bluuebunny/crossref_metadata_2025 huggingface dataset:
Mutations in VPS13D lead to a new recessive ataxia with spasticity and mitochondrial defects
Authors: Seong Eunju , Insolera Ryan , Dulovic Marija , Kamsteeg Erik‐Jan , Trinh Joanne , Brüggemann Norbert , Sandford Erin , Li Sheng , Ozel Ayse Bilge , Li Jun Z. , Jewett Tamison , Kievit Anneke J. A. , Münchau Alexander , Shakkottai Vikram , Klein Christine , Collins Catherine A. , Lohmann Katja , van de Warrenburg Bart P. , Burmeister Margit
Published: March 2018

Objective

To identify novel causes of recessive ataxias, including spinocerebellar ataxia with saccadic intrusions, spastic ataxias, and spastic paraplegia.

Methods

In an international collaboration, we independently performed exome sequencing in 7 families with recessive ataxia and/or spastic paraplegia. To evaluate the role of VPS13D mutations, we evaluated a Drosophila knockout model and investigated mitochondrial function in patient‐derived fibroblast cultures.

Results

Exome sequencing identified compound heterozygous mutations in VPS13D on chromosome 1p36 in all 7 families. This included a large family with 5 affected siblings with spinocerebellar ataxia with saccadic intrusions (SCASI), or spinocerebellar ataxia, recessive, type 4 (SCAR4). Linkage to chromosome 1p36 was found in this family with a logarithm of odds score of 3.1. The phenotypic spectrum in our 12 patients was broad. Although most presented with ataxia, additional or predominant spasticity was present in 5 patients. Disease onset ranged from infancy to 39 years, and symptoms were slowly progressive and included loss of independent ambulation in 5. All but 2 patients carried a loss‐of‐function (nonsense or splice site) mutation on one and a missense mutation on the other allele. Knockdown or removal of Vps13D in Drosophila neurons led to changes in mitochondrial morphology and impairment in mitochondrial distribution along axons. Patient fibroblasts showed altered morphology and functionality including reduced energy production.

Interpretation

Our study demonstrates that compound heterozygous mutations in VPS13D cause movement disorders along the ataxia–spasticity spectrum, making VPS13D the fourth VPS13 paralog involved in neurological disorders. Ann Neurol 2018
Palaeoproteomic Profiling of Conservation Layers on a 14th Century Italian Wall Painting
Authors: Mackie Meaghan , Rüther Patrick , Samodova Diana , Di Gianvincenzo Fabiana , Granzotto Clara , Lyon David , Peggie David A. , Howard Helen , Harrison Lynne , Jensen Lars Juhl , Olsen Jesper V. , Cappellini Enrico
Published: March 2018

Ahead of display, a non‐original layer was observed on the surface of a fragment of a wall painting by Ambrogio Lorenzetti (active 1319, died 1348/9). FTIR analysis suggested proteinaceous content. Mass spectrometry was used to better characterise this layer and revealed two protein components: sheep and cow glue and chicken and duck egg white. Analysis of post‐translational modifications detected several photo‐oxidation products, which suggest that the egg experienced prolonged exposure to UV light and was likely applied long before the glue layer. Additionally, glycation products detected may indicate naturally occurring glycoprotein degradation or reaction with a carbohydrate material such as starch, identified by ATR‐FTIR in a cross‐section of a sample taken from the painting. Palaeoproteomics is shown to provide detailed characterisation of organic layers associated with mural paintings and therefore aids reconstruction of the conservation history of these objects.
Monitoring of the ADP/ATP Ratio by Induced Circularly Polarised Europium Luminescence
Authors: Shuvaev Sergey , Fox Mark A. , Parker David
Published: March 2018

A series of three europium complexes bearing picolyl amine moieties was found to possess differing binding affinities towards Zn2+ and three nucleotides: AMP, ADP, and ATP. A large increase in the total emission intensity was observed upon binding Zn2+, followed by signal amplification upon the addition of nucleotides. The resulting adducts possessed strong induced circularly polarised emission, with ADP and ATP signals of opposite sign. Model DFT geometries of the adducts suggest the Δ diastereoisomer is preferred for ATP and the Λ isomer for ADP/AMP. This change in sign allows the ADP/ATP (or AMP/ATP) ratio to be assessed by monitoring changes in the emission dissymmetry factor, gem.
Atom‐Economic Silver‐Catalyzed Difunctionalization of the Isocyano Group with Cyclic Oximes: Towards Pyrimidinediones
Authors: Liang Hong‐Wen , Yang Zhen , Jiang Kun , Ye Ying , Wei Ye
Published: March 2018

An unprecedented silver‐catalyzed difunctionalization of the isocyano group with cyclic oximes is described. This method allows efficient and atom‐economic assembly of a vast array of structurally novel and interesting pyrimidinediones, and tolerates a range of functionalities. The resulting products can be easily converted into some useful compounds. Furthermore, the method can also be applied for the late‐stage modification of a few biologically active molecules.
Modified High‐Nickel Cathodes with Stable Surface Chemistry Against Ambient Air for Lithium‐Ion Batteries
Authors: You Ya , Celio Hugo , Li Jianyu , Dolocan Andrei , Manthiram Arumugam
Published: March 2018

High‐Ni layered oxides are promising next‐generation cathodes for lithium‐ion batteries owing to their high capacity and lower cost. However, as the Ni content increases over 70 %, they have a high dynamic affinity towards moisture and CO2 in ambient air, primarily reacting to form LiOH, Li2CO3, and LiHCO3 on the surface, which is commonly termed “residual lithium”. Air exposure occurs after synthesis as it is common practice to handle and store them under ambient conditions. The air exposure leads to significant performance losses, and hampers the electrode fabrication, impeding their practical viability. Herein, we show that substituting a small amount of Al for Ni in the crystal lattice notably improves the chemical stability against air by limiting the formation of LiOH, Li2CO3, LiHCO3, and NiO in the near‐surface region. The Al‐doped high‐Ni oxides display a high capacity retention with excellent rate capability and cycling stability after being exposed to air for 30 days.
Halogenaromatische π‐Wechselwirkungen modulieren die Verweilzeit von Inhibitoren
Authors: Heroven Christina , Georgi Victoria , Ganotra Gaurav K. , Brennan Paul , Wolfreys Finn , Wade Rebecca C. , Fernández‐Montalván Amaury E. , Chaikuad Apirat , Knapp Stefan
Published: March 2018

