bluuebunny/crossref_metadata_2025 huggingface dataset:
High-Mobility Group Box 1 Mediates Fibroblast Activity via RAGE-MAPK and NF-κB Signaling in Keloid Scar Formation
Authors: Kim Jihee , Park Jong-Chul , Lee Mi , Yang Chae , Lee Ju , Lee Won
Published: December 2017

Emerging studies have revealed the involvement of high-mobility group box 1 (HMGB1) in systemic fibrotic diseases, yet its role in the cutaneous scarring process has not yet been investigated. We hypothesized that HMGB1 may promote fibroblast activity to cause abnormal cutaneous scarring. In vitro wound healing assay with normal and keloid fibroblasts demonstrated that HMGB1 administration promoted the migration of both fibroblasts with increased speed and a greater traveling distance. Treatment of the HMGB1 inhibitor glycyrrhizic acid (GA) showed an opposing effect on both activities. To analyze the downstream mechanism, the protein levels of extracellular signal-regulated kinase (ERK) 1/2, protein kinase B (AKT), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) were measured by western blot analysis. HMGB1 increased the expression levels of ERK1/2, AKT, and NF-κB compared to the control, which was suppressed by GA. HMGB1 promoted both normal and keloid fibroblasts migration to a degree equivalent to that achieved with TGF-β. We concluded that HMGB1 activates fibroblasts via the receptor for advanced glycation end product (RAGE)—mitogen-activated protein kinases (MAPK) and NF-κB interaction signaling pathways. Further knowledge of the relationship of HMGB1 with skin fibrosis may lead to a promising clinical approach to manage abnormal scarring.
Integrated MicroRNA–mRNA Analysis Reveals miR-204 Inhibits Cell Proliferation in Gastric Cancer by Targeting CKS1B, CXCL1 and GPRC5A
Authors: Shrestha Sirjana , Yang Chi-Dung , Hong Hsiao-Chin , Chou Chih-Hung , Tai Chun-San , Chiew Men-Yee , Chen Wen-Liang , Weng Shun-Long , Chen Chung-Chu , Chang Yi-An , Lee Meng-Lin , Huang Wei-Yun , Hsu Sheng-Da , Chen Yi-Chang , Huang Hsien-Da
Published: December 2017

Gastric cancer (GC) is the second most frequent cause of cancer-related deaths worldwide. MicroRNAs are single-stranded RNA molecules of 21–23 nucleotides that regulate target gene expression through specific base-pairing interactions between miRNA and untranslated regions of targeted mRNAs. In this study, we generated a multistep approach for the integrated analysis of miRNA and mRNA expression. First, both miRNA and mRNA expression profiling datasets in gastric cancer from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) identified 79 and 1042 differentially expressed miRNAs and mRNAs, respectively, in gastric cancer. Second, inverse correlations between miRNA and mRNA expression levels identified 3206 miRNA–mRNA pairs combined with 79 dysregulated miRNAs and their 774 target mRNAs predicted by three prediction tools, miRanda, PITA, and RNAhybrid. Additionally, miR-204, which was found to be down-regulated in gastric cancer, was ectopically over-expressed in the AGS gastric cancer cell line and all down-regulated targets were identified by RNA sequencing (RNA-seq) analysis. Over-expression of miR-204 reduced the gastric cancer cell proliferation and suppressed the expression of three targets which were validated by qRT-PCR and luciferase assays. For the first time, we identified that CKS1B, CXCL1, and GPRC5A are putative targets of miR-204 and elucidated that miR-204 acted as potential tumor suppressor and, therefore, are useful as a promising therapeutic target for gastric cancer.
Synthesis, Crystal Structure, and Chemical-Bonding Analysis of BaZn(NCN)2
Authors: Corkett Alex J. , Konze Philipp M. , Dronskowski Richard
Published: December 2017

The ternary carbodiimide BaZn(NCN)2 was prepared by a solid-state metathesis reaction between BaF2, ZnF2, and Li2NCN in a 1:1:2 molar ratio, and its crystal structure was determined from Rietveld refinement of X-ray data. BaZn(NCN)2 represents the aristotype of the LiBa2Al(NCN)4 structure which is unique to carbodiimide/cyanamide chemistry and is well regarded as being constructed from ZnN4 tetrahedra, sharing edges and vertices through NCN2− units to form corrugated layers with Ba2+ in the interlayer voids. Structural anomalies in the shape of the cyanamide units are addressed via IR spectrometry and DFT calculations, which suggest the presence of slightly bent N=C=N2− carbodiimide units with C2v symmetry. Moreover, chemical-bonding analysis within the framework of crystal orbital Hamilton population (COHP) reveals striking similarities between the bonding interactions in BaZn(NCN)2 and SrZn(NCN)2 despite their contrasting crystal structures. BaZn(NCN)2 is only the second example of a ternary post-transition metal carbodiimide, and its realization paves the way for the preparation of analogues featuring divalent transition metals at the tetrahedral Zn2+ site.
Influence of Chromium-Cobalt-Molybdenum Alloy (ASTM F75) on Bone Ingrowth in an Experimental Animal Model
Authors: Zuchuat Jésica , Berli Marcelo , Maldonado Ysaí , Decco Oscar
Published: December 2017

