4,075 results on '"Rudolf E"'
Search Results
2. Validation of NIAAAm-CRP criteria to predict alcohol-associated steatohepatitis on liver histology
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Rudolf E. Stauber, Pierre-Emmanuel Rautou, Horia Stefanescu, Adelina Horhat, Maja Thiele, Carolin Lackner, Susan Davies, Helmut Denk, Sönke Detlefsen, Hans Peter Dienes, Viviane Gnemmi, Annette S.H. Gouw, Maria Guido, Rosa Miquel, Valerie Paradis, Ioana Rusu, Peter Schirmacher, Luigi Terracciano, and Dina Tiniakos
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Alcohol-associated liver disease ,noninvasive ,histology ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Background & Aims: In clinical practice, the diagnosis of alcohol-associated hepatitis (AH) is mostly based on non-invasive criteria, which were defined at a consensus conference by the National Institute on Alcohol Abuse and Alcoholism (NIAAA). These criteria were recently modified by adding C-reactive protein (CRP) and termed NIAAAm-CRP criteria, which showed superior diagnostic accuracy for presence of alcohol-associated steatohepatitis (ASH) on liver histology. The aim of our study was to validate the diagnostic accuracy of both original NIAAA criteria and NIAAAm-CRP criteria for presence of ASH on liver histology in an independent cohort. Methods: Data from a large multinational cohort of 445 patients with alcohol-associated liver disease (ALD) that served to establish a novel grading and staging system of alcohol-associated liver disease were analyzed retrospectively. Diagnosis of ASH was based on presence of hepatocyte ballooning plus lobular neutrophil infiltration and established in virtual consensus meetings of multiple expert liver pathologists. Results: Complete data including CRP values were available in 346 patients. Overall diagnostic accuracy for prediction of ASH was 73% for NIAAA criteria and 77% for NIAAAm-CRP criteria. In a subgroup with suspected severe AH (MELD >20, n = 123), overall diagnostic accuracy for prediction of ASH was 69% for NIAAA criteria and 74% for NIAAAm-CRP criteria. Conclusion: Our findings confirm recent data on suboptimal diagnostic accuracy of original NIAAA criteria and validate slightly better but still suboptimal performance of NIAAAm-CRP criteria for presence of ASH. Impact and Implications: Alcohol-associated steatohepatitis (ASH) is diagnosed on liver histology but liver biopsy is not always feasible. Non-invasive diagnosis based on clinical findings has been proposed using the National Institute on Alcohol Abuse and Alcoholism (NIAAA) criteria and recently improved using NIAAAm-CRP criteria. Our findings validate slightly better but still suboptimal performance of NIAAAm-CRP criteria for the presence of histological ASH. Clinical trials of novel drugs should focus on histologically proven ASH.
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- 2024
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3. Endurance Training Provokes Arrhythmogenic Right Ventricular Cardiomyopathy Phenotype in Heterozygous Desmoglein-2 Mutants: Alleviation by Preload Reduction
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Larissa Fabritz, Lisa Fortmueller, Katja Gehmlich, Sebastian Kant, Marcel Kemper, Dana Kucerova, Fahima Syeda, Cornelius Faber, Rudolf E. Leube, Paulus Kirchhof, and Claudia A. Krusche
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desmoglein 2 ,preload-reducing therapy ,arrhythmogenic right ventricular cardiomyopathy (ARVC) ,mouse model ,arrhythmogenic cardiomyopathy ,endurance exercise ,Biology (General) ,QH301-705.5 - Abstract
Desmoglein-2 mutations are detected in 5–10% of patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). Endurance training accelerates the development of the ARVC phenotype, leading to earlier arrhythmic events. Homozygous Dsg2 mutant mice develop a severe ARVC-like phenotype. The phenotype of heterozygous mutant (Dsg2mt/wt) or haploinsufficient (Dsg20/wt) mice is still not well understood. To assess the effects of age and endurance swim training, we studied cardiac morphology and function in sedentary one-year-old Dsg2mt/wt and Dsg20/wt mice and in young Dsg2mt/wt mice exposed to endurance swim training. Cardiac structure was only occasionally affected in aged Dsg20/wt and Dsg2mt/wt mice manifesting as small fibrotic foci and displacement of Connexin 43. Endurance swim training increased the right ventricular (RV) diameter and decreased RV function in Dsg2mt/wt mice but not in wild types. Dsg2mt/wt hearts showed increased ventricular activation times and pacing-induced ventricular arrhythmia without obvious fibrosis or inflammation. Preload-reducing therapy during training prevented RV enlargement and alleviated the electrophysiological phenotype. Taken together, endurance swim training induced features of ARVC in young adult Dsg2mt/wt mice. Prolonged ventricular activation times in the hearts of trained Dsg2mt/wt mice are therefore a potential mechanism for increased arrhythmia risk. Preload-reducing therapy prevented training-induced ARVC phenotype pointing to beneficial treatment options in human patients.
