bluuebunny/crossref_metadata_2025_split huggingface dataset:
RETRACTED ARTICLE: Cadherin 6 is activated by Epstein–Barr virus LMP1 to mediate EMT and metastasis as an interplay node of multiple pathways in nasopharyngeal carcinoma
Authors: Zuo L-L , Zhang J , Liu L-Z , Zhou Q , Du S-J , Xin S-Y , Ning Z-P , Yang J , Yu H-B , Yue W-X , Wang J , Zhu F-X , Li G-Y , Lu J-H 
Published: December 2017

AbstractNasopharyngeal carcinoma (NPC) is an epithelial malignancy, which is notorious among head-and-neck cancers with its metastatic feature. Epstein–Barr virus (EBV) infection plays a fundamental role in NPC development with the mechanism is not well understood. Here we demonstrate that EBV oncoprotein LMP1 drives EMT and metastasis of NPC by reactivating the adhesion molecule, cadherin 6 (CDH6), which normally occurs in embryogenesis with unknown role in NPC. CDH6 was found to be upregulated in LMP1-positive NPC tissues, and was identified as a target of the epithelium-specific miR-203. LMP1-activated NF-κB transcriptionally repressed the miR-203 expression by binding to the promoter region of miR-203 gene. CDH6 activation in turn induced EMT and promoted metastasis in NPC. CDH6 depletion, NF-κB inhibitor and miR-203 overexpression were able to impair the EMT effects. The miR-203 downregulation in NPC tissues was strongly associated with metastasis clinically. The CDH6 activator, Runt-related transcription factor 2 (RUNX2), was also activated by EBV in the event. For both CDH6 and RUNX2 are components at TGF-β downstream, CDH6 became a node protein for the interplay of multiple signalings including NF-κB and TGF-β. Therefore, the switch-on of miR-203 was important for nasopharyngeal epithelial cells to maintain normal phenotype. This study demonstrates that EBV has evolved sophisticated strategies by driving epithelial cells to obtain malignant features, particularly in NPC metastasis, providing novel biomarkers for the therapy and prognosis of EBV-associated NPC.
Strain profiling and epidemiology of bacterial species from metagenomic sequencing
Authors: Albanese Davide , Donati Claudio 
Published: December 2017

AbstractMicrobial communities are often composed by complex mixtures of multiple strains of the same species, characterized by a wide genomic and phenotypic variability. Computational methods able to identify, quantify and classify the different strains present in a sample are essential to fully exploit the potential of metagenomic sequencing in microbial ecology, with applications that range from the epidemiology of infectious diseases to the characterization of the dynamics of microbial colonization. Here we present a computational approach that uses the available genomic data to reconstruct complex strain profiles from metagenomic sequencing, quantifying the abundances of the different strains and cataloging them according to the population structure of the species. We validate the method on synthetic data sets and apply it to the characterization of the strain distribution of several important bacterial species in real samples, showing how its application provides novel insights on the structure and complexity of the microbiota.
Protein conformational flexibility modulates kinetics and thermodynamics of drug binding
Authors: Amaral M. , Kokh D. B. , Bomke J. , Wegener A. , Buchstaller H. P. , Eggenweiler H. M. , Matias P. , Sirrenberg C. , Wade R. C. , Frech M. 
Published: December 2017

AbstractStructure-based drug design has often been restricted by the rather static picture of protein–ligand complexes presented by crystal structures, despite the widely accepted importance of protein flexibility in biomolecular recognition. Here we report a detailed experimental and computational study of the drug target, human heat shock protein 90, to explore the contribution of protein dynamics to the binding thermodynamics and kinetics of drug-like compounds. We observe that their binding properties depend on whether the protein has a loop or a helical conformation in the binding site of the ligand-bound state. Compounds bound to the helical conformation display slow association and dissociation rates, high-affinity and high cellular efficacy, and predominantly entropically driven binding. An important entropic contribution comes from the greater flexibility of the helical relative to the loop conformation in the ligand-bound state. This unusual mechanism suggests increasing target flexibility in the bound state by ligand design as a new strategy for drug discovery.
Generic wound signals initiate regeneration in missing-tissue contexts
Authors: Owlarn Suthira , Klenner Felix , Schmidt David , Rabert Franziska , Tomasso Antonio , Reuter Hanna , Mulaw Medhanie A. , Moritz Sören , Gentile Luca , Weidinger Gilbert , Bartscherer Kerstin 
Published: December 2017

