bluuebunny/crossref_metadata_2025 huggingface dataset:
Multiple molecular mechanisms form a positive feedback loop driving amyloid β42 peptide-induced neurotoxicity via activation of the TRPM2 channel in hippocampal neurons
Authors: Li Xin , Jiang Lin-Hua
Published: February 2018

Emerging evidence supports an important role for the ROS-sensitive TRPM2 channel in mediating age-related cognitive impairment in Alzheimer’s disease (AD), particularly neurotoxicity resulting from generation of excessive neurotoxic Aβ peptides. Here we examined the elusive mechanisms by which Aβ42 activates the TRPM2 channel to induce neurotoxicity in mouse hippocampal neurons. Aβ42-induced neurotoxicity was ablated by genetic knockout (TRPM2-KO) and attenuated by inhibition of the TRPM2 channel activity or activation through PARP-1. Aβ42-induced neurotoxicity was also inhibited by treatment with TPEN used as a Zn2+-specific chelator. Cell imaging revealed that Aβ42-induced lysosomal dysfunction, cytosolic Zn2+ increase, mitochondrial Zn2+ accumulation, loss of mitochondrial function, and mitochondrial generation of ROS. These effects were suppressed by TRPM2-KO, inhibition of TRPM2 or PARP-1, or treatment with TPEN. Bafilomycin-induced lysosomal dysfunction also resulted in TRPM2-dependent cytosolic Zn2+ increase, mitochondrial Zn2+ accumulation, and mitochondrial generation of ROS, supporting that lysosomal dysfunction and accompanying Zn2+ release trigger mitochondrial Zn2+ accumulation and generation of ROS. Aβ42-induced effects on lysosomal and mitochondrial functions besides neurotoxicity were also suppressed by inhibition of PKC and NOX. Furthermore, Aβ42-induced neurotoxicity was prevented by inhibition of MEK/ERK. Therefore, our study reveals multiple molecular mechanisms, including PKC/NOX-mediated generation of ROS, activation of MEK/ERK and PARP-1, lysosomal dysfunction and Zn2+ release, mitochondrial Zn2+ accumulation, loss of mitochondrial function, and mitochondrial generation of ROS, are critically engaged in forming a positive feedback loop that drives Aβ42-induced activation of the TRPM2 channel and neurotoxicity in hippocampal neurons. These findings shed novel and mechanistic insights into AD pathogenesis.
PLEKHN1 promotes apoptosis by enhancing Bax-Bak hetro-oligomerization through interaction with Bid in human colon cancer
Authors: Kuriyama Sei , Tsuji Tadahiro , Sakuma Tetsushi , Yamamoto Takashi , Tanaka Masamistu
Published: February 2018

The anti-apoptotic nature of cancer cells often impedes the effects of anti-cancer therapeutic agents. Multiple death signals influence mitochondria during apoptosis, and though many studies have attempted to elucidate these complicated pathways, Bax oligomerization, an important step in the process, remains controversial. Here we demonstrate that pleckstrin-homology N1 (PLEKHN1), also known as cardiolipin phosphatidic acid binding protein, plays pro-apoptotic roles during reactive oxygen species (ROS)–induced apoptosis. Human PLEKHN1 was expressed in several cancer cell lines of differing origin. Its expression was regulated by hypoxia, and it existed in the mitochondrial fraction. Genome editing of hPLEKHN1 in human colon cancer HT-29 cells revealed enhanced survival of knockout cells compared with that of parental cells in vitro and in vivo. Thapsigargin or hydrogen peroxide treatment activated multiple death signals including JNK, Bcl-2 family members, and caspases. PLEKHN1 was bound to Bid, a pro-apoptotic protein, and not to Bax, and PLEKHN1 could remove Bid from transient Bid–Bax complexes. Fluorescent time-lapse imaging revealed that PLEKHN1 aggregated with Bid during thapsigargin- or hydrogen peroxide-induced apoptosis prior to Bax aggregation. Inhibition of PLEKHN1 led to attenuation of Bax-Bak hetero-oligomerization and Bid translocation. The immunohistochemistry of cancer patient specimens showed that PLEKHN1 expression was absent from cancer region at the transition area of normal/cancer tissues. Collectively, the silencing of PLEKHN1 may be the key that cancer cells acquire the drug resistance.
Na+/Ca2+ exchanger 1 on nuclear envelope controls PTEN/Akt pathway via nucleoplasmic Ca2+ regulation during neuronal differentiation
Authors: Secondo Agnese , Esposito Alba , Petrozziello Tiziana , Boscia Francesca , Molinaro Pasquale , Tedeschi Valentina , Pannaccione Anna , Ciccone Roselia , Guida Natascia , Di Renzo Gianfranco , Annunziato Lucio
Published: February 2018

