigation in the future. J. Cell. Biochem. 116: 628–639, 2015. © 2014 Wiley Periodicals, Inc.
lncRNA Expression Signatures in Periodontitis Revealed by Microarray: The Potential Role of lncRNAs in Periodontitis Pathogenesis
Authors: Zou Yaguang , Li Chun , Shu Fangpeng , Tian Zhihui , Xu Wenan , Xu Huiyong , Tian Hua , Shi Rong , Mao Xiangming
Published: November 2014

Periodontitis, a common chronic inflammatory disease of the periodontium, is caused by dental plaque formation induced by microorganisms. Recent studies have demonstrated that lncRNAs play a critical role in the regulation of gene expression and in the pathogenesis of diseases. To demonstrate that periodontitis is associated with lncRNAs, microarray analysis was used to detect differently expressed lncRNAs in chronic periodontitis and adjacent normal tissues. The results of some differently expressed lncRNAs were further confirmed using real‐time PCR. A total of 8925 differentially expressed lncRNAs were detected, including 4313 upregulated lncRNAs and 4612 downregulated lncRNAs. Further lncRNA subgroup analysis showed there were 589 enhancer‐like lncRNAs, 238 homeobox (HOX) cluster lncRNAs, and 1218 Rinn's lincRNAs, of which 656 lincRNAs were upregulated and 562 lincRNAs were downregulated. Therefore, we confirmed that lncRNAs were differently expressed in chronic periodontitis tissues compared with adjacent normal tissues, indicating that lncRNAs may exert partial or key roles in periodontitis pathogenesis and development. Taken together, this study may provide potential targets for future treatment of periodontitis and novel diagnostic biomarkers for periodontitis. J. Cell. Biochem. 116: 640–647, 2015. © 2014 Wiley Periodicals, Inc.
Safety considerations of mammalian target of rapamycin inhibitors in tuberous sclerosis complex and renal transplantation
Authors: Somers Michael J.G. , Paul Elahna
Published: November 2014

Rapamycin‐related mTOR inhibitors (rapalogs) possess immunosuppressive and antiproliferative properties. Their mechanism of action makes them attractive therapies for several disease states but also potentiates adverse effects associated with these drugs. The oral mTOR inhibitor everolimus was recently approved for the treatment of tuberous sclerosis complex (TSC)‐associated renal angiomyolipoma. As clinical use of rapalogs for the treatment of TSC increases, nephrologists and urologists who treat both children and adults with renal masses, as well as internists and geneticists with an interest in renal disease, should be aware of their safety profiles. This review presents the clinical experience of rapamycin‐related mTOR inhibitors in patients with TSC and summarizes their toxicity profiles in renal transplant and TSC populations. Increased usage of rapalogs in a variety of patient populations demands vigilant monitoring of their safety profiles and rigorous differentiation between disease‐specific and drug‐specific toxicities.
To retire or not to retire: That is not the question
Authors: Beehr Terry A.
Published: November 2014

Retirement decisions are multiple choice, not true–false, because retirement takes many forms. Multiple theories have been used to predict retirement and to do research on it, but rational‐economic decision‐making theories, often assuming intentional behavior, dominate the retirement research domain. Although employment serves both manifest (economic) and latent (psychological) functions, research on the decision to move from employment to retirement has focused on the manifest function. Economics tend to play a strong role in employees' retirement decisions, with health probably a close second predictor. Three phases of retirement decision‐making are evident: (i) imagining the possibility of one's future life during retirement; (ii) assessing the past to help decide when to retire; and (iii) the transition to retirement. Both predictors and consequences of retirement are reviewed, with special attention given to bridge employment, the phenomenon of retirees working for pay. Copyright © 2014 John Wiley & Sons, Ltd.
The Role of Childhood Trauma and PTSD in Postpartum Sleep Disturbance
Authors: Swanson Leslie M. , Hamilton Lindsay , Muzik Maria
Published: November 2014

