bluuebunny/crossref_metadata_2025 huggingface dataset:
Therapeutic Effects of a TANK‐Binding Kinase 1 Inhibitor in Germinal Center–Driven Collagen‐Induced Arthritis
Authors: Louis Cynthia , Ngo Devi , D'Silva Damian B. , Hansen Jacinta , Phillipson Louisa , Jousset Helene , Novello Patrizia , Segal David , Lawlor Kate E. , Burns Christopher J. , Wicks Ian P.
Published: July 2018

Objective

The production of class‐switched high‐affinity autoantibodies derived from organized germinal centers (GCs) is a hallmark of many autoimmune inflammatory diseases, including rheumatoid arthritis (RA). TANK‐binding kinase 1 (TBK‐1) is a serine/threonine kinase involved in the maturation of GC follicular helper T (Tfh) cells downstream of inducible costimulator signaling. We undertook this study to assess the therapeutic potential of TBK‐1 inhibition using the small‐molecule inhibitor WEHI‐112 in antibody‐dependent models of inflammatory arthritis.

Methods

Using the models of collagen‐induced arthritis (CIA), antigen‐induced arthritis (AIA), and K/BxN serum‐transfer–induced arthritis (STIA), we determined the effectiveness of WEHI‐112 at inhibiting clinical and histologic features of arthritis in C57BL/6 and DBA/1 mice. We used immunohistochemistry to characterize GC populations during CIA development, and we used enzyme‐linked immunosorbent assays to determine levels of Ig autoantibodies in WEHI‐112–treated mice compared to vehicle‐treated mice.

Results

WEHI‐112, a tool compound that is semiselective for TBK‐1 but that also has activity against IKKε and JAK2, abolished TBK‐1–dependent activation of interferon (IFN) regulatory factor 3 and inhibited type I IFN responses in vitro. In vivo, treatment with WEHI‐112 selectively abrogated clinical and histologic features of established, antibody‐dependent CIA, but had minimal effects on an antibody‐independent model of AIA or on K/BxN STIA. In keeping with these findings, WEHI‐112 reduced arthritogenic type II collagen–specific IgG1 and IgG2b antibody production. Furthermore, WEHI‐112 altered the GC Tfh cell phenotype and GC B cell function in CIA.

Conclusion

We report that TBK‐1 inhibition using WEHI‐112 abrogated antibody‐dependent CIA. As WEHI‐112 failed to inhibit non–antibody‐driven joint inflammation, we conclude that the major effect of this compound was most likely the targeting of TBK‐1–mediated mechanisms in the GC reaction. This approach may have therapeutic potential in RA and in other GC‐associated autoantibody‐driven inflammatory diseases.
Synthesis of Phlorin Analogues of Dithiacorrphycene and Their Use as Specific Chemodosimetric Sensors for Fe3+ Ions
Authors: Thorat Kishor G. , Ravikanth Mangalampalli
Published: July 2018

The first examples of stable phlorin analogues of dithiacorrphycene were synthesized by treating appropriate tetrapyrranes with two equivalents of trifluoroacetic acid in CH2Cl2 followed by oxidation with p‐chloranil. The oxidative coupling of tetrapyrrane resulted in the formation of two unexpected phlorin analogues of dithiacorrphycenes that differed from each other at the meso‐sp3‐carbon, and the two macrocycles were easily separated and isolated by column chromatography. The novel macrocycles were confirmed by X‐ray crystallography and characterized by HRMS, 1D and 2D NMR spectroscopy, absorption spectroscopy, cyclic voltammetry, and time‐dependent DFT studies. X‐ray structure analysis revealed the highly strained and distorted nature of the macrocycles. The macrocycles showed one ill‐defined absorption band at λ≈315 nm and a broad band at λ≈530 nm. Because both macrocycles possess two thiophene and two pyrrole rings with one ionizable inner NH, the cation‐sensing properties of the phlorin analogues of dithiacorrphycenes have been investigated. The phlorin analogues of dithiacorrphycenes act as specific chemodosimetric sensors for Fe3+ ions by converting phlorin analogues of dithiacorrphycenes into dithiacorrphycene.
Integrating Northern Ireland: Cross‐group friendships in integrated and mixed schools
Authors: Blaylock Danielle , Hughes Joanne , Wölfer Ralf , Donnelly Caitlin
Published: July 2018

While Northern Ireland strives to build a shared society, the current reality is that everyday experiences are still shaped by division along ethno‐religious lines. This is particularly pronounced in the education system, where more than 92% of pupils attend separate schools. Within the predominantly separate education system, however, exists a small collection of schools which cater to a more heterogeneous pupil body and offer the opportunity for young people from both communities to meet and interact, and potentially develop cross‐group friendships. The present study compares the network‐based cross‐group friendships within two such school types; an integrated and a separate post‐primary school. These schools boast a distinct ethos yet they similarly enrol students from Catholic and Protestant backgrounds. Findings reveal that both schools show a high level of interconnection between pupils; however, the integrated school, with an ethos that openly supports social cohesion, shows a greater tendency towards cross‐group interactions and best friendships than those found within the separate school. In line with contact theory, these findings suggest that it may not be enough to simply create opportunities for intergroup contact but that optimal conditions, such as institutional support, may be a prerequisite for positive relationships to flourish. Implications for educational policies designed to promote greater cross‐community contact are discussed.
Circular permutation of a bacterial tyrosinase enables efficient polyphenol‐specific oxidation and quantitative preparation of orobol
Authors: Lee Pyung‐Gang , Lee Sang‐Hyuk , Hong Eun Young , Lutz Stefan , Kim Byung‐Gee
Published: July 2018