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- 2024
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4. An Assessment of the Mechanophysical and Hormonal Impact on Human Endometrial Epithelium Mechanics and Receptivity
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Anna K. Sternberg, Liubov Izmaylova, Volker U. Buck, Irmgard Classen-Linke, and Rudolf E. Leube
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human endometrial epithelium ,menstrual cycle ,window of implantation ,Ishikawa cells ,trophoblast adhesion ,stiffness ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
The endometrial epithelium and underlying stroma undergo profound changes to support and limit embryo adhesion and invasion, which occur in the secretory phase of the menstrual cycle during the window of implantation. This coincides with a peak in progesterone and estradiol production. We hypothesized that the interplay between hormone-induced changes in the mechanical properties of the endometrial epithelium and stroma supports this process. To study it, we used hormone-responsive endometrial adenocarcinoma-derived Ishikawa cells growing on substrates of different stiffness. We showed that Ishikawa monolayers on soft substrates are more tightly clustered and uniform than on stiff substrates. Probing for mechanical alterations, we found accelerated stress–relaxation after apical nanoindentation in hormone-stimulated monolayers on stiff substrates. Traction force microscopy furthermore revealed an increased number of foci with high traction in the presence of estradiol and progesterone on soft substrates. The detection of single cells and small cell clusters positive for the intermediate filament protein vimentin and the progesterone receptor further underscored monolayer heterogeneity. Finally, adhesion assays with trophoblast-derived AC-1M-88 spheroids were used to examine the effects of substrate stiffness and steroid hormones on endometrial receptivity. We conclude that the extracellular matrix and hormones act together to determine mechanical properties and, ultimately, embryo implantation.
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- 2024
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5. Evaluating the Use of TiO2 Nanoparticles for Toxicity Testing in Pulmonary A549 Cells
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Bacova J, Knotek P, Kopecka K, Hromadko L, Capek J, Nyvltova P, Bruckova L, Schröterova L, Sestakova B, Palarcik J, Motola M, Cizkova D, Bezrouk A, Handl J, Fiala Z, Rudolf E, Bilkova Z, Macak JM, and Rousar T
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titanium dioxide ,nanoparticles ,p25 ,nanotoxicity ,a549 cells ,dispersion. ,Medicine (General) ,R5-920 - Abstract
Jana Bacova,1 Petr Knotek,2 Katerina Kopecka,2 Ludek Hromadko,3 Jan Capek,1 Pavlina Nyvltova,1 Lenka Bruckova,1 Ladislava Schröterova,4 Blanka Sestakova,4 Jiri Palarcik,5 Martin Motola,3 Dana Cizkova,6 Ales Bezrouk,7 Jiri Handl,1 Zdenek Fiala,8 Emil Rudolf,4 Zuzana Bilkova,1 Jan M Macak,3,9 Tomas Rousar1 1Department of Biological and Biochemical Sciences, Faculty of Chemical Technology, University of Pardubice, Pardubice, Czech Republic; 2Department of General and Inorganic Chemistry, Faculty of Chemical Technology, University of Pardubice, Pardubice, Czech Republic; 3Center of Materials and Nanotechnologies, Faculty of Chemical Technology, University of Pardubice, Pardubice, Czech Republic; 4Department of Medical Biology and Genetics, Faculty of Medicine in Hradec Kralove, Charles University, Hradec Kralove, Czech Republic; 5Institute of Environmental and Chemical Engineering, Faculty of Chemical Technology, University of Pardubice, Pardubice, Czech Republic; 6Department of Histology and Embryology, Faculty of Medicine in Hradec Kralove, Charles University, Hradec Kralove, Czech Republic; 7Department of Medical Biophysics, Faculty of Medicine in Hradec Kralove, Charles University, Hradec Kralove, Czech Republic; 8Department of Preventive Medicine, Faculty of Medicine in Hradec Kralove, Charles University, Hradec Kralove, Czech