bluuebunny/crossref_metadata_2025 huggingface dataset:
Sustainable In Situ Carbothermal Reduction Route to Biochar Stabilized Ru–Cu Nanoalloys from Lignocellulosic Biomass as a Highly Efficient and Durable Catalyst
Authors: Chen Si‐Qin , Ling Li‐Li , Zhang Shun , Jiang Shun‐Feng , Xu Zhuoran , Liu Wu‐Jun , Jiang Hong
Published: November 2017

Carbon‐based functional materials have extensive applications in the fields of catalysis, energy storage, and conversion, as well as environmental science. However, it remains challenging to synthesize these materials in an economically sustainable way. This work demonstrates an in situ carbothermal reduction route to prepare biochar stabilized Ru–Cu nanoalloys (Ru–Cu/biochar) with low Ru loading (0.16 wt%) by pyrolysis of lignocellulosic biomass waste. The as‐synthesized Ru–Cu/biochar shows excellent catalytic performance toward Cr(VI) reduction by hydrazine (N2H4·H2O), with 94% of the Cr(VI) reduced in aqueous solution within 150 s without any additional precipitation process. The catalyst also demonstrates high stability without significant loss of activity after nine cycles. This work offers a sustainable approach to utilize biomass waste to synthesize functional materials as highly efficient and durable catalysts.
Reaction of Thiocarbonyl Fluoride Generated from Difluorocarbene with Amines
Authors: Yu Jiao , Lin Jin‐Hong , Xiao Ji‐Chang
Published: November 2017

The reaction of thiocarbonyl fluoride, generated from difluorocarbene, with various amines under mild conditions is described. Secondary amines, primary amines, and o‐phenylenediamines are converted to thiocarbamoyl fluorides, isothiocyanates, and difluoromethylthiolated heterocycles, respectively. Thiocarbamoyl fluorides were further transformed into trifluoromethylated amines by using a one‐pot process. Thiocarbonyl fluoride is generated in situ and is rapidly fully converted in one pot under mild conditions; therefore, no special safety precautions are needed.
A Copper(II) Phenanthroline Metallopeptide That Targets and Disrupts Mitochondrial Function in Breast Cancer Stem Cells
Authors: Laws Kristine , Bineva‐Todd Ganka , Eskandari Arvin , Lu Chunxin , O'Reilly Nicola , Suntharalingam Kogularamanan
Published: November 2017

The breast cancer stem cell (CSC) and bulk breast cancer cell potency of a series of metallopeptides containing dichloro(1,10‐phenanthroline)copper(II) and various organelle‐targeting peptide sequences is reported. The mitochondria‐targeting metallopeptide 1 exploits the higher mitochondrial load in breast CSCs over the corresponding non‐CSCs and the vulnerability of breast CSCs to mitochondrial damage to potently and selectively kill breast CSCs. Strikingly, 1 reduces the formation and size of mammospheres to a greater extent than salinomycin, an established CSC‐potent agent. Mechanistic studies show that 1 enters CSC mitochondria, induces mitochondrial dysfunction, generates reactive oxygen species (ROS), activates JNK and p38 pathways, and prompts apoptosis. To the best of our knowledge, 1 is the first metallopeptide to selectivity kill breast CSCs in vitro.
A Gold‐Catalyzed Domino Cyclization Enabling Rapid Construction of Diverse Polyheterocyclic Frameworks
Authors: He Yi , Li Zhenghua , Robeyns Koen , Van Meervelt Luc , Van der Eycken Erik V.
Published: November 2017

We report herein an efficient gold(I)‐catalyzed post‐Ugi domino dearomatization/ipso‐cyclization/Michael sequence that enables access to libraries of diverse (hetero)arene‐annulated tricyclic heterocycles. This process affords novel complex polycyclic scaffolds in moderate to good yields from readily available acyclic precursors with excellent chemo‐, regio‐, and diastereoselectivity. The power of this strategy has been demonstrated by the rapid synthesis of 40 highly functionalized polyheterocycles bearing indole, pyrrole, (benzo)furan, (benzo)thiophene, pyrazole, and electron‐rich arene groups in two operational steps.
A Strontium‐ and Chlorine‐Free Pyrotechnic Illuminant of High Color Purity
Authors: Glück Johann , Klapötke Thomas M. , Rusan Magdalena , Sabatini Jesse J. , Stierstorfer Jörg
Published: November 2017

The development of a red‐light‐emitting pyrotechnic illuminant has garnered interest from the pyrotechnics community owing to potential regulations by the United States Environmental Protection Agency (U.S. EPA) regarding the use of strontium and chlorinated organic materials. To address these environmental regulatory concerns, the development of lithium‐based red‐light‐emitting pyrotechnic compositions of high purity and color quality is described. These formulations do not contain strontium or chlorinated organic materials. Rather, the disclosed formulations are based on a non‐hygroscopic dilithium nitrogen‐rich salt that serves as both oxidizer and red colorant. These formulations are likely to draw interest from the civilian fireworks and military pyrotechnics communities for further development as they both have a vested interest in the development of environmentally conscious formulations.
Application of industrial solid wastes in catalytic pyrolysis
Authors: Qiu Bingbing , Deng Na , Zhang Yufeng , Wan Haijun
Published: November 2017

