bluuebunny/crossref_metadata_2025_split huggingface dataset:
Topical ferumoxytol nanoparticles disrupt biofilms and prevent tooth decay in vivo via intrinsic catalytic activity
Authors: Liu Yuan , Naha Pratap C. , Hwang Geelsu , Kim Dongyeop , Huang Yue , Simon-Soro Aurea , Jung Hoi-In , Ren Zhi , Li Yong , Gubara Sarah , Alawi Faizan , Zero Domenick , Hara Anderson T. , Cormode David P. , Koo Hyun 
Published: July 2018

AbstractFerumoxytol is a nanoparticle formulation approved by the U.S. Food and Drug Administration for systemic use to treat iron deficiency. Here, we show that, in addition, ferumoxytol disrupts intractable oral biofilms and prevents tooth decay (dental caries) via intrinsic peroxidase-like activity. Ferumoxytol binds within the biofilm ultrastructure and generates free radicals from hydrogen peroxide (H2O2), causing in situ bacterial death via cell membrane disruption and extracellular polymeric substances matrix degradation. In combination with low concentrations of H2O2, ferumoxytol inhibits biofilm accumulation on natural teeth in a human-derived ex vivo biofilm model, and prevents acid damage of the mineralized tissue. Topical oral treatment with ferumoxytol and H2O2 suppresses the development of dental caries in vivo, preventing the onset of severe tooth decay (cavities) in a rodent model of the disease. Microbiome and histological analyses show no adverse effects on oral microbiota diversity, and gingival and mucosal tissues. Our results reveal a new biomedical application for ferumoxytol as topical treatment of a prevalent and costly biofilm-induced oral disease.
Sensitive and powerful single-cell RNA sequencing using mcSCRB-seq
Authors: Bagnoli Johannes W. , Ziegenhain Christoph , Janjic Aleksandar , Wange Lucas E. , Vieth Beate , Parekh Swati , Geuder Johanna , Hellmann Ines , Enard Wolfgang 
Published: July 2018

AbstractSingle-cell RNA sequencing (scRNA-seq) has emerged as a central genome-wide method to characterize cellular identities and processes. Consequently, improving its sensitivity, flexibility, and cost-efficiency can advance many research questions. Among the flexible plate-based methods, single-cell RNA barcoding and sequencing (SCRB-seq) is highly sensitive and efficient. Here, we systematically evaluate experimental conditions of this protocol and find that adding polyethylene glycol considerably increases sensitivity by enhancing cDNA synthesis. Furthermore, using Terra polymerase increases efficiency due to a more even cDNA amplification that requires less sequencing of libraries. We combined these and other improvements to develop a scRNA-seq library protocol we call molecular crowding SCRB-seq (mcSCRB-seq), which we show to be one of the most sensitive, efficient, and flexible scRNA-seq methods to date.
A mosquito salivary gland protein partially inhibits Plasmodium sporozoite cell traversal and transmission
Authors: Schleicher Tyler R. , Yang Jing , Freudzon Marianna , Rembisz Alison , Craft Samuel , Hamilton Madeleine , Graham Morven , Mlambo Godfree , Tripathi Abhai K. , Li Yue , Cresswell Peter , Sinnis Photini , Dimopoulos George , Fikrig Erol 
Published: July 2018

AbstractThe key step during the initiation of malaria is for motilePlasmodiumparasites to exit the host dermis and infect the liver. During transmission, the parasites in the form of sporozoites, are injected together with mosquito saliva into the skin. However, the contribution of vector saliva to sporozoite activity during the establishment of the initial infection of the liver is poorly understood. Here we identify a vector protein by mass spectrometry, with similarity to the human gamma interferon inducible thiol reductase (GILT), that is associated with saliva sporozoites of infectedAnophelesmosquitoes and has a negative impact on the speed and cell traversal activity ofPlasmodium. This protein, referred to as mosquito GILT (mosGILT) represents an example of a protein found in mosquito saliva that may negatively influence sporozoite movement in the host and could lead to new approaches to prevent malaria.
A review of asthma care in 50 general practices in Bedfordshire, United Kingdom
Authors: Levy Mark L , Garnett Fiona , Kuku Adedayo , Pertsovskaya Inna , McKnight Eddie , Haughney John 
Published: July 2018

