868 research outputs found
α-Synuclein Reduces Tension and Increases Undulations in Simulations of Small Unilamellar Vesicles
AbstractUsing coarse-grained molecular dynamics simulations we have explored the effect of α-Synuclein (αSyn) on the structural and mechanical properties of small unilamellar vesicles in the fluid-phase. The study is motivated by observations that a high density of membrane-bound αSyn inhibits the fusion of synthetic small unilamellar vesicles. By combining three-dimensional pressure tensor calculations with our recently developed spherical harmonics fluctuation analysis approach, we show a reduction in membrane surface tension and increased membrane undulations when αSyn is bound to the vesicle’s outer leaflet at a 200:1 L/P. The protein effects these changes by decreasing the negative pressure in the headgroup region of the outer leaflet and increasing the positive pressure throughout the hydrocarbon core
Open and Closed Conformations of the Isolated Transmembrane Domain of Death Receptor 5 Support a New Model of Activation
AbstractIt has long been presumed that activation of the apoptosis-initiating Death Receptor 5, as well as other structurally homologous members of the TNF-receptor superfamily, relies on ligand-stabilized trimerization of noninteracting receptor monomers. We and others have proposed an alternate model in which the TNF-receptor dimer—sitting at the vertices of a large supramolecular receptor network of ligand-bound receptor trimers—undergoes a closed-to-open transition, propagated through a scissorslike conformational change in a tightly bundled transmembrane (TM) domain dimer. Here we have combined electron paramagnetic resonance spectroscopy and potential-of-mean force calculations on the isolated TM domain of the long isoform of DR5. The experiments and calculations both independently validate that the opening transition is intrinsic to the physical character of the TM domain dimer, with a significant energy barrier separating the open and closed states
Polarized Virtual Photon Structure Function and Twist-3 Effects in QCD
We investigate the twist-3 effects in the polarized virtual photon structure.
The structure functions and of polarized photon could
be experimentally studied in the future polarized or colliders.
The leading contributions to are the twist-2 effects, while
another structure function , which only exists for the virtual
photon target, receives not only the twist-2 but also twist-3 contributions. We
first show that the twist-3 effects actually exist in the box-diagram
contributions and we extract the twist-3 part, which can also be reproduced by
the pure QED operator product expansion. We then calculate the non-trivial
lowest moment () of the twist-3 contribution to in QCD. For
large (the number of colors), the QCD analysis of the twist-3 effects in
the flavor nonsinglet part of becomes tractable and we can obtain
its moments in a compact form for all .Comment: 27 pages, LaTeX, 9 eps figures, eqsection.sty file included, Appendix
A added, some minor changes for Fig.
In search of the authentic nation: landscape and national identity in Canada and Switzerland
While the study of nationalism and national identity has flourished in the last decade, little attention has been devoted to the conditions under which natural environments acquire significance in definitions of nationhood. This article examines the identity-forming role of landscape depictions in two polyethnic nation-states: Canada and Switzerland. Two types of geographical national identity are identified. The first – what we call the ‘nationalisation of nature’– portrays zarticular landscapes as expressions of national authenticity. The second pattern – what we refer to as the ‘naturalisation of the nation’– rests upon a notion of geographical determinism that depicts specific landscapes as forces capable of determining national identity. The authors offer two reasons why the second pattern came to prevail in the cases under consideration: (1) the affinity between wild landscape and the Romantic ideal of pure, rugged nature, and (2) a divergence between the nationalist ideal of ethnic homogeneity and the polyethnic composition of the two societies under consideration
Susceptibility of hamsters to clostridium difficile isolates of differing toxinotype
Clostridium difficile is the most commonly associated cause of antibiotic associated disease (AAD), which caused ~21,000 cases of AAD in 2011 in the U.K. alone. The golden Syrian hamster model of CDI is an acute model displaying many of the clinical features of C. difficile disease. Using this model we characterised three clinical strains of C. difficile, all differing in toxinotype; CD1342 (PaLoc negative), M68 (toxinotype VIII) and BI-7 (toxinotype III). The naturally occurring non-toxic strain colonised all hamsters within 1-day post challenge (d.p.c.) with high-levels of spores being shed in the faeces of animals that appeared well throughout the entire experiment. However, some changes including increased neutrophil influx and unclotted red blood cells were observed at early time points despite the fact that the known C. difficile toxins (TcdA, TcdB and CDT) are absent from the genome. In contrast, hamsters challenged with strain M68 resulted in a 45% mortality rate, with those that survived challenge remaining highly colonised. It is currently unclear why some hamsters survive infection, as bacterial and toxin levels and histology scores were similar to those culled at a similar time-point. Hamsters challenged with strain BI-7 resulted in a rapid fatal infection in 100% of the hamsters approximately 26 hr post challenge. Severe caecal pathology, including transmural neutrophil infiltrates and extensive submucosal damage correlated with high levels of toxin measured in gut filtrates ex vivo. These data describes the infection kinetics and disease outcomes of 3 clinical C. difficile isolates differing in toxin carriage and provides additional insights to the role of each toxin in disease progression
Relativistic Correction to the First Moment of the Spin-Dependent Structure Function of the Deuteron in the Light-Cone Formalism
The deuteron is considered as a superposition of two-nucleon Fock states with
the invariant mass depending on the relative momentum in a proton-neutron pair.
