bluuebunny/crossref_metadata_2025 huggingface dataset:
A sharp Pif1-dependent threshold separates DNA double-strand breaks from critically short telomeres
Authors: Strecker Jonathan , Stinus Sonia , Caballero Mariana Pliego , Szilard Rachel K , Chang Michael , Durocher Daniel
Published: August 2017

DNA double-strand breaks (DSBs) and short telomeres are structurally similar, yet they have diametrically opposed fates. Cells must repair DSBs while blocking the action of telomerase on these ends. Short telomeres must avoid recognition by the DNA damage response while promoting telomerase recruitment. In Saccharomyces cerevisiae, the Pif1 helicase, a telomerase inhibitor, lies at the interface of these end-fate decisions. Using Pif1 as a sensor, we uncover a transition point in which 34 bp of telomeric (TG1-3)n repeat sequence renders a DNA end insensitive to Pif1 action, thereby enabling extension by telomerase. A similar transition point exists at natural chromosome ends, where telomeres shorter than ~40 bp are inefficiently extended by telomerase. This phenomenon is not due to known Pif1 modifications and we instead propose that Cdc13 renders TG34+ ends insensitive to Pif1 action. We contend that the observed threshold of Pif1 activity defines a dividing line between DSBs and telomeres.
Obturator Hernia in Elderly Female Patients
Authors: Cartı Erdem Barış , Yılmaz Eyüp Murat , Uçar Ahmet Deniz , Yıldırım Mehmet , Kutlutürk Koray
Published: August 2017

Obturator hernia (OH) constitutes 0.07% to 0.4% of all intraabdominal hernias and 0.2% to 5.8% of small intestinal hernias. OH is usually seen in elderly, multiparous females and patients with a low body weight. This multicenter study includes patients who were treated in Adnan Menderes University Medical Faculty Hospital, Bozyaka Education and Research Hospital and İnönü University Medical Faculty Hospital between January 2010 and June 2015. The diagnosis of OH was made preoperatively or perioperatively in patients who underwent emergency laparotomy for the treatment of ileus. A total of 14 patients were included in this study; 3 patients were treated by laparoscopic method (transabdominal approach) under general anesthesia and 2 of these patients (66.6%) died after the surgery. A total of 7 patients were treated by laparotomy. The remaining 4 patients were treated with a minimally invasive approach by using an epidural block without general anesthesia (3 patients with Pfannenstiel and 1 patient with a median inferior incision). The overall mortality rate was 42.8%. Anesthesia and surgery types have an important effect on mortality in elderly OH patients with multiple comorbidities. Minimally invasive approach with the use of epidural anesthesia can reduce the mortality rates in patients with OH. Abdominal computed tomography is the golden standard in the diagnosis of OH.
A mechanism for cancer‐associated inactivation of NQO1 due to P187S and its reactivation by the consensus mutation H80R
Authors: Muñoz Inés G. , Morel Bertrand , Medina‐Carmona Encarnación , Pey Angel L.
Published: August 2017

The cancer‐associated P187S polymorphism in the NAD(P)H:quinone oxidoreductase 1 (NQO1) abolishes enzyme activity by strongly reducing FAD binding affinity. A single mammalian consensus mutation (H80R) protects P187S from inactivation. To provide mechanistic insight into these effects, we report here a detailed structural and thermodynamic characterization of FAD binding to these NQO1 variants. Our results show that H80R causes a population shift in the conformational ensemble of apo‐P187S, remodelling the structure and dynamics of the FAD‐binding site and reducing the energetic penalization arising from the equilibrium between apo‐ and holo‐states. Our analyses illustrate how single amino acid changes can profoundly affect structural and mechanistic features of protein functional traits, with implications for our understanding of protein evolution and human disease.
Molecular and functional genetics of the proopiomelanocortin gene, food intake regulation and obesity
Authors: Rubinstein Marcelo , Low Malcolm J.
Published: August 2017

A specter is haunting the world, the specter of obesity. During the last decade, this pandemia has skyrocketed threatening children, adolescents and lower income families worldwide. Although driven by an increase in the consumption of ultraprocessed edibles of poor nutritional value, the obesogenic changes in contemporary human lifestyle affect people differently, revealing that some individuals are more prone to develop increased adiposity. During the last years, we performed a variety of genetic, evolutionary, biochemical and behavioral experiments that allowed us to understand how a group of neurons present in the arcuate nucleus of the hypothalamus regulate the expression of the proopiomelanocortin (Pomc) gene and induce satiety. We disentangled the neuronal transcriptional code of Pomc by identifying the cis‐acting regulatory elements and primary transcription factors controlling hypothalamic Pomc expression and determined their functional importance in the regulation of food intake and adiposity. Altogether, our studies reviewed here shed light on the power and limitations of the mammalian central satiety pathways and may contribute to the development of individual and collective strategies to reduce the debilitating effects of the self‐induced obesity pandemia.
Upper ocean cooling and air‐sea fluxes under typhoons: A case study
Authors: Potter Henry , Drennan William M. , Graber Hans C.
Published: August 2017

Direct observations of ocean temperatures and air‐sea energy exchange underneath three typhoons and a tropical storm encountered in the Philippine Sea during the 2010 Pacific typhoon season are examined. Data are reported from two buoys 180 km apart with ocean temperatures recorded to 150 m and wind speeds up to 26 m s−1. A detailed examination of the cold wakes is used to determine the mechanisms though which the ocean cools. The result show that net cooling varied between storms by two orders of magnitude, accounting for between 9 and 1000 MJ m−2 of heat loss, and were a result of entrainment, advection, and surface fluxes. In some cases a marked temperature increase below the mixed layer occurred due to entrainment of warm water across the thermocline. Mixed layer temperature decreases ranged from 0.35 to 1.6°C and found to be well predicted by typhoon translation speed and wind speed. Of the mixed layer heat loss, 12–47% was attributed to enthalpy fluxes, the upper range of which is much greater than previous reports. Results are discussed in terms of their relevance to tropical cyclone and climate modeling.
Sources and compositional distribution of organic carbon in surface sediments from the lower Pearl River to the coastal South China Sea
Authors: Li Xinxin , Zhang Zhaoru , Wade Terry L. , Knap Anthony H. , Zhang Chuanlun L.
Published: August 2017

