bluuebunny/crossref_metadata_2025 huggingface dataset:
CD200-CD200R imbalance correlates with microglia and pro-inflammatory activation in rat spinal cords exposed to amniotic fluid in retinoic acid-induced spina bifida
Authors: Oria Marc , Figueira Rebeca L. , Scorletti Federico , Sbragia Lourenco , Owens Kathryn , Li Zhen , Pathak Bedika , Corona Maria U. , Marotta Mario , Encinas Jose L. , Peiro Jose L.
Published: July 2018

Spina bifida aperta is a congenital malformation characterized by the failure of neural tube closure resulting in an unprotected fetal spinal cord. The spinal cord then undergoes progressive damage, likely due to chemical and mechanical factors related to exposure to the intrauterine environment. Astrogliosis in exposed spinal cords has been described in animal models of spina bifida during embryonic life but its relationship with neuroinflammatory processes are completely unknown. Using a retinoic acid-induced rat model of spina bifida we demonstrated that, when exposed to amniotic fluid, fetal spinal cords showed progressive astrogliosis with neuronal loss at mid-gestation (E15) compared to unexposed spinal cords. The number of microglial cells with a reactive phenotype and activation marker expression increased during gestation and exhibited progressive disruption in the inhibitory immune ligand-receptor system. Specifically we demonstrate down-regulation of CD200 expression and up-regulation of CD200R. Exposed spinal cords demonstrated neuroinflammation with increased tissue water content and cytokine production by the end of gestation (E20), which correlated with active Caspase3 expression in the exposed layers. Our findings provide new evidence that microglia activation, including the disruption of the endogenous inhibitory system (CD200-CD200R), may participate in the pathogenesis of spina bifida through late gestation.
Exploring the clinical features of narcolepsy type 1 versus narcolepsy type 2 from European Narcolepsy Network database with machine learning
Authors: Zhang Zhongxing , Mayer Geert , Dauvilliers Yves , Plazzi Giuseppe , Pizza Fabio , Fronczek Rolf , Santamaria Joan , Partinen Markku , Overeem Sebastiaan , Peraita-Adrados Rosa , da Silva Antonio Martins , Sonka Karel , Rio-Villegas Rafael del , Heinzer Raphael , Wierzbicka Aleksandra , Young Peter , Högl Birgit , Bassetti Claudio L. , Manconi Mauro , Feketeova Eva , Mathis Johannes , Paiva Teresa , Canellas Francesca , Lecendreux Michel , Baumann Christian R. , Barateau Lucie , Pesenti Carole , Antelmi Elena , Gaig Carles , Iranzo Alex , Lillo-Triguero Laura , Medrano-Martínez Pablo , Haba-Rubio José , Gorban Corina , Luca Gianina , Lammers Gert Jan , Khatami Ramin
Published: July 2018

Narcolepsy is a rare life-long disease that exists in two forms, narcolepsy type-1 (NT1) or type-2 (NT2), but only NT1 is accepted as clearly defined entity. Both types of narcolepsies belong to the group of central hypersomnias (CH), a spectrum of poorly defined diseases with excessive daytime sleepiness as a core feature. Due to the considerable overlap of symptoms and the rarity of the diseases, it is difficult to identify distinct phenotypes of CH. Machine learning (ML) can help to identify phenotypes as it learns to recognize clinical features invisible for humans. Here we apply ML to data from the huge European Narcolepsy Network (EU-NN) that contains hundreds of mixed features of narcolepsy making it difficult to analyze with classical statistics. Stochastic gradient boosting, a supervised learning model with built-in feature selection, results in high performances in testing set. While cataplexy features are recognized as the most influential predictors, machine find additional features, e.g. mean rapid-eye-movement sleep latency of multiple sleep latency test contributes to classify NT1 and NT2 as confirmed by classical statistical analysis. Our results suggest ML can identify features of CH on machine scale from complex databases, thus providing ‘ideas’ and promising candidates for future diagnostic classifications.
Cell surface nucleolin interacts with and internalizes Bothrops asper Lys49 phospholipase A2 and mediates its toxic activity
Authors: Massimino Maria Lina , Simonato Morena , Spolaore Barbara , Franchin Cinzia , Arrigoni Giorgio , Marin Oriano , Monturiol-Gross Laura , Fernández Julián , Lomonte Bruno , Tonello Fiorella
Published: July 2018

Phospholipases A2 are a major component of snake venoms. Some of them cause severe muscle necrosis through an unknown mechanism. Phospholipid hydrolysis is a possible explanation of their toxic action, but catalytic and toxic properties of PLA2s are not directly connected. In addition, viperid venoms contain PLA2-like proteins, which are very toxic even if they lack catalytic activity due to a critical mutation in position 49. In this work, the PLA2-like Bothrops asper myotoxin-II, conjugated with the fluorophore TAMRA, was found to be internalized in mouse myotubes, and in RAW264.7 cells. Through experiments of protein fishing and mass spectrometry analysis, using biotinylated Mt-II as bait, we found fifteen proteins interacting with the toxin and among them nucleolin, a nucleolar protein present also on cell surface. By means of confocal microscopy, Mt-II and nucleolin were shown to colocalise, at 4 °C, on cell membrane where they form Congo-red sensitive assemblies, while at 37 °C, 20 minutes after the intoxication, they colocalise in intracellular spots going from plasmatic membrane to paranuclear and nuclear area. Finally, nucleolin antagonists were found to inhibit the Mt-II internalization and toxic activity and were used to identify the nucleolin regions involved in the interaction with the toxin.
Non-invasive prediction of NAFLD severity: a comprehensive, independent validation of previously postulated serum microRNA biomarkers
Authors: López-Riera Mireia , Conde Isabel , Quintas Guillermo , Pedrola Laia , Zaragoza Ángela , Perez-Rojas Judith , Salcedo Mario , Benlloch Salvador , Castell José V. , Jover Ramiro
Published: July 2018