Tyrosinase is a type 3 copper oxygenase that catalyzes a phenol moiety into ortho‐diphenol, and subsequently to ortho‐quinone. Diverse tyrosinases have been observed across the kingdom including Animalia, Bacteria, Plantae, and Fungi. Among the tyrosinases, bacterial, and mushroom tyrosinases have been extensively exploited to prepare melanin, ortho‐hydroxy‐polyphenols, or novel plant secondary metabolites during the past decade. And their use as a biocatalyst to prepare various functional biocompounds have drawn great attention worldwide. Herein, we tailored a bacterial tyrosinase from Bacillus megaterium (BmTy) using circular permutation (CP) engineering technique which is a novel enzyme engineering technique to covalently link original N and C termini and create new termini on the middle of its polypeptide. To construct a smart rationally‐designed CP library, we introduced 18 new termini at the edge of each nine loops that link α‐helical secondary structure in BmTy. Among the small library, seven functional CP variants were successfully identified and they represented dramatic change in their enzyme characteristics including kinetic properties and substrate specificity. Especially, cp48, 102, and 245 showed dramatically decreased tyrosine hydroxylase activity, behaving like a catechol oxidase. Exploiting the dramatic increased polyphenol oxidation activity of cp48, orobol (3′‐hydroxy‐genistein) was quantitatively synthesized with 1.48 g/L, which was a 6‐fold higher yield of truncated wild‐type. We examined their kinetic characters through structural speculation, and suggest a strategy to solubilize the insoluble artificial variants effectively.
Review and in silico analysis of fermentation, bioenergy, fiber, and biopolymer genes of biotechnological interest inAgaveL. for genetic improvement and biocatalysis
Authors: Tamayo‐Ordóñez M. C. , Ayil‐Gutiérrez B. A. , Tamayo‐Ordóñez Y. J. , Rodríguez‐Zapata L. C. , Monforte‐González M. , De la Cruz‐Arguijo E. A. , García‐Castillo M. J. , Sánchez‐Teyer L. F.
Published: July 2018

Several of the over 200 known species of Agave L. are currently used for production of distilled beverages and biopolymers. The plants live in a wide range of stressful environments as a result of their resistance to abiotic stress (drought, salinity, and extreme temperature) and pathogens, which gives the genus potential for germplasm conservation and biotechnological applications that may minimize economic losses as a result of the global climate change. However, the limited knowledge in the genus of genome structure and organization hampers development of potential improved biotechnological applications by means of genetic manipulation and biocatalysis. We reviewed Agave and plant sequences in the GenBank NCBI database for identifying genes with biotechnological potential for fermentation, bioenergy, fiber improvement, and in vivo plant biopolymer production. Three‐dimensional modeling of enzyme structures in plant accessions revealed structural differences in sucrose 1‐fructosyltransferase, fructan 1‐fructosyltransferase, fructan exohydrolase (1‐FEH), cellulose synthase (CES), and glucanases (EGases) with possible effects in fructan, sugar, and biopolymer production. Although the coding genes of FEH and enzymes involved in biopolymer production (CES, sucrose synthase, and EGases) remain unidentified in Agave L., our results could aid isolation of such genes in Agave. By comparing nucleotide and amino acid sequences in accessions of Agave and other plants, knowledge may be gained about transcriptional regulation and enzymatic activity factors. Future study is needed of biotechnological application of Agave genes for crop breeding aided by genetic engineering and biocatalysis. © 2018 American Institute of Chemical EngineersBiotechnol. Prog., 34:1314–1334, 2018
An Insight on the Electrocatalytic Mechanistic Study of Pristine Ni MOF (BTC) in Alkaline Medium for Enhanced OER and UOR
Authors: Maruthapandian Viruthasalam , Kumaraguru Shanmugasundaram , Mohan Subramanian , Saraswathy Velu , Muralidharan Srinivasan
Published: July 2018

Hydrogen production plays a major role in technologies for renewable energy storage. Water and urea electrolysis (WE, UE) are promising processes in this regard. The oxygen evolution reaction (OER) and urea oxidation reaction (UOR), respectively, are limiting the efficiency of the overall process. As catalysts for these reactions, metal‐organic frameworks (MOF) have gained increasing attention due to their combinations and co‐existence of metal and organic moiety properties. Here, we investigated the catalytic behavior of Ni MOF (1,3,5‐Benzenetricarboxylic acid (BTC)) towards OER and UOR in alkaline medium on carbon paper (CP) as a support. The Ni MOF exhibits 346 mV overpotential (η) at a current density of 10 mA cm−2, 79.03 A g−1 specific‐mass activity at 400 mV of η than compared to wet chemically prepared (WCP) NiO and RuO2 for OER in 1 M KOH. Meanwhile, ≈230 mV of η at 10 mA cm−2 current density with appreciable stability for 12 hours for Ni MOF in 30 % KOH was also observed. For UOR in UE, Ni MOF shows an onset potential of 1.34 V vs. RHE and 63.15 mA cm−2 current density at 1.5 V vs RHE in 1 M KOH in the presence of 1 M urea. The observed results of OER and UOR catalytic behavior are better than wet chemically prepared (WCP) NiO and noble benchmark RuO2 catalyst under identical conditions. The results suggested that the MOF plays a major role in enhancing the catalytic activity by the facile formation of Ni(OH)2/NiOOH, stability and electronic properties due to their porous and interconnected structure.
Production Options for Psilocybin: Making of the Magic
Authors: Fricke Janis , Lenz Claudius , Wick Jonas , Blei Felix , Hoffmeister Dirk
Published: July 2018

