bluuebunny/crossref_metadata_2025 huggingface dataset:
Branching morphology determines signal propagation dynamics in neurons
Authors: Ofer Netanel , Shefi Orit , Yaari Gur
Published: August 2017

Computational modeling of signal propagation in neurons is critical to our understanding of basic principles underlying brain organization and activity. Exploring these models is used to address basic neuroscience questions as well as to gain insights for clinical applications. The seminal Hodgkin Huxley model is a common theoretical framework to study brain activity. It was mainly used to investigate the electrochemical and physical properties of neurons. The influence of neuronal structure on activity patterns was explored, however, the rich dynamics observed in neurons with different morphologies is not yet fully understood. Here, we study signal propagation in fundamental building blocks of neuronal branching trees, unbranched and branched axons. We show how these simple axonal elements can code information on spike trains, and how asymmetric responses can emerge in axonal branching points. This asymmetric phenomenon has been observed experimentally but until now lacked theoretical characterization. Together, our results suggest that axonal morphological parameters are instrumental in activity modulation and information coding. The insights gained from this work lay the ground for better understanding the interplay between function and form in real-world complex systems. It may also supply theoretical basis for the development of novel therapeutic approaches to damaged nervous systems.
TDAG8, TRPV1, and ASIC3 involved in establishing hyperalgesic priming in experimental rheumatoid arthritis
Authors: Hsieh Wei-Shan , Kung Chia-Chi , Huang Shir-Ly , Lin Shih-Chang , Sun Wei-Hsin
Published: August 2017

Rheumatoid arthritis (RA), characterized by chronic inflammation of synovial joints, is often associated with ongoing pain and increased pain sensitivity. High hydrogen ion concentration (acidosis) found in synovial fluid in RA patients is associated with disease severity. Acidosis signaling acting on proton-sensing receptors may contribute to inflammation and pain. Previous studies focused on the early phase of arthritis (<5 weeks) and used different arthritis models, so elucidating the roles of different proton-sensing receptors in the chronic phase of arthritis is difficult. We intra-articularly injected complete Freund’s adjuvant into mice once a week for 4 weeks to establish chronic RA pain. Mice with knockout of acid-sensing ion channel 3 (ASIC3) or transient receptor potential/vanilloid receptor subtype 1 (TRPV1) showed attenuated chronic phase (>6 weeks) of RA pain. Mice with T-cell death-associated gene 8 (TDAG8) knockout showed attenuated acute and chronic phases of RA pain. TDAG8 likely participates in the initiation of RA pain, but all three genes, TDAG8, TRPV1, and ASIC3, are essential to establish hyperalgesic priming to regulate the chronic phase of RA pain.
Ccdc3: A New P63 Target Involved in Regulation Of Liver Lipid Metabolism
Authors: Liao Wenjuan , Liu Hongbing , Zhang Yiwei , Jung Ji Hoon , Chen Jiaxiang , Su Xiaohua , Kim Yeong C. , Flores Elsa R , Wang San Ming , Czarny-Ratajczak Malwina , Li Wen , Zeng Shelya X. , Lu Hua
Published: August 2017

TAp63, a member of the p53 family, has been shown to regulate energy metabolism. Here, we report coiled coil domain-containing 3 (CCDC3) as a new TAp63 target. TAp63, but not ΔNp63, p53 or p73, upregulates CCDC3 expression by directly binding to its enhancer region. The CCDC3 expression is markedly reduced in TAp63-null mouse embryonic fibroblasts and brown adipose tissues and by tumor necrosis factor alpha that reduces p63 transcriptional activity, but induced by metformin, an anti-diabetic drug that activates p63. Also, the expression of CCDC3 is positively correlated with TAp63 levels, but conversely with ΔNp63 levels, during adipocyte differentiation. Interestingly, CCDC3, as a secreted protein, targets liver cancer cells and increases long chain polyunsaturated fatty acids, but decreases ceramide in the cells. CCDC3 alleviates glucose intolerance, insulin resistance and steatosis formation in transgenic CCDC3 mice on high-fat diet (HFD) by reducing the expression of hepatic PPARγ and its target gene CIDEA as well as other genes involved in de novo lipogenesis. Similar results are reproduced by hepatic expression of ectopic CCDC3 in mice on HFD. Altogether, these results demonstrate that CCDC3 modulates liver lipid metabolism by inhibiting liver de novo lipogenesis as a downstream player of the p63 network.
Gender differences in influences of temperament on olfactory reactivity and awareness
Authors: Martinec Nováková Lenka , Vojtušová Mrzílková Radka , Kernerová Anna
Published: August 2017

Children’s olfactory performance is associated with temperament but whether there is a link with olfactory reactivity and awareness is not known. In adults negative affectivity is linked to reactivity to environmental odours but it is not clear whether these associations extend to children. We aimed to investigate the effect of temperamental factors on olfactory reactivity and awareness. In so doing, we controlled for the effect of parenting styles on temperamental assessment and of verbal fluency on children’s olfactory reactivity and awareness. We hypothesised that children with a high degree of negative affectivity would show greater olfactory reactivity and awareness. 129 children (62 boys, mean age 6.83 ± 0.40 years) were interviewed about their olfactory reactivity and awareness in everyday life using the established Children’s Olfactory Behavior in Everyday Life questionnaire (COBEL). Parents assessed their child’s temperament using the 94-item short form of the Children’s Behavior Questionnaire. We found that the relationship between negative affectivity and total COBEL scores varied between the genders: there was a positive, medium to large effect in boys and a negative, small one in girls. Future studies could include behavioural observations of temperament and olfactory reactivity and awareness.
Lattice topology dictates photon statistics
Authors: Kondakci H. Esat , Abouraddy Ayman F. , Saleh Bahaa E. A.
Published: August 2017

