bluuebunny/crossref_metadata_2025_split huggingface dataset:
Therapeutic efficacy of a respiratory syncytial virus fusion inhibitor
Authors: Roymans Dirk , Alnajjar Sarhad S , Battles Michael B , Sitthicharoenchai Panchan , Furmanova-Hollenstein Polina , Rigaux Peter , Berg Joke Van den , Kwanten Leen , Ginderen Marcia Van , Verheyen Nick , Vranckx Luc , Jaensch Steffen , Arnoult Eric , Voorzaat Richard , Gallup Jack M. , Larios-Mora Alejandro , Crabbe Marjolein , Huntjens Dymphy , Raboisson Pierre , Langedijk Johannes P. , Ackermann Mark R. , McLellan Jason S , Vendeville Sandrine , Koul Anil 
Published: July 2017

AbstractRespiratory syncytial virus is a major cause of acute lower respiratory tract infection in young children, immunocompromised adults, and the elderly. Intervention with small-molecule antivirals specific for respiratory syncytial virus presents an important therapeutic opportunity, but no such compounds are approved today. Here we report the structure of JNJ-53718678 bound to respiratory syncytial virus fusion (F) protein in its prefusion conformation, and we show that the potent nanomolar activity of JNJ-53718678, as well as the preliminary structure–activity relationship and the pharmaceutical optimization strategy of the series, are consistent with the binding mode of JNJ-53718678 and other respiratory syncytial virus fusion inhibitors. Oral treatment of neonatal lambs with JNJ-53718678, or with an equally active close analog, efficiently inhibits established acute lower respiratory tract infection in the animals, even when treatment is delayed until external signs of respiratory syncytial virus illness have become visible. Together, these data suggest that JNJ-53718678 is a promising candidate for further development as a potential therapeutic in patients at risk to develop respiratory syncytial virus acute lower respiratory tract infection.
Charge carrier localised in zero-dimensional (CH3NH3)3Bi2I9 clusters
Authors: Ni Chengsheng , Hedley Gordon , Payne Julia , Svrcek Vladimir , McDonald Calum , Jagadamma Lethy Krishnan , Edwards Paul , Martin Robert , Jain Gunisha , Carolan Darragh , Mariotti Davide , Maguire Paul , Samuel Ifor , Irvine John 
Published: July 2017

AbstractA metal-organic hybrid perovskite (CH3NH3PbI3) with three-dimensional framework of metal-halide octahedra has been reported as a low-cost, solution-processable absorber for a thin-film solar cell with a power-conversion efficiency over 20%. Low-dimensional layered perovskites with metal halide slabs separated by the insulating organic layers are reported to show higher stability, but the efficiencies of the solar cells are limited by the confinement of excitons. In order to explore the confinement and transport of excitons in zero-dimensional metal–organic hybrid materials, a highly orientated film of (CH3NH3)3Bi2I9 with nanometre-sized core clusters of Bi2I93− surrounded by insulating CH3NH3+ was prepared via solution processing. The (CH3NH3)3Bi2I9 film shows highly anisotropic photoluminescence emission and excitation due to the large proportion of localised excitons coupled with delocalised excitons from intercluster energy transfer. The abrupt increase in photoluminescence quantum yield at excitation energy above twice band gap could indicate a quantum cutting due to the low dimensionality.
Membrane Targeting of Disheveled Can Bypass the Need for Arrow/LRP5
Authors: Kaur Prameet , Lam Vanessa Yuk Man , Mannava Anirudh Gautam , Suresh Jahnavi , Jenny Andreas , Tolwinski Nicholas S. 
Published: July 2017

AbstractThe highly conserved Wnt signaling pathway regulates cell proliferation and differentiation in vertebrates and invertebrates. Upon binding of a Wnt ligand to a receptor of the Fz family, Disheveled (Dsh/Dvl) transduces the signal during canonical and non-canonical Wnt signaling. The specific details of how this process occurs have proven difficult to study, especially as Dsh appears to function as a switch between different branches of Wnt signaling. Here we focus on the membrane-proximal events that occur once Dsh is recruited to the membrane. We show that membrane-tethering of the Dsh protein is sufficient to induce canonical Wnt signaling activation even in the absence of the Wnt co-receptor Arrow/LRP5/6. We map the protein domains required for pathway activation in membrane tethered constructs finding that both the DEP and PDZ domains are dispensable for canonical signaling only in membrane-tethered Dsh, but not in untethered/normal Dsh. These data lead to a signal activation model, where Arrow is required to localize Dsh to the membrane during canonical Wnt signaling placing Dsh downstream of Arrow.
Modified Western blotting for insulin and other diabetes-associated peptide hormones
Authors: Okita Naoyuki , Higami Yoshikazu , Fukai Fumio , Kobayashi Masaki , Mitarai Miku , Sekiya Takao , Sasaki Takashi 
Published: July 2017