Liver biopsy is currently the only reliable method to establish nonalcoholic fatty liver disease (NAFLD) severity. However, this technique is invasive and occasionally associated with severe complications. Thus, non-invasive diagnostic markers for NAFLD are needed. Former studies have postulated 18 different serum microRNA biomarkers with altered levels in NAFLD patients. In the present study, we have re-examined the predictive value of these serum microRNAs and found that 9 of them (miR-34a, -192, -27b, -122, -22, -21, -197, -30c and -16) associated to NAFLD severity in our independent cohort. Moreover, miR-192, -27b, -22, -197 and -30c appeared specific for NAFLD, when compared with patients with drug-induced liver injury. Preliminary serum RNAseq analysis allowed identifying novel potential miRNA biomarkers for nonalcoholic steatohepatitis (NASH). The classification performance of validated miRNAs (and their ratios) for NASH was better than that reached by AST, whereas for advanced fibrosis prediction miRNAs did not perform better than the FIB-4 algorithm. Cross-validated models combining both clinical and miRNA variables showed enhanced predictivity. In conclusion, the circulating microRNAs validated demonstrate a better diagnostic potential than conventional serum markers to identify NASH patients and could complement and improve current fibrosis prediction algorithms. The research in this field is still open.
Probing disorder in pyrochlore oxides using in situ synchrotron diffraction from levitated solids–A thermodynamic perspective
Authors: Maram Pardha S. , Ushakov Sergey V. , Weber Richard J. K. , Benmore Chris J. , Navrotsky Alexandra
Published: July 2018

Pyrochlore, an ordered derivative of the defect fluorite structure, shows complex disordering behavior as a function of composition, temperature, pressure, and radiation damage. We propose a thermodynamic model to calculate the disordering enthalpies for several RE2Zr2O7 (RE = Sm, Eu, Gd) pyrochlores from experimental site distribution data obtained by in situ high temperature synchrotron X-ray diffraction. Site occupancies show a gradual increase in disorder on both cation and anion sublattices with increasing temperature and even greater disorder is achieved close to the phase transition to defect fluorite. The enthalpy associated with cation disorder depends on the radius of the rare earth ion, while the enthalpy of oxygen disordering is relatively constant for different compositions. The experimental data support trends predicted by ab initio calculations, but the obtained enthalpies of disordering are less endothermic than the predicted values. Thermal expansion coefficients are in the range (8.6–10.8) × 10−6 K−1. These new experimental determinations of defect formation energies are important for understanding the stability of pyrochlore oxides and their disordering mechanisms, which are essential in the context of their potential applications in nuclear waste management and other technologies.
Wnt7a induces satellite cell expansion, myofiber hyperplasia and hypertrophy in rat craniofacial muscle
Authors: Cheng Xu , Huang Hanyao , Luo Xiangyou , Shi Bing , Li Jingtao
Published: July 2018

Craniofacial muscles drive critical functions in the head, including speech, feeding and expression. Compared with their counterparts in trunk and limbs, craniofacial muscles are of distinct embryonic origins, which might consequently lead to different growth patterns and regenerative potential. In this study, rat levator veli palatini muscle and masseter muscle were compared with tibialis anterior muscle in their response to exogenous Wnt7a stimulus, which has been proved effective in promoting muscle regeneration in the limbs. Histological, cellular and molecular analyses were performed both under basal condition and after a single dose injection of recombinant human Wnt7a. Under basal condition, levator veli palatini muscle demonstrated considerably more satellite cells than the others. After Wnt7a administration, regeneration-related activities, including satellite cell expansion, myofiber hyperplasia and hypertrophy were generally observed in all three muscles, but with obvious differences in the extent. The composition of fast/slow myofibers underwent substantial alterations, and the pattern varied among the three muscles. Location-specific alterations in the expression level of core components in planar cell polarity pathway, Akt/mTOR pathway and myostatin pathway were also observed. In conclusion, both craniofacial and limb muscles could be effectively expanded by exogenous Wnt7a stimulus, but muscle-to-muscle variations in response patterns existed.
Publisher Correction: Post-translational modifications in DNA topoisomerase 2α highlight the role of a eukaryote-specific residue in the ATPase domain
Authors: Bedez Claire , Lotz Christophe , Batisse Claire , Broeck Arnaud Vanden , Stote Roland H. , Howard Eduardo , Pradeau-Aubreton Karine , Ruff Marc , Lamour Valérie
Published: July 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
Vigour of self-paced reaching movement: cost of time and individual traits
Authors: Berret Bastien , Castanier Carole , Bastide Simon , Deroche Thomas
Published: July 2018

People usually move at a self-selected pace in everyday life. Yet, the principles underlying the formation of human movement vigour remain unclear, particularly in view of intriguing inter-individual variability. It has been hypothesized that how the brain values time may be the cornerstone of such differences, beyond biomechanics. Here, we focused on the vigour of self-paced reaching movement and assessed the stability of vigour via repeated measurements within participants. We used an optimal control methodology to identify a cost of time (CoT) function underlying each participant’s vigour, considering a model of the biomechanical cost of movement. We then tested the extent to which anthropometric or psychological traits, namely boredom proneness and impulsivity, could account for a significant part of inter-individual variance in vigour and CoT parameters. Our findings show that the vigour of reaching is largely idiosyncratic and tend to corroborate a relation between the relative steepness of the identified CoT and boredom proneness, a psychological trait relevant to one’s relationship with time in decision-making.
Long-term Progression and Risk Factors of Fundus Tessellation in the Beijing Eye Study
Authors: Yan Yan Ni , Wang Ya Xing , Yang Yan , Xu Liang , Xu Jie , Wang Qian , Yang Xuan , Yang Jing Yan , Zhou Wen Jia , Wei Wen Bin , Jonas Jost B.
Published: July 2018

