bluuebunny/crossref_metadata_2025_split huggingface dataset:
FCN1 (M-ficolin), which directly associates with immunoglobulin G1, is a molecular target of intravenous immunoglobulin therapy for Kawasaki disease
Authors: Okuzaki Daisuke , Ota Kaori , Takatsuki Shin-ichi , Akiyoshi Yukari , Naoi Kazuyuki , Yabuta Norikazu , Saji Tsutomu , Nojima Hiroshi 
Published: September 2017

AbstractKawasaki disease (KD), an acute systemic vasculitis of early childhood, is of unknown etiology. High-dose intravenous immunoglobulin (IVIG) is an effective treatment, but its molecular target remains elusive. DNA microarray analysis of peripheral blood mononuclear cells (PBMCs) revealed that at least 21 genes are drastically down-regulated after IVIG treatment in most KD patients. qRT-PCR analysis confirmed that the mRNA levels of five of these genes were considerably reduced in almost all KD patients after IVIG treatment. Western blot (Wb) of PBMC extracts revealed that levels of FCN1 (M-ficolin), a protein of the complement system that defends against infectious agents, were reduced after IVIG treatment in many KD patients. In another set of KD patients, Wb confirmed that levels of both FCN1 were greatly reduced after IVIG therapy. Wb revealed that the collagen-like domain of FCN1 directly bound to IgG1 in vitro through a portion of the CH1 and CH3 domains, and synthetic peptides corresponding to these domains of IgG1 efficiently inhibited these associations. These results suggest that FCN1 is a molecular target of intravenous IVIG in KD patients. We propose that these peptides and a humanized monoclonal antibody against FCN1 could be useful in combination therapy with IVIG.
A broadband photodetector based on Rhodamine B-sensitized ZnO nanowires film
Authors: Bai Zheng Qi , Liu Ze Wen 
Published: September 2017

AbstractA broadband photodetector has been developed on the basis of ZnO nanowires (NWs)/Rhodamine B (RhB) hybrid system. The device is fabricated by spraying NWs on to gold interdigital electrodes followed by modifying the NWs via an RhB solution-casting process. Measurements show that the as-fabricated device demonstrates photoresponsivity ranging from 300 nm to 700 nm with a bandwidth as large as 400 nm. The role of the dye sensitizer adsorbed on the surface of NWs is modeled to alter the transportation path of photo-generated carriers. The calculations based on the measurements reveal that the device exhibits a prominent responsivity in the interested band with maximum responsivity of 5.5 A/W for ultraviolet (UV) light and 3 A/W for visible (VIS) light under 8 V bias, respectively. The sensitization not only widens the response spectrum with external quantum efficiency leaping up to 771% at VIS but also improves UV responsivity with maximum 51% enhancement. From the time–dependent photo-current measurement, it is found that the response time (rise and decay times in total) of the device largely reduced from 17.5 s to 3.3 s after sensitization. A comparison of the obtained photodetector with other ZnO-based photodetectors is summarized from the view point of responsivity and bandwidth.
Long noncoding RNAs in the model species Brachypodium distachyon
Authors: De Quattro Concetta , Pè Mario Enrico , Bertolini Edoardo 
Published: September 2017

AbstractEukaryotic genomes are pervasively transcribed and only a small portion of the transcribed sequences belongs to protein coding genes. High-throughput sequencing technology contributed to consolidate this perspective, allowing the identification of numerous noncoding RNAs with key roles in biological processes. Long noncoding RNAs (lncRNAs) are transcripts longer than 200 nt with limited phylogenetic conservation, expressed at low levels and characterized by tissue/organ specific expression profiles. Although a large set of lncRNAs has been identified, the functional roles of lncRNAs are only beginning to be recognized and the molecular mechanism of lncRNA-mediated gene regulation remains largely unexplored, particularly in plants where their annotation and characterization are still incomplete. Using public and proprietary poly-(A)+RNA-seq data as well as a collection of full length ESTs from several organs, developmental stages and stress conditions in threeBrachypodium distachyoninbred lines, we describe the identification and the main features of thousands lncRNAs. Here we provide a genome-wide characterization of lncRNAs, highlighting their intraspecies conservation and describing their expression patterns among several organs/tissues and stress conditions. This work represents a fundamental resource to deepen our knowledge on long noncoding RNAs in C3cereals, allowing theBrachypodiumcommunity to exploit these results in future research programs.
Arf6 in lymphatic endothelial cells regulates lymphangiogenesis by controlling directional cell migration
Authors: Lin Yueh-Chien , Ohbayashi Norihiko , Hongu Tsunaki , Katagiri Naohiro , Funakoshi Yuji , Lee Hsinyu , Kanaho Yasunori 
Published: September 2017