The fungal genus Psilocybe and other genera comprise numerous mushroom species that biosynthesize psilocybin (4‐phosphoryloxy‐N,N‐dimethyltryptamine). It represents the prodrug to its dephosphorylated psychotropic analogue, psilocin. The colloquial term “magic mushrooms” for these fungi alludes to their hallucinogenic effects and to their use as recreational drugs. However, clinical trials have recognized psilocybin as a valuable candidate to be developed into a medication against depression and anxiety. We here highlight its recently elucidated biosynthesis, the concurrently developed concept of enzymatic in vitro and heterologous in vivo production, along with previous synthetic routes. The prospect of psilocybin as a promising therapeutic may entail an increased demand, which can be met by biotechnological production. Therefore, we also briefly touch on psilocybin's therapeutic relevance and pharmacology.
From Indium‐Doped Ag2S to AgInS2 Nanocrystals: Low‐Temperature In Situ Conversion of Colloidal Ag2S Nanoparticles and Their NIR Fluorescence
Authors: Shang Huishan , Di Qiumei , Ji Muwei , Bai Bing , Liu Jiajia , Chen Wenxing , Xu Meng , Rong Hongpan , Liu Jia , Zhang Jiatao
Published: July 2018

Focusing on ternary I‐III‐VI2 colloidal nanocrystals (NCs) synthesized with precise control of the composition (from doping to ternary composition) and NIR fluorescence performance, monodisperse binary In3+‐doped Ag2S NCs and ternary AgInS2 NCs have been achieved successfully by facile low‐temperature in situ conversion of colloidal Ag2S nanoparticles. In3+ ions were inserted into the crystal lattice of Ag2S NCs at a relatively low temperature as dopant and ternary AgInS2 NCs were obtained at a higher temperature following a phase transition. These doped Ag2S and AgInS2 NCs based on different indium precursor concentrations were explored with respect to the position and intensity of the near‐infrared photoluminescent emission at different doping levels and crystal phase evolution.
When Kinases Meet PROTACs
Authors: Tan Li , Gray Nathanael S.
Published: July 2018

Small molecule drugs targeting kinases have revolutionized treatment options for millions of patients worldwide, especially in oncology. These targeted treatments have less side effects because they inhibit a specific dysfunctional kinase usually with relatively narrow selectivity. However, kinase inhibitors do have well‐established liabilities, most prominently the emergence of drug resistance. Moreover, the majority of kinases are multidomain and multifunctional proteins that in addition to their enzymatic activity have scaffolding and other roles, and inhibitors seldom address these alternative functions. Recently, small molecule mediated targeted protein degradation emerged as a new pharmacological strategy. The majority of small molecule degraders are bispecific molecules called proteolysis targeting chimeras (PROTACs), and their mechanism of action is based on simultaneous recruitment of the target of interest and an E3 ligase, resulting in target polyubiquitination and eventual destruction by the proteasome. Over the last couple of years, PROTAC strategy has been developed and validated for a range of targets, including kinases. Here, we introduce the targeted protein degradation strategy, provide an overview of representative kinase PROTACs, and describe design rationales, efficacy and specificity. We also discuss their potential advantages, as well as comment on some of the limitations of this emerging pharmacological modality.
Progress in the Development of Platelet‐Activating Factor Receptor (PAFr) Antagonists and Applications in the Treatment of Inflammatory Diseases
Authors: Hyland Isabel K. , O'Toole Ronan F. , Smith Jason A. , Bissember Alex C.
Published: July 2018

Platelet‐activating factor (PAF) and its receptor (PAFr) have been implicated in a wide range of diseases and disorders that originate from the activation of inflammatory pathways. Although the exact structure of the binding site on the PAFr remains unknown, the PAFr is a well‐established therapeutic target, and an array of structurally diverse PAFr antagonists have been identified. These include compounds that are structurally similar to the natural PAF ligand, synthetic heterocycles, complex polycyclic natural products, and various metal complexes. This review provides an update on more than 20 years of progress in this area. The development and synthesis of new PAFr antagonists, structure–activity relationship studies, the biological activity of these molecules, and their therapeutic potential are discussed.
Production of Human β‐Actin Using a Bacterial Expression System with a Cold Shock Vector
Authors: Tamura Minoru
Published: July 2018

Actin is one of the most abundant proteins in the cytoplasm of eukaryotic cells and plays important roles in a variety of cellular functions. However, it has been difficult to produce actin in substantial amounts using bacterial expression systems. In this article, a new method is described for the production of recombinant actin in bacterial cells. Human β‐actin (His‐tagged) can be expressed using a cold shock vector, pCold, in a bacterial expression system and then separated with a Ni‐chelating resin, followed by a polymerization/depolymerization cycle or column chromatography with the Ni‐chelating resin. The purified recombinant β‐actin shows normal polymerization ability compared with commercially available β‐actin purified from human platelets. This article also describes the preparation of mutant actin(G168R). This purified mutant exhibits impaired polymerization ability. The system and procedures described here will provide a useful method for the production of actin isoforms and their mutants. © 2018 by John Wiley & Sons, Inc.
Using Fluorescence Anisotropy for Ligand Binding Kinetics of Membrane Proteins
Authors: Swonger Kirsten N. , Robinson Anne S.
Published: July 2018