Nuclear envelope (NE) is a Ca2+-storing organelle controlling neuronal differentiation through nuclear Ca2+ concentrations ([Ca2+]n). However, how [Ca2+]n regulates this important function remains unknown. Here, we investigated the role of the nuclear form of the Na+/Ca2+ exchanger 1(nuNCX1) during the different stages of neuronal differentiation and the involvement of PTEN/PI3’K/Akt pathway. In neuronal cells, nuNCX1 was detected on the inner membrane of the NE where protein expression and activity of the exchanger increased during NGF-induced differentiation. nuNCX1 activation by Na+-free perfusion induced a time-dependent activation of nuclear-resident PI3K/Akt pathway in isolated nuclei. To discriminate the contribution of nuNCX1 from those of plasma membrane NCX, we generated a chimeric protein composed of the fluorophore EYFP, the exchanger inhibitory peptide, and the nuclear localization signal, named XIP-NLS. Fura-2 measurements on single nuclei and patch-clamp experiments in whole-cell configuration showed that XIP-NLS selectively inhibited nuNCX1. Once it reached the nuclear compartment, XIP-NLS increased the nucleoplasmic Ca2+ peak elicited by ATP and reduced Akt phosphorylation, GAP-43 and MAP-2 expression through nuclear-resident PTEN induction. Furthermore, in accordance with the prevention of the neuronal phenotype, XIP-NLS significantly reduced TTX-sensitive Na+ currents and membrane potential during neuronal differentiation. The selective inhibition of nuNCX1 by XIP-NLS increased the percentage of β III tubulin-positive immature neurons in mature cultures of MAP-2-positive cortical neurons, thus unraveling a new function for nuNCX1 in regulating neuronal differentiation through [Ca2+]n-dependent PTEN/PI3K/Akt pathway.
Fluorogenic RNA Mango aptamers for imaging small non-coding RNAs in mammalian cells
Authors: Autour Alexis , C. Y. Jeng Sunny , D. Cawte Adam , Abdolahzadeh Amir , Galli Angela , Panchapakesan Shanker S. S. , Rueda David , Ryckelynck Michael , Unrau Peter J.
Published: February 2018

Despite having many key roles in cellular biology, directly imaging biologically important RNAs has been hindered by a lack of fluorescent tools equivalent to the fluorescent proteins available to study cellular proteins. Ideal RNA labelling systems must preserve biological function, have photophysical properties similar to existing fluorescent proteins, and be compatible with established live and fixed cell protein labelling strategies. Here, we report a microfluidics-based selection of three new high-affinity RNA Mango fluorogenic aptamers. Two of these are as bright or brighter than enhanced GFP when bound to TO1-Biotin. Furthermore, we show that the new Mangos can accurately image the subcellular localization of three small non-coding RNAs (5S, U6, and a box C/D scaRNA) in fixed and live mammalian cells. These new aptamers have many potential applications to study RNA function and dynamics both in vitro and in mammalian cells.
A CNOT gate between multiphoton qubits encoded in two cavities
Authors: Rosenblum S. , Gao Y. Y. , Reinhold P. , Wang C. , Axline C. J. , Frunzio L. , Girvin S. M. , Jiang Liang , Mirrahimi M. , Devoret M. H. , Schoelkopf R. J.
Published: February 2018

Entangling gates between qubits are a crucial component for performing algorithms in quantum computers. However, any quantum algorithm must ultimately operate on error-protected logical qubits encoded in high-dimensional systems. Typically, logical qubits are encoded in multiple two-level systems, but entangling gates operating on such qubits are highly complex and have not yet been demonstrated. Here we realize a controlled NOT (CNOT) gate between two multiphoton qubits in two microwave cavities. In this approach, we encode a qubit in the high-dimensional space of a single cavity mode, rather than in multiple two-level systems. We couple two such encoded qubits together through a transmon, which is driven by an RF pump to apply the gate within 190 ns. This is two orders of magnitude shorter than the decoherence time of the transmon, enabling a high-fidelity gate operation. These results are an important step towards universal algorithms on error-corrected logical qubits.
Differential patterns of contextual organization of memory in first-episode psychosis
Authors: Murty Vishnu P. , McKinney Rachel A. , DuBrow Sarah , Jalbrzikowski Maria , Haas Gretchen L. , Luna Beatriz
Published: February 2018

Contextual information is used to support and organize episodic memory. Prior research has reliably shown memory deficits in psychosis; however, little research has characterized how this population uses contextual information during memory recall. We employed an approach founded in a computational framework of free recall to quantify how individuals with first episode of psychosis (FEP, N = 97) and controls (CON, N = 55) use temporal and semantic context to organize memory recall. Free recall was characterized using the Hopkins Verbal Learning Test-Revised (HVLT-R). We compared FEP and CON on three measures of free recall: proportion recalled, temporal clustering, and semantic clustering. Measures of temporal/semantic clustering quantified how individuals use contextual information to organize memory recall. We also assessed to what extent these measures relate to antipsychotic use and differentiated between different types of psychosis. We also explored the relationship between these measures and intelligence. In comparison to CON, FEP had reduced recall and less temporal clustering during free recall (p < 0.05, Bonferroni-corrected), and showed a trend towards greater semantic clustering (p = 0.10, Bonferroni-corrected). Within FEP, antipsychotic use and diagnoses did not differentiate between free recall accuracy or contextual organization of memory. IQ was related to free recall accuracy, but not the use of contextual information during recall in either group (p < 0.05, Bonferroni-corrected). These results show that in addition to deficits in memory recall, FEP differed in how they organize memories compared to CON.
Type 2 Innate Lymphocytes Actuate Immunity Against Tumours and Limit Cancer Metastasis
Authors: Saranchova Iryna , Han Jeffrey , Zaman Rysa , Arora Hitesh , Huang Hui , Fenninger Franz , Choi Kyung Bok , Munro Lonna , Pfeifer Cheryl G. , Welch Ian , Takei Fumio , Jefferies Wilfred A.
Published: February 2018

Type 2 innate lymphoid cells (ILC2) potentiate immune responses, however, their role in mediating adaptive immunity in cancer has not been assessed. Here, we report that mice genetically lacking ILC2s have significantly increased tumour growth rates and conspicuously higher frequency of circulating tumour cells (CTCs) and resulting metastasis to distal organs. Our data support the model that IL-33 dependent tumour-infiltrating ILC2s are mobilized from the lungs and other tissues through chemoattraction to enter tumours, and subsequently mediate tumour immune-surveillance by cooperating with dendritic cells to promote adaptive cytolytic T cell responses. We conclude that ILC2s play a fundamental, yet hitherto undescribed role in enhancing anti-cancer immunity and controlling tumour metastasis.
Reconstruction of the sialylation pathway in the ancestor of eukaryotes
Authors: Petit Daniel , Teppa Elin , Cenci Ugo , Ball Steven , Harduin-Lepers Anne
Published: February 2018