The catalytic pyrolysis is one of the thermochemical patterns for producing chemical products consisting of solid char, liquid oil, and pyrolytic gas. A number of parameters affecting the catalytic pyrolysis process, yields, and properties of products such as the temperature, residence time, heating rate, feedstock type, and the use of catalyst were evaluated in details to promote the process of catalytic pyrolysis. Catalytic pyrolysis has emerged with the use of a catalyst such as red mud, fly ash, copper slag, blast furnace slag, coal gangue, and aluminum dross. In this paper, a brief discussion with recent development on industrial solid wastes as a catalyst in catalytic pyrolysis process is presented. In the process, the liquid oil is of higher quality; in addition, process by‐products such as solid char can be used as an adsorbent material, while the quality of pyrolysis gases is improved. Despite all the potential advantages with industrial solid wastes as a catalyst, some limitations such as less reuse of catalyst and high parasitic energy demand are still remaining. The recommended measurements for these challenges include exploration of suitable reactor, catalyst regeneration, and catalytic mechanism optimization.
Cartilage MicroRNA Dysregulation During the Onset and Progression of Mouse Osteoarthritis Is Independent of Aggrecanolysis and Overlaps With Candidates From End‐Stage Human Disease
Authors: Kung Louise H. W. , Ravi Varshini , Rowley Lynn , Angelucci Constanza , Fosang Amanda J. , Bell Katrina M. , Little Christopher B. , Bateman John F.
Published: November 2017

Objective

To identify candidate microRNAs (miRNAs) that potentially regulate the initiation and progression of osteoarthritis (OA).

Methods

OA was induced in 10–12‐week‐old male wild‐type C57BL/6 mice and in mice resistant to aggrecanase cleavage (Acan p.374ALGS→374NVYS) by destabilization of the medial meniscus (DMM). Pathologic changes of OA were scored histologically. RNA from cartilage and subchondral bone was harvested in parallel by laser microdissection at 1 week and 6 weeks postsurgery. Global miRNA expression profiling was performed using Agilent microarrays and was validated by quantitative polymerase chain reaction analysis.

Results

Wild‐type DMM mice had characteristic cartilage degeneration, subchondral bone sclerosis, and osteophyte formation. While no miRNA dysregulation was seen in subchondral bone, 139 miRNAs were differentially expressed in cartilage obtained at 1 and/or 6 weeks after OA initiation from wild‐type mice that underwent DMM. To prioritize OA candidates, dysregulated miRNAs with human orthologs were filtered, and paired miRNA/messenger RNA (mRNA) expression analysis was conducted to identify those with corresponding changes in mRNA target transcripts in the DMM mouse cartilage. An important cohort also overlapped with miRNAs identified in human end‐stage OA. Comparisons of miRNA dysregulation in DMM mouse cartilage where aggrecan cleavage was genetically ablated demonstrated that all candidates were independent of aggrecan breakdown, earmarking these as important to the critical stages of OA initiation. Furthermore, functional enrichment analysis and data annotation revealed the responses to mechanical stimuli, apoptotic processes, and core extracellular matrix structural and regulatory factors to be potentially influenced by OA‐dysregulated miRNA/mRNA networks.

Conclusion

Our comprehensive analyses identified high‐priority miRNA candidates that have potential as biomarkers and therapeutic targets in human OA.
Production of 1,2‐propanediol in photoautotrophic Synechocystis is linked to glycogen turn‐over
Authors: David Christian , Schmid Andreas , Adrian Lorenz , Wilde Annegret , Bühler Katja
Published: November 2017

We utilized a photoautotrophic organism to synthesize 1,2‐propanediol from carbon dioxide and water fueled by light. A synthetic pathway comprising mgsA (methylglyoxal synthase), yqhD (aldehyde reductase), and adh (alcohol dehydrogenase) was inserted into Synechocystis sp. PCC6803 to convert dihydroxyacetone phosphate to methylglyoxal, which is subsequently reduced to acetol and then to 1,2‐propanediol. 1,2‐propanediol could be successfully produced by Synechocystis, at an approximate rate of 55 μmol h−1 gCDW−1. Surprisingly, maximal productivity was observed in the stationary phase. The production of 1,2‐propanediol was clearly coupled to the turn‐over of intracellular glycogen. Upon depletion of the glycogen pool, product formation stopped. Reducing the carbon flux to glycogen significantly decreased final product titers. Optimization of cultivation conditions allowed final product titers of almost 1 g L−1 (12 mM), which belongs to the highest values published so far for photoautotrophic production of this compound.
Simultaneous determination of tilianin and its metabolites in mice using ultra‐high‐performance liquid chromatography with tandem mass spectrometry and its application to a pharmacokinetic study
Authors: Wang Liping , Chen Qingwei , Zhu Lijun , Zeng Xuejun , Li Qiang , Hu Ming , Wang Xinchun , Liu Zhongqiu
Published: November 2017

Tilianin is an active flavonoid glycoside found in many medical plants. Data are lacking regarding its pharmacokinetics and disposition in vivo. The objective of this study was to develop a sensitive, reliable and validated ultra‐high‐performance liquid chromatography with tandem mass spectrometry (UHPLC–MS/MS) method to simultaneously quantify tilianin and its main metabolites and to determine its pharmacokinetics in wild‐type and breast cancer resistance protein knockout (Bcrp1−/−) FVB mice. Chromatographic separation was accomplished on a C18 column by utilizing acetonitrile and 0.5 mm ammonium acetate as the mobile phase. Mass spectrometric detection was performed using electrospray ionization in both positive and negative modes. The results showed that the precision, accuracy and recovery, as well as the stability of tilianin and its metabolites in mouse plasma, were all within acceptable limits. Acacetin‐7‐glucuronide and acacetin‐7‐sulfate were the major metabolites of tilianin in mouse plasma. Moreover, systemic exposure of acacetin‐7‐sulfate was significantly higher in Bcrp1 (−/−) FVB mice compared with wild‐type FVB mice. In conclusion, the fully validated UHPLC–MS/MS method was sensitive, reliable, and was successfully applied to assess the pharmacokinetics of tilianin in wild‐type and Bcrp1 (−/−) FVB mice. Breast cancer resistance protein had a significant impact on the elimination of the sulfated metabolite of tilianin in vivo.
Dilemmas that undermine supervisor confidence
Authors: Thériault Anne , Gazzola Nicola
Published: November 2017

Background

Conventional wisdom links supervisor self‐confidence with experience in supervisory practice.