Despite robust associations between postpartum sleep difficulties and maternal psychopathology, little attention has been paid to the role of childhood trauma and posttraumatic stress disorder (PTSD). In the present study, we examined sleep complaints in postpartum women with a history of childhood trauma compared to postpartum women who were not exposed to childhood trauma. Participants (N = 173) completed questionnaires by telephone at 4‐months postpartum. After adjusting for nuisance variables, there were significantly higher rates of sleep disturbance (falling asleep and staying asleep) for women with a past history of neglect (OR = 4.84, p = .036 and 5.78, p = .006, respectively), physical abuse (OR = 9.20, p = .002 and 3.84, p = .044, respectively), and physical abuse with sexual abuse (OR = 5.95, p = .011 and 3.56, p = .045, respectively). Current PTSD was significantly associated with trouble staying asleep (OR = 4.21, p = .032) whereas recovery from PTSD was associated with trouble falling (OR = 4.19, p = .015) and staying asleep (OR = 3.69, p = .011). Our findings affirm the contribution of childhood trauma and PTSD to postpartum sleep.
Nocturnal Autonomic Balance and Sleep in PTSD and Resilience
Authors: Kobayashi Ihori , Lavela Joseph , Mellman Thomas A.
Published: November 2014

Posttraumatic stress disorder (PTSD) has been associated with heightened nocturnal autonomic nervous system (ANS) arousal and sleep disturbances. It has been suggested that relationships between sleep and nocturnal ANS activity are influenced by insomnia; however, investigation of this relationship has been limited in PTSD. This study examined nocturnal ANS activity and its relationship to sleep in PTSD and resilience. Physically healthy young adult African Americans with current PTSD (n = 20) or who had never had PTSD despite exposure to a high‐impact traumatic event (resilient, n = 18) were monitored with ambulatory electrocardiograms and actigraphy for 24‐hr periods. Frequency‐domain heart‐rate variability measures, that is, low‐frequency to high‐frequency ratios (LF/HF), which index sympathetic nervous system activity, and normalized HF (nHF), which indexes parasympathetic nervous system activity were examined. Normalized HF during the time‐in‐bed period was lower for those with PTSD than those with resilience (p = .041). Total sleep time was strongly correlated with time‐in‐bed LF/HF (r = −.72) and nHF (r = .75) in the resilient group, but these were not correlated in the PTSD group. The results suggest elevated nocturnal ANS arousal and dissociation between ANS activity and total sleep time in PTSD.
Photocontrol of Mechanical Properties of Pulp Fibers and Fiber‐to‐Fiber Bonds via Self‐Assembled Polysaccharide Derivatives
Authors: Grigoray Olga , Wondraczek Holger , Daus Stephan , Kühnöl Katrin , Latifi Seyed Kourosh , Saketi Pooya , Fardim Pedro , Kallio Pasi , Heinze Thomas
Published: November 2014

Photoresponsive pulp fibers are prepared by self‐assembly of photoactive cationic cellulose derivatives with pulp fibers in aqueous environment. Photoactive groups of the derivatives undergo 2π + 2π cycloaddition reaction under UV‐light irradiation. Fast photocrosslinking leads to the formation of the covalent bonds between the photoactive groups on the fiber surfaces. This results in drastic enhancement of the mechanical properties of the fiber network. Tensile strength and Z‐directional tensile strength increase by 81 and 84% compared to the original fiber network. Stiffness of the individual fibers increases by 60%. Such concept of controlling mechanical properties of the fiber materials by the light gives a possibility to design smart bio‐based materials and to increase end value of the fiber products.
Provide guidance to adjuncts teaching online when they need it
Authors: Hope Joan
Published: November 2014

Providing support to faculty members who teach online can be a challenge. That's especially true at an institution like Ashford University, where most of them are adjuncts who teach nights and weekends and work during the day at other jobs. But because so many adult learners opt for online classes because of the flexibility and convenience they offer, it's important that adjunct teaching in your distance programs have the resources and support they need to be good teachers.
Solar photovoltaic energy policy and globalization: a multiperspective approach with case studies of Germany, Japan, and China
Authors: Yu Hyun Jin Julie , Popiolek Nathalie , Geoffron Patrice
Published: November 2014