To assess the progression of fundus tessellation, color fundus photographs of the participants of the longitudinal population-based Beijing Eye Study were examined. The study included 4439 subjects in 2001 and 2695 (66.4% of the surviving) individuals in 2011. Larger progression in macular fundus tessellation (mean: 0.24 ± 0.48 grades) was associated (multivariate analysis; correlation coefficient r: 0.53) with thinner subfoveal choroidal thickness in 2011 (P < 0.001; standardized regression coefficient beta: −0.37), older age (P < 0.001; beta: 0.22), higher level of education (P < 0.001; beta: 0.09), more myopic change in refractive error (P < 0.001; beta: −0.09) and lower cognitive function score (P = 0.02; beta: −0.05). Larger increase in peripapillary fundus tessellation (mean: 0.19 ± 0.26 grades) correlated with thinner peripapillary choroidal thickness in 2011 (P < 0.001; beta: −0.35), older age (P < 0.001; beta: 0.20), worse best corrected visual acuity (P = 0.001; beta: 0.07), more myopic change in refractive error (P < 0.001; beta: −0.07) and higher prevalence of ever smoking (P = 0.004; beta: 0.05). The increase in macular fundus tessellation, as a surrogate for thinning of the posterior choroid, was associated with lower cognitive function, after adjusting for choroidal thickness, age, educational level and change in refractive error. The findings point to the clinical value of the assessment of fundus tessellation and suggest potential associations between cognitive function and fundus tessellation/choroidal thickness.
The thrombopoietin mimetic romiplostim leads to the complete rescue of mice exposed to lethal ionizing radiation
Authors: Yamaguchi Masaru , Hirouchi Tokuhisa , Yokoyama Koki , Nishiyama Ayaka , Murakami Sho , Kashiwakura Ikuo
Published: July 2018

For the primary treatment of emergency exposure to high-dose radiation, such as in the event of a radiation accident, the top priority is the reconstitution and restoration of haematopoiesis. In most radiation accidents, drug therapy is chosen as the most suitable treatment; the chosen drug should already be approved domestically, stably supplied and regularly stockpiled. In the present study, a single administration of romiplostim (RP), an approved thrombopoietin receptor agonist, produced a 100% survival rate in C57BL/6 J mice exposed to a lethal dose (7 Gy) of137Cs γ-rays, and all irradiated mice survived for more than 30 days with both 3- and 5-day consecutive administrations. By day 30, the peripheral blood cells, bone marrow cells and haematopoietic progenitor cells of the RP-administered irradiated mice had all recovered to a level that was not significantly different from that in non-irradiated mice. In contrast to myelosuppression, which did not fully recover until day 30, the expression of several bone marrow cell surface antigens recovered sooner, and DNA repair concurrently increased in haematopoietic cells, speeding the resolution of double strand breaks and reducing the rates of apoptosis. These findings suggest that RP may be a clinic-ready countermeasure to treat victims of radiation accidents.
Treatment of Cutting Fluid Waste using Activated Carbon Fiber Supported Nanometer Iron as a Heterogeneous Fenton Catalyst
Authors: Su Chunjian , Cao Gaohua , Lou Shumei , Wang Rui , Yuan Fengru , Yang Longyun , Wang Qing
Published: July 2018

Addressing the problem of high chemical oxygen demands (COD) of cutting fluid waste generated in the machining process, its complex composition, and the specific conditions required for the treatment process, a heterogeneous Fenton fibre catalyst (NZVI@ACF) made of nanometer-iron supported on activated carbon fiber using dip-molding was developed. NZVI was homogeneously loaded onto ACF surfaces to form NZVI@ACF, with a specific surface area (SBET) of 726.3642 m2/g. Using a multistage chemical pretreatment, the NZVI@ACF/H2O2 system was used to effectively treat cutting fluid waste. The results indicated that the rate of COD removal in the cutting fluid waste liquid pretreated with NZVI@ACF/H2O2 system was 99.8% when the reactions conditions were optimized to 20 nmol/L H2O2, 6 g/L NZVI@ACF, total reaction time of 120 min and pH 5. The treated waste solution passed China’s tertiary wastewater discharge standards. NZVI@ACF/H2O2 demonstrated an excellent catalytic performance compared to the traditional Fenton catalyst, increased the effective pH reaction range and had an adsorption effect on the waste liquid after the reaction.
Blocking CCL5-CXCL4 heteromerization preserves heart function after myocardial infarction by attenuating leukocyte recruitment and NETosis
Authors: Vajen Tanja , Koenen Rory R. , Werner Isabella , Staudt Mareike , Projahn Delia , Curaj Adelina , Sönmez Tolga Taha , Simsekyilmaz Sakine , Schumacher David , Möllmann Julia , Hackeng Tilman M. , Hundelshausen Philipp von , Weber Christian , Liehn Elisa A.
Published: July 2018

Myocardial infarction (MI) is a major cause of death in Western countries and finding new strategies for its prevention and treatment is thus of high priority. In a previous study, we have demonstrated a pathophysiologic relevance for the heterophilic interaction of CCL5 and CXCL4 in the progression of atherosclerosis. A specifically designed compound (MKEY) to block this CCL5-CXCR4 interaction is investigated as a potential therapeutic in a model of myocardial ischemia/reperfusion (I/R) damage. 8 week-old male C57BL/6 mice were intravenously treated with MKEY or scrambled control (sMKEY) from 1 day before, until up to 7 days after I/R. By using echocardiography and intraventricular pressure measurements, MKEY treatment resulted in a significant decrease in infarction size and preserved heart function as compared to sMKEY-treated animals. Moreover, MKEY treatment significantly reduced the inflammatory reaction following I/R, as revealed by specific staining for neutrophils and monocyte/macrophages. Interestingly, MKEY treatment led to a significant reduction of citrullinated histone 3 in the infarcted tissue, showing that MKEY can prevent neutrophil extracellular trap formation in vivo. Disrupting chemokine heterodimers during myocardial I/R might have clinical benefits, preserving the therapeutic benefit of blocking specific chemokines, and in addition, reducing the inflammatory side effects maintaining normal immune defence.
Novel triadius-like N4 specie of iron nitride compounds under high pressure
Authors: Chen Yuanzheng , Cai Xinyong , Wang Hongyan , Wang Hongbo , Wang Hui
Published: July 2018

