bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cryo-Electron Tomography and Proteomics studies of centrosomes from differentiated quiescent thymocytes
Authors: Busselez Johan , Chichón Francisco Javier , Rodríguez Maria Josefa , Alpízar Adan , Gharbi Séverine Isabelle , Franch Mònica , Melero Roberto , Paradela Alberto , Carrascosa José L. , Carazo José-Maria 
Published: May 2019

AbstractWe have used cryo Electron Tomography, proteomics and immunolabeling to study centrosomes isolated from the young lamb thymus, an efficient source of quiescent differentiated cells. We compared the proteome of thymocyte centrosomes to data published for KE37 cells, focusing on proteins associated with centriole disengagement and centrosome separation. The data obtained enhances our understanding of the protein system joining the centrioles, a system comprised of a branched network of fibers linked to an apparently amorphous density that was partially characterized here. A number of proteins were localized to the amorphous density by immunolabeling (C-NAP1, cohesin SMC1, condensin SMC4 and NCAPD2), yet not DNA. In conjuction, these data not only extend our understanding of centrosomes but they will help refine the model that focus on the protein system associated with the centriolar junction.
Novel aroylated phenylenediamine compounds enhance antimicrobial defense and maintain airway epithelial barrier integrity
Authors: Myszor Iwona T. , Parveen Zahida , Ottosson Håkan , Bergman Peter , Agerberth Birgitta , Strömberg Roger , Gudmundsson Gudmundur H. 
Published: May 2019

AbstractAroylated phenylenediamines (APDs) are novel inducers of innate immunity enhancing cathelicidin gene expression in human bronchial epithelial cell lines. Here we present two newly developed APDs and aimed at defining the response and signaling pathways for these compounds with reference to innate immunity and antimicrobial peptide (AMP) expression. Induction was initially defined with respect to dose and time and compared with the APD Entinostat (MS-275). The induction applies to several innate immunity effectors, indicating that APDs trigger a broad spectrum of antimicrobial responses. The bactericidal effect was shown in an infection model against Pseudomonas aeruginosa by estimating bacteria entering cells. Treatment with a selected APD counteracted Pseudomonas mediated disruption of epithelial integrity. This double action by inducing AMPs and enhancing epithelial integrity for one APD compound is unique and taken as a positive indication for host directed therapy (HDT). The APD effects are mediated through Signal transducer and activator of transcription 3 (STAT3) activation. Utilization of induced innate immunity to fight infections can reduce antibiotic usage, might be effective against multidrug resistant bacteria and is in line with improved stewardship in healthcare.
The Rho/MRTF pathway inhibitor CCG-222740 reduces stellate cell activation and modulates immune cell populations in KrasG12D; Pdx1-Cre (KC) mice
Authors: Leal Ana S. , Misek Sean A. , Lisabeth Erika M. , Neubig Richard R. , Liby Karen T. 
Published: May 2019

AbstractThe stromal reaction in pancreatic cancer creates a physical barrier that blocks therapeutic intervention and creates an immunosuppressive tumor microenvironment. The Rho/myocardin-related transcription factor (MRTF) pathway is implicated in the hyper-activation of fibroblasts in fibrotic diseases and the activation of pancreatic stellate cells. In this study we use CCG-222740, a small molecule, designed as a Rho/MRTF pathway inhibitor. This compound decreases the activation of stellate cells in vitro and in vivo, by reducing the levels of alpha smooth muscle actin (α-SMA) expression. CCG-222740 also modulates inflammatory components of the pancreas in KC mice (LSL-KrasG12D/+; Pdx-1-Cre) stimulated with caerulein. It decreases the infiltration of macrophages and increases CD4 T cells and B cells. Analysis of the pancreatic adenocarcinoma (PDA) TCGA dataset revealed a correlation between elevated RhoA, RhoC and MRTF expression and decreased survival in PDA patients. Moreover, a MRTF signature is correlated with a Th2 cell signature in human PDA tumors.
MinION sequencing technology to characterize unauthorized GM petunia plants circulating on the European Union market
Authors: Fraiture Marie-Alice , Ujhelyi Gabriella , Ovesná Jaroslava , Van Geel Dirk , De Keersmaecker Sigrid , Saltykova Assia , Papazova Nina , Roosens Nancy H. C. 
Published: May 2019