AbstractDespite the identification of numerous regulators of regeneration in different animal models, a fundamental question remains: why do some wounds trigger the full regeneration of lost body parts, whereas others resolve by mere healing? By selectively inhibiting regeneration initiation, but not the formation of a wound epidermis, here we create headless planarians and finless zebrafish. Strikingly, in both missing-tissue contexts, injuries that normally do not trigger regeneration activate complete restoration of heads and fin rays. Our results demonstrate that generic wound signals have regeneration-inducing power. However, they are interpreted as regeneration triggers only in a permissive tissue context: when body parts are missing, or when tissue-resident polarity signals, such as Wnt activity in planarians, are modified. Hence, the ability to decode generic wound-induced signals as regeneration-initiating cues may be the crucial difference that distinguishes animals that regenerate from those that cannot.
Access to stereodefined (Z)-allylsilanes and (Z)-allylic alcohols via cobalt-catalyzed regioselective hydrosilylation of allenes
Authors: Wang Chao , Teo Wei Jie , Ge Shaozhong 
Published: December 2017

AbstractHydrosilylation of allenes is the addition of a hydrogen atom and a silyl group to a carbon–carbon double bond of an allene molecule and represents a straightforward and atom-economical approach to prepare synthetically versatile allylsilanes and vinylsilanes. However, this reaction generally produces six possible isomeric organosilanes, and the biggest challenge in developing this reaction is to control both regioselectivity and stereoselectivity. The majorities of the developed allene hydrosilylation reactions show high selectivity towards the production of vinylsilanes or branched allylsilanes. By employing a cobalt catalyst generated from readily available and bench-stable cobalt precursor and phosphine-based ligands, here we show that this reaction proceeds under mild conditions in a regioselective and stereoselective manner, and affords synthetically challenging, but valuable linearcis-allylsilanes with excellent stereoselectivity (generallycistotransratios: >98:2). This cobalt-catalyzed (Z)-selective allene hydrosilylation provides a general approach to access molecules containing stereodefined (Z)-alkene units.
Methylation-regulated decommissioning of multimeric PP2A complexes
Authors: Wu Cheng-Guo , Zheng Aiping , Jiang Li , Rowse Michael , Stanevich Vitali , Chen Hui , Li Yitong , Satyshur Kenneth A. , Johnson Benjamin , Gu Ting-Jia , Liu Zuojia , Xing Yongna 
Published: December 2017

AbstractDynamic assembly/disassembly of signaling complexes are crucial for cellular functions. Specialized latency and activation chaperones control the biogenesis of protein phosphatase 2A (PP2A) holoenzymes that contain a common scaffold and catalytic subunits and a variable regulatory subunit. Here we show that the butterfly-shaped TIPRL (TOR signaling pathway regulator) makes highly integrative multibranching contacts with the PP2A catalytic subunit, selective for the unmethylated tail and perturbing/inactivating the phosphatase active site. TIPRL also makes unusual wobble contacts with the scaffold subunit, allowing TIPRL, but not the overlapping regulatory subunits, to tolerate disease-associated PP2A mutations, resulting in reduced holoenzyme assembly and enhanced inactivation of mutant PP2A. Strikingly, TIPRL and the latency chaperone, α4, coordinate to disassemble active holoenzymes into latent PP2A, strictly controlled by methylation. Our study reveals a mechanism for methylation-responsive inactivation and holoenzyme disassembly, illustrating the complexity of regulation/signaling, dynamic complex disassembly, and disease mutations in cancer and intellectual disability.
Molecular understanding of polyelectrolyte binders that actively regulate ion transport in sulfur cathodes
Authors: Li Longjun , Pascal Tod A. , Connell Justin G. , Fan Frank Y. , Meckler Stephen M. , Ma Lin , Chiang Yet-Ming , Prendergast David , Helms Brett A. 
Published: December 2017