The biosynthesis of sialylated molecules of crucial relevance for eukaryotic cell life is achieved by sialyltransferases (ST) of the CAZy family GT29. These enzymes are widespread in the Deuterostoma lineages and more rarely described in Protostoma, Viridiplantae and various protist lineages raising the question of their presence in the Last eukaryotes Common Ancestor (LECA). If so, it is expected that the main enzymes associated with sialic acids metabolism are also present in protists. We conducted phylogenomic and protein sequence analyses to gain insights into the origin and ancient evolution of ST and sialic acid pathway in eukaryotes, Bacteria and Archaea. Our study uncovered the unreported occurrence of bacterial GT29 ST and evidenced the existence of 2 ST groups in the LECA, likely originating from the endosymbiotic event that generated mitochondria. Furthermore, distribution of the major actors of the sialic acid pathway in the different eukaryotic phyla indicated that these were already present in the LECA, which could also access to this essential monosaccharide either endogenously or via a sialin/sialidase uptake mechanism involving vesicles. This pathway was lost in several basal eukaryotic lineages including Archaeplastida despite the presence of two different ST groups likely assigned to other functions.
A fluidic device for the controlled formation and real-time monitoring of soft membranes self-assembled at liquid interfaces
Authors: Mendoza-Meinhardt Arturo , Botto Lorenzo , Mata Alvaro
Published: February 2018

Membrane materials formed at the interface between two liquids have found applications in a large variety of technologies, from sensors to drug-delivery and catalysis. However, studying the formation of these membranes in real-time presents considerable challenges, owing to the difficulty of prescribing the location and instant of formation of the membrane, the difficulty of observing time-dependent membrane shape and thickness, and the poor reproducibility of results obtained using conventional mixing procedures. Here we report a fluidic device that facilitates characterisation of the time-dependent thickness, morphology and mass transport properties of materials self-assembled at fluid-fluid interfaces. In the proposed device the membrane forms from the controlled coalescence of two liquid menisci in a linear open channel. The linear geometry and controlled mixing of the solutions facilitate real-time visualisation, manipulation and improve reproducibility. Because of its small dimensions, the device can be used in conjunction with standard microscopy methods and reduces the required volumes of potentially expensive reagents. As an example application to tissue engineering, we use the device to characterise interfacial membranes formed by supra-molecular self-assembly of peptide-amphiphiles with either an elastin-like-protein or hyaluronic acid. The device can be adapted to study self-assembling membranes for applications that extend beyond bioengineering.
Impact of Gamma rays and DBD plasma treatments on wastewater treatment
Authors: Attri Pankaj , Tochikubo Fumiyoshi , Park Ji Hoon , Choi Eun Ha , Koga Kazunori , Shiratani Masaharu
Published: February 2018

The rapid growth in world population brings with it the need for improvement in the current technology for water purification, in order to provide adequate potable water to everyone. Although an advanced oxidation process has been used to purify wastewater, its action mechanism is still not clear. Therefore, in the present study we treat dye-polluted water with gamma rays and dielectric barrier discharge (DBD) plasma. We study the wastewater treatment efficiency of gamma rays and DBD plasma at different absorbed doses, and at different time intervals, respectively. Methyl orange and methylene blue dyes are taken as model dyes. To understand the effects of environment and humidity on the decolorization of these dyes, we use various gas mixtures in the DBD plasma reactor. In the plasma reactor, we use the ambient air and ambient air + other gas (oxygen, nitrogen, and argon) mixtures, respectively, for the treatment of dyes. Additionally, we study the humidity effect on the decolorization of dyes with air plasma. Moreover, we also perform plasma simulation in different environment conditions, to understand which major radicals are generated during the plasma treatments, and determine their probable densities.
Functional Variants Identified Efficiently through an Integrated Transcriptome and Epigenome Analysis
Authors: Meng Fanlin , Yuan Guohong , Zhu Xiurui , Zhou Yiming , Wang Dong , Guo Yong
Published: February 2018

Although genome-wide association studies (GWAS) have identified numerous genetic loci associated with complex diseases, the underlying molecular mechanisms of how these loci contribute to disease pathogenesis remain largely unknown, due to the lack of an efficient strategy to identify these risk variants. Here, we proposed a new strategy termed integrated transcriptome and epigenome analysis (iTEA) to identify functional genetic variants in non-coding elements. We considered type 2 diabetes mellitus as a model and identified a well-known diabetic risk variant rs35767 using iTEA. Furthermore, we discovered a new functional SNP, rs815815, involved in glucose metabolism. Our study provides an approach to directly and quickly identify functional genetic variants in type 2 diabetes mellitus, and this approach can be extended to study other complex diseases.
In vivo GluCEST MRI: Reproducibility, background contribution and source of glutamate changes in the MPTP model of Parkinson’s disease
Authors: Bagga Puneet , Pickup Stephen , Crescenzi Rachelle , Martinez Daniel , Borthakur Arijitt , D’Aquilla Kevin , Singh Anup , Verma Gaurav , Detre John A. , Greenberg Joel , Hariharan Hari , Reddy Ravinder
Published: February 2018