Propagation of coherent light through a disordered network is accompanied by randomization and possible conversion into thermal light. Here, we show that network topology plays a decisive role in determining the statistics of the emerging field if the underlying lattice is endowed with chiral symmetry. In such lattices, eigenmode pairs come in skew-symmetric pairs with oppositely signed eigenvalues. By examining one-dimensional arrays of randomly coupled waveguides arranged on linear and ring topologies, we are led to a remarkable prediction: the field circularity and the photon statistics in ring lattices are dictated by its parity while the same quantities are insensitive to the parity of a linear lattice. For a ring lattice, adding or subtracting a single lattice site can switch the photon statistics from super-thermal to sub-thermal, or vice versa. This behavior is understood by examining the real and imaginary fields on a lattice exhibiting chiral symmetry, which form two strands that interleave along the lattice sites. These strands can be fully braided around an even-sited ring lattice thereby producing super-thermal photon statistics, while an odd-sited lattice is incommensurate with such an arrangement and the statistics become sub-thermal.
Peroxiredoxin1, a novel regulator of pronephros development, influences retinoic acid and Wnt signaling by controlling ROS levels
Authors: Chae Soomin , Lee Hyun-Kyung , Kim Yoo-Kyung , Jung Sim Hyo , Ji Yoorim , Kim Chowon , Ismail Tayaba , Park Jeen-Woo , Kwon Oh-Shin , Kang Beom-Sik , Lee Dong-Seok , Bae Jong-Sup , Kim Sang-Hyun , Min Kyoung-Jin , Kyu Kwon Taeg , Park Mae-Ja , Han Jin-Kwan , Kwon Taejoon , Park Tae-Joo , Lee Hyun-Shik
Published: August 2017

Peroxiredoxin1 (Prdx1) is an antioxidant enzyme belonging to the peroxiredoxin family of proteins. Prdx1 catalyzes the reduction of H2O2 and alkyl hydroperoxide and plays an important role in different biological processes. Prdx1 also participates in various age-related diseases and cancers. In this study, we investigated the role of Prdx1 in pronephros development during embryogenesis. Prdx1 knockdown markedly inhibited proximal tubule formation in the pronephros and significantly increased the cellular levels of reactive oxygen species (ROS), which impaired primary cilia formation. Additionally, treatment with ROS (H2O2) severely disrupted proximal tubule formation, whereas Prdx1 overexpression reversed the ROS-mediated inhibition in proximal tubule formation. Epistatic analysis revealed that Prdx1 has a crucial role in retinoic acid and Wnt signaling pathways during pronephrogenesis. In conclusion, Prdx1 facilitates proximal tubule formation during pronephrogenesis by regulating ROS levels.
Control of unsteady laser-produced plasma-flow with a multiple-coil magnetic nozzle
Authors: Morita Taichi , Edamoto Masafumi , Miura Satoshi , Sunahara Atsushi , Saito Naoya , Itadani Yutaro , Kojima Tomihiko , Mori Yoshitaka , Johzaki Tomoyuki , Kajimura Yoshihiro , Fujioka Shinsuke , Yogo Akifumi , Nishimura Hiroaki , Nakashima Hideki , Yamamoto Naoji
Published: August 2017

We report an experimental demonstration of controlling plasma flow direction with a magnetic nozzle consisting of multiple coils. Four coils are controlled separately to form an asymmetric magnetic field to change the direction of laser-produced plasma flow. The ablation plasma deforms the topology of the external magnetic field, forming a magnetic cavity inside and compressing the field outside. The compressed magnetic field pushes the plasma via the Lorentz force on a diamagnetic current: j × B in a certain direction, depending on the magnetic field configuration. Plasma and magnetic field structure formations depending on the initial magnetic field were simultaneously measured with a self-emission gated optical imager and B-dot probe, respectively, and the probe measurement clearly shows the difference of plasma expansion direction between symmetric and asymmetric initial magnetic fields. The combination of two-dimensional radiation hydrodynamic and three-dimensional hybrid simulations shows the control of the deflection angle with different number of coils, forming a plasma structure similar to that observed in the experiment.
A novel c-di-GMP binding domain in glycosyltransferase BgsA is responsible for the synthesis of a mixed-linkage β-glucan
Authors: Pérez-Mendoza Daniel , Bertinetti Daniela , Lorenz Robin , Gallegos María-Trinidad , Herberg Friedrich W. , Sanjuán Juan
Published: August 2017

BgsA is the glycosyltransferase (GT) involved in the synthesis of a linear mixed-linkage β-glucan (MLG), a recently described exopolysaccharide activated by c-di-GMP in Sinorhizobium meliloti and other Rhizobiales. Although BgsA displays sequence and structural homology with bacterial cellulose synthases (CS), it does not contain any predictable c-di-GMP binding domain. In this work we demonstrate that the cytoplasmic C-terminal domain of BgsA (C-BgsA) binds c-di-GMP with both high affinity (KD = 0.23 μM) and specificity. C-BgsA is structurally different to the otherwise equivalent cytoplasmic C-terminal domain of CS, and does not contain PilZ motifs for c-di-GMP recognition. A combination of random and site-directed mutagenesis with surface plasmon resonance (SPR) allowed identification of the C-BgsA residues which are important not only for c-di-GMP binding, but also for BgsA GT activity. The results suggest that the C-BgsA domain is important for both, c-di-GMP binding and GT activity of BgsA. In contrast to bacterial CS where c-di-GMP has been proposed as a derepressor of GT activity, we hypothesize that the C-terminal domain of BgsA plays an active role in BgsA GT activity upon binding c-di-GMP.
Fractal evolution under in situ pressure and sorption conditions for coal and shale
Authors: Zhang Rui , Liu Shimin , Wang Yang
Published: August 2017