Various nitrogen species in nitrides are fascinating since they often appear with these nitride as superconductors, hard materials, and high-energy density. As a typical complex, though iron nitride has been intensively studied, nitrogen species in the iron–nitrogen (Fe-N) compounds only have been confined to single atom (N) or molecule nitrogen (N2). Using a structure search method based on the CALYPSO methodology, unexpectedly, we here revealed two new stable high pressure (HP) states at 1:2 and 1:4 compositions with striking nitrogen species. The results show that the proposed FeN2 stabilizes by a break up of molecule N2 into a novel planar N4 unit (P63/mcm, >228 GPa) while FeN4 stabilizes by a infinite 1D linear nitrogen chains N∞ (P-1, >50 GPa; Cmmm, >250 GPa). In the intriguing N4 specie of P63/mcm-FeN2, we find that it possesses three equal N = N covalent bonds and forms a perfect triadius-like configuration being never reported before. This uniqueness gives rise to a set of remarkable properties for the crystal phase: it is identified to have a good mechanical property and a potential for phonon-mediated superconductivity with a Tc of 4–8 K. This discovery puts the Fe-N system into a new class of desirable materials combining advanced mechanical properties and superconductivity.
Fundamentals of Stimuli-responsive Drug and Gene Delivery Systems
Authors: Torchilin Vladimir P.
Published: July 2018

This chapter provides a brief overview of the various stimuli that can be used to control the behaviour of drug delivery systems and drug release. The intrinsic stimuli characteristics of pathological sites, such as the local pH or temperature changes, redox status, overexpression of certain proteins, and hypoxia, as well as stimuli that can be applied from the outside of the body, such as ultrasound, temperature, magnetic fields, and light, are considered.
Thermo-responsive Nanomedicines for Drug Delivery in the Gastrointestinal Tract
Authors: Almeida Andreia , Macedo Helena , Neves José das , Sarmento Bruno
Published: July 2018

The design of systems that are able to deliver drugs in a controlled manner to specific organs, tissues and/or cells targets has been a major goal, as well as a huge challenge, in the field of nanomedicine. Besides the possibility of passive and active targeting, stimuli-responsive nanomedicines can effectively release drugs after being exposed to specific microenvironmental conditions, resulting from natural or pathological processes. In particular, thermo-responsive nanomedicines, systems that release the drug when triggered by variations in microenvironmental temperature, have been shown to be promising for the treatment of multiple medical conditions, including inflammation and cancer. Since inflammatory and cancerous tissues present temperature values above those considered physiological, several nanomedicines have been developed by using thermo-responsive polymers that can be engineered in order to release their cargo in response to mild temperature changes. In such a way, these systems may increase the drug concentration at the desired site, while healthy tissues are minimally affected. This chapter discusses the use of thermo-responsive nanomedicines for the delivery of drugs in the specific context of the gastrointestinal tract. In particular, the importance of nanotechnology in the development of thermo-responsive formulations for the treatment of inflammatory bowel diseases and gastrointestinal cancers is addressed.
Redox-responsive Drug Delivery Systems
Authors: Bhaw-Luximon Archana , Jhurry Dhanjay
Published: July 2018

Disbalanced reactive oxygen species (ROS) and glutathione (GSH) are characteristic features of tumor cells. High intracellular GSH concentration in tumor cells is a well-documented fact that leads to a very high reducing intracellular bio-milieu. High accumulation of ROS is known to occur in almost all cancers and can act as a two-edged sword during tumor development, by either promoting or inhibiting growth. These two features present unique opportunities to design drug delivery systems that are responsive to reduction or/and oxidation stimuli and has attracted accrued interest from researchers. These nanocarriers change their structural integrity, either through disassembly or degradation, to deliver their payload in the presence of the trigger. The aim of this chapter is to summarize the key developments in the design of materials with redox-responsive behaviour and their subsequent application in the field of nanomedicine targeting cancer. Strategies into exploiting both stimuli in a single nano drug delivery system to enhance therapeutic efficacy are also addressed.
Stimuli-responsive Materials in Theranostics
Authors: Wu Hao , Zhang Lu , Li Yuanpei , Lam Kit S.
Published: July 2018

There have been increasing interests in the development of theranostic agents, with both diagnostic and therapeutic components integrated into a single delivery system. Stimuli-responsive materials are ideal building blocks for the design and construction of smart theranostic systems with improved therapeutic and diagnostic functions against cancer and other diseases. This chapter will exclusively focus on the attempts towards the use of smart stimuli-responsive materials for developing theranostic systems.
Regulatory and Commercialization Challenges with Stimuli-responsive Nanomedicines
Authors: Singh Amit , Amiji Mansoor M.
Published: July 2018

