bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dysbiosis in chronic periodontitis: Key microbial players and interactions with the human host
Authors: Deng Zhi-Luo , Szafrański Szymon P. , Jarek Michael , Bhuju Sabin , Wagner-Döbler Irene 
Published: June 2017

AbstractPeriodontitis is an extremely prevalent disease worldwide and is driven by complex dysbiotic microbiota. Here we analyzed the transcriptional activity of the periodontal pocket microbiota from all domains of life as well as the human host in health and chronic periodontitis. Bacteria showed strong enrichment of 18 KEGG functional modules in chronic periodontitis, including bacterial chemotaxis, flagellar assembly, type III secretion system, type III CRISPR-Cas system, and two component system proteins. Upregulation of these functions was driven by the red-complex pathogens and candidate pathogens, e.g. Filifactor alocis, Prevotella intermedia, Fretibacterium fastidiosum and Selenomonas sputigena. Nine virulence factors were strongly up-regulated, among them the arginine deiminase arcA from Porphyromonas gingivalis and Mycoplasma arginini. Viruses and archaea accounted for about 0.1% and 0.22% of total putative mRNA reads, respectively, and a protozoan, Entamoeba gingivalis, was highly enriched in periodontitis. Fourteen human transcripts were enriched in periodontitis, including a gene for a ferric iron binding protein, indicating competition with the microbiota for iron, and genes associated with cancer, namely nucleolar phosphoprotein B23, ankyrin-repeat domain 30B-like protein and beta-enolase. The data provide evidence on the level of gene expression in vivo for the potentially severe impact of the dysbiotic microbiota on human health.
3D Super-Resolution Optical Profiling Using Microsphere Enhanced Mirau Interferometry
Authors: Kassamakov Ivan , Lecler Sylvain , Nolvi Anton , Leong-Hoï Audrey , Montgomery Paul , Hæggström Edward 
Published: June 2017

AbstractWe present quantitative three dimensional images of grooves on a writable Blu-ray Disc based on a single objective Mirau type interferometric microscope, enhanced with a microsphere which is considered as a photonic nanojet source. Along the optical axis the resolution of this microsphere assisted interferometry system is a few nanometers while the lateral resolution is around 112 nm. To understand the physical phenomena involved in this kind of imaging we have modelled the interaction between the photonic jet and the complex disc surface. Agreement between simulation and experimental results is demonstrated. We underline that although the ability of the microsphere to generate a photonic nanojet does not alone explain the resolution of the interferometer, the nanojet can be used to try to understand the imaging process. To partly explain the lateral super-resolution, the potential role of coherence is illustrated. The presented modality may have a large impact on many fields from bio-medicine to nanotechnology.
Epigenetic and antitumor effects of platinum(IV)-octanoato conjugates
Authors: Novohradsky Vojtech , Zanellato Ilaria , Marzano Cristina , Pracharova Jitka , Kasparkova Jana , Gibson Dan , Gandin Valentina , Osella Domenico , Brabec Viktor 
Published: June 2017

AbstractWe present the anticancer properties of cis, cis, trans-[Pt(IV)(NH3)2Cl2(OA)2] [Pt(IV)diOA] (OA = octanoato), Pt(IV) derivative of cisplatin containing two OA units appended to the axial positions of a six-coordinate Pt(IV) center. Our results demonstrate that Pt(IV)diOA is a potent cytotoxic agent against many cancer cell lines (the IC50 values are approximately two orders of magnitude lower than those of clinically used cisplatin or Pt(IV) derivatives with biologically inactive axial ligands). Importantly, Pt(IV)diOA overcomes resistance to cisplatin, is significantly more potent than its branched Pt(IV) valproato isomer and exhibits promising in vivo antitumor activity. The potency of Pt(IV)diOA is a consequence of several factors including enhanced cellular accumulation correlating with enhanced DNA platination and cytotoxicity. Pt(IV)diOA induces DNA hypermethylation and reduces mitochondrial membrane potential in cancer cells at levels markedly lower than the IC50 value of free OA suggesting the synergistic action of platinum and OA moieties. Collectively, the remarkable antitumor effects of Pt(IV)diOA are a consequence of the enhanced cellular uptake which makes it possible to simultaneously accumulate high levels of both cisplatin and OA in cells. The simultaneous dual action of cisplatin and OA by different mechanisms in tumor cells may result in a markedly enhanced and unique antitumor effects of Pt(IV) prodrugs.
Fabrication of modified hydrogenated castor oil/GPTMS-ZnO composites and effect on UV resistance of leather
Authors: Ma Jianzhong , Duan Limin , Lu Juan , Lyu Bin , Gao Dangge , Wu Xionghu 
Published: June 2017