AbstractIn order to characterize unauthorized genetically modified petunia, an integrated strategy has been applied here on several suspected petunia samples from the European market. More precisely, DNA fragments of interest were produced by DNA walking anchored on key targets, earlier detected by real-time PCR screening analysis, to be subsequently sequenced using the MinION platform from Oxford Nanopore Technologies. This way, the presence of genetically modified petunia was demonstrated via the characterization of their transgene flanking regions as well as unnatural associations of elements from their transgenic cassette.
Conserved, breed-dependent, and subline-dependent innate immune responses of Fayoumi and Leghorn chicken embryos to Newcastle disease virus infection
Authors: Schilling Megan A. , Memari Sahar , Cavanaugh Meredith , Katani Robab , Deist Melissa S. , Radzio-Basu Jessica , Lamont Susan J. , Buza Joram J. , Kapur Vivek 
Published: May 2019

AbstractNewcastle disease virus (NDV) is a threat to the global poultry industry, but particularly for smallholder farmers in low- and middle-income countries. Previous reports suggest that some breeds of chickens are less susceptible to NDV infection, however, the mechanisms contributing to this are unknown. We here examined the comparative transcriptional responses of innate immune genes to NDV infection in inbred sublines of the Fayoumi and Leghorn breeds known to differ in their relative susceptibility to infection as well as at the microchromosome bearing the major histocompatability complex (MHC) locus. The analysis identified a set of five core genes, Mx1, IRF1, IRF7, STAT1, and SOCS1, that are up-regulated regardless of subline. Several genes were differentially expressed in a breed- or subline-dependent manner. The breed-dependent response involved TLR3, NOS2, LITAF, and IFIH1 in the Fayoumi versus IL8, CAMP, and CCL4 in the Leghorn. Further analysis identified subline-dependent differences in the pro-inflammatory response within the Fayoumi breed that are likely influenced by the MHC. These results have identified conserved, breed-dependent, and subline-dependent innate immune responses to NDV infection in chickens, and provide a strong framework for the future characterization of the specific roles of genes and pathways that influence the susceptibility of chickens to NDV infection.
Possible nanoantenna control of chlorophyll dynamics for bioinspired photovoltaics
Authors: Gaponenko Sergey V. , Adam Pierre-Michel , Guzatov Dmitry V. , Muravitskaya Alina O. 
Published: May 2019

AbstractIn the context of using portions of a photosynthetic apparatus of green plants and photosynthesizing bacteria in bioinspired photovoltaic systems, we consider possible control of the chlorophyll excited state decay rate using nanoantennas in the form of a single metal and semiconductor nanoparticle. Since chlorophyll luminescence competes with electron delivery for chemical reactions chain and also to an external circuit, we examine possible excited state decay inhibition contrary to radiative rate enhancement. Both metal and semiconductor nanoparticles enable inhibition of radiative decay rate by one order of the magnitude as compared to that in vacuum, whereas a metal nanosphere cannot perform the overall decay inhibition since slowing down of radiative decay occurs only along with the similar growth of its nonradiative counterpart whereas a semiconductor nanoantenna is lossless. Additionally, at normal orientation of the emitter dipole moment to a nanoparticle surface, a silicon nanoparticle promotes enhancement of radiative decay by one order of the magnitude within the whole visible range. Our results can be used for other photochemical or photovoltaic processes, and strong radiative decay enhancement found for dielectric nanoantennas paves the way to radiative decays and light emitters engineering without non-radiative losses.
Structural Insights into Catalytic Versatility of the Flavin-dependent Hydroxylase (HpaB) from Escherichia coli
Authors: Shen Xiaolin , Zhou Dayong , Lin Yuheng , Wang Jia , Gao Shuaihua , Kandavelu Palani , Zhang Hua , Zhang Ruihua , Wang Bi-Cheng , Rose John , Yuan Qipeng , Yan Yajun 
Published: May 2019

Abstract4-Hydroxyphenylacetate 3-hydroxylase (EcHpaB) from Escherichia coli is capable of efficient ortho-hydroxylation of a wide range of phenolic compounds and demonstrates great potential for broad chemoenzymatic applications. To understand the structural and mechanistic basis of its catalytic versatility, we elucidated the crystal structure of EcHpaB by X-ray crystallography, which revealed a unique loop structure covering the active site. We further performed mutagenesis studies of this loop to probe its role in substrate specificity and catalytic activity. Our results not only showed the loop has great plasticity and strong tolerance towards extensive mutagenesis, but also suggested a flexible loop that enables the entrance and stable binding of substrates into the active site is the key factor to the enzyme catalytic versatility. These findings lay the groundwork for editing the loop sequence and structure for generation of EcHpaB mutants with improved performance for broader laboratory and industrial use.
Extending the depth-of-field of imaging systems with a scattering diffuser
Authors: Liao Meihua , Lu Dajiang , Pedrini Giancarlo , Osten Wolfgang , Situ Guohai , He Wenqi , Peng Xiang 
Published: May 2019

