bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prediction of allosteric sites and mediating interactions through bond-to-bond propensities
Authors: Amor B. R. C. , Schaub M. T. , Yaliraki S. N. , Barahona M. 
Published: August 2016

AbstractAllostery is a fundamental mechanism of biological regulation, in which binding of a molecule at a distant location affects the active site of a protein. Allosteric sites provide targets to fine-tune protein activity, yet we lack computational methodologies to predict them. Here we present an efficient graph-theoretical framework to reveal allosteric interactions (atoms and communication pathways strongly coupled to the active site) without a priori information of their location. Using an atomistic graph with energy-weighted covalent and weak bonds, we define a bond-to-bond propensity quantifying the non-local effect of instantaneous bond fluctuations propagating through the protein. Significant interactions are then identified using quantile regression. We exemplify our method with three biologically important proteins: caspase-1, CheY, and h-Ras, correctly predicting key allosteric interactions, whose significance is additionally confirmed against a reference set of 100 proteins. The almost-linear scaling of our method renders it suitable for high-throughput searches for candidate allosteric sites.
The tumour suppressor CYLD regulates the p53 DNA damage response
Authors: Fernández-Majada Vanesa , Welz Patrick-Simon , Ermolaeva Maria A. , Schell Michael , Adam Alexander , Dietlein Felix , Komander David , Büttner Reinhard , Thomas Roman K. , Schumacher Björn , Pasparakis Manolis 
Published: August 2016

AbstractThe tumour suppressor CYLD is a deubiquitinase previously shown to inhibit NF-κB, MAP kinase and Wnt signalling. However, the tumour suppressing mechanisms of CYLD remain poorly understood. Here we show that loss of CYLD catalytic activity causes impaired DNA damage-induced p53 stabilization and activation in epithelial cells and sensitizes mice to chemical carcinogen-induced intestinal and skin tumorigenesis. Mechanistically, CYLD interacts with and deubiquitinates p53 facilitating its stabilization in response to genotoxic stress. Ubiquitin chain-restriction analysis provides evidence that CYLD removes K48 ubiquitin chains from p53 indirectly by cleaving K63 linkages, suggesting that p53 is decorated with complex K48/K63 chains. Moreover, CYLD deficiency also diminishes CEP-1/p53-dependent DNA damage-induced germ cell apoptosis in the nematode Caenorhabditis elegans. Collectively, our results identify CYLD as a deubiquitinase facilitating DNA damage-induced p53 activation and suggest that regulation of p53 responses to genotoxic stress contributes to the tumour suppressor function of CYLD.
Colloidal cholesteric liquid crystal in spherical confinement
Authors: Li Yunfeng , Jun-Yan Suen Jeffrey , Prince Elisabeth , Larin Egor M. , Klinkova Anna , Thérien-Aubin Héloïse , Zhu Shoujun , Yang Bai , Helmy Amr S. , Lavrentovich Oleg D. , Kumacheva Eugenia 
Published: August 2016

AbstractThe organization of nanoparticles in constrained geometries is an area of fundamental and practical importance. Spherical confinement of nanocolloids leads to new modes of packing, self-assembly, phase separation and relaxation of colloidal liquids; however, it remains an unexplored area of research for colloidal liquid crystals. Here we report the organization of cholesteric liquid crystal formed by nanorods in spherical droplets. For cholesteric suspensions of cellulose nanocrystals, with progressive confinement, we observe phase separation into a micrometer-size isotropic droplet core and a cholesteric shell formed by concentric nanocrystal layers. Further confinement results in a transition to a bipolar planar cholesteric morphology. The distribution of polymer, metal, carbon or metal oxide nanoparticles in the droplets is governed by the nanoparticle size and yields cholesteric droplets exhibiting fluorescence, plasmonic properties and magnetic actuation. This work advances our understanding of how the interplay of order, confinement and topological defects affects the morphology of soft matter.
Asymmetric cryo-EM reconstruction of phage MS2 reveals genome structure in situ
Authors: Koning Roman I , Gomez-Blanco Josue , Akopjana Inara , Vargas Javier , Kazaks Andris , Tars Kaspars , Carazo José María , Koster Abraham J. 
Published: August 2016