Aims

This study explored the nature of confidence from an emic perspective.

Method

Twelve experienced Canadian supervisors were interviewed, and data was analysed using Structured Thematic Analysis.

Results

Aspects of the role and process produce tensions that create ambiguity that may diminish self‐confidence. Five main themes were distilled: (a) building supervisee confidence when experiencing self‐doubt as supervisor or clinician;(b) parallel process‐what disturbs therapy disturbs supervision; (c) expert vs. co‐explorer; (d) engaging in supervision while maintaining boundaries; and (e) catch 22 – inviting disclosures of difficulties and evaluation.

Conclusion

The study adds nuance to the scholarly work that informs supervisor self‐confidence.
Characterization of Novel Carbon Foam Corrugated Structured Packings with Varied Corrugation Angle
Authors: Li Hong , Shi Qiang , Yang Xinwei , Li Xingang , Gao Xin
Published: November 2017

Carbon foam was utilized to develop corrugated structured packing in distillation for the first time. The hydrodynamics and mass transfer performance of CFP‐400X and CFP‐500W with 60 and 75° corrugation angle were determined by total reflux experiments. The results indicate that increasing the corrugation angle will improve the capacity but decrease the mass transfer efficiency. Comparisons among CFP‐400X, SCFP‐500X, BX‐500, and B1‐500X were made with respect to the performance of hydrodynamics and mass transfer. CFP‐400X shows advantages in terms of capacity and efficiency compared with the other two metal packings. SCFP‐500X exhibits a higher mass transfer efficiency than CFP‐400X because of its superior wettability of test liquid which is supported by the liquid flow behavior experiment.
Multimodal image analysis in tissue diagnostics for skin melanoma
Authors: Guo Shuxia , Pfeifenbring Susanne , Meyer Tobias , Ernst Günther , von Eggeling Ferdinand , Maio Vincenza , Massi Daniela , Cicchi Riccardo , Pavone Francesco S. , Popp Jürgen , Bocklitz Thomas
Published: November 2017

Early diagnosis is a corner stone for a successful treatment of most diseases including melanoma, which cannot be achieved by traditional histopathological inspection. In this respect, multimodal imaging, the combination of TPEF and SHG, features a high diagnostic potential as an alternative approach. Multimodal imaging generates molecular contrast, but to use this technique in clinical practice, the optical signals must be translated into diagnostic relevant information. This translation requires automatic image analysis techniques. Within this contribution, we established an analysis pipeline for multimodal images to achieve melanoma diagnostics of skin tissue. The first step of the image analysis was the pre‐treatment, where the mosaicking artifacts were corrected and a standardization was performed. Afterwards, the local histogram‐based first‐order texture features and the local gray‐level co‐occurrence matrix (GLCM) texture features were extracted in multiple scales. Thereafter, we constructed a local hierarchical statistical model to distinguish melanoma, normal epithelium, and other tissue types. The results demonstrated the capability of multimodal imaging combined with image analysis to differentiate different tissue types. Furthermore, we compared the histogram and the GLCM‐based texture feature sets according to the Fisher's discriminant ratio (FDR) and the prediction of the classification, which demonstrated that the histogram‐based texture features are superior to the GLCM features for the given task. Finally, we performed a global classification to achieve a patient diagnostics with the clinical diagnosis as ground truth. The agreement of the prediction and the clinical results demonstrated the great potential of multimodal imaging for melanoma diagnostics.
Cubane Cross‐Coupling and Cubane–Porphyrin Arrays
Authors: Bernhard Stefan S. R. , Locke Gemma M. , Plunkett Shane , Meindl Alina , Flanagan Keith J. , Senge Mathias O.
Published: November 2017

Invited for the cover of this issue is the group of Mathias O. Senge at Trinity College Dublin. The image depicts cubanes and new methods to attach functionalities onto the cubane core. Read the full text of the article at 10.1002/chem.201704344.
The influence of Ni and Co concentration in the electroplating bath on Ni‐Co‐W alloys properties
Authors: Baldessin Caio Felipe , de Morais Nepel Thayane Carpanedo , de Almeida Neto Ambrósio Florêncio
Published: November 2017

In this study, we evaluated the influence of nickel and cobalt concentrations in an electrochemical bath for a ternary Ni‐Co‐W coating alloy electrodeposition. The X‐ray diffraction indicated formation of amorphous coating alloys for higher Co concentration and a crystalline coating alloys for higher Ni concentration. Statistical evaluation showed a mathematical model connecting the increase of alloy deposition efficiency and the Ni and Co concentration in the electrochemical bath. Corrosion tests indicated that coating alloys with higher Ni concentration, which are crystalline alloys, showed higher polarization resistance (in NaCl 0.1 mol/L) indicating that composition can influence the corrosion resistance more than the crystallinity.
Cover Picture: A Three‐dimensional Non‐fullerene Small Molecule Acceptor for Solution‐processed Organic Solar Cells (Chin. J. Chem. 11/2017)
Authors: Chang Meijia , Wang Yunchuang , Qiu Nailiang , Yi Yuan‐Qiu‐Qiang , Wan Xiangjian , Li Chenxi , Chen Yongshen
Published: November 2017

