bluuebunny/crossref_metadata_2025 huggingface dataset:
Native Chemical Ligation Directed by Photocleavable Peptide Nucleic Acid (PNA) Templates
Authors: Middel Stephen , Panse Cornelia H. , Nawratil Swantje , Diederichsen Ulf
Published: October 2017

A novel peptide–peptide ligation strategy is introduced that has the potential to provide peptide libraries of linearly or branched coupled fragments and will be suited to introduce simultaneous protein modifications at different ligation sites. Ligation is assisted by templating peptide nucleic acid (PNA) strands, and therefore, ligation specificity is solely encoded by the PNA sequence. PNA templating, in general, allows for various kinds of covalent ligation reactions. As a proof of principle, a native chemical ligation strategy was elaborated. This PNA‐templated ligation includes easy on‐resin procedures to couple linkers and PNA to the respective peptides, and a traceless photocleavage of the linker/PNA oligomer after the ligation step. A 4,5‐dimethoxy‐2‐nitrobenzaldehyde‐based linker that allowed the photocleavable linkage of two bio‐oligomers was developed.
CRISPR‐Cas9 mediated gene knockout in human coronary artery endothelial cells reveals a pro‐inflammatory role of TLR2
Authors: Wang Yingge , Chen Lu , Tian Zheng , Shen Xueyi , Wang Xiaohong , Wu Honghai , Wang Yayi , Zou Jiayu , Liang Jingyan
Published: October 2017

Endothelial inflammatory responses promote the development and progression of atherosclerosis. It was reported that Toll‐like receptors 2 (TLR2) is associated with endothelial inflammation. However, the effect of TLR2 on inflammatory responses in human coronary artery endothelial cells (HCAECs) remains largely unknown. Here, we tested the hypothesis that TLR2 can enhance inflammatory reactions in HCAECs after stimulated by TLR2 agonist. First, we used CRISPR‐Cas9 technology to knockout TLR2 gene in HCAECs. Then, TLR2‐KO and wild type HCAECs were treated with TLR2 agonist peptidoglycan (PGN). The expression levels of intercellular cell adhesion molecule‐1 (ICAM‐1), interleukin‐6 (IL‐6), and interleukin‐8 (IL‐8) were analyzed by real‐time PCR, Western blot, and ELISA. The expression status of myeloid differentiation primary response gene 88 (MyD88), phosphorylated IRAK‐1 (pIRAK‐1) and phosphorylated NF‐κB (pNF‐κB) were detected by Western blot. Our results show that after treated with TLR2 agonist, the expression levels of ICAM‐1, IL‐6, and IL‐8 were downregulated in TLR2‐KO cells compared to those of wild type cells. Further, Western blots of MyD88, pIRAK‐1, and pNF‐κB show that the expression levels of these pro‐inflammatory molecules were much lower in TLR2‐KO cells compared to that of wild type cells by stimulating with TLR2 agonist. We suggest that TLR2 may affect inflammatory reaction in HCAECs by introducing pro‐inflammatory molecules like MyD88, pIRAK‐1, and pNF‐κB.
Brain biopsy in the diagnosis of leptomeningeal involvement in stage I chronic lymphocytic leukemia
Authors: Cervilla Muñoz Eva , Demelo Rodríguez Pablo , García García Alejandra , Menarguez Palanca Javier , del Toro Cervera Jorge
Published: October 2017

Key Clinical Message

Leptomeningeal involvement of CLL is usually underdiagnosed as neurological symptoms are unspecific. It is important to carefully evaluate neurological status in these patients and consider this entity between the differential diagnosis of a neurological deterioration as adequate treatment improves the prognosis. Imaging techniques, analyses of cerebrospinal fluid, and brain biopsy are useful to establish a definitive diagnosis.
Molecular Viscosity Sensors with Two Rotators for Optimizing the Fluorescence Intensity–Contrast Trade‐Off
Authors: Lee Seung‐Chul , Lee Chang‐Lyoul , Heo Jeongyun , Jeong Chan‐Uk , Lee Gyeong‐Hui , Kim Sehoon , Yoon Woojin , Yun Hoseop , Park Sung O. , Kwak Sang Kyu , Park Sung‐Ha , Kwon O‐Pil
Published: October 2017

A series of fluorescent molecular rotors obtained by introducing two rotational groups (“rotators”), which exhibit different rotational and electron‐donating abilities, are discussed. Whereas the control molecular rotor, PH, includes a single rotator (the widely used phenyl group), the PO molecular rotors consist of two rotators (a phenyl group and an alkoxy group), which exhibit simultaneous strongly electron‐donating and easy rotational abilities. Compared with the control rotor PH, PO molecular rotors exhibited one order of magnitude higher quantum yield (fluorescence intensity) and simultaneously exhibited significantly higher fluorescence contrast. These properties are directly related to the strong electron‐donating ability and low energy barrier of rotation of the alkoxy group, as confirmed by dynamic fluorescence experiments and quantum chemical calculations. The PO molecular rotors exhibited two fluorescence relaxation pathways, whereas the PH molecular rotor exhibited a single fluorescence relaxation pathway. Cellular fluorescence imaging with PO molecular rotors for mapping cellular viscosity was successfully demonstrated.
The effective promotion of trace amount of Cu on Ce/WO3‐ZrO2‐TiO2 monolithic catalyst for the low‐temperature NH3‐SCR of NOx
Authors: Li Yuanshan , Xu Haidi , Feng Xi , Liu Shuang , Chen Yaoqiang
Published: October 2017