Längere Verweilzeiten vom Wirkstoff am Zielmolekül (Target) können zu länger anhaltender Arzneimittelwirksamkeit, verbesserten pharmakodynamischen Eigenschaften und kinetischer Selektivität gegenüber Antitargets mit schnellen Dissoziationsraten führen. Bisher wurden nur wenige Strategien gefunden, um die Verweilzeit des Wirkstoffs rational zu modulieren und dadurch diese Schlüsseleigenschaft in den Medikamentenentwicklungsprozess zu integrieren. Die Wechselwirkung zwischen einem Halogenrest am Inhibitor und einer aromatischen Seitenkette im Zielprotein kann die Inhibitorverweilzeit signifikant erhöhen. Als Modell für den archetypischen Bindungsmodus eines ATP‐kompetitiven Typ‐I‐Inhibitors mit einer konstitutiv aktiven Kinase wurde die Wechselwirkung der Serin/Threonin‐Kinase Haspin mit 5‐Iodotubercidin(5‐iTU)‐Derivaten verwendet und gezeigt, dass die Inhibitorverweilzeit deutlich mit der Größe und Polarisierbarkeit des Halogenatoms zunimmt. Mithilfe kinetischer, thermodynamischer und struktureller Messungen sowie Bindungsenergieberechnungen liefern wir eine detaillierte mechanistische Charakterisierung der halogenaromatischen π‐Interaktionen in Haspin‐Inhibitor‐Komplexen.
Side Methyl Groups Control the Conformation and Contribute to Symmetry Breaking of Isoprenoid Chromophores
Authors: Fiedor Leszek , Pilch Mariusz
Published: March 2018

Ab initio DFT computations reveal that the essential structural and photophysical features of the conjugated π‐electron system of retinal and carotenoids are dictated by “innocent” methyl substituents. These methyl groups shape the conformation and symmetry of the isoprenoid chromophores by causing a sigmoidal distortion of the polyene skeleton and increasing its flexibility, which facilitates fitting to their binding pockets in proteins. Comparison of in vacuo conformations of the chromophores with their native (protein‐bound) conformations showed, surprisingly, that the peripheral groups and interactions with the protein environment are much less significant than the methyl side groups in tuning their structural features. The methyl side groups also contribute to a loss of symmetry elements specific to linear polyenes. In effect, the symmetry‐imposed restrictions on the chromophore electronic properties are disabled, which is of tremendous relevance to their photophysics. This is evidenced by their non‐negligible permanent dipole moments and by the simulated and experimentally measured circular dichroism spectra, which necessarily reflect the chirality of the conjugated π‐electron system.
Doppelbindungen? Untersuchungen der Rotationsbarrieren von cumulenischen C=C‐Bindungen in Tetraaryl[n]cumulenen (n=3, 5, 7, 9)
Authors: Bühringer Martina U. , Padberg Kevin , Phleps Martin D. , Maid Harald , Placht Christian , Neiss Christian , Ferguson Michael J. , Görling Andreas , Tykwinski Rik R.
Published: March 2018

Bindungen spielen in der organischen Chemie eine wesentliche Rolle, jedoch wurde die Stärke von C=C‐Bindungen in [n]Cumulenen als Funktion zunehmender Kettenlänge für Verbindungen mit n>5 noch nicht experimentell nachgewiesen. Die Synthese einer Serie von apolaren, unsymmetrisch substituierten Tetraaryl[n]cumulenen (n=3, 5, 7, 9) wurde entwickelt und die Rotationsbarrieren für die Z/E‐Isomerisierung mit dynamischer VT‐NMR‐Spektroskopie ermittelt. Sowohl das Experiment als auch die Theorie bestätigen eine deutliche Abnahme der Rotationsbarriere (durch Bestimmung von ΔG≠rot für die Isomerisierung) von >24 zu 19 zu 15 zu 11 kcal−1 in [n]Cumulenen mit n=3, 5, 7, 9. Folglich führt die Abnahme der cumulenischen Bindung bei längeren Cumulenen zu Rotationsbarrieren, die eher charakteristisch für eine sterisch gehinderte Einfachbindung als für eine Doppelbindung sind.
Double Bonds? Studies on the Barrier to Rotation about the Cumulenic C=C Bonds of Tetraaryl[n]cumulenes (n=3, 5, 7, 9)
Authors: Bühringer Martina U. , Padberg Kevin , Phleps Martin D. , Maid Harald , Placht Christian , Neiss Christian , Ferguson Michael J. , Görling Andreas , Tykwinski Rik R.
Published: March 2018

Bonding is a fundamental aspect of organic chemistry, yet the magnitude of C=C bonding in [n]cumulenes as a function of increasing chain length has yet to be experimentally verified for derivatives longer than n=5. The synthesis of a series of apolar and unsymmetrically substituted tetraaryl[n]cumulenes (n=3, 5, 7, 9) was developed and rotational barriers for Z/E isomerization were measured using dynamic VTNMR spectroscopy. Both experiment and theory confirm a dramatic reduction in the rotational barrier (through estimation of ΔG≠rot for the isomerization) across the series, from >24 to 19 to 15 to 11 kcal−1 in [n]cumulenes with n=3, 5, 7, 9, respectively. The reduction in cumulenic bonding in longer cumulenes thus affords bond rotational barriers that are more characteristic of a sterically hindered single bond than that of a double bond.
Employing an Unsaturated Th4+ Site in a Porous Thorium–Organic Framework for Kr/Xe Uptake and Separation
Authors: Wang Yanlong , Liu Wei , Bai Zhuanling , Zheng Tao , Silver Mark A. , Li Yuxiang , Wang Yaxing , Wang Xia , Diwu Juan , Chai Zhifang , Wang Shuao
Published: March 2018

