bluuebunny/crossref_metadata_2025 huggingface dataset:
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

Degeneracy 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.
Parallel steady state studies on a milliliter scale accelerate fed‐batch bioprocess design for recombinant protein production with Escherichia coli
Authors: Schmideder Andreas , Cremer Johannes H. , Weuster‐Botz Dirk
Published: September 2016

In general, fed‐batch processes are applied for recombinant protein production with Escherichia coli (E. coli). However, state of the art methods for identifying suitable reaction conditions suffer from severe drawbacks, i.e. direct transfer of process information from parallel batch studies is often defective and sequential fed‐batch studies are time‐consuming and cost‐intensive. In this study, continuously operated stirred‐tank reactors on a milliliter scale were applied to identify suitable reaction conditions for fed‐batch processes. Isopropyl β‐d‐1‐thiogalactopyranoside (IPTG) induction strategies were varied in parallel‐operated stirred‐tank bioreactors to study the effects on the continuous production of the recombinant protein photoactivatable mCherry (PAmCherry) with E. coli. Best‐performing induction strategies were transferred from the continuous processes on a milliliter scale to liter scale fed‐batch processes. Inducing recombinant protein expression by dynamically increasing the IPTG concentration to 100 µM led to an increase in the product concentration of 21% (8.4 g L−1) compared to an implemented high‐performance production process with the most frequently applied induction strategy by a single addition of 1000 µM IPGT. Thus, identifying feasible reaction conditions for fed‐batch processes in parallel continuous studies on a milliliter scale was shown to be a powerful, novel method to accelerate bioprocess design in a cost‐reducing manner. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:1426–1435, 2016
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

Microenvironment 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

A 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

Oxygen‐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

To 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

An 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

There 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

We 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

Two 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

A [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

Synthesis 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

A 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

The 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

The 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

The 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

MetaboAnalyst (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

The 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.
Photostability and Moisture Stability of CH3NH3PbI3‐based Solar Cells by Ethyl Cellulose
Authors: He Jian , Ng Chun‐Fai , Young Wong King , Liu Weifeng , Chen Tao
Published: September 2016

Organic–inorganic hybrid perovskite solar cells have achieved high power conversion efficiencies (PCE) of around 22 %, comparable to conventional silicon and thin‐film solar cells. However, the poor stability of the perovskite material is one of the significant drawbacks for its practical application. In moderate humidity, the perovskite hydrates and decomposes within hours or a few days, which deteriorates the device efficiency rapidly. Herein, is demonstrated the moisture stability and photostability of CH3NH3PbI3 can be greatly improved through the interaction between ethyl cellulose (EC) and perovskite crystals. It is found that the CH3NH3PbI3 film with EC incorporation is stable over 5 days in 60 % relative humidity (RH) under ambient indoor light, whereas the conventional CH3NH3PbI3 film without EC is degraded in 1 day. After being stored in 60 % RH under ambient indoor light for 2.5 days, the solar cell with EC incorporation shows a PCE decrement from 14.08 % to 8.21 %, whereas that without EC is nearly entirely degraded (PCE=0 %). Nuclear magnetic resonance (NMR) spectroscopy shows that hydrogen bonding between EC and CH3NH3PbI3 accounts for the improved moisture stability by stabilizing the crystal structure.
Leveraging Industry‐Academia Collaborations in Adaptive Biomedical Innovation
Authors: Stewart SR , Barone PW , Bellisario A , Cooney CL , Sharp PA , Sinskey AJ , Natesan S , Springs SL
Published: September 2016