Coalbed methane (CBM) and shale gas become two most important unconventional natural gas resources in US. The fractal dimension, known as the degree of self-similarity or irregularity, is an important parameter to quantitatively characterize gas storage capacity and gas transport properties in pores of rock matrix. In this study, two coal and two shale samples were evaluated to estimate fractal dimensions using combined small angle X-ray scattering (SAXS), small angle neutron scattering (SANS) and low-pressure N2 adsorption techniques. The results show that surface fractal dimension D
s
of inaccessible pores is greater than that for total pores based on SANS results for all four tested samples. D
s
of accessible pores estimated by N2 desorption is greater than that for N2 adsorption for each linear section of each tested sample. Based on in situ SANS results, D
s
slightly decreases with increasing argon injecting pressure for San Juan coal. D
s
decreases with increasing methane and CO2 injecting pressure for samples with high D
s
. However, D
s
significantly increases when CO2 became liquid phase for samples with low D
s
. Furthermore, D
s
almost didn’t change after methane and argon penetrations for all these samples except Marcellus outcrop shale.
Integrative epigenomics, transcriptomics and proteomics of patient chondrocytes reveal genes and pathways involved in osteoarthritis
Authors: Steinberg Julia , Ritchie Graham R. S. , Roumeliotis Theodoros I. , Jayasuriya Raveen L. , Clark Matthew J. , Brooks Roger A. , Binch Abbie L. A. , Shah Karan M. , Coyle Rachael , Pardo Mercedes , Le Maitre Christine L. , Ramos Yolande F. M. , Nelissen Rob G. H. H. , Meulenbelt Ingrid , McCaskie Andrew W. , Choudhary Jyoti S. , Wilkinson J. Mark , Zeggini Eleftheria
Published: August 2017

Osteoarthritis (OA) is a common disease characterized by cartilage degeneration and joint remodeling. The underlying molecular changes underpinning disease progression are incompletely understood. We investigated genes and pathways that mark OA progression in isolated primary chondrocytes taken from paired intact versus degraded articular cartilage samples across 38 patients undergoing joint replacement surgery (discovery cohort: 12 knee OA, replication cohorts: 17 knee OA, 9 hip OA patients). We combined genome-wide DNA methylation, RNA sequencing, and quantitative proteomics data. We identified 49 genes differentially regulated between intact and degraded cartilage in at least two –omics levels, 16 of which have not previously been implicated in OA progression. Integrated pathway analysis implicated the involvement of extracellular matrix degradation, collagen catabolism and angiogenesis in disease progression. Using independent replication datasets, we showed that the direction of change is consistent for over 90% of differentially expressed genes and differentially methylated CpG probes. AQP1, COL1A1 and CLEC3B were significantly differentially regulated across all three –omics levels, confirming their differential expression in human disease. Through integration of genome-wide methylation, gene and protein expression data in human primary chondrocytes, we identified consistent molecular players in OA progression that replicated across independent datasets and that have translational potential.
CitH3: a reliable blood biomarker for diagnosis and treatment of endotoxic shock
Authors: Pan Baihong , Alam Hasan B. , Chong Wei , Mobley James , Liu Baoling , Deng Qiufang , Liang Yinjian , Wang Yanming , Chen Eric , Wang Tianbing , Tewari Muneesh , Li Yongqing
Published: August 2017

Current biomarkers for sepsis are limited by their non-specificity, short half-life, and insensitive response to therapy. Recently, we have demonstrated that citrullinated histone H3(CitH3) is released into the blood from neutrophil extracellular traps(NETs) in response to severe infection, and CitH3 may be a potential biomarker for sepsis. In the present study, we found that NET components were released in mouse models of both lipopolysaccharide(LPS)-induced shock (LPSS) and hemorrhagic shock (HS). To further quantify CitH3 in the NETs, we established a CitH3 specific enzyme-linked immunosorbent assay. Circulating CitH3 was found to be elevated only in LPSS but not in HS. Importantly, blood CitH3 was detected 30 minutes after LPS insult, and remained elevated for 24 hours (period of the highest mortality). Treatment of endotoxic mice with YW3-56, a peptidylarginine deiminase-2/4 inhibitor, significantly diminished levels of CitH3 in the blood. Interleukin-1β did not respond to LPS early, and interleukin-1β and interleukin-6 fluctuated although they responded to treatment. Procalcitonin reacted to LPS insult late. Compared to CitH3, these biomarkers were non-specifically induced in LPSS and HS. Collectively, our results demonstrate that YW3-56 protects animals from LPSS, and CitH3 is a reliable biomarker due to its early appearance, specificity, duration, and response to therapeutic intervention.
Integrated analysis of mRNA and miRNA expression in HeLa cells expressing low levels of Nucleolin
Authors: Kumar Sanjeev , Gomez Elizabhet Cruz , Chalabi-Dchar Mounira , Rong Cong , Das Sadhan , Ugrinova Iva , Gaume Xavier , Monier Karine , Mongelard Fabien , Bouvet Philippe
Published: August 2017