Republic; 9Central European Institute of Technology, Brno University of Technology, Brno, Czech RepublicCorrespondence: Tomas Rousar, Department of Biological and Biochemical Sciences, Faculty of Chemical Technology, University of Pardubice, Pardubice, Czech Republic, Tel +420 466 037 707, Fax +420 466 036 361, Email Tomas.Rousar@upce.czPurpose: Titanium dioxide nanoparticles, 25 nm in size of crystallites (TiO2 P25), are among the most produced nanomaterials worldwide. The broad use of TiO2 P25 in material science has implied a request to evaluate their biological effects, especially in the lungs. Hence, the pulmonary A549 cell line has been used to estimate the effects of TiO2 P25. However, the reports have provided dissimilar results on caused toxicity. Surprisingly, the physicochemical factors influencing TiO2 P25 action in biological models have not been evaluated in most reports. Thus, the objective of the present study is to characterize the preparation of TiO2 P25 for biological testing in A549 cells and to evaluate their biological effects.Methods: We determined the size and crystallinity of TiO2 P25. We used four techniques for TiO2 P25 dispersion. We estimated the colloid stability of TiO2 P25 in distilled water, isotonic NaCl solution, and cell culture medium. We applied the optimal dispersion conditions for testing the biological effects of TiO2 P25 (0– 100 μg.mL− 1) in A549 cells using biochemical assays (dehydrogenase activity, glutathione levels) and microscopy.Results: We found that the use of fetal bovine serum in culture medium is essential to maintain sufficient colloid stability of dispersed TiO2 P25. Under these conditions, TiO2 P25 were unable to induce a significant impairment of A549 cells according to the results of biochemical and microscopy evaluations. When the defined parameters for the use of TiO2 P25 in A549 cells were met, similar results on the biological effects of TiO2 P25 were obtained in two independent cell laboratories.Conclusion: We optimized the experimental conditions of TiO2 P25 preparation for toxicity testing in A549 cells. The results presented here on TiO2 P25-induced cellular effects are reproducible. Therefore, our results can be helpful for other researchers using TiO2 P25 as a reference material.Keywords: titanium dioxide, nanoparticles, P25, nanotoxicity, A549 cells, dispersion
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- 2022
6. Intermediate filament network perturbation in the C. elegans intestine causes systemic dysfunctions
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Florian Geisler, Sanne Remmelzwaal, Vera Jankowski, Ruben Schmidt, Mike Boxem, and Rudolf E Leube
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intermediate filament ,endotube ,intestine ,C. elegans ,Medicine ,Science ,Biology (General) ,QH301-705.5 - Abstract
Intermediate filaments (IFs) are major components of the metazoan cytoskeleton. A long-standing debate concerns the question whether IF network organization only reflects or also determines cell and tissue function. Using Caenorhabditis elegans, we have recently described mutants of the mitogen-activated protein kinase (MAPK) SMA-5 which perturb the organization of the intestinal IF cytoskeleton resulting in luminal widening and cytoplasmic invaginations. Besides these structural phenotypes, systemic dysfunctions were also observed. We now identify the IF polypeptide IFB-2 as a highly efficient suppressor of both the structural and functional deficiencies of mutant sma-5 animals by removing the aberrant IF network. Mechanistically, perturbed IF network morphogenesis is linked to hyperphosphorylation of multiple sites throughout the entire IFB-2 molecule. The rescuing capability is IF isotype-specific and not restricted to sma-5 mutants but extends to mutants that disrupt the function of the cytoskeletal linker IFO-1 and the IF-associated protein BBLN-1. The findings provide strong evidence for adverse consequences of the deranged IF networks with implications for diseases that are characterized by altered IF network organization.