The selective catalytic reduction of NOx with NH3 (NH3‐SCR) activity of 0.10 g/g CeO2/WO3‐ZrO2‐TiO2 (Ce/WZT) in low temperature range was greatly enhanced by the addition of 0.00010 g/g Cu (Cu/Ce mass ratio = 1:1000). The temperature of complete NOx conversion (T90) decreased as much as 36  °C (from 263  °C to 227  °C) under a gas hourly space velocity (GHSV) of 30 000 h−1. XPS, NH3/O2‐TPD, H2‐TPR, XRD, and FTIR characterizations revealed that the interaction between Cu and Ce, more active oxygen species, stronger NH3 and NO oxidation ability, better redox ability, together with the abundant Brønsted acid sites contributed to better catalytic activity of 0.00010 g/g Cu‐0.10 g/g Ce/WO3‐ZrO2‐TiO2 (CC/WZT) catalyst at low temperatures.
Extraction of carotenoids from Xanthophyllomyces dendrorhous using ultrasound‐assisted and chemical cell disruption methods
Authors: Urnau Letícia , Colet Rosicler , Soares Viviane Faria , Franceschi Elton , Valduga Eunice , Steffens Clarice
Published: October 2017

Carotenoids are natural pigments that can be synthesized by plants, algae, and microorganisms. Carotenoids are found intracellularly when bio‐produced by microorganisms. Thus, the cell wall rigidity makes pigment extraction difficult at times, so the application of various cell rupture and extraction techniques is made necessary. Therefore, this study aimed to perform Xanthophyllomyces dendrorhous Y‐10921 cell rupture using dimethyl sulphoxide (DMSO) and Ultrasound‐Assisted methods in order to recover carotenoids. The maximum recovery of specific carotenoids using the DMSO method was 680 μg/g associated with acetone extraction and 614 μg/g with the Ultrasound‐Assisted method (acetone:methanol, 7:3 v/v ratio). The results demonstrate that the Ultrasound‐Assisted method did not require a long extraction time, it had an easy biocompounds recovery, and furthermore, it was effective on yeast cell disruption.
Microwave‐Pyrolysis‐Assisted Preparation of Magnetic Iron‐Titanium Mixed Oxide Catalyst for Selective Catalytic Reduction of NOx with NH3
Authors: Zhou Fei , Xiong Z.‐b. , Lu Wei , Jin Jing , Ding X.‐c.
Published: October 2017

A kind of magnetic iron‐titanium oxide catalyst for selective catalytic reduction (SCR) of NOx with NH3 is obtained by the microwave‐pyrolysis co‐precipitation method. This catalyst is characterized in detail by various techniques such as X‐ray diffraction, N2 adsorption–desorption, X‐ray photoelectron spectroscopy, temperature‐programmed reduction of H2, and temperature‐programmed desorption of NH3/NO to investigate the influence of titanium oxide addition on the NH3‐SCR activity of magnetic iron oxide. Furthermore, the NH3‐SCR reaction mechanism over magnetic iron‐titanium oxide is also revealed. The NH3‐SCR activity over magnetic iron oxide is enhanced by the addition of titanium oxide, especially the low‐temperature activity. The addition of titanium oxide depresses the oxidization of γ‐Fe2O3 to α‐Fe2O3 in the precursor obtained through microwave‐pyrolysis co‐precipitation during the aging process, and also reduces the absorption ability of SO42− to the precursor. The crystallite of iron oxide in magnetic Fe1‐xTixOz‐500 (x = 0.25, 0.5, and 0.75) catalysts is mainly γ‐Fe2O3. Among these magnetic catalysts, magnetic Fe0.75Ti0.25Oz‐500 has two distinctive peaks in the pore size distribution curve and more active iron‐based sites on its surface for NH3‐SCR reaction. This catalyst shows the highest NH3‐SCR activity. The NH3‐SCR reaction over magnetic Fe0.75Ti0.25Oz‐500 at low‐temperature obeys both the Eley–Rideal mechanism and the Langmuir–Hinshelwood mechanism.
Estimation of cresyl and xylyl contents in phosphate esters‐based fire resistance hydraulic fluids by nuclear magnetic resonance spectroscopy
Authors: Kumar Ravindra , Mondal Sujit , Bansal Veena , Pandey Jai Narayan , Christopher Jayaraj , Kapur Gurpreet Singh , Saxena Deepak
Published: October 2017

In this work, a new analytical approach based on proton nuclear magnetic resonance spectroscopy has been optimized for the direct estimation of different phenolic components in a phosphate ester sample. In high resonance proton nuclear magnetic resonance spectrum of fire resistance hydraulic fluids, methyl protons of cresyl, xylyl, and other phosphates (ethyl, propyl, and butyl) are unambiguously distinguished by their different chemical shift and used for quantitative estimation. The developed methodology was validated by analyzing different synthetic blends prepared in lab and few fully formulated fire resistance hydraulic fluids. The methodology is fast, nondestructive, and useful for development of new products and troubleshooting.
The Distant Double Bond Determines the Fate of the Carboxylic Group in the Dissociative Photoionization of Oleic Acid
Authors: Heringa Maarten F. , Slowik Jay G. , Goldmann Maximilian , Signorell Ruth , Hemberger Patrick , Bodi Andras
Published: October 2017

