bluuebunny/crossref_metadata_2025_split huggingface dataset:
Copper-catalyzed methylative difunctionalization of alkenes
Authors: Bao Xu , Yokoe Takayuki , Ha Tu M. , Wang Qian , Zhu Jieping 
Published: September 2018

AbstractTrifluoromethylative difunctionalization and hydrofunctionalization of unactivated alkenes have been developed into powerful synthetic methodologies. On the other hand, methylative difunctionalization of olefins remains an unexplored research field. We report in this paper the Cu-catalyzed alkoxy methylation, azido methylation of alkenes using dicumyl peroxide (DCP), and di-tert-butyl peroxide (DTBP) as methyl sources. Using functionalized alkenes bearing a tethered nucleophile (alcohol, carboxylic acid, and sulfonamide), methylative cycloetherification, lactonization, and cycloamination processes are subsequently developed for the construction of important heterocycles such as 2,2-disubstituted tetrahydrofurans, tetrahydropyrans, γ-lactones, and pyrrolidines with concurrent generation of a quaternary carbon center. The results of control experiments suggest that the 1,2-alkoxy methylation of alkenes goes through a radical-cation crossover mechanism, whereas the 1,2-azido methylation proceeds via a radical addition and Cu-mediated azide transfer process.
The language profile of formal thought disorder
Authors: Çokal Derya , Sevilla Gabriel , Jones William Stephen , Zimmerer Vitor , Deamer Felicity , Douglas Maggie , Spencer Helen , Turkington Douglas , Ferrier Nicol , Varley Rosemary , Watson Stuart , Hinzen Wolfram 
Published: September 2018

AbstractFormal thought disorder (FTD) is clinically manifested as disorganized speech, but there have been only few investigations of its linguistic properties. We examined how disturbance of thought may relate to the referential function of language as expressed in the use of noun phrases (NPs) and the complexity of sentence structures. We used a comic strip description task to elicit language samples from 30 participants with schizophrenia (SZ), 15 with moderate or severe FTD (SZ + FTD), and 15 minimal or no FTD (SZ−FTD), as well as 15 first-degree relatives of people with SZ (FDRs) and 15 neurotypical controls (NC). We predicted that anomalies in the normal referential use of NPs, sub-divided into definite and indefinite NPs, would identify FTD; and also that FTD would also be linked to reduced linguistic complexity as specifically measured by the number of embedded clauses and of grammatical dependents. Participants with SZ + FTD produced more referential anomalies than NC and produced the fewest definite NPs, while FDRs produced the most and thus also differed from NC. When referential anomalies were classed according to the NP type in which they occurred, the SZ + FTD group produced more anomalies in definite NPs than NC. Syntactic errors did not distinguish groups, but the SZ + FTD group exhibited significantly less syntactic complexity than non-SZ groups. Exploratory regression analyses suggested that production of definite NPs distinguished the two SZ groups. These results demonstrate that FTD can be identified in specific grammatical patterns which provide new targets for detection, intervention, and neurobiological studies.
Enhanced-contrast optical readout in ultrafast broadband Raman quantum memories
Authors: Zheltikov A. M. 
Published: September 2018

AbstractThe signal-to-noise contrast of the optical readout in broadband Raman quantum memories is analyzed as a function of the pulse widths and phase properties of tailored optical field waveforms used to write in and read out broadband photon wave packets. Based on this analysis, we quantify the tradeoff between the readout contrast and the speed of such memories. Off-resonance coherent four-wave mixing is shown to provide a source of noise photons, lowering the readout contrast in broadband Raman quantum memories. This noise cannot be suppressed by phase matching, but can be radically reduced with a suitable polarization arrangement and proper field-waveform tailoring.
Innovative Biocatalysts as Tools to Detect and Inactivate Nerve Agents
Authors: Porzio Elena , Bettazzi Francesca , Mandrich Luigi , Del Giudice Immacolata , Restaino Odile F. , Laschi Serena , Febbraio Ferdinando , De Luca Valentina , Borzacchiello Maria G. , Carusone Teresa M. , Worek Franz , Pisanti Antonio , Porcaro Piero , Schiraldi Chiara , De Rosa Mario , Palchetti Ilaria , Manco Giuseppe 
Published: September 2018