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- 2023
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7. Desmoplakin Maintains Transcellular Keratin Scaffolding and Protects From Intestinal InjurySummary
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Annika Gross, Biaohuan Zhou, Lisa Bewersdorf, Nicole Schwarz, Gabriel M. Schacht, Peter Boor, Konrad Hoeft, Bernd Hoffmann, Elaine Fuchs, Rafael Kramann, Rudolf Merkel, Rudolf E. Leube, and Pavel Strnad
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Desmosome ,Keratin ,Apical Junctional Complex ,Intestinal Epithelial Barrier ,Cell Adhesion ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Background & Aims: Desmosomes are intercellular junctions connecting keratin intermediate filaments of neighboring cells. The cadherins desmoglein 2 (Dsg2) and desmocollin 2 mediate cell–cell adhesion, whereas desmoplakin (Dsp) provides the attachment of desmosomes to keratins. Although the importance of the desmosome–keratin network is well established in mechanically challenged tissues, we aimed to assess the currently understudied function of desmosomal proteins in intestinal epithelia. Methods: We analyzed the intestine-specific villin-Cre DSP (DSPΔIEC) and the combined intestine-specific DSG2/DSPΔIEC (ΔDsg2/Dsp) knockout mice. Cross-breeding with keratin 8–yellow fluorescent protein knock-in mice and generation of organoids was performed to visualize the keratin network. A Dsp-deficient colorectal carcinoma HT29-derived cell line was generated and the role of Dsp in adhesion and mechanical stress was studied in dispase assays, after exposure to uniaxial cell stretching and during scratch assay. Results: The intestine of DSPΔIEC mice was histopathologically inconspicuous. Intestinal epithelial cells, however, showed an accelerated migration along the crypt and an enhanced shedding into the lumen. Increased intestinal permeability and altered levels of desmosomal proteins were detected. An inconspicuous phenotype also was seen in ΔDsg2/Dsp mice. After dextran sodium sulfate treatment, DSPΔIEC mice developed more pronounced colitis. A retracted keratin network was seen in the intestinal epithelium of DSPΔIEC/keratin 8–yellow fluorescent protein mice and organoids derived from these mice presented a collapsed keratin network. The level, phosphorylation status, and solubility of keratins were not affected. Dsp-deficient HT29 cells had an impaired cell adhesion and suffered from increased cellular damage after stretch. Conclusions: Our results show that Dsp is required for proper keratin network architecture in intestinal epithelia, mechanical resilience, and adhesion, thereby protecting from injury.
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- 2022
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8. Editorial: The wetware credentials of intermediate filaments involves coordinating, organising and networking in cells and tissues
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Rudolf E. Leube and Roy A. Quinlan
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cytoskeleton ,intermediate filament ,cell junctions ,cell shape ,cell polarity and migration ,wetware ,Biology (General) ,QH301-705.5 - Published
- 2023
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9. Regionally specific levels and patterns of keratin 8 expression in the mouse embryo visceral endoderm emerge upon anterior-posterior axis determination
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Evangéline Despin-Guitard, Ronan Quenec’Hdu, Wallis Nahaboo, Nicole Schwarz, Rudolf E. Leube, Claire Chazaud, and Isabelle Migeotte
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mouse embryo development ,extra-embryonic tissues ,keratin intermediate filaments ,epithelia ,cytoskeleton ,Biology (General) ,QH301-705.5 - Abstract
The mechanical properties of the different germ layers of the early mammalian embryo are likely to be critical for morphogenesis. Cytoskeleton components (actin and myosin, microtubules, intermediate filaments) are major determinants of epithelial plasticity and resilience to stress. Here, we take advantage of a mouse reporter for Keratin 8 to record the pattern of the keratin intermediate filaments network in the first epithelia of the developing mouse embryo. At the blastocyst stage, Keratin 8 is strongly expressed in the trophectoderm, and undetectable in the inner cell mass and its derivatives, the epiblast and primitive endoderm. Visceral endoderm cells that differentiate from the primitive endoderm at the egg cylinder stage display apical Keratin 8 filaments. Upon migration of the Anterior Visceral Endoderm and determination of the anterior-posterior axis, Keratin 8 becomes regionally distributed, with a stronger expression in embryonic, compared to extra-embryonic, visceral endoderm. This pattern emerges concomitantly to a modification of the distribution of Filamentous (F)-actin, from a cortical ring to a dense apical shroud, in extra-embryonic visceral endoderm only. Those regional characteristics are maintained across gastrulation. Interestingly, for each stage and region of the embryo, adjacent germ layers display contrasted levels of keratin filaments, which may play a role in their adaptation to growth and morphological changes.