Despite the rapid pace of biomedical innovation, research and development (R&D) productivity in the pharmaceutical industry has not improved broadly. Increasingly, firms need to leverage new approaches to product development and commercial execution, while maintaining adaptability to rapid changes in the marketplace and in biomedical science. Firms are also seeking ways to capture some of the talent, infrastructure, and innovation that depends on federal R&D investment. As a result, a major transition to external innovation is taking place across the industry. One example of these external innovation initiatives is the Sanofi–MIT Partnership, which provided seed funding to MIT investigators to develop novel solutions and approaches in areas of interest to Sanofi. These projects were highly collaborative, with information and materials flowing both ways. The relatively small amount of funding and short time frame of the awards built an adaptable and flexible process to advance translational science.
An Inherited Genetic Variant in CEP72 Promoter Predisposes to Vincristine‐Induced Peripheral Neuropathy in Adults With Acute Lymphoblastic Leukemia
Authors: Stock W , Diouf B , Crews KR , Pei D , Cheng C , Laumann K , Mandrekar SJ , Luger S , Advani A , Stone RM , Larson RA , Evans WE
Published: September 2016

Peripheral neuropathy is a major toxicity of vincristine, yet no strategies exist for identifying adult patients at high‐risk. We used a case–control design of 48 adults receiving protocol therapy for acute lymphoblastic leukemia (ALL) who developed vincristine‐induced neuropathy (NCI grade 2–4) during treatment, and 48 matched controls who did not develop grade 2–4 neuropathy. Peripheral neuropathy was prospectively graded by National Cancer Institute (NCI) criteria. CEP72 promoter genotype (rs924607) was determined using polymerase chain reaction (PCR)‐based single nucleotide polymorphism (SNP) genotyping. Frequency of the CEP72 T/T genotype was higher in cases (31% vs. 10%, P = 0.0221) and the incidence of vincristine‐induced neuropathy (grades 2–4) was significantly higher in patients homozygous for the CEP72 T/T genotype. 75% of the 20 patients homozygous for the CEP72 T allele developed grade 2–4 neuropathy, compared to 44% of patients with CEP72 CC or CT genotype (P = 0.0221). The CEP72 polymorphism can identify adults at increased risk of vincristine‐induced peripheral neuropathy.
A distributed‐memory parallel lattice Kinetic Monte Carlo algorithm for crystal growth applied to barite (001) face
Authors: Abujas‐Pereira Jerónimo , Martin‐Bragado Ignacio , Pina Carlos M. , Pizarro Joaquín , Galindo Pedro L.
Published: September 2016

This work presents a parallel approach of the Kinetic Monte Carlo (KMC) algorithm using a distributed memory architecture. The resulting computer software was tested by conducting crystal growth simulations on barite (001) face. Execution times, simulated times and crystallization velocities are compared with a shared memory parallel KMC software (MMonCa). Finally, a ≈ 1 μm2 crystal growth simulation is performed and compared with atomic force microscopy crystal growth experiments. The capability of this approach is demonstrated: a) a significant reduction of parallel overhead is achieved when comparing to the shared memory parallel version of the software, b) a distributed memory approach achieves an increase in memory resources enough to perform simulations with lattice sizes about 1 μm2, allowing the study of larger structures than those in shared memory or sequential implementations, c) this approach should be used only with large scale simulations to take advantage of the distributed memory architecture, d) further improvements are needed for parallel KMC to be faster than serial KMC in small scale simulations, e) the KMC algorithm used is able to adequately simulate two‐dimensional nucleation on large areas of barite (001) faces.
Human derived cardiomyocytes: A decade of knowledge after the discovery of induced pluripotent stem cells
Authors: Barbuti Andrea , Benzoni Patrizia , Campostrini Giulia , Dell'Era Patrizia
Published: September 2016