Nanotechnology aids in the development of smart materials that are capable of overcoming biological barriers and deliver drugs and biologics to the desired site of action with precision. Design and development of such smart materials relies heavily on our improved understanding of the biological barriers, material–biology interaction and our ability to tailor the property of materials to perform a specific function based on the microenvironment of the target tissue and cell. Recent years have seen an increase in efforts to develop such smart materials, but their advancement into clinics and subsequently to the marketplace has been challenging and slow. Being an emerging technology, the challenges in part lie in the three-dimensional (3D) complexity of the nanomaterial constructs, the properties of which can be dramatically different from their individual components and thus the lack of an appropriate yardstick to ensure product quality impedes the development process. Prior experience suggests that a subtle change in the product profile can drastically influence its biological and pharmaceutical performance. This chapter will highlight some key developmental, manufacturing, and regulatory considerations in nanotechnology-based medicines.
Squaryl group modified phosphoglycolipid analogs as potential modulators of GPR55
Authors: Ding Feiqing , Guy Adam T. , Greimel Peter , Hirabayashi Yoshio , Kamiguchi Hiroyuki , Ito Yukishige
Published: July 2018

We report the facile synthesis of a series of LPGlc analogs, their GPR dependent biological activity and a systematic analysis of the structure–activity relationship in regards to GPR55 modulation.
A neptunium(v)-mediated interwoven transuranium-rotaxane network incorporating a mechanically interlocked [c2]daisy chain unit
Authors: Mei Lei , Xu Chao , Wu Qun-yan , Hu Kong-qiu , Yuan Li-yong , Chen Jing , Xiao Cheng-liang , Wang Shu-ao , Chai Zhi-fang , Shi Wei-qun
Published: July 2018

A combination of an NpVcenter and a cucurbituril-based pseudorotaxane ligand generates the first transuranium-rotaxane complex, NRCP-1, which has a mechanically-interlocked [c2]daisy chain unit.
Structural study of mono-, di- and tetranuclear complexes of the {Re(CO)3}+fragment with thiosemicarbazone/thiosemicarbazonate ligands containing benzothiazole or benzoxazole groups
Authors: Pino-Cuevas Arantxa , Graña Ana , Abram Ulrich , Carballo Rosa , Vázquez-López Ezequiel M.
Published: July 2018

Thiosemicarbazone form mononuclear and dinuclear complexes as bidentate ligands with {Re(CO)3}+and a tetranuclear complex with unusual bideprotonated thiosemicarbazonate.
Particulate photocatalyst sheets based on non-oxide semiconductor materials for water splitting under visible light irradiation
Authors: Hisatomi Takashi , Yamamoto Takahiro , Wang Qian , Nakanishi Takahiro , Higashi Tomohiro , Katayama Masao , Minegishi Tsutomu , Domen Kazunari
Published: July 2018

Photocatalyst sheets active in visible-light-driven water splitting, potentially under irradiation of up to 600 nm, are developed.
Sequential catalysis controls selectivity in electrochemical CO2 reduction on Cu
Authors: Lum Yanwei , Ager Joel W.
Published: July 2018

A sequential pathway with CO as an intermediate species allows for control of oxygenate selectivity in electrochemical reduction of CO2.
Stereochemistry-dependent hydrogen bonds stabilise stacked conformations in jet-cooled cyclic dipeptides: (LD) vs. (LL) cyclo tyrosine–tyrosine
Authors: BenNasr Feriel , Pérez-Mellor Ariel , Alata Ivan , Lepere Valeria , Jaïdane Nejm-Eddine , Zehnacker Anne
Published: July 2018

Changing the chirality of one residue prevents the formation of an OH⋯O intramolecular hydrogen bond in cyclo di-tyrosine.
Matrix complexity effect on platinum group metals analysis using inductively coupled plasma optical emission spectrometry
Authors: Kim Jihye , Anawati John , Azimi Gisele
Published: July 2018

Investigation of the effect of matrix complexity on the quantitative analysis of PGMs using ICP-OES.
A concise synthesis of cyclobrassinin and its analogues via a thiyl radical aromatic substitution
Authors: Zhong Xin , Chen Ning , Xu Jiaxi
Published: July 2018

Cyclobrassinin and its six and seven-membered ring analogues have been synthesized through a thiyl radical-mediated intramolecular aromatic substitution of brassinin derivatives.
Tunable thermal conductivity of π-conjugated two-dimensional polymers
Authors: Ma Hao , O'Donnel Erica , Tian Zhiting
Published: July 2018

Two-dimensional (2D) polymers are organic analogues of graphene.
High thermoelectric performance of Cu3SbSe4 nanocrystals with Cu2−xSe in situ inclusions synthesized by a microwave-assisted solvothermal method
Authors: Xie Dandan , Zhang Bin , Zhang Aijuan , Chen Yongjin , Yan Yanci , Yang Hengquan , Wang Guiwen , Wang Guoyu , Han Xiaodong , Han Guang , Lu Xu , Zhou Xiaoyuan
Published: July 2018

The Cu2–xSe nanoinclusions lead to reduced κL and enhanced zT in Cu3SbSe4.
Visualizing charges accumulated in an electric double layer by three-dimensional open-loop electric potential microscopy
Authors: Hirata Kaito , Kitagawa Takuya , Miyazawa Keisuke , Okamoto Takahiro , Fukunaga Akira , Takatoh Chikako , Fukuma Takeshi
Published: July 2018

Charge accumulation behavior at the Au–electrolyte interface was visualized by three-dimensional open-loop electric potential microscopy with a varying electrode potential.
Compartmentalized nanoparticles in aqueous solution through hierarchical self-assembly of triblock glycopolymers
Authors: Piloni Alberto , Walther Andreas , Stenzel Martina H.
Published: July 2018

Amphiphilic block copolymers can elegantly assemble in water to form well-defined nano-objects and through smart design of the polymers it is possible to efficiently prepare functional materials for biomedical applications such as drug carriers.
Structural, magnetic and electronic properties of CrO2 at multimegabar pressures
Authors: Huang Shengxuan , Wu Xiang , Niu Jingjing , Qin Shan
Published: July 2018