Glutamate Chemical Exchange Saturation Transfer (GluCEST) MRI is a recently developed technique to image glutamate. In the present study, we evaluated the reproducibility and background contamination to the GluCEST and source of the GluCEST changes in a mouse model of Parkinson’s disease. Repeated measurements in five mice demonstrated an intra-animal coefficient of variation (CV) of GluCEST signal to be 2.3 ± 1.3% and inter-animal CV of GluCEST to be 3.3 ± 0.3%. Mice were treated with MPTP to create a localized striatal elevation of glutamate. We found an elevation in the GluCEST contrast of the striatum following MPTP treatment (Control: 23.3 ± 0.8%, n = 16; MPTP: 26.2 ± 0.8%, n = 19; p ≤ 0.001). Additionally, the positive association between glutamate concentration measured via 1H MRS and GluCEST signal was used to estimate background contribution to the measured GluCEST. The contribution of signal from non-glutamate sources was found to be ~28% of the total GluCEST. Immunohistochemical analysis of the brain showed co-localization of glutamate with GFAP in the striatum. This suggests that the elevated glutamate present in the striatum in this mouse model reflects astroglial proliferation or reactivity due to the action of MPTP. The potential of GluCEST as a biomarker for imaging inflammation mediated gliosis is discussed.
Development of a bacterial cellulose-based hydrogel cell carrier containing keratinocytes and fibroblasts for full-thickness wound healing
Authors: Loh Evelyn Yun Xi , Mohamad Najwa , Fauzi Mh Busra , Ng Min Hwei , Ng Shiow Fern , Mohd Amin Mohd Cairul Iqbal
Published: February 2018

Bacterial cellulose (BC)/acrylic acid (AA) hydrogel has successfully been investigated as a wound dressing for partial-thickness burn wound. It is also a promising biomaterial cell carrier because it bears some resemblance to the natural soft tissue. This study assessed its ability to deliver human epidermal keratinocytes (EK) and dermal fibroblasts (DF) for the treatment of full-thickness skin lesions. In vitro studies demonstrated that BC/AA hydrogel had excellent cell attachment, maintained cell viability with limited migration, and allowed cell transfer. In vivo wound closure, histological, immunohistochemistry, and transmission electron microscopy evaluation revealed that hydrogel alone (HA) and hydrogel with cells (HC) accelerated wound healing compared to the untreated controls. Gross appearance and Masson’s trichrome staining indicated that HC was better than HA. This study suggests the potential application of BC/AA hydrogel with dual functions, as a cell carrier and wound dressing, to promote full-thickness wound healing.
In vitro patient-derived 3D mesothelioma tumor organoids facilitate patient-centric therapeutic screening
Authors: Mazzocchi Andrea R. , Rajan Shiny A. P. , Votanopoulos Konstantinos I. , Hall Adam R. , Skardal Aleksander
Published: February 2018

Variability in patient response to anti-cancer drugs is currently addressed by relating genetic mutations to chemotherapy through precision medicine. However, practical benefits of precision medicine to therapy design are less clear. Even after identification of mutations, oncologists are often left with several drug options, and for some patients there is no definitive treatment solution. There is a need for model systems to help predict personalized responses to chemotherapeutics. We have microengineered 3D tumor organoids directly from fresh tumor biopsies to provide patient-specific models with which treatment optimization can be performed before initiation of therapy. We demonstrate the initial implementation of this platform using tumor biospecimens surgically removed from two mesothelioma patients. First, we show the ability to biofabricate and maintain viable 3D tumor constructs within a tumor-on-a-chip microfluidic device. Second, we demonstrate that results of on-chip chemotherapy screening mimic those observed in subjects themselves. Finally, we demonstrate mutation-specific drug testing by considering the results of precision medicine genetic screening and confirming the effectiveness of the non-standard compound 3-deazaneplanocin A for an identified mutation. This patient-derived tumor organoid strategy is adaptable to a wide variety of cancers and may provide a framework with which to improve efforts in precision medicine oncology.
Characterization of 111In-labeled Glucose-Dependent Insulinotropic Polypeptide as a Radiotracer for Neuroendocrine Tumors
Authors: Willekens Stefanie M. A. , Joosten Lieke , Boerman Otto C. , Brom Maarten , Gotthardt Martin
Published: February 2018

Somatostatin receptor targeting is considered the standard nuclear medicine technique for visualization of neuroendocrine tumors (NET). Since not all NETs over-express somatostatin receptors, the search for novel targets, visualizing these NETs, is ongoing. Many NETs, expressing low somatostatin receptor levels, express glucose-dependent insulinotropic polypeptide (GIP) receptors (GIPR). Here, we evaluated the performance of [Lys37(DTPA)]N-acetyl-GIP1-42, a newly synthesized GIP analogue to investigate whether NET imaging via GIPR targeting is feasible. Therefore, [Lys37(DTPA)]N-acetyl-GIP1-42 was radiolabeled with 111In with specific activity up to 1.2 TBq/µmol and both in vitro and in vivo receptor targeting properties were examined. In vitro, [Lys37(111In-DTPA)]N-acetyl-GIP1-42 showed receptor-mediated binding to BHK-GIPR positive cells, NES2Y cells and isolated islets. In vivo, both NES2Y and GIPR-transfected BHK tumors were visualized on SPECT/CT. Furthermore, co-administration of an excess unlabeled GIP1-42 lowered tracer uptake from 0.7 ± 0.2%ID/g to 0.6 ± 0.01%ID/g (p = 0.78) in NES2Y tumors and significantly lowered tracer uptake from 3.3 ± 0.8 to 0.8 ± 0.2%ID/g (p = 0.0001) in GIPR-transfected BHK tumors. In conclusion, [Lys37(111In-DTPA)]N-acetyl-GIP1-42 shows receptor-mediated binding in various models. Furthermore, both GIPR-transfected BHK tumors and NES2Y tumors were visible on SPECT/CT using this tracer. Therefore, [Lys37(111In-DTPA)]N-acetyl-GIP1-42 SPECT seems promising for visualization of somatostatin receptor negative NETs.
The Model Structures of the Complement Component 5a Receptor (C5aR) Bound to the Native and Engineered hC5a
Authors: Sahoo Amita Rani , Mishra Richa , Rana Soumendra
Published: February 2018