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- 2022
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10. Desmoglein 2 regulates cardiogenesis by restricting hematopoiesis in the developing murine heart
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Hoda Moazzen, Kateryna Venger, Sebastian Kant, Rudolf E. Leube, and Claudia A. Krusche
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Medicine ,Science - Abstract
Abstract Cardiac morphogenesis relies on intricate intercellular signaling. Altered signaling impacts cardiac function and is detrimental to embryonic survival. Here we report an unexpected regulatory role of the desmosomal cell adhesion molecule desmoglein 2 (Dsg2) on murine heart development. A large percentage of Dsg2-mutant embryos develop pericardial hemorrhage. Lethal myocardial rupture is occasionally observed, which is not associated with loss of cardiomyocyte contact but with expansion of abnormal, non-myocyte cell clusters within the myocardial wall. Two types of abnormal cell clusters can be distinguished: Type A clusters involve endocard-associated, round-shaped CD31+ cells, which proliferate and invade the myocardium. They acquire Runx1- and CD44-positivity indicating a shift towards a hematopoietic phenotype. Type B clusters expand subepicardially and next to type A clusters. They consist primarily of Ter119+ erythroid cells with interspersed Runx1+/CD44+ cells suggesting that they originate from type A cell clusters. The observed pericardial hemorrhage is caused by migration of erythrocytes from type B clusters through the epicardium and rupture of the altered cardiac wall. Finally, evidence is presented that structural defects of Dsg2-depleted cardiomyocytes are primary to the observed pathogenesis. We propose that cardiomyocyte-driven paracrine signaling, which likely involves Notch1, directs subsequent trans-differentiation of endo- and epicardial cells. Together, our observations uncover a hitherto unknown regulatory role of Dsg2 in cardiogenesis.
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- 2021
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11. Cortical tension regulates desmosomal morphogenesis
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Marcin Moch, Jana Schieren, and Rudolf E. Leube
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Keratin ,myosin II ,desmosome ,desmoplakin ,desmoglein ,desmocollin ,Biology (General) ,QH301-705.5 - Abstract
Mechanical stability is a fundamental and essential property of epithelial cell sheets. It is in large part determined by cell-cell adhesion sites that are tightly integrated by the cortical cytoskeleton. An intimate crosstalk between the adherens junction-associated contractile actomyosin system and the desmosome-anchored keratin intermediate filament system is decisive for dynamic regulation of epithelial mechanics. A major question in the field is whether and in which way mechanical stress affects junctional plasticity. This is especially true for the desmosome-keratin scaffold whose role in force-sensing is virtually unknown. To examine this question, we inactivated the actomyosin system in human keratinocytes (HaCaT) and canine kidney cells (MDCK) and monitored changes in desmosomal protein turnover.Partial inhibition of myosin II by para-nitro-blebbistatin led to a decrease of the cells' elastic modulus and to reduced desmosomal protein turnover in regions where nascent desmosomes are formed and, to a lower degree, in regions where larger, more mature desmosomes are present. Interestingly, desmosomal proteins are affected differently: a significant decrease in turnover was observed for the desmosomal plaque protein desmoplakin I (DspI), which links keratin filaments to the desmosomal core, and the transmembrane cadherin desmoglein 2 (Dsg2). On the other hand, the turnover of another type of desmosomal cadherin, desmocollin 2 (Dsc2), was not significantly altered under the tested conditions. Similarly, the turnover of the adherens junction-associated E-cadherin was not affected by the low doses of para-nitro-blebbistatin. Inhibition of actin polymerization by low dose latrunculin B treatment and of ROCK-driven actomyosin contractility by Y-27632 treatment also induced a significant decrease in desmosomal DspI turnover. Taken together, we conclude that changes in the cortical force balance affect desmosome formation and growth. Furthermore, they differentially modulate desmosomal protein turnover resulting in changes of desmosome composition. We take the observations as evidence for a hitherto unknown desmosomal mechanosensing and mechanoresponse pathway responding to an altered force balance.
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- 2022
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12. Desmosomes in Cell Fate Determination: From Cardiogenesis to Cardiomyopathy
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Hoda Moazzen, Mistura Dolapo Bolaji, and Rudolf E. Leube
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desmosome ,cardiogenesis ,cell fate determination ,epithelial to mesenchymal transition ,arrhythmogenic cardiomyopathy ,Cytology ,QH573-671 - Abstract
Desmosomes play a vital role in providing structural integrity to tissues that experience significant mechanical tension, including the heart. Deficiencies in desmosomal proteins lead to the development of arrhythmogenic cardiomyopathy (AC). The limited availability of preventative measures in clinical settings underscores the pressing need to gain a comprehensive understanding of desmosomal proteins not only in cardiomyocytes but also in non-myocyte residents of the heart, as they actively contribute to the progression of cardiomyopathy. This review focuses specifically on the impact of desmosome deficiency on epi- and endocardial cells. We highlight the intricate cross-talk between desmosomal proteins mutations and signaling pathways involved in the regulation of epicardial cell fate transition. We further emphasize that the consequences of desmosome deficiency differ between the embryonic and adult heart leading to enhanced erythropoiesis during heart development and enhanced fibrogenesis in the mature heart. We suggest that triggering epi-/endocardial cells and fibroblasts that are in different “states” involve the same pathways but lead to different pathological outcomes. Understanding the details of the different responses must be considered when developing interventions and therapeutic strategies.
