bluuebunny/crossref_metadata_2025_split huggingface dataset:
Management of knee osteoarthritis. Current status and future trends
Authors: Ondrésik Marta , Azevedo Maia Fatima R. , da Silva Morais Alain , Gertrudes Ana C. , Dias Bacelar Ana H. , Correia Cristina , Gonçalves Cristiana , Radhouani Hajer , Amandi Sousa Rui , Oliveira Joaquim M. , Reis Rui L. 
Published: September 2016

ABSTRACTOsteoarthritis (OA) affects a large number of the population, and its incidence is showing a growing trend with the increasing life span. OA is the most prevalent joint condition worldwide, and currently, there is no functional cure for it. This review seeks to briefly overview the management of knee OA concerning standardized pharmaceutical and clinical approaches, as well as the new biotechnological horizons of OA treatment. The potential of biomaterials and state of the art of advanced therapeutic approaches, such as cell and gene therapy focused primarily on cartilage regeneration are the main subjects of this review. Biotechnol. Bioeng. 2017;114: 717–739. © 2016 Wiley Periodicals, Inc.
Synthetic gene design—The rationale for codon optimization and implications for molecular pharming in plants
Authors: Webster Gina R. , Teh Audrey Y.‐H. , Ma Julian K.‐C. 
Published: September 2016

ABSTRACTDegeneracy in the genetic code allows multiple codon sequences to encode the same protein. Codon usage bias in genes is the term given to the preferred use of particular synonymous codons. Synonymous codon substitutions had been regarded as “silent” as the primary structure of the protein was not affected; however, it is now accepted that synonymous substitutions can have a significant effect on heterologous protein expression. Codon optimization, the process of altering codons within the gene sequence to improve recombinant protein expression, has become widely practised. Multiple inter‐linked factors affecting protein expression need to be taken into consideration when optimizing a gene sequence. Over the years, various computer programmes have been developed to aid in the gene sequence optimization process. However, as the rulebook for altering codon usage to affect protein expression is still not completely understood, it is difficult to predict which strategy, if any, will design the “optimal” gene sequence. In this review, codon usage bias and factors affecting codon selection will be discussed and the evidence for codon optimization impact will be reviewed for recombinant protein expression using plants as a case study. These developments will be relevant to all recombinant expression systems; however, molecular pharming in plants is an area which has consistently encountered difficulties with low levels of recombinant protein expression, and should benefit from an evidence based rational approach to synthetic gene design. Biotechnol. Bioeng. 2017;114: 492–502. © 2016 Wiley Periodicals, Inc.
Infarcted cardiac microenvironment may hinder cardiac lineage differentiation of human embryonic stem cells
Authors: Wei Rui , Yang Jin , Gao Meijuan , Wang Haining , Hou Wenfang , Mu Yiming , Chen Guian , Hong Tianpei 
Published: September 2016

AbstractMicroenvironment regulates cell fate and function. In this study, we investigated the effects of the infarcted cardiac microenvironment on cardiac differentiation of human embryonic stem cells (hESCs). hESCs were intramyocardially transplanted into infarcted or uninjured rat hearts. After 4 weeks, mesodermal and cardiac lineage markers were detected by immunofluorescence. Cardiac function was assessed by echocardiography. hESCs were differentiated in vitro under hypoxic (5% O2), low‐nutrient (5% FBS), or control condition. The numbers of beating clusters, proportions of cardiac troponin T (cTnT)‐positive cells, and relative levels of cardiac‐specific markers were determined. Results showed that in both uninjured and infarcted hearts, hESCs survived, underwent development, and formed intracardiac grafts, with a higher proportion in the uninjured hearts. However, cells that were double positive for human fetal liver kinase 1 (Flk1), a marker of cardiac progenitors, and human β‐tubulin, a marker for labeling human cells, were found in the uninjured hearts but not in the infarcted hearts. hESC transplantation did not restore the cardiac function of acutely infarcted rats. In vitro, low FBS treatment was associated with fewer beating clusters, a lower proportion of cTnT‐positive cells and lower levels of cardiac troponin I (cTnI) and α‐myosin heavy chain (α‐MHC) expression than those in the control. Conversely, hypoxia treatment was associated with a higher proportion of cTnT‐positive cells and higher levels of cTnI expression. In conclusion, transplanted hESCs differentiate toward Flk1‐positive cardiac progenitors in the uninjured but not infarcted hearts. The infarcted cardiac microenvironment recapitulated is unsuitable for cardiac differentiation of hESCs, likely due to nutrient deprivation.
Triazine‐Based Porous Organic Polymer with Good CO2 Gas Adsorption Properties and an Efficient Organocatalyst for the One‐Pot Multicomponent Condensation Reaction
Authors: Bhanja Piyali , Chatterjee Sauvik , Bhaumik Asim 
Published: September 2016