The interaction of hC5a with C5aR, previously hypothesized to involve a “two-site” binding, (i) recognition of the bulk of hC5a by the N-terminus (NT) of C5aR (“site1”), and (ii) recognition of C-terminus (CT) of hC5a by the extra cellular surface (ECS) of the C5aR (“site2”). However, the pharmacological landscapes of such recognition sites are yet to be illuminated at atomistic resolution. In the context, unique model complexes of C5aR, harboring pharmacophores of diverse functionality at the “site2” has recently been described. The current study provides a rational illustration of the “two-site” binding paradigm in C5aR, by recruiting the native agonist hC5a and engineered antagonist hC5a(A8). The hC5a-C5aR and hC5a(A8)-C5aR complexes studied over 250 ns of molecular dynamics (MD) each in POPC bilayer illuminate the hallmark of activation mechanism in C5aR. The intermolecular interactions in the model complexes are well supported by the molecular mechanics Poisson–Boltzmann surface area (MM-PBSA) based binding free energy calculation, strongly correlating with the reported mutational studies. Exemplified in two unique and contrasting molecular complexes, the study provides an exceptional understanding of the pharmacological divergence observed in C5aR, which will certainly be useful for search and optimization of new generation “neutraligands” targeting the hC5a-C5aR interaction.
BiFC-based visualisation system reveals cell fusion morphology and heterokaryon incompatibility in the filamentous fungus Aspergillus oryzae
Authors: Okabe Tomoya , Katayama Takuya , Mo Taoning , Mori Noriko , Jin Feng Jie , Fujii Ikuo , Iwashita Kazuhiro , Kitamoto Katsuhiko , Maruyama Jun-ichi
Published: February 2018

Aspergillus oryzae is an industrially important filamentous fungus used for Japanese traditional food fermentation and heterologous protein production. Although cell fusion is important for heterokaryon formation and sexual/parasexual reproduction required for cross breeding, knowledge on cell fusion and heterokaryon incompatibility in A. oryzae is limited because of low cell fusion frequency. Therefore, we aimed to develop a BiFC system to specifically visualise fused cells and facilitate the analysis of cell fusion in A. oryzae. The cell fusion ability and morphology of 15 A. oryzae strains were investigated using heterodimerising proteins LZA and LZB fused with split green fluorescence protein. Morphological investigation of fused cells revealed that cell fusion occurred mainly as conidial anastomosis during the early growth stage. Self-fusion abilities were detected in most industrial A. oryzae strains, but only a few strain pairs showed non-self fusion. Protoplast fusion assay demonstrated that almost all the pairs capable of non-self fusion were capable of heterokaryon formation and vice versa, thus providing the first evidence of heterokaryon incompatibility in A. oryzae. The BiFC system developed in this study provides an effective method in studying morphology of fused cells and heterokaryon incompatibility in the filamentous fungal species with low cell fusion efficiency.
Hydrogen-bonding cyclodiphosphazanes: superior effects of 3,5-(CF3)2-substitution in anion-recognition and counter-ion catalysis
Authors: Wolf Florian F. , Neudörfl Jörg-M. , Goldfuss Bernd
Published: February 2018

Syntheses, X-ray characterization and employment of new cyclodiphosph(v)azane hydrogen-bonding catalysts in experimental and computational anion recognition and the N-acyl-Mannich reaction.
Efficient synthesis and characterization of novel indolizines: exploration ofin vitroCOX-2 inhibitory activity and molecular modelling studies
Authors: Chandrashekharappa Sandeep , Venugopala Katharigatta N. , Tratrat Christophe , Mahomoodally Fawzi M. , Aldhubiab Bandar E. , Haroun Michelyne , Venugopala Rashmi , Mohan Mahendra K. , Kulkarni Rashmi S. , Attimarad Mahesh V. , Harsha Sree , Odhav Bharti
Published: February 2018

Novel indolizine scaffolds as COX-2 inhibiting agents.
Role of topological scale in the differential fouling of Pseudomonas aeruginosa and Staphylococcus aureus bacterial cells on wrinkled gold-coated polystyrene surfaces
Authors: Nguyen Duy H. K. , Pham Vy T. H. , Truong Vi Khanh , Sbarski Igor , Wang James , Balčytis Armandas , Juodkazis Saulius , Mainwaring David E. , Crawford Russell J. , Ivanova Elena P.
Published: February 2018

Wrinkled patterns, which possess an extensive surface area over a limited planar space, can provide surface features ranging across the nano- and microscale.
Recyclable heat-resisting polymer poly(ether azaindole ketone)-H+via hydrogen bonding crosslinking
Authors: Yin Q. , Peng Y. , Zhang S. , Zhu F. , Li W. , Du K.
Published: February 2018

A novel recyclable hydrogen bonding crosslinked polymer PEAINKH+ was prepared, which possesses outstanding thermal stability.
Highly efficient transformation of linear poly(phenylene ethynylene)s into zigzag-shaped π-conjugated microporous polymers through boron-mediated alkyne benzannulation
Authors: Shoji Yoshiaki , Hwang Minsu , Sugiyama Haruka , Ishiwari Fumitaka , Takenouchi Kumiko , Osuga Ryota , Kondo Junko N. , Fujikawa Shigenori , Fukushima Takanori
Published: February 2018