AbstractPolymer binders in battery electrodes may be either active or passive. This distinction depends on whether the polymer influences charge or mass transport in the electrode. Although it is desirable to understand how to tailor the macromolecular design of a polymer to play a passive or active role, design rules are still lacking, as is a framework to assess the divergence in such behaviors. Here, we reveal the molecular-level underpinnings that distinguish an active polyelectrolyte binder designed for lithium–sulfur batteries from a passive alternative. The binder, a cationic polyelectrolyte, is shown to both facilitate lithium-ion transport through its reconfigurable network of mobile anions and restrict polysulfide diffusion from mesoporous carbon hosts by anion metathesis, which we show is selective for higher oligomers. These attributes allow cells to be operated for >100 cycles with excellent rate capability using cathodes with areal sulfur loadings up to 8.1 mg cm–2.
δ-Subunit Containing GABAA Receptors Modulate Respiratory Networks
Authors: Montandon Gaspard , Wu Haiying , Liu Hattie , Vu Michael T. , Orser Beverley A. , Horner Richard L. 
Published: December 2017

AbstractPersistent and stable respiratory activity across behavioral states is key to homeostasis. Extrasynaptic δ-subunit containing GABAA receptors (δGABAARs) mediate tonic inhibition and regulate network activity. However, the influence of δGABAARs on respiratory rhythm and motor outputs is unknown. We manipulated extra-synaptic GABAA receptor function in the preBötzinger Complex (preBötC), a site central to the generation of inspiratory motor activity in mammals. Activation of preBötC δGABAARs in anesthetized rats and wild-type mice decreased breathing rate. In δGABAAR knockout (Gabrd−/−) mice, however, δGABAARs activation had no effect on breathing rate. We then found that during active wakefulness associated with behaviors and movements, diaphragm activation was higher in the Gabrd−/− compared to wild-type mice, but not in other states. These findings identify that δGABAARs modulate the respiratory network, which is critical to understand how δGABAARs change breathing in pathological conditions affecting extra-synaptic GABAA receptor function such as exposure to anesthetics and neurosteroids.
Crude phosphorylation mixtures containing racemic lipid amphiphiles self-assemble to give stable primitive compartments
Authors: Fayolle Dimitri , Altamura Emiliano , D’Onofrio Alice , Madanamothoo Warren , Fenet Bernard , Mavelli Fabio , Buchet René , Stano Pasquale , Fiore Michele , Strazewski Peter 
Published: December 2017

AbstractIt is an open question how the chemical structure of prebiotic vesicle-forming amphiphiles complexified to produce robust primitive compartments that could safely host foreign molecules. Previous work suggests that comparingly labile vesicles composed of plausibly prebiotic fatty acids were eventually chemically transformed with glycerol and a suitable phosphate source into phospholipids that would form robust vesicles. Here we show that phosphatidic acid (PA) and phosphatidylethanolamine (PE) lipids can be obtained from racemic dioleoyl glycerol under plausibly prebiotic phosphorylation conditions. Upon in situ hydration of the crude phosphorylation mixtures only those that contained rac-DOPA (not rac-DOPE) generated stable giant vesicles that were capable of encapsulating water-soluble probes, as evidenced by confocal microscopy and flow cytometry. Chemical reaction side-products (identified by IR and MS and quantified by 1H NMR) acted as co-surfactants and facilitated vesicle formation. To mimic the compositional variation of such primitive lipid mixtures, self-assembly of a combinatorial set of the above amphiphiles was tested, revealing that too high dioleoyl glycerol contents inhibited vesicle formation. We conclude that a decisive driving force for the gradual transition from unstable fatty acid vesicles to robust diacylglyceryl phosphate vesicles was to avoid the accumulation of unphosphorylated diacylglycerols in primitive vesicle membranes.
Hydrolytic activity determination of Tail Tubular Protein A of Klebsiella pneumoniae bacteriophages towards saccharide substrates
Authors: Brzozowska Ewa , Pyra Anna , Pawlik Krzysztof , Janik Monika , Górska Sabina , Urbańska Natalia , Drulis-Kawa Zuzanna , Gamian Andrzej 
Published: December 2017