AbstractA new porous organic polymer PDVBTT‐1 (poly‐divinylbenzene‐co‐triallyloxytriazine) has been synthesized through radical co‐polymerization utilizing two monomers, that is, divinylbenzene and 2,4,6‐triallyloxy‐1,3,5‐triazine in the presence of AIBN (azobisisobutyronitrile) as a radical initiator under solvothermal conditions in the absence of any structure directing agent. The polymer has been characterized thoroughly by N2 sorption, FTIR, UV/Vis, and solid‐state 13C cross‐polarization magic angle spinning (CP MAS) NMR spectroscopy, field emission FE‐SEM, high‐resolution HR‐TEM, and thermogravimetric/differential thermal analysis (TG/DTA). Owing to the considerably good surface area of 644 m2 g−1 and surface basic sites (1.10 mmol g−1), the material showed very good CO2 adsorption properties. Furthermore, the porous polymer showed good catalytic activity in the base‐catalyzed, one‐pot, multicomponent condensation reaction between various substituted aromatic aldehydes, malononitrile, and activated phenols such as 2‐naphthol, resorcinol, etc., for the synthesis of 2‐amino‐chromenes in water and under solvent‐free microwave irradiation conditions. This N‐rich porous polymer is highly recyclable and thus it has potential for a wide range of base‐catalyzed organic transformations in the future.
Impact of Carbon Nanotube Surface Chemistry on Hydrogen Oxidation by Membrane‐Bound Oxygen‐Tolerant Hydrogenases
Authors: Monsalve Karen , Mazurenko Ievgen , Gutierrez‐Sanchez Cristina , Ilbert Marianne , Infossi Pascale , Frielingsdorf Stefan , Giudici‐Orticoni Marie Thérèse , Lenz Oliver , Lojou Elisabeth 
Published: September 2016

AbstractOxygen‐tolerant [NiFe] hydrogenases are attractive biocatalysts for utilization in H2/O2 fuel cells, which thereby reduces the amount of platinum‐based catalysts. The O2‐tolerant membrane‐bound hydrogenases isolated from Ralstonia eutropha and Aquifex aeolicus were previously studied at planar electrodes. The design of a powerful enzymatic fuel cell, however, requires a considerable increase in enzyme loading. Herein, we immobilized the two hydrogenases on carbon nanotubes, and we demonstrated that the enzyme binding and electron‐transfer properties on the 3D networks relied on the same surface chemistry as that of the planar electrodes. We evaluated how the intrinsic properties of each hydrogenase, that is, temperature and O2 tolerance, were affected by immobilization on different electrode surfaces. The role of the detergent used for protein purification was especially emphasized. We also demonstrated that O2 reduction products affected more seriously the enzyme activity than molecular O2. If immobilized on pyrene‐modified carbon nanotubes, both enzymes were used for the first time in a mild‐temperature, membraneless H2/O2 enzymatic fuel cell, fed with O2‐rich gas mixture, opening new avenues toward the development of alternative energy supplies.
Miniaturized Electrochemical Device from Assembled Cylindrical Macroporous Gold Electrodes
Authors: Karajić Aleksandar , Reculusa Stéphane , Ravaine Serge , Mano Nicolas , Kuhn Alexander 
Published: September 2016

AbstractTo design original electrochemical devices, self‐assembly and growth processes can be coupled to create a wide range of sophisticated architectures with interesting functionalities. In this work, we present a convergent strategy for the fabrication of a miniaturized, macroporous, and coaxial two‐electrode electrochemical cell with tunable porosity, thickness, and distance between individually addressable macroporous electrodes. The assembly presents a platform that could be used for the fabrication of high‐performance electrochemical devices such as miniaturized (bio)fuel cells, sensors, and batteries.
Enantioselective Formal C(sp2)−H Vinylation
Authors: Manna Madhu Sudan , Sarkar Rahul , Mukherjee Santanu 
Published: September 2016