Determining ligand binding kinetics provides an indirect route to probe the functional capabilities of the binding pocket of a membrane protein receptor. Presented in this unit are four ligand‐binding protocols that provide data useful for characterizing membrane proteins, including equilibrium binding, thermostability, competitive ligand binding, and kinetic ligand binding. These techniques use fluorescence anisotropy, which is safer, less costly, and simpler to execute than radioactive ligand binding. Each protocol may be used on its own or in combination with others to quantify a number of ligand binding constants. © 2018 by John Wiley & Sons, Inc.
An open outdoor algal growth system of improved productivity for biofuel production
Authors: Kannan Dheeban Chakravarthi , Venkat Devi
Published: July 2018

BACKGROUND

Microalgae are among the most promising options for renewable fuel production in the future. Translating high laboratory yields to outdoor productivity has been a major challenge. Outdoor sunlight intensity is much greater than the saturation light intensities of algae. An open outdoor growth system design has been developed based on systematic distribution of sunlight to improve the productivity.

RESULTS

The first stage of the light‐distribution design (1800 L) yielded 1.5–2.0 times better productivity than a standard open system, and the next stage (630 L) yielded 2–3 times better productivity. Productivities up to 36–42 g m−2 day−1 were obtained in a region where the climatic conditions are mostly adverse for algal growth. Comparison with other similar climatic conditions validated the performance improvement of the growth system over a wide range. Light distribution profiles illustrated the distribution patterns and gave cues for further improvement. Cost comparison of light distribution against the additional land and infrastructure indicates promising reductions.

CONCLUSION

The performance improvement shown by the designed growth system is significant and shows good potential for advancement of outdoor algal production for biofuels and related products. © 2018 Society of Chemical Industry
Co‐immobilization of P450 BM3 and glucose dehydrogenase on different supports for application as a self‐sufficient oxidative biocatalyst
Authors: Solé Jordi , Caminal Gloria , Schürmann Martin , Álvaro Gregorio , Guillén Marina
Published: July 2018

BACKGROUND

The oxy‐functionalization of non‐activated carbon bonds by the bacterial cytochrome P450 BM3 from Bacillus megaterium, presents a promising field in biosynthesis and it has gained much interest in recent decades. Nevertheless, the need for the expensive cofactor NADPH, together with low operational stability of the enzyme have made the implementation of this biocatalyst unfeasible in most cases for industry.

RESULTS

P450 BM3 and glucose dehydrogenase (GDH), as a cofactor regeneration enzyme, were successfully co‐immobilized obtaining a bi‐functional self‐sufficient oxidative biocatalyst. First, a broad screening of 13 different supports was carried out. Five selected agaroses with three different functionalities (epoxy, amine and aldehyde) were studied and their immobilization processes optimized. Finally, P450 BM3 and GDH were co‐immobilized on those supports showing the best performance for P450 BM3 immobilization: epoxy‐agarose (epoxy‐agarose‐UAB) presenting 83% and 20% retained activities respectively; AMINO‐agarose presenting 28% and 25%, and Lentikats® with which both enzymes retained 100% of the initial activity. Furthermore, the re‐utilization of the self‐sufficient immobilized derivatives was tested in five repeated cycles.

CONCLUSIONS

P450 BM3 and GDH have been successfully immobilized on three supports and their re‐usability has been tested in a model reaction. It represents a step forward for future P450 BM3 industrial implementations. © 2018 Society of Chemical Industry
Highly concentrated omega‐3 fatty acid ethyl esters by urea complexation and molecular distillation
Authors: Magallanes Leisa M , Tarditto Lorena V , Grosso Nelson R , Pramparo María C , Gayol María F
Published: July 2018

BACKGROUND

Raya liver deodorized oil contains high concentrations of eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA). The present study investigated the processes of urea complexation (UC) and molecular distillation (MD) to determine the most adequate operation conditions for each process, separately and together, aiming to obtain highly concentrated EPA, DPA and DHA ethyl esters with chemical indicator values permitted by the current legislation for edible oils.

RESULTS

In the second stage of MD, a concentration of 820.27 g kg−1 in the distillate and 951.06 g kg−1 of omega‐3 fatty acid ethyl esters in the residue was obtained. The distillate showed values of free fatty acids, peroxide and p‐anisidine lower than the maximum allowed for edible oils in accordance with the current legislation.

CONCLUSION

The use of UC and MD together has revealed a significant improvement in the total concentration of omega‐3 fatty acid ethyl esters in the final product and good application prospects. © 2018 Society of Chemical Industry
Enhancement of Istrian Malvasia wine aroma and hydroxycinnamate composition by hand and mechanical leaf removal
Authors: Bubola Marijan , Lukić Igor , Radeka Sanja , Sivilotti Paolo , Grozić Kristina , Vanzo Andreja , Bavčar Dejan , Lisjak Klemen
Published: July 2018

BACKGROUND

Leaf removal is a viticultural practice that promotes the biosynthesis of several important grape constituents by improving fruit zone microclimate. The purpose of this study was to assess the effects of hand and mechanical leaf removal, applied at the pea‐size stage of berry development, on fruit zone microclimate, volatile aroma compounds, hydroxycinnamates and sensory characteristics of Istrian Malvasia (Vitis vinifera L.) wines. Three different sunlight exposure conditions were applied: hand leaf removal (HLR), mechanical leaf removal (MLR) and untreated control (UC).

RESULTS

Both leaf removal treatments, and especially the more intense HLR, significantly increased the concentration of varietal thiol 3‐sulfanylhexan‐1‐ol, monoterpenes, β‐damascenone and esters. The higher concentration of these aromas contributed to the improvement of wine sensory quality, as expressed by more enhanced floral, fruity and tropical sensory attributes in leaf removal treatments. Hydroxycinnamates were increased only by HLR, a treatment with a greater degree of fruit exposure to sunlight than MLR.