The valence threshold photoionization of oleic acid has been studied using synchrotron VUV radiation and imaging photoelectron photoion coincidence (iPEPICO) spectroscopy. An oleic acid aerosol beam was impacted on a copper thermodesorber, heated to 130 °C, to evaporate the particles quantitatively. Upon threshold photoionization, oleic acid produces the intact parent ion first, followed by dehydration at higher energies. Starting at ca. 10 eV, a large number of fragment ions slowly rise suggesting several fragmentation coordinates with quasi‐degenerate activation energies. However, water loss is the dominant low‐energy dissociation channel, and it is shown to be closely related to the unsaturated carbon chain. In the lowest‐barrier process, one of the four allylic hydrogen atoms is transferred to the carboxyl group to form the leaving water molecule and a cyclic ketone fragment ion. A statistical model to analyze the breakdown diagram and measured rate constants yields a 0 K appearance energy of 9.77 eV, which can be compared with the density functional theory result of 9.19 eV. Alternative H‐transfer steps yielding a terminal C=O group are ruled out based on energetics and kinetics arguments. Some of the previous photoionization mass spectrometric studies also reported 2 amu and 26 amu loss fragment ions, corresponding to hydrogen and acetylene loss. We could not identify such peaks in the mass spectrum of oleic acid.
Mechanistic Model‐Informed Proarrhythmic Risk Assessment of Drugs: Review of the “CiPA” Initiative and Design of a Prospective Clinical Validation Study
Authors: Vicente Jose , Zusterzeel Robbert , Johannesen Lars , Mason Jay , Sager Philip , Patel Vikram , Matta Murali K. , Li Zhihua , Liu Jiang , Garnett Christine , Stockbridge Norman , Zineh Issam , Strauss David G.
Published: October 2017

The Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative is developing and validating a mechanistic‐based assessment of the proarrhythmic risk of drugs. CiPA proposes to assess a drug's effect on multiple ion channels and integrate the effects in a computer model of the human cardiomyocyte to predict proarrhythmic risk. Unanticipated or missed effects will be assessed with human stem cell‐derived cardiomyocytes and electrocardiogram (ECG) analysis in early phase I clinical trials. This article provides an overview of CiPA and the rationale and design of the CiPA phase I ECG validation clinical trial, which involves assessing an additional ECG biomarker (J‐Tpeak) for QT prolonging drugs. If successful, CiPA will 1) create a pathway for drugs with hERG block / QT prolongation to advance without intensive ECG monitoring in phase III trials if they have low proarrhythmic risk; and 2) enable updating drug labels to be more informative about proarrhythmic risk, not just QT prolongation.
Charge‐Transfer and Arrangement Effects on Delayed Photoluminescence from Phthalimide Cocrystals
Authors: Kita Yasuyuki , Nishida Jun‐ichi , Nishida Shota , Matsui Yasunori , Ikeda Hiroshi , Hirao Yasukazu , Kawase Takeshi
Published: October 2017

Cocrystals of N‐4‐trifluoromethylphenylphthalimides 1 a⊇2 a(1 %), composed of bromo (1 a) and dimethylamino (2 a) derivatives in a 99:1 ratio, display delayed photoluminescence (DPL) at λem=535 nm with a lifetime of 0.26 s. In contrast, pure materials 1 a and 2 a do not exhibit DPL. Similar DPL emission is also observed for cocrystals 1⊇2(1 %) of N‐4‐pyridyl, N‐phenyl, and N‐4‐tolyl derivatives. X‐Ray crystallographic analyses and the results of density functional theory calculations revealed that key for the occurrence of DPL is the formation of charge‐transfer (CT) excited states 1(2 a⋅1 a)CT* and the existence of regularly aligned networks in the cocrystals, which leads to generation of the long‐lived excited state 31 a via 3(2 a⋅1 a)CT* by intersystem crossing and localization of triplet energy.
Forgiving Computers: The Rise of Automation and Implications for Counseling
Authors: Prahl Andrew , Enright Robert D.
Published: October 2017

It is becoming common for decisions with serious consequences to be made by automation. Therefore, it is important for counselors to consider the challenges of working with clients who are affected. If a high‐consequence decision that leads to tragedy is made by a computer, does this change the counseling process? This article starts this discussion by investigating forgiveness therapy as it applies to computers. First, forgiving a human is qualitatively different from forgiving a computer. Next, examples of automated decisions are presented. Finally, the authors discuss issues that clients wishing to forgive a computer face, suggest interventions, and propose a research agenda.
Bad wrap: Myelin and myelin plasticity in health and disease
Authors: Gibson Erin M. , Geraghty Anna C. , Monje Michelle
Published: October 2017

Human central nervous system myelin development extends well into the fourth decade of life, and this protracted period underscores the potential for experience to modulate myelination. The concept of myelin plasticity implies adaptability in myelin structure and function in response to experiences during development and beyond. Mounting evidence supports this concept of neuronal activity‐regulated changes in myelin‐forming cells, including oligodendrocyte precursor cell proliferation, oligodendrogenesis and modulation of myelin microstructure. In healthy individuals, myelin plasticity in associative white matter structures of the brain is implicated in learning and motor function in both rodents and humans. Activity‐dependent changes in myelin‐forming cells may influence the function of neural networks that depend on the convergence of numerous neural signals on both a temporal and spatial scale. However, dysregulation of myelin plasticity can disadvantageously alter myelin microstructure and result in aberrant circuit function or contribute to pathological cell proliferation. Emerging roles for myelin plasticity in normal neurological function and in disease are discussed. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 78: 123–135, 2018
Neurodevelopmental disease mechanisms, primary cilia, and endosomes converge on the BLOC‐1 and BORC complexes
Authors: Hartwig Cortnie , Monis William J. , Chen Xun , Dickman Dion K. , Pazour Gregory J. , Faundez Victor
Published: October 2017