AbstractIn this paper, the enzymatic activity, substrate specificity and antibiofilm feature of bacteriophage dual-function tail proteins are presented. So far, tail tubular proteins A–TTPAgp31 and TTPAgp44-have been considered as structural proteins of Klebsiella pneumoniae bacteriophages KP32 and KP34, respectively. Our results show that TTPAgp31 is able to hydrolyze maltose as well as Red-starch. The activity of 1 µM of the protein was calculated as 47.6 milli-Units/assay relating to the α-amylase activity. It degrades capsular polysaccharides (cPS), slime polysaccharides (sPS) and lipopolysaccharide (LPS) of K. pneumoniae PCM 2713 and shows antibiofilm reactivity towards S. aureus PCM 519 and E. faecalis PCM 2673. TTPAgp44 hydrolyses trehalose and cPS of E. faecium PCM 1859. TTPAgp44′s activity was also observed in the antibiofilm test against P. aeruginosa PCM 2710 and B. subtilis PCM 2021. TTPAgp31 has been identified as α-1,4-glucosidase whereas, TTPAgp44 exhibits trehalase-like activity. Both proteins contain aspartate and glutamate residues in the β-stranded region which are essential for catalytic activity of glycoside hydrolases. The significant novelty of our results is that for the first time the bacteriophage tubular proteins are described as the unique enzymes displaying no similarity to any known phage hydrolases. They can be used as antibacterial agents directed against bacterial strains producing exopolysaccharides and forming a biofilm.
Radiosensitization of Prostate Cancers In Vitro and In Vivo to Erbium-filtered Orthovoltage X-rays Using Actively Targeted Gold Nanoparticles
Authors: Khoo Allison M. , Cho Sang Hyun , Reynoso Francisco J. , Aliru Maureen , Aziz Kathryn , Bodd Monica , Yang Xi , Ahmed Md F. , Yasar Selcuk , Manohar Nivedh , Cho Jongmin , Tailor Ramesh , Thames Howard D. , Krishnan Sunil 
Published: December 2017

AbstractTheoretical investigations suggest that gold nanoparticle (GNP)-mediated radiation dose enhancement and radiosensitization can be maximized when photons interact with gold, predominantly via photoelectric absorption. This makes ytterbium (Yb)-169, which emits photons with an average energy of 93 keV (just above the K-edge of gold), an ideal radioisotope for such purposes. This investigation tests the feasibility of tumor-specific prostate brachytherapy achievable with Yb-169 and actively targeted GNPs, using an external beam surrogate of Yb-169 created from an exotic filter material - erbium (Er) and a standard copper-filtered 250 kVp beam. The current in vitro study shows that treatment of prostate cancer cells with goserelin-conjugated gold nanorods (gGNRs) promotes gonadotropin releasing hormone receptor-mediated internalization and enhances radiosensitivity to both Er-filtered and standard 250 kVp beams, 14 and 10%, respectively. While the degree of GNP-mediated radiosensitization as seen from the in vitro study may be considered moderate, the current in vivo study shows that gGNR treatment plus Er-filtered x-ray irradiation is considerably more effective than radiation treatment alone (p < 0.0005), resulting in a striking reduction in tumor volume (50% smaller) 2 months following treatment. Overall, the current results provide strong evidence for the feasibility of tumor-specific prostate brachytherapy with Yb-169 and gGNRs.
Clay content and pH: soil characteristic associations with the persistent presence of chronic wasting disease in northern Illinois
Authors: Dorak Sheena J. , Green Michelle L. , Wander Michelle M. , Ruiz Marilyn O. , Buhnerkempe Michael G. , Tian Ting , Novakofski Jan E. , Mateus-Pinilla Nohra E. 
Published: December 2017

AbstractEnvironmental reservoirs are important to infectious disease transmission and persistence, but empirical analyses are relatively few. The natural environment is a reservoir for prions that cause chronic wasting disease (CWD) and influences the risk of transmission to susceptible cervids. Soil is one environmental component demonstrated to affect prion infectivity and persistence. Here we provide the first landscape predictive model for CWD based solely on soil characteristics. We built a boosted regression tree model to predict the probability of the persistent presence of CWD in a region of northern Illinois using CWD surveillance in deer and soils data. We evaluated the outcome for possible pathways by which soil characteristics may increase the probability of CWD transmission via environmental contamination. Soil clay content and pH were the most important predictive soil characteristics of the persistent presence of CWD. The results suggest that exposure to prions in the environment is greater where percent clay is less than 18% and soil pH is greater than 6.6. These characteristics could alter availability of prions immobilized in soil and contribute to the environmental risk factors involved in the epidemiological complexity of CWD infection in natural populations of white-tailed deer.
Multiple Cryptic Binding Sites are Necessary for Robust Fibronectin Assembly: An In Silico Study
Authors: Lemmon Christopher A. , Weinberg Seth H. 
Published: December 2017