CONCLUSION

Leaf removal applied at the pea‐size stage of berry development in a season characterized by abundant rainfall improves both the chemical composition and sensory quality of Istrian Malvasia wine, even when performed by machine, implying that this technique might be successfully applied in large‐scale viticultural production. © 2018 Society of Chemical Industry
Effects of α‐, β‐ and maltosyl‐β‐cyclodextrins use on the glucoraphanin–sulforaphane system of broccoli juice
Authors: Martínez‐Hernández Ginés B , Venzke‐Klug Tâmmila , Carrión‐Monteagudo María del Mar , Artés Calero Francisco , López‐Nicolás José M , Artés‐Hernández Francisco
Published: July 2018

Cyclodextrins (CDs) are macromolecules with several industrial applications, being particularly used in the food industry as health‐promoting compounds protection agents, as flavour stabilizers, or to eliminate undesired tastes and browning reactions, among others. This study shows the effects of α‐ (10, 30 and 40 mmol L−1), β‐ (3, 6 and 10 mmol L−1) and maltosyl‐β‐CDs (30, 60 and 90 mmol L−1) use on the health‐promoting glucoraphanin–sulforaphane system of a broccoli juice up to 24 h at 22 °C. Maltosyl‐β‐CD (90 mmol L−1) highly retained glucoraphanin content after 24 h at 22 °C, showing better effectiveness than β‐CD (10 mmol L−1). Sulforaphane was efficiently encapsulated with β‐CD at just 3 mmol L−1, and the sulforaphane formed was stable during 3 h at 22 °C. On the other hand, 40 mmol L−1 α‐CD retained a high glucoraphanin content in broccoli juice. In contrast, glucoraphanin levels in juice without CDs decreased by 71% after 24 h. Consequently, CDs addition may potentially preserve glucoraphanin in this broccoli juice during industrial processing with the possibility to be later transformed by endogenous myrosinase after ingestion to the health‐promoting sulforaphane. © 2018 Society of Chemical Industry
Miniaturized capillary ion chromatograph with UV light‐emitting diode based indirect absorbance detection for anion analysis in potable and environmental waters
Authors: Murray Eoin , Li Yan , Currivan Sinead A. , Moore Breda , Morrin Aoife , Diamond Dermot , Macka Mirek , Paull Brett
Published: July 2018

A miniaturized, flexible, and low‐cost capillary ion chromatography system has been developed for anion analysis in water. The ion chromatography has an open platform, modular design, and allows for ease of modification. The assembled platform weighs ca. 0.6 kg and is 25 × 25 cm in size. Isocratic separation of common anions (F–, Cl–, NO2–, Br–, and NO3–) could be achieved in under 15 min using sodium benzoate eluent at a flow rate of 3 μL/min, a packed capillary column (0.150 × 150 mm) containing Waters IC‐Pak 10 μm anion exchange resin, and light‐emitting diode based indirect UV detection. Several low UV light‐emitting diodes were assessed in terms of sensitivity, including a new 235 nm light‐emitting diode, however, the highest sensitivity was demonstrated using a 255 nm light‐emitting diode. Linear calibration ranges applicable to typical natural water analysis were obtained. For retention time and peak area repeatability, relative standard deviation values ranged from 0.60–0.95 and 1.95–3.53%, respectively. Several water samples were analysed and accuracy (recovery) was demonstrated through analysis of a prepared mixed anion standard. Relative errors of –0.36, –1.25, –0.80, and –0.76% were obtained for fluoride, chloride, nitrite, and nitrate, respectively.
Second‐order calibration serves as a remedial measure for the simultaneous determination of andrographolide and dehydroandrographolide in Andrographis paniculata and its preparations by HPLC without complete baseline separation
Authors: Yin Xiao‐Li , Gu Hui‐Wen , Wu Qiao , Peng Tian‐Qin , Zhang Shan‐Hui , Liu Yang
Published: July 2018

In this work, high‐performance liquid chromatography with diode array detection was applied for the simultaneous determination of andrographolide and dehydroandrographolide in Andrographis paniculata and its preparations. As a result of the incomplete baseline separation caused by complex backgrounds, the classical univariate calibration method failed to determine accurate contents of the analytes. On this occasion, chemometric second‐order calibration based on the well‐known alternating trilinear decomposition algorithm was then explored to serve as a post‐experimental remedial tool to solve this problem. By using the intelligent “mathematical separation” of alternating trilinear decomposition, the peak areas of the analytes do not need to be directly measured and the predictive results become accurate. The contents of andrographolide and dehydroandrographolide were determined to be (7.95 ± 0.15) and (1.85 ± 0.02) μg/mL for Andrographis paniculata, (1.34 ± 0.01) and (5.53 ± 0.04) μg/mL for its preparations, which was in agreement with those obtained by a reference liquid chromatography with mass spectrometry method. This study showed the superiority of second‐order calibration method over classical univariate calibration method for simultaneous determination of multi‐analytes in complex samples. It also proved that second‐order calibration may be a good choice for remedying incomplete baseline separation problem, with the accompanied reduction of experimental burden and toxic organic solvents as well as analysis time and cost.
Effect of Equisetum arvense extract as corrosion inhibitor of A36 steel in sulfuric acid solution
Authors: Ramírez‐Peralta Gladiola I. , León‐Silva Ulises , Nicho Díaz Maria E. , Valladares‐Cisneros María G.
Published: July 2018

