| 1. |
- Hyde, K. D., et al.
(author)
-
Global consortium for the classification of fungi and fungus-like taxa
- 2023
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In: MYCOSPHERE. - : Mushroom Research Foundation. - 2077-7000 .- 2077-7019. ; 14:1, s. 1960-2012
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Journal article (peer-reviewed)abstract
- The Global Consortium for the Classification of Fungi and fungus-like taxa is an international initiative of more than 550 mycologists to develop an electronic structure for the classification of these organisms. The members of the Consortium originate from 55 countries/regions worldwide, from a wide range of disciplines, and include senior, mid-career and early-career mycologists and plant pathologists. The Consortium will publish a biannual update of the Outline of Fungi and fungus-like taxa, to act as an international scheme for other scientists. Notes on all newly published taxa at or above the level of species will be prepared and published online on the Outline of Fungi website (https://www.outlineoffungi.org/), and these will be finally published in the biannual edition of the Outline of Fungi and fungus-like taxa. Comments on recent important taxonomic opinions on controversial topics will be included in the biannual outline. For example, 'to promote a more stable taxonomy in Fusarium given the divergences over its generic delimitation', or 'are there too many genera in the Boletales?' and even more importantly, 'what should be done with the tremendously diverse 'dark fungal taxa?' There are undeniable differences in mycologists' perceptions and opinions regarding species classification as well as the establishment of new species. Given the pluralistic nature of fungal taxonomy and its implications for species concepts and the nature of species, this consortium aims to provide a platform to better refine and stabilise fungal classification, taking into consideration views from different parties. In the future, a confidential voting system will be set up to gauge the opinions of all mycologists in the Consortium on important topics. The results of such surveys will be presented to the International Commission on the Taxonomy of Fungi (ICTF) and the Nomenclature Committee for Fungi (NCF) with opinions and percentages of votes for and against. Criticisms based on scientific evidence with regards to nomenclature, classifications, and taxonomic concepts will be welcomed, and any recommendations on specific taxonomic issues will also be encouraged; however, we will encourage professionally and ethically responsible criticisms of others' work. This biannual ongoing project will provide an outlet for advances in various topics of fungal classification, nomenclature, and taxonomic concepts and lead to a community-agreed classification scheme for the fungi and fungus-like taxa. Interested parties should contact the lead author if they would like to be involved in future outlines.
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| 2. |
- Abramowski, A., et al.
(author)
-
The 2010 very high energy gamma-RAY flare and 10 years of multi-wavelength observations of M 87
- 2012
-
In: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 746:2, s. 151-
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Journal article (peer-reviewed)abstract
- The giant radio galaxy M 87 with its proximity (16 Mpc), famous jet, and very massive black hole ((3-6) x 10(9) M-circle dot) provides a unique opportunity to investigate the origin of very high energy (VHE; E > 100 GeV) gamma-ray emission generated in relativistic outflows and the surroundings of supermassive black holes. M 87 has been established as a VHE gamma-ray emitter since 2006. The VHE gamma-ray emission displays strong variability on timescales as short as a day. In this paper, results from a joint VHE monitoring campaign on M 87 by the MAGIC and VERITAS instruments in 2010 are reported. During the campaign, a flare at VHE was detected triggering further observations at VHE (H.E.S.S.), X-rays (Chandra), and radio (43 GHz Very Long Baseline Array, VLBA). The excellent sampling of the VHE gamma-ray light curve enables one to derive a precise temporal characterization of the flare: the single, isolated flare is well described by a two-sided exponential function with significantly different flux rise and decay times of tau(rise)(d) = (1.69 +/- 0.30) days and tau(decay)(d) = (0.611 +/- 0.080) days, respectively. While the overall variability pattern of the 2010 flare appears somewhat different from that of previous VHE flares in 2005 and 2008, they share very similar timescales (similar to day), peak fluxes (Phi(>0.35 TeV) similar or equal to (1-3) x 10(-11) photons cm(-2) s(-1)), and VHE spectra. VLBA radio observations of 43 GHz of the inner jet regions indicate no enhanced flux in 2010 in contrast to observations in 2008, where an increase of the radio flux of the innermost core regions coincided with a VHE flare. On the other hand, Chandra X-ray observations taken similar to 3 days after the peak of the VHE gamma-ray emission reveal an enhanced flux from the core (flux increased by factor similar to 2; variability timescale <2 days). The long-term (2001-2010) multi-wavelength (MWL) light curve of M 87, spanning from radio to VHE and including data from Hubble Space Telescope, Liverpool Telescope, Very Large Array, and European VLBI Network, is used to further investigate the origin of the VHE gamma-ray emission. No unique, common MWL signature of the three VHE flares has been identified. In the outer kiloparsec jet region, in particular in HST-1, no enhanced MWL activity was detected in 2008 and 2010, disfavoring it as the origin of the VHE flares during these years. Shortly after two of the three flares (2008 and 2010), the X-ray core was observed to be at a higher flux level than its characteristic range (determined from more than 60 monitoring observations: 2002-2009). In 2005, the strong flux dominance of HST-1 could have suppressed the detection of such a feature. Published models for VHE gamma-ray emission from M 87 are reviewed in the light of the new data.
