bluuebunny/crossref_metadata_2025_split huggingface dataset:
Selective binding of choline by a phosphate-coordination-based triple helicate featuring an aromatic box
Authors: Jia Chuandong , Zuo Wei , Yang Dong , Chen Yanming , Cao Liping , Custelcean Radu , Hostaš Jiří , Hobza Pavel , Glaser Robert , Wang Yao-Yu , Yang Xiao-Juan , Wu Biao 
Published: October 2017

AbstractIn nature, proteins have evolved sophisticated cavities tailored for capturing target guests selectively among competitors of similar size, shape, and charge. The fundamental principles guiding the molecular recognition, such as self-assembly and complementarity, have inspired the development of biomimetic receptors. In the current work, we report a self-assembled triple anion helicate (host 2) featuring a cavity resembling that of the choline-binding protein ChoX, as revealed by crystal and density functional theory (DFT)-optimized structures, which binds choline in a unique dual-site-binding mode. This similarity in structure leads to a similarly high selectivity of host 2 for choline over its derivatives, as demonstrated by the NMR and fluorescence competition experiments. Furthermore, host 2 is able to act as a fluorescence displacement sensor for discriminating choline, acetylcholine, l-carnitine, and glycine betaine effectively.
Myoblasts and macrophages are required for therapeutic morpholino antisense oligonucleotide delivery to dystrophic muscle
Authors: Novak James S. , Hogarth Marshall W. , Boehler Jessica F. , Nearing Marie , Vila Maria C. , Heredia Raul , Fiorillo Alyson A. , Zhang Aiping , Hathout Yetrib , Hoffman Eric P. , Jaiswal Jyoti K. , Nagaraju Kanneboyina , Cirak Sebahattin , Partridge Terence A. 
Published: October 2017

AbstractExon skipping is a promising therapeutic strategy for Duchenne muscular dystrophy (DMD), employing morpholino antisense oligonucleotides (PMO-AO) to exclude disruptive exons from the mutant DMD transcript and elicit production of truncated dystrophin protein. Clinical trials for PMO show variable and sporadic dystrophin rescue. Here, we show that robust PMO uptake and efficient production of dystrophin following PMO administration coincide with areas of myofiber regeneration and inflammation. PMO localization is sustained in inflammatory foci where it enters macrophages, actively differentiating myoblasts and newly forming myotubes. We conclude that efficient PMO delivery into muscle requires two concomitant events: first, accumulation and retention of PMO within inflammatory foci associated with dystrophic lesions, and second, fusion of PMO-loaded myoblasts into repairing myofibers. Identification of these factors accounts for the variability in clinical trials and suggests strategies to improve this therapeutic approach to DMD.
NMI and IFP35 serve as proinflammatory DAMPs during cellular infection and injury
Authors: Xiahou Zhikai , Wang Xiangli , Shen Juan , Zhu Xiaoxiao , Xu Feng , Hu Rong , Guo Deyin , Li Henan , Tian Yong , Liu Yingfang , Liang Huanhuan 
Published: October 2017

AbstractDamage-associated molecular patterns (DAMP) trigger innate immune response and exacerbate inflammation to combat infection and cellular damage. Identifying DAMPs and revealing their functions are thus of crucial importance. Here we report that two molecules, N-myc and STAT interactor (NMI) and interferon-induced protein 35 (IFP35) act as DAMPs and are released by activated macrophages during lipopolysaccharide-induced septic shock or acetaminophen-induced liver injury. We show that extracellular NMI and IFP35 activate macrophages to release proinflammatory cytokines by activating nuclear factor-κB through the Toll-like receptor 4 pathway. In addition, the serum levels of NMI are increased in patients who succumbed to severe inflammation. NMI deficiency reduces inflammatory responses and mortality in mouse models of sepsis and liver injury. We therefore propose that extracellular NMI and IFP35 exacerbate inflammation as DAMPs, making them potential therapeutic targets for clinical intervention.
PKCε phosphorylates MIIP and promotes colorectal cancer metastasis through inhibition of RelA deacetylation
Authors: Chen Tao , Li Jingjie , Xu Meidong , Zhao Qin , Hou Yingyong , Yao Liqing , Zhong Yunshi , Chou Ping-Chieh , Zhang Wei , Zhou Pinghong , Jiang Yuhui 
Published: October 2017