CrO2 can undergo the pressure-induced phase transition sequence of rutile-type → CaCl2-type → pyrite-type → Pnma → (Fe2P-type→) I4/mmm.
Dewetting transitions coupled to K-channel activation in cytochrome c oxidase
Authors: Supekar Shreyas , Kaila Ville R. I.
Published: July 2018

Cytochrome c oxidase (CcO) drives aerobic respiratory chains in all organisms by transducing the free energy from oxygen reduction into an electrochemical proton gradient across a biological membrane.
The role of Ag in aqueous solution processed (Ag,Cu)2ZnSn(S,Se)4kesterite solar cells: antisite defect elimination and importance of Na passivation
Authors: Huang Wei-Chih , Wei Shih-Yuan , Cai Chung-Hao , Ho Wei-Hao , Lai Chih-Huang
Published: July 2018

Kesterite with a high Ag content processed at low temperature without CuZnantisite defects using aqueous spray pyrolysis reaches 10% efficiency.
A new and highly robust light-responsive Azo-UiO-66 for highly selective and low energy post-combustion CO2 capture and its application in a mixed matrix membrane for CO2/N2 separation
Authors: Prasetya Nicholaus , Donose Bogdan C. , Ladewig Bradley P.
Published: July 2018

A new and robust generation-2 light-responsive MOF with UiO-66 topology applicable for post combustion CO2 capture has been successfully synthesized and is described in this article.
Enhancing the sensitivity of colorimetric lateral flow assay (CLFA) through signal amplification techniques
Authors: Ye Haihang , Xia Xiaohu
Published: July 2018

This article highlights recent signal amplification techniques for enhancing the detection sensitivity of colorimetric lateral flow assay.
Single molecular precursor ink for AgBiS2 thin films: synthesis and characterization
Authors: Gu Ening , Lin Xianzhong , Tang Xiaofeng , Matt Gebhard J. , Osvet Andres , Hou Yi , Jäger Sebastian , Xie Chen , Karl André , Hock Rainer , Brabec Christoph J.
Published: July 2018

The coordination chemistry of Ag–Bi–TU–DMSO molecular ink was studied. AgBiS2 thin films feature mixed band structures and show photoconductivity response.
Mitochondrial dysfunction and neurodegenerative proteinopathies: mechanisms and prospects for therapeutic intervention
Authors: Briston Thomas , Hicks Amy R.
Published: July 2018

Neurodegenerative proteinopathies are a group of pathologically similar, progressive disorders of the nervous system, characterised by structural alterations within and toxic misfolding of susceptible proteins. Oligomerisation of Aβ, tau, α-synuclein and TDP-43 leads to a toxin gain- or loss-of-function contributing to the phenotype observed in Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and frontotemporal dementia. Misfolded proteins can adversely affect mitochondria, and post-mitotic neurones are especially sensitive to metabolic dysfunction. Misfolded proteins impair mitochondrial dynamics (morphology and trafficking), preventing functional mitochondria reaching the synapse, the primary site of ATP utilisation. Furthermore, a direct association of misfolded proteins with mitochondria may precipitate or augment dysfunctional oxidative phosphorylation and mitochondrial quality control, causing redox dyshomeostasis observed in disease. As such, a significant interest lies in understanding mechanisms of mitochondrial toxicity in neurodegenerative disorders and in dissecting these mechanisms with a view of maintaining mitochondrial homeostasis in disease. Recent advances in understanding mitochondrially controlled cell death pathways and elucidating the mitochondrial permeability pore bioarchitecture are beginning to present new avenues to target neurodegeneration. Novel mitochondrial roles of deubiquitinating enzymes are coming to light and present an opportunity for a new class of proteins to target therapeutically with the aim of promoting mitophagy and the ubiquitin–proteasome system. The brain is enormously metabolically active, placing a large emphasis on maintaining ATP supply. Therefore, identifying mechanisms to sustain mitochondrial function may represent a common intervention point across all proteinopathies.
Intratubular and intracellular renin–angiotensin system in the kidney: a unifying perspective in blood pressure control
Authors: Li Xiao C. , Zhu Dongmin , Zheng Xiaowen , Zhang Jiangfeng , Zhuo Jia L.
Published: July 2018

The renin–angiotensin system (RAS) is widely recognized as one of the most important vasoactive hormonal systems in the physiological regulation of blood pressure and the development of hypertension. This recognition is derived from, and supported by, extensive molecular, cellular, genetic, and pharmacological studies on the circulating (tissue-to-tissue), paracrine (cell-to-cell), and intracrine (intracellular, mitochondrial, nuclear) RAS during last several decades. Now, it is widely accepted that circulating and local RAS may act independently or interactively, to regulate sympathetic activity, systemic and renal hemodynamics, body salt and fluid balance, and blood pressure homeostasis. However, there remains continuous debate with respect to the specific sources of intratubular and intracellular RAS in the kidney and other tissues, the relative contributions of the circulating RAS to intratubular and intracellular RAS, and the roles of intratubular compared with intracellular RAS to the normal control of blood pressure or the development of angiotensin II (ANG II)-dependent hypertension. Based on a lecture given at the recent XI International Symposium on Vasoactive Peptides held in Horizonte, Brazil, this article reviews recent studies using mouse models with global, kidney- or proximal tubule-specific overexpression (knockin) or deletion (knockout) of components of the RAS or its receptors. Although much knowledge has been gained from cell- and tissue-specific transgenic or knockout models, a unifying and integrative approach is now required to better understand how the circulating and local intratubular/intracellular RAS act independently, or with other vasoactive systems, to regulate blood pressure, cardiovascular and kidney function.
Der akute Gichtanfall in der zentralen Notaufnahme
Authors: Engel Bettina , Schacher Sylvia , Weckbecker Klaus , Stausberg Annika , Gräff Ingo
Published: July 2018

Hintergrund Die akute Arthritis urica ist eine i. d. R. durch Allgemeinmediziner behandelte Erkrankung. Die Prävalenz beträgt etwa 1,4% und kommt im höheren Lebensalter häufiger vor (bis zu 4,2% bei Männern > 75 Jahre). Bisher wurde in Deutschland noch nicht evaluiert, wann und bei welchen Patienten mit akuter Arthritis urica eine Behandlung in einer zentralen Notaufnahme stattfindet und ob diese leitliniengerecht stattfindet. Diese Studie evaluiert daher Charakteristika und Behandlungspfade von Notfallpatienten mit akutem Gichtanfall in einer zentralen Notaufnahme in Deutschland.