Actinide based metal–organic frameworks (MOFs) are unique not only because compared to the transition‐metal and lanthanide systems they are substantially less explored, but also owing to the uniqueness of actinide ions in bonding and coordination. Now a 3D thorium–organic framework (SCU‐11) contains a series of cages with an effective size of ca. 21×24 Å. Th4+ in SCU‐11 is 10‐coordinate with a bicapped square prism coordination geometry, which has never been documented for any metal cation complexes. The bicapped position is occupied by two coordinated water molecules that can be removed to afford a very unique open Th4+ site, confirmed by X‐ray diffraction, color change, thermogravimetry, and spectroscopy. The degassed phase (SCU‐11‐A) exhibits a Brunauer–Emmett–Teller surface area of 1272 m2 g−1, one of the highest values among reported actinide materials, enabling it to sufficiently retain water vapor, Kr, and Xe with uptake capacities of 234 cm3 g−1, 0.77 mmol g−1, 3.17 mmol g−1, respectively, and a Xe/Kr selectivity of 5.7.
A Multicontrolled Enamine Configurational Switch Undergoing Dynamic Constitutional Exchange
Authors: Ren Yansong , Svensson Per H. , Ramström Olof
Published: March 2018

A multiresponsive enamine‐based molecular switch is presented, in which forward/backward configurational rotation around the C=C bond could be precisely controlled by the addition of an acid/base or metal ions. Fluorescence turn‐on/off effects and large Stokes shifts were observed while regulating the switching process with CuII. The enamine functionality furthermore enabled double dynamic regimes, in which configurational switching could operate in conjunction with constitutional enamine exchange of the rotor part. This behavior was used to construct a prototypical dynamic covalent switch system through enamine exchange with primary amines. The dynamic exchange process could be readily turned on/off by regulating the switch status with pH.
Preparation of 4‐(4‐hydroxyphenoxy)phenol diglycidyl ether with improved toughness behavior
Authors: Liu Caizhao , Sun Mingming , Zhang Bin , Zhang Xugang , Li Jianhui , Xue Gang , Wang Lei , Zhao Ming , Song Caiyu , Li Qili , Jia Jingxia
Published: March 2018

A high‐performance difunctional epoxy resin, 4‐(4‐hydroxyphenoxy)phenol diglycidyl ether (DHPOP), was synthesized by a two‐step method. The curing behavior of DHPOP was investigated by nonisothermal differential scanning calorimetry method and the curing kinetics results revealed that the introduction of ether linkage could improve the activity of epoxy groups, leading to a lower curing temperature and apparent activation energy compared with that of the commercial bisphenol‐A diglycidyl ether (DGEBA). A series of copolymers were then prepared by varying the mass ratio of DHPOP and DGEBA, which were cured with 4,4′‐diaminodiphenyl methane. The effect of DHPOP contents on thermal and mechanical properties and fracture morphology was studied. As expected, with the increase of DHPOP in the network, the impact strength and char yield were significantly enhanced, while the glass transition temperature (Tg) remained unchanged because of the increase of crosslink density. The excellent toughness endows the DHPOP with the promising potential for the application as high‐performance resin matrix. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 46458.
Rheological behavior of high‐density polyethylene (HDPE) filled with paper mill sludge
Authors: Soucy Joël , Godard François , Rivard Pierre , Koubaa Ahmed
Published: March 2018

A comparative study was conducted of composites made with sludge from three different paper mills. Sludges were obtained from a thermomechanical pulp (TMP), a chemico‐TMP (CTMP), and a Kraft mill with a feedstock of primarily black spruce. The primary sludge (PS) and secondary sludge (SS) were mixed at two different ratios (PS:SS = 7:3 and 9:1) and blended with high‐density polyethylene (HDPE) at 20%, 30%, and 40% proportion. The blends were tested using plate–plate geometry before subjection to frequency sweep by oscillation rheometry. The storage modulus (G′), loss modulus (G″), and complex viscosity (η*) increased with increasing paper sludge content. Decreasing the PS:SS ratio from 9:1 to 7:3 decreased G′, G″, and η*. Differential scanning calorimetry showed that sludge addition increased both the melting and crystallization temperature, for a positive effect on crystallinity. Although the behavior of sludge–high‐density polyethylene blends differed from that of traditional wood plastic composite made with wood flour, they obtained G′, G″, and η* values of the same magnitude. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 46484.
Synthesis of statistical PET/PEN random block copolymers and their crystallizability in the bulk and at the surface
Authors: Shinotsuka Kei , Assender Hazel E. , Claridge Timothy D. W.
Published: March 2018

A series of PET/PEN copolyesters were synthesized by molten transesterification. The degree of randomness and the sequence length of the copolymers were determined by 1H NMR spectroscopy, and the changes in the bulk glass transition temperature (TgB), bulk crystallization temperature (TcB), and bulk melting temperature (TmB) were observed by DSC. A clear relationship was obtained between the observed enthalpy of melting (ΔHm) and degree of randomness (B), and TmB was suppressed for the midcompositions. As with their homopolymer counterparts, there was significant depression in crystallization temperature at the surface (TcS) of the random/block copolymers compared with the bulk, and so surface‐localized crystallization could be induced in spin‐coated thick films (thickness ranging from ca. 400 to 700 nm) by annealing at a temperature in which the surface region is mobile, but the bulk is not. The formation of these clear surface crystals allows the morphology to be directly imaged by AFM, and we observed that the crystallizability and the lamellar morphology of the surface crystals deviated from those of the original homopolymers, depending on the mixing ratio of PET/PEN and degree of randomness. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 46515.
Raspberry Pi–powered imaging for plant phenotyping
Authors: Tovar Jose C. , Hoyer J. Steen , Lin Andy , Tielking Allison , Callen Steven T. , Elizabeth Castillo S. , Miller Michael , Tessman Monica , Fahlgren Noah , Carrington James C. , Nusinow Dmitri A. , Gehan Malia A.
Published: March 2018

Premise of the Study

Image‐based phenomics is a powerful approach to capture and quantify plant diversity. However, commercial platforms that make consistent image acquisition easy are often cost‐prohibitive. To make high‐throughput phenotyping methods more accessible, low‐cost microcomputers and cameras can be used to acquire plant image data.