AbstractEGFR signaling is implicated in NF-κB activation. However, the concrete mechanisms by which the core transducer of NF-κB signaling pathway, RelA/p65 is regulated under EGFR activation remains to be further clarified. Here, we show that EGF stimulation induces PKCε-dependent phosphorylation of migration and invasion inhibitory protein (MIIP) at Ser303; this phosphorylation promotes the interaction between MIIP and RelA in the nucleus, by which MIIP prevents histone deacetylase 6 (HDAC6)-mediated RelA deacetylation, and thus enhances transcriptional activity of RelA and facilitates tumor metastasis. Meanwhile PP1, which functions as a phosphatase, is found to mediate MIIP-S303 dephosphorylation and its expression level inversely correlates with metastatic capability of tumor cells. Moreover, clinical analyses indicate the level of MIIP-S303 phosphorylation correlates with colorectal cancer (CRC) metastasis and prognosis. These findings uncover an unidentified mechanism underlying the precise regulation of NF-κB by EGF, and highlight the critical role of nuclear MIIP in tumor metastasis.
Correlated states in β-Li2IrO3 driven by applied magnetic fields
Authors: Ruiz Alejandro , Frano Alex , Breznay Nicholas P. , Kimchi Itamar , Helm Toni , Oswald Iain , Chan Julia Y. , Birgeneau R. J. , Islam Zahirul , Analytis James G. 
Published: October 2017

AbstractMagnetic honeycomb iridates are thought to show strongly spin-anisotropic exchange interactions which, when highly frustrated, lead to an exotic state of matter known as the Kitaev quantum spin liquid. However, in all known examples these materials magnetically order at finite temperatures, the scale of which may imply weak frustration. Here we show that the application of a relatively small magnetic field drives the three-dimensional magnet β-Li2IrO3 from its incommensurate ground state into a quantum correlated paramagnet. Interestingly, this paramagnetic state admixes a zig-zag spin mode analogous to the zig-zag order seen in other Mott-Kitaev compounds. The rapid onset of the field-induced correlated state implies the exchange interactions are delicately balanced, leading to strong frustration and a near degeneracy of different ground states.
Projected gradient descent algorithms for quantum state tomography
Authors: Bolduc Eliot , Knee George C. , Gauger Erik M. , Leach Jonathan 
Published: October 2017

AbstractAccurate quantum tomography is a vital tool in both fundamental and applied quantum science. It is a task that involves processing a noisy measurement record in order to construct a reliable estimate of an unknown quantum state, and is central to quantum computing, metrology and communication. To date, many different approaches to quantum state estimation have been developed, yet no one method fits all applications, and all fail relatively quickly as the dimensionality of the unknown state grows. In this work, we suggest that projected gradient descent is a method that can evade some of these shortcomings. We present three tomography algorithms that use projected gradient descent and compare their performance with state-of-the-art alternatives, i.e., the diluted iterative algorithm and convex programming. Our results find in favour of the general class of projected gradient descent methods due to their speed, applicability to large states, and the range of conditions in which they perform as well as providing insight into which variant of projected gradient descent ought to be used in various measurement scenarios.
Distinct mechanisms of acquisition of mcr-1 –bearing plasmid by Salmonella strains recovered from animals and food samples
Authors: Cui Mingquan , Zhang Jinfei , Zhang Chunping , Li Ruichao , Wai-chi Chan Edward , Wu Chenbin , Wu Congming , Chen Sheng 
Published: October 2017

AbstractSince the report of its discovery in E. coli in late 2015, the plasmid-mediated colistin resistance gene, mcr-1, has been detected in various bacterial species in clinical setting and various environmental niches. However, the transmission mechanisms of this gene in Salmonella is less defined. In this study, we conducted a comprehensive study to characterize the genetic features of mcr-1-positive Salmonella strains isolated from animals and foods. Our data revealed that Salmonella recovered from animals and food specimens exhibited highly different PFGE patterns, and acquired mcr-1-encoding plasmids via different mechanism. Plasmids harboring mcr-1 in Salmonella food isolates were all conjugative and similar as plasmids reported in other species of Enterobacteriaceae, whereas mcr-1-bearing plasmids from animal Salmonella isolates were not conjugative, and belonged to the IncHI2 type. The lack of a region carrying the tra genes was found to account for the inability to undergo conjugation for various sizes of IncHI2 plasmids harbored by animal strains. These data suggest that transmission of mcr-1-positive Salmonella from animal to food might not be a common event and food isolates may have acquired mcr-1-bearing plasmids from other mcr-1-positive bacteria such as E. coli, which co-exist in food samples.
Improved electrochemical properties of morphology-controlled titania/titanate nanostructures prepared by in-situ hydrothermal surface modification of self-source Ti substrate for high-performance supercapacitors
Authors: Banerjee Arghya Narayan , Anitha V. C. , Joo Sang W. 
Published: October 2017