AbstractThe mechanism of assembly of the extracellular matrix protein fibronectin (FN) into elastic, insoluble fibrils is still poorly understood. FN fibrillogenesis requires cell-generated forces, which expose cryptic FN-FN binding sites buried in FN Type III domains. The number and location of cryptic binding sites have been debated, but experimental evidence suggests multiple domains may contain FN-FN binding sites. The requirement of cell-dependent forces to generate FN fibrils restricts investigation of the mechanism of assembly. To address this, we use a recently developed biophysical model of fibrillogenesis to test competing hypotheses for the location and number of cryptic FN-FN binding sites and quantify the effect of these molecular alterations on assembled FN fibril properties. Simulations predict that a single FN-FN binding site facilitates either negligible fibrillogenesis or produces FN fibrils that are neither robust nor physiological. However, inclusion of multiple FN-FN binding sites predicts robust fibrillogenesis, which minimally depends on individual domain properties. Multiple FN-FN binding site models predict a heterogeneous fibril population that contains two distinct phenotypes with unique viscoelastic properties, which we speculate may play a key role in generating heterogeneous mechanical signaling in the extracellular matrix of developing and regenerating tissues.
Optimising monitoring efforts for secretive snakes: a comparison of occupancy and N-mixture models for assessment of population status
Authors: Ward Robert J. , Griffiths Richard A. , Wilkinson John W. , Cornish Nina 
Published: December 2017

AbstractA fifth of reptiles are Data Deficient; many due to unknown population status. Monitoring snake populations can be demanding due to crypsis and low population densities, with insufficient recaptures for abundance estimation via Capture-Mark-Recapture. Alternatively, binomial N-mixture models enable abundance estimation from count data without individual identification, but have rarely been successfully applied to snake populations. We evaluated the suitability of occupancy and N-mixture methods for monitoring an insular population of grass snakes (Natrix helvetica) and considered covariates influencing detection, occupancy and abundance within remaining habitat. Snakes were elusive, with detectability increasing with survey effort (mean: 0.33 ± 0.06 s.e.m.). The probability of a transect being occupied was moderate (mean per kilometre: 0.44 ± 0.19 s.e.m.) and increased with transect length. Abundance estimates indicate a small threatened population associated to our transects (mean: 39, 95% CI: 20–169). Power analysis indicated that the survey effort required to detect occupancy declines would be prohibitive. Occupancy models fitted well, whereas N-mixture models showed poor fit, provided little extra information over occupancy models and were at greater risk of closure violation. Therefore we suggest occupancy models are more appropriate for monitoring snakes and other elusive species, but that population trends may go undetected.
Alternative dominance of the parental genomes in hybrid cells generated through the fusion of mouse embryonic stem cells with fibroblasts
Authors: Matveeva Natalia M. , Fishman Veniamin S. , Zakharova Irina S. , Shevchenko Alexander I. , Pristyazhnyuk Inna E. , Menzorov Aleksei G. , Serov Oleg L. 
Published: December 2017

AbstractFor the first time, two types of hybrid cells with embryonic stem (ES) cell-like and fibroblast-like phenotypes were produced through the fusion of mouse ES cells with fibroblasts. Transcriptome analysis of 2,848 genes differentially expressed in the parental cells demonstrated that 34–43% of these genes are expressed in hybrid cells, consistent with their phenotypes; 25–29% of these genes display intermediate levels of expression, and 12–16% of these genes maintained expression at the parental cell level, inconsistent with the phenotype of the hybrid cell. Approximately 20% of the analyzed genes displayed unexpected expression patterns that differ from both parents. An unusual phenomenon was observed, namely, the illegitimate activation of Xist expression and the inactivation of one of two X-chromosomes in the near-tetraploid fibroblast-like hybrid cells, whereas both Xs were active before and after in vitro differentiation of the ES cell-like hybrid cells. These results and previous data obtained on heterokaryons suggest that the appearance of hybrid cells with a fibroblast-like phenotype reflects the reprogramming, rather than the induced differentiation, of the ES cell genome under the influence of a somatic partner.