Solar photovoltaic (PV) systems have experienced strong market growth over the last decade. Since the mid‐2000s, the increase in demand in line with policy supports in Europe has attracted the Chinese players into the PV manufacturing market. Chinese production soared in a short time and managed to quickly reduce the cost thanks to large‐scale supply with mass‐produced products. Faced with the global economic crisis, the European countries began reducing their policy supports that caused a decrease in the demand for PV installations. Despite such a market situation, Chinese PV manufacturers have continued to produce large quantities of solar PV products and thereby aggravated the global PV industry situation with a global supply–demand imbalance. China's rapid market expansion without domestic market development has brought unexpected results with an oversupply of PV materials and equipment in a global market and destabilized the PV market. It influenced the PV policy mechanisms of other countries. Many PV firms in the world have since gone into bankruptcy. China and Europe lately went through a trade dispute over the Chinese solar panel imports (dumping suspicion). In this context, this study aims to identify the PV policy mechanisms based on a multiperspective approach in Germany, Japan, and China. A systematic logical framework is proposed and then used to explain each country's PV policy strategy and results. Moreover, PV globalization impacts and interactions among them are studied using the international trade theory. At the end, this research also attempts to seek optimal strategies to improve the global PV mechanisms. Copyright © 2014 John Wiley & Sons, Ltd.
Isobutylene‐rich macromonomers: Dynamics and yields of peroxide‐initiated crosslinking
Authors: Dakin Jackson M. , Shanmugam Karthik Vikram Siva , Twigg Christopher , Whitney Ralph A. , Parent J. Scott
Published: November 2014

New isobutylene‐rich elastomers bearing multiple pendant styrenic, acrylic, maleimidic, vinylic, and allylic functional groups have been prepared and examined in the context of peroxide‐initiated crosslinking. Halide displacement from brominated poly(isobutylene‐co‐isoprene) (BIIR) by the requisite carboxylate nucleophiles in homogeneous toluene solutions provide the desired esters in quantitative yield without complications from dehydrohalogenation or premature crosslinking. Heating the resulting macromonomers with dicumyl peroxide to 160 °C under solvent‐free conditions gives thermoset derivatives, with reaction rates and yields depending markedly on functional group structure. In general, high cure extents can only be achieved using highly reactive pendant functional groups, owing to the competitive balance between crosslinking through CC oligomerization, and degradation through β‐scission of backbone macroradical intermediates. Independent control of crosslinking rates and cure extents is gained through the use of nitroxyl radical traps bearing acrylate functionality. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015, 53, 123–132
Asymmetric mutations in the tetrameric R67 dihydrofolate reductase reveal high tolerance to active‐site substitutions
Authors: Ebert Maximilian C. C. J. C. , Morley Krista L. , Volpato Jordan P. , Schmitzer Andreea R. , Pelletier Joelle N.
Published: November 2014

Type II R67 dihydrofolate reductase (DHFR) is a bacterial plasmid‐encoded enzyme that is intrinsically resistant to the widely‐administered antibiotic trimethoprim. R67 DHFR is genetically and structurally unrelated to E. coli chromosomal DHFR and has an unusual architecture, in that four identical protomers form a single symmetrical active site tunnel that allows only one substrate binding/catalytic event at any given time. As a result, substitution of an active‐site residue has as many as four distinct consequences on catalysis, constituting an atypical model of enzyme evolution. Although we previously demonstrated that no single residue of the native active site is indispensable for function, library selection here revealed a strong bias toward maintenance of two native protomers per mutated tetramer. A variety of such “half‐native” tetramers were shown to procure native‐like catalytic activity, with similar KM values but kcat values 5‐ to 33‐fold lower, illustrating a high tolerance for active‐site substitutions. The selected variants showed a reduced thermal stability (Tm ∼12°C lower), which appears to result from looser association of the protomers, but generally showed a marked increase in resilience to heat denaturation, recovering activity to a significantly greater extent than the variant with no active‐site substitutions. Our results suggest that the presence of two native protomers in the R67 DHFR tetramer is sufficient to provide native‐like catalytic rate and thus ensure cellular proliferation.
Chloroplast outer envelope protein P39 in Arabidopsis thaliana belongs to the Omp85 protein family
Authors: Hsueh Yi‐Ching , Flinner Nadine , Gross Lucia E. , Haarmann Raimund , Mirus Oliver , Sommer Maik S. , Schleiff Enrico
Published: November 2014