Methoden Retrospektive Analyse der Patienten mit den ICD-Codes M10.xx von 05/2013 bis 04/2016 in der zentralen Notaufnahme eines universitären Krankenhauses.

Ergebnisse 65 Patienten stellten sich im o. g. Zeitraum aufgrund eines akuten Gichtanfalles vor. 42 Patienten (65%) stellten sich außerhalb der Praxisöffnungszeiten vor. Anamnestisch gaben 31 (47,69%) Patienten eine bekannte Hyperurikämie an, davon 22 (70,96%) mit Gichtanfall in der Vorgeschichte. Es stellten sich 48 (73%) Patienten mit einer Monarthritis vor, davon 40 mit Podagra (68%). Diagnostisch wurde bei 57 (86%) eine Blutentnahme durchgeführt. Eine Röntgenaufnahme des betroffenen Gelenks erfolgte bei 31 (48%) Patienten, 67% davon ohne Indikation. Eine Gelenkpunktion mit Kristallnachweis erfolgte bei 4 Patienten. Zwölf Patienten (18%) wurden fachspezifisch stationär aufgenommen zur chirurgischen Revision und/oder antibiotischen Behandlung. 51 Patienten (78%) erhielten primär nicht steroidale Antirheumatika (NSAR), 7 in Kombination mit Glukokortikoiden und 4 Kolchizin. Vor der NSAR-Gabe war bei 17 Patienten die Nierenfunktion nicht bekannt oder eingeschränkt. Elf Patienten (16%) erhielten weder NSAR, Kortison noch Kolchizin. Zehn Patienten (15%) erhielten im akuten Gichtanfall eine harnsäuresenkende Therapie bzw. deren Dosierung wurde verändert. Zusätzlich erhielten 63% der Patienten eine Empfehlung zur Durchführung nicht medikamentöser Maßnahmen.

Schlussfolgerungen Wir konnten zeigen, dass die pharmakologische Behandlung der Patienten mit einem akuten Gichtanfall größtenteils leitliniengerecht erfolgt. Jedoch sollte die Vigilanz bez. der Nierenfunktion vor NSAR-Gabe geschärft werden. Überwiegend stellten sich die Patienten außerhalb der Praxisöffnungszeiten vor, was die primär ambulante Versorgung der Gichtpatienten bestätigt. Die aktuellen Leitlinien empfehlen die Diagnose der unkomplizierten Gicht anhand rein klinischer Diagnosekriterien. Dementgegen fand sich eine Überversorgung mit diagnostischen Maßnahmen in der zentralen Notaufnahme. Abschließend zeigte unsere Untersuchung, dass diese klinischen Diagnosekriterien besser im klinischen Alltag implementiert werden sollten, um unnötige Röntgen- und Laboruntersuchungen zu vermeiden.
Welche Behandlung wirkt beim Hörsturz am besten?
Authors: Schartinger Volker
Published: July 2018

Ashtiani MK at al. Efficacy of systemic and intratympanic corticosteroid combination therapy versus intratympanic or systemic therapy in patients with idiopathic
sudden sensorineural hearing loss: a randomized controlled trial. Eur Arch Otorhinolaryngol 2018; 275: 89–7

Iranische HNO-Ärzte verglichen die Heilungsraten einer Behandlung des idiopathischen Hörsturzes mit oralen und intratympanalen Kortikosteroidgaben in Mono-
und Kombinationstherapien.
Ergebnisse der langjährigen Substitutionsbehandlung Opiatabhängiger – die SubsCare-Studie
Authors: Zippel-Schultz Bettina , Specka Michael , Stöver Heino , Nowak Manfred , Cimander Konrad , Maryschok Markus , Poehlke Thomas , Helms Thomas , Scherbaum Norbert
Published: July 2018

Ziel Erhebung des gesundheitlichen und sozialen Zustands von mehr als 5 Jahre opiatsubstituierten Patienten.

Methodik 130 Patienten aus 12 Praxen wurden über 2 Jahre beobachtet und mittels standardisierter Fragebögen befragt.

Ergebnisse Die Haltequote über 2 Jahre betrug 82,3%; nur 4 Patienten beendeten die Behandlung regulär. 25% waren durchgehend frei von Alkohol und Drogen. 25% waren kontinuierlich sozialversicherungspflichtig beschäftigt. Die Mehrheit wies Komorbiditäten sowie Defizite in der sozialen Teilhabe auf.

Schlussfolgerung Viele Patienten erreichten Stabilität im Hinblick auf Abstinenz von Suchtmitteln und soziale Teilhabe. Jedoch zeigt eine große Patientengruppe körperliche und psychische Begleiterkrankungen sowie noch erhebliche Defizite in der Teilhabe. Vor allem für diese Patienten erscheint eine zeitliche Limitierung der Substitutionsbehandlung nicht realitätsgerecht.
Warum die Zertifizierung von Darmkrebszentren die chirurgische Ergebnisqualität nicht verbessert
Authors: Vogel Peter Alexander
Published: July 2018

Hintergrund Die Zertifizierung von Darmkrebszentren führt zu einer interdisziplinären Behandlung nach Leitlinien. Die Ergebnisse der zertifizierten Zentren werden jährlich publiziert. Die Jahresvergleiche zeigen, dass sich die chirurgische Ergebnisqualität gemessen anhand der Indikatoren Anastomoseninsuffizienz, Wundinfekt und Revisionsoperationen zwischen 2009 und 2015 nicht verbessert hat.

