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  • Result 1-9 of 9
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1.
  • Agirre, Jon, et al. (author)
  • The CCP4 suite: integrative software for macromolecular crystallography
  • 2023
  • In: Acta Crystallographica Section D. - : INT UNION CRYSTALLOGRAPHY. - 2059-7983. ; 79, s. 449-461
  • Journal article (peer-reviewed)abstract
    • The Collaborative Computational Project No. 4 (CCP4) is a UK-led international collective with a mission to develop, test, distribute and promote software for macromolecular crystallography. The CCP4 suite is a multiplatform collection of programs brought together by familiar execution routines, a set of common libraries and graphical interfaces. The CCP4 suite has experienced several considerable changes since its last reference article, involving new infrastructure, original programs and graphical interfaces. This article, which is intended as a general literature citation for the use of the CCP4 software suite in structure determination, will guide the reader through such transformations, offering a general overview of the new features and outlining future developments. As such, it aims to highlight the individual programs that comprise the suite and to provide the latest references to them for perusal by crystallographers around the world.
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2.
  • Cardenas, Eduardo I, et al. (author)
  • Munc18-2, not Munc18-1 or Munc18-3, regulates platelet exocytosis, hemostasis, and thrombosis
  • 2019
  • In: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 294:13, s. 4784-4792
  • Journal article (peer-reviewed)abstract
    • Platelet degranulation, a form of regulated exocytosis, is crucial for hemostasis and thrombosis. Exocytosis in platelets is mediated by SNARE proteins, and in most mammalian cells this process is controlled by Munc18 (mammalian homolog of C. elegans uncoordinated gene 18) proteins. Platelets express all Munc18 paralogs (Munc18‑1, ‑2, and ‑3), but their roles in platelet secretion and function have not been fully characterized. Using Munc18‑1, ‑2, and ‑3 conditional knockout mice, here we deleted expression of these proteins in platelets and assessed granule exocytosis. We measured products secreted by each type of platelet granule and analyzed EM platelet profiles by design-based stereology. We observed that removal of Munc18‑2 ablates release of alpha, dense, and lysosomal granules from platelets, but we found no exocytic role for Munc18‑1 or ‑3 in platelets. In vitro, Munc18‑2-deficient platelets exhibited defective aggregation at low doses of collagen and impaired thrombus formation under shear stress. In vivo, megakaryocyte-specific Munc18‑2 conditional knockout mice had a severe hemostatic defect and prolonged arterial and venous bleeding times. They were also protected against arterial thrombosis in a chemically-induced model of arterial injury. Taken together, our results indicate that Munc18‑2, but not Munc18‑1 or Munc18‑3, is essential for regulated exocytosis in platelets and platelet participation in thrombosis and hemostasis.
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3.
  • Cardenas, Eduardo I, et al. (author)
  • Platelet Munc13-4 regulates hemostasis, thrombosis and airway inflammation.
  • 2018
  • In: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 0390-6078 .- 1592-8721. ; 103:7, s. 1235-1244
  • Journal article (peer-reviewed)abstract
    • Platelet degranulation is crucial for hemostasis and may participate in inflammation. Exocytosis in platelets is mediated by SNARE proteins and should be controlled by Munc13 proteins. We found that platelets express Munc13-2 and -4. We assessed platelet granule exocytosis in Munc13-2 and -4 global and conditional knockout (KO) mice, and observed that deletion of Munc13-4 ablates dense granule release and indirectly impairs alpha granule exocytosis. We found no exocytic role for Munc13-2 in platelets, not even in the absence of Munc13-4. In vitro, Munc13-4-deficient platelets exhibited defective aggregation at low doses of collagen. In a flow chamber assay, we observed that Munc13-4 acted as a rate-limiting factor in the formation of thrombi. In vivo, we observed a dose-dependency between Munc13-4 expression in platelets and both venous bleeding time and time to arterial thrombosis. Finally, in a model of allergic airway inflammation, we found that platelet-specific Munc13-4 KO mice had a reduction in airway hyper-responsiveness and eosinophilic inflammation. Taken together, our results indicate that Munc13-4-dependent platelet dense granule release plays essential roles in hemostasis, thrombosis and allergic inflammation.
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6.
  • Katritsis, Demosthenes G, et al. (author)
  • Executive Summary : European Heart Rhythm Association Consensus Document on the Management of Supraventricular Arrhythmias
  • 2016
  • In: Arrhythmia & electrophysiology review. - 2050-3369. ; 5:3, s. 210-224
  • Journal article (peer-reviewed)abstract
    • This paper is an executive summary of the full European Heart Rhythm Association (EHRA) consensus document on the management of supraventricular arrhythmias, published in Europace. It summarises developments in the field and provides recommendations for patient management, with particular emphasis on new advances since the previous European Society of Cardiology guidelines. The EHRA consensus document is available to read in full at http://europace.oxfordjournals.org.
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7.
  • Lane, Deirdre A, et al. (author)
  • Cardiac tachyarrhythmias and patient values and preferences for their management : the European Heart Rhythm Association (EHRA) consensus document endorsed by the Heart Rhythm Society (HRS), Asia Pacific Heart Rhythm Society (APHRS), and Sociedad Latinoamericana de Estimulación Cardíaca y Electrofisiología (SOLEACE).