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| 3. |
- Polme, S., et al.
(author)
-
FungalTraits: a user-friendly traits database of fungi and fungus-like stramenopiles
- 2020
-
In: Fungal Diversity. - : Springer Science and Business Media LLC. - 1560-2745 .- 1878-9129. ; 105:1, s. 1-16
-
Journal article (peer-reviewed)abstract
- The cryptic lifestyle of most fungi necessitates molecular identification of the guild in environmental studies. Over the past decades, rapid development and affordability of molecular tools have tremendously improved insights of the fungal diversity in all ecosystems and habitats. Yet, in spite of the progress of molecular methods, knowledge about functional properties of the fungal taxa is vague and interpretation of environmental studies in an ecologically meaningful manner remains challenging. In order to facilitate functional assignments and ecological interpretation of environmental studies we introduce a user friendly traits and character database FungalTraits operating at genus and species hypothesis levels. Combining the information from previous efforts such as FUNGuild and Fun(Fun) together with involvement of expert knowledge, we reannotated 10,210 and 151 fungal and Stramenopila genera, respectively. This resulted in a stand-alone spreadsheet dataset covering 17 lifestyle related traits of fungal and Stramenopila genera, designed for rapid functional assignments of environmental studies. In order to assign the trait states to fungal species hypotheses, the scientific community of experts manually categorised and assigned available trait information to 697,413 fungal ITS sequences. On the basis of those sequences we were able to summarise trait and host information into 92,623 fungal species hypotheses at 1% dissimilarity threshold.
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| 4. |
- Crous, P. W., et al.
(author)
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Fungal Planet description sheets : 785-867
- 2018
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In: Persoonia. - : Naturalis Biodiversity Center. - 0031-5850 .- 1878-9080. ; 41, s. 238-417
-
Journal article (peer-reviewed)abstract
- Novel species of fungi described in this study include those from various countries as follows: Angola, Gnomoniopsis angolensis and Pseudopithomyces angolensis on unknown host plants. Australia, Dothiora cotymbiae on Corymbia citriodora, Neoeucasphaeria eucalypti (incl. Neoeucasphaeria gen. nov.) on Eucalyptus sp., Fumagopsis stellae on Eucalyptus sp., Fusculina eucalyptorum (incl. Fusculinaceae fam. nov.) on Eucalyptus socialis, Harknessia cotymbiicola on Corymbia maculata, Neocelosporium eucalypti (incl. Neocelosporium gen. nov., Neocelosporiaceae fam. nov. and Neocelosporiales ord. nov.) on Eucalyptus cyanophylla, Neophaeomoniella corymbiae on Corymbia citriodora, Neophaeomoniefia eucalyptigena on Eucalyptus pilularis, Pseudoplagiostoma corymbiicola on Corymbia citriodora, Teratosphaeria gracilis on Eucalyptus gracilis, Zasmidium corymbiae on Corymbia citriodora. Brazil, Calonectria hemileiae on pustules of Hemileia vastatrix formed on leaves of Coffea arabica, Calvatia caatinguensis on soil, Cercospora solani-betacei on Solanum betaceum, Clathrus natalensis on soil, Diaporthe poincianellae on Poincianella pyramidalis, Geastrum piquiriunense on soil, Geosmithia