Methods and Results

We used low‐cost Raspberry Pi computers and cameras to manage and capture plant image data. Detailed here are three different applications of Raspberry Pi–controlled imaging platforms for seed and shoot imaging. Images obtained from each platform were suitable for extracting quantifiable plant traits (e.g., shape, area, height, color) en masse using open‐source image processing software such as PlantCV.

Conclusions

This protocol describes three low‐cost platforms for image acquisition that are useful for quantifying plant diversity. When coupled with open‐source image processing tools, these imaging platforms provide viable low‐cost solutions for incorporating high‐throughput phenomics into a wide range of research programs.
Comparison of taxon‐specific versus general locus sets for targeted sequence capture in plant phylogenomics
Authors: Chau John H. , Rahfeldt Wolfgang A. , Olmstead Richard G.
Published: March 2018

Premise of the Study

Targeted sequence capture can be used to efficiently gather sequence data for large numbers of loci, such as single‐copy nuclear loci. Most published studies in plants have used taxon‐specific locus sets developed individually for a clade using multiple genomic and transcriptomic resources. General locus sets can also be developed from loci that have been identified as single‐copy and have orthologs in large clades of plants.

Methods

We identify and compare a taxon‐specific locus set and three general locus sets (conserved ortholog set [COSII], shared single‐copy nuclear [APVO SSC] genes, and pentatricopeptide repeat [PPR] genes) for targeted sequence capture inBuddleja(Scrophulariaceae) and outgroups. We evaluate their performance in terms of assembly success, sequence variability, and resolution and support of inferred phylogenetic trees.

Results

The taxon‐specific locus set had the most target loci. Assembly success was high for all locus sets inBuddlejasamples. For outgroups, general locus sets had greater assembly success. Taxon‐specific andPPRloci had the highest average variability. The taxon‐specific data set produced the best‐supported tree, but all data sets showed improved resolution over previous non‐sequence capture data sets.

Discussion

General locus sets can be a useful source of sequence capture targets, especially if multiple genomic resources are not available for a taxon.
A simple, rapid method for detecting seven common invasive fish species in Europe from environmental DNA
Authors: Clusa Laura , García‐Vázquez E.
Published: March 2018

Biological invasions are a global threat to biodiversity, and many arise from deliberate introductions.

The American freshwater fish Micropterus salmoides and Ameiurus spp. (Ameiurus melas and Ameiurus nebulosus) were introduced to Europe for recreational fishing, Gambusia holbrooki and Gambusia affinis were introduced for mosquito population control, and Lepomis gibbosus was introduced as an ornamental species. The Asiatic Pseudorasbora parva was acquired inadvertently as an accompanying species in fish consignments.

This article presents a novel approach for detecting these species directly from water samples based on a panel of five taxon‐specific primers within 16S rDNA.

The primers were validated from tissue, in aquarium experiments, and from Ebro River water samples (Spain). With a simple polymerase chain reaction (PCR) protocol, followed by visualization in agarose gel or capillary electrophoresis, it was possible to detect these species from environmental DNA concentrations as low as 0.89–100 pg mL–1.

This sensitive and economical tool can be used to control European invasions of these species and to preserve native biodiversity.
First characterization of fucosidases in spiders
Authors: Perrella Natalia N. , Fuzita Felipe J. , Moreti Rodrigo , Verhaert Peter D. E. M. , Lopes Adriana R.
Published: March 2018

l‐fucose is a constituent of glycoconjugates in different organisms. Fucosidases catalyze the removal of fucose residues, and have been correlated to different physiological and pathological processes, such as fertilization, cancer, fucosidosis, and digestion in molluscs and ticks. An α‐l‐fucosidase sequence was identified from the transcriptome and proteome from the midgut diverticula of the synanthropic spider Nephilingis cruentata. In this article, we describe the isolation of this α‐l‐fucosidase and the characterization of its activity using substrates and inhibitors demonstrating different specificities among fucosidases. The enzyme had a Km of 32 and 400 μM for 4‐methylumbelliferyl α‐l‐fucopyranoside and 4‐nitrophenyl α‐l‐fucopyranoside, respectively; and was unable to hydrolyze fucoidan. Nephilingis cruentata α‐l‐fucosidase was inhibited competitively by fucose and fuconojyrimycin. The fucosidase had two distinct pH optima even in the isolated form, due to oligomerization dependent on pH, as previously described to other fucosidases. Alignment and molecular homology modeling of the protein sequence with other fucosidases indicated that the active sites and catalytic residues were different, including residues involved in acid/base catalysis. Phylogenetic analysis showed, for the first time, gene‐duplication events for fucosidases in Arachnida species. All these data reveal that studies on fucosidases in organisms distinct from bacteria, fungi, and humans are important.
Risk, Timing, and Predictors of Disease Flare After Discontinuation of Anti–Tumor Necrosis Factor Therapy in Children With Polyarticular Forms of Juvenile Idiopathic Arthritis With Clinically Inactive Disease
Authors: Lovell Daniel J. , Johnson Anne L. , Huang Bin , Gottlieb Beth S. , Morris Paula W. , Kimura Yukiko , Onel Karen , Li Suzanne C. , Grom Alexei A. , Taylor Janalee , Brunner Hermine I. , Huggins Jennifer L. , Nocton James J. , Haines Kathleen A. , Edelheit Barbara S. , Shishov Michael , Jung Lawrence K. , Williams Calvin B. , Tesher Melissa S. , Costanzo Denise M. , Zemel Lawrence S. , Dare Jason A. , Passo Murray H. , Ede Kaleo C. , Olson Judyann C. , Cassidy Elaine A. , Griffin Thomas A. , Wagner‐Weiner Linda , Weiss Jennifer E. , Vogler Larry B. , Rouster‐Stevens Kelly A. , Beukelman Timothy , Cron Randy Q. , Kietz Daniel , Schikler Kenneth , Schmidt Kara M. , Mehta Jay , Wahezi Dawn M. , Ting Tracy V. , Verbsky James W. , Eberhard B. Anne , Spalding Steven , Chen Chen , Giannini Edward H.
Published: March 2018