The Pearl River plays an important role in transporting terrestrial organic carbon (OC) to the South China Sea (SCS). However, the sources and compositional distribution of OC in the system are poorly understood. This study focused on delineating the sources and determining the fate of surface sedimentary OC from the Feilaixia Hydropower Station to the coastal SCS. Elemental, stable carbon/nitrogen isotope (δ13C and δ15N), and lignin‐phenol analyses have been conducted. The total OC (TOC) from the upstream sites were generally derived from vascular plants (higher C/N and and depleted δ13C) and soils. Additional input was attributed to riverine primary production (lower C/N and enriched δ13C), which was enhanced near the dam‐created reservoir. The C/N and δ13C values were not significantly different among sites in the midstream. The estuary/coastal sites witnessed hydrodynamically sorted riverine OC, which was diluted by marine primary production (lower C/N and more enriched δ13C). The lignin concentration was the highest in the upstream sites, remained relatively unchanged in the midstream sites, and decreased significantly along the estuary/coastal sites, which was corroborated by variation in TOC. A comprehensive five‐end‐member Monte Carlo simulation suggested that previous studies had underestimated the C4 plant input by 14 ± 11% and overestimated the riverbank soil input by 21 ± 17%. Thus, our study provided valuable information for more accurate source and mass balance studies of terrestrial OC transported to the SCS, which helped to further understand the carbon cycling in the large river‐ocean continuum.
Accuracy of Magnetic Resonance Imaging for Grading of Subglottic Stenosis in Patients With Granulomatosis With Polyangiitis: Correlation With Pulmonary Function Tests and Laryngoscopy
Authors: Henes Frank O. , Laudien Martin , Linsenhoff Laura , Bremer Jan P. , Oqueka Tim , Adam Gerhard , Schön Gerhard , Bannas Peter
Published: August 2017

Objective

To compare magnetic resonance imaging (MRI)–based and laryngoscopy‐based subglottic stenosis (SGS) grading with pulmonary function testing (PFT) in patients with granulomatosis with polyangiitis (GPA).

Methods

In this retrospective study, we included 118 examinations of 44 patients with GPA and suspected SGS. All patients underwent MRI, laryngoscopy, and PFT. Stenosis was graded on a 4‐point scale by endoscopy and MRI using the Meyer‐Cotton (MC) score (score 1: ≤50%, 2: 51–70%, 3: 71–99%, and 4: 100%) and as percentage by MRI. Results were compared with peak expiratory flow (PEF) and maximum inspiratory flow (MIF) from PFT, serving as objective functional reference.

Results

In MRI, 112 of 118 examinations (95%) were rated positive for SGS (grade 1 [n = 82], grade 2 [n = 26], and grade 3 [n = 4]), whereas in laryngoscopy 105 of 118 examinations (89%) were rated positive for SGS (grade 1 [n = 73], grade 2 [n = 24], and grade 3 [n = 8]). MRI and laryngoscopy agreed in 75 of 118 examinations (64%). MRI determined higher scores in 20 examinations (17%) and lower scores in 23 examinations (19%) compared to laryngoscopy. MC scores as determined by both MRI and laryngoscopy showed comparable correlations with PEF (r = −0.363, P = 0.016, and r = −0.376, P = 0.012, respectively) and MIF (r = −0.340, P = 0.024, and r = −0.320, P = 0.034, respectively). The highest correlation was found between MRI‐based stenosis grading in percentage with PEF (r = −0.441, P = 0.003) and MIF (r = −0.413, P = 0.005).

Conclusion

MRI and laryngoscopy provide comparable results for grading of SGS in GPA and correlate well with PFT. MRI is an attractive noninvasive and radiation‐free alternative for monitoring the severity of SGS in patients with GPA.
Impact of Comorbidities on Tumor Necrosis Factor Inhibitor Therapy in Psoriatic Arthritis: A Population‐Based Cohort Study
Authors: Ballegaard Christine , Højgaard Pil , Dreyer Lene , Cordtz René , Jørgensen Tanja Schjødt , Skougaard Marie , Tarp Simon , Kristensen Lars Erik
Published: August 2017

Objective

The objective of this population‐based cohort study was to investigate the impact of comorbidities on disease activity, treatment response, and persistence with the first‐tried tumor necrosis factor inhibitor (TNFi) in patients with psoriatic arthritis (PsA).

Methods

Data on patient characteristics, disease activity, and treatment response and persistence were obtained from the DANBIO registry. Information on comorbidities according to the Charlson Comorbidity Index (CCI) was obtained through linkage with the Danish National Patient Register. Kaplan‐Meier plots and Cox proportional hazard regression analyses were performed. Percentages of patients achieving relevant clinical responses were calculated.

Results

We identified 1,750 patients eligible for analyses. Patients with higher CCI scores had higher disease activity measures at baseline and increased occurrence of depression and/or anxiety. Kaplan‐Meier curves showed shorter persistence with treatment for patients with a CCI score ≥2 (log‐rank P < 0.001) and for patients with depression and/or anxiety (P = 0.027) compared to patients without comorbidities. In multivariate analysis, a CCI score ≥2 was associated with reduced TNFi persistence compared with patients without comorbidities (hazard ratio 1.72 [95% confidence interval 1.26–2.37]; P = 0.001). A smaller proportion of patients with a CCI score ≥2 achieved European League Against Rheumatism (EULAR) good response (P < 0.001) and EULAR good‐or‐moderate response (P < 0.001) at 6 months compared with patients without comorbidities.