Cr-Co-Mo (ASTM F75) alloy has been used in the medical environment, but its use as a rigid barrier membrane for supporting bone augmentation therapies has not been extensively investigated. In the present study, Cr-Co-Mo membranes of different heights were placed in New Zealand white, male rabbit tibiae to assess the quality and volume of new bone formation, without the use of additional factors. Animals were euthanized at 20, 30, 40, and 60 days. Bone formation was observed in all of the cases, although the tibiae implanted with the standard membranes reached an augmentation of bone volume that agreed with the density values over the timecourse. In all cases, plasmatic exudate was found under the membrane and in contact with the new bone. Histological analysis indicated the presence of a large number of chondroblasts adjacent to the inner membrane surface in the first stages, and osteoblasts and osteocytes were observed under them. The bone formation was appositional. The Cr-Co-Mo alloy provides a scaffold with an adequate microenvironment for vertical bone volume augmentation, and the physical dimensions and disposition of the membrane itself influence the new bone formation.
In-Situ Imaging of Liquid Phase Separation in Molten Alloys Using Cold Neutrons
Authors: Derimow Nicholas , Santodonato Louis , Mills Rebecca , Abbaschian Reza
Published: December 2017

Understanding the liquid phases and solidification behaviors of multicomponent alloy systems becomes difficult as modern engineering alloys grow more complex, especially with the discovery of high-entropy alloys (HEAs) in 2004. Information about their liquid state behavior is scarce, and potentially quite complex due to the presence of perhaps five or more elements in equimolar ratios. These alloys are showing promise as high strength materials, many composed of solid-solution phases containing equiatomic CoCrCu, which itself does not form a ternary solid solution. Instead, this compound solidifies into highly phase separated regions, and the liquid phase separation that occurs in the alloy also leads to phase separation in systems in which Co, Cr, and Cu are present. The present study demonstrates that in-situ neutron imaging of the liquid phase separation in CoCrCu can be observed. The neutron imaging of the solidification process may resolve questions about phase separation that occurs in these alloys and those that contain Cu. These results show that neutron imaging can be utilized as a characterization technique for solidification research with the potential for imaging the liquid phases of more complex alloys, such as the HEAs which have very little published data about their liquid phases. This imaging technique could potentially allow for observation of immiscible liquid phases becoming miscible at specific temperatures, which cannot be observed with ex-situ analysis of solidified structures.
Role of Hydrophobins in Aspergillus fumigatus
Authors: Valsecchi Isabel , Dupres Vincent , Stephen-Victor Emmanuel , Guijarro J. , Gibbons John , Beau Rémi , Bayry Jagadeesh , Coppee Jean-Yves , Lafont Frank , Latgé Jean-Paul , Beauvais Anne
Published: December 2017

Resistance of Aspergillus fumigatus conidia to desiccation and their capacity to reach the alveoli are partly due to the presence of a hydrophobic layer composed of a protein from the hydrophobin family, called RodA, which covers the conidial surface. In A. fumigatus there are seven hydrophobins (RodA–RodG) belonging to class I and III. Most of them have never been studied. We constructed single and multiple hydrophobin-deletion mutants until the generation of a hydrophobin-free mutant. The phenotype, immunogenicity, and virulence of the mutants were studied. RODA is the most expressed hydrophobin in sporulating cultures, whereas RODB is upregulated in biofilm conditions and in vivo Only RodA, however, is responsible for rodlet formation, sporulation, conidial hydrophobicity, resistance to physical insult or anionic dyes, and immunological inertia of the conidia. None of the hydrophobin plays a role in biofilm formation or its hydrophobicity. RodA is the only needed hydrophobin in A. fumigatus, conditioning the structure, permeability, hydrophobicity, and immune-inertia of the cell wall surface in conidia. Moreover, the defect of rodlets on the conidial cell wall surface impacts on the drug sensitivity of the fungus.
Introducing the Special Issue: Bilingualism in the Hispanic and Lusophone World
Authors: Brandl Anel , González Carolina , Leeser Michael , Muntendam Antje , Couto M. , Reglero Lara
Published: December 2017

This Special Issue of Languages includes nine selected and peer‐reviewed papers from the second meeting of Bilingualism in the Hispanic and Lusophone World (BHL), an international conference that took place at Florida State University, in Tallahassee, Florida, USA, in January 2017 [...]
Additively Manufactured Pneumatically Driven Skin Electrodes
Authors: Schubert Martin , Schmidt Martin , Wolter Paul , Malberg Hagen , Zaunseder Sebastian , Bock Karlheinz
Published: December 2017

Telemedicine focuses on improving the quality of health care, particularly in out-of-hospital settings. One of the most important applications is the continuous remote monitoring of vital parameters. Long-term monitoring of biopotentials requires skin-electrodes. State-of-the-art electrodes such as Ag/AgCl wet electrodes lead, especially during long-term application, to complications, e.g., skin irritations. This paper presents a low-cost, on-demand electrode approach for future long-term applications. The fully printed module comprises a polymeric substrate with electrodes on a flexible membrane, which establishes skin contact only for short time in case of measurement. The membranes that produce airtight seals for pressure chambers can be pneumatically dilated and pressed onto the skin to ensure good contact, and subsequently retracted. The dilatation depends on the pressure and membrane thickness, which has been tested up to 150 kPa. The electrodes were fabricated in screen and inkjet printing technology, and compared during exemplary electrodermal activity measurement (EDA). The results show less amplitude compared to conventional EDA electrodes but similar behavior. Because of the manufacturing process the module enables high individuality for future applications.
Thermotropic Liquid Crystal-Assisted Chemical and Biological Sensors
Authors: Popov Nicolai , Honaker Lawrence W. , Popova Maia , Usol’tseva Nadezhda , Mann Elizabeth K. , Jákli Antal , Popov Piotr
Published: December 2017