AbstractLarge depth of field (DOF) is a longstanding goal in optical imaging field. In this paper we presented a simple but efficient method to extend the DOF of a diffraction-limited imaging system using a thin scattering diffuser. The DOF characteristic of the imaging system with random phase modulation was analyzed based on the analytical model of ambiguity function as a polar display of the optical transfer function (OTF). The results of numerical simulation showed that more high-frequency components existed in the defocused OTF curve when the exit pupil of the imaging system exhibited a random phase modulation. It proved the important role of the scattering diffuser in extending the DOF of imaging systems. For the reconstruction, a stack of point spread functions (PSFs) corresponding to different axial locations within a measurement range were superimposed to construct the stacked PSF. Then the large DOF image was recovered from a speckle pattern by deconvolution. In this proof-of-concept, we experimentally demonstrated the single-shot imaging with larger DOF using a thin glass scattering diffuser in both a single-lens imaging system and a microscopic imaging system.
A Novel 3D In Vitro Platform for Pre-Clinical Investigations in Drug Testing, Gene Therapy, and Immuno-oncology
Authors: Candini Olivia , Grisendi Giulia , Foppiani Elisabetta Manuela , Brogli Matteo , Aramini Beatrice , Masciale Valentina , Spano Carlotta , Petrachi Tiziana , Veronesi Elena , Conte Pierfranco , Mari Giorgio , Dominici Massimo 
Published: May 2019

AbstractTumors develop within complex cell-to-cell interactions, with accessory cells playing a relevant role starting in the early phases of cancer progression. This event occurs in a three-dimensional (3D) environment, which to date, has been difficult to reproduce in vitro due to its complexity. While bi-dimensional cultures have generated substantial data, there is a progressive awareness that 3D culture strategies may rapidly increase the understanding of tumor development and be used in anti-cancer compound screening and for predicting response to new drugs utilizing personalized approaches. However, simple systems capable of rapidly rebuilding cancer tissues ex-vivo in 3D are needed and could be used for a variety of applications. Therefore, we developed a flat, handheld and versatile 3D cell culture bioreactor that can be loaded with tumor and/or normal cells in combination which can be monitored using a variety of read-outs. This biocompatible device sustained 3D growth of tumor cell lines representative of various cancers, such as pancreatic and breast adenocarcinoma, sarcoma, and glioblastoma. The cells repopulated the thin matrix which was completely separated from the outer space by two gas-permeable membranes and was monitored in real-time using both microscopy and luminometry, even after transportation. The device was tested in 3D cytotoxicity assays to investigate the anti-cancer potential of chemotherapy, biologic agents, and cell-based therapy in co-cultures. The addition of luciferase in target cancer cells is suitable for comparative studies that may also involve parallel in vivo investigations. Notably, the system was challenged using primary tumor cells harvested from lung cancer patients as an innovative predictive functional assay for cancer responsiveness to checkpoint inhibitors, such as nivolumab. This bioreactor has several novel features in the 3D-culture field of research, representing a valid tool useful for cancer investigations, drug screenings, and other toxicology approaches.
A Bio-inspired Hypoxia Sensor using HIF1a-Oxygen-Dependent Degradation Domain
Authors: Iglesias Pablo , Penas Cristina , Barral-Cagiao Laura , Pazos Elena , Costoya Jose A. 
Published: May 2019