AbstractNow, the quantification of proinsulin/insulin contents within organisms tends to be evaluated only by enzyme-linked immunosorbent assay (ELISA), although assessing the adequacy of results by some quantification method is important. Remarkably, few scientific papers use detection by Western blotting (WB), another immunological assay, of proinsulin/insulin. We found two problems with quantification of insulin and proinsulin by general WB: the shape of an insulin band in gel electrophoresis is distorted, and the retention potency to a blotting membrane of the peptide hormones (mainly insulin) is low. We solved the first problem by optimizing the sodium dodecyl sulfate concentration in the sample buffer and the second problem by glutaraldehyde fixation following treatment with a blocking solution for a short time. The improvements were confirmed by quantification of proinsulin/insulin in standards, MIN6c4 cell lysates, and MIN6c4 culture supernatants. Furthermore, we showed that the modified WB is applicable to other diabetes-associated peptide hormones: insulin analogs, glucagon, GLP-1s, somatostatins, ghrelins, and pancreatic polypeptide. Our data showed that the modified WB can contribute to qualitative or quantitative analyses of diabetes-associated peptides by providing analytical information based on electrophoresis, although ELISA, which is an almost exclusive method in the quantification of peptide hormones, supplies only numerical data.
Biosynthesis of brain cytoplasmic 200 RNA
Authors: Kim Youngmi , Lee Jungmin , Shin Heegwon , Jang Seonghui , Kim Sun Chang , Lee Younghoon 
Published: July 2017

AbstractBrain cytoplasmic 200 RNA (BC200 RNA), a neuron-specific non-coding RNA, is also highly expressed in a number of tumors of non-neuronal origin. However, the biosynthesis of BC200 RNA remains poorly understood. In this study, we show that the efficient transcription of BC200 RNA requires both internal and upstream promoter elements in cancer cells. The transcription complex seems to interact with a broad range of sequences within the upstream 100-bp region. The cellular levels and half-lives of BC200 RNA were found to differ across various cancer cell types, but there was no significant correlation between these parameters. Exogenously expressed BC200 RNA had a shorter half-life than that observed for the endogenous version in cancer cells, suggesting that BC200 RNA might be protected by some limiting factor(s) in cancer cells. Transient transfection experiments showed that the transcriptional activity of the exogenous BC200 RNA promoter element varied depending on the cancer cell type. However, the promoter activities together with the half-life data could not explain the differences in the levels of BC200 RNA among different cell types, suggesting that there is another level of transcriptional regulation beyond that detected by our transient transfection experiments.
Ethylene, an early marker of systemic inflammation in humans
Authors: Paardekooper Laurent M. , van den Bogaart Geert , Kox Matthijs , Dingjan Ilse , Neerincx Anne H. , Bendix Maura B. , Beest Martin ter , Harren Frans J. M. , Risby Terence , Pickkers Peter , Marczin Nandor , Cristescu Simona M. 
Published: July 2017

AbstractEthylene is a major plant hormone mediating developmental processes and stress responses to stimuli such as infection. We show here that ethylene is also produced during systemic inflammation in humans and is released in exhaled breath. Traces of ethylene were detected by laser spectroscopy bothin vitroin isolated blood leukocytes exposed to bacterial lipopolysaccharide (LPS) as well asin vivofollowing LPS administration in healthy volunteers. Exposure to LPS triggers formation of ethylene as a product of lipid peroxidation induced by the respiratory burst. In humans, ethylene was detected prior to the increase of blood levels of inflammatory cytokines and stress-related hormones. Our results highlight that ethylene release is an early and integral component ofin vivolipid peroxidation with important clinical implications as a breath biomarker of bacterial infection.
Serotonin hormonally regulates lacrimal gland secretory function via the serotonin type 3a receptor
Authors: Imada Toshihiro , Nakamura Shigeru , Hisamura Ryuji , Izuta Yusuke , Jin Kai , Ito Masataka , Kitamura Naoki , Tanaka Kenji F. , Mimura Masaru , Shibuya Izumi , Tsubota Kazuo 
Published: July 2017