Nucleolin is an essential protein that plays important roles in the regulation of cell cycle and cell proliferation. Its expression is up regulated in many cancer cells but its molecular functions are not well characterized. Nucleolin is present in the nucleus where it regulates gene expression at the transcriptional and post-transcriptional levels. Using HeLa cells depleted in nucleolin we performed an mRNA and miRNA transcriptomics analysis to identify biological pathways involving nucleolin. Bioinformatic analysis strongly points to a role of nucleolin in lipid metabolism, and in many signaling pathways. Down regulation of nucleolin is associated with lower level of cholesterol while the amount of fatty acids is increased. This could be explained by the decreased and mis-localized expression of the transcription factor SREBP1 and the down-regulation of enzymes involved in the beta-oxidation and degradation of fatty acids. Functional classification of the miRNA-mRNA target genes revealed that deregulated miRNAs target genes involved in apoptosis, proliferation and signaling pathways. Several of these deregulated miRNAs have been shown to control lipid metabolism. This integrated transcriptomic analysis uncovers new unexpected roles for nucleolin in metabolic regulation and signaling pathways paving the way to better understand the global function of nucleolin within the cell.
Vascular channels in metacarpophalangeal joints: a comparative histologic and high-resolution imaging study
Authors: Scharmga A. , Keller K. K. , Peters M. , van Tubergen A. , van den Bergh J. P. , van Rietbergen B. , Weijers R. , Loeffen D. , Hauge E. M. , Geusens P.
Published: August 2017

We evaluated whether cortical interruptions classified as vascular channel (VC) on high-resolution peripheral quantitative computed tomography (HR-pQCT) could be confirmed by histology. We subsequently evaluated the image characteristics of histologically identified VCs on matched single and multiplane HR-pQCT images. Four 3-mm thick portions in three anatomic metacarpophalangeal joint specimens were selected for histologic sectioning. First, VCs identified with HR-pQCT were examined for confirmation on histology. Second and independently, VCs identified by histology were matched to single and multiplane HR-pQCT images to assess for presence of cortical interruptions. Only one out of five cortical interruptions suggestive for VC on HR-pQCT could be confirmed on histology. In contrast, 52 VCs were identified by histology of which 39 (75%) could be classified as cortical interruption or periosteal excavation on matched single HR-pQCT slices. On multiplane HR-pQCT images, 11 (21%) showed a cortical interruption in at least two consecutive slices in two planes, 36 (69%) in at least one slice in two planes and five (10%) showed no cortical interruption. Substantially more VCs were present in histology sections than initially suggested by HR-pQCT. The small size and heterogeneous presentation, limit the identification as VC on HR-pQCT.
On the surface effects of citrates on nano-apatites: evidence of a decreased hydrophilicity
Authors: Ivanchenko Pavlo , Delgado-López José Manuel , Iafisco Michele , Gómez-Morales Jaime , Tampieri Anna , Martra Gianmario , Sakhno Yuriy
Published: August 2017

The surface structure and hydrophilicity of synthetic nanocrystalline apatite with strongly bound citrates on their surface are here investigated at the molecular level, by combining advanced IR spectroscopy, microgravimetry and adsorption microcalorimetry. Citrate are found to form unidentate-like and ionic-like complexes with surface Ca2+ ions, with a surface coverage closely resembling that present in bone apatite platelets (i.e., 1 molecule/(n nm)2, with n ranging between 1.4 and 1.6). These surface complexes are part of a hydrated non-apatitic surface layer with a sub-nanometre thickness. Noticeably, it is found that the hydrophilicity of the nanoparticles, measured in terms of adsorption of water molecules in the form of multilayers, decreases in a significant extent in relation to the presence of citrates, most likely because of the exposure toward the exterior of –CH2 groups. Our findings provide new insights on the surface properties of bio-inspired nano-apatites, which can be of great relevance for better understanding the role of citrate in determining important interfacial properties, such as hydrophobicity, of bone apatite platelets. The evaluation and comprehension of surface composition and structure is also of paramount interest to strictly control the functions of synthetic biomaterials, since their surface chemistry strongly affects the hosting tissue response.
Bifunctional quorum-quenching and antibiotic-acylase MacQ forms a 170-kDa capsule-shaped molecule containing spacer polypeptides
Authors: Yasutake Yoshiaki , Kusada Hiroyuki , Ebuchi Teppei , Hanada Satoshi , Kamagata Yoichi , Tamura Tomohiro , Kimura Nobutada
Published: August 2017

Understanding the molecular mechanisms of bacterial antibiotic resistance will help prepare against further emergence of multi-drug resistant strains. MacQ is an enzyme responsible for the multi-drug resistance of Acidovorax sp. strain MR-S7. MacQ has acylase activity against both N-acylhomoserine lactones (AHLs), a class of signalling compounds involved in quorum sensing, and β-lactam antibiotics. Thus, MacQ is crucial as a quencher of quorum sensing as well as in conferring antibiotic resistance in Acidovorax. Here, we report the X-ray structures of MacQ in ligand-free and reaction product complexes. MacQ forms a 170-kDa capsule-shaped molecule via face-to-face interaction with two heterodimers consisting of an α-chain and a β-chain, generated by the self-cleaving activity of a precursor polypeptide. The electron density of the spacer polypeptide in the hollow of the molecule revealed the close orientation of the peptide-bond atoms of Val20SP-Gly21SP to the active-site, implying a role of the residues in substrate binding. In mutational analyses, uncleaved MacQ retained degradation activity against both AHLs and penicillin G. These results provide novel insights into the mechanism of self-cleaving maturation and enzymatic function of N-terminal nucleophile hydrolases.
Three-dimensional plasmonic Ag/TiO2 nanocomposite architectures on flexible substrates for visible-light photocatalytic activity
Authors: Zhao Zhi-Jun , Hwang Soon Hyoung , Jeon Sohee , Hwang Boyeon , Jung Joo-Yun , Lee Jihye , Park Sang-Hu , Jeong Jun-Ho
Published: August 2017