In this review article, we analyze recent progress in the application of liquid crystal-assisted advanced functional materials for sensing biological and chemical analytes. Multiple research groups demonstrate substantial interest in liquid crystal (LC) sensing platforms, generating an increasing number of scientific articles. We review trends in implementing LC sensing techniques and identify common problems related to the stability and reliability of the sensing materials as well as to experimental set-ups. Finally, we suggest possible means of bridging scientific findings to viable and attractive LC sensor platforms.
Thermal, Spectral and Laser Properties of Er3+:Yb3+:GdMgB5O10: A New Crystal for 1.5 μm Lasers
Authors: Huang Yisheng , Yuan Feifei , Sun Shijia , Lin Zhoubin , Zhang Lizhen
Published: December 2017

A novel laser crystal of Er3+:Yb3+:GdMgB5O10 with dimension of 26 × 16 × 12 mm3 was grown successfully from K2Mo3O10 flux by the top seeded solution growth method. The thermal diffusivity and specific heat capacity were measured to calculate the thermal conductivity of the crystal. The absorption and fluorescence properties of the crystal at room temperature were investigated in detail. The Judd-Ofelt method was used to analyze the polarized absorption spectra. The emission cross-section of the 4I13/2→4I15/2 transition was calculated by the Füchtbauer-Ladenburg formula and the relevant gain cross-sections were estimated. Continuous-wave laser output of 140 mW at 1569 nm with the slope efficiency of 17.8% was demonstrated in a plano-concave resonator. The results reveal that Er3+:Yb3+:GdMgB5O10 crystal is a promising material for 1.5 μm lasers.
Novel Magnesium Elektron21-AlN Nanocomposites Produced by Ultrasound-Assisted Casting; Microstructure, Thermal and Electrical Conductivity
Authors: Saboori Abdollah , Padovano Elisa , Pavese Matteo , Badini Claudio
Published: December 2017

In the current work, a novel magnesium alloy Elektron21 reinforced by ceramic AlN nanoparticles were produced by an ultrasound-assisted casting. The fabricated nanocomposites were investigated to evaluate their microstructure, hardness, physical, thermal and electrical conductivity. The microstructural evolutions show that a uniform dispersion of the ceramic particles within the matrix can be achieved by employing the ultrasound-assisted stirring. However, some nanoparticles were found to be pushed by the solidification front. According to the Vickers hardness results, the addition of AlN nanoparticles results in a slight improvement of the mechanical properties of the nanocomposites. What is surprising is that both electrical and thermal conductivity of the nanocomposite were improved significantly as a consequence of AlN addition. This improvement in the conductivity characteristics of the nanocomposite is mainly corresponding to the structural effect of nanoparticles within the matrix.
Detection of Singlet Oxygen Formation inside Photoactive Biohybrid Composite Material
Authors: Hajdu Kata , Ur Rehman Ateeq , Vass Imre , Nagy László
Published: December 2017

Photosynthetic reaction center proteins (RCs) are the most efficient light energy converter systems in nature. The first steps of the primary charge separation in photosynthesis take place in these proteins. Due to their unique properties, combining RCs with nano-structures promising applications can be predicted in optoelectronic systems. In the present work RCs purified from Rhodobacter sphaeroides purple bacteria were immobilized on multiwalled carbon nanotubes (CNTs). Carboxyl—and amine-functionalised CNTs were used, so different binding procedures, physical sorption and chemical sorption as well, could be applied as immobilization techniques. Light-induced singlet oxygen production was measured in the prepared photoactive biocomposites in water-based suspension by histidine mediated chemical trapping. Carbon nanotubes were applied under different conditions in order to understand their role in the equilibration of singlet oxygen concentration in the suspension. CNTs acted as effective quenchers of 1O2 either by physical (resonance) energy transfer or by chemical (oxidation) reaction and their efficiency showed dependence on the diffusion distance of 1O2.
DFT Study on Intermetallic Pd–Cu Alloy with Cover Layer Pd as Efficient Catalyst for Oxygen Reduction Reaction
Authors: Liu Ji , Fan Xiaofeng , Sun Chang , Zhu Weiguang
Published: December 2017

Detailed density functional theory (DFT) calculations of the adsorption energies (Ead) for oxygen on monolayer Pd on top of the Pd–Cu face-centered cubic (FCC) alloy and intermetallic B2 structure revealed a linear correspondence between the adsorption energies and the d-band center position. The calculated barrier (Ebarrier) for oxygen dissociation depends linearly on the reaction energy difference (ΔE). The O2 has a stronger adsorption strength and smaller barrier on the intermetallic Pd–Cu surface than on its FCC alloy surface. The room-temperature free energy (ΔG) analysis suggests the oxygen reduction reaction (ORR) pathways proceed by a direct dissociation mechanism instead of hydrogenation into OOH. These results might be of use in designing intermetallic Pd–Cu as ORR electrocatalysts.
Applications, Surface Modification and Functionalization of Nickel Nanorods
Authors: Schrittwieser Stefan , Reichinger Daniela , Schotter Joerg
Published: December 2017

The growing number of nanoparticle applications in science and industry is leading to increasingly complex nanostructures that fulfill certain tasks in a specific environment. Nickel nanorods already possess promising properties due to their magnetic behavior and their elongated shape. The relevance of this kind of nanorod in a complex measurement setting can be further improved by suitable surface modification and functionalization procedures, so that customized nanostructures for a specific application become available. In this review, we focus on nickel nanorods that are synthesized by electrodeposition into porous templates, as this is the most common type of nickel nanorod fabrication method. Moreover, it is a facile synthesis approach that can be easily established in a laboratory environment. Firstly, we will discuss possible applications of nickel nanorods ranging from data storage to catalysis, biosensing and cancer treatment. Secondly, we will focus on nickel nanorod surface modification strategies, which represent a crucial step for the successful application of nanorods in all medical and biological settings. Here, the immobilization of antibodies or peptides onto the nanorod surface adds another functionality in order to yield highly promising nanostructures.
Analysis of the Microstructure and Selected Properties of the Aluminium Alloys Used in Automotive Air-Conditioning Systems
Authors: Leszczyńska-Madej Beata , Richert Maria , Wąsik Anna , Szafron Adam
Published: December 2017