Objective

To determine the frequency, time to flare, and predictors of disease flare upon withdrawal of anti–tumor necrosis factor (anti‐TNF) therapy in children with polyarticular forms of juvenile idiopathic arthritis (JIA) who demonstrated ≥6 months of continuous clinically inactive disease.

Methods

In 16 centers 137 patients with clinically inactive JIA who were receiving anti‐TNF therapy (42% of whom were also receiving methotrexate [MTX]) were prospectively followed up. If the disease remained clinically inactive for the initial 6 months of the study, anti‐TNF was stopped and patients were assessed for flare at 1, 2, 3, 4, 6, and 8 months. Life‐table analysis, t‐tests, chi‐square test, and Cox regression analysis were used to identify independent variables that could significantly predict flare by 8 months or time to flare.

Results

Of 137 patients, 106 (77%) maintained clinically inactive disease while receiving anti‐TNF therapy for the initial 6 months and were included in the phase of the study in which anti‐TNF therapy was stopped. Stopping anti‐TNF resulted in disease flare in 39 (37%) of 106 patients by 8 months. The mean/median ± SEM time to flare was 212/250 ± 9.77 days. Patients with shorter disease duration at enrollment, older age at onset and diagnosis, shorter disease duration prior to experiencing clinically inactive disease, and shorter time from onset of clinically inactive disease to enrollment were found to have significantly lower hazard ratios for likelihood of flare by 8 months (P < 0.05).

Conclusion

Over one‐third of patients with polyarticular JIA with sustained clinically inactive disease will experience a flare by 8 months after discontinuation of anti‐TNF therapy. Several predictors of lower likelihood of flare were identified.
Alleviation of Murine Osteoarthritis by Cartilage‐Specific Deletion of IκBζ
Authors: Choi Moon‐Chang , MaruYama Takashi , Chun Churl‐Hong , Park Yoonkyung
Published: March 2018

Objective

IκBζ, an atypical IκB family member, regulates gene expression in the nucleus as a transcriptional cofactor. Although IκBζ has been extensively studied in the immune system, its specific roles in osteoarthritis (OA) are currently unknown. The objective of this study was to investigate the potential role of IκBζ in chondrocyte catabolism and OA pathogenesis. We also determined the molecular mechanism underlying its relationship to the transcription factor NF‐κB.

Methods

We determined expression levels of IκBζ in mouse chondrocytes treated with interleukin‐1β (IL‐1β), in human OA cartilage, and in mouse experimental OA cartilage. Adenovirus‐mediated overexpression and small interfering RNA knockdown of IκBζ were performed to determine the impact of IκBζ on catabolic gene expression in vitro. Cartilage‐specific IκBζ‐transgenic and ‐knockout mice were generated and used for in vivo studies. Experimental and spontaneous OA were induced by surgical destabilization of the medial meniscus and by aging, respectively. Coimmunoprecipitation assay was used to examine the association between IκBζ and NF‐κB subunits.

Results

IκBζ was highly up‐regulated in chondrocytes in response to IL‐1β and in OA cartilage of human and mouse knee joints. Overexpression of IκBζ in chondrocytes promoted spontaneous OA development by activating chondrocyte catabolism. Genetic ablation of IκBζ in chondrocytes abolished catabolic gene induction by IL‐1β and protected against the development of experimental OA. IκBζ formed complexes with NF‐κB members to regulate catabolic factor expression.

Conclusion

These findings demonstrate a critical role for IκBζ in OA pathogenesis. Inhibition of IκBζ function might be an effective therapeutic approach for OA treatment.
Mechanism of Evolution of Koneramine Complexes from One‐Pot Reactions: Snapshots of Intermediates Offer Facile Routes to New Dipicolylamines
Authors: Raje Sakthi , Mondivagu Nandakishor , Chahal Manoj , Butcher Ray J. , Angamuthu Raja
Published: March 2018

Koneramines (LROR′, R=Ph or Ts; R′=Me, iPr) and their complexes were found to emerge from the system of pyridine‐2‐carboxaldehyde and N‐phenyl/tosylethylenediamine when a primary or secondary alcohol was used as solvent. Imidazolidinylpyridines (LR, R=Ph or Ts) became major emergents whereas hemi‐aminals (LROH, R=Ph or Ts) are minor emergents of the system when tertiary butanol was used as the solvent; the bulky tertiary butyl group prevented the addition of alcohol to the iminium ion that diverted the equilibrium towards imidazolidinylpyridines. By playing with the components of the reaction mixture, crystals of the metastable intermediates bound to copper(II) and/or zinc(II) were obtained and the structures were determined by X‐ray diffraction analysis. The reported results shed light on how to control the emergents of the multicomponent reaction mixture that forms koneramines. Reactivity studies of the intermediates pave the way for a new type of koneramine complexes that are new dipicolylamines where the two pyridine moieties of the resulting koneramine are not the same.
Synthetic Applications of Transition‐Metal‐Catalyzed C−P Bond Cleavage
Authors: Wang Lili , Chen Hui , Duan Zheng
Published: March 2018