Proteins of the Omp85 family chaperone the membrane insertion of β‐barrel‐shaped outer membrane proteins in bacteria, mitochondria, and probably chloroplasts and facilitate the transfer of nuclear‐encoded cytosolically synthesized preproteins across the outer envelope of chloroplasts. This protein family is characterized by N‐terminal polypeptide transport‐associated (POTRA) domains and a C‐terminal membrane‐embedded β‐barrel. We have investigated a recently identified Omp85 family member of Arabidopsis thaliana annotated as P39. We show by in vitro and in vivo experiments that P39 is localized in chloroplasts. The electrophysiological properties of P39 are consistent with those of other Omp85 family members confirming the sequence based assignment of P39 to this family. Bioinformatic analysis showed that P39 lacks any POTRA domain, while a complete 16 stranded β‐barrel including the highly conserved L6 loop is proposed. The electrophysiological properties are most comparable to Toc75‐V, which is consistent with the phylogenetic clustering of P39 in the Toc75‐V rather than the Toc75‐III branch of the Omp85 family tree. Taken together P39 forms a pore with Omp85 family protein characteristics. The bioinformatic comparison of the pore region of Toc75‐III, Toc75‐V, and P39 shows distinctions of the barrel region most likely related to function. Proteins 2017; 85:1391–1401. © 2014 Wiley Periodicals, Inc.
Homology models of the HIV‐1 attachment inhibitor BMS‐626529 bound to gp120 suggest a unique mechanism of action
Authors: Langley David R. , Roy Kimura S. , Sivaprakasam Prasanna , Zhou Nannan , Dicker Ira , McAuliffe Brian , Wang Tao , Kadow John F. , Meanwell Nicholas A. , Krystal Mark
Published: November 2014

HIV‐1 gp120 undergoes multiple conformational changes both before and after binding to the host CD4 receptor. BMS‐626529 is an attachment inhibitor (AI) in clinical development (administered as prodrug BMS‐663068) that binds to HIV‐1 gp120. To investigate the mechanism of action of this new class of antiretroviral compounds, we constructed homology models of unliganded HIV‐1 gp120 (UNLIG), a pre‐CD4 binding‐intermediate conformation (pCD4), a CD4 bound‐intermediate conformation (bCD4), and a CD4/co‐receptor‐bound gp120 (LIG) from a series of partial structures. We also describe a simple pathway illustrating the transition between these four states. Guided by the positions of BMS‐626529 resistance substitutions and structure–activity relationship data for the AI series, putative binding sites for BMS‐626529 were identified, supported by biochemical and biophysical data. BMS‐626529 was docked into the UNLIG model and molecular dynamics simulations were used to demonstrate the thermodynamic stability of the different gp120 UNLIG/BMS‐626529 models. We propose that BMS‐626529 binds to the UNLIG conformation of gp120 within the structurally conserved outer domain, under the antiparallel β20–β21 sheet, and adjacent to the CD4 binding loop. Through this binding mode, BMS‐626529 can inhibit both CD4‐induced and CD4‐independent formation of the “open state” four‐stranded gp120 bridging sheet, and the subsequent formation and exposure of the chemokine co‐receptor binding site. This unique mechanism of action prevents the initial interaction of HIV‐1 with the host CD4+ T cell, and subsequent HIV‐1 binding and entry. Our findings clarify the novel mechanism of BMS‐626529, supporting its ongoing clinical development. Proteins 2015; 83:331–350. © 2014 Wiley Periodicals, Inc.
Insect P450 inhibitors and insecticides: challenges and opportunities
Authors: Feyereisen René
Published: November 2014

P450 enzymes are encoded by a large number of genes in insects, often over a hundred. They play important roles in insecticide metabolism and resistance, and growing numbers of P450 enzymes are now known to catalyse important physiological reactions, such as hormone metabolism or cuticular hydrocarbon synthesis. Ways to inhibit P450 enzymes specifically or less specifically are well understood, as P450 inhibitors are found as drugs, as fungicides, as plant growth regulators and as insecticide synergists. Yet there are no P450 inhibitors as insecticides on the market. As new modes of action are constantly needed to support insecticide resistance management, P450 inhibitors should be considered because of their high potential for insect selectivity, their well‐known mechanisms of action and the increasing ease of rational design and testing. © 2014 Society of Chemical Industry
Metal–Organic Framework‐Derived Bamboo‐like Nitrogen‐Doped Graphene Tubes as an Active Matrix for Hybrid Oxygen‐Reduction Electrocatalysts
Authors: Li Qing , Pan Hengyu , Higgins Drew , Cao Ruiguo , Zhang Guoqi , Lv Haifeng , Wu Kangbing , Cho Jaephil , Wu Gang
Published: November 2014