The results of microstructure examinations and studies of selected mechanical properties of four aluminium alloys used in the production of automotive air-conditioning ducts (AA3103, AA5049, AA6060, AA6063) before and after the ASTM G85:A3 SWAAT Test (Sea Water Acetic Acid Test) for corrosion resistance are presented. Materials used for the manufacture of such components should be temperature stable, and therefore thermal resistance tests were carried out in a wide range of temperatures, i.e., −25 °C, 25 °C, 40 °C, 60 °C, 80 °C, 100 °C, 140 °C, 180 °C, and 220 °C. Annealing was performed for 72 h and 240 h, followed by cooling in water. The obtained results have proved that the non-precipitation-hardenable AA3103 and AA5049 alloys remain stable in the entire range of the investigated temperatures. The measured microhardness of these alloys was 43–46 HV0.1 for AA3103 and 56–64 HV0.1 for AA5049. The microhardness of the 6xxx series aluminium alloys was not stable in the investigated range of temperatures. The maximum was observed in the temperature range of 100–140 °C, which corresponded to the precipitation process of intermetallic phases, as further confirmed by microstructure observations. After the corrosion test, the mechanical properties and elongation decreased by about 5–20%.
Experimental Study of Back Wall Dross and Surface Roughness in Fiber Laser Microcutting of 316L Miniature Tubes
Authors: García-López Erika , Medrano-Tellez Alexis , Ibarra-Medina Juansethi , Siller Hector , Rodriguez Ciro
Published: December 2017

Laser cutting is a key technology for the medical devices industry, providing the flexibility, and precision for the processing of sheets, and tubes with high quality features. In this study, extensive experimentation was used to evaluate the effect of fiber laser micro-cutting parameters over average surface roughness ( R a ) and back wall dross ( D bw ) in AISI 316L stainless steel miniature tubes. A factorial design analysis was carried out to investigate the laser process parameters: pulse frequency, pulse width, peak power, cutting speed, and gas pressure. A real laser beam radius of 32.1 μm was fixed in all experiments. Through the appropriate combination of process parameters (i.e., high level of pulse overlapping factor, and pulse energy below 32 mJ) it was possible to achieve less than 1 μm in surface roughness at the edge of the laser-cut tube, and less than 3.5% dross deposits at the back wall of the miniature tube.
Research of a Novel Ultra-High Pressure Sensor with High-Temperature Resistance
Authors: Zhang Guo-Dong , Zhao Yu-Long , Zhao Yun , Wang Xin-Chen , Wei Xue-Yong
Published: December 2017

Ultra-high pressure measurement has significant applications in various fields such as high pressure synthesis of new materials and ultra-high pressure vessel monitoring. This paper proposes a novel ultra-high pressure sensor combining a truncated-cone structure and a silicon-on-insulator (SOI) piezoresistive element for measuring the pressure up to 1.6 GPa. The truncated-cone structure attenuates the measured pressure to a level that can be detected by the SOI piezoresistive element. Four piezoresistors of the SOI piezoresistive element are placed along specific crystal orientation and configured as a Wheatstone bridge to obtain voltage signals. The sensor has an advantage of high-temperature resistance, in that the structure of the piezoresistive element can avoid the leakage current at high temperature and the truncated-cone structure separates the piezoresistive element from the heat environment. Furthermore, the upper surface diameter of the truncated-cone structure is designed to be 2 mm for the application of small scale. The results of static calibration show that the sensor exhibits a good performance in hysteresis and repeatability. The temperature experiment indicates that the sensor can work steadily at high temperature. This study would provide a better insight to the research of ultra-high pressure sensors with larger range and smaller size.
The Viability of Single Cancer Cells after Exposure to Hydrodynamic Shear Stresses in a Spiral Microchannel: A Canine Cutaneous Mast Cell Tumor Model
Authors: Ketpun Dettachai , Sailasuta Achariya , Suwannaphan Thammawit , Bhanpattanakul Sudchaya , Pimpin Alongkorn , Srituravanich Werayut , Sripumkhai Witsaroot , Jeamsaksiri Wutthinan , Piyaviriyakul Prapruddee
Published: December 2017

Our laboratory has the fundamental responsibility to study cancer stem cells (CSC) in various models of human and animal neoplasms. However, the major impediments that spike our accomplishment are the lack of universal biomarkers and cellular heterogeneity. To cope with these restrictions, we have tried to apply the concept of single cell analysis, which has hitherto been recommended throughout the world as an imperative solution pack for resolving such dilemmas. Accordingly, our first step was to utilize a predesigned spiral microchannel fabricated by our laboratory to perform size-based single cell separation using mast cell tumor (MCT) cells as a model. However, the impact of hydrodynamic shear stresses (HSS) on mechanical cell injury and viability in a spiral microchannel has not been fully investigated so far. Intuitively, our computational fluid dynamics (CFD) simulation has strongly revealed the formations of fluid shear stress (FSS) and extensional fluid stress (EFS) in the sorting system. The panel of biomedical assays has also disclosed cell degeneration and necrosis in the model. Therefore, we have herein reported the combinatorically detrimental effect of FSS and EFS on the viability of MCT cells after sorting in our spiral microchannel, with discussion on the possibly pathogenic mechanisms of HSS-induced cell injury in the study model.
Hydrometallurgical Processing Technology of Titanomagnetite Ores
Authors: Sachkov Victor , Nefedov Roman , Orlov Vladislav , Medvedev Rodion , Sachkova Anna
Published: December 2017