AbstractThe small GTPase Arf6 plays pivotal roles in a wide variety of cellular events such as endocytosis, exocytosis, and actin cytoskeleton reorganization. However, the physiological functions of Arf6 at the whole animal level have not yet been thoroughly understood. Here, we show that Arf6 regulates developmental and tumor lymphangiogenesis in mice. Lymphatic endothelial cell (LEC)-specific Arf6 conditional knockout (LEC-Arf6 cKO) mouse embryos exhibit severe skin edema and impairment in the formation of lymphatic vessel network at the mid-gestation stage. Knockdown of Arf6 in human LECs inhibits in vitro capillary tube formation and directed cell migration induced by vascular endothelial growth factor-C (VEGF-C) by inhibiting VEGF-C-induced internalization of β1 integrin. Finally, we found that LEC-Arf6 cKO mice transplanted with B16 melanoma cells attenuated tumor lymphangiogenesis and progression. Collectively, these results demonstrate that Arf6 in LECs plays a crucial role in physiological and pathological lymphangiogenesis.
In situ vocal fold properties and pitch prediction by dynamic actuation of the songbird syrinx
Authors: Düring Daniel N. , Knörlein Benjamin J. , Elemans Coen P. H. 
Published: September 2017

AbstractThe biomechanics of sound production forms an integral part of the neuromechanical control loop of avian vocal motor control. However, we critically lack quantification of basic biomechanical parameters describing the vocal organ, the syrinx, such as material properties of syringeal elements, forces and torques exerted on, and motion of the syringeal skeleton during song. Here, we present a novel marker-based 3D stereoscopic imaging technique to reconstruct 3D motion of servo-controlled actuation of syringeal muscle insertions sites in vitro and focus on two muscles controlling sound pitch. We furthermore combine kinematic analysis with force measurements to quantify elastic properties of sound producing medial labia (ML). The elastic modulus of the zebra finch ML is 18 kPa at 5% strain, which is comparable to elastic moduli of mammalian vocal folds. Additionally ML lengthening due to musculus syringealis ventralis (VS) shortening is intrinsically constraint at maximally 12% strain. Using these values we predict sound pitch to range from 350–800 Hz by VS modulation, corresponding well to previous observations. The presented methodology allows for quantification of syringeal skeleton motion and forces, acoustic effects of muscle recruitment, and calibration of computational birdsong models, enabling experimental access to the entire neuromechanical control loop of vocal motor control.
The neural basis of spatial vision losses in the dysfunctional visual system
Authors: Huang Jinfeng , Zhou Yifeng , Liu Caiyuan , Liu Zhongjian , Luan Chunmeng , Tzvetanov Tzvetomir 
Published: September 2017

AbstractHuman vision relies on correct information processing from the eye to various visual areas. Disturbances in the visual perception of simple features are believed to come from low-level network (e.g., V1) disruptions. In the present study, we modelled monocular losses in spatial vision through plausible multiple network modifications in early visual coding. We investigated perceptual deficits in anisometropic amblyopia and used the monocular tilt illusion as a probe of primary visual cortex orientation coding and inhibitory interactions. The psychophysical results showed that orientation misperception was higher in amblyopic eyes (AE) than in the fellow and neurotypical eyes and was correlated with the subject’s AE peak contrast sensitivity. The model fitted to the experimental results allowed to split these observations between different network characteristics by showing that these observations were explained by broader orientation tuning widths in AEs and stronger lateral inhibition in abnormal amblyopic system that had strong contrast sensitivity losses. Through psychophysics measures and computational modelling of V1, our study links multiple perceptual changes with localized modifications in the primary visual cortex.
Dextromethorphan Exhibits Anti-inflammatory and Immunomodulatory Effects in a Murine Model of Collagen-Induced Arthritis and in Human Rheumatoid Arthritis
Authors: Chen Der-Yuan , Lin Chi-Chien , Chen Yi-Ming , Chao Ya-Hsuan , Yang Deng-Ho 
Published: September 2017