AbstractAn enantioselective formal C(sp2)−H vinylation of prochiral 2,2‐disubstituted cyclopentene‐1,3‐dione is presented. This vinylative desymmetrization is realized by using a two‐step procedure that consists of a catalytic enantioselective vinylogous Michael addition of deconjugated butenolides to cyclopentene‐1,3‐dione and a base‐mediated decarboxylation. The overall process utilizes deconjugated butenolides as the source of the highly substituted vinyl unit. Five‐membered carbocycles containing a remote all‐carbon quaternary stereogenic center are obtained in good yields and with good to high enantioselectivities.
Fragment‐Based Drug Design Facilitated by Protein‐Templated Click Chemistry: Fragment Linking and Optimization of Inhibitors of the Aspartic Protease Endothiapepsin
Authors: Mondal Milon , Unver M. Yagiz , Pal Asish , Bakker Matthijs , Berrier Stephan P. , Hirsch Anna K. H. 
Published: September 2016

AbstractThere is an urgent need for the development of efficient methodologies that accelerate drug discovery. We demonstrate that the strategic combination of fragment linking/optimization and protein‐templated click chemistry is an efficient and powerful method that accelerates the hit‐identification process for the aspartic protease endothiapepsin. The best binder, which inhibits endothiapepsin with an IC50 value of 43 μm, represents the first example of triazole‐based inhibitors of endothiapepsin. Our strategy could find application on a whole range of drug targets.
A Divergent Approach to the Marine Diterpenoids (+)‐Dictyoxetane and (+)‐Dolabellane V
Authors: Hugelshofer Cedric L. , Magauer Thomas 
Published: September 2016

AbstractWe present a full account of the development of a strategy that culminated in the first total syntheses of the unique oxetane‐containing natural product (+)‐dictyoxetane and the macrocyclic diterpene (+)‐dolabellane V. Our retrosynthetic planning was guided by both classical and nonconventional strategies to construct the oxetane, which is embedded in an unprecedented 2,7‐dioxatricyclo[4.2.1.03,8]nonane ring system. Highlights of the successful approach include highly diastereoselective carbonyl addition reactions to assemble the full carbon skeleton, a Grob fragmentation to construct the 11‐membered macrocycle of (+)‐dolabellane V, and a bioinspired 4‐exo‐tet, 5‐exo‐trig cyclization sequence to form the complex dioxatricyclic framework of (+)‐dictyoxetane. Furthermore, an unprecedented strain‐releasing type I dyotropic rearrangement of an epoxide‐oxetane substrate was developed.
Classical/Non‐classical Polyoxometalate Hybrids
Authors: Izarova Natalya V. , Santiago‐Schübel Beatrix , Willbold Sabine , Heß Volkmar , Kögerler Paul 
Published: September 2016

AbstractTwo polyanions [SeI V2PdII4WVI14O56H]11− and [SeI V4PdII4WVI28O108H12]12− are the first hybrid polyoxometalates in which classical (Group 5/6 metal based) and non‐classical (late transition‐metal based) polyoxometalate units are joined. Requiring no supporting groups, this co‐condensation of polyoxotungstate and isopolyoxopalladate constituents also provides a logical link between POM‐PdII coordination complexes and the young subclass of polyoxopalladates. Solid‐state, solution, and gas‐phase studies suggest interesting specific reactivities for these hybrids and point to several potential derivatives and functionalization strategies.
A Highly Active Pd(II) Complex with 1‐Tritylimidazole Ligand for Suzuki‐Miyaura and Heck Coupling Reactions
Authors: Liu Chengxin , Liu Guiyan , Zhao Hongkun 
Published: September 2016

AbstractA [Pd(1‐tritylimidazole)2Cl2] complex was synthesized and characterized by 1H and 13C NMR spectroscopy, elemental analysis, and X‐ray crystallography. The X‐ray analysis confirmed that the Pd(II) has a four‐coordinated square planar structure. The palladium complex was used to carry out Suzuki‐Miyaura coupling reactions of aryl chlorides with a variety of phenylboronic acids in i‐PrOH‐H2O (1:1, V:V) at room temperature and Heck coupling reactions of aryl halides with methyl acrylate in DMF at 110°C. High yields of the cross‐coupling products were obtained.
One‐Pot Synthesis of Triarylmethanes via Metal‐Free Reductive Coupling of Diaryl Ketones, Tosylhydrazide, and Arylboronic Acids
Authors: Shen Xu , Gu Ningning , Liu Ping , Ma Xiaowei , Xie Jianwei , Liu Yan , Dai Bin 
Published: September 2016