The wide occurrence of carbon–phosphorus bond activation in modern organic synthesis, catalyst deactivation, and biological process has attracted interest for synthetic applications. Over the past few decades, transition‐metal‐mediated transformations have become extremely powerful tools in organic synthesis. In this review, considerable progress that has been made in catalytic activations and transformations of carbon–phosphorus bonds within the coordination sphere of transition metals is described. Mechanistic information is also presented, and it is hoped that this review not only provides an account of the state of the art in the field, but also highlights the future potential of these reactions in organic synthesis.
Further Results on Quasi‐Synchronization of Delayed Chaotic Systems with Parameter Mismatches Via Intermittent Control
Authors: Jiang Yan , Zhai Junyong
Published: March 2018

This paper focuses on the problem of quasi‐synchronization of delayed chaotic systems with parameter mismatches via aperiodically intermittent control. First, the intermittently controlled systems are modeled as switched systems with two modes. Then, piecewise switching‐time‐dependent Lyapunov functional/function are introduced for stability analysis of the switched systems. As a result, two novel sufficient conditions for quasi‐synchronization are established under a small error bound. Based on the obtained quasi‐synchronization criteria, the existence of the aperiodically intermittent controllers is presented in the form of Linear Matrix Inequalities (LMIs). Finally, chaotic neural networks and Chua's circuit are provided to verify the validity of the proposed method.
Forty years of solar radio observations at Metsähovi Radio Observatory
Authors: Kallunki J. , Tornikoski M. , Tammi J. , Kinnunen E. , Korhonen K. , Kesäläinen S. , Arkko O.
Published: March 2018

The Aalto University Metsähovi Radio Observatory in Finland began regular solar radio observations over 40 years ago, in 1978. It is one of the longest solar radio data collections at millimeter wavelengths, and the data have been widely used in the field of solar radio physics over the years. The main research topics have been microwave solar radio bursts, oscillations, and pulsations in various solar features, for example, radio brightenings and the overall long‐term solar radio variability. Currently, Metsähovi has three different solar radio instruments, operating at wavelengths from 8 mm to 6 m. Most of the observations have been made with the 13.7‐m antenna at 8 mm, but data have also been collected at 3 mm and 1.3 cm. Radio brightenings at 8 mm are a good indicator of the general solar activity level. They show the phase of the solar cycle equally accurately as the traditional solar sunspot number. In this paper, we compare the daily value of the maximum radio brightness temperature and the daily sunspot number in 1989–2017, Solar Cycles 21–24. A more detailed analysis and comparison is performed for Solar Cycle 24 from 2008 onward. We also compare our radio observations to the daily 10.7 cm total radio flux values in Solar Cycle 24.
Structural determinants of ligand binding in truncated hemoglobins: Resonance Raman spectroscopy of the native states and their carbon monoxide and hydroxide complexes
Authors: Feis Alessandro , Howes Barry D. , Milazzo Lisa , Coppola Daniela , Smulevich Giulietta
Published: March 2018

The ligand binding characteristics of heme‐containing proteins are determined by a number of factors, including the nature and conformation of the distal residues and their capability to stabilize the heme‐bound ligand via hydrogen‐bonding and electrostatic interactions. In this regard, the heme pockets of truncated hemoglobins (TrHbs) constitute an interesting case study as they share many common features, including a number of polar cavity residues. In this review, we will focus on three proteins of group II TrHbs, from Thermobifida fusca (Tf‐HbO) and Pseudoalteromonas haloplanktis TAC125 (Ph‐HbO). Although the residues in positions G8 (Trp) and B10 (Tyr) are conserved in all three proteins, the CD1 residue is a Tyr in T. fusca and a His in P. haloplanktis. Comparison of the ligand binding characteristics of these proteins, in particular the hydroxo and CO ligands by means of resonance Raman spectroscopy, reveals that this single difference in the key heme cavity residues markedly affects their ligand binding capability and conformation. Furthermore, although the two Ph‐HbOs (Ph‐HbO‐2217 and Ph‐HbO‐0030) have identical key cavity residues, they display distinct ligand binding properties.
Cardiopulmonary fitness before and after neoadjuvant chemotherapy in patients with oesophagogastric cancer
Authors: Navidi M , Phillips A W , Griffin S M , Duffield K E , Greystoke A , Sumpter K , Sinclair R C F
Published: March 2018

Background

Neoadjuvant chemotherapy may have a detrimental impact on cardiorespiratory reserve. Determination of oxygen uptake at the anaerobic threshold by cardiopulmonary exercise testing (CPET) provides an objective measure of cardiorespiratory reserve. Anaerobic threshold can be used to predict perioperative risk. A low anaerobic threshold is associated with increased morbidity after oesophagogastrectomy. The aim of this study was to establish whether neoadjuvant chemotherapy has an adverse effect on fitness, and whether there is recovery of fitness before surgery for oesophageal and gastric adenocarcinoma.

Methods

CPET was completed before, immediately after (week 0), and at 2 and 4 weeks after neoadjuvant chemotherapy. The ventilatory anaerobic threshold and peak oxygen uptake (Vo2 peak) were used as objective, reproducible measures of cardiorespiratory reserve. Anaerobic threshold and Vo2 peak were compared before and after neoadjuvant chemotherapy, and at the three time intervals.