AbstarctTi substrate surface is modified into two-dimensional (2D) TiO2nanoplatelet or one-dimensional (1D) nanorod/nanofiber (or a mixture of both) structure in a controlled manner via a simple KOH-based hydrothermal technique. Depending on the KOH concentration, different types of TiO2nanostructures (2D platelets, 1D nanorods/nanofibers and a 2D+1D mixed sample) are fabricated directly onto the Ti substrate surface. The novelty of this technique is thein-situmodification of the self-source Ti surface into titania nanostructures, and its direct use as the electrochemical microelectrode without any modifications. This leads to considerable improvement in the interfacial properties between metallic Ti and semiconducting TiO2. Since interfacial states/defects have profound effect on charge transport properties of electronic/electrochemical devices, therefore this near-defect-free interfacial property of Ti-TiO2microelectrode has shown high supercapacitive performances for superior charge-storage devices. Additionally, by hydrothermally tuning the morphology of titania nanostructures, the electrochemical properties of the electrodes are also tuned. A Ti-TiO2electrode comprising of a mixture of 2D-platelet+1D-nanorod structure reveals very high specific capacitance values (~7.4 mF.cm−2) due to the unique mixed morphology which manifests higher active sites (hence, higher utilization of the active materials) in terms of greater roughness at the 2D-platelet structures and higher surface-to-volume-ratio in the 1D-nanorod structures.
Transcriptome analysis of Spodoptera frugiperda Sf9 cells reveals putative apoptosis-related genes and a preliminary apoptosis mechanism induced by azadirachtin
Authors: Shu Benshui , Zhang Jingjing , Sethuraman Veeran , Cui Gaofeng , Yi Xin , Zhong Guohua 
Published: October 2017

AbstractAs an important botanical pesticide, azadirachtin demonstrates broad insecticidal activity against many agricultural pests. The results of a previous study indicated the toxicity and apoptosis induction of azadirachtin in Spodoptera frugiperda Sf9 cells. However, the lack of genomic data has hindered a deeper investigation of apoptosis in Sf9 cells at a molecular level. In the present study, the complete transcriptome data for Sf9 cell line was accomplished using Illumina sequencing technology, and 97 putative apoptosis-related genes were identified through BLAST and KEGG orthologue annotations. Fragments of potential candidate apoptosis-related genes were cloned, and the mRNA expression patterns of ten identified genes regulated by azadirachtin were examined using qRT-PCR. Furthermore, Western blot analysis showed that six putative apoptosis-related proteins were upregulated after being treated with azadirachtin while the protein Bcl-2 were downregulated. These data suggested that both intrinsic and extrinsic apoptotic signal pathways comprising the identified potential apoptosis-related genes were potentially active in S. frugiperda. In addition, the preliminary results revealed that caspase-dependent or caspase-independent apoptotic pathways could function in azadirachtin-induced apoptosis in Sf9 cells.
High rates of organic carbon processing in the hyporheic zone of intermittent streams
Authors: Burrows Ryan M. , Rutlidge Helen , Bond Nick R. , Eberhard Stefan M. , Auhl Alexandra , Andersen Martin S. , Valdez Dominic G. , Kennard Mark J. 
Published: October 2017

AbstractOrganic carbon cycling is a fundamental process that underpins energy transfer through the biosphere. However, little is known about the rates of particulate organic carbon processing in the hyporheic zone of intermittent streams, which is often the only wetted environment remaining when surface flows cease. We used leaf litter and cotton decomposition assays, as well as rates of microbial respiration, to quantify rates of organic carbon processing in surface and hyporheic environments of intermittent and perennial streams under a range of substrate saturation conditions. Leaf litter processing was 48% greater, and cotton processing 124% greater, in the hyporheic zone compared to surface environments when calculated over multiple substrate saturation conditions. Processing was also greater in more saturated surface environments (i.e. pools). Further, rates of microbial respiration on incubated substrates in the hyporheic zone were similar to, or greater than, rates in surface environments. Our results highlight that intermittent streams are important locations for particulate organic carbon processing and that the hyporheic zone sustains this fundamental process even without surface flow. Not accounting for carbon processing in the hyporheic zone of intermittent streams may lead to an underestimation of its local ecological significance and collective contribution to landscape carbon processes.
One Dimensional Coordination Polymer of Zn(II) for Developing Multifunctional Nanoparticles
Authors: Agarwal Rashmi A. 
Published: October 2017