Conclusion

The presence of comorbidities was associated with higher baseline disease activity, shorter TNFi persistence, and reduced clinical response rates in a cohort of Danish patients with PsA.
Atomic‐Scale CoOx Species in Metal–Organic Frameworks for Oxygen Evolution Reaction
Authors: Dou Shuo , Dong Chung‐Li , Hu Zhe , Huang Yu‐Cheng , Chen Jeng‐lung , Tao Li , Yan Dafeng , Chen Dawei , Shen Shaohua , Chou Shulei , Wang Shuangyin
Published: August 2017

The activity of electrocatalysts strongly depends on the number of active sites, which can be increased by downsizing electrocatalysts. Single‐atom catalysts have attracted special attention due to atomic‐scale active sites. However, it is a huge challenge to obtain atomic‐scale CoOx catalysts. The Co‐based metal–organic frameworks (MOFs) own atomically dispersed Co ions, which motivates to design a possible pathway to partially on‐site transform these Co ions to active atomic‐scale CoOx species, while reserving the highly porous features of MOFs. In this work, for the first time, the targeted on‐site formation of atomic‐scale CoOx species is realized in ZIF‐67 by O2 plasma. The abundant pores in ZIF‐67 provide channels for O2 plasma to activate the Co ions in MOFs to on‐site produce atomic‐scale CoOx species, which act as the active sites to catalyze the oxygen evolution reaction with an even better activity than RuO2.
High Performance Solid Polymer Electrolytes for Rechargeable Batteries: A Self‐Catalyzed Strategy toward Facile Synthesis
Authors: Cui Yanyan , Liang Xinmiao , Chai Jingchao , Cui Zili , Wang Qinglei , He Weisheng , Liu Xiaochen , Liu Zhihong , Cui Guanglei , Feng Jiwen
Published: August 2017

It is urgent to seek high performance solid polymer electrolytes (SPEs) via a facile chemistry and simple process. The lithium salts are composed of complex anions that are stabilized by a Lewis acid agent. This Lewis acid can initiate the ring opening polymerization. Herein, a self‐catalyzed strategy toward facile synthesis of crosslinked poly(ethylene glycol) diglycidyl ether‐based solid polymer electrolyte (C‐PEGDE) is presented. It is manifested that the poly(ethylene glycol) diglycidyl ether‐based solid polymer electrolyte possesses a superior electrochemical stability window up to 4.5 V versus Li/Li+ and considerable ionic conductivity of 8.9 × 10−5 S cm−1 at ambient temperature. Moreover, the LiFePO4/C‐PEGDE/Li batteries deliver stable charge/discharge profiles and considerable rate capability. It is demonstrated that this self‐catalyzed strategy can be a very effective approach for high performance solid polymer electrolytes.
Organic‐Free Synthesis of a Highly Siliceous Faujasite Zeolite with Spatially Biased Q4(nAl) Si Speciation
Authors: Oleksiak Matthew D. , Muraoka Koki , Hsieh Ming‐Feng , Conato Marlon T. , Shimojima Atsushi , Okubo Tatsuya , Chaikittisilp Watcharop , Rimer Jeffrey D.
Published: August 2017

We report the most siliceous FAU‐type zeolite, HOU‐3, prepared via a one‐step organic‐free synthesis route. Computational studies indicate that it is thermodynamically feasible to synthesize FAU with SAR=2–7, though kinetic factors seemingly impose a more restricted upper limit for HOU‐3 (SAR≈3). Our findings suggest that a slow rate of crystallization and/or low concentration of Na+ ions in HOU‐3 growth mixtures facilitate Si incorporation into the framework. Interestingly, Q4(nAl) Si speciation measured by solid‐state NMR can only be modeled with a few combinations of Al positioning at tetrahedral sites in the crystal unit cell, indicating the distribution of Si(‐O‐Si)4−n(‐O‐Al)n species is spatially biased as opposed to being random. Achieving higher SAR is desirable for improved zeolite (hydro)thermal stability and enhanced catalytic performance, which we demonstrate in benchmark tests that show HOU‐3 is superior to commercial zeolite Y.
Organic Nanocrystals with Bright Red Persistent Room‐Temperature Phosphorescence for Biological Applications
Authors: Fateminia S. M. Ali , Mao Zhu , Xu Shidang , Yang Zhiyong , Chi Zhenguo , Liu Bin
Published: August 2017

Persistent room‐temperature phosphorescence (RTP) in pure organic materials has attracted great attention because of their unique optical properties. The design of organic materials with bright red persistent RTP remains challenging. Herein, we report a new design strategy for realizing high brightness and long lifetime of red‐emissive RTP molecules, which is based on introducing an alkoxy spacer between the hybrid units in the molecule. The spacer offers easy Br−H bond formation during crystallization, which also facilitates intermolecular electron coupling to favor persistent RTP. As the majority of RTP compounds have to be confined in a rigid environment to quench nonradiative relaxation pathways for bright phosphorescence emission, nanocrystallization is used to not only rigidify the molecules but also offer the desirable size and water‐dispersity for biomedical applications.
Stereoselective Total Synthesis of Bisorbicillinoid Natural Products by Enzymatic Oxidative Dearomatization/Dimerization
Authors: Sib Anna , Gulder Tobias A. M.
Published: August 2017