Linear poly(phenylene ethynylene)s are directly converted into zigzag-shaped π-conjugated microporous polymers.
Lysine-based amino-functionalized lipids for gene transfection: the influence of the chain composition on 2D properties
Authors: Tassler Stephanie , Pawlowska Dorota , Janich Christopher , Dobner Bodo , Wölk Christian , Brezesinski Gerald
Published: February 2018

Stiff TH10 and fluid OO10 Langmuir monolayers were investigated in the absence and presence of calf thymus DNA at different pH values.
A first-principles study of stability of surface confined mixed metal oxides with corundum structure (Fe2O3, Cr2O3, V2O3)
Authors: Jonayat A. S. M. , Kramer Alan , Bignardi Luca , Lacovig Paolo , Lizzit Silvano , van Duin Adri C.T. , Batzill Matthias , Janik Michael J.
Published: February 2018

Surface-confined mixed corundum metal oxides stability is shown to follow the stability trend of their similar pure oxide terminations.
Regioselective living polymerization of allylcyclohexane and precise synthesis of hydrocarbon block copolymers with cyclic units
Authors: Gao Jie , Ying Zonghang , Zhong Liu , Liao Heng , Gao Haiyang , Qing Wu
Published: February 2018

Regioselective living polymerization of allylcyclohexane was catalyzed by a bulky α-diimine nickel catalyst. Well-defined hydrocarbon block copolymers with cyclic units were constructed by sequential monomer addition.
Correction: Gas sensing performance at room temperature of nanogap interdigitated electrodes for detection of acetone at low concentration
Authors: Minh Q. Nguyen , Tong H. D. , Baggerman J. , Kuijk A. , Pujari S. P. , van der Bent J. F. , Beekman P. , van Rijn C. J. M.
Published: February 2018

Correction for ‘Gas sensing performance at room temperature of nanogap interdigitated electrodes for detection of acetone at low concentration’ by Q. Nguyen Minh et al., RSC Adv., 2017, 7, 50279–50286.
Cognitive Profiles of Finnish Preschool Children With Expressive and Receptive Language Impairment
Authors: Saar Virpi , Levänen Sari , Komulainen Erkki
Published: February 2018

Purpose

The aim of this study was to compare the verbal and nonverbal cognitive profiles of children with specific language impairment (SLI) with problems predominantly in expressive (SLI-E) or receptive (SLI-R) language skills. These diagnostic subgroups have not been compared before in psychological studies.

Method

Participants were preschool-age Finnish-speaking children with SLI diagnosed by a multidisciplinary team. Cognitive profile differences between the diagnostic subgroups and the relationship between verbal and nonverbal reasoning skills were evaluated.

Results

Performance was worse for the SLI-R subgroup than for the SLI-E subgroup not only in verbal reasoning and short-term memory but also in nonverbal reasoning, and several nonverbal subtests correlated significantly with the composite verbal index. However, weaknesses and strengths in the cognitive profiles of the subgroups were parallel.

Conclusions

Poor verbal comprehension and reasoning skills seem to be associated with lower nonverbal performance in children with SLI. Performance index (Performance Intelligence Quotient) may not always represent the intact nonverbal capacity assumed in SLI diagnostics, and a broader assessment is recommended when a child fails any of the compulsory Performance Intelligence Quotient subtests. Differences between the SLI subgroups appear quantitative rather than qualitative, in line with the new Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM V) classification (American Psychiatric Association, 2013).
On the Horizon: Older Adults With Autism in a Changing Health Care Environment
Authors: Smith Pamela A.
Published: February 2018

For many years, our health care system has been in a state of change, with most changes occurring as a result of economic issues and not clinical issues. Clinicians working in skilled nursing facilities (SNFs) have navigated a complex web of regulations and processes that are expected to change from a volume-driven system to a value-driven system. Such issues are challenging enough when clinicians are working with disorders with which they have received training and gained practical experience, but the growing population of residents in our facilities who are aging with autism will further complicate the SNF landscape. Because of the increases in prevalence of autism in the general population, the number of patients who will be entering our SNFs will only grow. New regulations and processes will require practice-based evidence and functional outcomes, data which do not exist with adults with autism. This article will discuss the impact of changes in our health care system, specifically in the SNF, and how these changes may impact the provision of care to a growing population of elders with autism.
Modelling and validating photovoltaic power inverter model for power system stability analysis
Authors: Ma Jin , Zhao Da‐Wei , Qian Min‐Hui , Zhu Ling‐Zhi , Geng Hua
Published: February 2018

This study presents model development and validation of the photovoltaic (PV) power using the real test data. The major contributions of this research are in two‐fold: First, the western electricity coordinating council (WECC) PV power plant model is discussed through comparison with tested data from one commercial PV inverter in China. The WECC PV model is modified and the improvement can provide more holistic view on the PV power plant dynamics. Second, the hybrid data simulation method is applied to validate the validity of the generic PV power model based on the real‐test data. The model simulation outputs are compared with the real measurements under typical scenarios. The research results presented in the study propose the application range for the generic PV power model for the electromechanic related stability analysis. Furthermore, the study also proposes the model improvement suggestions to increase the model credibility in simulating large system stability dynamics.
Impulsive radio and hard X-ray emission from an M-class flare
Authors: Zhang Ping , Guo Yang , Wang Lu , Liu Siming
Published: February 2018

Context. Impulsive radio and hard X-ray emission from large solar flares are usually attributed to a hard distribution of high-energy electrons accelerated in the energy dissipation process of magnetic reconnection.

Aims. We report the detection of impulsive radio and hard X-ray emissions produced by a population of energetic electrons with a very soft distribution in an M-class flare: SOL2015-08-27T05:45 .