The condition of the transversality of the polarization vectors should be
imposed at the Fock component level and these vectors depend on the invariant
mass of the Fock component. Such "running" longitudinal polarization vector was
not used in early estimates of relativistic effects. The technique for the
calculation of the average helicity of the proton in the deuteron has been
considered in the light-cone variables. A receipt has been proposed for the
consistent calculation of relativistic nuclear corrections to the average
helicity of the proton in the deuteron and to the first moment of the
spin-dependent structure function of the deuteron.Comment: 34 pages, 6 figures, an extended version of the paper published in
Journal of Experimental and Theoretical Physics, 201
Complimentary electrostatics dominate T-cell receptor binding to a psoriasis-associated peptide antigen presented by human leukocyte antigen C∗06:02
Psoriasis is a chronic skin disease characterized by hyperproliferative epidermal lesions infiltrated by autoreactive T cells. Individuals expressing the human leukocyte antigen (HLA) C∗06:02 allele are at highest risk for developing psoriasis. An autoreactive T cell clone (termed Vα3S1/Vβ13S1) isolated from psoriatic plaques is selective for HLA-C∗06:02, presenting a peptide derived from the melanocyte-specific autoantigen ADAMTSL5 (VRSRRCLRL). Here we determine the crystal structure of this psoriatic TCR–HLA-C∗06:02 ADAMTSL5 complex with a stabilized peptide. Docking of the TCR involves an extensive complementary charge network formed between negatively charged TCR residues interleaving with exposed arginine residues from the self-peptide and the HLA-C∗06:02 α1 helix. We probed these interactions through mutagenesis and activation assays. The charged interface spans the polymorphic region of the C1/C2 HLA group. Notably the peptide-binding groove of HLA-C∗06:02 appears exquisitely suited for presenting highly charged Arg-rich epitopes recognized by this acidic psoriatic TCR. Overall, we provide a structural basis for understanding the engagement of melanocyte antigen-presenting cells by a TCR implicated in psoriasis while simultaneously expanding our knowledge of how TCRs engage HLA-C
The mechanisms and processes of connection: developing a causal chain model capturing impacts of receiving recorded mental health recovery narratives.
BACKGROUND: Mental health recovery narratives are a core component of recovery-oriented interventions such as peer support and anti-stigma campaigns. A substantial number of recorded recovery narratives are now publicly available online in different modalities and in published books. Whilst the benefits of telling one's story have been investigated, much less is known about how recorded narratives of differing modalities impact on recipients. A previous qualitative study identified connection to the narrator and/or to events in the narrative to be a core mechanism of change. The factors that influence how individuals connect with a recorded narrative are unknown. The aim of the current study was to characterise the immediate effects of receiving recovery narratives presented in a range of modalities (text, video and audio), by establishing the mechanisms of connection and the processes by which connection leads to outcomes. METHOD: A study involving 40 mental health service users in England was conducted. Participants were presented with up to 10 randomly-selected recovery narratives and were interviewed on the immediate impact of each narrative. Thematic analysis was used to identify the mechanisms of connection and how connection leads to outcome. RESULTS: Receiving a recovery narrative led participants to reflect upon their own experiences or those of others, which then led to connection through three mechanisms: comparing oneself with the narrative and narrator; learning about other's experiences; and experiencing empathy. These mechanisms led to outcomes through three processes: the identification of change (through attending to narrative structure); the interpretation of change (through attending to narrative content); and the internalisation of interpretations. CONCLUSIONS: This is the first study to identify mechanisms and processes of connection with recorded recovery narratives. The empirically-based causal chain model developed in this study describes the immediate effects on recipients. This model can inform selection of narratives for use in interventions, and be used to support peer support workers in recounting their own recovery narratives in ways which are maximally beneficial to others
Lambda and Antilambda polarization from deep inelastic muon scattering
We report results of the first measurements of Lambda and Antilambda
polarization produced in deep inelastic polarized muon scattering on the
nucleon. The results are consistent with an expected trend towards positive
polarization with increasing x_F. The polarizations of Lambda and Antilambda
appear to have opposite signs. A large negative polarization for Lambda at low
positive x_F is observed and is not explained by existing models.A possible
interpretation is presented.Comment: 9 pages, 2 figure
Shadowing in Inelastic Scattering of Muons on Carbon, Calcium and Lead at Low XBj
Nuclear shadowing is observed in the per-nucleon cross-sections of positive
muons on carbon, calcium and lead as compared to deuterium. The data were taken
by Fermilab experiment E665 using inelastically scattered muons of mean
incident momentum 470 GeV/c. Cross-section ratios are presented in the
kinematic region 0.0001 < XBj <0.56 and 0.1 < Q**2 < 80 GeVc. The data are
consistent with no significant nu or Q**2 dependence at fixed XBj. As XBj
decreases, the size of the shadowing effect, as well as its A dependence, are
found to approach the corresponding measurements in photoproduction.Comment: 22 pages, incl. 6 figures, to be published in Z. Phys.
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