AbstractTears are extracellular fluid secreted from the lacrimal gland (LG). Tears consist of a dynamic tri-layered film composed of secretions from the LG, Meibomian gland, and conjunctival goblet cells. The LG secretes the aqueous component of the tear, the Meibomian gland secretes the lipid component, and conjunctival goblet cells secrete mucin. The regulation of LG activity via the autonomic nervous system has been recognized as fundamental to maintaining aqueous tear flow. Here, we describe the role of a hormone, peripheral serotonin, in tear secretion. We found that blood serotonin concentration, changed by feeding a diet deprived of the serotonin precursor tryptophan, correlated with tear secretion, and that a sustained decrease in serotonin resulted in LG atrophy and autophagy. The combination of a decrease in serotonin with the interruption of autonomic neural stimuli to the LG preceded these alterations. Furthermore, we found that the serotonin type 3a receptor expressed in LG acinar cells is involved in tear secretion via intracellular calcium mobilization. Our findings demonstrate that hormonal regulation by serotonin, in cooperation with the autonomic nervous system, regulates tear secretion.
Protected State Transfer via an Approximate Quantum Adder
Authors: Gatti G. , Barberena D. , Sanz M. , Solano E. 
Published: July 2017

AbstractWe propose a decoherence protected protocol for sending single photon quantum states through depolarizing channels. This protocol is implemented via an approximate quantum adder engineered through spontaneous parametric down converters, and shows higher success probability than distilled quantum teleportation protocols for distances below a threshold depending on the properties of the channel.
Diurnal preference, mood and the response to morning light in relation to polymorphisms in the human clock gene PER3
Authors: Turco M. , Biscontin A. , Corrias M. , Caccin L. , Bano M. , Chiaromanni F. , Salamanca M. , Mattei D. , Salvoro C. , Mazzotta G. , De Pittà C. , Middleton B. , Skene D. J. , Montagnese S. , Costa R. 
Published: July 2017

AbstractPER3gene polymorphisms have been associated with differences in human sleep-wake phenotypes, and sensitivity to light. The aims of this study were to assess:i) the frequency of allelic variants at twoPER3polymorphic sites (rs57875989 length polymorphism:PER34,PER35; rs228697 SNP:PER3C,PER3G) in relation to sleep-wake timing;ii) the effect of morning light on behavioural/circadian variables inPER34/PER34andPER35/PER35homozygotes. 786 Caucasian subjects living in Northern Italy donated buccal DNA and completed diurnal preference, sleep quality/timing and sleepiness/mood questionnaires. 19PER34/PER34and 11PER35/PER35homozygotes underwent morning light administration, whilst monitoring sleep-wake patterns and the urinary 6-sulphatoxymelatonin (aMT6s) rhythm. No significant relationship was observed between the length polymorphism and diurnal preference. By contrast, a significant association was observed between thePER3Gvariant and morningness (OR = 2.10), and between thePER3G-PER34haplotype and morningness (OR = 2.19), for which a mechanistic hypothesis is suggested. No significant differences were observed in sleep timing/aMT6s rhythms betweenPER35/PER35andPER34/PER34subjects at baseline. After light administration,PER34/PER34subjects advanced their aMT6s acrophase (p < 0.05), and showed a trend of advanced sleep-wake timing. In conclusion, significant associations were observed betweenPER3polymorphic variants/their combinations and both diurnal preference and the response to light.
Characterisation and pharmacological analysis of a crustacean G protein-coupled receptor: the red pigment-concentrating hormone receptor of Daphnia pulex
Authors: Marco Heather G. , Verlinden Heleen , Vanden Broeck Jozef , Gäde Gerd 
Published: July 2017

AbstractThis is the first pharmacological characterisation of a neuropeptide G protein-coupled receptor (GPCR) in a crustacean. We cloned the ORF of the red pigment-concentrating hormone from a German strain of Daphnia pulex (Dappu-RPCH), as well as that of the cognate receptor (Dappu-RPCHR). Dappu-RPCHR has the hallmarks of the rhodopsin superfamily of GPCRs, and is more similar to insect adipokinetic hormone (AKH) receptor sequences than to receptor sequences for AKH/corazonin-like peptide or corazonin. We provide experimental evidence that Dappu-RPCH specifically activates the receptor (EC50 value of 65 pM) in a mammalian cell-based bioluminescence assay. We further characterised the properties of the ligands for the Dappu-RPCHR by investigating the activities of a variety of naturally-occurring peptides (insect AKH and crustacean RPCH peptides). The insect AKHs had lower EC50 values than the crustacean RPCHs. In addition, we tested a series of Dappu-RPCH analogues, where one residue at a time is systematically replaced by an alanine to learn about the relative importance of the termini and side chains for activation. Mainly amino acids in positions 1 to 4 and 8 of Dappu-RPCH appear responsible for effective activation of Dappu-RPCHR. The substitution of Phe4 in Dappu-RPCH had the most damaging effect on its agonistic activity.
Laser induced strong-field ionization gas jet tomography
Authors: Tchulov Oshrat , Negro Matteo , Stagira Salvatore , Devetta Michele , Vozzi Caterina , Frumker Eugene 
Published: July 2017