Methods. The absence of impulsive emission at 34 GHz and hard X-ray emission above 50 keV and the presence of distinct impulsive emission at 17 GHz and lower frequencies and in the 25–50 keV X-ray band imply a very soft distribution of energetic electrons producing the impulsive radio emission via the gyro-synchrotron process, and impulsive X-rays via bremsstrahlung.

Results. The spectrum of the impulsive hard X-ray emission can be fitted equally well with a power-law model with an index of ∼6.5 or a super-hot thermal model with a temperature as high as 100 MK. Imaging observations in the extreme-UV and X-ray bands and extrapolation of the magnetic field structure using a nonlinear force-free model show that energetic electrons trapped in coronal loops are responsible for these impulsive emissions.

Conclusions. Since the index of the power-law model is nearly constant during the impulsive phase, the power-law distribution or the super-hot component should be produced by a bulk energization process such as the Fermi and betatron acceleration of collapsing magnetic loops.
Multi-spacecraft observations and transport simulations of solar energetic particles for the May 17th 2012 event
Authors: Battarbee M. , Guo J. , Dalla S. , Wimmer-Schweingruber R. , Swalwell B. , Lawrence D. J.
Published: February 2018

Context. The injection, propagation and arrival of solar energetic particles (SEPs) during eruptive solar events is an important and current research topic of heliospheric physics. During the largest solar events, particles may have energies up to a few GeVs and sometimes even trigger ground-level enhancements (GLEs) at Earth. These large SEP events are best investigated through multi-spacecraft observations.

Aims. We aim to study the first GLE-event of solar cycle 24, from 17th May 2012, using data from multiple spacecraft (SOHO, GOES, MSL, STEREO-A, STEREO-B and MESSENGER). These spacecraft are located throughout the inner heliosphere, at heliocentric distances between 0.34 and 1.5 astronomical units (au), covering nearly the whole range of heliospheric longitudes.

Methods. We present and investigate sub-GeV proton time profiles for the event at several energy channels, obtained via different instruments aboard the above spacecraft. We investigated issues caused by magnetic connectivity, and present results of three-dimensional SEP propagation simulations. We gathered virtual time profiles and perform qualitative and quantitative comparisons with observations, assessed longitudinal injection and transport effects as well as peak intensities.

Results. We distinguish different time profile shapes for well-connected and weakly connected observers, and find our onset time analysis to agree with this distinction. At select observers, we identify an additional low-energy component of Energetic Storm Particles (ESPs). Using well-connected observers for normalisation, our simulations are able to accurately recreate both time profile shapes and peak intensities at multiple observer locations.

Conclusions. This synergetic approach combining numerical modelling with multi-spacecraft observations is crucial for understanding the propagation of SEPs within the interplanetary magnetic field. Our novel analysis provides valuable proof of the ability to simulate SEP propagation throughout the inner heliosphere, at a wide range of longitudes. Accurate simulations of SEP transport allow for better constraints of injection regions at the Sun, and thus, better understanding of acceleration processes.
Opportunities for Audiologists to Use Patient-Centered Communication during Hearing Device Monitoring Encounters
Authors: Muñoz Karen , Ong Clarissa , Butcher Grayson , Nelson Lauri , Twohig Michael , Coleman Corinne
Published: February 2018

Patient-centered care incorporates patient's priorities, values, and goals. Audiologists can increase patient engagement when they use patient-centered principles during communication. Recent research, however, has revealed counseling gaps in audiology that could be detrimental to the intervention process. The present study sought to understand the extent patient-centered communication strategies were used during hearing device monitoring visits by analyzing audio recordings. Counseling portions of the appointments were transcribed using conversation analysis. Missed opportunities were observed, including not validating patients' emotional concerns, providing technical responses to emotional concerns, providing information without determining patient desire for the information, and not engaging the patient in a shared planning process. Training opportunities to enhance audiological services will be discussed.
Counseling in Audiology: Au.D. Students' Perspectives and Experiences
Authors: Muñoz Karen , Schultz Jared , Whicker John
Published: February 2018

Counseling in audiology is an important aspect of service delivery. How audiologists interact with patients and foster counseling relationships to help patients and families understand and live with hearing loss can impact outcomes of audiological interventions. Currently, variability exists in how graduate training programs are teaching counseling skills, and the extent to which counseling skills development is supported in clinical experiences is unclear. This article seeks to explore the perspectives related to the importance of counseling and counseling training experiences received through clinical instruction of Au.D. students beginning their final year of study, to identify where counseling training might be limited, and to examine how counseling skills might be better supported. Findings revealed that students generally appreciate the importance of counseling in audiology. Data suggest that how students are supported in developing counseling skills appears to be variable and unstructured.
Efficiency of Emergency Physicians: Insights from an Observational Study using EHR Log Files
Authors: Kannampallil Thomas , Denton Courtney , Shapiro Jason , Patel Vimla
Published: February 2018

Objective With federal mandates and incentives since the turn of this decade, electronic health records (EHR) have been widely adopted and used for clinical care. Over the last several years, we have seen both positive and negative perspectives on its use. Using an analysis of log files of EHR use, we investigated the nature of EHR use and their effect on an emergency department's (ED) throughput and efficiency.

Methods EHR logs of time spent by attending physicians on EHR-based activities over a 6-week period (n = 2,304 patients) were collected. For each patient encounter, physician activities in the EHR were categorized into four activities: documentation, review, orders, and navigation. Four ED-based performance metrics were also captured: door-to-provider time, door-to-doctor time, door-to-disposition time, and length of stay (LOS). Association between the four EHR-based activities and corresponding ED performance metrics were evaluated.