In this study, a periodic three-dimensional (3D) Ag/TiO2nanocomposite architecture of nanowires was fabricated on a flexible substrate to enhance the plasmonic photocatalytic activity of the composite. Layer-by-layer nanofabrication based on nanoimprint lithography, vertical e-beam evaporation, nanotransfer, and nanowelding was applied in a new method to create different 3D Ag/TiO2nanocomposite architectures. The fabricated samples were characterized by scanning electron microscopy, transmission electron microscopy, focused ion-beam imaging, X-ray photoelectron spectrometry, and UV–visible spectroscopy. The experiment indicated that the 3D nanocomposite architectures could effectively enhance photocatalytic activity in the degradation of methylene blue solution under visible light irradiation. We believe that our method is efficient and stable, which could be applied to various fields, including photocatalysis, solar energy conversion, and biotechnology.
Ibuprofen and ketoprofen potentiate UVA-induced cell death by a photosensitization process
Authors: Bignon Emmanuelle , Marazzi Marco , Besancenot Vanessa , Gattuso Hugo , Drouot Guillaume , Morell Christophe , Eriksson Leif A. , Grandemange Stephanie , Dumont Elise , Monari Antonio
Published: August 2017

Nonsteroidal 2-arylproprionic acids are widely used, over-the-counter, anti-inflammatory drugs. Photosensitivity is a commonly overlooked adverse effect of these drugs. Based on the combined use of cell viability assays and molecular modeling, we prove and rationalize the photochemical pathways triggering photosensitization for two drugs, ibuprofen and ketoprofen. As its parent compound benzophenone, ketoprofen produces singlet oxygen, upon triplet manifold population. However, ibuprofen and ketoprofen photodissociate and hence may generate two highly reactive radicals. The formation of metastable aggregates between the two drugs and B-DNA is also directly probed by molecular dynamics. Our approach characterizes the coupled influence of the drug’s intrinsic photochemistry and the interaction pattern with DNA. The photosensitization activity of nonsteroidal 2-arylproprionic acids, being added to gels and creams for topical use, should be crucially analyzed and rationalized to enact the proper preventive measures.
Analysis of mononucleotides by tandem mass spectrometry: investigation of fragmentation pathways for phosphate- and ribose-modified nucleotide analogues
Authors: Strzelecka Dominika , Chmielinski Sebastian , Bednarek Sylwia , Jemielity Jacek , Kowalska Joanna
Published: August 2017

Synthetic nucleotide and nucleic acid analogues are useful research tools and modern therapeutics. Hence, methods for the rapid and unambiguous identification of mononucleotides derived from organic syntheses or biological materials are of broad interest. Here, we analysed over 150 mononucleotides (mostly nucleoside 5′-mono-, 5′-di-, and 5′-triphosphates) and their structurally related nucleobase-, phosphate-, and ribose-modified analogues by electrospray tandem mass spectrometry (ESI/MS/MS), identifying characteristic fragmentation ions that may be helpful in structure determination. While positive-ion mode yielded fragments derived mainly from nucleobases, negative-ion mode provided insight into the structures of phosphoryl and phosphoribosyl moieties, enabling the determination of structural features such as the number of phosphate groups and the presence of ribose or phosphate substitutions. Based on these data, we proposed fragmentation pathways that were confirmed by experiments with [18O]-isotopologues. We demonstrated the utility of ESI(−)/MS/MS in the analysis of structurally related compounds by analysing isomeric and isobaric nucleotides and applying ESI(−)/MS/MS to rapid identification of nucleotide synthesis products. We formulated general rules regarding nucleotide structure–fragmentation pattern relationships and indicating characteristic fragmentation ions for the interpretation of ESI(−)/MS/MS spectra of nucleotides and their analogues. The ESI(−)/MS/MS spectra of all nucleotides are available in an on-line database, msTide, at www.msTide-db.com.
Chemotherapy with cisplatin: insights into intracellular pH and metabolic landscape of cancer cells in vitro and in vivo
Authors: Shirmanova Marina V. , Druzhkova Irina N. , Lukina Maria M. , Dudenkova Varvara V. , Ignatova Nadezhda I. , Snopova Ludmila B. , Shcheslavskiy Vladislav I. , Belousov Vsevolod V. , Zagaynova Elena V.
Published: August 2017

Although cisplatin plays a central role in cancer chemotherapy, the mechanisms of cell response to this drug have been unexplored. The present study demonstrates the relationships between the intracellular pH (pHi), cell bioenergetics and the response of cervical cancer to cisplatin. pHi was measured using genetically encoded sensor SypHer2 and metabolic state was accessed by fluorescence intensities and lifetimes of endogenous cofactors NAD(P)H and FAD. Our data support the notion that cisplatin induces acidification of the cytoplasm early after the treatment. We revealedin vitrothat a capacity of cells to recover and maintain alkaline pHi after the initial acidification is the crucial factor in mediating the cellular decision to survive and proliferate at a vastly reduced rate or to undergo cell death. Additionally, we showed for the first time that pHi acidification occurs after prolonged therapyin vitroandin vivo, and this, likely, favors metabolic reorganization of cells. A metabolic shift from glycolysis towards oxidative metabolism accompanied the cisplatin-induced inhibition of cancer cell growthin vitroandin vivo. Overall, these findings contribute to an understanding of the mechanisms underlying the responsiveness of an individual cell and tumor to therapy and are valuable for developing new therapeutic strategies.
TRAF4 promotes lung cancer aggressiveness by modulating tumor microenvironment in normal fibroblasts
Authors: Kim EunGi , Kim Wanyeon , Lee Sungmin , Chun Jahyun , Kang JiHoon , Park Gaeul , Han IkJoon , Yang Hee Jung , Youn HyeSook , Youn BuHyun
Published: August 2017