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- 2023
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13. Steatotic Liver Disease: Metabolic Dysfunction, Alcohol, or Both?
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Katharina Staufer and Rudolf E. Stauber
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non-alcoholic fatty liver disease (NAFLD) ,metabolic-dysfunction associated steatotic liver disease (MASLD) ,metabolic dysfunction-associated steatohepatitis (MASH) ,alcohol-related liver disease (ALD) ,steatotic liver disease (SLD) ,Biology (General) ,QH301-705.5 - Abstract
Non-alcoholic fatty liver disease (NAFLD) and alcohol-related liver disease (ALD), both of them accounting for fatty liver disease (FLD), are among the most common chronic liver diseases globally, contributing to substantial public health burden. Both NAFLD and ALD share a similar picture of clinical presentation yet may have differences in prognosis and treatment, which renders early and accurate diagnosis difficult but necessary. While NAFLD is the fastest increasing chronic liver disease, the prevalence of ALD has seemingly remained stable in recent years. Lately, the term steatotic liver disease (SLD) has been introduced, replacing FLD to reduce stigma. SLD represents an overarching term to primarily comprise metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), as well as alcohol-related liver disease (ALD), and MetALD, defined as a continuum across which the contribution of MASLD and ALD varies. The present review discusses current knowledge on common denominators of NAFLD/MASLD and ALD in order to highlight clinical and research needs to improve our understanding of SLD.
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- 2023
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14. Fibroscan® probe selection for lean adults
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Vanessa Stadlbauer, Iohanes Negrean, Andreas Posch, Andrea Streit, Nicole Feldbacher, Rudolf E Stauber, and Angela Horvath
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agreement ,bias ,examination ,liver stiffness ,meal ,preparation ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Abstract Background and Aim Fibroscan® is used to assess fibrosis and steatosis of the liver noninvasively. The company suggests to use the S+‐probe in people 75 cm and adults with a skin–liver capsule distance 75 cm in fasting state and after intake of a standardized light meal (300 kcal). Results We examined 50 volunteers (26 female, 24 ± 3 years). Twenty‐two participants were in the TC ≤75 cm group and 28 in TC >75 cm group. LS values with the S+‐probe were 15% higher than with the M+‐probe in both groups (median difference 0.6 kPa, P
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- 2021
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15. Albumin in patients with liver disease shows an altered conformation
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Margret Paar, Vera H. Fengler, Daniel J. Rosenberg, Angelika Krebs, Rudolf E. Stauber, Karl Oettl, and Michal Hammel
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Biology (General) ,QH301-705.5 - Abstract
Paar et al. propose a SAXS-based approach to study conformations of human serum albumin (HSA) from patients with liver disease and a structural understanding of HSA dynamicity and its correlation with clinical variables are provided. Using it on real clinical samples, this study has concrete practical implications too.
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- 2021
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16. Combining Image Restoration and Traction Force Microscopy to Study Extracellular Matrix-Dependent Keratin Filament Network Plasticity
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Sungjun Yoon, Reinhard Windoffer, Aleksandra N. Kozyrina, Teodora Piskova, Jacopo Di Russo, and Rudolf E. Leube
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cytoskeleton ,intermediate filaments ,keratin ,image restoration ,traction force microscopy ,extracellular matrix ,Biology (General) ,QH301-705.5 - Abstract
Keratin intermediate filaments are dynamic cytoskeletal components that are responsible for tuning the mechanical properties of epithelial tissues. Although it is known that keratin filaments (KFs) are able to sense and respond to changes in the physicochemical properties of the local niche, a direct correlation of the dynamic three-dimensional network structure at the single filament level with the microenvironment has not been possible. Using conventional approaches, we find that keratin flow rates are dependent on extracellular matrix (ECM) composition but are unable to resolve KF network organization at the single filament level in relation to force patterns. We therefore developed a novel method that combines a machine learning-based image restoration technique and traction force microscopy to decipher the fine details of KF network properties in living cells grown on defined ECM patterns. Our approach utilizes Content-Aware Image Restoration (CARE) to enhance the temporal resolution of confocal fluorescence microscopy by at least five fold while preserving the spatial resolution required for accurate extraction of KF network structure at the single KF/KF bundle level. The restored images are used to segment the KF network, allowing numerical analyses of its local properties. We show that these tools can be used to study the impact of ECM composition and local mechanical perturbations on KF network properties and corresponding traction force patterns in size-controlled keratinocyte assemblies. We were thus able to detect increased curvature but not length of KFs on laminin-322 versus fibronectin. Photoablation of single cells in microprinted circular quadruplets revealed surprisingly little but still significant changes in KF segment length and curvature that were paralleled by an overall reduction in traction forces without affecting global network orientation in the modified cell groups irrespective of the ECM coating. Single cell analyses furthermore revealed differential responses to the photoablation that were less pronounced on laminin-332 than on fibronectin. The obtained results illustrate the feasibility of combining multiple techniques for multimodal monitoring and thereby provide, for the first time, a direct comparison between the changes in KF network organization at the single filament level and local force distribution in defined paradigms.