carolliae on wing of Carollia perspicillata, Henningsia resupinata on wood, Penicillium guaibinense from soil, Periconia caespitosa from leaf litter, Pseudocercospora styracina on Styrax sp., Simplicillium filiforme as endophyte from Citrullus lanatus, Thozetella pindobacuensis on leaf litter, Xenosonderhenia coussapoae on Coussapoa floccosa. Canary Islands (Spain), Orbilia amarilla on Euphorbia canariensis, Cape Verde Islands, Xylodon jacobaeus on Eucalyptus camaldulensis. Chile, Colletotrichum arboricola on Fuchsia magellanica. Costa Rica, Lasiosphaeria miniovina on tree branch. Ecuador, Ganoderma chocoense on tree trunk. France, Neofitzroyomyces nerii (incl. Neofitzroyomyces gen. nov.) on Nerium oleander. Ghana, Castanediella tereticornis on Eucalyptus tereticornis, Falcocladium africanum on Eucalyptus brassiana, Rachicladosporium corymbiae on Corymbia citriodora. Hungary, Entoloma silvae-frondosae in Carpinus betulus-Pinus sylvestris mixed forest. Iran, Pseudopyricularia persiana on Cyperus sp. Italy, lnocybe roseascens on soil in mixed forest. Laos, Ophiocordyceps houaynhangensis on Coleoptera larva. Malaysia, Monilochaetes melastomae on Melastoma sp. Mexico, Absidia terrestris from soil. Netherlands, Acaulium pannemaniae, Conioscypha boutwelliae, Fusicolla septimanifiniscientiae, Gibellulopsis simonii, Lasionectria hilhorstii, Lectera nordwiniana, Leptodiscella rintelii, Parasarocladium debruynii and Sarocladium dejongiae (incl. Sarocladiaceae fam. nov.) from soil. New Zealand, Gnomoniopsis rosae on Rosa sp. and Neodevriesia metrosideri on Metrosideros sp. Puerto Rico, Neodevriesia coccolobae on Coccoloba uvifera, Neodevriesia tabebuiae and Alfaria tabebuiae on Tabebuia chrysantha. Russia, Amanita paludosa on bogged soil in mixed deciduous forest, Entoloma tiliae in forest of Tilia x europaea, Kwoniella endophytica on Pyrus communis. South Africa, Coniella diospyri on Diospyros mespiliformis, Neomelanconiella combreti (incl. Neomelanconiellaceae fam. nov. and Neomelanconiella gen. nov.) on Combretum sp., Polyphialoseptoria natalensis on unidentified plant host, Pseudorobillarda bolusanthi on Bolusanthus speciosus, Thelonectria pelargonii on Pelargonium sp. Spain, Vermiculariopsiella lauracearum and Anungitopsis lauri on Laurus novocanariensis, Geosmithia xerotolerans from a darkened wall of a house, Pseudopenidiella gallaica on leaf litter. Thailand, Corynespora thailandica on wood, Lareunionomyces loeiensis on leaf litter, Neocochlearomyces chromolaenae (incl. Neocochlearomyces gen. nov.) on Chromolaena odorata, Neomyrmecridium septatum (incl. Neomyrmecridium gen. nov.), Pararamichloridium caricicola on Carex sp., Xenodactylaria thailandica (incl. Xenodactylariaceae fam. nov. and Xenodactylaria gen. nov.), Neomyrmecridium asiaticum and Cymostachys thailandica from unidentified vine. USA, Carolinigaster bonitoi (incl. Carolinigaster gen. nov.) from soil, Penicillium fortuitum from house dust, Phaeotheca shathenatiana (incl. Phaeothecaceae fam. nov.) from twig and cone litter, Pythium wohlseniorum from stream water, Superstratomyces tardicrescens from human eye, Talaromyces iowaense from office air. Vietnam, Fistulinella olivaceoalba on soil. Morphological and culture characteristics along with DNA barcodes are provided.
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| 5. |
- Fomalont, E. B., et al.