AbstractDextromethorphan (d-3-methoxy-17-methylmorphinan, DXM) is a commonly used antitussive with a favorable safety profile. Previous studies have demonstrated that DXM has anti-inflammatory and immunomodulatory properties; however, the effect of DXM in rheumatoid arthritis (RA) remains unknown. Herein, we found that DXM treatment attenuated arthritis severity and proinflammatory cytokine expression levels, including TNF-α, IL-6, and IL-17A, in paw tissues of CIA mice. DXM treatment also reduced serum TNF-α, IL-6, and IL-17A levels of CIA mice and patients with RA. DXM further decreased the production of anti-CII IgG, IFN-γ, and IL-17A in collagen-reactive CD4+T cells extracted from the lymph nodes of CIA mice.In vitroincubation of bone marrow–derived dendritic cells with DXM limited CD4+T-cell proliferation and inflammatory cytokine secretion. In conclusion, our results showed that DXM attenuated arthritis symptoms in CIA mice and significantly reduced proinflammatory cytokines in patients with RA, suggesting that it can be used as an anti-arthritic agent.
Transgenerational exposure of North Atlantic bivalves to ocean acidification renders offspring more vulnerable to low pH and additional stressors
Authors: Griffith Andrew W. , Gobler Christopher J. 
Published: September 2017

AbstractWhile early life-stage marine bivalves are vulnerable to ocean acidification, effects over successive generations are poorly characterized. The objective of this work was to assess the transgenerational effects of ocean acidification on two species of North Atlantic bivalve shellfish, Mercenaria mercenaria and Argopecten irradians. Adults of both species were subjected to high and low pCO2 conditions during gametogenesis. Resultant larvae were exposed to low and ambient pH conditions in addition to multiple, additional stressors including thermal stress, food-limitation, and exposure to a harmful alga. There were no indications of transgenerational acclimation to ocean acidification during experiments. Offspring of elevated pCO2-treatment adults were significantly more vulnerable to acidification as well as the additional stressors. Our results suggest that clams and scallops are unlikely to acclimate to ocean acidification over short time scales and that as coastal oceans continue to acidify, negative effects on these populations may become compounded and more severe.
Synthesis and Evaluation of GM2-Monophosphoryl Lipid A Conjugate as a Fully Synthetic Self-Adjuvant Cancer Vaccine
Authors: Zhou Zhifang , Mandal Satadru S. , Liao Guochao , Guo Jiatong , Guo Zhongwu 
Published: September 2017

AbstractAn efficient method was developed for the synthesis of a GM2 derivative suitable for the conjugation with various biomolecules. This GM2 derivative was covalently linked to keyhole limpet hemocyanin (KLH) and monophosphoryl lipid A (MPLA) to form novel therapeutic cancer vaccines. Immunological evaluations of the resultant conjugates in mice revealed that they elicited robust GM2-specific overall and IgG antibody responses. Moreover, the GM2-MPLA conjugate was disclosed to elicit strong immune responses without the use of an adjuvant, proving its self-adjuvant property. The antisera of both conjugates showed strong binding and mediated similarly effective complement-dependent cytotoxicity to GM2-expressing cancer cell line MCF-7. Based on these results, it was concluded that both GM2-MPLA and GM2-KLH are promising candidates as therapeutic cancer vaccines, whereas fully synthetic GM2-MPLA, which has homogeneous and well-defined structure and self-adjuvant property, deserves more attention and studies.
A Brain-Derived Neurotrophic Factor Mimetic Is Sufficient to Restore Cone Photoreceptor Visual Function in an Inherited Blindness Model
Authors: Daly Conor , Shine Lisa , Heffernan Theresa , Deeti Sudhakar , Reynolds Alison L. , O’Connor John J. , Dillon Eugène T. , Duffy David J. , Kolch Walter , Cagney Gerard , Kennedy Breandán N. 
Published: September 2017