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- 2022
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17. Quantitative mapping of keratin networks in 3D
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Reinhard Windoffer, Nicole Schwarz, Sungjun Yoon, Teodora Piskova, Michael Scholkemper, Johannes Stegmaier, Andrea Bönsch, Jacopo Di Russo, and Rudolf E Leube
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cytoskeleton ,intermediate filament ,keratin ,retinal pigment epithelium ,3D network ,virtual reality ,Medicine ,Science ,Biology (General) ,QH301-705.5 - Abstract
Mechanobiology requires precise quantitative information on processes taking place in specific 3D microenvironments. Connecting the abundance of microscopical, molecular, biochemical, and cell mechanical data with defined topologies has turned out to be extremely difficult. Establishing such structural and functional 3D maps needed for biophysical modeling is a particular challenge for the cytoskeleton, which consists of long and interwoven filamentous polymers coordinating subcellular processes and interactions of cells with their environment. To date, useful tools are available for the segmentation and modeling of actin filaments and microtubules but comprehensive tools for the mapping of intermediate filament organization are still lacking. In this work, we describe a workflow to model and examine the complete 3D arrangement of the keratin intermediate filament cytoskeleton in canine, murine, and human epithelial cells both, in vitro and in vivo. Numerical models are derived from confocal airyscan high-resolution 3D imaging of fluorescence-tagged keratin filaments. They are interrogated and annotated at different length scales using different modes of visualization including immersive virtual reality. In this way, information is provided on network organization at the subcellular level including mesh arrangement, density and isotropic configuration as well as details on filament morphology such as bundling, curvature, and orientation. We show that the comparison of these parameters helps to identify, in quantitative terms, similarities and differences of keratin network organization in epithelial cell types defining subcellular domains, notably basal, apical, lateral, and perinuclear systems. The described approach and the presented data are pivotal for generating mechanobiological models that can be experimentally tested.
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- 2022
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18. BASS. XXXV. The M BH–σ* Relation of 105 Month Swift-BAT Type 1 AGNs
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Turgay Caglar, Michael J. Koss, Leonard Burtscher, Benny Trakhtenbrot, M. Kiyami Erdim, Julian E. Mejía-Restrepo, Federica Ricci, Meredith C. Powell, Claudio Ricci, Richard Mushotzky, Franz E. Bauer, Tonima T. Ananna, Rudolf E. Bär, Bernhard Brandl, Jarle Brinchmann, Fiona Harrison, Kohei Ichikawa, Darshan Kakkad, Kyuseok Oh, Rogério Riffel, Lia F. Sartori, Krista L. Smith, Daniel Stern, and C. Megan Urry
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Supermassive black holes ,X-ray surveys ,AGN host galaxies ,X-ray active galactic nuclei ,Active galaxies ,Galaxies ,Astrophysics ,QB460-466 - Abstract
We present two independent measurements of stellar velocity dispersions ( σ _⋆ ) from the Ca ii H+K λ 3969, 3934 and Mg i b λ 5183, 5172, 5167 region (3880–5550 Å) and the calcium triplet region (8350–8750 Å) for 173 hard X-ray-selected Type 1 active galactic nuclei (AGNs; z ≤ 0.08) from the 105 month Swift-BAT catalog. We construct one of the largest samples of local Type 1 AGNs that have both single-epoch virial black hole mass ( M _BH ) estimates and σ _⋆ measurements obtained from high spectral resolution data, allowing us to test the usage of such methods for supermassive black hole studies. We find that the two independent σ _⋆ measurements are highly consistent with each other, with an average offset of only 0.002 ± 0.001 dex. Comparing M _BH estimates based on broad emission lines and stellar velocity dispersion measurements, we find that the former is systematically lower by ≈0.12 dex. Consequently, Eddington ratios estimated through broad-line M _BH determinations are similarly biased (but in the opposite way). We argue that the discrepancy is driven by extinction in the broad-line region. We also find an anticorrelation between the offset from the M _BH – σ _⋆ relation and the Eddington ratio. Our sample of Type 1 AGNs shows a shallower M _BH – σ _⋆ relation (with a power-law exponent of ≈3.5) compared with that of inactive galaxies (with a power-law exponent of ≈4.5), confirming earlier results obtained from smaller samples.