(author)
-
THE 2014 ALMA LONG BASELINE CAMPAIGN: AN OVERVIEW
- 2015
-
In: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 808:1
-
Journal article (peer-reviewed)abstract
- A major goal of the Atacama Large Millimeter/submillimeter Array (ALMA) is to make accurate images with resolutions of tens of milliarcseconds, which at submillimeter (submm) wavelengths requires baselines up to similar to 15 km. To develop and test this capability, a Long Baseline Campaign (LBC) was carried out from 2014 September to late November, culminating in end-to-end observations, calibrations, and imaging of selected Science Verification (SV) targets. This paper presents an overview of the campaign and its main results, including an investigation of the short-term coherence properties and systematic phase errors over the long baselines at the ALMA site, a summary of the SV targets and observations, and recommendations for science observing strategies at long baselines. Deep ALMA images of the quasar 3C 138 at 97 and 241 GHz are also compared to VLA 43 GHz results, demonstrating an agreement at a level of a few percent. As a result of the extensive program of LBC testing, the highly successful SV imaging at long baselines achieved angular resolutions as fine as 19 mas at similar to 350 GHz. Observing with ALMA on baselines of up to 15 km is now possible, and opens up new parameter space for submm astronomy.
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| 6. |
- Yáñez-Mó, María, et al.
(author)
-
Biological properties of extracellular vesicles and their physiological functions.
- 2015
-
In: Journal of extracellular vesicles. - : Wiley. - 2001-3078. ; 4
-
Research review (peer-reviewed)abstract
- In the past decade, extracellular vesicles (EVs) have been recognized as potent vehicles of intercellular communication, both in prokaryotes and eukaryotes. This is due to their capacity to transfer proteins, lipids and nucleic acids, thereby influencing various physiological and pathological functions of both recipient and parent cells. While intensive investigation has targeted the role of EVs in different pathological processes, for example, in cancer and autoimmune diseases, the EV-mediated maintenance of homeostasis and the regulation of physiological functions have remained less explored. Here, we provide a comprehensive overview of the current understanding of the physiological roles of EVs, which has been written by crowd-sourcing, drawing on the unique EV expertise of academia-based scientists, clinicians and industry based in 27 European countries, the United States and Australia. This review is intended to be of relevance to both researchers already working on EV biology and to newcomers who will encounter this universal cell biological system. Therefore, here we address the molecular contents and functions of EVs in various tissues and body fluids from cell systems to organs. We also review the physiological mechanisms of EVs in bacteria, lower eukaryotes and plants to highlight the functional uniformity of this emerging communication system.
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| 7. |
- Fritz, N., et al.
(author)
-
The serotonin receptor 3E variant is a risk factor for female IBS-D
- 2022
-
In: Journal of Molecular Medicine-Jmm. - : Springer Science and Business Media LLC. - 0946-2716 .- 1432-1440. ; 100:11, s. 1617-1627
-
Journal article (peer-reviewed)abstract
- Irritable bowel syndrome (IBS) is a gut-brain disorder of multifactorial origin. Evidence of disturbed serotonergic function in IBS accumulated for the 5-HT3 receptor family. 5-HT(3)Rs are encoded by HTR3 genes and control GI function, and peristalsis and secretion, in particular. Moreover, 5-HT3R antagonists are beneficial in the treatment of diarrhea predominant IBS (IBS-D). We previously reported on functionally relevant SNPs in HTR3A c.-42C > T (rs1062613), HTR3C p.N163K (rs6766410), and HTR3E c.*76G > A (rs56109847 = rs62625044) being associated with IBS-D, and the HTR3B variant p.Y129S (rs1176744) was also described within the context of IBS. We performed a multi-center study to validate previous results and provide further evidence for the relevance of HTR3 genes in IBS pathogenesis. Therefore, genotype data of 2682 IBS patients and 9650 controls from 14 cohorts (Chile, Germany (2), Greece, Ireland, Spain, Sweden (2), the UK (3), and the USA (3)) were taken into account. Subsequent meta-analysis confirmed HTR3E c.*76G > A (rs56109847 = rs62625044) to be associated with female IBS-D (OR = 1.58; 95% CI (1.18, 2.12)). Complementary expression studies of four GI regions (jejunum, ileum, colon, sigmoid colon) of 66 IBS patients and 42 controls revealed only HTR3E to be robustly expressed. On top, HTR3E transcript levels were significantly reduced in the sigma of IBS patients (p = 0.0187); more specifically, in those diagnosed with IBS-D (p = 0.0145). In conclusion, meta-analysis confirmed rs56109847 = rs62625044 as a risk factor for female IBS-D. Expression analysis revealed reduced HTR3E levels in the sigmoid colon of IBS-D patients, which underlines the relevance of HTR3E in the pathogenesis of IBS-D.