Normal fibroblasts surrounding tumor cells play a crucial role in cancer progression through formation of the tumor microenvironment. Because factors secreted from normal fibroblasts can modulate the tumor microenvironment, it is necessary to identify key factors associated with regulation of secreted factors and to investigate the molecular mechanisms contributing to the tumor microenvironment formation process. In this study, we found that radiation induced the expression and K63-linkage poly-ubiquitination of TRAF4 in normal lung fibroblasts. The K63-linkage poly-ubiquitinated TRAF4 formed complexes with NOX2 or NOX4 by mediating phosphorylated p47-phox in normal lung fibroblasts. Moreover, we showed that TRAF4 stabilized NOX complexes by decreasing lysosomal degradation of NOX2 and NOX4 after irradiation. NOX complexes increased endosomal ROS levels that were permeable into cytoplasm, leading to NF-κB-mediated ICAM1 up-regulation. Soluble ICAM1 was subsequently secreted into conditioned media of radiation-activated normal lung fibroblasts. The conditioned media from irradiated normal fibroblasts enhanced proliferation and epithelial-mesenchymal transition of non-small cell lung cancer cells both in vitro and in vivo. These results demonstrate that TRAF4 in irradiated fibroblasts is positively associated with aggressiveness of adjacent cancer cells by altering the tumor microenvironment. Thus, we suggest that regulation of TRAF4 might be a promising strategy for cancer therapy.
Characterization and structural determination of a new anti-MET function-blocking antibody with binding epitope distinct from the ligand binding domain
Authors: DiCara Danielle M. , Chirgadze Dimitri Y. , Pope Anthony R. , Karatt-Vellatt Aneesh , Winter Anja , Slavny Peter , van den Heuvel Joop , Parthiban Kothai , Holland Jane , Packman Len C. , Mavria Georgia , Hoffmann Jens , Birchmeier Walter , Gherardi Ermanno , McCafferty John
Published: August 2017

The growth and motility factor Hepatocyte Growth Factor/Scatter Factor (HGF/SF) and its receptor, the product of the MET proto-oncogene, promote invasion and metastasis of tumor cells and have been considered potential targets for cancer therapy. We generated a new Met-blocking antibody which binds outside the ligand-binding site, and determined the crystal structure of the Fab in complex with its target, which identifies the binding site as the Met Ig1 domain. The antibody, 107_A07, inhibited HGF/SF-induced cell migration and proliferation in vitro and inhibited growth of tumor xenografts in vivo. In biochemical assays, 107_A07 competes with both HGF/SF and its truncated splice variant NK1 for MET binding, despite the location of the antibody epitope on a domain (Ig1) not reported to bind NK1 or HGF/SF. Overlay of the Fab-MET crystal structure with the InternalinB-MET crystal structure shows that the 107_A07 Fab comes into close proximity with the HGF/SF-binding SEMA domain when MET is in the “compact”, InternalinB-bound conformation, but not when MET is in the “open” conformation. These findings provide further support for the importance of the “compact” conformation of the MET extracellular domain, and the relevance of this conformation to HGF/SF binding and signaling.
Low TIM3 expression indicates poor prognosis of metastatic prostate cancer and acts as an independent predictor of castration resistant status
Authors: Wu Junlong , Lin Guowen , Zhu Yao , Zhang Hailiang , Shi Guohai , Shen Yijun , Zhu Yiping , Dai Bo , Ye Dingwei
Published: August 2017

T cell immunoglobulin 3 (TIM3) is a cell surface star molecule expressed on T cells, and also marks dysfunctional CD8+ T cells in various kinds of cancers. However, there are few studies focusing on the expression of TIM3 in tumor cells. In our study, we recruited 139 patients with metastatic prostate cancer (mPCa) who received transurethral resection of the prostate (TURP) consecutively to examine whether TIM3 expression level is associated with overall survival (OS) in mPCa patients. Immunohistochemistry was performed to determine TIM3 expression in prostate cancer tissues and then patients were divided into two groups. In multivariate Cox analysis, we revealed that mPCa patients with negative TIM3 expression, younger age, no radiotherapy, higher Gleason score, higher cT stage and patients of mCRPC had a shorter OS. Therefore, a predictive nomogram was generated with identified independent prognostic factors to assess patients’ OS at 3 years. Multivariate logistic regression revealed that higher cT stage, higher Gleason score and low TIM3 expression were independent predictors of metastatic castration resistant prostate cancer (mCRPC). In conclusion, low expression level of TIM3 in prostate cancer tissues is an independent prognostic factor of poor prognosis for mPCa patients, and also an independent predictor of mCRPC.
A Faraday laser lasing on Rb 1529 nm transition
Authors: Chang Pengyuan , Peng Huanfa , Zhang Shengnan , Chen Zhangyuan , Luo Bin , Chen Jingbiao , Guo Hong
Published: August 2017