AbstractA variety of nanoparticles (NPs) including Ag, Au, Pd, Cr and mixed Cu/Fe have been synthesized in a non-activated (without solvent removal) one dimensional coordination polymer (CP) of Zn(II) via two different mechanisms, acid formation and redox activity of the framework. Main driving force to grow these NPs within the cavities of CP is the presence of free oxygens of one of the monodentate carboxylate groups of BDC ligand. These free oxygens act as anchoring sites for the metal ions of the metal precursors. Chemical and physical characteristics of the NPs within the framework have been evaluated by the high resolution transmission electron microscopic (HRTEM) images. Excluding Ag(0) and Pd(0) other NPs are present as combinations of their elemental as well as oxide forms (Au/Au2O3, Cr/Cr2O3/CrO2 and Cu/Cu2O, Fe/FeO). Synthesized Ag NPs within the framework show remarkable antibacterial efficacy at extremely low concentrations. Ag, Au and Cu/Fe NPs show ferromagnetic properties within the framework at room temperature. This polymer has potential to sequester highly toxic Cr(VI) to non toxic Cr(0), Cr(III) and Cr(IV) species.
Non-steroidal anti-inflammatory drug delays corneal wound healing by reducing production of 12-hydroxyheptadecatrienoic acid, a ligand for leukotriene B4 receptor 2
Authors: Iwamoto Satoshi , Koga Tomoaki , Ohba Mai , Okuno Toshiaki , Koike Masato , Murakami Akira , Matsuda Akira , Yokomizo Takehiko 
Published: October 2017

AbstractNon-steroidal anti-inflammatory drugs (NSAIDs) are widely used to reduce inflammation by suppressing cyclooxygenases (COXs). NSAID eye drops are frequently prescribed after ocular surgery to reduce inflammation and pain, but this treatment has clinically significant side effects, including corneal ulcer and perforation. The molecular mechanisms underlying these side effects remain unknown. Recently, the COX product 12(S)-hydroxyheptadeca-5Z,8E,10E-trienoic acid (12-HHT) was identified as an endogenous ligand for leukotriene B4 receptor 2 (BLT2), which is important in maintenance of epithelial homeostasis. We hypothesized that NSAID-dependent corneal damage is caused by reduced production of 12-HHT. Diclofenac eye drops decreased the abundance of downstream products of COX and delayed corneal wound healing in BALB/c mice. Expression of BLT2 was observed in murine ocular tissues including cornea, and in human corneal epithelial cell line and human primary corneal epithelial cells. In BLT2-knockout mice, corneal wound healing was delayed, but the diclofenac-dependent delay in corneal wound healing disappeared. 12-HHT accelerated wound closure both in BLT2-transfected corneal cell line and human primary corneal epithelial cells. Thus, our results reveal that NSAIDs delay corneal wound healing by inhibiting 12-HHT production, and suggest that stimulation of the 12-HHT/BLT2 axis represents a novel therapeutic approach to corneal wound healing.
Probing ligand recognition of the opioid pan antagonist AT-076 at nociceptin, kappa, mu, and delta opioid receptors through structure-activity relationships
Authors: Journigan V. Blair , Polgar Willma E. , Tuan Edward W. , Lu James , Daga Pankaj R. , Zaveri Nurulain T. 
Published: October 2017