AbstractLeather products are made from the natural skin collagen fibers. It is vulnerable to the environmental factor such as solar ultraviolet irradiation in the using process. Therefore anti-UV performance is a very important quality, particularly for chrome-free leather. ZnO is a well-known UV absorber commonly used in the cosmetic industry. We have investigated its potential to increase the anti-UV performance of chrome-free leather. Modified hydrogenated castor oil/GPTMS-ZnO (MHCO/ GPTMS-ZnO) composites were prepared using spherical ZnO nanoparticles, hydrogenated castor oil, maleic anhydride and sodium bisulfite. MHCO/GPTMS-ZnO composites have better anti-UV ability and stability. MHCO/GPTMS-ZnO composites were applied to the leather processing. The treated samples were exposed to artificial sunlight. Anti-yellowing tests showed that MHCO/GPTMS-ZnO composites significantly improved anti-UV performance of leather.
Metabolic and evolutionary patterns in the extremely acidophilic archaeon Ferroplasma acidiphilum YT
Authors: Golyshina Olga V. , Tran Hai , Reva Oleg N. , Lemak Sofia , Yakunin Alexander F. , Goesmann Alexander , Nechitaylo Taras Y. , LaCono Violetta , Smedile Francesco , Slesarev Alexei , Rojo David , Barbas Coral , Ferrer Manuel , Yakimov Michail M. , Golyshin Peter N. 
Published: June 2017

AbstractFerroplasmaceaerepresent ubiquitous iron-oxidising extreme acidophiles with a number of unique physiological traits. In a genome-based study ofFerroplasma acidiphilumYT, the only species of the genusFerroplasmawith a validly published name, we assessed its central metabolism and genome stability during a long-term cultivation experiment. Consistently with physiology, the genome analysis points toF. acidiphilumYThaving an obligate peptidolytic oligotrophic lifestyle alongside with anaplerotic carbon assimilation. This narrow trophic specialisation abridges the sugar uptake, although all genes for glycolysis and gluconeogenesis, including bifunctional unidirectional fructose 1,6-bisphosphate aldolase/phosphatase, have been identified. Pyruvate and 2-oxoglutarate dehydrogenases are substituted by ‘ancient’ CoA-dependent pyruvate and alpha-ketoglutarate ferredoxin oxidoreductases. In the lab culture, after ~550 generations, the strain exhibited the mutation rate of ≥1.3 × 10−8single nucleotide substitutions per site per generation, which is among the highest values recorded for unicellular organisms. All but one base substitutions were G:C to A:T, their distribution between coding and non-coding regions and synonymous-to-non-synonymous mutation ratios suggest the neutral drift being a prevalent mode in genome evolution in the lab culture. Mutations in nature seem to occur with lower frequencies, as suggested by a remarkable genomic conservation inF. acidiphilumYTvariants from geographically distant populations.
Enhanced Optical Properties of ZnO and CeO2-coated ZnO Nanostructures Achieved Via Spherical Nanoshells Growth On A Polystyrene Template
Authors: Eltayeb Asmaa , Daniels Stephen , McGlynn Enda 
Published: June 2017

AbstractIn this paper, ZnO, CeO2 and CeO2-coated ZnO nanostructures were synthesised by simple and efficient low temperature wet chemical methods on Si (100) and quartz substrates. The ZnO films were prepared by a drop coating deposition method. This was then combined with a thin layer of the redox active material CeO2 to form CeO2-coated ZnO films. Spherical ZnO nanoshell structures and CeO2-coated ZnO nanoshells have been prepared using polystyrene (PS) sphere monolayer templates. The structural properties and morphologies of the nanostructures were analysed by x-ray diffraction (XRD) and scanning electron microscopy (SEM). The nanostructure compositions are studied in more detail using secondary ion mass spectroscopy (SIMS). The optical properties of the nanostructures were measured using ultraviolet-visible (UV-Vis) absorption spectroscopy in order to ascertain the effects of the nanoshell structures and the whispering gallery modes associated with these structures on the optical properties of the deposits. Our data show UV and visible light absorption was very significantly enhanced due to this nanostructuring.
Adenovirus-mediated suppression of hypothalamic glucokinase affects feeding behavior
Authors: Uranga Romina María , Millán Carola , Barahona María José , Recabal Antonia , Salgado Magdiel , Martinez Fernando , Ordenes Patricio , Elizondo-Vega Roberto , Sepúlveda Fernando , Uribe Elena , García-Robles María de los Ángeles 
Published: June 2017