In this work, large size (i.e., diameter > 100 nm) graphene tubes with nitrogen‐doping are prepared through a high‐temperature graphitization process of dicyandiamide (DCDA) and Iron(II) acetate templated by a novel metal–organic framework (MIL‐100(Fe)). The nitrogen‐doped graphene tube (N‐GT)‐rich iron‐nitrogen‐carbon (Fe‐N‐C) catalysts exhibit inherently high activity towards the oxygen reduction reaction (ORR) in more challenging acidic media. Furthermore, aiming to improve the activity and stability of conventional Pt catalysts, the ORR active N‐GT is used as a matrix to disperse Pt nanoparticles in order to build a unique hybrid Pt cathode catalyst. This is the first demonstration of the integration of a highly active Fe‐N‐C catalyst with Pt nanoparticles. The synthesized 20% Pt/N‐GT composite catalysts demonstrate significantly enhanced ORR activity and H2‐air fuel cell performance relative to those of 20% Pt/C, which is mainly attributed to the intrinsically active N‐GT matrix along with possible synergistic effects between the non‐precious metal active sites and the Pt nanoparticles. Unlike traditional Pt/C, the hybrid catalysts exhibit excellent stability during the accelerated durability testing, likely due to the unique highly graphitized graphene tube morphologies, capable of providing strong interaction with Pt nanoparticles and then preventing their agglomeration.
An earlyMiocene deep‐water decapod crustacean faunule from theSlovenian part of theStyrianBasin, and its palaeoenvironmental and palaeobiogeographical significance
Authors: Gašparič Rok , Hyžný Matúš
Published: November 2014

A new decapod crustacean faunule is described from the earlyMiocene of theSlovenian part of theStyrianBasin. TheIvnikBeds exposed at theČinžat locality contain seven species:Calliax michelottii(Axiidea:Callianassidae),Lepidophthalmus paratethyensissp. nov. (Axiidea:Callianassidae),Jaxea kuemeli(Gebiidea:Laomediidae),Styrioplax exiguus(Brachyura:Chasmocarcinidae),Goneplax gulderi(Brachyura:Goneplacidae),Neopilumnoplax pohorjensissp. nov. (Brachyura:Mathildellidae) andRetropluma slovenicasp. nov. (Brachyura:Retroplumidae). Numerous specimens of well‐preservedStyrioplax exiguuspermitted its redescription and re‐assignment of its familial placement toChasmocarcinidae.Neopilumnoplax pohorjensissp. nov. constitutes the first fossil occurrence of the genus known to date. The decapod association, as well as other faunal elements, suggests low‐energy deep‐water depositional environment with epibathyal water depth of more than 125 m. The studied locality is situated in theRibnica–Selnica graben filled with sediments once deposited in theCentralParatethys sea. Based on the affinities of decapod genera of theCentralParatethys and theProto‐Mediterranean, we conclude that the exchange of decapod faunas between these regions was probably regulated by an anti‐estuarine circulation permitting an easier incursion of species from theProto‐Mediterranean into theParatethys and simultaneous hindering theParatethyan endemics (Styrioplax) from entering theMediterranean.
A unified method for the design of steel beam‐columns
Authors: Höglund Torsten
Published: November 2014

In Eurocode 3, Part 1‐1 [1] two methods are given for the design of beam‐columns. They have been criticized for their complexity. Furthermore, internal plastic redistribution of stresses of class 3 cross‐sections is not utilized in the code. These shortcomings were resolved in proposal for amended rules in [5], however, the procedures for beam‐columns are still complicated and difficult to understand.

An approximate method for the design of beam‐columns was proposed 1968 in [6] which was addressed in the Commentary to the Swedish regulations for steel structures [10] and used in Sweden since then [11]. It was accepted also in Eurocode 9 for aluminium [4], where it is especially convenient to allow for softening of the material at local transverse welds, see [9]. The method is here proposed to be included also in Eurocode 3.

In this paper the resistance of class 3 cross‐sections is discussed and the unified method for beam‐columns is presented. Four worked examples are presented, three of them on rather complicated structures, to show the capability to treat such structures as well.
Concise Reviews: Can Mesenchymal Stromal Cells Differentiate into Corneal Cells? A Systematic Review of Published Data
Authors: Harkin Damien G. , Foyn Leanne , Bray Laura J. , Sutherland Allison J. , Li Fiona J. , Cronin Brendan G.
Published: November 2014