The biogenesis of lysosome‐related organelles complex‐1 (BLOC‐1) and the bloc‐one‐related complex (BORC) are the cytosolic protein complexes required for specialized membrane protein traffic along the endocytic route and the spatial distribution of endosome‐derived compartments, respectively. BLOC‐1 and BORC complex subunits and components of their interactomes have been associated with the risk and/or pathomechanisms of neurodevelopmental disorders. Thus, cellular processes requiring BLOC‐1 and BORC interactomes have the potential to offer novel insight into mechanisms underlying behavioral defects. We focus on interactions between BLOC‐1 or BORC subunits with the actin and microtubule cytoskeleton, membrane tethers, and SNAREs. These interactions highlight requirements for BLOC‐1 and BORC in membrane movement by motors, control of actin polymerization, and targeting of membrane proteins to specialized cellular domains such as the nerve terminal and the primary cilium. We propose that the endosome–primary cilia pathway is an underappreciated hub in the genesis and mechanisms of neurodevelopmental disorders. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 78: 311–330, 2018
Is zebrafish (Danio rerio) a tool for human‐like metabolism study?
Authors: de Souza Anselmo Carina , Sardela Vinicius Figueiredo , Matias Bernardo Fonseca , de Carvalho Amanda Reis , de Sousa Valeria Pereira , Pereira Henrique Marcelo Gualberto , de Aquino Neto Francisco Radler
Published: October 2017

One of the greatest challenges in anti‐doping science is the large number of substances available and the difficulty in finding the best analytical targets to detect their misuse. Therefore, metabolism studies involving prohibited substances are fundamental. However, metabolism studies in humans could face an important ethical bottleneck, especially for non‐approved substances. An emerging model for metabolism assessment is the zebrafish, due to its genetic similarities with humans. In the present study, the ability of adult zebrafish to produce metabolites of sibutramine and stanozolol, substances with a well‐known metabolism that are widely used as doping agents in sports, was evaluated. They represent 2 of the most abused classes of doping agents, namely, stimulants and anabolic steroids. These are classes that have been receiving attention because of the upsurge of synthetic analogues, for which the side effects in humans have not been assessed. The samples collected from the zebrafish tank water were hydrolysed, extracted by solid‐phase extraction, and analysed by liquid chromatography with high resolution mass spectrometry (LC–HRMS). Adult zebrafish could produce several sibutramine and stanozolol metabolites, including demethylated, hydroxylated, dehydroxylated, and reduced derivatives, all of which have already been detected in human urine. This study demonstrates that adult zebrafish can absorb, oxidise, and excrete several metabolites in a manner similar to humans. Therefore, adult zebrafish seem to be a very promising tool to study human‐like metabolism when aiming to find analytical targets for doping control. Copyright © 2017 John Wiley & Sons, Ltd.
Fuel‐reduction management alters plant composition, carbon and nitrogen pools, and soil thaw in Alaskan boreal forest
Authors: Melvin April M. , Celis Gerardo , Johnstone Jill F. , McGuire A. David , Genet Helene , Schuur Edward A. G. , Rupp T. Scott , Mack Michelle C.
Published: October 2017

Increasing wildfire activity in Alaska's boreal forests has led to greater fuel‐reduction management. Management has been implemented to reduce wildfire spread, but the ecological impacts of these practices are poorly known. We quantified the effects of hand‐thinning and shearblading on above‐ and belowground stand characteristics, plant species composition, carbon (C) and nitrogen (N) pools, and soil thaw across 19 sites dominated by black spruce (Picea mariana) in interior Alaska treated 2–12 years prior to sampling. The density of deciduous tree seedlings was significantly higher in shearbladed areas compared to unmanaged forest (6.4 vs. 0.1 stems/m2), and unmanaged stands exhibited the highest mean density of conifer seedlings and layers (1.4 stems/m2). Understory plant community composition was most similar between unmanaged and thinned stands. Shearblading resulted in a near complete loss of aboveground tree biomass C pools while thinning approximately halved the C pool size (1.2 kg C/m2compared to 3.1 kg C/m2in unmanaged forest). Significantly smaller soil organic layer (SOL) C and N pools were observed in shearbladed stands (3.2 kg C/m2and 116.8 g N/m2) relative to thinned (6.0 kg C/m2and 192.2 g N/m2) and unmanaged (5.9 kg C/m2and 178.7 g N/m2) stands. No difference in C and N pool sizes in the uppermost 10 cm of mineral soil was observed among stand types. Total C stocks for measured pools was 2.6 kg C/m2smaller in thinned stands and 5.8 kg C/m2smaller in shearbladed stands when compared to unmanaged forest. Soil thaw depth averaged 13 cm deeper in thinned areas and 46 cm deeper in shearbladed areas relative to adjacent unmanaged stands, although variability was high across sites. Deeper soil thaw was linked to shallowerSOLdepth for unmanaged stands and both management types, however for any givenSOLdepth, thaw tended to be deeper in shearbladed areas compared to unmanaged forest. These findings indicate that fuel‐reduction management alters plant community composition, C and N pools, and soil thaw depth, with consequences for ecosystem structure and function beyond those intended for fire management.
Echocardiographic estimation of left ventricular and pulmonary pressures in patients with heart failure and preserved ejection fraction: a study utilizing simultaneous echocardiography and invasive measurements
Authors: Hummel Yoran M. , Liu Licette C.Y. , Lam Carolyn S.P. , Fonseca‐Munoz Daniel F. , Damman Kevin , Rienstra Michiel , van der Meer Peter , Rosenkranz Stephan , van Veldhuisen Dirk J. , Voors Adriaan A. , Hoendermis Elke S.
Published: October 2017

Aims

Although echocardiography is generally used for the diagnosis of heart failure with preserved ejection fraction (HFpEF), invasive measurements of filling pressures are the gold standard. Studies simultaneously performing echocardiography and invasive measurements in HFpEF are sparse.