AbstractGlucokinase (GK), the hexokinase involved in glucosensing in pancreatic β-cells, is also expressed in arcuate nucleus (AN) neurons and hypothalamic tanycytes, the cells that surround the basal third ventricle (3V). Several lines of evidence suggest that tanycytes may be involved in the regulation of energy homeostasis. Tanycytes have extended cell processes that contact the feeding-regulating neurons in the AN, particularly, agouti-related protein (AgRP), neuropeptide Y (NPY), cocaine- and amphetamine-regulated transcript (CART) and proopiomelanocortin (POMC) neurons. In this study, we developed an adenovirus expressing GK shRNA to inhibit GK expression in vivo. When injected into the 3V of rats, this adenovirus preferentially transduced tanycytes. qRT-PCR and Western blot assays confirmed GK mRNA and protein levels were lower in GK knockdown animals compared to the controls. In response to an intracerebroventricular glucose injection, the mRNA levels of anorexigenic POMC and CART and orexigenic AgRP and NPY neuropeptides were altered in GK knockdown animals. Similarly, food intake, meal duration, frequency of eating events and the cumulative eating time were increased, whereas the intervals between meals were decreased in GK knockdown rats, suggesting a decrease in satiety. Thus, GK expression in the ventricular cells appears to play an important role in feeding behavior.
Both interferon alpha and lambda can reduce all intrahepatic HDV infection markers in HBV/HDV infected humanized mice
Authors: Giersch Katja , Homs Maria , Volz Tassilo , Helbig Martina , Allweiss Lena , Lohse Ansgar W. , Petersen Jörg , Buti Maria , Pollicino Teresa , Sureau Camille , Dandri Maura , Lütgehetmann Marc 
Published: June 2017

AbstractCo-infection with hepatitis B (HBV) and D virus (HDV) is associated with the most severe course of liver disease. Interferon represents the only treatment currently approved. However, knowledge about the impact of interferons on HDV in human hepatocytes is scant. Aim was to assess the effect of pegylated interferon alpha (peg-IFNα) and lambda (peg-IFNλ), compared to the HBV-polymerase inhibitor entecavir (ETV) on all HDV infection markers using human liver chimeric mice and novel HDV strand-specific qRT-PCR and RNA in situ hybridization assays, which enable intrahepatic detection of HDV RNA species. Peg-IFNα and peg-IFNλ reduced HDV viremia (1.4 log and 1.2 log, respectively) and serum HBsAg levels (0.9-log and 0.4-log, respectively). Intrahepatic quantification of genomic and antigenomic HDV RNAs revealed a median ratio of 22:1 in untreated mice, resembling levels determined in HBV/HDV infected patients. Both IFNs greatly reduced intrahepatic levels of genomic and antigenomic HDV RNA, increasing the amounts of HDAg- and antigenomic RNA-negative hepatocytes. ETV-mediated suppression of HBV replication (2.1-log) did not significantly affect HBsAg levels, HDV productivity and/or release. In humanized mice lacking adaptive immunity, IFNs but not ETV suppressed HDV. Viremia decrease reflected the intrahepatic reduction of all HDV markers, including the antigenomic template, suggesting that intracellular HDV clearance is achievable.
Qualifying a eukaryotic cell-free system for fluorescence based GPCR analyses
Authors: Zemella Anne , Grossmann Solveig , Sachse Rita , Sonnabend Andrei , Schaefer Michael , Kubick Stefan 
Published: June 2017