AbstractThe United Kingdom (UK) National Review of Asthma Deaths (NRAD) (2011–2014) identified a number of contributory risk factors which had not previously been recognized by those caring for people with asthma. Only one of the 19 NRAD recommendations has so far been implemented nationally, and that only partially, and as yet systems are not in place to identify patients at risk of attacks and dying from asthma. In 2015/2016 Bedfordshire Clinical Commissioning Group (CCG) in England, UK, initiated a quality asthma audit of people with asthma to identify some of the risk factors identified in the NRAD report with the aim of optimizing patient care. Fifty (89%) of the General Practices caring for 415,152 patients (27,587 diagnosed with asthma (prevalence 7%; range 4–12%)), participated and the results identified a wide variation in process of care and presence of risk factors including: excess short acting reliever and insufficient preventer prescriptions, failure to issue personal asthma action plans, and to perform annual reviews or check inhaler technique. Identification of these patients involved high-intensity input by trained asthma nurses using sophisticated data extraction software. GP computer systems used in primary care currently do not have the functionally, without the need for manual audit, to implement the NRAD recommendations, starting with the identification of patients at risk. Modifications to existing systems within both primary and secondary care are required in order to prevent unnecessary deaths related to asthma. There is a pressing need to move towards a more pro-active model of care.
Differential regulation of the Wnt/β-catenin pathway by hepatitis C virus recombinants expressing core from various genotypes
Authors: Aicher Stephanie , Kakkanas Athanasios , Cohen Lisette , Blumen Brigitte , Oprisan Gabriela , Njouom Richard , Meurs Eliane F. , Mavromara Penelope , Martin Annette 
Published: July 2018

AbstractClinical studies have suggested association of some hepatitis C virus (HCV) subtypes or isolates with progression toward hepatocellular carcinoma (HCC). HCV core protein has been reported to interfere with host Wnt/β-catenin pathway, a cell fate-determining pathway, which plays a major role in HCC. Here, we investigated the impact of HCV core genetic variability in the dysregulation of Wnt/β-catenin pathway. We used both transient expression of core proteins from clinical isolates of HCV subtypes 1a (Cambodia), 4a (Romania) and 4f (Cameroon) and infection systems based on a set of engineered intergenotypic recombinant viruses encoding core from these various clinical strains. We found that TCF transcription factor-dependent reporter activity was upregulated by core in a strain-specific manner. We documented core sequence-specific transcriptional upregulation of several β-catenin downstream target genes associated with cell proliferation and malignant transformation, fibrogenesis or fat accumulation. The extent of β-catenin nuclear translocation varied in accordance with β-catenin downstream gene upregulation in infected cells. Pairwise comparisons of subgenotypic core recombinants and mutated core variants unveiled the critical role of core residues 64 and 71 in these dysregulations. In conclusion, this work identified natural core polymorphisms involved in HCV strain-specific activation of Wnt/β-catenin pathway in relevant infection systems.
Isosteviol Derivative Inhibits Osteoclast Differentiation and Ameliorates Ovariectomy-Induced Osteoporosis
Authors: Tzeng Huey-En , Huang Po-Hao , Tsai Chun-Hao , Tsay Gregory J , Lee Yi-Ju , Huang Tsurng-Juhn , Lin Tzu-Hung , Chiu Ying-Ming , Wu Yi-Ying 
Published: July 2018

AbstractNC-8 (ent-16-oxobeyeran-19-N-methylureido) is an isosteviol-derived analogue with multiple biological effects, including anti-inflammation and anti-bacterial activities and inhibition of HBV viral surface antigen gene expression. In this study, we explored the effects of NC-8 on the formation of osteoclasts from RAW 264.7 cells. We found that NC-8 exerts the novel effect of inhibiting osteoclast-like cell formation. Our experiments showed that RANKL-induced ERK, p38, and JNK phosphorylation were inhibited by NC-8. An ovariectomy-induced osteoporosis animal model was used to examine the protective effects of oral treatment with NC-8. Serum analysis was used to examine markers of osteoblasts, osteoclasts, and renal and hepatic function in rats. Micro CT scanning and histological analysis were used to measure bone loss in ovariectomized rats. Oral administration of NC-8 effectively decreased excess bone resorption and significantly antagonized trabecular bone loss in ovariectomized rats. Serum analysis of C-terminal telopeptide of type-I collagen, an osteoclast marker, also showed that NC-8 administration inhibited excess bone resorption. Furthermore, serum analysis showed that renal and liver function were not affected by these doses of NC-8 during long-term treatment. Our results demonstrate that NC-8 inhibits osteoclast differentiation and effectively ameliorates ovariectomy-induced osteoporosis.
Tailoring carbon nanotubes optical properties through chirality-wise silicon ring resonators
Authors: Durán-Valdeiglesias Elena , Zhang Weiwei , Alonso-Ramos Carlos , Serna Samuel , Le Roux Xavier , Maris-Morini Delphine , Caselli Niccolò , Biccari Francesco , Gurioli Massimo , Filoramo Arianna , Cassan Eric , Vivien Laurent 
Published: July 2018