Methods and results

Invasive haemodynamic and echocardiographic measurements were simultaneously performed in 98 patients with heart failure New York Heart Association class ≥II, left ventricular ejection fraction (LVEF) ≥45%, and suspected pulmonary hypertension on a previous echocardiogram. Multivariable linear regression analyses were used to establish echocardiographic predictors of pulmonary artery wedge pressure (PAWP), left ventricular end‐diastolic pressure (LVEDP), and mean pulmonary arterial pressure (mPAP). Mean age of the study patients was 74 ± 9 years, 68% were female, mean LVEF was 57 ± 5%, and 30% had atrial fibrillation at the time of measurement. Mean PAWP, LVEDP and mPAP were 17.2 ± 6.2, 16.7 ± 5.8 and 30.9 ± 10.2 mmHg, respectively. Isovolumetric relaxation time (IVRT) and left atrial reservoir strain could moderately estimate PAWP (r = 0.656; P < 0.001). LVEDP was only modestly predicted by IVRT and right ventricular wall thickness (r = 0.548; P < 0.001). Surprisingly, a low correlation was found between E/e'mean and PAWP (r = 0.240; P = 0.019), E/e'mean and LVEDP (r = 0.081; P = 0.453). Correlation coefficients were similar in patients with and without atrial fibrillation.

Conclusion

In patients with HFpEF, echocardiographic measurements, including the E/e' ratio, have a poor to moderate predictive value for the estimation of invasively acquired LVEDP and PAWP. This limitation should be taken into account for the diagnosis and evaluation of patients with HFpEF.
Surface‐Amine‐Implanting Approach for Catalyst Functionalization: Prominently Enhancing Catalytic Hydrogen Generation from Formic Acid
Authors: Zhu De‐Jie , Wen Yue‐Hong , Xu Qiang , Zhu Qi‐Long , Wu Xin‐Tao
Published: October 2017

Highly efficient hydrogen generation from formic acid is a vital process in the clean energy and chemical industry fields. In this work, a universal and efficient surface‐amine‐implanting approach (SAIA) was proposed to fabricate highly active nanocatalysts with controllable nucleation and growth of small‐sized metal nanoparticles (NPs) and desired environments around the active sites. The highly dispersed ultrafine palladium NPs supported by the amine‐implanted porous carbon (Pd/APC) exhibited catalytic activity that was increased nearly threefold relative to that of the unmodified catalyst and showed high selectivity for the dehydrogenation of formic acid under mild conditions. Detailed investigations demonstrated that the amine species densely implanted on the pore surface of carbon by hydrothermal treatment with ammonium hydroxide played an important role in dispersing the metal NPs and in promoting the catalytic processes. The presented approach provides powerful entry into highly active catalysts to elicit enhanced catalytic performance for various catalytic reactions and to promote the dehydrogenation of formic acid for practical applications.
The β‐lactam clavulanic acid mediates glutamate transport‐sensitive pain relief in a rat model of neuropathic pain
Authors: Kristensen P.J. , Gegelashvili G. , Munro G. , Heegaard A.M. , Bjerrum O.J.
Published: October 2017

Background

Following nerve injury, down‐regulation of astroglial glutamate transporters (GluTs) with subsequent extracellular glutamate accumulation is a key factor contributing to hyperexcitability within the spinal dorsal horn. Some β‐lactam antibiotics can up‐regulate GluTs, one of which, ceftriaxone, displays analgesic effects in rodent chronic pain models.

Methods

Here, the antinociceptive actions of another β‐lactam clavulanic acid, which possesses negligible antibiotic activity, were compared with ceftriaxone in rats with chronic constriction injury (CCI)‐induced neuropathic pain. In addition, the protein expression of glutamate transporter‐1 (GLT1), its splice variant GLT1b and glutamate‐aspartate transporter (GLAST) was measured in the spinal cord of CCI rats. Finally, protein expression of the same GluTs was evaluated in cultured astrocytes obtained from rodents and humans.

Results

Repeated injection of ceftriaxone or clavulanic acid over 10 days alleviated CCI‐induced mechanical hypersensitivity, whilst clavulanic acid was additionally able to affect the thermal hypersensitivity. In addition, clavulanic acid up‐regulated expression of GLT1b within the spinal cord of CCI rats, whereas ceftriaxone failed to modulate expression of any GluTs in this model. However, both clavulanic acid and ceftriaxone up‐regulated GLT1 expression in rat cortical and human spinal astrocyte cultures. Furthermore, clavulanic acid increased expression of GLT1b and GLAST in rat astrocytes in a dose‐dependent manner.

Conclusions

Thus, clavulanic acid up‐regulates GluTs in cultured rodent‐ and human astroglia and alleviates CCI‐induced hypersensitivity, most likely through up‐regulation of GLT1b in spinal dorsal horn.