Ten years ago Yamanaka's lab identified a way to reprogram terminally differentiated cells to a pluripotent state, similar to that of embryonic stem cell. This procedure opened the road for the generation of postmitotic human cells, that have completely lost the replication potential. The initial excitement waned when it was observed that the cells produced by this method are somehow immature and do not resemble the adult phenotype. In the absence of cellular markers that recognize the various maturation steps of induced pluripotent stem cell‐derived human cardiomyocytes, we propose to follow their maturation looking at their electrophysiological profile. For this reason, we are first reviewing the most common methods of differentiation, from the preliminary complex procedures to the newly‐identified two‐step protocols and, second, we report the electrical characteristics of the cells, through electrophysiological analysis of ionic currents that give rise to the action potential. We are aware that each protocol leads to the generation of different cardiomyocyte precursors, thus suggesting the need for a wider standardization. The identification of the electrophysiological characteristics of the cells could help in identifying the type and the maturation stage of the obtained cardiomyocyte, thus compensating for the lack of specific markers. Developmental Dynamics 245:1145–1158, 2016. © 2016 Wiley Periodicals, Inc.
The clonal root system of balsam poplar in upland sites of Quebec and Alberta
Authors: Adonsou Kokouvi E. , DesRochers Annie , Tremblay Francine , Thomas Barb R. , Isabel Nathalie
Published: September 2016

Balsam poplar seeds are short‐lived and require moist seedbeds soon after they are released to germinate. In addition to sexual reproduction, balsam poplar stands can regenerate clonally by root suckering. The origin of stands will in turn affect their genetic structure and root system architecture, which are poorly understood for upland forest stands. Three stands were hydraulically excavated in Quebec (moist) and Alberta (dry) to determine the origin of trees and to characterize root systems with respect to presence of parental roots and root grafts connections. Clones were identified using single‐nucleotide polymorphism (SNPs), and all stems, roots and root grafts were aged using dendrochronology techniques. All 82 excavated trees were of sucker origin, and four of the six stands contained a single clone. Parental root connections were found between 22% and 25% of excavated trees, and 53% and 48% of trees were linked with a root graft between the same or different clones, in Alberta and Quebec, respectively. Mean distance between trees connected by parental root was significantly lower than the distance between unconnected trees (0.47 ± 0.25 m vs. 3.14 ± 0.15 m and 1.55 ± 0.27 m vs. 4.25 ± 0.13 m) in Alberta and in Quebec, respectively. The excavations also revealed many dead stumps with live roots, maintained through root connections with live trees. This research highlights that balsam poplar growing in upland stands is a clonal species that can maintain relatively high genotypic diversity, with frequent root connections between trees at maturity. Maintaining an extensive root system through root connections increases the chances of a clone surviving when the above ground tree is dead and may also enhance the resilience of balsam poplar stands after disturbance.
Multiple interaction types determine the impact of ant predation of caterpillars in a forest community
Authors: Clark Robert E. , Farkas Timothy E. , Lichter‐Marck Isaac , Johnson Emily R. , Singer Michael S.
Published: September 2016

Direct and indirect effects of predators are highly variable in complex communities, and understanding the sources of this variation is a research priority in community ecology. Recent evidence indicates that herbivore community structure is a primary determinant of predation strength and its cascading impacts on plants. In this study, we use variation in herbivore community structure among plant species to experimentally test two hypotheses in a temperate forest food web. First, variation in the strength of predator effects, such as ant predation of caterpillars, is predicted to be density dependent, exhibiting stronger effects when prey abundance is high (density‐dependent predation hypothesis). Second, mutualistic interactions between ants and sap‐feeding herbivores are expected to increase the abundance of predatory ants, strengthening predation effects on herbivores with cascading effects on host plants (keystone mutualism hypothesis). Using a large‐scale predator exclusion experiment across eight dominant tree species, we tracked changes in insect density on 862 plants across two years, recording 2,322 ants, 1,062 sap‐feeders, 5,322 caterpillars, and quantifying herbivory on 199, 338 leaves. In this experiment, density‐dependent predation did not explain variation in the direct or indirect effects of ants on caterpillars and herbivory. In partial support of the keystone mutualism hypothesis, sap‐feeders strengthened top‐down effects of ants on caterpillars under some conditions. However, stronger ant predation of caterpillars did not lead to measurable trophic cascades on trees occupied by sap‐feeders. Instead, the presence of sap‐feeders was associated with increased per capita feeding damage by caterpillars, and this bottom‐up effect attenuated the indirect effects of ants on host plants. These findings demonstrate that examining the multi‐trophic impacts of mutualisms and predation in the context of the broader community can reveal patterns otherwise masked by compensatory interactions.
Native–exotic richness relationships: a biogeographic approach using turnover in island plant populations
Authors: Burns K. C.
Published: September 2016