AbstractMembrane proteins are key elements in cell-mediated processes. In particular, G protein-coupled receptors (GPCRs) have attracted increasing interest since they affect cellular signaling. Furthermore, mutations in GPCRs can cause acquired and inheritable diseases. Up to date, there still exist a number of GPCRs that has not been structurally and functionally analyzed due to difficulties in cell-based membrane protein production. A promising approach for membrane protein synthesis and analysis has emerged during the last years and is known as cell-free protein synthesis (CFPS). Here, we describe a simply portable method to synthesize GPCRs and analyze their ligand-binding properties without the requirement of additional supplements such as liposomes or nanodiscs. This method is based on eukaryotic cell lysates containing translocationally active endogenous endoplasmic reticulum-derived microsomes where the insertion of GPCRs into biologically active membranes is supported. In this study we present CFPS in combination with fast fluorescence-based screening methods to determine the localization, orientation and ligand-binding properties of the endothelin B (ET-B) receptor upon expression in an insect-based cell-free system. To determine the functionality of the cell-free synthesized ET-B receptor, we analyzed the binding of its ligand endothelin-1 (ET-1) in a qualitative fluorescence-based assay and in a quantitative radioligand binding assay.
A new paradigm for antiangiogenic therapy through controlled release of bevacizumab from PLGA nanoparticles
Authors: Sousa Flávia , Cruz Andrea , Fonte Pedro , Pinto Inês Mendes , Neves-Petersen Maria Teresa , Sarmento Bruno 
Published: June 2017

AbstractMonoclonal antibodies have deserved a remarkable interest for more than 40 years as a vital tool for the treatment of various diseases. Still, there is a raising interest to develop advanced monoclonal antibody delivery systems able to tailor pharmacokinetics. Bevacizumab is a humanized immunoglobulin IgG1 used in antiangiogenic therapies due to its capacity to inhibit the interaction between vascular endothelial growth factor and its receptor. However, bevacizumab-based antiangiogenic therapy is not always effective due to poor treatment compliance associated to multiples administrations and drug resistance. In this work, we show a promising strategy of encapsulating bevacizumab to protect and deliver it, in a controlled manner, increasing the time between administrations and formulation shelf-life. Nanoencapsulation of bevacizumab represents a significant advance for selective antiangiogenic therapies since extracellular, cell surface and intracellular targets can be reached. The present study shows that bevacizumab-loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles does not impair its native-like structure after encapsulation and fully retain the bioactivity, making this nanosystem a new paradigm for the improvement of angiogenic therapy.
The efficacy and toxicities of intensive induction chemotherapy followed by concurrent chemoradiotherapy in nasopharyngeal carcinoma patients with N3 disease
Authors: Zhang Yingying , Chen Mingqiu , Chen Cheng , Kong Lin , Lu Jiade J. , Xu Benhua 
Published: June 2017

AbstractTo assess the feasibility, efficacy and safety of 4 cycles of induction chemotherapy (ICT) followed by concurrent chemoradiotherapy (CRT) in nasopharyngeal carcinoma (NPC) patients with N3 disease. ICT consisting of paclitaxel (135 mg/m2) and nedaplatin (80 mg/m2) given every 3 weeks for 4 cycles followed by cisplatin-based CRT was planned. 22 patients completed 4 cycles of TP regimen ICT and the CRT according to the protocol. After 4 cycles of ICT, the ORR of the primary site was 100% (CR 22.7%, PR 77.3%), and that of the cervical lymph nodes was 95.5% (CR 27.3%, PR 68.2%). After the completion of CRT, the ORR of the primary site was 100% (CR 81.8%, PR 18.2%), and that of the cervical lymph nodes also reached 100% (CR 86.4%, PR 3.6%). The main hematological adverse events were grade 1 to 2 (G1/G2) neutropenia/anemia without febrile neutropenia. The most frequent toxicities during CRT were G1/G2 neutropenia, asthenia, oropharyngeal mucositis and skin injury. The median follow-up time was 46.5 (14 to 75) months. The 3-year PFS, DMFS, LRFS and OS were 81.8%, 81.8%, 100%, and 90.9%, respectively. The results suggest that intensive ICT followed by CRT in NPC patients with N3 disease is effective and well tolerated.
A Nationwide Study of Severe and Protracted Diarrhoea in Patients with Primary Immunodeficiency Diseases
Authors: Lee Wen-I , Chen Chien-Chang , Jaing Tang-Her , Ou Liang-Shiou , Hsueh Chuen , Huang Jing-Long 
Published: June 2017