In this paper, we study the possibility of obtaining iron and titanium-vanadium concentrates with highest contents of iron and titanium, respectively, through hydrometallurgical processing of the titanomagnetite ores of the Chineisk deposit. We varied two key parameters to determine the efficiency of the process: (a) concentration of leaching solution (ammonium fluoride); and (b) acidity of solution. Ammonium fluoride concentration was varied from 0.08 mol/L to 4.2 mol/L with the other fixed parameters. It was shown that optimum ammonium fluoride concentration for leaching the ore is 0.42 mol/L; at these concentrations iron and titanium contents are about 62.8 wt % and 3.5 wt % in solid phase, respectively. The acidity of solution was changed by adding of hydrofluoric acid with varied concentration (from 0.86 mol/L to 4.07 mol/L) to ammonium fluoride solution with fixed concentration of 0.42 mol/L. The best results (degree of titanium extraction = 63.7%) were obtained when using a solution of hydrofluoric acid with concentration 4.07 mol/L. In this case, the addition of acid makes it possible to increase the Fe/Ti ratio by 3.4 times in comparison with the original ore. Thus, we conclude that acidity and the concentration of ammonium fluoride solution significantly influences the selectivity of the hydrometallurgical process.
CO2 Recycling to Dimethyl Ether: State-of-the-Art and Perspectives
Authors: Catizzone Enrico , Bonura Giuseppe , Migliori Massimo , Frusteri Francesco , Giordano Girolamo
Published: December 2017

This review reports recent achievements in dimethyl ether (DME) synthesis via CO2 hydrogenation. This gas-phase process could be considered as a promising alternative for carbon dioxide recycling toward a (bio)fuel as DME. In this view, the production of DME from catalytic hydrogenation of CO2 appears as a technology able to face also the ever-increasing demand for alternative, environmentally-friendly fuels and energy carriers. Basic considerations on thermodynamic aspects controlling DME production from CO2 are presented along with a survey of the most innovative catalytic systems developed in this field. During the last years, special attention has been paid to the role of zeolite-based catalysts, either in the methanol-to-DME dehydration step or in the one-pot CO2-to-DME hydrogenation. Overall, the productivity of DME was shown to be dependent on several catalyst features, related not only to the metal-oxide phase—responsible for CO2 activation/hydrogenation—but also to specific properties of the zeolites (i.e., topology, porosity, specific surface area, acidity, interaction with active metals, distributions of metal particles, …) influencing activity and stability of hybridized bifunctional heterogeneous catalysts. All these aspects are discussed in details, summarizing recent achievements in this research field.
Structural Basis for the Substrate Inhibition of Proline Utilization A by Proline
Authors: Korasick David , Pemberton Travis , Arentson Benjamin , Becker Donald , Tanner John
Published: December 2017

Proline utilization A (PutA) is a bifunctional flavoenzyme that catalyzes the two-step oxidation of l-proline to l-glutamate using spatially separated proline dehydrogenase (PRODH) and l-glutamate-γ-semialdehyde dehydrogenase (GSALDH) active sites. Substrate inhibition of the coupled PRODH-GSALDH reaction by proline is a common kinetic feature of PutAs, yet the structural basis for this phenomenon remains unknown. To understand the mechanism of substrate inhibition, we determined the 2.15 Å resolution crystal structure of Bradyrhizobium japonicum PutA complexed with proline. Proline was discovered in five locations remote from the PRODH active site. Most notably, strong electron density indicated that proline bound tightly to the GSAL binding site of the GSALDH active site. The pose and interactions of proline bound in this site are remarkably similar to those of the natural aldehyde substrate, GSAL, implying that proline inhibits the GSALDH reaction of PutA. Kinetic measurements show that proline is a competitive inhibitor of the PutA GSALDH reaction. Together, the structural and kinetic data show that substrate inhibition of the PutA coupled reaction is due to proline binding in the GSAL site.
A Concise Review of the Conflicting Roles of Dopamine-1 versus Dopamine-2 Receptors in Wound Healing
Authors: Vaughn Alexandra , Davis Michael , Sivamani Raja , Isseroff Roslyn
Published: December 2017

Catecholamines play an important regulatory role in cutaneous wound healing. The exact role of dopamine in human epidermis has yet to be fully elucidated. Current published evidence describes its differential effects on two separate families of G protein coupled receptors: D1-like and D2-like dopamine receptors. Dopamine may enhance angiogenesis and wound healing through its action on dopamine D1 receptors, while impairing wound healing when activating D2 receptors. This review summarizes the evidence for the role of dopamine in wound healing and describes potential mechanisms behind its action on D1 versus D2-like receptors in the skin.
Structure, Chemical Analysis, Biosynthesis, Metabolism, Molecular Engineering, and Biological Functions of Phytoalexins
Authors: Jeandet Philippe
Published: December 2017

Plants in their natural environment are facing large numbers of pathogenic microorganisms, mainly fungi and bacteria.[…]
Molecular Basis for Converting (2S)-Methylsuccinyl-CoA Dehydrogenase into an Oxidase
Authors: Burgener Simon , Schwander Thomas , Romero Elvira , Fraaije Marco , Erb Tobias
Published: December 2017