AbstractSemiconducting single walled carbon nanotubes (s-SWNT) have an immense potential for the development of active optoelectronic functionalities in ultra-compact hybrid photonic circuits. Specifically, s-SWNT have been identified as a very promising solution to implement light sources in the silicon photonics platform. Still, two major challenges remain to fully exploit the potential of this hybrid technology: the limited interaction between s-SWNTs and Si waveguides and the low quantum efficiency of s-SWNTs emission. Silicon micro-ring resonators have the potential capability to overcome these limitations, by providing enhanced light s-SWNT interaction through resonant light recirculation. Here, we demonstrate that Si ring resonators provide SWNT chirality-wise photoluminescence resonance enhancement, releasing a new degree of freedom to tailor s-SWNT optical properties. Specifically, we show that judicious design of the micro-ring geometry allows selectively promoting the emission enhancement of either (8,6) or (8,7) SWNT chiralities present in a high-purity polymer-sorted s-SWNT solution. In addition, we present an analysis of nanometric-sized silicon-on-insulator waveguides that predicts stronger light s-SWNT interaction for transverse-magnetic (TM) modes than for conventionally used transverse-electric (TE) modes.
In-Vivo Nucleus Pulposus-Specific Regulation of Adult Murine Intervertebral Disc Degeneration via Wnt/Beta-Catenin Signaling
Authors: Holguin Nilsson , Silva Matthew J. 
Published: July 2018

AbstractB-Catenin, transcription factor of Wnt signaling, is promoted in patients with intervertebral disc (IVD) degeneration, but Wnt signaling decreases with aging. We hypothesize that IVD degeneration is associated with decreased Wnt signaling despite more b-Catenin. Chronic compression of tail IVDs of young-adult and aged Wnt-reporter (TOPGAL) animals initiated an age-related cascade of degenerative-like changes, which included reduced Wnt ligand expression and Wnt signaling in nucleus pulposus cells, despite elevation of b-Catenin protein and gene expression. To determine the effect of upregulated and downregulated Wnt signaling in adult discs, b-Catenin in the nucleus pulposus was stabilized (Shh-CreErT2/b-Cateninfl(Ex3)/fl(Ex3), cACT) or knocked out (Shh-CreErT2/b-Cateninfl/fl, cKO). cACT discs had promoted expression of Wnt-targets and -ligands, brachyury, extracellular matrix production and 34% greater compressive stiffness than WT (b-Cateninfl(Ex3)/fl(Ex3)) discs, but 50% less tensile stiffness. By contrast, knockout reversed the cACT phenotype: less protein expression of b-catenin in the nucleus pulposus, less expression of brachyury, heightened expression of extracellular matrix breakdown and 46% less compressive stiffness than wild-type (b-Cateninfl/fl,WT) discs. These data suggest that intervertebral disc degeneration is associated with loss of Wnt signaling and that the concomitant increase in b-catenin is a regenerative response, potentially offering a therapeutic approach to degeneration.
Functional expression of TLR5 of different vertebrate species and diversification in intestinal pathogen recognition
Authors: Faber Eugenia , Tedin Karsten , Speidel Yvonne , Brinkmann Melanie M. , Josenhans Christine 
Published: July 2018

AbstractToll-like receptor 5 (TLR5) is activated by bacterial flagellins and plays a crucial role in the first-line defence against pathogenic bacteria and in immune homeostasis, and is highly conserved in vertebrate species. However, little comparative information is available on TLR5 functionality. In this study, we compared TLR5 activation using full-length and chimeric TLR5 of various vertebrate species (human, chicken, mouse, pig, cattle). Chimeric TLR5 receptors, consisting of human transmembrane and intracellular domains, linked to extracellular domains of animal origin, were generated and expressed. The comparison of chimeric TLR5s and their full-length counterparts revealed significant functional disparities. While porcine and chicken full-length TLR5s showed a strongly reduced functionality in human cells, all chimeric receptors were functional when challenged with TLR5 ligand Salmonella FliC. Using chimeric receptors as a tool allowed for the identification of ectodomain-dependent activation potential and partially host species-specific differences in response to various enteric bacterial strains and their purified flagellins. We conclude that both the extra- and intracellular determinants of TLR5 receptors are crucial for compatibility with the species expression background and hence for proper receptor functionality. TLR5 receptors with a common intracellular domain provide a useful system to investigate bacteria- and host-specific differences in receptor activation.
Intracellular oligonucleotide delivery using the cell penetrating peptide Xentry
Authors: Coutinho Frazer P. , Green Colin R. , Rupenthal Ilva D. 
Published: July 2018