AbstractWe introduce a novel in-situ strong field ionization tomography approach for characterizing the spatial density distribution of gas jets. We show that for typical intensities in high harmonic generation experiments, the strong field ionization mechanism used in our approach provides an improvement in the resolution close to factor of 2 (resolving about 8 times smaller voxel volume), when compared to linear/single-photon imaging modalities. We find, that while the depth of scan in linear tomography is limited by resolution loss due to the divergence of the driving laser beam, in the proposed approach the depth of focus is localized due to the inherent physical nature of strong-field interaction and discuss implications of these findings. We explore key aspects of the proposed method and compare it with commonly used single- and multi-photon imaging mechanisms. The proposed method will be particularly useful for strong field and attosecond science experiments.
Combined serum levels of multiple proteins in tPA-BDNF pathway may aid the diagnosis of five mental disorders
Authors: Chen Suzhen , Jiang Haitang , Liu Yang , Hou Zhenhua , Yue Yingying , Zhang Yuqun , Zhao Fuying , Xu Zhi , Li Yinghui , Mou Xiaodong , Li Lei , Wang Tianyu , Zhao Jingjing , Han Chongyang , Sui Yuxiu , Wang Ming , Yang Zhong , Lu Yan , Zhu Yifeng , Li Jianhua , Shen Xinhua , Sun Fei , Chen Qingsong , Chen Huanxin , Yuan Yonggui 
Published: July 2017

AbstractMental disorders are severe, disabling conditions with unknown etiology and are commonly misdiagnosed when clinical symptomology criteria are solely used. Our previous work indicated that combination of serum levels of multiple proteins in tissue plasminogen activator (tPA)-brain-derived neurotrophic factor (BDNF) pathway improved accuracy of diagnosis of major depressive disorder (MDD). Here, we measured serum levels of tPA, plasminogen activator inhibitor-1 (PAI-1), BDNF, precursor-BDNF (proBDNF), tropomyosin-related kinase B (TrkB) and neurotrophin receptor p75 (p75NTR) in patients with paranoid schizophrenia (SZ, n = 34), MDD (n = 30), bipolar mania (BM, n = 30), bipolar depression (BD, n = 22), panic disorder (PD, n = 30), and healthy controls (HCs, n = 30) by Enzyme-linked immunosorbent assay kits. We used receiver operating characteristic (ROC) curve to analyze diagnostic potential of these proteins. We found, compared with HCs, that serum tPA and proBDNF were lower in SZ, BM and BD; TrkB was lower in SZ and BD; and p75NTR was declined in SZ and BM. ROC analysis showed that combined serum level of tPA, PAI-1, BDNF, proBDNF, TrkB and p75NTR was better than any single protein in accuracy of diagnosis and differentiation, suggesting that the combination of multiple serum proteins levels in tPA-BDNF pathway may have a potential for a diagnostic panel in mental disorders.
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(4.2 K, 31.2 T) beyond 1 kA/mm2 of a ~3.2 μm thick, 20 mol% Zr-added MOCVD REBCO coated conductor
Authors: Xu A. , Zhang Y. , Gharahcheshmeh M. Heydari , Yao Y. , Galstyan E. , Abraimov D. , Kametani F. , Polyanskii A. , Jaroszynski J. , Griffin V. , Majkic G. , Larbalestier D. C. , Selvamanickam V. 
Published: July 2017

AbstractA main challenge that significantly impedes REBa2Cu3Ox (RE = rare earth) coated conductor applications is the low engineering critical current density J
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because of the low superconductor fill factor in a complicated layered structure that is crucial for REBa2Cu3Ox to carry supercurrent. Recently, we have successfully achieved engineering critical current density beyond 2.0 kA/mm2 at 4.2 K and 16 T, by growing thick REBa2Cu3Ox layer, from ∼1.0 μm up to ∼3.2 μm, as well as controlling the pinning microstructure. Such high engineering critical current density, the highest value ever observed so far, establishes the essential role of REBa2Cu3Ox coated conductors for very high field magnet applications. We attribute such excellent performance to the dense c-axis self-assembled BaZrO3 nanorods, the elimination of large misoriented grains, and the suppression of big second phase particles in this ~3.2 μm thick REBa2Cu3Ox film.
The basal translation rate of authentic HIV-1 RNA is regulated by 5’UTR nt-pairings at junction of R and U5
Authors: Boeras I. , Seufzer B. , Brady S. , Rendahl A. , Heng X. , Boris-Lawrie K. 
Published: July 2017