Although flavoenzymes have been studied in detail, the molecular basis of their dioxygen reactivity is only partially understood. The members of the flavin adenosine dinucleotide (FAD)-dependent acyl-CoA dehydrogenase and acyl-CoA oxidase families catalyze similar reactions and share common structural features. However, both enzyme families feature opposing reaction specificities in respect to dioxygen. Dehydrogenases react with electron transfer flavoproteins as terminal electron acceptors and do not show a considerable reactivity with dioxygen, whereas dioxygen serves as a bona fide substrate for oxidases. We recently engineered (2S)-methylsuccinyl-CoA dehydrogenase towards oxidase activity by rational mutagenesis. Here we characterized the (2S)-methylsuccinyl-CoA dehydrogenase wild-type, as well as the engineered (2S)-methylsuccinyl-CoA oxidase, in detail. Using stopped-flow UV-spectroscopy and liquid chromatography-mass spectrometry (LC-MS) based assays, we explain the molecular base for dioxygen reactivity in the engineered oxidase and show that the increased oxidase function of the engineered enzyme comes at a decreased dehydrogenase activity. Our findings add to the common notion that an increased activity for a specific substrate is achieved at the expense of reaction promiscuity and provide guidelines for rational engineering efforts of acyl-CoA dehydrogenases and oxidases.
Structure Related Inhibition of Enzyme Systems in Cholinesterases and BACE1 In Vitro by Naturally Occurring Naphthopyrone and Its Glycosides Isolated from Cassia obtusifolia
Authors: Shrestha Srijan , Seong Su , Paudel Pradeep , Jung Hyun , Choi Jae
Published: December 2017

Cassia obtusifolia Linn. have been used to improve vision, inflammatory diseases, and as hepatoprotective agents and to promote urination from ancient times. In the present study, we investigated the influence of glycosylation of components of C. obtusifolia and structure-activity relationships (SARs) with respect to the inhibition of acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and β-site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1), which are related to Alzheimer’s disease (AD). All six C. obtusifolia-derived compounds, rubrofusarin (1), rubrofusarin 6-O-β-d-glucopyranoside (2), rubrofusarin 6-O-β-d-gentiobioside (3), nor-rubrofusarin 6-O-β-d-glucoside (4), isorubrofusarin 10-O-β-d-gentiobioside (5), and rubrofusarin 6-O-β-d-triglucoside (6) showed promising inhibitory activity against AChE/BACE1. Compounds 3 and 4 showed most significant inhibition against AChE and BACE1, respectively. The SARs results emphasized the importance of gentiobiosyl moiety in the rubrofusarin for AChE inhibition, whereas the presence of hydroxyl group at C-8 and the glucosyl moiety at the C-6 position in the nor-rubrofusarin appeared to largely determine BACE1 inhibition. Kinetics and docking studies showed the lowest binding energy and highest affinity for mixed-type inhibitors, 3 and 4. Hydrophobic bonds interactions and the number of hydrogen bonds determined the strength of the protein-inhibitor interaction. These results suggest that C. obtusifolia and its constituents have therapeutic potential, and that the SARs of its active components are further explored with a view towards developing a treatment for AD.
Improvement of Image Sticking in Liquid Crystal Display Doped with γ-Fe2O3 Nanoparticles
Authors: Ye Wenjiang , Yuan Rui , Dai Yayu , Gao Lin , Pang Ze , Zhu Jiliang , Meng Xiangshen , He Zhenghong , Li Jian , Cai Minglei , Wang Xiaoyan , Xing Hongyu
Published: December 2017

Image sticking in thin film transistor-liquid crystal displays (TFT-LCD) is related to the dielectric property of liquid crystal (LC) material. Low threshold value TFT LC materials have a weak stability and the free ions in them will be increased because of their own decomposition. In this study, the property of TFT LC material MAT-09-1284 doped with γ-Fe2O3 nanoparticles was investigated. The capacitances of parallel-aligned nematic LC cells and vertically aligned nematic LC cells with different doping concentrations were measured at different temperatures and frequencies. The dielectric constants perpendicular and parallel to long axis of the LC molecules ε⊥ and ε//, as well as the dielectric anisotropy Δε, were obtained. The dynamic responses and the direct current threshold voltages in parallel-aligned nematic LC cells for different doping concentrations were also measured. Although the dielectric anisotropy Δε decreased gradually with increasing temperature and frequency at the certain frequency and temperature in LC state for each concentration, the doping concentration of γ-Fe2O3 nanoparticles less than or equal to 0.145 wt % should be selected for maintaining dynamic response and decreasing free ions. This study has some guiding significance for improving the image sticking in TFT-LCD.
Prevention of Synaptic Alterations and Neurotoxic Effects of PAMAM Dendrimers by Surface Functionalization
Authors: Vidal Felipe , Vásquez Pilar , Cayumán Francisca , Díaz Carola , Fuentealba Jorge , Aguayo Luis , Yévenes Gonzalo , Alderete Joel , Guzmán Leonardo
Published: December 2017