  • 2015
  • In: Europace. - : Oxford University Press (OUP). - 1099-5129 .- 1532-2092. ; 17:12, s. 1747-1769
  • Journal article (peer-reviewed)abstract
    • Cardiac tachyarrhythmias are recurrent or chronic and in some cases life-threatening conditions. Heart rhythm disturbances are often highly symptomatic and the psychological impact of the disease can be significant. Patients' beliefs and knowledge about their health (and illness), medications, and healthcare they receive are important determinants of whether or not they accept recommended treatments; influence their coping responses to their illness and treatment; adherence to recommended therapy; and ultimately affects health outcomes. Incorporation of patients' values and preferences for therapy should now be considered as an integral part of the decision-making process and treatment strategy.It is important to acknowledge and understand the impact of cardiac tachyarrhythmias on the patient. To address this issue, a Task Force was convened by the European Heart Rhythm Association (EHRA), and endorsed by the Heart Rhythm Society (HRS), Asia-Pacific Heart Rhythm Society (APHRS), and Sociedad Latinoamericana de Estimulación Cardíaca y Electrofisiología (SOLEACE), with the remit to comprehensively review the published evidence available, to publish a joint consensus document on patient values and preferences for the management of cardiac tachyarrhythmias, and to provide up-to-date consensus recommendations for use in clinical practice.Hence this unique consensus document focuses on patients, summarizing the available literature on patients' experiences of living with various cardiac tachyarrhythmias and their treatment preferences, and identifies gaps in knowledge which will help to inform clinical practice and future research. The document will also summarize key points for discussions with patients during consultations regarding their condition, treatment options, disease trajectory, treatment goals, and outcomes. Finally, this document provides links to useful resources and patient advocacy groups and organizations and professional societies relevant to each group of cardiac tachyarrhythmias.
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8.
  • Neudecker, Denise, et al. (author)
  • Templates of expected measurement uncertainties
  • 2023
  • In: EPJ NUCLEAR SCIENCES & TECHNOLOGIES. - : EDP Sciences. - 2491-9292. ; 9
  • Journal article (peer-reviewed)abstract
    • The covariance committee of CSEWG (Cross Section Evaluation Working Group) established templates of expected measurement uncertainties for neutron-induced total, (n,gamma), neutron-induced charged-particle, and (n,xn) reaction cross sections as well as prompt fission neutron spectra, average prompt and total fission neutron multiplicities, and fission yields. Templates provide a list of what uncertainty sources are expected for each measurement type and observable, and suggest typical ranges of these uncertainties and correlations based on a survey of experimental data, associated literature, and feedback from experimenters. Information needed to faithfully include the experimental data in the nuclear-data evaluation process is also provided. These templates could assist (a) experimenters and EXFOR compilers in delivering more complete uncertainties and measurement information relevant for evaluations of new experimental data, and (b) evaluators in achieving a more comprehensive uncertainty quantification for evaluation purposes. This effort might ultimately lead to more realistic evaluated covariances for nuclear-data applications. In this topical issue, we cover the templates coming out of this CSEWG effort-typically, one observable per paper. This paper here prefaces this topical issue by introducing the concept and mathematical framework of templates, discussing potential use cases, and giving an example of how they can be applied (estimating missing experimental uncertainties of 235U(n,f) average prompt fission neutron multiplicities), and their impact on nuclear-data evaluations.
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9.
  • Rodarte, Elsa M, et al. (author)
  • Munc13 proteins control regulated exocytosis in mast cells.
  • 2018
  • In: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 293:1, s. 345-358
  • Journal article (peer-reviewed)abstract
    • Mast cells (MCs) are involved in host defenses against pathogens and inflammation. Stimulated MCs release substances stored in their granules via regulated exocytosis. In other cell types, Munc13 (mammalian homolog of Caenorhabditis elegans uncoordinated gene 13) proteins play essential roles in regulated exocytosis. Here, we found that MCs express Munc13-2 and -4, and we studied their roles using global and conditional knock-out (KO) mice. In a model of systemic anaphylaxis, we found no difference between WT and Munc13-2 KO mice, but global and MC-specific Munc13-4 KO mice developed less hypothermia. This protection correlated with lower plasma histamine levels and with histological evidence of defective MC degranulation but not with changes in MC development, distribution, numbers, or morphology. In vitro assays revealed that the defective response in Munc13-4-deficient MCs was limited to regulated exocytosis, leaving other MC secretory effector responses intact. Single cell capacitance measurements in MCs from mouse mutants differing in Munc13-4 expression levels in their MCs revealed that as levels of Munc13-4 decrease, the rate of exocytosis declines first, and then the total amount of exocytosis decreases. A requirement for Munc13-2 in MC exocytosis was revealed only in the absence of Munc13-4. Electrophysiology and EM studies uncovered that the number of multigranular compound events (i.e. granule-to-granule homotypic fusion) was severely reduced in the absence of Munc13-4. We conclude that although Munc13-2 plays a minor role, Munc13-4 is essential for regulated exocytosis in MCs, and that this MC effector response is required for a full anaphylactic response.
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  • Result 1-9 of 9

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