The majority of stem cell therapies for corneal repair are based upon the use of progenitor cells isolated from corneal tissue, but a growing body of literature suggests a role for mesenchymal stromal cells (MSC) isolated from noncorneal tissues. While the mechanism of MSC action seems likely to involve their immuno-modulatory properties, claims have emerged of MSC transdifferentiation into corneal cells. Substantial differences in methodology and experimental outcomes, however, have prompted us to perform a systematic review of the published data. Key questions used in our analysis included: the choice of markers used to assess corneal cell phenotype, the techniques used to detect these markers, adequate reporting of controls, and tracking of MSC when studied in vivo. Our search of the literature revealed 28 papers published since 2006, with half appearing since 2012. MSC cultures established from bone marrow and adipose tissue have been best studied (22 papers). Critically, only 11 studies used appropriate markers of corneal cell phenotype, along with necessary controls. Ten out of these eleven papers, however, contained positive evidence of corneal cell marker expression by MSC. The clearest evidence is observed with respect to expression of markers for corneal stromal cells by MSC. In comparison, the evidence for MSC conversion into either corneal epithelial cells or corneal endothelial cells is often inconsistent or inconclusive. Our analysis clarifies this emerging body of literature and provides guidance for future studies of MSC differentiation within the cornea as well as other tissues. Stem Cells  2015;33:785–791
Make FERPA training fun with educational videos
Authors: Hope Joan
Published: November 2014

Educating your campus community about the Family Educational Rights and Privacy Act is a critical job for a registrar. At Brigham Young University, FERPA training videos make learning about the regulations fun. Barry Allred, registrar, and Jearlene Leishman, senior associate registrar, explained their FERPA training program at the American Association of Collegiate Registrars and Admissions Officers annual meeting.
Managing access to full-time public daycare and preschool services in Romania: Planfulness, cream-skimming and ‘interventions’
Authors: Kovács Borbála
Published: November 2014

This article engages with differently qualified parents’ experiences of and success in accessing public full-time early childhood education and care (ECEC) services in a Romanian urban context to illustrate the ways in which post-socialist welfare states are transformed not only from above, through formal rules, but also from below, through informal practices. Through the exploration of the narratives of both parents and managers, the article finds that parental planfulness, qualification-based differences in demand for full-time places and formal rules of access are insufficient to explain clear-cut qualification- and income-based differences in access. The article describes the crucial importance of hidden, informal cream-skimming strategies that daycare and preschool managers employ in the pre-enrolment phase and of the informal tactics of relying on ‘interventions’ with which unsuccessful parents respond to managers’ refusals to enrol. In the context of full-time place shortages, managerial autonomy in enrolment and insufficient institutional budgets, public ECEC institutions engage in hidden processes of redistribution through selective access, favouring well-educated, high-income parents and their children.
Imperatives in informal organizational resource exchange in Central Europe
Authors: Jancsics David
Published: November 2014

This paper challenges the mainstream social scientific approach that emphasizes “moral inferiority” in corruption and bribery in Central and Eastern Europe. We argue that in many cases, people participate in informal organizational resource exchanges not because of immorality or greed but rather because of powerful external forces. By using the case of contemporary Hungary to support this argument, this paper provides a systematic analysis of such imperatives. The findings of 50 in-depth qualitative interviews suggest that two main imperatives can be distinguished; macro-level social and meso-level organizational forces. Macro-level forces may be linked to historical paths, Hungary's socialist and pre-socialist social conditions, and its post-socialist welfare state development. Meso-level organizational forces are more general phenomena and can be found in many other countries in the world. Moreover, there are numerous categories within each theme. Some of them represent normative imperatives, while others are more material structural forces.
Crystal structures of sialyltransferase from Photobacterium damselae
Authors: Huynh Nhung , Li Yanhong , Yu Hai , Huang Shengshu , Lau Kam , Chen Xi , Fisher Andrew J.
Published: November 2014

Sialyltransferase structures fall into either GT‐A or GT‐B glycosyltransferase fold. Some sialyltransferases from the Photobacterium genus have been shown to contain an additional N‐terminal immunoglobulin (Ig)‐like domain. Photobacterium damselae α2–6‐sialyltransferase has been used efficiently in enzymatic and chemoenzymatic synthesis of α2–6‐linked sialosides. Here we report three crystal structures of this enzyme. Two structures with and without a donor substrate analog CMP‐3F(a)Neu5Ac contain an immunoglobulin (Ig)‐like domain and adopt the GT‐B sialyltransferase fold. The binary structure reveals a non‐productive pre‐Michaelis complex, which are caused by crystal lattice contacts that prevent the large conformational changes. The third structure lacks the Ig‐domain. Comparison of the three structures reveals small inherent flexibility between the two Rossmann‐like domains of the GT‐B fold.
RPA‐1 from Leishmania amazonensis (LaRPA‐1) structurally differs from other eukaryote RPA‐1 and interacts with telomeric DNA via its N‐terminal OB‐fold domain
Authors: Pavani R.S. , Fernandes C. , Perez A.M. , Vasconcelos E.J.R. , Siqueira-Neto J.L. , Fontes M.R. , Cano M.I.N.
Published: November 2014