Results

Some 31 patients were recruited. The mean anaerobic threshold was lower following neoadjuvant treatment: 15·3 ml per kg per min before chemotherapy versus 11·8, 12·1 and 12·6 ml per kg per min at week 0, 2 and 4 respectively (P < 0·010). Measurements were also significantly different at each time point (P < 0·010). The same pattern was noted for Vo2 peak between values before chemotherapy (21·7 ml per kg per min) and at weeks 0, 2 and 4 (17·5, 18·6 and 19·3 ml per kg per min respectively) (P < 0·010). The reduction in anaerobic threshold and Vo2 peak did not improve during the time between completion of neoadjuvant chemotherapy and surgery.

Conclusion

There was a decrease in cardiorespiratory reserve immediately after neoadjuvant chemotherapy that was sustained up to the point of surgery at 4 weeks after chemotherapy.
Practice patterns and outcomes of chemoradiotherapy versus radiotherapy alone for older patients with nasopharyngeal cancer
Authors: Verma Vivek , Surkar Swati M. , Moreno Amy C. , Lin Chi , Simone Charles B.
Published: March 2018

Older patients are at increased risk of toxicities from aggressive oncologic therapy and of nononcologic death. A meta‐analysis of non‐nasopharyngeal head and neck cancers showed no statistical benefit in adding chemotherapy to radiotherapy (RT) in older patients; another meta‐analysis of RT versus chemoradiotherapy (CRT) in NPC found advantages to CRT, but vastly under‐represented patients ≥70 years old. This is the largest study to date evaluating outcomes of CRT versus RT alone in this population. The National Cancer Data Base (NCDB) was queried for primary nasopharyngeal cancer cases (2004–2013) in patients ≥70 years old receiving RT alone or CRT. Patients with unknown RT/chemotherapy and T1N0 or M1 disease were excluded. Logistic regression analysis ascertained factors associated with CRT delivery. Kaplan–Meier analysis evaluated overall survival (OS) between both cohorts. Cox proportional hazards modeling determined variables associated with OS. In total, 930 patients were analyzed (n = 713 (77%) CRT, n = 217 (23%) RT). Groups were relatively balanced; CRT was less frequently delivered in patients with advancing age, lower nodal burden, and females (P < 0.05 for all). Median OS in the CRT and RT groups were 35.3 versus 20.0 months, respectively (P = 0.002). On multivariate analysis, independent predictors of OS included age, comorbidities, income and insurance status, tumor grade, and stage (P < 0.05 for all). Notably, receipt of chemotherapy independently predicted for improved OS (P = 0.036). CRT, compared to RT alone, was independently associated with improved survival in NPC patients ≥70 years old. CRT appears to be a promising approach in this population, but treatment‐related toxicity risks should continue to be weighed against potential oncologic benefits.
Are U.S. consumers using MyPlate and restaurant menu labels and does their use equate with dietary and exercise behavior?
Authors: Vaccaro Joan A. , Huffman Fatma G.
Published: March 2018

The U.S. government provided a website, entitled MyPlate, and required menu labels to state calories to help the population make healthy dietary and exercise choices. The purpose of this study is to assess the awareness and use of nutrition information provided by MyPlate and by restaurant menu labels with dietary and exercise behavior for U.S. adults considering race/ethnicity and gender. This study uses data from the National Health and Nutrition Examination Survey 2013–2014 for adults, aged 20 years and older, from 3 racial/ethnic groups N = 4924: 1,275 Hispanics, 1,177 non‐Hispanic Blacks (NHB); 2,472 non‐Hispanic Whites to assess awareness and who reported seeing nutrition information at fast‐food/pizza places and waitstaff restaurants and answered affirmatively to hearing about MyPlate (N = 749). Dietary behaviors for controlling or losing weight, reducing fat, and increasing exercise was significantly higher for those who tried MyPlate as compared with those who stated they did not try MyPlate. Over half the individuals who reported that they tried MyPlate stated that they would often use nutrition information for fast‐food/pizza places and waitstaff restaurants as compared with less than one‐third of individuals who declared that they have not tried MyPlate. Males, Hispanics, NHB, individuals with a lower education level, current smokers, and older adults had higher percent of not hearing about MyPlate. NHB, males, and older adults had a lower percent of using menu nutrition information. Increasing use of MyPlate and menu calorie labeling may serve to encourage vulnerable groups to make healthy dietary and exercise choices.
Peptide‐Based Scaffold for Nitric Oxide Induced Differentiation of Neuroblastoma Cells
Authors: Pal Hilal Ahmad , Singh Anamika , Sheikh Parvaiz A. , Panjla Apurva , Kumar Ashok , Verma Sandeep
Published: March 2018

Nitric oxide is a gaseous messenger involved in neuronal differentiation, development and synaptogenesis, in addition to many other physiological functions. Therefore, it is imperative to maintain an optimal nitric oxide concentration to ensure its biochemical function. A sustained nitric oxide releasing scaffold, which supports neuronal cell differentiation, as determined by morphometric analysis of neurite outgrowth, is described. Moreover, the effect of nitric oxide on the neuroblastoma cell line was also confirmed by immunofluorescent analysis of neuronal nuclear protein (NeuN), specific neuronal marker and neurofilament (NF) protein, which revealed a significant increase in their expression levels, in comparison with undifferentiated cells.
Comparison of two different culture conditions for derivation of early hiPSC
Authors: Hey Caroline A. B. , Saltõkova Katarina B. , Bisgaard Hanne C. , Møller Lisbeth B.
Published: March 2018