Results We found positive correlations between physician review of patient charts, and door-to-disposition time (r = 0.43, p < 0.05), and with LOS (r = 0.48, p < 0.05). There were no statistically significant associations between any of the other performance metrics and EHR activities.

Conclusion The results highlight that longer time spent on reviewing information on the EHR is potentially associated with decreased ED throughput efficiency. Balancing these competing goals is often a challenge of physicians, and its implications for patient safety is discussed.
Prospective evaluation of EUS-guided fine needle biopsy in pancreatic mass lesions
Authors: Larsen M. , Fristrup C. , Detlefsen S. , Mortensen M.
Published: February 2018

Background and study aim Due to the scarcity of specific data on endoscopic ultrasound (EUS)-guided fine-needle biopsies (SharkCore) FNB in the evaluation of pancreatic lesions, we performed a prospective study of the diagnostic performance of EUS SharkCore FNB in patients with pancreatic lesions. The aim of this study was to evaluate the diagnostic accuracy.

Patients and methods Single-center prospective study of 41 consecutive patients referred for EUS-FNB from October 2015 to April 2016 at our center. EUS-FNB was obtained in a predefined setting regarding the procedure and pathological evaluation. Data regarding demographics, lesion, technical parameters, and diagnostic accuracy were obtained.

Results The study included 41 consecutive patients (22 males (54 %); median age 68 years). The average size of the lesions was 28 mm (median: 30 mm). A diagnostic specimen was identified in 40 (98 %) cases during microscopy with an average of 2.4 passes. The route was trans-duodenal in 20 cases (49 %). The histological diagnosis of the specimens was malignant in 29 cases (71 %), benign in 8 (20 %), suspicious in 2 (5 %), atypical in 1 (2 %) and in 1 (2 %) no material for microscopic evaluation was obtained. This led to a diagnostic accuracy of 93 %, sensitivity of 91 % and a specificity of 100 %. 2 cases (5 %) of self-limiting bleeding were observed. The diagnosis at follow up was malignant in 32 (78 %) of the patients.

Conclusions EUS-FNB of pancreatic mass lesions with the SharkCore needle produced specimens with a diagnostic accuracy of 93 %. The procedure was safe and easy to perform, and these data support the use of EUS-FNB in a routine setting.
Usefulness of a multifunctional snare designed for colorectal hybrid endoscopic submucosal dissection (with video)
Authors: Ohata Ken , Muramoto Takashi , Minato Yohei , Chiba Hideyuki , Sakai Eiji , Matsuhashi Nobuyuki
Published: February 2018

Since colorectal endoscopic submucosal dissection (ESD) remains technically difficult, hybrid ESD was developed as an alternative therapeutic option to achieve en bloc resection of relatively large lesions. In this feasibility study, we evaluated the safety and efficacy of hybrid colorectal ESD using a newly developed multifunctional snare. From June to August 2016, we prospectively enrolled 10 consecutive patients with non-pedunculated intramucosal colorectal tumors 20 – 30 mm in diameter. All of the hybrid ESD steps were performed using the “SOUTEN” snare. The knob-shaped tip attached to the loop top helps to stabilize the needle-knife, making it less likely to slip during circumferential incision and enables partial submucosal dissection. All of the lesions were curatively resected by hybrid ESD, with a short mean procedure time (16.1 ± 4.8 minutes). The mean diameters of the resected specimens and tumors were 30.5 ± 4.9 and 26.0 ± 3.5 mm, respectively. No perforations occurred, while delayed bleeding occurred in 1 patient. In conclusion, hybrid ESD using a multifunctional snare enables easy, safe, and cost-effective resection of relatively large colorectal tumors to be achieved.

Study registration: UMIN000022545
Endobronchial Ultrasound (EBUS) – Update 2017
Authors: Darwiche Kaid , Özkan Filiz , Wolters Celina , Eisenmann Stephan
Published: February 2018

Endobronchial ultrasound (EBUS) has revolutionized the diagnosis of lung cancer over the last decade. This minimally invasive diagnostic method has also become increasingly important in the case of other diseases such as sarcoidosis, thereby helping to avoid unnecessary diagnostic interventions. This review article provides an update regarding EBUS and discusses current and future developments of this method.
Gaze patterns hold key to unlocking successful search strategies and increasing polyp detection rate in colonoscopy
Authors: Lami Mariam , Singh Harsimrat , Dilley James , Ashraf Hajra , Edmondon Matthew , Orihuela-Espina Felipe , Hoare Jonathan , Darzi Ara , Sodergren Mikael
Published: February 2018

Background The adenoma detection rate (ADR) is an important quality indicator in colonoscopy. The aim of this study was to evaluate the changes in visual gaze patterns (VGPs) with increasing polyp detection rate (PDR), a surrogate marker of ADR.

Methods 18 endoscopists participated in the study. VGPs were measured using eye-tracking technology during the withdrawal phase of colonoscopy. VGPs were characterized using two analyses – screen and anatomy. Eye-tracking parameters were used to characterize performance, which was further substantiated using hidden Markov model (HMM) analysis.

Results Subjects with higher PDRs spent more time viewing the outer ring of the 3 × 3 grid for both analyses (screen-based: r = 0.56, P = 0.02; anatomy: r = 0.62, P < 0.01). Fixation distribution to the “bottom U” of the screen in screen-based analysis was positively correlated with PDR (r = 0.62, P = 0.01). HMM demarcated the VGPs into three PDR groups.

Conclusion This study defined distinct VGPs that are associated with expert behavior. These data may allow introduction of visual gaze training within structured training programs, and have implications for adoption in higher-level assessment.