The cover picture shows a new three‐dimensional non‐fullerene small molecular acceptor for solution‐processed organic solar cells. The acceptor was named SFTTIC using spiro‐bifluorene as the core unit linking with four thieno[3,2‐b]thiophenes and end‐capped with 2‐(3‐oxo‐2,3‐dihydro‐1H‐inden‐1‐ylidene)malononitrile. SFTTIC has a high absorption coefficient, good thermal stability and appropriate energy levels and the optimized power conversion efficiency (PCE) of 5.66% was achieved for the devices with PBDB‐T as donor material. These results indicate that the 3D non‐fullerene small molecule is potential for achieving high photovoltaic performance. More details are discussed in the article by Chen et al. on page 1687–1692.

image
ShapeFit: Exact Location Recovery from Corrupted Pairwise Directions
Authors: Hand Paul , Lee Choongbum , Voroninski Vladislav
Published: November 2017

Let t1,…,tn ∊ ℝd for d ≥ 2 and consider the location recovery problem: given a subset of pairwise direction observations , where a constant fraction of these observations are arbitrarily corrupted, find up to a global translation and scale. We propose a novel algorithm for the location recovery problem, which consists of a simple convex program over $dn$ real variables. We prove that this program recovers a set of n i.i.d. Gaussian locations exactly and with high probability if the observations are given by an Erdős‐Rényi graph, with d large enough, and provided that at most a constant fraction of observations involving any particular location are adversarially corrupted. We also prove that the program exactly recovers Gaussian locations for d = 3 if the fraction of corrupted observations at each location is, up to poly‐logarithmic factors, at most a constant. Both of these recovery theorems are based on a set of deterministic conditions that we prove are sufficient for exact recovery. © 2017 Wiley Periodicals, Inc.
Industry Perspective on Biomarker Development and Qualification
Authors: Gerlach Cory V. , Derzi Mazin , Ramaiah Shashi K. , Vaidya Vishal S.
Published: November 2017

Pharmaceutical and biotechnology companies routinely use biomarkers to obtain quantitative metrics for drug exposure, efficacy, and safety and to inform clinical trial design with regard to patient selection, treatments, and outcomes. Biomarker science has the unique capability to catalyze precompetitive collaborations between academia, industry, regulatory agencies, and other stakeholders with the ultimate goal of accelerating the delivery of safe and effective medicines to patients, particularly in areas of high unmet need.
Epidemiology of type 1 diabetes in Polish children: A multicentre cohort study
Authors: Szalecki Mieczysław , Wysocka‐Mincewicz Marta , Ramotowska Anna , Mazur Artur , Lisowicz Lucyna , Beń‐Skowronek Iwona , Sieniawska Joanna , Klonowska Bożena , Charemska Dorota , Nawrotek Jolanta , Jałowiec Irena , Bossowski Artur , Jamiołkowska Milena , Pyrżak Beata , Miszkurka Grażyna , Szypowska Agnieszka
Published: November 2017

Background

The incidence of childhood type 1 diabetes (T1D) varies greatly between populations, and the estimates and/or predictions of the rates would aid in adequate planning of health care resources. The study's aim was to assess the incidence of T1D in the paediatric population of eastern and central Poland.

Methods

In this cohort study covering the period from January 2010 to December 2014, data were collected for children and adolescents below 18 years of age with newly diagnosed T1D living in eastern and central Poland. A total of 2174 children were included in the analysis. The population estimates were from the Central Statistical Office of Poland.

Results

Overall, the annual incidence of T1D increased from 12.84/100,000 in 2010 to 18.46/100,000 in 2014 with the incidence rate (IR) ratio of 1.5 (an increase in the IR by 12.7% per year over 5 years). The lowest increase in the IR by 7.1% per year was seen in 15 to 17‐year‐olds. In the urban population (age 0‐17 years), the overall incidence rate was significantly higher than in subjects from rural communities (P < .02). The incidence of T1D in rural areas was significantly higher (p = .004) in voivodeships of higher population density. Such dependence was not observed in urban areas.

Conclusions

The incidence of T1D in children living in eastern and central Poland increased 1.5‐fold over the 5‐year observation period with the highest rise in 10 to 14‐year‐olds and significantly higher rates in urban children compared with their peers living in rural areas.
Reintroduction of the endangered and endemic plant speciesCochlearia bavarica—Implications from conservation genetics
Authors: Kaulfuß Franziska , Reisch Christoph
Published: November 2017

Population reintroduction is a common practice in conservation, but often fails, also due to the effects of inbreeding or outbreeding depression.Cochlearia bavaricais a strongly endangered plant species endemic to Bavaria in Germany, constantly declining since the late 1980s. Therefore, population reintroduction is intended. In this study, we analyzed genetic diversity within and genetic differentiation between all 32 remnant populations of the species in Swabia and Upper Bavaria using amplified fragment length polymorphisms. Our aim was to increase reintroduction success by providing data to avoid negative effects of inbreeding and outbreeding and to preserve the natural genetic pattern of the species. Genetic diversity within populations was low but similar to other rare and endemic species and varied strongly between populations but did not depend on population size. Our analysis revealed a strong geographic pattern of genetic variation. Genetic differentiation was strongest between Swabia and Upper Bavaria and at the population level, whereas differentiation between subpopulations was comparatively low. Isolation by distance and genetic differentiation was stronger among populations from Upper Bavaria than from Swabia. From the results of our study, we derived recommendations for a successful reintroduction of the species. We suggest using rather genetically variable than large populations as reintroduction sources. Moreover, the exchange of plant material between Swabia and Upper Bavaria should be completely avoided. Within these regions, plant material from genetically similar populations should preferably be used for reintroduction, whereas the exchange among subpopulations seems to be possible without a negative impact on genetic variation due to natural gene flow.
The value of information for woodland management: updating a state–transition model
Authors: Morris William K. , Runge Michael C. , Vesk Peter A.
Published: November 2017