AbstractPesticides and warfare nerve agents are frequently organophosphates (OPs) or related compounds. Their acute toxicity highlighted more than ever the need to explore applicable strategies for the sensing, decontamination and/or detoxification of these compounds. Herein, we report the use of two different thermostable enzyme families capable to detect and inactivate OPs. In particular, mutants of carboxylesterase-2 from Alicyclobacillus acidocaldarius and of phosphotriesterase-like lactonases from Sulfolobus solfataricus and Sulfolobus acidocaldarius, have been selected and assembled in an optimized format for the development of an electrochemical biosensor and a decontamination formulation, respectively. The features of the developed tools have been tested in an ad-hoc fabricated chamber, to mimic an alarming situation of exposure to a nerve agent. Choosing ethyl-paraoxon as nerve agent simulant, a limit of detection (LOD) of 0.4 nM, after 5 s of exposure time was obtained. Furthermore, an optimized enzymatic formulation was used for a fast and efficient environmental detoxification (>99%) of the nebulized nerve agent simulants in the air and on surfaces. Crucial, large-scale experiments have been possible thanks to production of grams amounts of pure (>90%) enzymes.
Hypophosphatemia Regulates Molecular Mechanisms of Circadian Rhythm
Authors: Noguchi Takashi , Hussein Amira I. , Horowitz Nina , Carroll Deven , Gower Adam C. , Demissie Serkalem , Gerstenfeld Louis C. 
Published: September 2018

AbstractTranscriptomic analysis showed that the central circadian pathway genes had significantly altered expression in fracture calluses from mice fed a low phosphate diet. This led us to hypothesize that phosphate deficiency altered the circadian cycle in peripheral tissues. Analysis of the expression of the central clock genes over a 24–36 hour period in multiple peripheral tissues including fracture callus, proximal tibia growth plate and cardiac tissues after 12 days on a low phosphate diet showed higher levels of gene expression in the hypophosphatemia groups (p < 0.001) and a 3 to 6 hour elongation of the circadian cycle. A comparative analysis of the callus tissue transcriptome genes that were differentially regulated by hypophosphatemia with published data for the genes in bone that are diurnally regulated identified 1879 genes with overlapping differential regulation, which were shown by ontology assessment to be associated with oxidative metabolism and apoptosis. Network analysis of the central circadian pathway genes linked their expression to the up regulated expression of the histone methyltransferase gene EZH2, a gene that when mutated in both humans and mice controls overall skeletal growth. These data suggest that phosphate is an essential metabolite that controls circadian function in both skeletal and non skeletal peripheral tissues and associates its levels with the overall oxidative metabolism and skeletal growth of animals.
Critical steps in clinical shotgun metagenomics for the concomitant detection and typing of microbial pathogens
Authors: Couto Natacha , Schuele Leonard , Raangs Erwin C. , Machado Miguel P. , Mendes Catarina I. , Jesus Tiago F. , Chlebowicz Monika , Rosema Sigrid , Ramirez Mário , Carriço João A. , Autenrieth Ingo B. , Friedrich Alex W. , Peter Silke , Rossen John W. 
Published: September 2018

AbstractHigh throughput sequencing has been proposed as a one-stop solution for diagnostics and molecular typing directly from patient samples, allowing timely and appropriate implementation of measures for treatment, infection prevention and control. However, it is unclear how the variety of available methods impacts the end results. We applied shotgun metagenomics on diverse types of patient samples using three different methods to deplete human DNA prior to DNA extraction. Libraries were prepared and sequenced with Illumina chemistry. Data was analyzed using methods likely to be available in clinical microbiology laboratories using genomics. The results of microbial identification were compared to standard culture-based microbiological methods. On average, 75% of the reads corresponded to human DNA, being a major determinant in the analysis outcome. None of the kits was clearly superior suggesting that the initial ratio between host and microbial DNA or other sample characteristics were the major determinants of the proportion of microbial reads. Most pathogens identified by culture were also identified through metagenomics, but substantial differences were noted between the taxonomic classification tools. In two cases the high number of human reads resulted in insufficient sequencing depth of bacterial DNA for identification. In three samples, we could infer the probable multilocus sequence type of the most abundant species. The tools and databases used for taxonomic classification and antimicrobial resistance identification had a key impact on the results, recommending that efforts need to be aimed at standardization of the analysis methods if metagenomics is to be used routinely in clinical microbiology.
The Atlantic salmon (Salmo salar) antimicrobial peptide cathelicidin-2 is a molecular host-associated cue for the salmon louse (Lepeophtheirus salmonis)
Authors: Núñez-Acuña Gustavo , Gallardo-Escárate Cristian , Fields David M. , Shema Steven , Skiftesvik Anne Berit , Ormazábal Ignacio , Browman Howard I. 
Published: September 2018