AbstractDiarrhoea lasting longer than 14 days and failing to respond to conventional management is defined as severe and protracted diarrhoea (SD). In this study, we investigated the prevalence, pathogens and prognosis of SD in primary immunodeficiency diseases (PIDs). Among 246 patients with predominantly paediatric-onset PIDs from 2003–2015, 21 [Btk (six), IL2RG (four), WASP, CD40L, gp91 (three each), gp47, RAG2 (one each)] and five [CVID (four), SCID (one)] without identified mutations had SD before prophylactic treatment. Detectable pathogens included pseudomonas, salmonella (six each), E. coli, cytomegalovirus, coxsackie virus and cryptosporidium (one each), all of whom improved after a mean 17 days of antibiotics and/or IVIG treatment. Seven (7/26; 27.0%) patients died [respiratory failure (four), lymphoma, sepsis and intracranial haemorrhage (one each)]. The patients with WAS, CGD and CD40L and SD had a higher mortality rate than those without. Another five males with mutant XIAP, STAT1, FOXP3 (one each) and STAT3 (two) had undetectable-pathogenic refractory diarrhoea (RD) that persisted >21 days despite aggressive antibiotic/steroid treatment and directly resulted in mortality. For the patients with RD without anti-inflammatory optimization, those with mutant XIAP and FOXP3 died of Crohn’s-like colitis and electrolyte exhaustion in awaiting transplantation, while transplantation cured the STAT1 patient.
Regulation of sub-compartmental targeting and folding properties of the Prion-like protein Shadoo
Authors: Pepe Anna , Avolio Rosario , Matassa Danilo Swann , Esposito Franca , Nitsch Lucio , Zurzolo Chiara , Paladino Simona , Sarnataro Daniela 
Published: June 2017

AbstractShadoo (Sho), a member of prion protein family, has been shown to prevent embryonic lethality in Prnp0/0 mice and to be reduced in the brains of rodents with terminal prion diseases. Sho can also affect PrP structural dynamics and can increase the prion conversion into its misfolded isoform (PrPSc), which is amyloidogenic and strictly related to expression, intracellular localization and association of PrPC to lipid rafts. We reasoned that if Sho possesses a natural tendency to convert to amyloid-like forms in vitro, it should be able to exhibit “prion-like” properties, such as PK-resistance and aggregation state, also in live cells. We tested this hypothesis, by different approaches in neuronal cells, finding that Sho shows folding properties partially dependent on lipid rafts integrity whose alteration, as well as proteasomal block, regulated generation of intermediate Sho isoforms and exacerbated its misfolding. Moreover, a 18 kDa isoform of Sho, likely bearing the signal peptide, was targeted to mitochondria by interacting with the molecular chaperone TRAP1 which, in turn controlled Sho dual targeting to ER or mitochondria. Our studies contribute to understand the role of molecular chaperones and of PrP-related folding intermediates in “prion-like” conversion.
Nucleotide based covalent inhibitors of KRas can only be efficient in vivo if they bind reversibly with GTP-like affinity
Authors: Müller Matthias P. , Jeganathan Sadasivam , Heidrich Angelika , Campos Jeremy , Goody Roger S. 
Published: June 2017

AbstractSimple reversible competitive inhibition of nucleotide binding of GTP to Ras family GTPases has long been recognized as an unlikely approach to manipulating the activity of such proteins for experimental or therapeutic purposes. This is due to the high affinity of GTP to GTPases coupled with high cellular GTP concentrations, but also to problems of specificity for the highly conserved binding sites in GTPases. A recent approach suggested that these problems might be overcome by using GDP derivatives that can undergo a covalent reaction with disease specific mutants, in particular addressing inhibition of KRasG12C using GDP equipped with an electrophilic group at the β-phosphate. We show here that a major drawback to this approach is a loss of reversible affinity of such β-modified derivatives for Ras of at least 104 compared to GTP and GDP. With the help of a thorough kinetic characterization, we show that this leads to covalent reaction times that are too slow to make the compounds attractive for intracellular use, but that generation of a hypothetical reactive GDP derivative that retains the high reversible affinity of GDP/GTP to Ras might be a viable alternative.
Recovery of the first full-length genome sequence of a parapoxvirus directly from a clinical sample
Authors: Günther Thomas , Haas Ludwig , Alawi Malik , Wohlsein Peter , Marks Jerzy , Grundhoff Adam , Becher Paul , Fischer Nicole 
Published: June 2017

AbstractWe recovered the first full-length poxvirus genome, including the terminal hairpin region, directly from complex clinical material using a combination of second generation short read and third generation nanopore sequencing technologies. The complete viral genome sequence was directly recovered from a skin lesion of a grey seal thereby preventing sequence changes due to in vitro passaging of the virus. Subsequent analysis of the proteins encoded by this virus identified genes specific for skin adaptation and pathogenesis of parapoxviruses. These data warrant the classification of seal parapoxvirus, tentatively designated SePPV, as a new species within the genus Parapoxvirus.