AbstractFew opioid ligands binding to the three classic opioid receptor subtypes, mu, kappa and delta, have high affinity at the fourth opioid receptor, the nociceptin/orphanin FQ receptor (NOP). We recently reported the discovery of AT-076 (1), (R)-7-hydroxy-N-((S)-1-(4-(3-hydroxyphenyl)piperidin-1-yl)-3-methylbutan-2-yl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamide, a pan antagonist with nanomolar affinity for all four subtypes. Since AT-076 binds with high affinity at all four subtypes, we conducted a structure-activity relationship (SAR) study to probe ligand recognition features important for pan opioid receptor activity, using chemical modifications of key pharmacophoric groups. SAR analysis of the resulting analogs suggests that for the NOP receptor, the entire AT-076 scaffold is crucial for high binding affinity, but the binding mode is likely different from that of NOP antagonists C-24 and SB-612111 bound in the NOP crystal structure. On the other hand, modifications of the 3-hydroxyphenyl pharmacophore, but not the 7-hydroxy Tic pharmacophore, are better tolerated at kappa and mu receptors and yield very high affinity multifunctional (e.g. 12) or highly selective (e.g. 16) kappa ligands. With the availability of the opioid receptor crystal structures, our SAR analysis of the common chemotype of AT-076 suggests rational approaches to modulate binding selectivity, enabling the design of multifunctional or selective opioid ligands from such scaffolds.
Vitamin D and cognitive function: A Mendelian randomisation study
Authors: Maddock Jane , Zhou Ang , Cavadino Alana , Kuźma Elżbieta , Bao Yanchun , Smart Melissa C. , Saum Kai-Uwe , Schöttker Ben , Engmann Jorgen , Kjærgaard Marie , Karhunen Ville , Zhan Yiqiang , Lehtimäki Terho , Rovio Suvi P. , Byberg Liisa , Lahti Jari , Marques-Vidal Pedro , Sen Abhijit , Perna Laura , Schirmer Henrik , Singh-Manoux Archana , Auvinen Juha , Hutri-Kähönen Nina , Kähönen Mika , Kilander Lena , Räikkönen Katri , Melhus Håkan , Ingelsson Erik , Guessous Idris , Petrovic Katja E , Schmidt Helena , Schmidt Reinhold , Vollenweider Peter , Lind Lars , Eriksson Johan G. , Michaëlsson Karl , Raitakari Olli T. , Hägg Sara , Pedersen Nancy L. , Herzig Karl-Heinz , Järvelin Marjo-Riitta , Veijola Juha , Kivimaki Mika , Jorde Rolf , Brenner Hermann , Kumari Meena , Power Chris , Llewellyn David J. , Hyppönen Elina 
Published: October 2017

AbstractThe causal nature of the association between hypovitaminosis D and poor cognitive function in mid- to later-life is uncertain. Using a Mendelian randomisation(MR) approach, we examined the causal relationship between 25(OH)D and cognitive function. Data came from 172,349 participants from 17 cohorts. DHCR7(rs12785878), CYP2R1 rs12794714) and their combined synthesis score were chosen to proxy 25(OH)D. Cognitive tests were standardised into global and memory scores. Analyses were stratified by 25(OH)D tertiles, sex and age. Random effects meta-analyses assessed associations between 25(OH)D and cognitive function. Associations of serum 25(OH)D with global and memory-related cognitive function were non-linear (lower cognitive scores for both low and high 25(OH)D, pcurvature ≤ 0.006), with much of the curvature attributed to a single study. DHCR7, CYP2R1, and the synthesis score were associated with small reductions in 25(OH)D per vitamin D-decreasing allele. However, coefficients for associations with global or memory-related cognitive function were non-significant and in opposing directions for DHCR7 and CYP2R1, with no overall association observed for the synthesis score. Coefficients for the synthesis score and global and memory cognition were similar when stratified by 25(OH)D tertiles, sex and age. We found no evidence for serum 25(OH)D concentration as a causal factor for cognitive performance in mid- to later life.
A novel machine learning approach reveals latent vascular phenotypes predictive of renal cancer outcome
Authors: Ing Nathan , Huang Fangjin , Conley Andrew , You Sungyong , Ma Zhaoxuan , Klimov Sergey , Ohe Chisato , Yuan Xiaopu , Amin Mahul B. , Figlin Robert , Gertych Arkadiusz , Knudsen Beatrice S. 
Published: October 2017

AbstractGene expression signatures are commonly used as predictive biomarkers, but do not capture structural features within the tissue architecture. Here we apply a 2-step machine learning framework for quantitative imaging of tumor vasculature to derive a spatially informed, prognostic gene signature. The trained algorithms classify endothelial cells and generate a vascular area mask (VAM) in H&E micrographs of clear cell renal cell carcinoma (ccRCC) cases from The Cancer Genome Atlas (TCGA). Quantification of VAMs led to the discovery of 9 vascular features (9VF) that predicted disease-free-survival in a discovery cohort (n = 64, HR = 2.3). Correlation analysis and information gain identified a 14 gene expression signature related to the 9VF’s. Two generalized linear models with elastic net regularization (14VF and 14GT), based on the 14 genes, separated independent cohorts of up to 301 cases into good and poor disease-free survival groups (14VF HR = 2.4, 14GT HR = 3.33). For the first time, we successfully applied digital image analysis and targeted machine learning to develop prognostic, morphology-based, gene expression signatures from the vascular architecture. This novel morphogenomic approach has the potential to improve previous methods for biomarker development.