AbstractSynthesis of triarylmethanes via metal‐free reductive coupling of diaryl ketone, tosylhydrazide, and arylboronic acids has been developed. This methodology is realized via one‐pot two‐step reactions involving the preparation of N‐tosylhydrazones by reacting tosylhydrazide with diaryl ketone derivatives, followed by the reductive coupling with arylboronic acid in the presence of potassium carbonate to afford various triarylmethanes analogues in moderate to good yields. Importantly, the system presented here enables the use of easily accessible starting materials and a series of substrates with diverse functional group could be tolerant in this reaction. This approach could also be particularly useful for the synthesis of triaryl‐substituted carbazolyl compounds.
Fluorescent Detection of Trace Water in Methanol Based on an Al(III) Chemical Sensor
Authors: Hao Liang , Qiu Qi‐ming , Wang Wen‐jie , Gu Leilei , Li Hui 
Published: September 2016

AbstractA colorimetric and fluorescent sensor for trace water in methanol has been designed and characterized, which is a kind of aluminium‐Schiff base coordination complex derived from diaminomaleonitrile. The fluorescence properties of this complex have been studied based on excited state intramolecular proton transfer (ESIPT) and intramolecular charge transfer (ICT) mechanism. The fluorescent emission of Al‐L complex can be quenched by 0.1% water and distinguished by naked eyes. The detection limitation is 0.01% recognized by fluorescence spectra.
Nogo‐A does not inhibit retinal axon regeneration in the lizard Gallotia galloti
Authors: Lang Dirk M. , Romero‐Alemán Maria del Mar , Dobson Bryony , Santos Elena , Monzón‐Mayor Maximina 
Published: September 2016

ABSTRACTThe myelin‐associated protein Nogo‐A contributes to the failure of axon regeneration in the mammalian central nervous system (CNS). Inhibition of axon growth by Nogo‐A is mediated by the Nogo‐66 receptor (NgR). Nonmammalian vertebrates, however, are capable of spontaneous CNS axon regeneration, and we have shown that retinal ganglion cell (RGC) axons regenerate in the lizard Gallotia galloti. Using immunohistochemistry, we observed spatiotemporal regulation of Nogo‐A and NgR in cell bodies and axons of RGCs during ontogeny. In the adult lizard, expression of Nogo‐A was associated with myelinated axon tracts and upregulated in oligodendrocytes during RGC axon regeneration. NgR became upregulated in RGCs following optic nerve injury. In in vitro studies, Nogo‐A‐Fc failed to inhibit growth of lizard RGC axons. The inhibitor of protein kinase A (pkA) activity KT5720 blocked growth of lizard RGC axons on substrates of Nogo‐A‐Fc, but not laminin. On patterned substrates of Nogo‐A‐Fc, KT5720 caused restriction of axon growth to areas devoid of Nogo‐A‐Fc. Levels of cyclic adenosine monophosphate (cAMP) were elevated over sustained periods in lizard RGCs following optic nerve lesion. We conclude that Nogo‐A and NgR are expressed in a mammalian‐like pattern and are upregulated following optic nerve injury, but the presence of Nogo‐A does not inhibit RGC axon regeneration in the lizard visual pathway. The results of outgrowth assays suggest that outgrowth‐promoting substrates and activation of the cAMP/pkA signaling pathway play a key role in spontaneous lizard retinal axon regeneration in the presence of Nogo‐A. Restriction of axon growth by patterned Nogo‐A‐Fc substrates suggests that Nogo‐A may contribute to axon guidance in the lizard visual system. J. Comp. Neurol. 525:936–954, 2017. © 2016 Wiley Periodicals, Inc.
Combining diffusion magnetic resonance tractography with stereology highlights increased cross‐cortical integration in primates
Authors: Charvet Christine J. , Hof Patrick R. , Raghanti Mary Ann , Van Der Kouwe Andre J. , Sherwood Chet C. , Takahashi Emi 
Published: September 2016

ABSTRACTThe isocortex of primates is disproportionately expanded relative to many other mammals, yet little is known about what the expansion of the isocortex entails for differences in cellular composition and connectivity patterns in primates. Across the depth of the isocortex, neurons exhibit stereotypical patterns of projections. Upper‐layer neurons (i.e., layers II–IV) project within and across cortical areas, whereas many lower‐layer pyramidal neurons (i.e., layers V–VI) favor connections to subcortical regions. To identify evolutionary changes in connectivity patterns, we quantified upper (i.e., layers II–IV)‐ and lower (i.e., layers V–VI)‐layer neuron numbers in primates and other mammals such as rodents and carnivores. We also used MR tractography based on high‐angular resolution diffusion imaging and diffusion spectrum imaging to compare anterior‐to‐posterior corticocortical tracts between primates and other mammals. We found that primates possess disproportionately more upper‐layer neurons as well as an expansion of anterior‐to‐posterior corticocortical tracts compared with other mammals. Taken together, these findings demonstrate that primates deviate from other mammals in exhibiting increased cross‐cortical connectivity. J. Comp. Neurol. 525:1075–1093, 2017. © 2016 Wiley Periodicals, Inc.
Oxytocin receptors are expressed on dopamine and glutamate neurons in the mouse ventral tegmental area that project to nucleus accumbens and other mesolimbic targets
Authors: Peris Joanna , MacFadyen Kaley , Smith Justin A. , de Kloet Annette D. , Wang Lei , Krause Eric G. 
Published: September 2016