Significance

Chronic dosing of clavulanic acid alleviates neuropathic pain in rats and up‐regulates glutamate transporters both in vitro and in vivo. Crucially, a similar up‐regulation of glutamate transporters in human spinal astrocytes by clavulanic acid supports the development of novel β‐lactam‐based analgesics, devoid of antibacterial activity, for the clinical treatment of chronic pain.
Efficacy, acceptability and safety of cognitive behavioural therapies in fibromyalgia syndrome – A systematic review and meta‐analysis of randomized controlled trials
Authors: Bernardy K. , Klose P. , Welsch P. , Häuser W.
Published: October 2017

This updated systematic review aimed at evaluating the efficacy, acceptability and safety of cognitive behavioural therapies (CBTs) in fibromyalgia syndrome (FMS). Clinicaltrials.gov, Cochrane Library, MEDLINE, PsycINFO and SCOPUS were searched from September 2013 to May 2017. Randomized controlled trials (RCTs) comparing CBTs with controls were analysed. Primary outcomes were ≥50% pain relief, ≥20% improvement of health‐related quality of life (HRQoL), negative mood, fatigue, disability, acceptability and safety at end of therapy and at 6 months follow‐up. Effects were summarized by a random effects model using risk differences (RD) or standardized mean differences (SMD) with 95% confidence intervals (CI). 29 RCTs with 2509 subjects were included. CBTs were superior to controls (waiting list, attention control, treatment as usual, other active non‐pharmacological therapies) in pain relief of 50% or greater (RD 0.05 [95% CI 0.02–0.07] (high‐quality evidence), improvement of HRQoL of 20% or greater (RD 0.13 [95% CI 0.00–0.26], (moderate quality evidence), and in reducing negative mood (SMD −0.43 [95% CI −0.62 to −0.24]) (high‐quality evidence), disability (SMD −0.30 [95% CI −0.52 to −0.08]) (high‐quality evidence) and fatigue (SMD – 0–27 [95% CI −0.50 to −0.03]) (high‐quality evidence). There were no statistically significant differences between CBTs and controls in acceptability and safety (high‐quality evidence). The update did not change the major findings of the previous review. CBTs provided a clinically relevant benefit over control interventions in reducing some key symptoms of FMS and disability at the end of treatment.

Significance

This updated systematic review with meta‐analysis on cognitive behavioural therapies (CBTs) including acceptance‐based CBTs endorse the efficacy and tolerability of CBTs in reducing key symptoms and disability in FMS in the short‐ and long‐term if compared to waiting list, treatment as usual, attention controls and active non‐pharmacological therapies. CBTs did not differ in efficacy except superiority for coping with pain and tolerability from recommended drug therapy (pregabalin and/or duloxetine).
Occurrence and distribution of organophosphate ester flame retardants in indoor dust and their potential health exposure risk
Authors: Zeng Xiangying , Wu Yang , Liu Zhiyang , Gao Shutao , Yu Zhiqiang
Published: October 2017

The occurrence and distribution of 10 organophosphate ester (OP) flame retardants/plasticizers were studied in indoor dust collected in 2 districts of Wuhan City. Total concentrations of the 10 OPs (ΣOPs) varied from 86.5 to 6389 ng/g in 26 dust samples in Caidian District and from 300 to 10 186 ng/g in 27 samples in Jiang'an District. In most dust samples tris(2-chloroethyl) phosphate was dominant over the other OPs, with concentrations of 9.14 to 2722 ng/g (mean 388 ng/g) in Caidian District and 57.3 to 3718 ng/g (mean 616 ng/g) in Jiang'an District. The calculated hazard indices, based on estimated exposure dose via dust ingestion to the reference dose, were much lower than 1. The results suggested that the inhabitants in the 2 regions were at low risk of exposure through dust ingestion. Environ Toxicol Chem 2018;37:345–352. © 2017 SETAC
Mixtures of Cu, Ni, and Zn act mostly noninteractively on Pseudokirchneriella subcapitata growth in natural waters
Authors: Van Regenmortel Tina , De Schamphelaere Karel A.C.
Published: October 2017

Freshwater biota are usually exposed to mixtures of different metals in the environment, which raises concern because risk-assessment procedures for metals are still mainly based on single-metal toxicity. Because microalgae are primary producers and therefore at the base of the food web, it is of utmost importance to understand the effects of metal mixtures on these organisms. Most studies that have investigated the combined interactive effects of mixtures on microalgae performed tests in only one specific water. The objective of the present study was to test if combined effects of mixtures to Pseudokirchneriella subcapitata were the same or different across natural waters showing diverse water-chemistry characteristics. This was done by performing experiments with ternary Cu–Ni–Zn mixtures in 3 natural waters and with binary Cu–Ni mixtures in 5 natural waters. We showed that the ternary mixture acted noninteractively on algal growth, except in one water in which the mixture acted antagonistically. We suggest that a low–cationic competition situation in the latter water could be the reason for the antagonistic interaction between the metals. On the other hand, the binary mixture acted noninteractively on algal growth in all tested waters. We showed that both the concentration addition and independent action models can serve as accurate models for toxicity of ternary Cu–Ni–Zn and binary Cu–Ni mixtures to P. subcapitata in most cases and as protective models in all cases. In addition, we developed a metal mixture bioavailability model, by combining the independent action model and the single-metal bioavailability models, that can be used to predict Cu–Ni–Zn and Cu–Ni toxicity to P. subcapitata as a function of metal concentration and water characteristics. Environ Toxicol Chem 2018;37:587–598. © 2017 SETAC
How effective and efficient are social programs on food and nutritional security?
Authors: Pillaca‐Medina Susan , Chavez‐Dulanto Perla Noemi
Published: October 2017