Value of information (VOI) analyses reveal the expected benefit of reducing uncertainty to a decision maker. Most ecological VOI analyses have focused on population models rarely addressing more complex community models. We performed a VOI analysis for a complex state–transition model of Box‐Ironbark Forest and Woodland management. With three management alternatives (limited harvest/firewood removal (HF), ecological thinning (ET), and no management), managing the system optimally (for 150 yr) with the original information would, on average, increase the amount of forest in a desirable state from 19% to 35% (a 16‐percentage point increase). Resolving all uncertainty would, on average, increase the final percentage to 42% (a 19‐percentage point increase). However, only resolving the uncertainty for a single parameter was worth almost two‐thirds the value of resolving all uncertainty. We found the VOI to depend on the number of management options, increasing as the management flexibility increased. Our analyses show it is more cost‐effective to monitor low‐density regrowth forest than other states and more cost‐effective to experiment with the no‐management alternative than the other management alternatives. Importantly, the most cost‐effective strategies did not include either the most desired forest states or the least understood management strategy, ET. This implies that managers cannot just rely on intuition to tell them where the most VOI will lie, as critical uncertainties in a complex system are sometimes cryptic.
Multiple species of cuckoos are superior predictors of bird species richness in Asia
Authors: Møller Anders Pape , Morelli Federico , Benedetti Yanina , Mousseau Timothy , Su Tongping , Zhou Bo , Tryjanowski Piotr , Liang Wei
Published: November 2017

The abundance and the presence of common cuckoos Cuculus canorus have been shown to predict species richness of birds across Europe, while there are no such analyses available for other continents where species richness of parasitic cuckoos is larger. Here, we tested whether species richness of birds increased with the number of cuckoo species in two study areas in China and one in Japan. We also tested whether species richness of birds can be predicted by the number of cuckoo individuals. Furthermore, we compared the strength of association between overall bird species richness and species richness of cuckoos, Paridae, Corvidae, and birds of prey. This is the first study demonstrating that cuckoo species richness is more strongly associated with overall bird species richness than richness of species belonging to other families, and rather than occurrence of a single cuckoo species, as already demonstrated for the common cuckoo in Europe. The number of cuckoo species was positively associated with both non‐host and host species richness. We found evidence of the number of cuckoo species being associated with species richness of birds independently of country and year, while abundance of individual cuckoos was not a statistically significant predictor. Furthermore, we showed that richness of host species is strongly positively correlated with overall bird species richness in both countries. This implies that the high species richness of cuckoos in South‐East Asia is a reliable predictor of overall bird species richness.
Calcineurin inhibitor‐induced complement system activation via ERK1/2 signalling is inhibited by SOCS‐3 in human renal tubule cells
Authors: Loeschenberger Beatrix , Niess Lea , Würzner Reinhard , Schwelberger Hubert , Eder Iris E. , Puhr Martin , Guenther Julia , Troppmair Jakob , Rudnicki Michael , Neuwirt Hannes
Published: November 2017

One factor that significantly contributes to renal allograft loss is chronic calcineurin inhibitor (CNI) nephrotoxicity (CIN). Among other factors, the complement (C‐) system has been proposed to be involved CIN development. Hence, we investigated the impact of CNIs on intracellular signalling and the effects on the C‐system in human renal tubule cells. In a qPCR array, CNI treatment upregulated C‐factors and downregulated SOCS‐3 and the complement inhibitors CD46 and CD55. Additionally, ERK1/‐2 was required for these regulations. Following knock‐down and overexpression of SOCS‐3, we found that SOCS‐3 inhibits ERK1/‐2 signalling. Finally, we assessed terminal complement complex formation, cell viability and apoptosis. Terminal complement complex formation was induced by CNIs. Cell viability was significantly decreased, whereas apoptosis was increased. Both effects were reversed under complement component‐depleted conditions. In vivo, increased ERK1/‐2 phosphorylation and SOCS‐3 downregulation were observed at the time of transplantation in renal allograft patients who developed a progressive decline of renal function in the follow‐up compared to stable patients. The progressive cohort also had lower total C3 levels, suggesting higher complement activity at baseline. In conclusion, our data suggest that SOCS‐3 inhibits CNI‐induced ERK1/‐2 signalling, thereby blunting the negative control of C‐system activation.
Electrocatalytic Oxidation of Carbohydrates Mediated by Nitroxyl Radical‐modified Electrodes in Aqueous Solution
Authors: Ono Tetsuya , Sato Katsuhiko , Shimizu Syunki , Yoshida Kentaro , Dairaku Takenori , Suzuki Yasuhiro , Kashiwagi Yoshitomo
Published: November 2017