Natural products are a virtually inexhaustible source of small molecules with spectacular molecular architectures and biomedical potential. Their structural complexity generates formidable challenges to total synthesis but often also precludes time‐ and resource‐efficient, stereoselective synthetic access. Biosynthetically, nature frequently uses dimerization and oligomerization reactions to produce highly challenging frameworks from simple starting materials. Impressive examples are the bisorbicillinoids, a family of fungal natural products thought to originate from the polyketide precursor sorbicillin. Utilizing the recombinant oxidoreductase SorbC from the sorbicillin biosynthetic gene cluster, a robust, fully stereoselective synthesis of bisorbicillinoid natural products and unnatural side‐chain analogues was developed.
On‐Surface Formation of Cumulene by Dehalogenative Homocoupling of Alkenyl gem‐Dibromides
Authors: Sun Qiang , Tran Bay V. , Cai Liangliang , Ma Honghong , Yu Xin , Yuan Chunxue , Stöhr Meike , Xu Wei
Published: August 2017

The on‐surface activation of carbon–halogen groups is an efficient route to produce radicals for constructing various hydrocarbons and carbon nanostructures. To date, the employed halide precursors have only one halogen attached to a carbon atom. It is thus of interest to study the effect of attaching more than one halogen atom to a carbon atom with the aim of producing multiple unpaired electrons. By introducing an alkenyl gem‐dibromide, cumulene products were fabricated on a Au(111) surface by dehalogenative homocoupling reactions. The reaction products and pathways were unambiguously characterized by a combination of high‐resolution scanning tunneling microscopy and non‐contact atomic force microscopy measurements together with density functional calculations. This study further supplements the database of on‐surface synthesis strategies and provides a facile manner for incorporation of more complicated carbon scaffolds into surface nanostructures.
Dithiocarbamate functionalized Al(OH)3‐polyacrylamide adsorbent for rapid and efficient removal of Cu(II) and Pb(II)
Authors: Liu Ya , Qian Peng , Yu Yang , Xiao Li , Wang Yongliang , Ye Shufeng , Chen Yunfa
Published: August 2017

Heavy metal ions such as Cu2+ and Pb2+ impose a significant risk to the environment and human health due to their high toxicity and non‐degradable characteristics. Herein, Al(OH)3‐polyacrylamide chemically modified with dithiocarbamates (Al‐PAM‐DTCs) was synthesized using formaldehyde, diethylenetriamine, carbon disulfide, and sodium hydroxide for rapid and efficient removal of Cu2+ and Pb2+. The synthesized adsorbent was characterized by Fourier transform infrared (FTIR) spectroscopy, thermogravimetric analysis, scanning electron microscopy–energy dispersive X‐ray spectroscopy analysis, and transmission electron microscope measurements. Al‐PAM‐DTCs showed rapid removal of Cu2+ (<30 min) and Pb2+ (<15 min) with high adsorption capacities of 416.959 mg/g and 892.505 mg/g for Cu2+ and Pb2+ respectively. Al‐PAM‐DTCs also had high capacities in removing suspended solids and metal ions simultaneously in turbid bauxite suspensions. FTIR, thermodynamic study, and elemental mapping were used to determine the adsorption mechanism. The rapid, convenient, and effective adsorption of Cu2+ and Pb2+ indicated that Al‐PAM‐DTCs has great potential for practical applications in purification of other heavy metal ions from aquatic systems. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134, 45431.
Holistic Information Integration in Child Decision Making
Authors: Lindow Stefanie , Lang Anna , Betsch Tilmann
Published: August 2017

Weighted‐additive (WADD) strategies require decision makers to integrate multiple values weighted by their relevance. From what age can children make choices in line with such a WADD‐strategy? We compare multi‐attribute decisions of children (6–7; 8–10; 11–12‐year‐olds) with adults in an open information‐board environment without pre‐decisional information search. In two experiments, we classify decision strategies based on individual choice patterns and find that in all age groups the majority of participants are users of a WADD‐strategy. Simple decision heuristics such as lexicographic strategies were applied rarely by children and not at all by adults. In two additional follow‐up studies, we further investigate the underlying process of WADD‐application by analysing decision latencies in combination with a retrospective think‐aloud study. Results suggest that children did not apply WADD‐strategies in a deliberate fashion in our experiments. Overall, our findings demonstrate that the ability to make good and quick decisions by holistically integrating information is already present in young children. Copyright © 2017 John Wiley & Sons, Ltd.
Dual, Site‐Specific Modification of Antibodies by Using Solid‐Phase Immobilized Microbial Transglutaminase
Authors: Spycher Philipp R. , Amann Christian A. , Wehrmüller Jöri E. , Hurwitz David R. , Kreis Olivier , Messmer Daniel , Ritler Andreas , Küchler Andreas , Blanc Alain , Béhé Martin , Walde Peter , Schibli Roger
Published: August 2017

Microbial transglutaminase (MTG) was stably solid‐phase immobilized on glass microbeads by using a second‐generation dendronized polymer. Immobilized MTG enabled the efficient generation of site‐specifically conjugated proteins, including antibody fragments, as well as whole antibodies through distinct glutamines and, unprecedentedly, also through lysines with various bifunctional substrates with defined stoichiometries. With this method, we generated dual, site‐specifically modified antibodies comprising a fluorescent probe and a metal chelator for radiolabeling—a strategy anticipated to design antibodies for imaging and simultaneous therapy. Furthermore, we provide evidence that immobilized MTG features higher siteselectivity than soluble MTG.
Synthetic Arabinomannan Heptasaccharide Glycolipids Inhibit Biofilm Growth and Augment Isoniazid Effects in Mycobacterium smegmatis
Authors: Maiti Krishnagopal , Syal Kirtimaan , Chatterji Dipankar , Jayaraman Narayanaswamy
Published: August 2017