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| 8. |
- Kehoe, Laura, et al.
(author)
-
Make EU trade with Brazil sustainable
- 2019
-
In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
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Journal article (other academic/artistic)
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| 9. |
- Mohr, S., et al.
(author)
-
The alternative serotonin transporter promoter P2 impacts gene function in females with irritable bowel syndrome
- 2021
-
In: Journal of Cellular and Molecular Medicine. - : Wiley. - 1582-1838 .- 1582-4934. ; 25:16, s. 8047-8061
-
Journal article (peer-reviewed)abstract
- Irritable bowel syndrome (IBS) is a gut-brain disorder in which symptoms are shaped by serotonin acting centrally and peripherally. The serotonin transporter gene SLC6A4 has been implicated in IBS pathophysiology, but the underlying genetic mechanisms remain unclear. We sequenced the alternative P2 promoter driving intestinal SLC6A4 expression and identified single nucleotide polymorphisms (SNPs) that were associated with IBS in a discovery sample. Identified SNPs built different haplotypes, and the tagging SNP rs2020938 seems to associate with constipation-predominant IBS (IBS-C) in females. rs2020938 validation was performed in 1978 additional IBS patients and 6,038 controls from eight countries. Meta-analysis on data from 2,175 IBS patients and 6,128 controls confirmed the association with female IBS-C. Expression analyses revealed that the P2 promoter drives SLC6A4 expression primarily in the small intestine. Gene reporter assays showed a functional impact of SNPs in the P2 region. In silico analysis of the polymorphic promoter indicated differential expression regulation. Further follow-up revealed that the major allele of the tagging SNP rs2020938 correlates with differential SLC6A4 expression in the jejunum and with stool consistency, indicating functional relevance. Our data consolidate rs2020938 as a functional SNP associated with IBS-C risk in females, underlining the relevance of SLC6A4 in IBS pathogenesis.
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| 10. |
- Wallström, Sofia, 1988, et al.
(author)
-
ALMA Compact Array observations of the Fried Egg nebula: Evidence for large-scale asymmetric mass-loss from the yellow hypergiant IRAS 17163-3907
- 2017
-
In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 597, s. A99, pp. 1-10
-
Journal article (peer-reviewed)abstract
- Yellow hypergiants are rare and represent a fast evolutionary stage of massive evolved stars. That evolutionary phase is characterised by a very intense mass loss, the understanding of which is still very limited. Here we report ALMA Compact Array observations of a 50??-mosaic toward the Fried Egg nebula, around one of the few Galactic yellow hypergiants IRAS 17163-3907. The emission from the 12CO J = 2-1 line, H30? recombination line, and continuum is imaged at a resolution of ~8??, revealing the morphology of the molecular environment around the star. The continuum emission is unresolved and peaks at the position of the star. The radio recombination line H30? shows unresolved emission at the star, with an approximately Gaussian spectrum centered on a velocity of 21 ± 3km s-1 with a width of 57 ± 6km s-1. In contrast, the CO 2-1 emission is complex and decomposes into several components beyond the contamination from interstellar gas in the line of sight. The CO spectrum toward the star is a broad plateau, centered at the systemic velocity of +18 km s-1 and with an expansion velocity of 100 ± 10km s-1. Assuming isotropic and constant mass-loss, we estimate a mass-loss rate of 8 ± 1.5 × 10-5M? yr-1. At a radius of 25?? from the star, we detect CO emission associated with the dust ring previously imaged by Herschel. The kinematics of this ring, however, is not consistent with an expanding shell, but show a velocity gradient of vsys ± 20km s-1. In addition, we find a puzzling bright feature radially connecting the star to the CO ring, at a velocity of +40 km s-1 relative to the star. This spur feature may trace a unidirectional ejection event from the star. Our ACA observations reveal the complex morphology around IRAS 17163 and illustrate the breakthroughs that ALMA will bring to the field of massive stellar evolution.
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| 11. |
- Cervantes-Madrid, Diana Lizeth, 1987, et al.
(author)
-
Repotrectinib (TPX-0005), effectively reduces growth of ALK driven neuroblastoma cells.