The Equisetum arvense extract was prepared by the maceration technique and experimentally tested as a corrosion inhibitor of A36 steel in 0.5 M sulfuric acid at room temperature. The corrosion resistance was estimated by the determination of the polarization curves, linear polarization resistance (LPR) and electrochemical impedance spectroscopy (EIS). In order to study the effect of the Equisetum arvense extract on the superficial morphology of metal, scanning electronic microscopy (SEM) was used. The results indicated a decrease of about two orders of magnitude in the corrosion rate, an increase in polarization resistance and a greater efficiency of inhibition by increasing the concentration of extract. The corrosion mechanism was mainly controlled by charge transfer from metal to the environment through the double electrochemical layer. The SEM images corroborated the results obtained in the corrosion tests, at higher concentration of extract less metal surface damage was observed.
Healthcare professionals’ ethical competence: A scoping review
Authors: Koskenvuori Janika , Stolt Minna , Suhonen Riitta , Leino‐Kilpi Helena
Published: July 2018

Aim

The aim of this study was to examine the extent and nature of the available research literature on healthcare professionals’ ethical competence and to summarize the research findings in this field.

Design

A scoping review guided by Arksey and O'Malleys methodological framework was conducted.

Methods

Six databases including Pubmed/Medline, CINAHL, Web of Science Core Collection, PsycInfo, Philosophers’ Index, and Scopus were searched systematically. Of 1,476 nonduplicate citations, 17 matched the inclusion criteria.

Results

Findings revealed that healthcare professionals’ ethical competence is a limited but topical research area. The focus areas of the studies were conceptualization, measuring, and realization of the ethical competence. The studies provided varying definitions and constructions for ethical competence and a few instruments to measure ethical competence were identified. Research in this area seems to be in a transition phase from theorization to empirical measurement. Methodologically, the research was rather heterogeneous and mainly focused on nurses.
Fear of graft rejection 1–5 years after lung transplantation—A nationwide cohort study
Authors: Forsberg Anna , Nilsson Madeleine , Jakobsson Sofie , Lennerling Annette , Kisch Annika
Published: July 2018

Aim

To explore the perceived threat of the risk of graft rejection and its relationship to psychological general well‐being and self‐efficacy 1–5 years after lung transplantation.

Design

A nationwide, cross‐sectional cohort study as a part of the Self‐management after thoracic transplantation study.

Methods

A total of 117 lung transplant recipients due for their yearly follow‐up one (N = 35), two (N = 28), three (N = 23), four (N = 20) and 5 years (N = 11) after lung transplantation were included. We used three instruments; the Perceived Threat of the Risk of Graft Rejection, the Psychological General Well‐being and Self‐efficacy in chronic illness.

Results

The lung recipients reported an overall low perceived threat of the risk of graft rejection with no gender differences. Intrusive anxiety explained 24.7% of the variance in the PGWB‐sum (p ≤ 0.001) and makes a statistically significant (β = −497;p ≤ 0.001) unique contribution to the overall psychological general well‐being (95%CI 3.004—1.515).
Trends: Who's using social, and how often?
Authors: Talarico Donna
Published: July 2018

As you're working on your marketing budgets and communication strategy into the new fiscal year, are you keeping digital in mind? If so, you might want to take the latest usage research into consideration.
Fatal correlation between YAP1 expression and glioma aggressiveness: clinical and molecular evidence
Authors: Guichet Pierre‐Olivier , Masliantsev Konstantin , Tachon Gaëlle , Petropoulos Christos , Godet Julie , Larrieu Delphine , Milin Serge , Wager Michel , Karayan‐Tapon Lucie
Published: July 2018

During the last decade, large‐scale genomic analyses have clarified the somatic alterations in gliomas, providing new molecular classification based on IDH1/2 mutations and 1p19q codeletion with more accurate patient prognostication. The Hippo pathway downstream effectors, YAP1 and TAZ, have recently emerged as major determinants of malignancy by inducing proliferation, chemoresistance, and metastasis in solid tumors. In this study, we investigated the expression of YAP1 in 117 clinical samples of glioma described according to the WHO 2016 classification. We showed for the first time that YAP1 was tightly associated with glioma molecular subtypes and patient outcome. We validated our results in an independent cohort from the TCGA database. More interestingly, we found that YAP1 may have prognostic significance for predicting patient survival, especially in low‐grade gliomas. Using patient‐derived glioblastoma stem cell cultures, we demonstrated that YAP1 was activated and that it controlled cell proliferation. Transcriptome analysis revealed lower expression of YAP1 in the proneural GBM subtype. Furthermore, we found that overexpression of YAP1 was sufficient to inhibit the OLIG2 proneural marker, suggesting its involvement in maintenance of the GBM phenotype. Taken together, our results showed that YAP1 could be a relevant prognostic biomarker and a potential therapeutic target in glioma. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Insulin and glucose homeostasis in childhood cancer survivors treated with abdominal radiation: A pilot study
Authors: Friedman Danielle Novetsky , Hilden Patrick , Moskowitz Chaya S. , Wolden Suzanne L. , Tonorezos Emily S. , Antal Zoltan , Carlow Dean , Modak Shakeel , Cheung Nai‐Kong , Oeffinger Kevin C. , Sklar Charles A.
Published: July 2018

Background

Childhood cancer survivors exposed to abdominal radiation (abdRT) are at increased risk for both insulin‐dependent and non–insulin‐dependent diabetes. We sought to clarify the pathophysiology of diabetes after abdRT by performing dynamic studies of insulin and glucose and testing for type 1 diabetes‐associated autoantibodies.