We present the design and performance characterization of a Faraday laser directly lasing on the Rb 1529 nm transition (Rb, 5P3/2 − 4D5/2) with high stability, narrow spectral linewidth and low cost. This system does not need an additional frequency-stabilized pump laser as a prerequisite to preparing Rb atom from 5S to 5P excited state. Just by using a performance-improved electrodeless discharge lamp-based excited-state Faraday anomalous dispersion optical filter (LESFADOF), we realized a heterogeneously Faraday laser with the frequency corresponding to atomic transition, working stably over a range of laser diode (LD) current from 85 mA to 171 mA and the LD temperature from 11 °C to 32 °C, as well as the 24-hour long-term frequency fluctuation range of no more than 600 MHz. Both the laser linewidth and relative intensity noisy (RIN) are measured. The Faraday laser lasing on Rb 1529 nm transition (telecom C-band) can be applied to further research on metrology, microwave photonics and optical communication systems. Besides, since the transitions correspongding to the populated excited-states of alkali atoms within lamp are extraordinarily rich, this scheme can increase the flexibility for choosing proper wavelengths for Faraday laser and greatly expand the coverage of wavelength corresponding to atomic transmission for laser frequency stabilization.
NMR and Rheological Study of Anion Size Influence on the Properties of Two Imidazolium-based Ionic Liquids
Authors: Green Stephen M. , Ries Michael E. , Moffat Jamie , Budtova Tatiana
Published: August 2017

NMR self-diffusion and relaxation, coupled with viscosity, were used to study the properties and structure of two imidazolium-based ionic liquids, 1-ethyl-3-methylimidazolium acetate [C2MIM][OAc] and 1-ethyl-3-methylimidazolium octanoate [C2MIM][OOct]. The experimental results point to the formation of different types of aggregates in each ionic liquid. These aggregates are small and stable under flow and temperature in [C2MIM][OAc], whereas the aggregates are large and sensitive to flow and temperature in [C2MIM][OOct]. In the latter case the size of aggregates decreases both under flow and temperature increase.
Composite Photocatalysts Containing BiVO4 for Degradation of Cationic Dyes
Authors: Pingmuang Kanlaya , Chen Jun , Kangwansupamonkon Wiyong , Wallace Gordon G. , Phanichphant Sukon , Nattestad Andrew
Published: August 2017

The creation of composite structures is a commonly employed approach towards enhanced photocatalytic performance, with one of the key rationales for doing this being to separate photoexcited charges, affording them longer lifetimes in which to react with adsorbed species. Here we examine three composite photocatalysts using either WO3, TiO2 or CeO2 with BiVO4 for the degradation of model dyes Methylene Blue and Rhodamine B. Each of these materials (WO3, TiO2 or CeO2) has a different band edge energy offset with respect to BiVO4, allowing for a systematic comparison of these different arrangements. It is seen that while these offsets can afford beneficial charge transfer (CT) processes, they can also result in the deactivation of certain reactions. We also observed the importance of localized dye concentrations, resulting from a strong affinity between it and the surface, in attaining high overall photocatalytic performance, a factor not often acknowledged. It is hoped in the future that these observations will assist in the judicious selection of semiconductors for use as composite photocatalysts.
Excellent low-voltage operating flexible ferroelectric organic transistor nonvolatile memory with a sandwiching ultrathin ferroelectric film
Authors: Xu Ting , Xiang Lanyi , Xu Meili , Xie Wenfa , Wang Wei
Published: August 2017

The high operating voltage is a primary issue preventing the commercial application of the ferroelectric organic field-effect transistor (Fe-OFET) nonvolatile memory (NVM). In this work, we propose a novel route to resolve this issue by employing two ultrathin AlOX interfacial layers sandwiching an ultrathin ferroelectric polymer film with a low coercive field, in the fabricated flexible Fe-OFET NVM. The operation voltage of Fe-OFET NVMs decreases with the downscaling thickness of the ferroelectric film. By inserting two ultrathin AlOX interfacial layers at both sides of the ultrathin ferroelectric film, not only the gate leakage is prominently depressed but also the mobility is greatly improved. Excellent memory performances, with large mobility of 1.7 ~ 3.3 cm2 V−1 s−1, high reliable memory switching endurance over 2700 cycles, high stable data storage retention capability over 8 × 104 s with memory on-off ratio larger than 102, are achieved at the low operating voltage of 4 V, which is the lowest value reported to data for all Fe-OFET NVMs. Simultaneously, outstanding mechanical fatigue property with the memory performances maintaining well over 7500 bending cycles at a bending radius of 5.5 mm is also achieved in our flexible FE-OFET NVM.
The profile of selected single nucleotide polymorphisms in patients with hypertension and heart failure with preserved and mid-range ejection fraction
Authors: Bielecka-Dabrowa Agata , Sakowicz Agata , Pietrucha Tadeusz , Misztal Małgorzata , Chruściel Piotr , Rysz Jacek , Banach Maciej
Published: August 2017