Biofilm formation, involving attachment to an adherent surface, is a critical survival strategy of mycobacterial colonies in hostile environmental conditions. Here we report the synthesis of heptasaccharide glycolipids based on mannopyranoside units anchored on to a branched arabinofuranoside core. Two types of glycolipids—2,3‐branched and 2,5‐branched—were synthesized and evaluated for their efficacies in inhibiting biofilm growth by the non‐pathogenic mycobacterium variant Mycobacterium smegmatis. Biofilm formation was inhibited at a minimum biofilm growth inhibition concentration (MBIC) of 100 μg mL−1 in the case of the 2,5‐branched heptasaccharide glycolipid. Further, we were able to ascertain that a combination of the drug isoniazid with the branched heptasaccharide glycolipid (50 μg mL−1) potentiates the drug, making it three times more effective, with an improved MBIC of 30 μg mL−1. These studies establish that synthetic glycolipids not only act as inhibitors of biofilm growth, but also provide a synergistic effect when combined with significantly lowered concentrations of isoniazid to disrupt the biofilm structures of the mycobacteria.
Selecting Chiral BINOL‐Derived Phosphoric Acid Catalysts: General Model To Identify Steric Features Essential for Enantioselectivity
Authors: Reid Jolene P. , Goodman Jonathan M.
Published: August 2017

Choosing the optimal catalyst for a new transformation is challenging because the ideal molecular requirements of the catalyst for one reaction do not always simply translate to another. Large groups at the 3,3′ positions of the binaphthol rings are important for efficient stereoinduction but if they are too large this can lead to unusual or poor results. By applying a quantitative steric assessment of the substituents at the 3,3′ positions of the binaphthol ring, we have systematically studied the effect of modulating this group on enantioselectivity for a wide range of reactions involving imines, and verified this analysis using ONIOM calculations. We have shown that in most reactions, the stereochemical outcome depends on both proximal and remote sterics. Summarising detailed calculations into a simple qualitative model identifies and explains the steric features required for high selectivity. This model is consistent with seventy seven papers reporting reactions (over 1000 transformations in total), and provides a straightforward decision tree for selecting the best catalyst.
Optical Detection of Photorelease Kinetics on Gold and Glass Surfaces using Streptavidin‐Coupled Biotinylated Photolabile Protecting Groups for Nucleosides
Authors: Drexler Katja , Smirnova Julia , Galetskaya Marina , Schweizer Nina , Gauglitz Günter. , Steiner Ulrich E.
Published: August 2017

Five biotinylated photolabile compounds of the general structure Bt‐L1‐NPPOC‐X‐L2 were synthesized, in which Bt represents a biotin unit, L1 is a 3,6‐dioxa‐n‐octane or an n‐hexane spacer, NPPOC is the photolabile protecting group 2‐(2‐nitrophenyl)propoxycarbonyl, and X is a thymidine unit as a representative nucleoside or a direct linkage to L2, an ω‐mercapto‐ or ω‐aminohexoyl linker, for coupling to a substrate surface. These compounds served for testing the photocleavage kinetics in self‐assembled monolayers on gold or glass by using surface plasmon resonance (SPR) on gold or reflectometric interference spectroscopy (RIfS) on glass, whereby the biotin moiety offered the possibility to increase the bulkiness of the leaving group by binding to streptavidin, which thereby largely enhanced the SPR or RIfS signals. The photokinetics, found to consist in a dominating fast stage and a less contributing slow stage, were quantitatively analyzed, and the quantum yield of the fast part reached values up to almost 1 in favorable cases. A direct comparison of the results from SPR and RIfS yielded almost identical results. The present investigations pave the way to in situ monitoring of the photolithographic synthesis of DNA chips.
Beyond Ryff's scale: Comprehensive measures of eudaimonic well‐being in clinical populations. A systematic review
Authors: Brandel Martina , Vescovelli Francesca , Ruini Chiara
Published: August 2017

Eudaimonic well‐being that protects mental and physical health has received increasing attention. This investigation aimed to review which comprehensive instruments for measuring eudaimonic well‐being were applied with clinical populations (reporting mental or physical illnesses), beyond Ryff's Psychological Well‐Being Scale.

Articles citing at least 1 of the measures of eudaimonic well‐being identified by previous theoretical work were extracted from medical and psychological electronic databases and screened. Only investigations involving clinical populations were included and reviewed.

An initial screening identified 5,065 articles using eudaimonic well‐being measures, out of which only 28 articles encompassed clinical populations and could be included. Sixteen involved patients with mental disorders and 12 populations with medical conditions. In these articles, only 4 measures of eudaimonic well‐being were used (Mental Health Continuum, Flourishing Scale, General Causality Orientations Scale, and Orientations to Happiness Subscales), out of the 12 currently available in literature. The Mental Health Continuum was the most used instrument, particularly in adults with depression, whose levels of eudaimonic well‐being are impaired, but may be improved by specific interventions. Autonomy appeared to influence patients' motivation to treatment, both in mental and physical disorders.

