1,721,013 research outputs found
Distinguishing Bicontinuous Lipid Cubic Phases from Isotropic Membrane Morphologies Using 31P Solid-State NMR Spectroscopy
No full textavailable in PMC 2015 October 16Nonlamellar lipid membranes are frequently induced by proteins that fuse, bend, and cut membranes. Understanding the mechanism of action of these proteins requires the elucidation of the membrane morphologies that they induce. While hexagonal phases and lamellar phases are readily identified by their characteristic solid-state NMR line shapes, bicontinuous lipid cubic phases are more difficult to discern, since the static NMR spectra of cubic-phase lipids consist of an isotropic [superscript 31]P or [superscript 2]H peak, indistinguishable from the spectra of isotropic membrane morphologies such as micelles and small vesicles. To date, small-angle X-ray scattering is the only method to identify bicontinuous lipid cubic phases. To explore unique NMR signatures of lipid cubic phases, we first describe the orientation distribution of lipid molecules in cubic phases and simulate the static [superscript 31]P chemical shift line shapes of oriented cubic-phase membranes in the limit of slow lateral diffusion. We then show that 31P T[subscript 2] relaxation times differ significantly between isotropic micelles and cubic-phase membranes: the latter exhibit 2 orders of magnitude shorter T[subscript 2] relaxation times. These differences are explained by the different time scales of lipid lateral diffusion on the cubic-phase surface versus the time scales of micelle tumbling. Using this relaxation NMR approach, we investigated a DOPE membrane containing the transmembrane domain (TMD) of a viral fusion protein. The static [superscript 31]P spectrum of DOPE shows an isotropic peak, whose T[subscript 2] relaxation times correspond to that of a cubic phase. Thus, the viral fusion protein TMD induces negative Gaussian curvature, which is an intrinsic characteristic of cubic phases, to the DOPE membrane. This curvature induction has important implications to the mechanism of virus–cell fusion. This study establishes a simple NMR diagnostic probe of lipid cubic phases, which is expected to be useful for studying many protein-induced membrane remodeling phenomena in biology.National Institutes of Health (U.S.) (NIH Grant GM066976
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Viral fusion protein transmembrane domain adopts β-strand structure to facilitate membrane topological changes for virus–cell fusion
Full text linkThe C-terminal transmembrane domain (TMD) of viral fusion proteins such as HIV gp41 and influenza hemagglutinin (HA) is traditionally viewed as a passive α-helical anchor of the protein to the virus envelope during its merger with the cell membrane. The conformation, dynamics, and lipid interaction of these fusion protein TMDs have so far eluded high-resolution structure characterization because of their highly hydrophobic nature. Using magic-angle-spinning solid-state NMR spectroscopy, we show that the TMD of the parainfluenza virus 5 (PIV5) fusion protein adopts lipid-dependent conformations and interactions with the membrane and water. In phosphatidylcholine (PC) and phosphatidylglycerol (PG) membranes, the TMD is predominantly α-helical, but in phosphatidylethanolamine (PE) membranes, the TMD changes significantly to the β-strand conformation. Measured order parameters indicate that the strand segments are immobilized and thus oligomerized. [superscript 31]P NMR spectra and small-angle X-ray scattering (SAXS) data show that this β-strand–rich conformation converts the PE membrane to a bicontinuous cubic phase, which is rich in negative Gaussian curvature that is characteristic of hemifusion intermediates and fusion pores. [superscript 1]H-[superscript 31]P 2D correlation spectra and [superscript 2]H spectra show that the PE membrane with or without the TMD is much less hydrated than PC and PG membranes, suggesting that the TMD works with the natural dehydration tendency of PE to facilitate membrane merger. These results suggest a new viral-fusion model in which the TMD actively promotes membrane topological changes during fusion using the β-strand as the fusogenic conformation.National Institutes of Health (U.S.) (Grant GM066976
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
zhypan/Functional-Annotation-of-Pig: Functional-Annotation-of-Pig
No full textZhangyuan Pan#, Yuelin Yao#, Hongwei Yin, Zexi Cai, Ying Wang, Lijing Bai, Colin Kern, Michelle Halstead, Kelly Chanthavixay, Nares Trakooljul, Klaus Wimmers, Goutam Sahana, Guosheng Su, Mogens Sandø Lund, Merete Fredholm, Peter Karlskov-Mortensen, Catherine W. Ernst, Pablo Ross, Christopher K. Tuggle, Lingzhao Fang, Huaijun Zhou. Pig genome functional annotation enhances biological interpretations of complex traits and comparative epigenomics. Nature Communications
Solid-State Nuclear Magnetic Resonance Investigation of the Structural Topology and Lipid Interactions of a Viral Fusion Protein Chimera Containing the Fusion Peptide and Transmembrane Domain
No full textThe fusion peptide
(FP) and transmembrane domain (TMD) of viral
fusion proteins play important roles during virus–cell membrane
fusion, by inducing membrane curvature and transient dehydration.
The structure of the water-soluble ectodomain of viral fusion proteins
has been extensively studied crystallographically, but the structures
of the FP and TMD bound to phospholipid membranes are not well understood.
We recently investigated the conformations and lipid interactions
of the separate FP and TMD peptides of parainfluenza virus 5 (PIV5)
fusion protein F using solid-state nuclear magnetic resonance. These
studies provide structural information about the two domains when
they are spatially well separated in the fusion process. To investigate
how these two domains are structured relative to each other in the
postfusion state, when the ectodomain forms a six-helix bundle that
is thought to force the FP and TMD together in the membrane, we have
now expressed and purified a chimera of the FP and TMD, connected
by a Gly-Lys linker, and measured the chemical shifts and interdomain
contacts of the protein in several lipid membranes. The FP–TMD
chimera exhibits α-helical chemical shifts in all the membranes
examined and does not cause strong curvature of lamellar membranes
or membranes with negative spontaneous curvature. These properties
differ qualitatively from those of the separate peptides, indicating
that the FP and TMD interact with each other in the lipid membrane.
However, no 13C–13C cross peaks are observed
in two-dimensional correlation spectra, suggesting that the two helices
are not tightly associated. These results suggest that the ectodomain
six-helix bundle does not propagate into the membrane to the two hydrophobic
termini. However, the loosely associated FP and TMD helices are found
to generate significant negative Gaussian curvature to membranes that
possess spontaneous positive curvature, consistent with the notion
that the FP–TMD assembly may facilitate the transition of the
membrane from hemifusion intermediates to the fusion pore
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