AbstractIn single-stranded ribonucleic acid (RNA) viruses, virus capsid assembly and genome packaging are intertwined processes. Using cryo-electron microscopy and single particle analysis we determined the asymmetric virion structure of bacteriophage MS2, which includes 178 copies of the coat protein, a single copy of the A-protein and the RNA genome. This reveals that in situ, the viral RNA genome can adopt a defined conformation. The RNA forms a branched network of stem-loops that almost all allocate near the capsid inner surface, while predominantly binding to coat protein dimers that are located in one-half of the capsid. This suggests that genomic RNA is highly involved in genome packaging and virion assembly.
Immune modulation enables a specialist insect to benefit from antibacterial withanolides in its host plant
Authors: Barthel Andrea , Vogel Heiko , Pauchet Yannick , Pauls Gerhard , Kunert Grit , Groot Astrid T. , Boland Wilhelm , Heckel David G. , Heidel-Fischer Hanna M. 
Published: August 2016

AbstractThe development of novel plant chemical defenses and counter adaptations by herbivorous insect could continually drive speciation, producing more insect specialists than generalists. One approach to test this hypothesis is to compare closely related generalist and specialist species to reveal the associated costs and benefits of these different adaptive strategies. We use the specialized mothHeliothis subflexa, which feeds exclusively on plants in the genusPhysalis, and its close generalist relativeH. virescens.Specialization onPhysalisplants necessitates the ability to tolerate withanolides, the secondary metabolites ofPhysalisspecies that are known to have feeding deterrent and immune inhibiting properties for other insects. Here we find that onlyH. subflexabenefits from the antibacterial properties of withanolides, and thereby gains a higher tolerance of the pathogenBacillus thuringiensis. We argue that the specialization inH. subflexahas been guided to a large extent by a unique role of plant chemistry on ecological immunology.
Single-molecule imaging of UvrA and UvrB recruitment to DNA lesions in living Escherichia coli
Authors: Stracy Mathew , Jaciuk Marcin , Uphoff Stephan , Kapanidis Achillefs N. , Nowotny Marcin , Sherratt David J. , Zawadzki Pawel 
Published: August 2016

AbstractNucleotide excision repair (NER) removes chemically diverse DNA lesions in all domains of life. In Escherichia coli, UvrA and UvrB initiate NER, although the mechanistic details of how this occurs in vivo remain to be established. Here, we use single-molecule fluorescence imaging to provide a comprehensive characterization of the lesion search, recognition and verification process in living cells. We show that NER initiation involves a two-step mechanism in which UvrA scans the genome and locates DNA damage independently of UvrB. Then UvrA recruits UvrB from solution to the lesion. These steps are coordinated by ATP binding and hydrolysis in the ‘proximal’ and ‘distal’ UvrA ATP-binding sites. We show that initial UvrB-independent damage recognition by UvrA requires ATPase activity in the distal site only. Subsequent UvrB recruitment requires ATP hydrolysis in the proximal site. Finally, UvrA dissociates from the lesion complex, allowing UvrB to orchestrate the downstream NER reactions.
A possible four-phase coexistence in a single-component system
Authors: Akahane Kenji , Russo John , Tanaka Hajime 
Published: August 2016

AbstractFor different phases to coexist in equilibrium at constant temperature T and pressure P, the condition of equal chemical potential μ must be satisfied. This condition dictates that, for a single-component system, the maximum number of phases that can coexist is three. Historically this is known as the Gibbs phase rule, and is one of the oldest and venerable rules of thermodynamics. Here we make use of the fact that, by varying model parameters, the Gibbs phase rule can be generalized so that four phases can coexist even in single-component systems. To systematically search for the quadruple point, we use a monoatomic system interacting with a Stillinger–Weber potential with variable tetrahedrality. Our study indicates that the quadruple point provides flexibility in controlling multiple equilibrium phases and may be realized in systems with tunable interactions, which are nowadays feasible in several soft matter systems such as patchy colloids.
Molecular logic of the Zur-regulated zinc deprivation response in Bacillus subtilis
Authors: Shin Jung-Ho , Helmann John D. 
Published: August 2016