The study aimed to assess the clinical significance of selected single nucleotide polymorphisms (SNPs) in patients with diastolic heart failure (HF): inflammation [-174 G/C Interleukin -6 (IL-6) rs1800795, tumor necrosis factor (TNF)-608 G/A rs1800629], fibrosis [Arg25Pro transforming growth factor β (TGF β) rs1800471], endothelial function [-786 T/C nitric oxide synthase (NOS) rs2070744], glucose and lipid metabolism [Pro12Ala peroxisome proliferator activated receptor (PPAR)γ rs1801282], and vitamin D metabolism [cytochrome P450 27B1 (CYP27B1) C-1260A].110 patients with HF with preserved and mid-range ejection fraction (HFpEF and HFmrEF) were recruited. GG homozygotes in 174 G/C of IL6 polymorphism are characterized by higher values of estimated glomerular filtration rate based on the study Modification of Diet in Renal Disease (eGFR MDRD) and C allele in the NOS polymorphism and AA profile in C-1260A of CYP27B1 polymorphism correlated with a lower eGFR (MDRD). In multivariate analysis the CG genotype for 174 G/C of IL-6 and allele A in C-1260A of CYP27B1 are the only SNPs independently associated with worse course of HFpEF and HFmrEF. These data confirm the importance of the selected SNPs in aggravation and complications of hypertension.
Thickness-controlled electronic structure and thermoelectric performance of ultrathin SnS2 nanosheets
Authors: Li Jun , Shen Jinni , Ma Zuju , Wu Kechen
Published: August 2017

The thermoelectric conversion efficiency of a material relies on a dimensionless parameter (ZT = S2σT/κ). It is a great challenge in enhancing the ZT value basically due to that the related transport factors of most of the bulk materials are inter-conditioned to each other, making it very difficult to simultaneously optimize these parameters. In this report, the negative correlation between power factor and thermal conductivity of nano-scaled SnS2 multilayers is predicted by high-level first-principle computations combined with Boltzmann transport theory. By diminishing the thickness of SnS2 nanosheet to about 3 L, the S and σ along a direction simultaneously increase whereas κ decreases, achieving a high ZT value of 1.87 at 800 K. The microscopic mechanisms for this unusual negative correlation in nano-scaled two dimensional (2D) material are elucidated and attributed to the quantum confinement effect. The results may open a way to explore the high ZT thermoelectric nano-devices for the practical thermoelectric applications.
Experimental Study of Hysteresis behavior of Foam Generation in Porous Media
Authors: Kahrobaei S. , Vincent-Bonnieu S. , Farajzadeh R.
Published: August 2017

Foam can be used for gas mobility control in different subsurface applications. The success of foam-injection process depends on foam-generation and propagation rate inside the porous medium. In some cases, foam properties depend on the history of the flow or concentration of the surfactant, i.e., the hysteresis effect. Foam may show hysteresis behavior by exhibiting multiple states at the same injection conditions, where coarse-textured foam is converted into strong foam with fine texture at a critical injection velocity or pressure gradient. This study aims to investigate the effects of injection velocity and surfactant concentration on foam generation and hysteresis behavior as a function of foam quality. We find that the transition from coarse-foam to strong-foam (i.e., the minimum pressure gradient for foam generation) is almost independent of flowrate, surfactant concentration, and foam quality. Moreover, the hysteresis behavior in foam generation occurs only at high-quality regimes and when the pressure gradient is below a certain value regardless of the total flow rate and surfactant concentration. We also observe that the rheological behavior of foam is strongly dependent on liquid velocity.
Functional and proteomic analysis of Ceratonova shasta (Cnidaria: Myxozoa) polar capsules reveals adaptations to parasitism
Authors: Piriatinskiy Gadi , Atkinson Stephen D. , Park Sinwook , Morgenstern David , Brekhman Vera , Yossifon Gilad , Bartholomew Jerri L. , Lotan Tamar
Published: August 2017

Myxozoa is a diverse, speciose group of microscopic parasites, recently placed within the phylum Cnidaria. Myxozoans are highly reduced in size and complexity relative to free-living cnidarians, yet they have retained specialized organelles known as polar capsules, akin to the nematocyst stinging capsules of free-living species. Whereas in free-living cnidarians the stinging capsules are used for prey capture or defense, in myxozoans they have the essential function of initiating the host infection process. To explore the evolutionary adaptation of polar capsules to parasitism, we used as a model organism Ceratonova shasta, which causes lethal disease in salmonids. Here, we report the first isolation of C. shasta myxospore polar capsules using a tailored dielectrophoresis-based microfluidic chip. Using electron microscopy and functional analysis we demonstrated that C. shasta tubules have no openings and are likely used to anchor the spore to the host. Proteomic analysis of C. shasta polar capsules suggested that they have retained typical structural and housekeeping proteins found in nematocysts of jellyfish, sea anemones and Hydra, but have lost the most important functional group in nematocysts, namely toxins. Our findings support the hypothesis that polar capsules and nematocysts are homologous organelles, which have adapted to their distinct functions.
A multimodal dataset for various forms of distracted driving
Authors: Taamneh Salah , Tsiamyrtzis Panagiotis , Dcosta Malcolm , Buddharaju Pradeep , Khatri Ashik , Manser Michael , Ferris Thomas , Wunderlich Robert , Pavlidis Ioannis
Published: August 2017

We describe a multimodal dataset acquired in a controlled experiment on a driving simulator. The set includes data for n=68 volunteers that drove the same highway under four different conditions: No distraction, cognitive distraction, emotional distraction, and sensorimotor distraction. The experiment closed with a special driving session, where all subjects experienced a startle stimulus in the form of unintended acceleration—half of them under a mixed distraction, and the other half in the absence of a distraction. During the experimental drives key response variables and several explanatory variables were continuously recorded. The response variables included speed, acceleration, brake force, steering, and lane position signals, while the explanatory variables included perinasal electrodermal activity (EDA), palm EDA, heart rate, breathing rate, and facial expression signals; biographical and psychometric covariates as well as eye tracking data were also obtained. This dataset enables research into driving behaviors under neatly abstracted distracting stressors, which account for many car crashes. The set can also be used in physiological channel benchmarking and multispectral face recognition.