AbstractFunctional imaging has become an important tool in oncology because it not only provides information about the size and localization of the tumour, but also about the pathophysiological features of the tumoural cells. One of the characteristic features of some tumour types is that their fast growth leads to deficient intratumoral vascularization, which results in low oxygen availability. To overcome this lack of oxygen, tumoural cells activate the neoangiogenic program by upregulating the transcription factor HIF-1α. Herein we report a non-invasive in vitro detection method of hypoxia using designed fluorescent peptide probes based on the oxygen-dependent degradation domain of HIF-1α. The fluorescent probe retains the oxygen-sensing capability of HIF-1α, so that it is stabilized under hypoxia and readily degraded by the proteasome under normoxia, thus providing direct information of the cellular oxygen availability.
Nanoparticle-Infused UHMWPE Layer as Multifunctional Coating for High-Performance PPTA Single Fibers
Authors: Zhang Zhuolei , Zhao Yao , Li Haoqi , Percec Simona , Yin Jie , Ren Fei 
Published: May 2019

AbstractHigh-performance fibers made of poly-(p-phenylene terephthalamide) (PPTA) with high stiffness and high strength are widely used in body armor for protection due to their high degree of molecular chain alignment along the fiber direction. However, their poor mechanical properties in the transverse direction and low surface friction are undesirable for applications requiring resistance to ballistic impact. Here we provide a simple yet effective surface engineering strategy to improve both the transverse mechanical properties and the tribological property by coating PPTA fibers with ultra-high molecular weight polyethylene (UHMWPE) embedded with silica nanoparticles. The coated-PPTA fiber shows remarkable enhancement in transverse mechanical properties including ~127% increase of Young’s modulus, which is attributed to both the alignment of UHMWPE chains in the transverse direction and the embeded ceramic nanoparticles. Meanwhile, the surface friction of the coated fiber increases twofold as a result of the ceramic nanoparticles. In addition, the coated fibers exhibit an enhanced chemical resistance to external harsh environment. The improved transverse mechanical properties, surface frictional characteristics, and chemical resistance demonstrate that coating with UHMWPE and ceramic nanoparticles can be used as an effective approach to enhance the performance of PPTA and other high-performance polymer fibers for body armor applications.
Mesenchymal stem cells of Systemic Sclerosis patients, derived from different sources, show a profibrotic microRNA profiling
Authors: Di Benedetto Paola , Panzera Noemi , Cipriani Paola , Mastroiaco Valentina , Tessitore Alessandra , Liakouli Vasiliki , Ruscitti Piero , Berardicurti Onorina , Carubbi Francesco , Guggino Giuliana , Bianchi Andrea , Di Marco Antinisca , Ciccia Francesco , Alesse Edoardo , Giacomelli Roberto 
Published: May 2019

AbstractSystemic Sclerosis (SSc) is a disease with limited therapeutic possibilities. Mesenchymal stem cells (MSCs)-therapy could be a promising therapeutic option, however the ideal MSCs source has not yet been found. To address this problem, we perform comparison between bone marrow (BM)-MSCs and adipose (A)-MSCs, by the miRs expression profile, to identify the gene modulation in these two MSCs source. MicroRNAs (miRs) are RNAs sequences, regulating gene expression and MSCs, derived from different tissues, may differently respond to the SSc microenvironment. The miRs array was used for the miRs profiling and by DIANA-mirPath tool we identified the biological functions of the dysregulated miRs. In SSc-BM-MSCs, 6 miRs were significantly down-regulated and 4 miRs up-regulated. In SSc-A-MSCs, 11 miRs were significantly down-regulated and 3 miRs up-regulated. Interestingly, in both the sources, the involved pathways included the senescence mechanisms and the pro-fibrotic behaviour. Furthermore, both the MSCs sources showed potential compensatory ability. A deeper knowledge of this miRs signature might give more information about some pathogenic steps of the disease and in the same time clarify the possible therapeutic role of autologous MSCs in the regenerative therapy in SSc.
Time-dependent prediction of arrhythmia recurrences during long-term follow-up in patients undergoing catheter ablation of atrial fibrillation: The Leipzig Heart Center AF Ablation Registry
Authors: Kornej Jelena , Schumacher Katja , Zeynalova Samira , Sommer Philipp , Arya Arash , Weiß Manuela , Piorkowski Christopher , Husser Daniela , Bollmann Andreas , Lip Gregory Y. H. , Hindricks Gerhard 
Published: May 2019