Spatial variation in exotic species richness is often correlated with native species richness, for reasons that are poorly understood. To better understand the mechanisms underpinning native–exotic richness relationships, I quantified the colonization and extinction of 18 exotic and 16 native plant species on 39 small islands located off the coast of New Zealand for 8 consecutive yr. Results revealed a positive native–exotic richness relationship, which could be explained by similar demographic responses of native and exotic species to island area. However, native and exotic species showed subtle differences in their response to other island attributes. Turnover in native species declined with island isolation, whereas turnover in exotic species increased with the exposure of islands to ocean‐borne disturbances. Overall results illustrate how long‐term observations of species turnover can be used to better understand the mechanisms underpinning native–exotic richness relationships, and demonstrate that large, exposed islands can be especially susceptible to invasions by exotic species.
NR4A1‐dependent Ly6Clow monocytes contribute to reducing joint inflammation in arthritic mice through Treg cells
Authors: Brunet Alexandre , LeBel Manon , Egarnes Benoit , Paquet‐Bouchard Carine , Lessard Anne‐Julie , Brown Jacques P. , Gosselin Jean
Published: September 2016

Monocytes are central to the physiopathology of arthritis, but their roles in progression and resolution of the disease remain to be clarified. Using NR4A1−/− mice, which lack patrolling lymphocyte antigen 6C (Ly6Clow) monocytes, we found that inflammatory Ly6Chigh monocytes contribute to rapid development of arthritis in a serum transfer‐induced arthritis (STIA) model. Our experiments suggest that patrolling monocytes do not promote the initiation and progression of arthritis in mice, as severity of symptoms was amplified in NR4A1−/− mice. Moreover, we show that treatment of arthritic wild type (WT) mice with cytosporone B (Csn‐B), a NR4A1‐specific agonist, significantly reduces severity of disease. Effects of Csn‐B were absent in monocyte‐depleted mice treated with clodronate until Ly6Clow monocytes were restored. Adoptive transfer of Ly6Clow monocytes in arthritic NR4A1−/− mice treated with Csn‐B reduces joint inflammation, supporting the regulatory role of Ly6Clow subset on disease development. Our results also reveal that administration of Csn‐B to arthritic mice enhances levels of circulating CD4+CD25+FoxP3+ Treg cells, a process requiring the presence of Ly6Clow monocytes. Together, these data indicate that Ly6Chigh monocytes are involved in the initiation and progression of arthritis and Ly6Clow monocytes contribute to reduce joint inflammation through the mobilization of Treg cells.
Size‐Dependent Self‐Assembly of Lanthanide‐Based Coordination Frameworks with Phenanthroline‐2,9‐dicarboxylic Acid as a Preorganized Ligand in Hybrid Materials
Authors: Alipour Mahboubeh , Akintola Oluseun , Buchholz Axel , Mirzaei Masoud , Eshtiagh‐Hosseini Hossein , Görls Helmar , Plass Winfried
Published: September 2016