Procedure

Cross‐sectional analysis of 2‐year childhood cancer survivors treated with abdRT at age ≤21 years who underwent oral glucose tolerance testing and assessment of diabetes‐related autoantibodies from December 2014 to September 2016. Prevalence of insulin/glucose derangements, indices of insulin sensitivity/secretion (homeostatic model assessment of insulin resistance [HOMA‐IR], whole‐body insulin sensitivity, insulinogenic index), autoantibody positivity, and treatment/demographic factors associated with adverse metabolic outcomes were assessed.

Results

Among 40 participants previously exposed to abdRT (57.5% male; median age at cancer diagnosis, 3.3 years [range, 0.5–20.1]; median age at study 14.3 years [range, 8.3–49.8]; none with obesity), 9 (22.5%) had glucose derangements (n = 4 with impaired fasting glucose [≥100 mg/dL]; n = 4 with impaired glucose tolerance [2‐hour glucose 140–199 mg/dL]; n = 1 with previously unrecognized diabetes [2‐hour glucose ≥200 mg/dL]). Three of the four individuals with impaired fasting glucose also had insulin resistance, as measured by HOMA‐IR; an additional four subjects with normal glucose tolerance were insulin resistant. The subject with diabetes had normal HOMA‐IR. No participant had absolute insulinopenia or >1 positive diabetes‐related autoantibody.

Conclusions

This study suggests that radiation‐induced damage to the insulin‐producing β‐cells is an unlikely explanation for the early derangements in glucose metabolism observed after abdRT. Research into alternative pathways leading to diabetes after abdRT is needed.
Compound heterozygous variants in POR gene identified by whole‐exome sequencing in a Chinese pedigree with cytochrome P450 oxidoreductase deficiency
Authors: Hao Chanjuan , Guo Jun , Guo Ruolan , Qi Zhan , Li Wei , Ni Xin
Published: July 2018

Importance

Cytochrome P450 oxidoreductase deficiency (PORD) is a rare disease exhibiting a variety of clinical manifestations. This condition specifically leads to disordered steroidogenesis, which can affect the development of the reproductive system, skeleton, and other parts of the body. The severe form of PORD is difficult to differentiate with Antley‐Bixler syndrome (ABS). The genetic characters and clinical evaluation of PORD are still unclear in China.

Objective

To perform an exome analysis and identify the pathogenic cause in order to assist clinicians to obtain a proper evaluation on the genetic condition.

Methods

The proband underwent detailed physical evaluations. DNA of the proband and his parents was isolated and whole‐exome sequencing (WES) was performed. Variants were analyzed and evaluation according to the ACMG guideline.

Results

A 1‐year‐old Chinese boy with midface hypoplasia, choanal stenosis, multiple joint contractures, micropenis and right cryptorchidism was misdiagnosed with Crouzon syndrome. By trio‐whole‐exome sequencing, we identified an unreported compound heterozygous mutation (c.667C>T, p.R223* and c.1370G>A, p.R457H) in POR in the proband. This mutation was inherited from healthy heterozygous parents, supporting the diagnosis of PORD, which was further confirmed by biochemical characteristics.

Interpretation

We have identified a pathogenic variant with an unreported compound heterozygous POR mutation, which expands the clinical and genetic spectra of PORD and emphasizes the usefulness of WES for genetic diagnosis.
Serotypes of human enteroviruses causing pediatric viral encephalitis and meningitis in Hebei province, China, from 2013 to 2015
Authors: Chen Xiangpeng , Guo Jiayun , Li Jingjie , Li Qiuping , Ai Junhong , Sun Suzhen , Xie Zhengde
Published: July 2018

Importance

Viral encephalitis and meningitis are severe infectious diseases responsible for substantial morbidity and mortality in children. Enteroviruses are typically the most common causative agents of viral encephalitis and meningitis.

Objective

This study aimed to investigate the etiology of viral encephalitis and meningitis among children in Hebei province, China.

Methods

Cerebrospinal fluid samples from children with viral encephalitis (n=309) and meningitis (n=133) were collected between Nov 2013 and Dec 2015 and viral pathogens were identified by real‐time and multiplex PCR. Amplification and sequencing of partial VP1 genes was used to type enteroviruses.

Results

The causative pathogen was successfully detected in 176 (57%) patients with viral encephalitis and 82 (61.7%) patients with viral meningitis. The most common causative agents of both viral encephalitis and meningitis were enteroviruses (55.7% and 64.6% of cases, respectively). The most common enterovirus serotypes identified were echovirus 18, echovirus 6 and echovirus 30. Echovirus 18 accounted for 74.4% of all typed enteroviruses and caused a viral encephalitis and meningitis outbreak in Hebei province in 2015. By contrast, the major enterovirus serotypes circulating in 2014 were echovirus 6 and echovirus 30.