Replication protein A‐1 (RPA‐1) is a single‐stranded DNA‐binding protein involved in DNA metabolism. We previously demonstrated the interaction between LaRPA‐1 and telomeric DNA. Here, we expressed and purified truncated mutants of LaRPA‐1 and used circular dichroism measurements and molecular dynamics simulations to demonstrate that the tertiary structure of LaRPA‐1 differs from human and yeast RPA‐1. LaRPA‐1 interacts with telomeric ssDNA via its N‐terminal OB‐fold domain, whereas RPA from higher eukaryotes show different binding modes to ssDNA. Our results show that LaRPA‐1 is evolutionary distinct from other RPA‐1 proteins and can potentially be used for targeting trypanosomatid telomeres.
Prediction of neonatal respiratory distress syndrome in term pregnancies by assessment of fetal lung volume and pulmonary artery resistance index
Authors: Laban Mohamed , Mansour Ghada M. , Elsafty Mohammed S.E. , Hassanin Alaa S. , EzzElarab Sahar S.
Published: November 2014

Objective

To develop reference cutoff values for mean fetal lung volume (FLV) and pulmonary artery resistance index (PA‐RI) for prediction of neonatal respiratory distress syndrome (RDS) in low‐risk term pregnancies.

Methods

As part of a cross‐sectional study, women aged 20–35 years were enrolled and admitted to a tertiary hospital in Cairo, Egypt, for elective repeat cesarean at 37–40 weeks of pregnancy between January 1, 2012, and July 31, 2013. FLV was calculated by virtual organ computer‐aided analysis, and PA‐RI was measured by Doppler ultrasonography before delivery.

Results

A total of 80 women were enrolled. Neonatal RDS developed in 11 (13.8%) of the 80 newborns. Compared with neonates with RDS, healthy neonates had significantly higher FLVs (P < 0.001) and lower PA‐RIs (P < 0.001). Neonatal RDS is less likely with FLV of at least 32 cm3 or PA‐RI less than or equal to 0.74. Combining these two measures improved the accuracy of prediction.

Conclusion

The use of either FLV or PA‐RI predicted neonatal RDS. The predictive value increased when these two measures were combined.
Types of consent in reproductive health care
Authors: Dickens Bernard M. , Cook Rebecca J.
Published: November 2014

Healthcare providers require prior consent to treat patients. Consent can be different for legal purposes, and be expressed in different ways. Simple consent affords providers protection from liability for assault, but negligence can arise if the consent is inadequately informed. Providers cannot coerce or improperly induce consent; patients’ agreement that a provider wrongly influences is compliance, not true consent. Attempts to rescue patients in peril may be lawful on the presumption of their implied consent, unless patients negate the presumption. In special cases, laws may require that consent be written, but generally consent can be given by speech or conduct. Informed consent depends on patients’ comprehension, but consent for treatment of uncomprehending patients may come from third parties, including legally recognized substitutes or judges. There may be legal limits to reproductive procedures to which patients may consent, under laws that can be respectfully tested, but have to be obeyed.
The importance of client heterogeneity in predicting make‐or‐buy decisions
Authors: Kistruck Geoffrey M. , Morris Shad S. , Webb Justin W. , Stevens Charles E.
Published: November 2014

Scholars have begun to merge the transaction cost economics and capabilities perspectives to examine outsourcing decisions. Further integrating these perspectives with intermediation theory, we assert that a firm's decision to use an intermediary when entering a foreign market is largely a function of the intermediary's relative capabilities and relative transaction costs (i.e., relative advantage). We hypothesize that the intermediary's relative advantage is influenced by three significantly intertwined exchange conditions: client heterogeneity, intermediary risk, and firm learning. Using a sample of 929 new foreign market initiatives by a global consulting firm, our results support our theory.
Reappraisal of the effectiveness of 99mTc‐dimercaptosuccinic acid scans for selective voiding cystourethrography in children with a first febrile urinary tract infection
Authors: Shih Bing‐Fu , Tsai Jeng‐Daw , Tsao Chin‐Ho , Huang Fu‐Yuan
Published: November 2014