- 2019
-
In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1
-
Journal article (peer-reviewed)abstract
- Neuroblastoma is the most commonly diagnosed extracranial tumor in the first year of life. Approximately 9% of neuroblastoma patients present germline or somatic aberrations in the gene encoding for anaplastic lymphoma kinase (ALK). This increases in high-risk neuroblastomas, which have a 14% frequency of ALK aberrations at the time of diagnosis and show increasing numbers at relapse. Abrogating ALK activity with kinase inhibitors is employed as clinical therapy in malignancies such as non-small cell lung cancer and has shown good results in pediatric inflammatory myofibroblastic tumors and anaplastic large cell lymphomas. A phase I clinical trial of the first generation ALK inhibitor, crizotinib, in neuroblastoma patients showed modest results and suggested that further investigation was needed. Continuous development of ALK inhibitors has resulted in the third generation inhibitor repotrectinib (TPX-0005), which targets the active kinase conformations of ALK, ROS1 and TRK receptors. In the present study we investigated the effects of repotrectinib in a neuroblastoma setting in vitro and in vivo. Neuroblastoma cell lines were treated with repotrectinib to investigate inhibition of ALK and to determine its effect on proliferation. PC12 cells transfected with different ALK mutant variants were used to study the efficacy of repotrectinib to block ALK activation/signaling. The in vivo effect of repotrectinib was also analyzed in a neuroblastoma xenograft model. Our results show that repotrectinib is capable of inhibiting signaling activity of a range of ALK mutant variants found in neuroblastoma patients and importantly it exhibits strong antitumor effects in a xenograft model of neuroblastoma.
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| 12. |
- Cespedes, PF, et al.
(author)
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T-cell trans-synaptic vesicles are distinct and carry greater effector content than constitutive extracellular vesicles
- 2022
-
In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 3460-
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Journal article (peer-reviewed)abstract
- The immunological synapse is a molecular hub that facilitates the delivery of three activation signals, namely antigen, costimulation/corepression and cytokines, from antigen-presenting cells (APC) to T cells. T cells release a fourth class of signaling entities, trans-synaptic vesicles (tSV), to mediate bidirectional communication. Here we present bead-supported lipid bilayers (BSLB) as versatile synthetic APCs to capture, characterize and advance the understanding of tSV biogenesis. Specifically, the integration of juxtacrine signals, such as CD40 and antigen, results in the adaptive tailoring and release of tSV, which differ in size, yields and immune receptor cargo compared with steadily released extracellular vesicles (EVs). Focusing on CD40L+tSV as model effectors, we show that PD-L1 trans-presentation together with TSG101, ADAM10 and CD81 are key in determining CD40L vesicular release. Lastly, we find greater RNA-binding protein and microRNA content in tSV compared with EVs, supporting the specialized role of tSV as intercellular messengers.
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| 13. |
- Dobreanu, Dan, et al.
(author)
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Current practice for diagnosis and management of silent atrial fibrillation : results of the European Heart Rhythm Association survey
- 2013
-
In: Europace. - : Oxford University Press (OUP). - 1099-5129 .- 1532-2092. ; 15:8, s. 1223-1225
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Journal article (peer-reviewed)abstract
- Although it is well known that silent atrial fibrillation (AF) is associated with morbidity and mortality rates similar to those of symptomatic AF, no specific strategy for screening and management of this form of AF has been advocated. The purpose of this survey was to identify current practices for the diagnosis and management of silent AF. This survey is based on an electronic questionnaire sent to the European Heart Rhythm Association Research Network partners. Responses were received from 33 centres in 16 countries. The preferred screening methods for silent AF in patients with rhythm control by pharmacological therapy was 12-lead electrocardiogram (ECG) at outpatient visits (31.3%) and periodical 24 h Holter ECG recordings (34.4%), while after pulmonary vein isolation the corresponding figures were 6.3 and 65.6%, respectively. No consensus has been reached concerning the therapeutic approach for such patients. Most responders preferred rate control over rhythm control in patients with silent AF, although some favoured pulmonary vein isolation in young patients. However, oral anticoagulant therapy in patients at high thromboembolic risk was considered mandatory by most, provided that at least one episode of silent AF was documented, without recommending further investigations. The results of this survey have confirmed that there is currently no consensus regarding the screening and management of patients with silent AF and that clinical practice is not always consistent with the few existing evidence-based recommendations.
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| 14. |
- Hernández-Madrid, Antonio, et al.