AbstractThe current study investigated the use of two cationic peptides, Xentry-KALA (XK) and Xentry-Protamine (XP), for intracellular delivery of Connexin43 antisense oligonucleotides (Cx43AsODN). The charge and size of Cx43AsODN:XK and Cx43AsODN:XP complexes was determined by Zetasizer analysis. The earliest positive zeta potential reading was obtained at a 1:2 and 1:1.2 charge ratio of Cx43AsODN:XK and Cx43AsODN:XP respectively, with Cx43AsODN:XK resulting in overall larger complexes than Cx43AsODN:XP. Gel shift mobility assays revealed complete complex formation at a 1:2.5 and 1:2.2 charge ratio of Cx43AsODN:XK and Cx43AsODN:XP, respectively. Cellular uptake studies were carried out in ARPE-19 cells. While both complexes were able to enter the cells, Cx43AsODN:XK uptake appeared punctate and circular indicative of endosomal containment. Cx43AsODN:XP uptake, in contrast, resulted in diffuse appearance inside the cell suggesting endosomal escape of the cargo. Finally, western blot analysis confirmed that Cx43AsODN:XP was able to knockdown Cx43 expression in these cells under normal and hypoxic conditions.
Imaging the development of chronic Chagas disease after oral transmission
Authors: Lewis Michael D. , Francisco Amanda F. , Jayawardhana Shiromani , Langston Harry , Taylor Martin C. , Kelly John M. 
Published: July 2018

AbstractChagas disease is a zoonosis caused by the protozoan parasite Trypanosoma cruzi. Transmission cycles are maintained by haematophagous triatomine bug vectors that carry infective T. cruzi in their faeces. Most human infections are acquired by contamination of mucosal membranes with triatomine faeces after being bitten, however, T. cruzi can be transmitted by several other routes. Oral transmission is an increasingly important aspect of Chagas disease epidemiology, typically involving food or drink products contaminated with triatomines. This has recently caused numerous outbreaks and been linked to unusually severe acute infections. The long-term impact of oral transmission on infection dynamics and disease pathogenesis is unclear. We used highly sensitive bioluminescence imaging and quantitative histopathology to study orally transmitted T. cruzi infections in mice. Both metacyclic and bloodform trypomastigotes were infectious via the oral cavity, but only metacyclics led to established infections by intra-gastric gavage. Mice displayed only mild acute symptoms but later developed significantly increased myocardial collagen content (p = 0.017), indicative of fibrosis. Gastrointestinal tissues and skin were the principal chronic infection reservoirs. Chronic phase parasite load profiles, tissue distribution and myocardial fibrosis severity were comparable to needle-injected controls. Thus, the oral route neither exacerbates nor ameliorates experimental Chagas disease.
Twist and Polar Glide Symmetries: an Additional Degree of Freedom to Control the Propagation Characteristics of Periodic Structures
Authors: Ghasemifard Fatemeh , Norgren Martin , Quevedo-Teruel Oscar 
Published: July 2018

AbstractNew high-frequency 5G and satellite communication systems require fully-metallic antennas and electromagnetic components. These components can be implemented with truncated versions of periodic structures. In order to achieve the desired performance of these future devices, it is of crucial importance to have a precise control of the propagation properties, i.e. the frequency dispersion behavior and stop-bands. Here, we demonstrate the potential use of higher symmetries to diminish the frequency dispersion of periodic structures and control the width of stop-bands with a new type of fully-metallic transmission line, which is loaded with holes on a twist-symmetric configuration. Simulated and experimental results confirm the intrinsic link between the propagation characteristics and the symmetries of a periodic structure. Additionally, we provide a definitive explanation of the recently discovered polar glide symmetry and its potential combination with twist symmetries to produce low-dispersive materials and reconfigurable stop-bands. The promising properties of these structures are demonstrated with a fully-metallic reconfigurable filter, which could be used for future high-frequency 5G and satellite communication systems.
Identification of an INa-dependent and Ito-mediated proarrhythmic mechanism in cardiomyocytes derived from pluripotent stem cells of a Brugada syndrome patient
Authors: Ma Dongrui , Liu Zhenfeng , Loh Li Jun , Zhao Yongxing , Li Guang , Liew Reginald , Islam Omedul , Wu Jianjun , Chung Ying Ying , Teo Wee Siong , Ching Chi Keong , Tan Boon Yew , Chong Daniel , Ho Kah Leng , Lim Paul , Yong Rita Yu Yin , Panama Brian K. , Kaplan Aaron D. , Bett Glenna C. L. , Ware James , Bezzina Connie R. , Verkerk Arie O. , Cook Stuart A. , Rasmusson Randall L. , Wei Heming 
Published: July 2018