One of the most studied nanocarriers for drug delivery are polyamidoamine (PAMAM) dendrimers. However, the alterations produced by PAMAM dendrimers in neuronal function have not been thoroughly investigated, and important aspects such as effects on synaptic transmission remain unexplored. We focused on the neuronal activity disruption induced by dendrimers and the possibility to prevent these effects by surface chemical modifications. Therefore, we studied the effects of fourth generation PAMAM with unmodified positively charged surface (G4) in hippocampal neurons, and compared the results with dendrimers functionalized in 25% of their surface groups with folate (PFO25) and polyethylene glycol (PPEG25). G4 dendrimers significantly reduced cell viability at 1 µM, which was attenuated by both chemical modifications, PPEG25 being the less cytotoxic. Patch clamp recordings demonstrated that G4 induced a 7.5-fold increment in capacitive currents as a measure of membrane permeability. Moreover, treatment with this dendrimer increased intracellular Ca2+ by 8-fold with a complete disruption of transients pattern, having as consequence that G4 treatment increased the synaptic vesicle release and frequency of synaptic events by 2.4- and 3-fold, respectively. PFO25 and PPEG25 treatments did not alter membrane permeability, total Ca2+ intake, synaptic vesicle release or synaptic activity frequency. These results demonstrate that cationic G4 dendrimers have neurotoxic effects and induce alterations in normal synaptic activity, which are generated by the augmentation of membrane permeability and a subsequent intracellular Ca2+ increase. Interestingly, these toxic effects and synaptic alterations are prevented by the modification of 25% of PAMAM surface with either folate or polyethylene glycol.
Association between Malnutrition and 28-Day Mortality and Intensive Care Length-of-Stay in the Critically ill: A Prospective Cohort Study
Authors: Lew Charles , Wong Gabriel , Cheung Ka , Chua Ai , Chong Mary , Miller Michelle
Published: December 2017

There is limited evidence for the association between malnutrition and mortality as well as Intensive Care Unit length-of-stay (ICU-LOS) in critically ill patients. We aimed to examine the aforementioned associations by conducting a prospective cohort study in an ICU of a Singapore tertiary hospital. Between August 2015 and October 2016, all adult patients with ≥ 24 h of ICU-LOS were included. The 7-point Subjective Global Assessment (7-point SGA) was used to determine patients’ nutritional status within 48 h of ICU admission. Multivariable regressions were conducted in two ways: (1) presence versus absence of malnutrition, and (2) dose-dependent association for each 1-point decrease in the 7-point SGA. There were 439 patients of which 28.0% were malnourished, and the 28-day mortality rate was 28.0%. Malnutrition was associated with an increased risk of 28-day mortality (adjusted Relative Risk 1.33 (95% Confidence Interval: 1.05–1.69)), and this risk increased with a greater degree of malnutrition (adjusted Relative Risk 1.08 (95% Confidence Interval: 1.00–1.16) for each 1-point decrease in the 7-point SGA). No significant association was found between malnutrition and ICU-LOS. The results of this study indicated a clear association between malnutrition and higher 28-day mortality in critically ill patients. The association between malnutrition and ICU-LOS could not be replicated and hence requires further evaluation.
Vitamin D Vitamers Affect Vitamin D Status Differently in Young Healthy Males
Authors: Jakobsen Jette , Andersen Elisabeth , Christensen Tue , Andersen Rikke , Bügel Susanne
Published: December 2017

Dietary intake of vitamin D includes vitamin D3 (vitD3), 25-hydroxyvitamin D3 (25OH-D3), and vitamin D2 (vitD2). However, the bioactivity of the different species has not been scientifically established. The hypothesis in this study was that vitD3, 25OH-D3, and vitD2 have an equal effect on 25-hydroxyvitamin D in serum (vitamin D status). To test our hypothesis, we performed a randomized, crossover study. Twelve young males consumed 10 µg/day vitD3 during a four-week run-in period, followed by 3 × 6 weeks of 10 µg/day vitD3, 10 µg/day 25OH-D3, and 10 µg/day vitD2. The content of vitD3, vitD2, 25OH-D3, and 25-hydroxyvitamin D2 (25OH-D2) in serum was quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The hypothesis that the three sources of vitamin D affect vitamin D status equally was rejected. Based on the assumption that 1 µg vitD3/day will show an increase in vitamin D status of 1.96 nmol/L, the results showed that 23 µg vitD2 and 6.8 µg 25OH-D3 was similar to 10 µg vitD3. These results demonstrate that further investigations are necessary to determine how to quantify the total vitamin D activity based on chemical quantification of the individual vitamin D metabolites to replace the total vitamin D activity assessed in biological rat models.
Potential Role of Amino Acid/Protein Nutrition and Exercise in Serum Albumin Redox State
Authors: Wada Yasuaki , Takeda Yasuhiro , Kuwahata Masashi
Published: December 2017

Albumin is the major protein in the serum of mammals. It is synthesized exclusively in the liver, before being secreted into the circulation. Similar to skeletal muscle protein, albumin synthesis is stimulated by dietary amino acids and proteins as well as exercise. Albumin has three isoforms based on the redox states of the free cysteine residue at position 34. The redox state of serum albumin has long been extensively investigated in terms of oxidative stress-related chronic diseases, with the redox state of serum albumin having been regarded as a marker of systemic oxidative stress. However, according to recent animal studies, the redox state of serum albumin is modulated by albumin turnover and may also reflect amino acid/protein nutritional status. Furthermore, as the redox state of serum albumin is modulated by exercise training, measuring the pre- and post-exercise redox states of serum albumin in athletes may be useful in assessing amino acid/protein nutritional status and exercise-induced oxidative stress, which are closely associated with skeletal muscle adaptive responses. This article extensively reviews serum albumin and the redox state of albumin in the context of amino acid/protein nutritional status and exercise training.
Effects of Sleeve Gastrectomy vs. Roux-en-Y Gastric Bypass on Eating Behavior and Sweet Taste Perception in Subjects with Obesity
Authors: Nance Katie , Eagon J. Christopher , Klein Samuel , Pepino Marta Yanina
Published: December 2017