(author)
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Cardioversion for atrial fibrillation in current European practice : results of the European Heart Rhythm Association survey
- 2013
-
In: Europace. - : Oxford University Press (OUP). - 1099-5129 .- 1532-2092. ; 15:6, s. 915-918
-
Journal article (peer-reviewed)abstract
- This survey was conducted to provide an insight into the current clinical practice regarding the use of cardioversion for atrial fibrillation (AF) in Europe. Responses were received from 57 centres across Europe, 71.9% of which were university hospitals. For electrical cardioversion, general anaesthesia was managed by an anaesthesiologist in 73.9% of centres and by a cardiologist in 37%. In the majority of centres, electrical cardioversion was performed using a biphasic defibrillator (85.1%). Antiarrhythmic drugs were routinely prescribed prior to electrical cardioversion by 54.3% of hospitals. For pharmacological cardioversion in patients with no or minimal heart disease, the majority of centres (63.1%) chose intravenous flecainide or propafenone, whereas vernakalant was used by 35% of centres in patients with no or minimal-to-moderate structural heart disease. Most centres (71.7%) used a mandatory strategy of 3 weeks of oral anticoagulation prior to elective cardioversion in patients AF > 48 h, but 28.3% performed immediate cardioversion after a transoesophageal echocardiogram. Many centres are now performing electrical cardioversion on treatment with novel oral anticoagulants (up to 23.6% of cardioversions).
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| 15. |
- Lenarczyk, Radoslaw, et al.
(author)
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The use of wearable cardioverter-defibrillators in Europe : results of the European Heart Rhythm Association survey
- 2016
-
In: Europace. - : Oxford University Press (OUP). - 1099-5129 .- 1532-2092. ; 18:1, s. 146-150
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Journal article (peer-reviewed)abstract
- The aim of this European Heart Rhythm Association (EHRA) survey was to collect data on the use of wearable cardioverter-defibrillators (WCDs) among members of the EHRA electrophysiology research network. Of the 50 responding centres, 23 (47%) reported WCD use. Devices were fully reimbursed in 17 (43.6%) of 39 respondents, and partially reimbursed in 3 centres (7.7%). Eleven out of 20 centres (55%) reported acceptable patients' compliance (WCD worn for > 90% of time). The most common indications for WCD (8 out of 10 centres; 80%) were covering the period until re-implantation of ICD explanted due to infection, in patients with left ventricular impairment due to myocarditis or recent myocardial infarction and those awaiting heart transplantation. Patient life expectancy of < 12 months and poor compliance were the most commonly reported contraindications for WCD (24 of 46 centres, 52.2%). The major problems encountered by physicians managing patients with WCD were costs (8 of 18 centres, 44.4%), non-compliance, and incorrect use of WCD. Four of 17 centres (23.5%) reported inappropriate WCD activations in < 5% of patients. The first shock success rate in terminating ventricular arrhythmias was 95-100% in 6 of 15 centres (40%), 85-95% in 4 (26.7%), 75-85% in 2 (13.3%), and < 75% in 3 centres (20%). The survey has shown that the use of WCD in Europe is still restricted and depends on reimbursement. Patients' compliance remains low. Heterogeneity of indications for WCD among centres underscores the need for further research and a better definition of indications for WCD in specific patient groups.
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| 16. |
- Mont, Lluís, et al.
(author)
-
Pre-participation cardiovascular evaluation for athletic participants to prevent sudden death: Position paper from the EHRA and the EACPR, branches of the ESC. Endorsed by APHRS, HRS, and SOLAECE.
- 2017
-
In: Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology. - : Oxford University Press (OUP). - 1532-2092 .- 1099-5129. ; 19:1, s. 139-163
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Journal article (peer-reviewed)
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| 17. |
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| 18. |
- Onischenko, Evgeny, et al.