AbstractThe paradigm protein synthesis rate is regulated by structural complexity of the 5′untranslated region (UTR) derives from bacterial and other riboswitches. In-solution, HIV-1 5′UTR forms two interchangeable long-range nucleotide (nt) -pairings, one sequesters the gag start codon promoting dimerization while the other sequesters the dimer initiation signal preventing dimerization. While the effect of these nt-pairings on dimerization and packaging has been documented their effect on authentic HIV translation in cellulo has remained elusive until now. HIVNL4-3 5′UTR substitutions were designed to individually stabilize the dimer-prone or monomer-prone conformations, validated in-solution, and introduced to molecular clones. The effect of 5′UTR conformation on ribosome loading to HIV unspliced RNA and rate of Gag polypeptide synthesis was quantified in cellulo. Monomer- and dimer-prone 5′UTRs displayed equivalent, basal rate of translation. Gain-of-function substitution U103, in conjunction with previously defined nt-pairings that reorient AUG to flexible nt-pairing, significantly activated the translation rate, indicating the basal translation rate is under positive selection. The observed translation up-mutation focuses attention to nt-pairings at the junction of R and U5, a poorly characterized structure upstream of the characterized HIV riboswitch and demonstrates the basal translation rate of authentic HIV RNA is regulated independently of monomer:dimer equilibrium of the 5′UTR.
A Glucose Sensing System Based on Transmission Measurements at Millimetre Waves using Micro strip Patch Antennas
Authors: Saha Shimul , Cano-Garcia Helena , Sotiriou Ioannis , Lipscombe Oliver , Gouzouasis Ioannis , Koutsoupidou Maria , Palikaras George , Mackenzie Richard , Reeve Thomas , Kosmas Panagiotis , Kallos Efthymios 
Published: July 2017

AbstractWe present a sensing system operating at millimetre (mm) waves in transmission mode that can measure glucose level changes based on the complex permittivity changes across the signal path. The permittivity of a sample can change significantly as the concentration of one of its substances varies: for example, blood permittivity depends on the blood glucose levels. The proposed sensing system uses two facing microstrip patch antennas operating at 60 GHz, which are placed across interrogated samples. The measured transmission coefficient depends on the permittivity change along the signal path, which can be correlated to the change in concentration of a substance. Along with theoretical estimations, we experimentally demonstrate the sensing performance of the system using controlled laboratory samples, such as water-based glucose-loaded liquid samples. We also present results of successful glucose spike detection in humans during an in-vivo Intravenous Glucose Tolerance Test (IVGTT). The system could eventually be developed into a non-invasive glucose monitor for continuous monitoring of glucose levels for people living with diabetes, as it can detect as small as 1.33 mmol/l (0.025 wt%) glucose concentrations in the controlled water-based samples satisfactorily, which is well below the typical human glucose levels of 4 mmol/l.
Exendin-4 reduces food intake via the PI3K/AKT signaling pathway in the hypothalamus
Authors: Yang Yan , Choi Pique P. , Smith Wanli W. , Xu Weijie , Ma Delin , Cordner Zachary A. , Liang Nu-Chu , Moran Timothy H. 
Published: July 2017

AbstractExendin-4 (EX-4), a glucagon-like peptide-1 (GLP-1) receptor agonist, has been shown to reduce food intake and to increase proopiomelanocortin (POMC) gene expression in the hypothalamus. In this study, we examined the potential neural mechanisms by which these effects occur. Male Sprague Dawley rats were implanted with a cannula in the third ventricle of the brain through which an inhibitor of phosphatidylinositol-3 kinase (PI3K) (wortmannin) was administered, and EX-4 or vehicle was administered via intraperitoneal (IP) injection. The activity of PI3K/protein kinase B (AKT) and insulin receptor substrate-1 (IRS-1) in the hypothalamic arcuate was determined. We found that EX-4 treatment significantly decreased food intake and body weight. However, there were almost no changes in food intake and body weight when wortmannin injection (into the third ventricle) occurred prior to EX-4 IP injection. EX-4 not only increased the activity of PI3K/AKT, but it also increased IRS-1 activity. These results show that EX-4 likely suppresses food intake due to its ability to enhance insulin signaling.