AbstractThe mesolimbic dopamine (DA) circuitry determines which behaviors are positively reinforcing and therefore should be encoded in the memory to become a part of the behavioral repertoire. Natural reinforcers, like food and sex, activate this pathway, thereby increasing the likelihood of further consummatory, social, and sexual behaviors. Oxytocin (OT) has been implicated in mediating natural reward and OT‐synthesizing neurons project to the ventral tegmental area (VTA) and nucleus accumbens (NAc); however, direct neuroanatomical evidence of OT regulation of DA neurons within the VTA is sparse. To phenotype OT‐receptor (OTR) expressing neurons originating within the VTA, we delivered Cre‐inducible adeno‐associated virus that drives the expression of fluorescent marker into the VTA of male mice that had Cre‐recombinase driven by OTR gene expression. OTR‐expressing VTA neurons project to NAc, prefrontal cortex, the extended amygdala, and other forebrain regions but less than 10% of these OTR‐expressing neurons were identified as DA neurons (defined by tyrosine hydroxylase colocalization). Instead, almost 50% of OTR‐expressing cells in the VTA were glutamate (GLU) neurons, as indicated by expression of mRNA for the vesicular GLU transporter (vGluT). About one‐third of OTR‐expressing VTA neurons did not colocalize with either DA or GLU phenotypic markers. Thus, OTR expression by VTA neurons implicates that OT regulation of reward circuitry is more complex than a direct action on DA neurotransmission. J. Comp. Neurol. 525:1094–1108, 2017. © 2016 Wiley Periodicals, Inc.
Using MetaboAnalyst 3.0 for Comprehensive Metabolomics Data Analysis
Authors: Xia Jianguo , Wishart David S. 
Published: September 2016

AbstractMetaboAnalyst (http://www.metaboanalyst.ca) is a comprehensive Web application for metabolomic data analysis and interpretation. MetaboAnalyst handles most of the common metabolomic data types from most kinds of metabolomics platforms (MS and NMR) for most kinds of metabolomics experiments (targeted, untargeted, quantitative). In addition to providing a variety of data processing and normalization procedures, MetaboAnalyst also supports a number of data analysis and data visualization tasks using a range of univariate, multivariate methods such as PCA (principal component analysis), PLS‐DA (partial least squares discriminant analysis), heatmap clustering and machine learning methods. MetaboAnalyst also offers a variety of tools for metabolomic data interpretation including MSEA (metabolite set enrichment analysis), MetPA (metabolite pathway analysis), and biomarker selection via ROC (receiver operating characteristic) curve analysis, as well as time series and power analysis. This unit provides an overview of the main functional modules and the general workflow of the latest version of MetaboAnalyst (MetaboAnalyst 3.0), followed by eight detailed protocols. © 2016 by John Wiley & Sons, Inc.
Using the Tools and Resources of the RCSB Protein Data Bank
Authors: Costanzo Luigi Di , Ghosh Sutapa , Zardecki Christine , Burley Stephen K. 
Published: September 2016

AbstractThe Protein Data Bank (PDB) archive is the worldwide repository of experimentally determined three‐dimensional structures of large biological molecules found in all three kingdoms of life. Atomic‐level structures of these proteins, nucleic acids, and complex assemblies thereof are central to research and education in molecular, cellular, and organismal biology, biochemistry, biophysics, materials science, bioengineering, ecology, and medicine. Several types of information are associated with each PDB archival entry, including atomic coordinates, primary experimental data, polymer sequence(s), and summary metadata. The Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB) serves as the U.S. data center for the PDB, distributing archival data and supporting both simple and complex queries that return results. These data can be freely downloaded, analyzed, and visualized using RCSB PDB tools and resources to gain a deeper understanding of fundamental biological processes, molecular evolution, human health and disease, and drug discovery. © 2016 by John Wiley & Sons, Inc.