Recent studies have yielded conflicting results regarding the ability of technetium‐99m dimercaptosuccinic acid (99mTc‐DMSA) renal scans for identifying high‐grade vesicoureteral reflux (VUR) in children with a first febrile urinary tract infection (UTI). This study aimed to reevaluate the effectiveness of 99mTc‐DMSA renal scans for selective voiding cystourethrography (VCUG) in children with a first febrile UTI. The medical records of children aged ≤ 5 years who were admitted with a first febrile UTI were retrospectively reviewed. Ultrasonography (US) and DMSA renal scans were performed within 3–5 days after admission, and VCUG was performed 7–10 days after antibiotics treatment. A total of 653 children were enrolled for analysis, including 579 patients aged < 2 years (Group A) and 74 patients aged 2–5 years (Group B). In Group A, DMSA scans were abnormal for 346 patients (59.8%), and normal for 233 patients (40.2%). High‐grade VUR was present in 99 of 346 patients (28.9%) with abnormal DMSA scans, but present in only 16 of 233 patients (6.9%) with normal DMSA scans (p < 0.001). Regarding the prediction of high‐grade VUR, the sensitivity and negative predictive value (NPV) for the DMSA scans were 86.1% and 93.1%, respectively. In Group B, DMSA scans were abnormal for 36 patients (48.6%), and normal for 38 patients (51.4%). High‐grade VUR was present in 12 of 36 patients (33.3%) with abnormal DMSA scans, whereas none of the 38 patients with normal DMSA scans had high‐grade VUR (p < 0.001). The sensitivity and NPV of the DMSA scans were both 100%. Using the selective VCUG strategy, approximately 40% of Group A patients and 50% of Group B patients could be spared an unnecessary VCUG, respectively. Our study results suggest that 99mTc‐DMSA renal scans are effective in identifying children with a first febrile UTI for selective VCUG.
Is governance for everybody?
Authors: Peters B Guy
Published: November 2014

The term governance has come to be used commonly in both academic discourse and in ordinary discussions about how the public sector, and other institutions, manage themselves and their relationships with the broader society. The emphasis on governance in many ways reflects public concerns about the capacity of their political systems to act effectively and decisively to solve public problems. In this short paper I take a generic stance on the nature of governance. Rather than assuming that one set of actors or another is the appropriate source of governance, I will advance a conception of governance that focuses on the basic functions that must be performed in order to govern. Further, rather than forcing a choice between one set of actors or another, this more general conception of governance focuses on the possible mixtures of actors which can govern most effectively.
A mixed diet supplemented with l-arabinose does not alter glycaemic or insulinaemic responses in healthy human subjects
Authors: Halschou-Jensen Kia , Bach Knudsen Knud E. , Nielsen Søren , Bukhave Klaus , Andersen Jens R.
Published: November 2014

In addition to a yet-to-be published study showing arabinose to have an inhibiting effect on maltase, in vitro studies have shown l-arabinose to exert an inhibiting effect on small-intestinal sucrase and maltase and the consumption of a sucrose-rich drink containing l-arabinose to exert positive effects on postprandial blood glucose, insulin and C-peptide responses in humans. However, the effects of adding l-arabinose to mixed meals on the indices of glucose control are unknown. The purpose of the present study was to investigate whether the positive effects of l-arabinose added to a sugar drink could be reproduced in subjects consuming a mixed meal containing sucrose and/or starch from wheat flour. A total of seventeen healthy men participated in study 1, a randomised, double-blind, cross-over trial. In this study, the subjects consumed two different breakfast meals containing sucrose and starch from wheat flour (meal A) or starch from wheat flour (meal B) supplemented with 0, 5 and 10 % l-arabinose by weight after a 12 h fast. A total of six healthy men participated in study 2, a randomised, double-blind, cross-over trial. In this study, the subjects also consumed meal B served in two different textures and a liquid meal with maltose supplemented with 0 and 20 % l-arabinose. In addition, 1·5 g of paracetamol was chosen as an indirect marker to assess gastric emptying. Postprandial plasma glucose, insulin and C-peptide concentrations were measured regularly for 3 h. The results of the present study showed that the peak plasma concentration, time to reach peak plasma concentration or AUC values of glucose, insulin and C-peptide were not altered after consumption of the test meals. Overall, it was not possible to reproduce the beneficial effects of l-arabinose added to sucrose drinks when l-arabinose was mixed in a solid or semi-solid mixed meal.