The electrocatalytic activity of a 2,2,6,6‐tetramethylpipridine‐N‐oxyl (TEMPO)‐modified electrode toward the oxidation of carbohydrates in phosphate buffer solution was investigated under neutral aqueous solution conditions at 25 °C. The modified electrode was prepared on the surface of a glassy carbon electrode by the electrochemical polymerization of a TEMPO precursor containing a pyrrole side chain. Cyclic voltammetric studies showed that the anodic peak current increased with the concentration of carbohydrates in a dose‐dependent manner.
Contribute of crude glycerin to increase the efficiency of anaerobic digestion process of dairy cattle manure
Authors: Simm Silvana , Amorim Orrico Ana Carolina , Previdelli Orrico Junior Marco Antonio , da Silva Sunada Natália , Watte Schwingel Alice , Teixeira Lopes Walter Renato , Lima Whittinghill Karla , Miranda de Vargas Fernando , Sarolli Silva de Mendonça Costa Mônica
Published: November 2017

The objective of this study was to determine the optimal inclusion doses of crude glycerin in anaerobic co‐digestion with dairy cattle manure processed at 10, 17, and 24 days of retention in order to maximize reductions in solid and fibrous constituents and increase the productions of biogas and methane. Semi‐continuous digesters were fed with daily loads of substrates containing doses of 0, 5 and 10% (based on total solids, TS) of crude glycerin and dairy cattle manure. The highest specific productions of biogas and methane with the 10‐day HRT were also achieved in substrates with 0% glycerin, reaching values of 0.91 and 1.27 L/g of TS and solids (VS) added, respectively. In substrates retained for 17 and 24 days the values were maximal with addition of glycerin doses between 2.7 and 3.6% resulting in yields of 1.72 and 2.42 L of biogas per gram of TS added and 2.37 and 3.31 L of biogas per gram of VS added, respectively. For methane production, the optimal inclusion doses of crude glycerin with HRTs of 10, 17, and 24 days were 0.0, 3.7, and 3.3%, generating 0.70, 1.43, and 1.86 L of methane per gram of VS added. The inclusion of crude glycerin in co‐digestion with dairy cattle manure is not recommended for digesters operated with retention time of 10 days. However, when substrates remain for 17 or 24 days this inclusion promotes reductions of solids constituents while maximizing the specific productions of biogas and methane. © 2017 American Institute of Chemical Engineers Environ Prog, 37: 1305–1311, 2018
Early Mesozoic intracontinental deformation in the eastern North China Block: Implication for an indentation model of North China to South China blocks
Authors: Lan Haoyuan , Li Sanzhong , Li Xiyao , Wang Pengcheng , Somerville Ian D. , Guo Lingli , Wang Qian , Guo Runhua , Zhang Jian , Tao Jianli
Published: November 2017

The Qinling‐Dabie‐Sulu Orogen was formed by the collision of the North and South China blocks during the Indosinian Period. The intracontinental deformation was subsequently developed during the Late Triassic to Early Jurassic in the northeastern, eastern, and southeastern parts of eastern North China Block with different structural patterns. In this paper, we present structural analysis of the Indosinian deformation in the western Shandong and southern Liaoning provinces and synthesized the previous studies of the Triassic‐Early Jurassic deformation in different areas of the eastern North China Block, from the northeastern, central to southeastern parts. Integrating the previous studies of petrology, geochronology, and geophysics, we suggested that (1) a series of top‐to‐the‐northwest thrust‐nappes were formed in the Sulu Orogen, and the southeastward antithetic faults developed in the South China Block. In the eastern North China Block, the Indosinian intracontinental deformation is intensely developed near the orogenic belt as thrust‐nappes and away from the belt developed open folds. (2) The present‐day structural lines in the northeastern, central, and southeastern parts of eastern North China Block show the S‐N‐, E‐W‐, and NE‐trending lines, respectively. It could be the structural response to the dynamics of an orocline or indentation induced by Triassic collision of the North and South China blocks; (3) the eastern margin of the North China Block subducted southeastward beneath the South China Block along the Wulian‐Qingdao‐Yantai Fault during the Indosinian Period.
A critical role of TRPM2 channel in Aβ42‐induced microglial activation and generation of tumor necrosis factor‐α
Authors: Alawieyah Syed Mortadza Sharifah , Sim Joan A. , Neubrand Veronika E. , Jiang Lin‐Hua
Published: November 2017

Amyloid β (Aβ)‐induced neuroinflammation plays an important part in Alzheimer's disease (AD). Emerging evidence supports a role for the transient receptor potential melastatin‐related 2 (TRPM2) channel in Aβ‐induced neuroinflammation, but how Aβ induces TRPM2 channel activation and this relates to neuroinflammation remained poorly understood. We investigated the mechanisms by which Aβ42 activates the TRPM2 channel in microglial cells and the relationships to microglial activation and generation of tumor necrosis factor‐α (TNF‐α), a key cytokine implicated in AD. Exposure to 10–300 nM Aβ42 induced concentration‐dependent microglial activation and generation of TNF‐α that were ablated by genetically deleting (TRPM2 knockout ;TRPM2‐KO) or pharmacologically inhibiting the TRPM2 channel, revealing a critical role of this channel in Aβ42‐induced microglial activation and generation of TNF‐α. Mechanistically, Aβ42 activated the TRPM2 channel via stimulating generation of reactive oxygen species (ROS) and activation of poly(ADPR) polymerase‐1 (PARP‐1). Aβ42‐induced generation of ROS and activation of PARP‐1 and TRPM2 channel were suppressed by inhibiting protein kinase C (PKC) and NADPH oxidases (NOX). Aβ42‐induced activation of PARP‐1 and TRPM2 channel was also reduced by inhibiting PYK2 and MEK/ERK. Aβ42‐induced activation of PARP‐1 was attenuated by TRPM2‐KO and moreover, the remaining PARP‐1 activity was eliminated by inhibiting PKC and NOX, but not PYK2 and MEK/ERK. Collectively, our results suggest that PKC/NOX‐mediated generation of ROS and subsequent activation of PARP‐1 play a role in Aβ42‐induced TRPM2 channel activation and TRPM2‐dependent activation of the PYK2/MEK/ERK signalling pathway acts as a positive feedback to further facilitate activation of PARP‐1 and TRPM2 channel. These findings provide novel insights into the mechanisms underlying Aβ‐induced AD‐related neuroinflammation.
Risk of death associated with new benzodiazepine use among persons with Alzheimer disease: A matched cohort study
Authors: Saarelainen Laura , Tolppanen Anna‐Maija , Koponen Marjaana , Tanskanen Antti , Tiihonen Jari , Hartikainen Sirpa , Taipale Heidi
Published: November 2017