The goal of this study was to test the hypothesis that weight loss induced by Roux-en-Y gastric bypass (RYGB) has greater effects on taste perception and eating behavior than comparable weight loss induced by sleeve gastrectomy (SG). We evaluated the following outcomes in 31 subjects both before and after ~20% weight loss induced by RYGB (n = 23) or SG (n = 8): (1) sweet, savory, and salty taste sensitivity; (2) the most preferred concentrations of sucrose and monosodium glutamate; (3) sweetness palatability, by using validated sensory testing techniques; and (4) eating behavior, by using the Food Craving Inventory and the Dutch Eating Behavior Questionnaire. We found that neither RYGB nor SG affected sweetness or saltiness sensitivity. However, weight loss induced by either RYGB or SG caused the same decrease in: (1) frequency of cravings for foods; (2) influence of emotions and external food cues on eating behavior; and (3) shifted sweetness palatability from pleasant to unpleasant when repetitively tasting sucrose (all p-values ≤ 0.01). Therefore, when matched on weight loss, SG and RYGB cause the same beneficial effects on key factors involved in the regulation of eating behavior and hedonic component of taste perception.
Carbohydrates for Soccer: A Focus on Skilled Actions and Half-Time Practices
Authors: Hills Samuel , Russell Mark
Published: December 2017

Carbohydrate consumption is synonymous with soccer performance due to the established effects on endogenous energy store preservation, and physical capacity maintenance. For performance-enhancement purposes, exogenous energy consumption (in the form of drinks, bars, gels and snacks) is recommended on match-day; specifically, before and during match-play. Akin to the demands of soccer, limited opportunities exist to consume carbohydrates outside of scheduled breaks in competition, such as at half-time. The link between cognitive function and blood glucose availability suggests that carbohydrates may influence decision-making and technical proficiency (e.g., soccer skills). However, relatively few reviews have focused on technical, as opposed to physical, performance while also addressing the practicalities associated with carbohydrate consumption when limited in-play feeding opportunities exist. Transient physiological responses associated with reductions in activity prevalent in scheduled intra-match breaks (e.g., half-time) likely have important consequences for practitioners aiming to optimize match-day performance. Accordingly, this review evaluated novel developments in soccer literature regarding (1) the ergogenic properties of carbohydrates for skill performance; and (2) novel considerations concerning exogenous energy provision during half-time. Recommendations are made to modify half-time practices in an aim to enhance subsequent performance. Viable future research opportunities exist regarding a deeper insight into carbohydrate provision on match-day.
Characterisation of L-Type Amino Acid Transporter 1 (LAT1) Expression in Human Skeletal Muscle by Immunofluorescent Microscopy
Authors: Hodson Nathan , Brown Thomas , Joanisse Sophie , Aguirre Nick , West Daniel , Moore Daniel , Baar Keith , Breen Leigh , Philp Andrew
Published: December 2017

The branch chain amino acid leucine is a potent stimulator of protein synthesis in skeletal muscle. Leucine rapidly enters the cell via the L-Type Amino Acid Transporter 1 (LAT1); however, little is known regarding the localisation and distribution of this transporter in human skeletal muscle. Therefore, we applied immunofluorescence staining approaches to visualise LAT1 in wild type (WT) and LAT1 muscle-specific knockout (mKO) mice, in addition to basal human skeletal muscle samples. LAT1 positive staining was visually greater in WT muscles compared to mKO muscle. In human skeletal muscle, positive LAT1 staining was noted close to the sarcolemmal membrane (dystrophin positive staining), with a greater staining intensity for LAT1 observed in the sarcoplasmic regions of type II fibres (those not stained positively for myosin heavy-chain 1, Type II—25.07 ± 5.93, Type I—13.71 ± 1.98, p < 0.01), suggesting a greater abundance of this protein in these fibres. Finally, we observed association with LAT1 and endothelial nitric oxide synthase (eNOS), suggesting LAT1 association close to the microvasculature. This is the first study to visualise the distribution and localisation of LAT1 in human skeletal muscle. As such, this approach provides a validated experimental platform to study the role and regulation of LAT1 in human skeletal muscle in response to various physiological and pathophysiological models.
Tongue Abnormalities Are Associated to a Maternal Folic Acid Deficient Diet in Mice
Authors: Maldonado Estela , López-Gordillo Yamila , Partearroyo Teresa , Varela-Moreiras Gregorio , Martínez-Álvarez Concepción , Pérez-Miguelsanz Juliana
Published: December 2017

It is widely accepted that maternal folic acid (FA) deficiency during pregnancy is a risk factor for abnormal development. The tongue, with multiple genes working together in a coordinated cascade in time and place, has emerged as a target organ for testing the effect of FA during development. A FA-deficient (FAD) diet was administered to eight-week-old C57/BL/6J mouse females for 2–16 weeks. Pregnant dams were sacrificed at gestational day 17 (E17). The tongues and heads of 15 control and 210 experimental fetuses were studied. In the tongues, the maximum width, base width, height and area were compared with width, height and area of the head. All measurements decreased from 10% to 38% with increasing number of weeks on maternal FAD diet. Decreased head and tongue areas showed a harmonic reduction (Spearman nonparametric correlation, Rho = 0.802) with respect to weeks on a maternal FAD diet. Tongue congenital abnormalities showed a 10.9% prevalence, divided in aglossia (3.3%) and microglossia (7.6%), always accompanied by agnathia (5.6%) or micrognathia (5.2%). This is the first time that tongue alterations have been related experimentally to maternal FAD diet in mice. We propose that the tongue should be included in the list of FA-sensitive birth defect organs due to its relevance in several key food and nutrition processes.