(author)
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Role of the Ndc1 interaction network in yeast nuclear pore complex assembly and maintenance
- 2009
-
In: Journal of Cell Biology. - : The Rockefeller University Press. - 0021-9525 .- 1540-8140. ; 185:3, s. 475-91
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Journal article (peer-reviewed)abstract
- The nuclear pore complex (NPC) mediates all nucleocytoplasmic transport, yet its structure and biogenesis remain poorly understood. In this study, we have functionally characterized interaction partners of the yeast transmembrane nucleoporin Ndc1. Ndc1 forms a distinct complex with the transmembrane proteins Pom152 and Pom34 and two alternative complexes with the soluble nucleoporins Nup53 and Nup59, which in turn bind to Nup170 and Nup157. The transmembrane and soluble Ndc1-binding partners have redundant functions at the NPC, and disruption of both groups of interactions causes defects in Ndc1 targeting and in NPC structure accompanied by significant pore dilation. Using photoconvertible fluorescent protein fusions, we further show that the depletion of Pom34 in cells that lack NUP53 and NUP59 blocks new NPC assembly and leads to the reversible accumulation of newly made nucleoporins in cytoplasmic foci. Therefore, Ndc1 together with its interaction partners are collectively essential for the biosynthesis and structural integrity of yeast NPCs.
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- Umapathy, Ganesh, et al.
(author)
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MEK inhibitor trametinib does not prevent the growth of anaplastic lymphoma kinase (ALK)-addicted neuroblastomas.
- 2017
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In: Science signaling. - : American Association for the Advancement of Science (AAAS). - 1937-9145 .- 1945-0877. ; 10:507
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Journal article (peer-reviewed)abstract
- Activation of the RAS-RAF-MEK-ERK signaling pathway is implicated in driving the initiation and progression of multiple cancers. Several inhibitors targeting the RAS-MAPK pathway are clinically approved as single- or polyagent therapies for patients with specific types of cancer. One example is the MEK inhibitor trametinib, which is included as a rational polytherapy strategy for treating EML4-ALK-positive, EGFR-activated, or KRAS-mutant lung cancers and neuroblastomas that also contain activating mutations in the RAS-MAPK pathway. In addition, in neuroblastoma, a heterogeneous disease, relapse cases display an increased rate of mutations in ALK, NRAS, and NF1, leading to increased activation of RAS-MAPK signaling. Co-targeting ALK and the RAS-MAPK pathway is an attractive option, because monotherapies have not yet produced effective results in ALK-addicted neuroblastoma patients. We evaluated the response of neuroblastoma cell lines to MEK-ERK pathway inhibition by trametinib. In contrast to RAS-MAPK pathway-mutated neuroblastoma cell lines, ALK-addicted neuroblastoma cells treated with trametinib showed increased activation (inferred by phosphorylation) of the kinases AKT and ERK5. This feedback response was mediated by the mammalian target of rapamycin complex 2-associated protein SIN1, resulting in increased survival and proliferation that depended on AKT signaling. In xenografts in mice, trametinib inhibited the growth of EML4-ALK-positive non-small cell lung cancer and RAS-mutant neuroblastoma but not ALK-addicted neuroblastoma. Thus, our results advise against the seemingly rational option of using MEK inhibitors to treat ALK-addicted neuroblastoma.
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- Van den Eynden, Jimmy, 1977, et al.
(author)
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Phosphoproteome and gene expression profiling of ALK inhibition in neuroblastoma cell lines reveals conserved oncogenic pathways.
- 2018
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In: Science signaling. - : American Association for the Advancement of Science (AAAS). - 1937-9145 .- 1945-0877. ; 11:557
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Journal article (peer-reviewed)abstract
- Anaplastic lymphoma kinase (ALK) is a tyrosine kinase receptor that is a clinical target of major interest in cancer. Mutations and rearrangements in ALK trigger the activation of the encoded receptor and its downstream signaling pathways. ALK mutations have been identified in both familial and sporadic neuroblastoma cases as well as in 30 to 40% of relapses, which makes ALK a bona fide target in neuroblastoma therapy. Tyrosine kinase inhibitors (TKIs) that target ALK are currently in clinical use for the treatment of patients with ALK-positive non-small cell lung cancer. However, monotherapy with the ALK inhibitor crizotinib has been less encouraging in neuroblastoma patients with ALK alterations, raising the question of whether combinatorial therapy would be more effective. In this study, we established both phosphoproteomic and gene expression profiles of ALK activity in neuroblastoma cells exposed to first- and third-generation ALK TKIs, to identify the underlying molecular mechanisms and identify relevant biomarkers, signaling networks, and new therapeutic targets. This analysis has unveiled various important leads for novel combinatorial treatment strategies for patients with neuroblastoma and an increased understanding of ALK signaling involved in this disease.
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