Objective

To investigate the risk of death associated with new benzodiazepine and related drug (BZDR) use in a nationwide cohort of persons with Alzheimer disease (AD).

Methods

The register‐based MEDALZ cohort, including all community‐dwelling Finns diagnosed with AD during 2005 to 2011 (n = 70 718), was used. Clinically verified AD diagnoses were obtained from the Special Reimbursement Register. Drug use periods were modeled from BZDR purchases, derived from the Prescription Register. To study new users, persons who had any BZDR use during the year preceding the AD diagnosis were excluded.

For each person initiating BZDR use (n = 10 380), 2 nonusers (n = 20 760) were matched on age, gender, and time since AD diagnosis. The outcome was 180‐day mortality, and BZDR use was compared with nonuse with Cox regression. Multivariable analyses were adjusted for Charlson comorbidity index, socioeconomic position, hip fractures, psychiatric disorders, substance abuse, stroke, and other psychotropic drug use.

Results

During the follow‐up, 5 excess deaths per 100 person‐years occurred during BZDR use in comparison to nonuse, and mortality rates were 13.4 (95% confidence interval [CI], 12.2‐14.5) and 8.5 (95% CI, 7.9‐9.1), respectively. Benzodiazepine and related drug use was associated with an increased risk of death (adjusted hazard ratio = 1.4 [95% CI, 1.2‐1.6]), and the association was significant from the initiation of use. Benzodiazepine use was associated with an increased risk of death, whereas benzodiazepine‐related drug use was not.

Conclusions

Benzodiazepine and related drug use was associated with an increased risk of death in persons with AD. Our results support treatment guidelines stating that nonpharmacological approaches should be the first‐line option for symptomatic treatment of AD.
Central pain processing in “drug‐naïve” pain‐free patients with Parkinson's disease
Authors: Tessitore Alessandro , Russo Antonio , De Micco Rosa , Fratello Michele , Caiazzo Giuseppina , Giordano Alfonso , Cirillo Mario , Tedeschi Gioacchino , Esposito Fabrizio
Published: November 2017

Background

Despite its clinical relevance, the pathophysiology of pain in Parkinson's disease (PD) is still largely unknown, and both central and peripheral mechanisms have been invoked.

Objectives

To investigate whether central pain processing is altered in “drug‐naive” pain‐free PD (dnPD) patients.

Methods

Using event‐related functional MRI (fMRI), functional response to forearm heat stimulation (FHS) at two different intensities (41°C and 53°C) was investigated in 20 pain‐free dnPD patients, compared with 18 healthy controls (HCs). Secondary analyses were performed to evaluate associations between BOLD signal changes and PD clinical features and behavioral responses.

Results

During low‐innocuous FHS (41°C), no activation differences were found between dnPD patients and HCs. During high‐noxious FHS (53°C) a significantly increased activation in the left somatosensory cortex, left cerebellum, and right low pons was observed in dnPD patients compared to HCs. In the latter experimental condition, fMRI BOLD signal changes in the right low pons (p < .0001; R = −0.8) and in the cerebellum (p = .004; R = −0.7) were negatively correlated with pain intensity ratings only in dnPD patients. No statistically significant difference in experimental pain perception was detected between dnPD patients and HCs.

Conclusions

Our findings suggest that a functional remodulation of pain processing pathways occurs even in the absence of clinically overt pain symptoms in dnPD patients. These mechanisms may eventually become dysfunctional over time, contributing to the emergence of pain symptoms in more advanced PD stages. The comprehension of pain‐related mechanisms may improve the clinical approach and therapeutic management of this disabling nonmotor symptom.
Intraductal papillary mucinous neoplasm of the pancreas rapidly xenografts in chicken eggs and predicts aggressiveness
Authors: Zhao Zhefu , Bauer Nathalie , Aleksandrowicz Ewa , Yin Libo , Gladkich Jury , Gross Wolfgang , Kaiser Jörg , Hackert Thilo , Strobel Oliver , Herr Ingrid
Published: November 2017