The analysis of the impact assessment of social programs allows to identify whether they fulfil the established objectives and evidencing the weaknesses to be strengthened in future actions, and modify or propose new intervention strategies. In Peru, the substantial economic progress since the 90s decade promoted dramatical investments in the social sector, especially on children well‐being, as around 30% of the total Peru population are children under the age of 15, being the age group most affected by poverty in the country. This review was aimed to present an overview of the current situation of social programs in Peru in terms of food (and nutritional) security (FS), emphasizing on the institutional framework and the impact of the social programs implemented by the Government, as well as some social programs implemented by nongovernmental organizations. To this end, information available on the world wide web, including peer‐reviewed papers on databases (mainly SciELOand LiLACs for their relevance for the Latin American region) regardingFSin Peru from 1989 onwards, and information published by the Peruvian official organisms directly involved inFS, was used. Studies addressing at least four of the seven points of the food and nutritional security in Peru analyzed in this paper (access, availability, consumption, biological use, stability, current situation, and institutionality) were considered. It was concluded that investment and resources should be used to improve social programs strategies designed according to the reality of each focused area, as in Peru, the achievements show an enormous potential for replicability of the interventions. Children must be prioritized through child‐sensitive programs, instead of considering them just as indicators and investments for the future—especially in rural areas whipped by the past internal conflicts—in order to contribute to the sustainable development of the country and assuringFS.
On the use of the continuous adjoint method to compute nongeometric sensitivities
Authors: Hayashi M. T. , Volpe E. V. , Ceze M. A.
Published: October 2017

This work explores an alternative approach to computing sensitivity derivatives of functionals, with respect to a broader range of control parameters. It builds upon the complementary character of Riemann problems that describe the Euler flow and adjoint solutions. In a previous work, we have discussed a treatment of the adjoint boundary problem, which made use of such complementarity as a means to ensure well‐posedness. Here, we show that the very same adjoint solution that satisfies those boundary conditions also conveys information on other types of sensitivities. In essence, then, that formulation of the boundary problem can extend the range of applications of the adjoint method to a host of new possibilities.
ADAM8 expression in breast cancer derived brain metastases: Functional implications on MMP‐9 expression and transendothelial migration in breast cancer cells
Authors: Conrad Catharina , Götte Malena , Schlomann Uwe , Roessler Marion , Pagenstecher Axel , Anderson Peter , Preston Jane , Pruessmeyer Jessica , Ludwig Andreas , Li Ran , Kamm Roger D. , Ritz Rainer , Carl Barbara , Nimsky Christopher , Bartsch Jörg W.
Published: October 2017

Metastatic breast cancer affects long‐term survival and is a major cause of cancer death for women worldwide. The Metalloprotease‐Disintegrin ADAM8 promotes breast cancer development and brain metastasis in a mouse breast cancer model. Here, abundant ADAM8 expression was detected in primary human breast tumors and associated brain metastases. To investigate the function of ADAM8 in metastasis, MB‐231 breast cancer cells with ADAM8 knockdown (MB‐231_shA8) and scramble control cells (MB‐231_shCtrl) were analyzed for their capability to develop metastases. In vitro, formation of metastatic complexes in hanging drops is dependent on ADAM8 and blocked by ADAM8 inhibition. MB‐231_shA8 in contrast to MB‐231_shCtrl cells were impaired in transmigration through an endothelial and a reconstituted blood‐brain barrier. Out of 23 MMP and 22 ADAM genes, only the MMP‐9 gene was affected by ADAM8 knockdown in MB‐231_shA8 cells. Following re‐expression of wild‐type ADAM8 in contrast to ADAM8 lacking the cytoplasmic domain in MB‐231_shA8 cells caused increased levels of activated pERK1/2 and pCREB (S133) that were associated with elevated MMP‐9 transcription. Application of ADAM8 and MMP‐9 antibodies reduced transmigration of MB‐231 cells suggesting that ADAM8 affects transmigration of breast cancer cells by MMP‐9 regulation. ADAM8‐dependent transmigration was confirmed in Hs578t cells overexpressing ADAM8. Moreover, transmigration of MB‐231 and Hs578t cells was significantly reduced for cells treated with an antibody directed against P‐selectin glycoprotein ligand (PSGL‐1), a substrate of ADAM8. From these data we conclude that ADAM8 promotes early metastatic processes such as transendothelial migration by upregulation of MMP‐9 and shedding of PSGL‐1 from breast cancer cells.
A VISION FOR HUMAN‐MODEL INTERACTION IN INTERACTIVE MODEL‐CENTRIC SYSTEMS ENGINEERING
Authors: Rhodes Donna H. , Ross Adam M.
Published: October 2017

The Interactive Model‐Centric Systems Engineering (IMCSE) research program arises from the unique opportunity to investigate the various aspects of humans interacting with models and model‐generated data, in the context of systems engineering practice. This paper explores the dimensions of this interaction and shares findings from a recent workshop organized to seed the initial research agenda. Many open areas of inquiry exist; examples include: use cases for stakeholders interacting with models; how multiple stakeholders interact with each other using models and model generated information; facets of human interaction with visualizations and large data sets; and underlying fundamentals such as model purpose and model handling. Realizing the envisioned future for an interactive model‐centric systems engineering experience will require new knowledge and ways of working, and innovation in constructs and technologies. A shared research agenda is proposed as a means to provide a common frame for alignment and synergies of research across the community. Research needs and progress are discussed and several ongoing research projects are briefly discussed.
Business, housing, and credit cycles
Authors: Rünstler Gerhard , Vlekke Marente
Published: October 2017