AbstractBrugada syndrome (BrS) is an inherited cardiac arrhythmia commonly associated with SCN5A mutations, yet its ionic mechanisms remain unclear due to a lack of cellular models. Here, we used human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from a BrS patient (BrS1) to evaluate the roles of Na+ currents (INa) and transient outward K+ currents (Ito) in BrS induced action potential (AP) changes. To understand the role of these current changes in repolarization we employed dynamic clamp to “electronically express” IK1 and restore normal resting membrane potentials and allow normal recovery of the inactivating currents, INa, ICa and Ito. HiPSC-CMs were generated from BrS1 with a compound SCN5A mutation (p. A226V & p. R1629X) and a healthy sibling control (CON1). Genome edited hiPSC-CMs (BrS2) with a milder p. T1620M mutation and a commercial control (CON2) were also studied. CON1, CON2 and BrS2, had unaltered peak INa amplitudes, and normal APs whereas BrS1, with over 75% loss of INa, displayed a loss-of-INa basal AP morphology (at 1.0 Hz) manifested by a reduced maximum upstroke velocity (by ~80%, p < 0.001) and AP amplitude (p < 0.001), and an increased phase-1 repolarization pro-arrhythmic AP morphology (at 0.1 Hz) in ~25% of cells characterized by marked APD shortening (~65% shortening, p < 0.001). Moreover, Ito densities of BrS1 and CON1 were comparable and increased from 1.0 Hz to 0.1 Hz by ~ 100%. These data indicate that a repolarization deficit could be a mechanism underlying BrS.
Incoherent Nuclear Resonant Scattering from a Standing Spin Wave
Authors: Gollwitzer Jakob , Bocklage Lars , Schlage Kai , Herlitschke Marcus , Wille Hans Christian , Leupold Olaf , Adolff Christian F. , Meier Guido , Röhlsberger Ralf 
Published: July 2018

AbstractWe introduce a method to study the spatial profiles of standing spin waves in ferromagnetic microstructures. The method relies on Nuclear Resonant Scattering of 57Fe using a microfocused beam of synchrotron radiation, the transverse coherence length of which is smaller than the length scale of lateral variations in the magnetization dynamics. Using this experimental method, the nuclear resonant scattering signal due to a confined spin wave is determined on the basis of an incoherent superposition model. From the fits of the Nuclear Resonant Scattering time spectra, the precessional amplitude profile across the stripe predicted by an analytical model is reconstructed. Our results pave the way for studying non-homogeneous dynamic spin configurations in microstructured magnetic systems using nuclear resonant scattering of synchrotron light.
Magnetite-Gold nanohybrids as ideal all-in-one platforms for theranostics
Authors: Efremova Maria V. , Naumenko Victor A. , Spasova Marina , Garanina Anastasiia S. , Abakumov Maxim A. , Blokhina Anastasia D. , Melnikov Pavel A. , Prelovskaya Alexandra O. , Heidelmann Markus , Li Zi-An , Ma Zheng , Shchetinin Igor V. , Golovin Yuri I. , Kireev Igor I. , Savchenko Alexander G. , Chekhonin Vladimir P. , Klyachko Natalia L. , Farle Michael , Majouga Alexander G. , Wiedwald Ulf 
Published: July 2018

AbstractHigh-quality, 25 nm octahedral-shaped Fe3O4 magnetite nanocrystals are epitaxially grown on 9 nm Au seed nanoparticles using a modified wet-chemical synthesis. These Fe3O4-Au Janus nanoparticles exhibit bulk-like magnetic properties. Due to their high magnetization and octahedral shape, the hybrids show superior in vitro and in vivo T2 relaxivity for magnetic resonance imaging as compared to other types of Fe3O4-Au hybrids and commercial contrast agents. The nanoparticles provide two functional surfaces for theranostic applications. For the first time, Fe3O4-Au hybrids are conjugated with two fluorescent dyes or the combination of drug and dye allowing the simultaneous tracking of the nanoparticle vehicle and the drug cargo in vitro and in vivo. The delivery to tumors and payload release are demonstrated in real time by intravital microscopy. Replacing the dyes by cell-specific molecules and drugs makes the Fe3O4-Au hybrids a unique all-in-one platform for theranostics.