AbstractBacteria respond dynamically to the changes in zinc availability. Repression by the Bacillus subtilis transcription factor Zur requires Zn(II), which binds with negative cooperativity to two regulatory sites per dimer to form, sequentially, Zur2:Zn3 and Zur2:Zn4 forms of the repressor. Here we show that, as cells transition from zinc sufficiency to deficiency, operons regulated by Zur are derepressed in three distinct waves. The first includes the alternative RpmEB(L31*) and RpmGC(L33*) ribosomal proteins, which mobilize zinc from the ribosome, whereas the second includes the ZnuACB uptake system and the YciC metallochaperone. Finally, as zinc levels decrease further, the Zur2:Zn3 form loses Zn(II) leading to derepression of RpsNB(S14*) and FolE2, which allow continued ribosome assembly and folate synthesis, respectively. We infer that zinc mobilization from intracellular zinc stores takes priority over energy-dependent import, and our results link the biochemistry of zinc sensing by Zur to the molecular logic of the zinc deprivation response.
Hypersensitivity to DNA damage in antephase as a safeguard for genome stability
Authors: Feringa Femke M. , Krenning Lenno , Koch André , van den Berg Jeroen , van den Broek Bram , Jalink Kees , Medema René H. 
Published: August 2016

AbstractActivation of the DNA-damage response can lead to the induction of an arrest at various stages in the cell cycle. These arrests are reversible in nature, unless the damage is too excessive. Here we find that checkpoint reversibility is lost in cells that are in very late G2, but not yet fully committed to enter mitosis (antephase). We show that antephase cells exit the cell cycle and enter senescence at levels of DNA damage that induce a reversible arrest in early G2. We show that checkpoint reversibility critically depends on the presence of the APC/C inhibitor Emi1, which is degraded just before mitosis. Importantly, ablation of the cell cycle withdrawal mechanism in antephase promotes cell division in the presence of broken chromosomes. Thus, our data uncover a novel, but irreversible, DNA-damage response in antephase that is required to prevent the propagation of DNA damage during cell division.
Integrative proteomic profiling of ovarian cancer cell lines reveals precursor cell associated proteins and functional status
Authors: Coscia F. , Watters K. M. , Curtis M. , Eckert M. A. , Chiang C. Y. , Tyanova S. , Montag A. , Lastra R. R. , Lengyel E. , Mann M. 
Published: August 2016

AbstractA cell line representative of human high-grade serous ovarian cancer (HGSOC) should not only resemble its tumour of origin at the molecular level, but also demonstrate functional utility in pre-clinical investigations. Here, we report the integrated proteomic analysis of 26 ovarian cancer cell lines, HGSOC tumours, immortalized ovarian surface epithelial cells and fallopian tube epithelial cells via a single-run mass spectrometric workflow. The in-depth quantification of >10,000 proteins results in three distinct cell line categories: epithelial (group I), clear cell (group II) and mesenchymal (group III). We identify a 67-protein cell line signature, which separates our entire proteomic data set, as well as a confirmatory publicly available CPTAC/TCGA tumour proteome data set, into a predominantly epithelial and mesenchymal HGSOC tumour cluster. This proteomics-based epithelial/mesenchymal stratification of cell lines and human tumours indicates a possible origin of HGSOC either from the fallopian tube or from the ovarian surface epithelium.
Room-temperature tetragonal non-collinear Heusler antiferromagnet Pt2MnGa
Authors: Singh Sanjay , D’Souza S. W. , Nayak J. , Suard E. , Chapon L. , Senyshyn A. , Petricek V. , Skourski Y. , Nicklas M. , Felser C. , Chadov S. 
Published: August 2016

AbstractAntiferromagnetic spintronics is a rapidly growing field, which actively introduces new principles of magnetic storage. Despite that, most applications have been suggested for collinear antiferromagnets. In this study, we consider an alternative mechanism based on long-range helical order, which allows for direct manipulation of the helicity vector. As the helicity of long-range homogeneous spirals is typically fixed by the Dzyaloshinskii–Moriya interactions, bi-stable spirals (left- and right-handed) are rare. Here, we report a non-collinear room-temperature antiferromagnet in the tetragonal Heusler group. Neutron diffraction reveals a long-period helix propagating along its tetragonal axis. Ab-initio analysis suggests its pure exchange origin and explains its helical character resulting from a large basal plane magnetocrystalline anisotropy. The actual energy barrier between the left- and right-handed spirals is relatively small and might be easily overcome by magnetic pulse, suggesting Pt2MnGa as a potential candidate for non-volatile magnetic memory.
Individual-based approach to epidemic processes on arbitrary dynamic contact networks
Authors: Rocha Luis E. C. , Masuda Naoki 
Published: August 2016