AbstractChemical signals are a key element of host-parasite interactions. In marine ecosystems, obligate ectoparasites, such as sea lice, use chemical cues and other sensory signals to increase the probability of encountering a host and to identify appropriate hosts on which they depend to complete their life cycle. The chemical compounds that underlie host identification by the sea lice are not fully described or characterized. Here, we report a novel compound - the Atlantic salmon (Salmo salar) antimicrobial peptide cathelicidin-2 (Cath-2) – that acts as an activation cue for the marine parasitic copepod Lepeophtheirus salmonis. L. salmonis were exposed to 0, 7, 70 and 700 ppb of Cath-2 and neural activity, swimming behaviour and gene expression profiles of animals in response to the peptide were evaluated. The neurophysiological, behavioural and transcriptomic results were consistent: L. salmonis detects Cath-2 as a water-soluble peptide released from the skin of salmon, triggering chemosensory neural activity associated with altered swimming behaviour of copepodids exposed to the peptide, and chemosensory-related genes were up-regulated in copepodids exposed to the peptide. L. salmonis are activated by Cath-2, indicating a tight link between this peptide and the salmon louse chemosensory system.
X-ray structure of full-length human RuvB-Like 2 – mechanistic insights into coupling between ATP binding and mechanical action
Authors: Silva Sara T. N. , Brito José A. , Arranz Rocío , Sorzano Carlos Óscar S. , Ebel Christine , Doutch James , Tully Mark D. , Carazo José-María , Carrascosa José L. , Matias Pedro M. , Bandeiras Tiago M. 
Published: September 2018

AbstractRuvB-Like transcription factors function in cell cycle regulation, development and human disease, such as cancer and heart hyperplasia. The mechanisms that regulate adenosine triphosphate (ATP)-dependent activity, oligomerization and post-translational modifications in this family of enzymes are yet unknown. We present the first crystallographic structure of full-length human RuvBL2 which provides novel insights into its mechanistic action and biology. The ring-shaped hexameric RuvBL2 structure presented here resolves for the first time the mobile domain II of the human protein, which is responsible for protein-protein interactions and ATPase activity regulation. Structural analysis suggests how ATP binding may lead to domain II motion through interactions with conserved N-terminal loop histidine residues. Furthermore, a comparison between hsRuvBL1 and 2 shows differences in surface charge distribution that may account for previously described differences in regulation. Analytical ultracentrifugation and cryo electron microscopy analyses performed on hsRuvBL2 highlight an oligomer plasticity that possibly reflects different physiological conformations of the protein in the cell, as well as that single-stranded DNA (ssDNA) can promote the oligomerization of monomeric hsRuvBL2. Based on these findings, we propose a mechanism for ATP binding and domain II conformational change coupling.
A new method for discovering EMAST sequences in animal models of cancer
Authors: Bhaskaran Nitya , Luu Jennifer , Kelley Scott T. , Khan Mohammad W. , Mamindla Priyadarshini , McGuire Kathleen L. 
Published: September 2018

AbstractElevated Microsatellite Alterations at Selected Tetranucleotide repeats (EMAST) occur in up to 60% of colorectal cancers and may associate with aggressive and advanced disease in patients. Although EMAST occurs in many cancer types, current understanding is limited due to the lack of an animal model. Reported here is the design and implementation of an algorithm for detecting EMAST repeats in mice. This algorithm incorporates properties of known human EMAST sequences to identify repeat sequences in animal genomes and was able to identify EMAST-like sequences in the mouse. Seven of the identified repeats were analyzed further in a colon cancer mouse model and six of the seven displayed EMAST instability characteristic of that seen in human colorectal cancers. In conclusion, the algorithm developed successfully identified EMAST repeats in an animal genome and, for the first time, EMAST has been shown to occur in a mouse model of colon cancer.
Low survival of strongly footed pheasants may explain constraints on lateralization
Authors: Whiteside Mark A. , Bess Mackenzie M. , Frasnelli Elisa , Beardsworth Christine E. , Langley Ellis J. G. , van Horik Jayden O. , Madden Joah R. 
Published: September 2018