Intraductal papillary mucinous neoplasm (IPMN) of the pancreas has a high risk of progressing to invasive pancreatic ductal adenocarcinoma (PDA), but experimental models for IPMN are largely missing. New experimental systems for the molecular characterization of IPMN and for personalized prognosis and treatment options for IPMN are urgently needed. We analyzed the potential use of fertilized chicken eggs for the culture of freshly resected IPMN tissue. We transplanted 49 freshly resected IPMN tissues into eggs and compared the growth characteristics to IPMN tissues transplanted into mice; this was followed by an analysis of histology, morphology, and marker expression. Of the IPMN tissues transplanted into eggs, 63% formed tumor xenografts within 4 days, while none of the 12 IPMN tissues transplanted into immunodeficient mice engrafted. In the eggs, the grafting efficiency of high‐grade (n = 14) and intermediate‐grade (n = 17) dysplasia was 77% and was significantly higher than the 39% grafting efficiency of low‐grade dysplasia (n = 18). According to mucinous expression, 46 IPMN tissues were classified into gastric (n = 6), intestinal (n = 3), oncocytic (n = 23), and pancreatobiliary (n = 14) subtypes. The grafting efficiency was highest for the pancreatobiliary subtype (86%), followed by the oncocytic (70%), gastric (33%) and intestinal (33%) subtypes. The morphology and expression patterns of mucins, progression markers and pancreatic ductal markers were comparable between the primary IPMN tissues and their xenograft copies. The individual tumor environment was largely maintained during subtransplantation, as evaluated upon passage 6. This new IPMN model may facilitate experimental studies and treatment decisions for the optimal personalized management of IPMN.
Trophic dynamics of macroinvertebrate communities of a subtropical river in China
Authors: Wang Lixiao , Deng Shan , Qiu Shuang , Yan Yunjun
Published: November 2017

This study was the first attempt to resolve both spatial and temporal patterns of macroinvertebrate trophic dynamics in a Chinese subtropical river continuum, the Shengli River, from 1st to 4th order. Gut content analysis was adopted to assess the trophic basis and consumption rates of communities. Furthermore, annual energy flow food webs were constructed. Trophic basis analyses showed that 34–79% of the diet of macrozoobenthos in the Shengli River and its tributaries was amorphous detritus. Leaf litter was the second most important food source, followed by animal material. Filamentous algae, diatoms, and fungi served only as subsidies, contributing no more than 5% to total consumption. The macroinvertebrates in 1st and 3rd order streams appeared to show seasonal consumption patterns of different food types, while the communities in 2nd and 4th order streams had the same diet composition throughout the year. Total consumption rates of the communities increased from 1st to 3rd order streams, and declined in 4th order streams. The energy flow food web of 1st order streams was simpler than those of higher‐order streams. With increasing stream order, the food webs increased in complexity until 3rd order, and became simpler again in 4th order streams.
Intermittent compressive force induces human mandibular‐derived osteoblast differentiation via WNT/β‐catenin signaling
Authors: Sindhavajiva Pimrumpai R. , Sastravaha Panunn , Arksornnukit Mansuang , Pavasant Prasit
Published: November 2017

Mechanical force induces an efflux of ATP that regulates osteoblast differentiation. However, the effect of mechanical force‐induced ATP efflux on WNT/β‐catenin signaling remains unclarified. The aim of this study was to investigate the effect of intermittent compressive force (ICF) and ICF‐induced extracellular ATP on osteoblast differentiation via WNT/β‐catenin signaling in human mandibular‐derived osteoblast precursors (hMOBPs). The hMOBPs were subjected to ICF (1.5 g/cm2, 0.3 Hz) for 20 h. To investigate the role of ATP, Apyrase (0.5 units/mL), an enzyme that hydrolyzes ATP, was added 30 min before ICF was applied. The extracellular ATP levels were measured immediately after ICF was removed. The mRNA expression of osteogenic related genes, including WNT was evaluated via quantitative real time polymerase chain reaction. In vitro mineralization was determined by Alizarin Red S staining. The localization of β‐catenin was detected using immunofluorescence staining and lentiviral‐TOP‐dGFP reporter assay. The results demonstrated that ICF increased ATP efflux and in vitro mineralization by hMOBPs. In addition, OSX, ALP, and WNT3A mRNA expression and β‐catenin nuclear translocation increased when ICF was applied. The upregulation of these genes was reduced by Apyrase, suggesting the role of ICF‐induced ATP on osteoblast differentiation. Notably, ICF altered the mRNA expression of purinergic 2X receptors (P2XRs). A P2X1R antagonist (NF449) downregulated ICF‐induced WNT3A, OSX, and ALP mRNA expression. Moreover, when 25 μM α, β‐meATP, a P2X1R agonist, was added, WNT3A, and OSX expression increased. In conclusion, our results demonstrate that ICF‐induced ATP enhanced hMOBP differentiation. This enhancement was associated with WNT/β‐catenin signaling and P2X1R activation.
Biological evaluation and energetic analyses of novel GSK‐3βinhibitors
Authors: Zhang Denan , Liu Lei , Pang Lin , Jin Qing , Ke Kehui , Hu Ming , Yang Jingbo , Ma Weifang , Xie Hongbo , Chen Xiujie
Published: November 2017

Glycogen synthase kinase‐3 beta (GSK‐3β) is involved in multiple signaling pathways. Consistent with its critical roles in normal cells, abnormalities in GSK‐3βactivity have been implicated in diabetes, heart disease, Parkinson disease, and Alzheimer's disease. In this study, a series of new scaffolds of small molecule inhibitors of GSK‐3βwere identified by virtual screening and bioassay. Candidates that adhere to drug‐like criteria from a virtual library of compounds were tested using computational docking studies. Twenty selected compounds were tested, which led to the discovery of two hits. Compound14(IC50 = 8.48 µM) and compound19(IC50 = 2.19 µM) were identified with high affinity. Molecular dynamics (MD) simulations, in conjunction with molecular mechanics/Poisson‐Boltzmann surface area binding free‐energy analysis, were employed to gain insight into the binding modes and energetics of GSK‐3βinhibitors. The detailed analysis of molecular dynamics results shows that Ile62, Val70, Tyr134, and Leu188 in GSK‐3βare key residues responsible to the binding of compound14and compound19. Importantly, our results also validated this combined virtual screening and biophysical technique approach to discovery kinase inhibitors, which may be applied for future inhibitor discovery work for GSK‐3β.