The need for a larger consensus regarding specific measures of eudaimonic well‐being for clinical populations emerged. The importance of including assessment of positive functioning as an indicator of recovery in clinical domains is discussed.
Combining Cytotoxicity Assessment and Xenopus laevis Phenotypic Abnormality Assay as a Predictor of Nanomaterial Safety
Authors: Al‐Yousuf Karamallah , Webster Carl A. , Wheeler Grant N. , Bombelli Francesca Baldelli , Sherwood Victoria
Published: August 2017

The African clawed frog, Xenopus laevis, has been used as an efficient pre‐clinical screening tool to predict drug safety during the early stages of the drug discovery process. X. laevis is a relatively inexpensive model that can be used in whole organism high‐throughput assays whilst maintaining a high degree of homology to the higher vertebrate models often used in scientific research. Despite an ever‐increasing volume of biomedical nanoparticles (NPs) in development, their unique physico‐chemical properties challenge the use of standard toxicology assays. Here, we present a protocol that directly compares the sensitivity of X. laevis development as a tool to assess potential NP toxicity by observation of embryo phenotypic abnormalities/lethality after NP exposure, to in vitro cytotoxicity obtained using mammalian cell lines. In combination with conventional cytotoxicity assays, the X. laevis phenotypic assay provides accurate data to efficiently assess the safety of novel biomedical NPs. © 2017 by John Wiley & Sons, Inc.
Intracellular Cytokine Detection by Flow Cytometry in Surface Marker‐Defined Human Peripheral Blood Mononuclear T Cells
Authors: Lauer Fredine T. , Denson Jesse L. , Beswick Ellen , Burchiel Scott W.
Published: August 2017

In a recent unit in this series, protocols for the isolation, cryopreservation, thawing, and immunophenotyping of HPBMC isolated from peripheral whole blood using cell surface marker (CSM) staining and multi‐color flow cytometry analysis were presented. The current procedure describes the detection and quantification of CSM and intracellular markers (ICM), including transcription factors and cytokines, following activation and differentiation of CD4+ T‐cells using multi‐color flow cytometry. Results indicated that repeatable and robust detection of ICM could be obtained in surface marker‐defined T cells that identify functional subsets of cells. There were no observed differences between fresh and cryopreserved HPBMC in eight phenotypes analyzed (T‐CD3, Th‐CD4, Tmem‐CD45RO, activated T‐CD3/CD25, Treg‐ Foxp3/CD25, Th1‐IFNγ, Th2‐ IL‐4, Th17‐IL‐17A). There was an observed difference in activated T‐ CD3/CD69 in the short term (30‐90 days) cryopreserved samples as compared to the freshly isolated samples, which may have resulted from the variance in controls or small sample size. © 2017 by John Wiley & Sons, Inc.
Use of Human Pluripotent Stem Cell Derived‐Cardiomyocytes to Study Drug‐Induced Cardiotoxicity
Authors: Maillet Agnes , Tan Kim Peng , Brunham Liam R.
Published: August 2017

Drug‐induced cardiotoxicity is the one of the most common causes of drug withdrawal from market. A major barrier in managing the risk of drug‐induced cardiotoxicity has been the lack of relevant models to study cardiac safety. Human pluripotent stem cell‐derived cardiomyocytes (hPSC‐CMs) have great potential in drug discovery and cardiotoxcity screens as they display many characteristics of the human myocardium and offer unlimited supply. This unit describes how to use pluripotent stem cells derived cardiomyocytes to study drug‐induced cardiotoxicty using doxorubicin as an example. We present a workflow that explains procedure for editing hPSC using the CRISPR/Cas9 system and for differentiation of hPSC into cardiomyocytes. We also report protocols to study drug effect on ROS production, intracellular calcium concentration, formation of DNA double strand breaks, gene expression and electrophysiological properties of hPSC‐CMs. © 2017 by John Wiley & Sons, Inc.
Evaluating Dihydroazulene/Vinylheptafulvene Photoswitches for Solar Energy Storage Applications
Authors: Wang Zhihang , Udmark Jonas , Börjesson Karl , Rodrigues Rita , Roffey Anna , Abrahamsson Maria , Nielsen Mogens Brøndsted , Moth‐Poulsen Kasper
Published: August 2017

Invited for this month′s cover are the groups of Kasper Moth‐Poulsen at Chalmers University of Technology and Mogens Brøndsted Nielsen at University of Copenhagen. The cover image shows a conceptual graphic of molecular solar thermal energy storage system (MOST) for outdoor facilities. The Full Paper itself is available at 10.1002/cssc.201700679.
Case of chondroid syringoma mimicking a nodular hidradenoma: A diagnostic pitfall on cytopathology
Authors: Shalini Bahadur , Akshi Katyal , Namrata Nargotra , Shilpi Soni , Manupriya Nain
Published: August 2017

Limited literature is available on the use of fine needle aspiration (FNA) for skin tumors. Awareness of cytological features of these lesions is important to prevent misdiagnosis. A 45‐year‐old male, presented with slowly growing swelling over the thigh since 4 years. FNA from multiple sites yielded highly cellular smears with a dual cell population consisting of cells with small round nucleus scanty cytoplasm and polygonal cells with moderate to abundant cytoplasm. Extracellular basement membrane like material was also noted. A diagnosis of benign adnexal neoplasm, suggestive of nodular hidradenoma was made. Paraffin sections showed an encapsulated dermal tumor composed of ductal and myoepithelial cells in ducts, sheets, strands with chondromyxoid stroma. A final diagnosis of chondroid syringoma was given following evaluation of histopathology slides and Immunohistochemistry. FNA interpretation of skin tumors can be challenging since literature is limited. The placement of tumors into benign or malignant category is realistic and can direct management guidelines. Greater awareness of these lesions and following stringent diagnostic criteria can help in establishing a more accurate diagnosis.
Metformin Protects against Experimental Acrylamide Neuropathy in Rats
Authors: Oda Samah S.
Published: August 2017