A family of lanthanide‐based inorganic–organic hybrids, [Ce4(PDA)4(H2O)9(SiW12O40)]·6H2O (1, PDA = 1,10‐phenanthroline‐2,9‐dicarboxylic acid), [Nd5(PDA)5(H2O)13(OH)(SiW12O40)]·8H2O (2), [Sm3(PDA)2(H2O)13(OH)(SiW12O40)]·16.5H2O (3), and [Dy4(PDA)4(H2O)11(SiW12O40)]·7H2O (4), has been hydrothermally synthesized with the [SiW12O40]4– Keggin‐type anion as a building block. Characterization by IR spectroscopy, elemental analysis, thermogravimetric analysis (TGA), and single‐crystal X‐ray diffraction revealed that 1–4 are all coordination polymers with different structural features owing to the lanthanide‐contraction effect. Compound 1 is composed of cationic layers interconnected by Keggin anions in three dimensions. Compounds 2 and 3 are 1D rectangular tubelike and 1D ladderlike coordination polymers, respectively. The Keggin anion appears to play a different role in each of these hybrid structures, as its coordination mode varies between mono‐, bi‐, and tetradentate in 3, 1, and 2, respectively. In 4, the Keggin anions only reside in the interspace between two adjacent 2D cationic layers as discrete counterions. Magnetic measurements indicate that 4 exhibits frequency‐dependent alternating‐current (ac) magnetic susceptibilities indicative of slow relaxation of the magnetization.
Diastereomeric Glycosyl Sulfoxides Display Different Recognition Features versus E. coli β‐Galactosidase
Authors: Colomer Juan P. , Fernández de Toro Beatriz , Cañada F. Javier , Corzana Francisco , Jiménez Barbero Jesús , Canales Ángeles , Varela Oscar
Published: September 2016

The conformational analysis of the (S) and (R) diastereoisomers of benzyl 3‐deoxy‐4S‐(β‐d‐galactopyranosyl)‐4‐thio‐β‐d‐threo‐pentopyranoside S‐oxide (1S and 1R, respectively) has been performed by using NMR spectroscopy assisted by molecular modelling methods. The results point out that sulfoxide 1S and 1R display rather different conformational behaviors, 1S being significantly more flexible than 1R. Both sulfoxides have shown to be competitive inhibitors of the β‐galactosidase from E. coli, although with different potencies. The key structural features of the molecular recognition process have been characterized.
Evaluating feeding strategies for microbial oil production from glycerol by Rhodotorula glutinis
Authors: Karamerou Eleni E. , Theodoropoulos Constantinos , Webb Colin
Published: September 2016

Oil production, from biodiesel by‐product glycerol, through microbial fermentation provides a promising option as part of an integrated biorefinery process. However, bioprocessing improvements are required to make the process more efficient. In the present work, different glycerol feeding strategies were evaluated under fed‐batch cultivation of the oleaginous yeast Rhodotorula glutinis. Results showed that the concept of targeting first a cell proliferation stage and then a lipid accumulation stage had beneficial effects on both biomass and oil yields. Continual feeding and pulsed feedings, delivering the same total amount of nutrients, resulted in similar values of cellular biomass (∼25 g/L) and oil content (∼40%). In contrast, continual supply of nutrients at higher rates ( >0.8 g/L/h) led to an increase in both cell densities (30 g/L) and oil content (53%), attaining a high oil yield of 16.28 g/L. This suggests that a continual cultivation with two different rates for each stage constitutes an efficient approach to enhance microbial oil production.
Normal fault growth and linkage in the Gediz (Alaşehir) Graben, Western Turkey, revealed by transient river long‐profiles and slope‐break knickpoints
Authors: Kent Emiko , Boulton Sarah J. , Whittaker Alexander C. , Stewart Iain S. , Cihat Alçiçek M.
Published: September 2016

The Gediz (Alaşehir) Graben is located in the highly tectonically active and seismogenic region of Western Turkey. The rivers upstream of the normal fault‐bounded graben each contain a non‐lithologic knickpoint, including those that drain through inferred fault segment boundaries. Knickpoint heights measured vertically from the fault scale with footwall relief and documented fault throw (vertical displacement). Consequently, we deduce these knickpoints were initiated by an increase in slip rate on the basin‐bounding fault, driven by linkage of the three main fault segments of the high‐angle graben bounding fault array. Fault interaction theory and ratios of channel steepness suggest that the slip rate enhancement factor on linkage was a factor of 3. We combine this information with geomorphic and structural constraints to estimate that linkage took place between 0.6 Ma and 1 Ma. Calculated pre‐ and post‐linkage throw rates are 0.6 and 2 mm/yr respectively. Maximum knickpoint retreat rates upstream of the faults range from 4.5 to 28 mm/yr, faster than for similar catchments upstream of normal faults in the Central Apennines and the Hatay Graben of Turkey, and implying a fluvial landscape response time of 1.6 to 2.7 Myr. We explore the relative controls of drainage area and precipitation on these retreat rates, and conclude that while climate variation and fault throw rate partially explain the variations seen, lithology remains a potentially important but poorly characterised variable. Copyright © 2016 John Wiley & Sons, Ltd.
Surgical preparation of nasal defects to enhance the implant‐retained facial prostheses: A case report
Authors: Hofstede Theresa M. , Jacob Rhonda F. , Montgomery Patricia , Wesley Peggy
Published: September 2016