AbstractBrain lateralization is considered adaptive because it leads to behavioral biases and specializations that bring fitness benefits. Across species, strongly lateralized individuals perform better in specific behaviors likely to improve survival. What constrains continued exaggerated lateralization? We measured survival of pheasants, finding that individuals with stronger bias in their footedness had shorter life expectancies compared to individuals with weak biases. Consequently, weak, or no footedness provided the highest fitness benefits. If, as suggested, footedness is indicative of more general brain lateralization, this could explain why continued brain lateralization is constrained even though it may improve performance in specific behaviors.
Noninvasive assessment of characteristics of novel anti-HER2 antibodies by molecular imaging in a human gastric cancer xenograft-bearing mouse model
Authors: Kuo Wei-Ying , Lin Jia-Jia , Hsu Hung-Ju , Chen Hong-Sen , Yang An-Suei , Wu Chun-Yi 
Published: September 2018

AbstractHuman epidermal growth factor receptor 2 (HER2) overexpression occurs in various types of cancers. Regarding the anti-HER2 targeted therapies showed superior treatment outcomes in several (pre)clinical studies, we used multimodality image to rapidly select novel HER2-targeting antibodies for further therapeutics development. The four anti-HER2 antibodies (H32 IgG, 75 IgG, 61 IgG, and trastuzumab) labeled with either In-111 or a DyLight680 fluorescent dye were applied to perform cellular uptake, endocytosis, optical/microSPECT/CT imaging and biodistribution studies. In vitro and in vivo relative effectiveness of these antibodies were also compared in an N87 gastric cancer xenograft model. The internalized radioactivity of [111In]61 IgG in N87 cells increased from 33% at 12 hr to 56% at 48 hr after incubation, while the majority of other antibodies stayed on the cell membranes. Among these antibodies, 61 IgG showed the highest accumulation in tumors with the tumor-to-muscle ratio (T/M) of 131 ± 61.4 and 19.13 ± 3.42 conducted by IVIS and microSPECT/CT, respectively. We demonstrated that multimodality imaging is a reliable approach for selecting potential antibodies and found that 61 IgG manifested significant tumor accumulation with elevated internalization rate thus could be a suitable candidate for further development of new HER2-targeted therapies.
Fabrication and Characterization of Glucose Biosensors by Using Hydrothermally Grown ZnO Nanorods
Authors: Ridhuan Nur Syafinaz , Abdul Razak Khairunisak , Lockman Zainovia 
Published: September 2018

AbstractHighly oriented ZnO nanorod (NR) arrays were fabricated on a seeded substrate through a hydrothermal route. The prepared ZnO nanorods were used as an amperometric enzyme electrode, in which glucose oxidase (GOx) was immobilised through physical adsorption. The modified electrode was designated as Nafion/GOx/ZnO NRs/ITO. The morphology and structural properties of the fabricated ZnO nanorods were analysed using field-emission scanning electron microscope and X-ray diffractometer. The electrochemical properties of the fabricated biosensor were studied by cyclic voltammetry and amperometry. Electrolyte pH, electrolyte temperature and enzyme concentration used for immobilisation were the examined parameters influencing enzyme activity and biosensor performance. The immobilised enzyme electrode showed good GOx retention activity. The amount of electroactive GOx was 7.82 × 10−8mol/cm2, which was relatively higher than previously reported values. The Nafion/GOx/ZnO NRs/ITO electrode also displayed a linear response to glucose ranging from 0.05 mM to 1 mM, with a sensitivity of 48.75 µA/mM and a low Michaelis–Menten constant of 0.34 mM. Thus, the modified electrode can be used as a highly sensitive third-generation glucose biosensor with high resistance against interfering species, such as ascorbic acid, uric acid andL-cysteine. The applicability of the modified electrode was tested using human blood samples. Results were comparable with those obtained using a standard glucometer, indicating the excellent performance of the modified electrode.
Suppression of GPR56 expression by pyrrole-imidazole polyamide represents a novel therapeutic drug for AML with high EVI1 expression
Authors: Saha Hasi Rani , Kaneda-Nakashima Kazuko , Shimosaki Shunsuke , Suekane Akira , Sarkar Bidhan , Saito Yusuke , Ogoh Honami , Nakahata Shingo , Inoue Kentaro , Watanabe Takayoshi , Nagase Hiroki , Morishita Kazuhiro 
Published: September 2018