Preclinical Research

To investigate the potential neuroprotective effects of metformin against experimental acrylamide neuropathy in rats, 24 rats were distributed into four equal groups (6 each). Group 1 was kept as a control. Group 2 (MET) was orally given metformin (200 mg/kg BW/day). Group 3 (ACR) was injected IP with acrylamide (50 mg/kg BW/day). Animals in group 4 (ACR + MET) were administered both MET and ACR at the same dose and route used in groups 2 and 3. Treatments were administered three times a week for three weeks. ACR induced an increase in lipid peroxidation in brain and spinal cord. This was associated with down regulation of bcl2 and up regulation of caspase3 in cerebrum, cerebellum, spinal cord, and sciatic nerve in the ACR‐treated group. ACR‐treated rats revealed neuronal degeneration and glial cell reaction in brain and spinal cord with axonal degeneration and myelin sheath irregularities in sciatic nerve. MET restored lipid peroxidation in brain and spinal cord, decreased caspase3 activity and up regulated bcl2 expression in cerebrum and sciatic nerve. Histopathological findings in ACR + MET group were lesser severe than those established in ACR‐group indicating that MET ameliorates the neuropathic effects of ACR in rats. Drug Dev Res 78 : 349‐359, 2017. © 2017 Wiley Periodicals, Inc.
IgG subclass and vaccination stimulus determine changes in antigen specific antibody glycosylation in mice
Authors: Kao Daniela , Lux Anja , Schaffert Anja , Lang Roland , Altmann Friedrich , Nimmerjahn Falk
Published: August 2017

Immunoglobulin G (IgG) glycosylation can modulate antibody effector functions. Depending on the precise composition of the sugar moiety attached to individual IgG glycovariants either pro‐ or anti‐inflammatory effector pathways can be initiated via differential binding to type I or type II Fc‐receptors. However, an in depth understanding of how individual IgG subclasses are glycosylated during the steady state and how their glycosylation pattern changes during vaccination is missing. To monitor IgG subclass glycosylation during the steady state and upon vaccination of mice with different T‐cell dependent and independent antigens, tryptic digests of serum, and antigen‐specific IgG preparations were analyzed by reversed phase‐liquid chromatography‐mass spectrometry. We show that there is a remarkable difference with respect to how individual IgG subclasses are glycosylated during the steady state. More importantly, upon T‐cell dependent and independent vaccinations, individual antigen‐specific IgG subclasses reacted differently with respect to changes in individual glycoforms, suggesting that the IgG subclass itself is a major determinant of restricting or allowing alterations in specific IgG glycovariants.
Competency‐based IT personnel selection using a hybrid SWARA and ARAS‐G methodology
Authors: Heidary Dahooie Jalil , Beheshti Jazan Abadi Elham , Vanaki Amir Salar , Firoozfar Hamid Reza
Published: August 2017

In the knowledge economy, human capital is a key factor in any organization to achieve a sustainable competitive advantage. Thus, selection of competent personnel is the most important function of human resource managers. However, because of a wide range of criteria and organizational factors that affect the process, personnel selection is often regarded as a complex problem that can be answered through multicriteria decision‐making (MCDM) procedures. Despite the great importance of determining a comprehensive set of criteria, it has not gained enough attention in the literature. This study presents a competency framework with five criteria for choosing the best information technology (IT) expert from five alternatives. The stepwise weight assessment ratio analysis (SWARA) and grey additive ratio assessment (ARAS‐G) methods are also used to derive the criteria weights and provide the final alternative, respectively. The results reveal that subject competency is the major criteria in IT personnel selection.
Coadministration of a tumor‐penetrating peptide improves the therapeutic efficacy of paclitaxel in a novel air‐grown lung cancer 3D spheroid model
Authors: Gupta Sweta K. , Torrico Guzmán Elisa A. , Meenach Samantha A.
Published: August 2017

Three‐dimensional (3 D) cell culture platforms are increasingly being used in cancer research and drug development since they mimic avascular tumors in vitro. In this study, we focused on the development of a novel air‐grown multicellular spheroid (MCS) model to mimic in vivo tumors for understanding lung cancer biology and improvement in the evaluation of aerosol anticancer therapeutics. 3 D MCS were formed using A549 lung adenocarcinoma cells, comprising cellular heterogeneity with respect to different proliferative and metabolic gradients. The growth kinetics, morphology and 3 D structure of air‐grown MCS were characterized by brightfield, fluorescent and scanning electron microscopy. MCS demonstrated a significant decrease in growth when the tumor‐penetrating peptide iRGD and paclitaxel (PTX) were coadministered as compared with PTX alone. It was also found that when treated with both iRGD and PTX, A549 MCS exhibited an increase in apoptosis and decrease in clonogenic survival capacity in contrast to PTX treatment alone. This study demonstrated that coadministration of iRGD resulted in the improvement of the tumor penetration ability of PTX in an in vitro A549 3 D MCS model. In addition, this is the first time a high‐throughput air‐grown lung cancer tumor spheroid model has been developed and evaluated.
Immune Suppressive and Bone Inhibitory Effects of Prednisolone in Growing and Regenerating Zebrafish Tissues
Authors: Geurtzen Karina , Vernet Aude , Freidin Andrew , Rauner Martina , Hofbauer Lorenz C , Schneider Jürgen E , Brand Michael , Knopf Franziska
Published: August 2017