Interpretation

Enteroviruses were the main causative agents of viral encephalitis and meningitis in children in Hebei province from Nov 2013 to Dec 2015. Echovirus 18 became the leading cause of viral encephalitis and meningitis for the first time in Hebei province in 2015.
Critical components for designing and implementing randomized controlled trials
Authors: Nie Xiaolu , Guang Pengya , Peng Xiaoxia
Published: July 2018

Randomized controlled trials (RCTs) are considered the first level of evidence to assess the efficacy of novel interventions/therapies. Proper design and implementation of an RCT can result in convincing causal inferences. RCTs often represent the gold standard for clinical trials when appropriately designed, conducted and reported. However, there are limitations in implementation of RCTs, including sufficiency of randomized allocation (especial for allocation concealment), implementing standard intervention, maintaining follow‐up and statement of conflicting interests. Therefore, the basic principles of RCTs are outlined here so that pediatric investigators can further understand what is the best evidence based on RCTs. More importantly, the quality of pediatric RCTs may be improved by following challenges in pediatric clinical trials outlined here.
Preparation of functionalized cellulose nanoparticles and their effect on the crystallization behaviors of poly(l‐lactide) based nanocomposites
Authors: Tan Huang , Wang Hanqing , Tang Yue , Zhang Shuyang , Yang Wei , Liu Zhengying , Yang Mingbo
Published: July 2018

A rather low crystallization rate has greatly limited the application of poly(l‐lactide) (PLLA) in many fields. Thus, functionalized cellulose nanoparticles (CPNs) were prepared based on cellulose aerogel through a novel and simple approach and were then applied as biobased nucleating agents to improve the crystallization rate of PLLA. First, isolated individual CPNs with a mean diameter around 37.2 nm and regular circular shape were obtained. Subsequently, PLLA based nanocomposites with various contents of CPNs were prepared by solution blending. As a result, CPNs promoted the crystallization rate of PLLA significantly. Compared with that of neat PLLA, the crystallinity (Xc) of the nanocomposites increased dramatically more than 30 times to 36.65% at a CPN loading of 0.5 wt%, and the half‐crystal time (t1/2) at 130 °C decreased by about 91%. Furthermore, due to the presence of CPNs, which provided a large number of nucleation sites in the PLLA matrix, the chain conformational and crystallization kinetics behavior of the PLLA based nanocomposites during isothermal crystallization were changed in the early stages, and based on this result a proposal for the nucleation process for CPNs in a PLLA matrix is presented. © 2018 Society of Chemical Industry
Ice wedges as archives of winter paleoclimate: A review
Authors: Opel Thomas , Meyer Hanno , Wetterich Sebastian , Laepple Thomas , Dereviagin Alexander , Murton Julian
Published: July 2018

Ice wedges are a characteristic feature of northern permafrost landscapes and grow mainly by snowmelt that refreezes in thermal contraction cracks that open in winter. In high latitudes the stable‐isotope composition of precipitation (δ18O and δD) is sensitive to air temperature. Hence, the integrated climate information of winter precipitation is transferred to individual ice veins and can be preserved over millennia, allowing ice wedges to be used to reconstruct past winter climate. Recent studies indicate a promising potential of ice‐wedge‐based paleoclimate reconstructions for more comprehensive reconstructions of Arctic past climate evolution. We briefly highlight the potential and review the current state of ice‐wedge paleoclimatology. Existing knowledge gaps and challenges are outlined and priorities for future ice‐wedge research are suggested. The major research topics are (1) frost cracking and infilling dynamics, (2) formation and preservation of the stable‐isotope information, (3) ice‐wedge dating, (4) age‐model development and (5) interpretation of stable‐isotope time series. Progress in each of these topics will help to exploit the paleoclimatic potential of ice wedges, particularly in view of their unique cold‐season information, which is not adequately covered by other terrestrial climate archives.
Corpora amylacea in prostatectomy tissue and associations with molecular, histological, and lifestyle factors
Authors: DuPre Natalie C. , Flavin Richard , Sfanos Karen S. , Unger Robert H. , To Samantha , Gazeeva Elizaveta , Fiorentino Michelangelo , De Marzo Angelo M. , Rider Jennifer R. , Mucci Lorelei A. ,   Transdisciplinary Prostate Cancer Partnership(ToPCaP)
Published: July 2018

Background

Corpora amylacea are amyloid bodies commonly found adjacent to damaged prostate epithelium. Little is known about their formation or function. The current study sought to characterize corpora amylacea in prostate tissue and to describe their relationship with clinical, histological, molecular, and lifestyle factors, especially with chronic inflammation which is associated with aggressive disease.

Methods

We studied a cohort of 355 men with prostate cancer and tissue specimens from the Health Professionals Follow‐Up Study. Pathologists examined H&E slides and undertook a standardized review for histologic data and inflammation. Trained observers counted corpora amylacea within the benign and predominately tumor areas. Immunohistochemistry biomarkers were available from tissue microarrays. We used multivariable logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) to assess associations of chronic inflammation, clinical, histological, molecular, and lifestyle factors with the presence of corpora amylacea.

Results

Corpora amylacea were present in benign tissue area for 298 men (84%). Specimens with moderate‐to‐severe chronic inflammation were more likely to have corpora amylacea in benign regions (OR = 5.4 95%CI 1.9, 15.6). Moreover, corpora amylacea were more common in men with higher body mass index (OR = 1.13 95%CI 1.01, 1.26). In contrast, Gleason grade (OR = 0.4 95%CI 0.2, 0.8), proliferation index (OR = 0.6 95%CI 0.3, 1.2) and the presence of the TMPRSS2:ERG fusion (OR = 0.4 95%CI 0.2, 0.8) were inversely associated with corpora amylacea presence. TURP specimens were less likely to have corpora amylacea than prostatectomy specimens (OR = 0.12 95%CI 0.03, 0.47). Age, PSA, stage, biomarkers of angiogenesis and PTEN, and vasectomy were not significantly associated with corpora amylacea.

Conclusion

Corpora amylacea were common among men with prostate cancer and were associated with pro‐inflammatory factors, some markers of less aggressive disease, and lack of the TMPRSS2:ERG fusion.