Different culture‐systems for derivation of induced pluripotent stem cells (iPSC) in vitro from human fibroblasts have been established. Here, we compared the efficacy of two different feeder‐free culture‐systems; Matrigel‐coated surfaces in combination with mTeSR1 medium versus Vitronectin‐coated surfaces in combination with Essential 8 (E8) medium. The comparison was performed by counting the number of emerging iPSC‐looking colonies of re‐programmed fibroblasts. The fibroblasts were re‐programmed using episomal plasmids expressing OCT3/4, SOX2, KLF4, L‐MYC, LIN28, and a p53 knock down shP53. Three different fibroblast lines, K40 and K48 from healthy controls and BBS1 from a patient with Bardet–Biedl syndrome, were used in two independent setups. The BBS1 line was used in both setups in combination with K40 and K48 respectively. In all four re‐programming experiments, we observed a significantly higher number of emerging colonies with the combination Matrigel/mTeSR1 as compared to the combination Vitronectin/E8. The presence of iPSC was verified by alkaline phosphatase and Tra‐1‐60 staining. Furthermore, a higher expression of the pluripotency‐associated markers NANOG and SOX2 in cells under Matrigel/mTeSR1 conditions compared with Vitronectin/E8 supported the higher proportion of iPSC on Matrigel/mTeSR1 plates. In conclusion, the combination Matrigel/mTeSR1 is more efficient for derivation of iPSC compared to the Vitronectin/E8 combination.
Small‐scale methods to assess the gluten properties of durum wheat
Authors: Sissons Mike , Smit Jenny
Published: March 2018

Background and objectives

Durum breeders are interested in being able to remove weak gluten genotypes from their crossing populations. Although numerous tests exist to measure gluten strength, methods that can be used in early generations, use minimal sample with little processing and have good discrimination are lacking. The purpose of this work was to evaluate several small‐scale methods to predict gluten strength in durum wheat with emphasis on the gluten aggregation behavior measured using a GlutoPeak device.

Findings

Using as little as 9 g of wholemeal (or semolina), a reproducible GlutoPeak aggregation curve is developed at the end of 5 min. Wholemeal gave higher precision than semolina and is more convenient to prepare when screening breeders’ material. The GlutoPeak Area and Peak Mixing Time (PMT) are good predictors of mixograph and gluten index (GI), which are traditional measures of gluten strength. Good correlations between these parameters were obtained using a diverse set of 145 durum genotypes. GlutoPeak Area gave the best prediction of GI from wholemeal samples allowing a breeder to remove weak‐moderate GI samples from a population using as little as 9 g of wholemeal. The GlutoPeak test showed higher correlations with mixograph and GI than the small‐scale biochemical methods, was easier to perform and uses no chemicals. However, GlutoPeak is not suitable when only mg quantities of sample are available.

Conclusions

The utility of the GlutoPeak device has been further validated in this work for screening durum wheat lines for gluten strength. Wholemeal is a suitable sample (9 g minimum) and provides good precision and reproducibility with a short analysis time of 5 min and requires minimal operator skill. It is suited to screening breeders’ populations for gluten strength and is preferred over SIG, HPLC determination of UPP and IP% determination using a turbidity assay.

Significance and novelty

The GlutoPeak can be used to effectively screen out low‐intermediate gluten strength in a durum wheat breeders’ population using 9 g of wholemeal with a 5 min run time.
High protein S activity due to C4b‐binding protein deficiency in a 34‐year‐old Surinamese female with ischemic retinopathy
Authors: Mulder René , de Vries Jeroen K. , Müskens Rogier P.H.M. , Mulder André B. , Lukens Michaël V.
Published: March 2018

Key Clinical Message

In this study, we present the first case of a 34‐year‐old Surinamese female with ischemic retinopathy and increased free protein S due to C4BP deficiency. Possibly, the low PS/C4BP complex level has increased the risk of arterial thrombosis in our patient.
Artificial Interface Derived from Diphenyl Ether Additive for High‐Voltage LiNi0.5Mn1.5O4 Cathode
Authors: Yue Hong Yun , Han Zhan Li , Tao Liang Liang , Zhang Yao Fa , Wang Lan , Li Xiang Nan , Yin Yan Hong , Yang Wei Guang , Yang Shu Ting
Published: March 2018

Diphenyl ether (DPE) is investigated as a film‐forming additive to improve the cyclic stability of LiNi0.5Mn1.5O4 at high voltage and elevated temperature (55 °C). Addition of DPE in the baseline electrolyte significantly improves the capacity retention of LiNi0.5Mn1.5O4 at elevated temperature. Its capacity retention increases from 41.2 % at the baseline electrolyte to 90.5 % after 0.1 vol% DPE is added to the baseline electrolyte in 100 cycles. Calculations demonstrate that DPE is oxidized preferentially to the baseline electrolyte. The experimental results show that a robust and uniform film is generated on the LiNi0.5Mn1.5O4 surface, alleviating the subsequent electrolyte decomposition and protecting LiNi0.5Mn1.5O4 from transition metal dissolution and structural destruction.
Hybrid Iron Oxide on Three‐Dimensional Exfoliated Graphite Electrode with Ultrahigh Capacitance for Energy Storage Applications
Authors: Sun Zhen , Cai Xiang , Feng Dong‐Yang , Huang Zi‐Hang , Song Yu , Liu Xiao‐Xia
Published: March 2018

Electrode materials with low cost, large theoretical capacity, and fast ion/electron transport rate are highly desirable for capacitive applications. Pseudocapacitive iron oxide materials (e. g., Fe2O3, Fe3O4) satisfy the first two aspects, but are electrically/ionically insulating, hindering their practical applications in energy storage. Here, hybrid mesoporous iron oxide (Fe2O3/Fe3O4) materials are integrated with a three‐dimensional electrochemically exfoliated graphite substrate (EG) using an electrodeposition coupled with a post‐chemical transition strategy. The hybrid Fe2O3/Fe3O4 materials on EG exhibit an ultrahigh specific capacitance of 1530 F g−1 at current density of 1 A g−1. This material with such high capacitance ranks on the top of the reported iron oxide materials for capacitive applications. In addition, the assembled device with EG@Fe2O3/Fe3O4 as anode can deliver a high gravimetric energy density of 21.6 Wh kg−1 at a power density of 225 W kg−1, based on the total mass of the two electrodes (including the mass of the current collectors). This system can power various electronic devices, suggesting its great potential for energy storage applications.