Glucocorticoids are widely used as therapeutic agents to treat immune-mediated diseases in humans because of their anti-inflammatory and immunosuppressive effects. However, glucocorticoids have various adverse effects, in particular rapid and pronounced bone loss associated with fractures in glucocorticoid-induced osteoporosis, a common form of secondary osteoporosis. In zebrafish, which are increasingly used to study processes of bone regeneration and disease, glucocorticoids show detrimental effects on bone tissue; however, the underlying cellular mechanisms are incompletely understood. Here, we show that treatment with the glucocorticoid prednisolone impacts on the number, activity and differentiation of osteoblasts, osteoclasts, and immune cells during ontogenetic growth, homeostasis, and regeneration of zebrafish bone. Macrophage numbers are reduced in both larval and adult tissues, correlating with decreased generation of myelomonocytes and enhanced apoptosis of these cells. In contrast, osteoblasts fail to proliferate, show decreased activity, and undergo incomplete differentiation. In addition, prednisolone treatment mitigates the number and recruitment of osteoclasts to sites of bone regeneration in adult fish. In combination, these effects delay bone growth and impair bone regeneration. Our study demonstrates the many-faceted effects of glucocorticoids in non-mammalian vertebrates and helps to further establish the zebrafish as a model to study glucocorticoid-induced osteoporosis. © 2017 American Society for Bone and Mineral Research.
A20 restores phorbol ester‐induced differentiation of THP‐1 cells in the absence of nuclear factor‐κB activation
Authors: Osako Miho , Itsumi Momoe , Yamaguchi Haruka , Takeuchi Hiroaki , Yamaoka Shoji
Published: August 2017

A20, also referred to as tumor necrosis factor alpha (TNFα)‐induced protein 3 (TNFAIP3), is an ubiquitin‐editing enzyme whose expression is enhanced by NF‐κB activation, and plays an important role in silencing NF‐κB activity. Another well‐known role for A20 is to protect cells from TNFα‐induced apoptosis. Depletion of NF‐κB in differentiating U937 monocytic leukemia cells is known to cause apoptotic cell death; however, much remains to be explored about the molecules that are expressed in an NF‐κB‐dependent manner and which support monocyte‐macrophage differentiation. Using the monocytic cell line THP‐1, and peripheral blood monocytes, we show here a sustained increase in A20 expression during monocyte‐macrophage differentiation, which coincided with high NF‐κB‐dependent transcriptional activity. Depletion of NF‐κB by stable expression of a super‐repressor form of IκBα in THP‐1 cells caused remarkable cell death during phorbol 12‐myristate 13‐acetate (PMA)‐induced differentiation. A20 expression in these cells did not alter this NF‐κB suppression, but was sufficient to protect the cells and restore the cell surface expression of a differentiation marker (CD11b) and phagocytic activity. Mutational analyses revealed that this A20 activity requires the carboxy‐terminal zinc‐finger domain, but not its deubiquitinase activity. Based on these findings, we conclude that A20, when ectopically expressed, can support both survival and differentiation of THP‐1 cells in the absence of sustained NF‐κB activity.
Atorvastatin ameliorates LPS‐induced inflammatory response by autophagy via AKT/mTOR signaling pathway
Authors: Han Fei , Xiao Qing‐Qing , Peng Shi , Che Xin‐Yu , Jiang Li‐Sheng , Shao Qin , He Ben
Published: August 2017

Macrophages play crucial roles in immune response and atherosclerosis‐related cardiovascular disease. Recent evidence of macrophage autophagy has demonstrated a novel pathway through which contributes to vascular inflammation. The aim of this study was to elucidate the role of autophagy in the inhibition of inflammatory response in macrophages by atorvastatin. We found that atorvastatin promoted autophagy flow determined by up‐regulating the expression of autophagy‐related protein microtubule‐associated protein light chain (LC3B), inducing the formation of autophagosomes and down‐regulating the expression of SQSTM1/P62, which is consumed during autophagy. Atorvastatin also inhibited the expression of inflammatory factors IL‐1β and TNFα induced by LPS in RAW264.7 cells. Furthermore, pretreatment with an autophagy inhibitor 3MA or LY294002 attenuated the suppressive effect of atorvastatin on LPS‐induced IL‐1β and TNFα expression. Additionally, knockdown autophagy‐related gene 5(Atg5) with a special siRNA also prevented the role of atorvastatin in decreasing IL‐1β and TNFα release induced by LPS. Finally, we detected that AKT/mTOR/P70S6K signaling pathway was involved in atorvastatin‐induced autophagy in macrophages. These data suggest that atorvastatin attenuates LPS‐induced inflammatory factors secretion, at least in part, through enhancing autophagy by AKT/mTOR signaling pathway. Our findings provide a novel evidence that statins exert anti‐inflammatory effect in atherosclerosis by autophagy activation.
A study on the biological reference interval of urinary alpha 1‐microglobulin in a group of Chinese people
Authors: Zhang Qian , Jiang Xu , Cui Xiao‐Fan , Liu Rui
Published: August 2017

Objective

The aim of this study was to explore the possible influences of age and gender on urinary Alpha 1‐Microglobulin (α1‐MG) concentrations and establish specific reference values of urinary α1‐MG in a group of healthy adults.

Methods

Two hundred and ninety‐nine adults (141 males and 158 females) aged 20‐60 were selected and grouped by gender and age. Urinary levels of α1‐MG were detected in morning spot‐urine samples, and statistical analysis was performed to explore the association between urinary α1‐MG and clinical parameters, and the differences between groups were compared. The 95th percentile of distribution was used as the normal upper limit.

Results

The value of urinary α1‐MG was sex‐dependent (P<0.001), the 95th percentile of urinary α1‐MG of males was 26.4 mg/L, whereas females was 8.6 mg/L. Whereas urinary α1‐microglobulin‐to‐creatinine ratio (α1‐MG/Cr) was both gender‐and age‐dependent (both P<0.001), and age 30 may be the cut‐off point in this study. The 95th percentile of males and females aged 20‐30 was 16.9 mg/g, of males aged 31‐60 was 19.8 mg/g, of females aged 31‐60 was 28.5 mg/g.

Discussions

The relationship between urinary α1‐MG concentrations and gender, age is different from previous studies. It is recommended that hospitals and laboratories should develop their own α1‐MG reference intervals based on their experimental conditions.