AbstractThe prediction of arrhythmia recurrences after catheter ablation of atrial fibrillation (AF) remains challenging. The aim of current analysis was to investigate the time-dependent prediction of arrhythmia recurrences after AF catheter ablation during long-term follow-up. The study included 879 patients (61 ± 10 years; 64% males; 39% persistent AF) undergoing first AF catheter ablation. Rhythm outcomes were documented using 7-days Holter monitoring. The APPLE score (Age, Persistent AF, imPaired eGFR, Left atrium (LA), EF) was calculated at baseline, while MB-LATER score (Male gender, Bundle branch block, LA, AF Type, Early Recurrences) 3 months after ablation. The median follow-up time was 37 months [95%CI 35;39]. ERAF and LRAF occurred in 45% and 64%, respectively. On multivariable analysis, ERAF (HR 2.095, 95%CI 1.762–2.490, p < 0.001) was strongly associated with LRAF. The APPLE (HR 1.385, 95%CI 1.276–1.505, p < 0.001) and MB-LATER (HR 1.326, 95%CI 1.239–1.419, p < 0.001) scores significantly predicted LRAF during follow-up. On the ROC analysis, APPLE (AUC 0.640, 95%CI 0.602–0.677, p < 0.001) and MB-LATER (AUC 0.654, 95%CI 0.616–0.691, p < 0.001) demonstrated moderate prediction. Summarizing, ERAF was the strongest predictor for LRAF in time-dependent manner. The APPLE and MB-LATER scores demonstrated moderate prediction of arrhythmia recurrences during long term follow-up.
Formation and stability of complex metallic phases including quasicrystals explored through combinatorial methods
Authors: Wolf Witor , Kube Sebastian A. , Sohn Sungwoo , Xie Yujun , Cha Judy J. , Scanley B. Ellen , Kiminami Claudio S. , Bolfarini Claudemiro , Botta Walter J. , Schroers Jan 
Published: May 2019

AbstractAluminum-based quasicrystals typically form across narrow composition ranges within binary to quaternary alloys, which makes their fabrication and characterization challenging. Here, we use combinatorial approaches together with fast characterization techniques to study a wide compositional range including known quasicrystal forming compositions. Specifically, we use magnetron co-sputtering to fabricate libraries of ~140 Al-Cu-Fe and ~300 Al-Cu-Fe-Cr alloys. The alloys compositions are measured through automated energy dispersive X-ray spectroscopy. Phase formation and thermal stability are investigated for different thermal processing conditions (as-sputtered and annealed at 400 °C, 520 °C and 600 °C for Al-Cu-Fe libraries; annealed at 600 °C for Al-Cu-Fe-Cr libraries) using automated X-ray diffraction and transmission electron microscopy. In both systems the compositional regions across which the quasicrystalline phase forms are identified. In particular, we demonstrate that the quasicrystalline phase forms across an unusually broad composition range in the Al-Cu-Fe-Cr system. Additionally, some of the considered alloys vitrify during sputtering, which also allows us to study their nucleation behavior. We find that phases with polytetrahedral symmetry, such as the icosahedral quasicrystal and the λ-Al13Fe4 phase, exhibit higher nucleation rates but lower growth rates, as compared to other phases with a lower degree of polytetrahedral order. Altogether, the here used combinatorial approach is powerful to identify compositional regions of quasicrystals.
Differential microRNA profile underlies the divergent healing responses in skin and oral mucosal wounds
Authors: Simões Alyne , Chen Lin , Chen Zujian , Zhao Yan , Gao Shang , Marucha Phillip T. , Dai Yang , DiPietro Luisa A. , Zhou Xiaofeng 
Published: May 2019

AbstractOral mucosal wounds heal faster than skin wounds, yet the role of microRNAs in this differential healing has never been examined. To delineate the role of microRNAs in this site-specific injury response, we first compared the microRNAome of uninjured skin and oral mucosa in mice. A total of 53 tissue-specific microRNAs for skin and oral mucosa epithelium were identified. The most striking difference was the high abundance of miR-10a/b in skin (accounting for 21.10% of the skin microRNAome) as compared to their low expression in oral mucosa (2.87%). We further examined the dynamic changes of microRNAome throughout the time course of skin and oral mucosal wound healing. More differentially expressed microRNAs were identified in skin wounds than oral wounds (200 and 33, respectively). More specifically, miR-10a/b was significantly down-regulated in skin but not oral wounds. In contrast, up-regulation of miR-21 was observed in both skin and oral wounds. The therapeutic potential of miR-10b and miR-21 in accelerating wound closure was demonstrated in in vitro assays and in a murine skin wound model. Thus, we provided the first site-specific microRNA profile of skin and oral mucosal wound healing, and demonstrate the feasibility of a microRNA-based therapy for promoting wound closure.