AbstractThe dynamics of contact networks and epidemics of infectious diseases often occur on comparable time scales. Ignoring one of these time scales may provide an incomplete understanding of the population dynamics of the infection process. We develop an individual-based approximation for the susceptible-infected-recovered epidemic model applicable to arbitrary dynamic networks. Our framework provides, at the individual-level, the probability flow over time associated with the infection dynamics. This computationally efficient framework discards the correlation between the states of different nodes, yet provides accurate results in approximating direct numerical simulations. It naturally captures the temporal heterogeneities and correlations of contact sequences, fundamental ingredients regulating the timing and size of an epidemic outbreak and the number of secondary infections. The high accuracy of our approximation further allows us to detect the index individual of an epidemic outbreak in real-life network data.
Variations in Multiple Syndromic Deafness Genes Mimic Non-syndromic Hearing Loss
Authors: Bademci G. , Cengiz F. B. , Foster II J. , Duman D. , Sennaroglu L. , Diaz-Horta O. , Atik T. , Kirazli T. , Olgun L. , Alper H. , Menendez I. , Loclar I. , Sennaroglu G. , Tokgoz-Yilmaz S. , Guo S. , Olgun Y. , Mahdieh N. , Bonyadi M. , Bozan N. , Ayral A. , Ozkinay F. , Yildirim-Baylan M. , Blanton S. H. , Tekin M. 
Published: August 2016

AbstractThe genetics of both syndromic (SHL) and non-syndromic hearing loss (NSHL) is characterized by a high degree of genetic heterogeneity. We analyzed whole exome sequencing data of 102 unrelated probands with apparently NSHL without a causative variant in known NSHL genes. We detected five causative variants in different SHL genes (SOX10, MITF, PTPN11, CHD7, and KMT2D) in five (4.9%) probands. Clinical re-evaluation of these probands shows that some of them have subtle syndromic findings, while none of them meets clinical criteria for the diagnosis of the associated syndrome (Waardenburg (SOX10 and MITF), Kallmann (CHD7 and SOX10), Noonan/LEOPARD (PTPN11), CHARGE (CHD7), or Kabuki (KMT2D). This study demonstrates that individuals who are evaluated for NSHL can have pathogenic variants in SHL genes that are not usually considered for etiologic studies.
Mechanistic target of rapamycin (mTOR) regulates trophoblast folate uptake by modulating the cell surface expression of FR-α and the RFC
Authors: Rosario Fredrick J. , Powell Theresa L. , Jansson Thomas 
Published: August 2016

AbstractFolate deficiency in fetal life is strongly associated with structural malformations and linked to intrauterine growth restriction. In addition, limited availability of methyl donors, such as folate, during pregnancy may result in abnormal gene methylation patterns and contribute to developmental programming. The fetus is dependent on placental transfer of folate, however the molecular mechanisms regulating placental folate transport are unknown. We used cultured primary human trophoblast cells to test the hypothesis that mechanistic target of rapamycin complex 1 (mTORC1) and 2 (mTORC2) regulate folate transport by post-translational mechanisms. Silencing raptor (inhibits mTORC1) or rictor (inhibits mTORC2) markedly decreased basal folate uptake. Folate uptake stimulated by insulin + IGF-1 was mediated by mTORC2 but did not involve mTORC1. mTORC1 or mTORC2 silencing markedly decreased the plasma membrane expression of FR-α and RFC transporter isoforms without affecting global protein expression. Inhibition of the ubiquitin ligase Nedd4-2 had no effect on folate transport. In conclusion, we report for the first time that mTORC1/C2 are positive regulators of cellular folate uptake by modulating the cell surface abundance of specific transporter isoforms. We propose that regulation of placental folate transport by mTOR signaling provide a direct link between placental function, gene methylation and fetal programming.
Generation of a macroscopic entangled coherent state using quantum memories in circuit QED
Authors: Liu Tong , Su Qi-Ping , Xiong Shao-Jie , Liu Jin-Ming , Yang Chui-Ping , Nori Franco 
Published: August 2016

AbstractW-type entangled states can be used as quantum channels for, e.g., quantum teleportation, quantum dense coding and quantum key distribution. In this work, we propose a way to generate a macroscopicW-type entangled coherent state using quantum memories in circuit QED. The memories considered here are nitrogen-vacancy center ensembles (NVEs), each located in a different cavity. This proposal does not require initially preparing each NVE in a coherent state instead of a ground state, which should significantly reduce its experimental difficulty. For most of the operation time, each cavity remains in a vacuum state, thus decoherence caused by the cavity decay and the unwanted inter-cavity crosstalk are greatly suppressed. Moreover, only one external-cavity coupler qubit is needed, which simplifies the circuit.
A novel mass spectrometric strategy “BEMAP” reveals Extensive O-linked protein glycosylation in Enterotoxigenic Escherichia coli
Authors: Boysen Anders , Palmisano Giuseppe , Krogh Thøger Jensen , Duggin Iain G. , Larsen Martin R. , Møller-Jensen Jakob 
Published: August 2016