Background

Skin cancers requiring nasal resection may be surgically reconstructed and/or prosthetically reconstructed. Singular surgical reconstruction may be ideal for smaller defects in which the nasal bone and cartilaginous portions of the nose are maintained, but surgical reconstruction falls short of providing acceptable aesthetic results for more extensive nasal defects. Prosthetic rehabilitation, or a combination of surgical and prosthetic rehabilitation, is more appropriate for larger defects, but prosthesis retention can be challenging when adhesives are required on adjacent mobile and secreting skin.

Methods

We report 2 cases of patients with extensive nasal defects who were successfully rehabilitated with nasal prostheses. The nasal defects were surgically optimized with immediate preparation of the surgical margins, placement of a split‐thickness skin graft (STSG) within the nasal cavities and exposed maxillary sinuses, and immediate placement of osseointegrated implants.

Results

Excellent prosthetic retention can be achieved without the need for adhesives. A skin graft‐lined defect has minimal secretions and allows for improved defect cleansing.

Conclusion

The success of a nasal prosthesis depends on appropriate surgical management of the defect, and, thus, collaboration between the various surgical and prosthetic teams is essential. © 2016 Wiley Periodicals, Inc. Head Neck 39: E4–E11, 2017
The impact of ditch blocking on the hydrological functioning of blanket peatlands
Authors: Holden Joseph , Green Sophie M. , Baird Andy J. , Grayson Richard P. , Dooling Gemma P. , Chapman Pippa J. , Evans Christopher D. , Peacock Mike , Swindles Graeme
Published: September 2016

Ditch blocking in blanket peatlands is common as part of peatland restoration. The effects of ditch blocking on flow regimes and nearby water tables were examined in a field trial. After an initial 6‐month monitoring period, eight ditches had peat dams installed 10 m apart along their entire length (dammed), four of these ditches were also partially infilled through bank reprofiling (reprofiled). Four ditches were left open with no dams or reprofiling (open). These 12 ditches and the surrounding peat were monitored for 4 more years. An initial five‐fold reduction in discharge occurred in the dammed and the reprofiled ditches with the displaced water being diverted to overland flow and pathways away from the ditches. However, there was a gradual change over time in ditch flow regime in subsequent years, with the overall volume of water leaving the dammed and the reprofiled ditches increasing per unit of rainfall to around twice that which occurred in the first year after blocking. Hence, monitoring for greater than one year is important for understanding hydrological impacts of peatland restoration. Overland flow and flow in the upper ~4 cm of peat was common and occurred in the inter‐ditch areas for over half of the time after ditch blocking. There was strong evidence that topographic boundaries of small ditch catchments, despite being defined using a high‐resolution Light Detection And Ranging‐based terrain model, were not always equivalent to actual catchment areas. Hence, caution is needed when upscaling area‐based fluxes, such as aquatic carbon fluxes, from smaller scale studies including those using ditches and small streams. The effect of ditch blocking on local water tables was spatially highly variable but small overall (time‐weighted mean effect <2 cm). Practitioners seeking to raise water tables through peatland restoration should first be informed either by prior measurement of water tables or by spatial modelling to show whether the peatland already has shallow water tables or whether there are locations that could potentially undergo large water‐table recoveries.