AbstractControversially, histone deacetylase inhibitors (HDACi) are in clinical trial for the treatment of inherited retinal degeneration. Utilizing the zebrafish dye
ucd6
model, we determined if treatment with HDACi can rescue cone photoreceptor-mediated visual function. dye exhibit defective visual behaviour and retinal morphology including ciliary marginal zone (CMZ) cell death and decreased photoreceptor outer segment (OS) length, as well as gross morphological defects including hypopigmentation and pericardial oedema. HDACi treatment of dye results in significantly improved optokinetic (OKR) (~43 fold, p < 0.001) and visualmotor (VMR) (~3 fold, p < 0.05) responses. HDACi treatment rescued gross morphological defects and reduced CMZ cell death by 80%. Proteomic analysis of dye eye extracts suggested BDNF-TrkB and Akt signaling as mediators of HDACi rescue in our dataset. Co-treatment with the TrkB antagonist ANA-12 blocked HDACi rescue of visual function and associated Akt phosphorylation. Notably, sole treatment with a BDNF mimetic, 7,8-dihydroxyflavone hydrate, significantly rescued dye visual function (~58 fold increase in OKR, p < 0.001, ~3 fold increase in VMR, p < 0.05). In summary, HDACi and a BDNF mimetic are sufficient to rescue retinal cell death and visual function in a vertebrate model of inherited blindness.
Acetyl-4′-phosphopantetheine is stable in serum and prevents phenotypes induced by pantothenate kinase deficiency
Authors: Di Meo Ivano , Colombelli Cristina , Srinivasan Balaji , de Villiers Marianne , Hamada Jeffrey , Jeong Suh Y. , Fox Rachel , Woltjer Randall L. , Tepper Pieter G. , Lahaye Liza L. , Rizzetto Emanuela , Harrs Clara H. , de Boer Theo , van der Zwaag Marianne , Jenko Branko , Čusak Alen , Pahor Jerca , Kosec Gregor , Grzeschik Nicola A. , Hayflick Susan J. , Tiranti Valeria , Sibon Ody C. M. 
Published: September 2017

AbstractCoenzyme A is an essential metabolite known for its central role in over one hundred cellular metabolic reactions. In cells, Coenzyme A is synthesized de novo in five enzymatic steps with vitamin B5 as the starting metabolite, phosphorylated by pantothenate kinase. Mutations in the pantothenate kinase 2 gene cause a severe form of neurodegeneration for which no treatment is available. One therapeutic strategy is to generate Coenzyme A precursors downstream of the defective step in the pathway. Here we describe the synthesis, characteristics and in vivo rescue potential of the acetyl-Coenzyme A precursor S-acetyl-4′-phosphopantetheine as a possible treatment for neurodegeneration associated with pantothenate kinase deficiency.
Enhancing laser-driven proton acceleration by using micro-pillar arrays at high drive energy
Authors: Khaghani Dimitri , Lobet Mathieu , Borm Björn , Burr Loïc , Gärtner Felix , Gremillet Laurent , Movsesyan Liana , Rosmej Olga , Toimil-Molares Maria Eugenia , Wagner Florian , Neumayer Paul 
Published: September 2017

AbstractThe interaction of micro- and nano-structured target surfaces with high-power laser pulses is being widely investigated for its unprecedented absorption efficiency. We have developed vertically aligned metallic micro-pillar arrays for laser-driven proton acceleration experiments. We demonstrate that such targets help strengthen interaction mechanisms when irradiated with high-energy-class laser pulses of intensities ~1017–18 W/cm2. In comparison with standard planar targets, we witness strongly enhanced hot-electron production and proton acceleration both in terms of maximum energies and particle numbers. Supporting our experimental results, two-dimensional particle-in-cell simulations show an increase in laser energy conversion into hot electrons, leading to stronger acceleration fields. This opens a window of opportunity for further improvements of laser-driven ion acceleration systems.
Anti-Aβ single-chain variable fragment antibodies restore memory acquisition in a Drosophila model of Alzheimer’s disease
Authors: Martin-Peña Alfonso , Rincon-Limas Diego E. , Fernandez-Funez Pedro 
Published: September 2017