AbstractThe attachment of sugars to proteins via side-chain oxygen atoms (O-linked glycosylation) is seen in all three domains of life. However, a lack of widely-applicable analytical tools has restricted the study of this process, particularly in bacteria. In E. coli, only four O-linked glycoproteins have previously been characterized. Here we present a glycoproteomics technique, termed BEMAP, which is based on the beta-elimination of O-linked glycans followed by Michael-addition of a phosphonic acid derivative and subsequent titanium dioxide enrichment. This strategy allows site-specific mass-spectrometric identification of proteins with O-linked glycan modifications in a complex biological sample. Using BEMAP we identified cell surface-associated and membrane vesicle glycoproteins from Enterotoxigenic E. coli (ETEC) and non-pathogenic E. coli K-12. We identified 618 glycosylated Serine and Threonine residues mapping to 140 proteins in ETEC, including several known virulence factors and 34 in E. coli K-12. The two strains had 32 glycoproteins in common. Remarkably, the majority of the ETEC glycoproteins were conserved in both strains but nevertheless were only glycosylated in the pathogen. Therefore, bacterial O-linked glycosylation is much more extensive than previously thought and is especially important to the pathogen.
Magneto-elasto-electroporation (MEEP): In-vitro visualization and numerical characteristics
Authors: Betal Soutik , Shrestha Binita , Dutta Moumita , Cotica Luiz F. , Khachatryan Edward , Nash Kelly , Tang Liang , Bhalla Amar S. , Guo Ruyan 
Published: August 2016

AbstractA magnetically controlled elastically driven electroporation phenomenon, or magneto-elasto-electroporation (MEEP), is discovered while studying the interactions between core-shell magnetoelectric nanoparticles (CSMEN) and biological cells in the presence of an a.c. magnetic field. In this paper we report the effect of MEEP observed via a series of in-vitro experiments using core (CoFe2O4)-shell (BaTiO3) structured magnetoelectric nanoparticles and human epithelial cells (HEP2). The cell electroporation phenomenon and its correlation with the magnetic field modulated CSMEN are described in detail. The potential application of CSMEN in electroporation is confirmed by analyzing crystallographic phases, multiferroic properties of the fabricated CSMEN, influences of d.c. and a.c. magnetic fields on the CSMEN and cytotoxicity tests. The mathematical formalism to quantitatively describe the phenomena is also reported. The reported findings provide insights into the underlying MEEP mechanism and demonstrate the utility of CSMEN as an electric pulse-generating nano-probe in electroporation experiments with a potential application toward accurate and efficient targeted cell permeation.
Skeletal muscle ATP synthesis and cellular H+ handling measured by localized 31P-MRS during exercise and recovery
Authors: Fiedler Georg B. , Schmid Albrecht I. , Goluch Sigrun , Schewzow Kiril , Laistler Elmar , Niess Fabian , Unger Ewald , Wolzt Michael , Mirzahosseini Arash , Kemp Graham J. , Moser Ewald , Meyerspeer Martin 
Published: August 2016

Abstract31P magnetic resonance spectroscopy (MRS) is widely used for non-invasive investigation of muscle metabolism dynamics. This study aims to extend knowledge on parameters derived from these measurements in detail and comprehensiveness: proton (H+) efflux, buffer capacity and the contributions of glycolytic (L) and oxidative (Q) rates to ATP synthesis were calculated from the evolutions of phosphocreatine (PCr) and pH. Data are reported for two muscles in the human calf, for each subject and over a wide range of exercise intensities. 22 subjects performed plantar flexions in a 7T MR-scanner, leading to PCr changes ranging from barely noticeable to almost complete depletion, depending on exercise protocol and muscle studied by localized MRS. Cytosolic buffer capacity was quantified for the first time non-invasively and individually, as was proton efflux evolution in early recovery. Acidification started once PCr depletion reached 60–75%. Initial and end-exercise L correlated with end-exercise levels of PCr and approximately linear with pH. Q calculated directly from PCr and pH derivatives was plausible, requiring fewer assumptions than the commonly used ADP-model. In conclusion, the evolution of parameters describing cellular energy metabolism was measured over a wide range of exercise intensities, revealing a relatively complete picture of muscle metabolism.