AbstractG protein-coupled receptor 56 (GPR56) is highly expressed in acute myeloid leukemia (AML) cells with high EVI1 expression (EVI1high AML). Because GPR56 is a transcriptional target of EVI1 and silencing of GPR56 expression induces apoptosis, we developed a novel drug to suppress GPR56 expression in EVI1high AML cells. For this purpose, we generated pyrrole-imidazole (PI) polyamides specific to GPR56 (PIP/56-1 or PIP/56-2) as nuclease-resistant novel compounds that interfere with the binding of EVI1 to the GPR56 promoter in a sequence-specific manner. Treatment of EVI1high AML cell lines (UCSD/AML1 and Kasumi-3) with PIP/56-1 or PIP/56-2 effectively suppressed GPR56 expression by inhibiting binding of EVI1 to its promoter, leading to suppression of cell growth with increased rates of apoptosis. Moreover, intravenous administration of PIP/56-1 into immunodeficient Balb/c-RJ mice subcutaneously transplanted with UCSD/AML1 cells significantly inhibited tumor growth and extended survival. Furthermore, organ infiltration by leukemia cells in immunodeficient Balb/c-RJ mice, which were intravenously transplanted using UCSD/AML1 cells, was successfully inhibited by PIP/56-1 treatment with no apparent effects on murine hematopoietic cells. In addition, PIP treatment did not inhibit colony formation of human CD34+ progenitor cells. Thus, PI polyamide targeting of GPR56 using our compound is promising, useful, and safe for the treatment of EVI1high AML.
Cd induces G2/M cell cycle arrest by up-regulating miR-133b via directly targeting PPP2R2D in L02 hepatocytes
Authors: Zhang Yujing , Xiao Fang , Zhong Caigao , Zeng Ming , Zou Lianhong 
Published: September 2018

Abstract
Previous research has shown that cadmium (Cd), which accumulates primarily in the liver and kidneys, could cause cell cycle arrest in various cell types. In the present study, the effect of Cd on the cell cycle progression of hepatocytes and the underlying mechanisms were investigated. Our results showed that Cd inhibited the growth and proliferation of L02 hepatocytes. Further study revealed that Cd significantly induced G2-phase cell cycle arrest accompanied by an overproduction of reactive oxygen species (ROS). Cd-induced G2-phase arrest could be prevented by inhibiting ROS with the use of antioxidant Trolox. Additionally, treatment with Cd induced an increase in the expression of miR-133b, which could be reversed with Trolox pretreatment. Moreover, miR-133b was shown to regulate PPP2R2D expression by binding to the 3′-untranslated region (UTR) of PPP2R2D mRNA. We also found that treatment with Cd decreased the expression of PPP2R2D, and inhibition of PPP2R2D expression by siRNA partially aggravated Cd-induced cell cycle arrest. By artificially increasing the expression of the protein phosphatase 2A-B55δ subunit (PP2A-B55δ, encoded by the PPP2R2D gene), we confirmed that PPP2R2D can be regulated by miR-133b in Cd-treated cells, and the G2-phase arrest effect could be suppressed by PP2A-B55δ. Collectively, these findings indicated that Cd increased ROS and induced the expression of miR-133b, which consequently inhibited the expression of PPP2R2D and led to G2-phase arrest in L02 hepatocytes. This study provides novel insights into the molecular mechanisms of Cd-induced cell cycle arrest.
Single‐phase hybrid‐H6 transformerless PV grid‐tied inverter
Authors: Ma Lan , Xu Hongbing , Huang Alex Q. , Wang Xiaodong , Zou Jianxiao 
Published: September 2018

Transformerless inverter for grid‐tied photovoltaic (PV) system has been widely used due to lower cost, higher efficiency and lighter weight. Various transformerless inverter topologies have been proposed to meet the safety requirement of low leakage current and obtain the reactive power capability. To get better performance, a novel transformerless hybrid‐H6 inverter with an improved modulation technique is proposed in this study. By adopting the improved modulation technique, two symmetry paths are realised to share the current during the freewheeling mode. Thus, without paralleling any additional capacitors to the switch, the inverter can reduce the influence of junction capacitance on common mode voltage naturally which results in mitigating the leakage current issue. Thanks to the dead time reduction through the improved modulation, the qualities of output waveforms are improved. Moreover, reactive power control is achieved without any modification of the inverter structure. Finally, a 1 kW prototype is simulated and tested to verify the theoretical analysis of this study. Not only the reactive power capability is obtained for the proposed inverter, but also the small common mode voltage fluctuation is achieved at the same time. In addition, the total harmonic distortion of the current is decreased by more than 1.7%.