AbstractAlzheimer’s disease (AD) is a prevalent neurodegenerative disorder triggered by the accumulation of soluble assemblies of the amyloid-β42 (Aβ42) peptide. Despite remarkable advances in understanding the pathogenesis of AD, the development of palliative therapies is still lacking. Engineered anti-Aβ42 antibodies are a promising strategy to stall the progression of the disease. Single-chain variable fragment (scFv) antibodies increase brain penetration and offer flexible options for delivery while maintaining the epitope targeting of full antibodies. Here, we examined the ability of two anti-Aβ scFv antibodies targeting the N-terminal (scFv9) and C-terminal (scFv42.2) regions of Aβ42 to suppress the progressive memory decline induced by extracellular deposition of Aβ42 in Drosophila. Using olfactory classical conditioning, we observe that both scFv antibodies significantly improve memory performance in flies expressing Aβ42 in the mushroom body neurons, which are intimately involved in the coding and storage of olfactory memories. The scFvs effectively restore memory at all ages, from one-day post-eclosion to thirty-day-old flies, proving their ability to prevent the toxicity of different pathogenic assemblies. These data support the application of this paradigm of Aβ42-induced memory loss in Drosophila to investigate the protective activity of Aβ42–binding agents in an AD-relevant functional assay.
Saturated mutagenesis of ketoisovalerate decarboxylase V461 enabled specific synthesis of 1-pentanol via the ketoacid elongation cycle
Authors: Chen Grey S. , Siao Siang Wun , Shen Claire R. 
Published: September 2017

AbstractIterative ketoacid elongation has been an essential tool in engineering artificial metabolism, in particular the synthetic alcohols. However, precise control of product specificity is still greatly challenged by the substrate promiscuity of the ketoacid decarboxylase, which unselectively hijacks ketoacid intermediates from the elongation cycle along with the target ketoacid. In this work, preferential tuning of the Lactococcus lactis ketoisovalerate decarboxylase (Kivd) specificity toward 1-pentanol synthesis was achieved via saturated mutagenesis of the key residue V461 followed by screening of the resulting alcohol spectrum. Substitution of V461 with the small and polar amino acid glycine or serine significantly improved the Kivd selectivity toward the 1-pentanol precursor 2-ketocaproate by lowering its catalytic efficiency for the upstream ketoacid 2-ketobutyrate and 2-ketovalerate. Conversely, replacing V461 with bulky or charged side chains displayed severely adverse effect. Increasing supply of the iterative addition unit acetyl-CoA by acetate feeding further drove 2-ketoacid flux into the elongation cycle and enhanced 1-pentanol productivity. The Kivd V461G variant enabled a 1-pentanol production specificity around 90% of the total alcohol content with or without oleyl alcohol extraction. This work adds insight to the selectivity of Kivd active site.
Heterogeneity Aware Random Forest for Drug Sensitivity Prediction
Authors: Rahman Raziur , Matlock Kevin , Ghosh Souparno , Pal Ranadip 
Published: September 2017

AbstractSamples collected in pharmacogenomics databases typically belong to various cancer types. For designing a drug sensitivity predictive model from such a database, a natural question arises whether a model trained on diverse inter-tumor heterogeneous samples will perform similar to a predictive model that takes into consideration the heterogeneity of the samples in model training and prediction. We explore this hypothesis and observe that ensemble model predictions obtained when cancer type is known out-perform predictions when that information is withheld even when the samples sizes for the former is considerably lower than the combined sample size. To incorporate the heterogeneity idea in the commonly used ensemble based predictive model of Random Forests, we propose Heterogeneity Aware Random Forests (HARF) that assigns weights to the trees based on the category of the sample. We treat heterogeneity as a latent class allocation problem and present a covariate free class allocation approach based on the distribution of leaf nodes of the model ensemble. Applications on CCLE and GDSC databases show that HARF outperforms traditional Random Forest when the average drug responses of cancer types are different.
Urban heat island impacted by fine particles in Nanjing, China
Authors: Wu Hao , Wang Tijian , Riemer Nicole , Chen Pulong , Li Mengmeng , Li Shu 
Published: September 2017

AbstractAtmospheric aerosol particles (especially particles with aerodynamic diameters equal to or less than 2.5 μm, called PM2.5) can affect the surface energy balance and atmospheric heating rates and thus may impact the intensity of urban heat islands. In this paper, the effect of fine particles on the urban heat island intensity in Nanjing was investigated via the analysis of observational data and numerical modelling. The observations showed that higher PM2.5 concentrations over the urban area corresponded to lower urban heat island (UHI) intensities, especially during the day. Under heavily polluted conditions, the UHI intensity was reduced by up to 1 K. The numerical simulation results confirmed the weakening of the UHI intensity due to PM2.5 via the higher PM2.5 concentrations present in the urban region than those in the suburban areas. The effects of the fine particles on the UHI reduction were limited to the lowest 500–1000 m. The daily range of the surface air temperature was also reduced by up to 1.1 K due to the particles’ radiative effects. In summary, PM2.5 noticeably impacts UHI intensity, which should be considered in future studies on air pollution and urban climates.