We use multivariate unobserved components models to estimate trend and cyclical components in gross domestic product (GDP), credit volumes, and house prices for the USA and the five largest European economies. With the exception of Germany, we find large and long cycles in credit and house prices, which are highly correlated with a medium‐term component in GDP cycles. Differences across countries in the length and size of cycles appear to be related to the properties of national housing markets. The precision of pseudo real‐time estimates of credit and house price cycles is roughly comparable to that of GDP cycles.
Improving Markov switching models using realized variance
Authors: Liu Jia , Maheu John M.
Published: October 2017

This paper proposes a class of models that jointly model returns and ex post variance measures under a Markov switching framework. Both univariate and multivariate return versions of the model are introduced. Estimation can be conducted under a fixed dimension state space or an infinite one. The proposed models can be seen as nonlinear common factor models subject to Markov switching and are able to exploit the information content in both returns and ex post volatility measures. Applications to equity returns compare the proposed models to existing alternatives. The empirical results show that the joint models improve density forecasts for returns and point predictions of return variance. Using the information in ex post volatility measures can increase the precision of parameter estimates, sharpen the inference on the latent state variable, and improve portfolio decisions.
Evaluation of a novel poly(amidoamine) with pendant aminobutyl group on the cellular properties of transfected bone marrow mesenchymal stem cells
Authors: Chen Lili , Long Dan , Huang Shishu , Yang Qian , Hao Jin , Wu Nan , Peng Lin
Published: October 2017

Stem cell‐based gene therapy has been considered in the treatment of many degenerative diseases. Gene‐modified stem cells should maintain its reproductive activity without losing stem cell properties, including genetic phenotype and differentiation potential. In the study, a novel poly (amidoamine) with pendant aminobutyl group (PAA‐BA) designed by our group was used in the transfection of bone marrow mesenchymal stromal cells (BMSCs) and the cellular properties post‐transfection were evaluated, including DNA content, colony forming capacity, genetic phenotype, and multi‐directional differentiation. Two classical non‐viral gene delivery vectors, polyethylenimine (PEI) and Lipofectamine 2000 (LP2000) were also used. Compared to non‐transfected group, PAA‐BA showed minor decreased DNA content but maintained BMSCs’ phenotype, reproductive activity and multi‐differentiation potential (osteogenic, chondrogenic, adipogenic, and neurogenic differentiation). Both PAA‐BA and PEI transfected BMSCs demonstrated improved osteogenic differentiation ability at late stage but suppressed adipogenic as well as mature neural differentiationin vitro. LP2000 and PEI transfected BMSCs displayed significantly lower DNA content and reproductive activity. These findings suggest that PAA‐BA is one of safe gene delivery vectors in BMSCs transfection and plays a role in stem cell's osteogenic and neurogenic differentiation. This study proposes the potential application of PAA‐BA in BMSCs based gene therapy, in particular bone and nerve relative diseases. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 686–697, 2018.
Modeling of the interaction between osteoblasts and biocompatible substrates as a function of adhesion strength
Authors: Portan D. V. , Deligianni D. D. , Deligianni K. , Kroustalli A. A. , Tyllianakis M. , Papanicolaou G. C.
Published: October 2017

A goal of current implantology research is to design devices that induce controlled, guided, and rapid healing. Nanoscale structured substrates [e.g., titania nanotubes (TNTs) or carbon nanotubes (CNTs)] dramatically improve the functions of conventional biomaterials. The present investigation evaluated the behavior of osteoblasts cells cultured on smooth and nanostructured substrates, by measuring osteoblasts specific biomarkers [alkaline phosphatase (AP) and total protein] and cells adhesion strength to substrates, followed by semi‐empirical modeling to predict the experimental results. Findings were in total agreement with the current state of the art. The proliferation, as well as the AP and total protein levels were higher on the nanostructure phases (TNTs, CNTs) comparing to the smooth ones (plastic and pure titanium). Cells adhesion strength measured was found higher on the nanostructured materials. This coincided with a higher value of proteins which are directly implicated in the process of adherence. Results were accurately predicted through the Viscoelastic Hybrid Interphase Model. A gradual adherence of bone cells to implants using multilayered biomaterials that involve biodegradable polymeric films and a nanoscale modification of titanium surface is suggested to improve performance through an interphase‐mediated osteointegration of orthopedic implants. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 621–628, 2018.
In vivo diabetic wound healing with nanofibrous scaffolds modified with gentamicin and recombinant human epidermal growth factor
Authors: Dwivedi Charu , Pandey Ishan , Pandey Himanshu , Patil Sandip , Mishra Shanti Bhushan , Pandey Avinash C. , Zamboni Paolo , Ramteke Pramod W , Singh Ajay Vikram
Published: October 2017

Diabetic wounds are susceptible to microbial infection. The treatment of these wounds requires a higher payload of growth factors. With this in mind, the strategy for this study was to utilize a novel payload comprising of Eudragit RL/RS 100 nanofibers carrying the bacterial inhibitor gentamicin sulfate (GS) in concert with recombinant human epidermal growth factor (rhEGF); an accelerator of wound healing. GS containing Eudragit was electrospun to yield nanofiber scaffolds, which were further modified by covalent immobilization of rhEGF to their surface. This novel fabricated nanoscaffold was characterized using scanning electron microscopy, Fourier transform infrared spectroscopy, and X‐ray diffraction. The thermal behavior of the nanoscaffold was determined using thermogravimetric analysis and differential scanning calorimetry. In the in vitro antibacterial assays, the nanoscaffolds exhibited comparable antibacterial activity to pure gentemicin powder. In vivo work using female C57/BL6 mice, the nanoscaffolds induced faster wound healing activity in dorsal wounds compared to the control. The paradigm in this study presents a robust in vivo model to enhance the applicability of drug delivery systems in wound healing applications. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 641–651, 2018.