Patienten und Methoden In einer nach London-Protokoll strukturierten Morbiditäts- und Mortalitätskonferenz (M+M-Konferenz) wurden Patienten mit Anastomoseninsuffizienz (AI) nach kolorektaler Resektion wegen Adenokarzinom analysiert. Die Ergebnisse wurden mit den im Erhebungsbogen der Deutschen Krebsgesellschaft (DKG) für die Zertifizierung von Zentren genannten Prozess- und Strukturparametern verglichen.

Ergebnisse Von 2015 bis 2017 wurden 387 kolorektale Resektionen durchgeführt. 158 Resektionen erfolgten unter der Diagnose eines kolorektalen Karzinoms. Bei 13/149 Resektionen mit Anastomose musste eine Insuffizienz diagnostiziert werden (8,7%). Alle Patienten mit einer AI wurden in einer nach London-Protokoll strukturierten M+M-Konferenz analysiert. Bei 10/13 Patienten wurden Auffälligkeiten im Bereich von Struktur- oder Prozessqualität benannt. Dies betraf hinsichtlich der Prozessqualität die Handhabung von Standards (n = 6/10), die Kommunikation (n = 3/10) und das Fehlen benötigter Untersuchungsergebnisse (n = 1/10). Hinsichtlich der Strukturqualität standen nicht ausreichende materielle Ressourcen im Vordergrund (3/10). Nur 1/13 Auffälligkeiten wird in den im Erhebungsbogen (EB) genannten Struktur- oder Prozessparametern abgebildet.

Schlussfolgerung Voraussetzung dafür, dass Prozesse und Strukturen die Ergebnisqualität verbessern, ist, dass sie relevanten Einfluss auf die Ergebnisqualität haben. Unsere Untersuchung ergab, dass nur 1/13 der in der nach London-Protokoll strukturierten M+M-Konferenz gefundenen Auffälligkeiten im EB abgefragt wird. Um Prozess- und Strukturparameter, die in der konkreten klinischen Praxis an der Entstehung und am Verlauf von Komplikationen (hier AI) beteiligt sind, besser abzubilden, sollten Ergänzungen im EB der DKG diskutiert werden.
Homzygous Protein S Deficiency due to a One Base Pair Deletion that Leads to a Stop Codon in Exon III of the Protein S Gene
Authors: Gómez E , Ledford M R , Pegelow C H , Reitsma P H , Bertina R M
Published: July 2018

Homozygous protein S (PS) deficiency is a very rare disorder that causes purpura fulminans in affected newborns. This report describes the molecular genetic abnormality of a severe PS deficient child who developed purpura fulminans shortly after birth. The mutation was identified as a deletion of one adenine in codon 43 of exon III of the PROS 1 gene. This mutation results in a frameshift and a novel stop codon at position 45. The proband was apparently homozygous and his mother heterozygous for this mutation. The proband’s father was not available for study.

The single base pair deletion predicts a truncated translation product, where Lys 43 and Tyr 44 have been replaced by Asn 43 and Thr 44. This putative protein (predicted mw of 5.696 daltons) contains only the gammacarboxyglutamic acid (Gla) domain and the aromatic stack.
Assessment of the Validity of the INR System for Patients with Liver Impairment
Authors: Kovacs M J , Wong A , MacKinnon K , Weir K , Keeney M , Boyle E , Cruickshank M
Published: July 2018

The INR system was developed to standardize PT reporting in patients on oral anticoagulants. We prospectively collected blood samples from 29 patients with liver impairment (INR 1.5-3.5). Control patients were on warfarin (n = 31). PT’s were measured on an ACL-300 with three thromboplastin reagents. INR’s were calculated using instrument specific ISI’s. Other tests performed were FDP’s, fibrinogen, aPTT, factors II, V, VII and X. The INR’s for each patient in the study population using the three thromboplastin reagents were significantly different (p = 0.0001). Those for the control population were not (p = 0.0658). Fibrinogen, factors V, II and X were different at the 5% level of significance between the populations. FDP’s were detected in 17 study subjects. The INR system is not valid for comparison of patients with liver impairment because different reagents do not give the same INR for the same sample. It is, however, no less valid than the use of PT with different thromboplastin reagents. Further study is recommended.
Non-Fasting Factor VII Coagulant Activity (FVII:C) Increased by High-Fat Diet
Authors: Bladbjerg E M , Marckmann P , Sandström B , Jespersen J
Published: July 2018

Preliminary observations have suggested that non-fasting factor VII coagulant activity (FVII:C) may be related to the dietary fat content. To confirm this, we performed a randomised cross-over study. Seventeen young volunteers were served 2 controlled isoenergetic diets differing in fat content (20% or 50% of energy). The 2 diets were served on 2 consecutive days. Blood samples were collected at 8.00 h, 16.30 h and 19.30 h, and analysed for triglycerides, FVII coagulant activity using human (FVII:C) or bovine thromboplastin (FVII:Bt), and FVII amidolytic activity (FVIPAm). The ratio FVII:Bt/FVII:Am (a measure of FVII activation) increased from fasting levels on both diets, but most markedly on the high-fat diet. In contrast, FVII: Am (a measure of FVII protein) tended to decrease from fasting levels on both diets. FVII:C rose from fasting levels on the high-fat diet, but not on the low-fat diet. The findings suggest that high-fat diets increase non-fasting FVII:C, and consequently may be associated with increased risk of thrombosis.