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- 2023
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19. Launching the VASCO Citizen Science Project
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Beatriz Villarroel, Kristiaan Pelckmans, Enrique Solano, Mikael Laaksoharju, Abel Souza, Onyeuwaoma Nnaemeka Dom, Khaoula Laggoune, Jamal Mimouni, Hichem Guergouri, Lars Mattsson, Aurora Lago García, Johan Soodla, Diego Castillo, Matthew E. Shultz, Rubby Aworka, Sébastien Comerón, Stefan Geier, Geoffrey W. Marcy, Alok C. Gupta, Josefine Bergstedt, Rudolf E. Bär, Bart Buelens, Emilio Enriquez, Christopher K. Mellon, Almudena Prieto, Dismas Simiyu Wamalwa, Rafael S. de Souza, and Martin J. Ward
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surveys ,transients ,SETI ,citizen science ,Elementary particle physics ,QC793-793.5 - Abstract
The Vanishing & Appearing Sources during a Century of Observations (VASCO) project investigates astronomical surveys spanning a time interval of 70 years, searching for unusual and exotic transients. We present herein the VASCO Citizen Science Project, which can identify unusual candidates driven by three different approaches: hypothesis, exploratory, and machine learning, which is particularly useful for SETI searches. To address the big data challenge, VASCO combines three methods: the Virtual Observatory, user-aided machine learning, and visual inspection through citizen science. Here we demonstrate the citizen science project and its improved candidate selection process, and we give a progress report. We also present the VASCO citizen science network led by amateur astronomy associations mainly located in Algeria, Cameroon, and Nigeria. At the moment of writing, the citizen science project has carefully examined 15,593 candidate image pairs in the data (ca. 10% of the candidates), and has so far identified 798 objects classified as “vanished”. The most interesting candidates will be followed up with optical and infrared imaging, together with the observations by the most potent radio telescopes.
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- 2022
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20. A Ca2+-Mediated Switch of Epiplakin from a Diffuse to Keratin-Bound State Affects Keratin Dynamics
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Sonia Ratajczyk, Corinne Drexler, Reinhard Windoffer, Rudolf E. Leube, and Peter Fuchs
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cytoskeleton ,keratin ,intermediate filaments ,plakin protein family ,epiplakin ,Cytology ,QH573-671 - Abstract
Keratins exert important structural but also cytoprotective functions. They have to be adaptable to support cellular homeostasis. Epiplakin (EPPK1) has been shown to decorate keratin filaments in epithelial cells and to play a protective role under stress, but the mechanism is still unclear. Using live-cell imaging of epithelial cells expressing fluorescently tagged EPPK1 and keratin, we report here an unexpected dynamic behavior of EPPK1 upon stress. EPPK1 was diffusely distributed throughout the cytoplasm and not associated with keratin filaments in living cells under standard culture conditions. However, ER-, oxidative and UV-stress, as well as cell fixation, induced a rapid association of EPPK1 with keratin filaments. This re-localization of EPPK1 was reversible and dependent on the elevation of cytoplasmic Ca2+ levels. Moreover, keratin filament association of EPPK1 led to significantly reduced keratin dynamics. Thus, we propose that EPPK1 stabilizes the keratin network in stress conditions, which involve increased cytoplasmic Ca2+.
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- 2022
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21. Non-invasive markers of liver fibrosis and outcome in large vessel occlusion stroke
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Simon Fandler-Höfler, Rudolf E. Stauber, Markus Kneihsl, Gerit Wünsch, Melanie Haidegger, Birgit Poltrum, Alexander Pichler, Hannes Deutschmann, Christian Enzinger, Peter Fickert, and Thomas Gattringer
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Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Background: Liver fibrosis has been identified as an outcome predictor in cardiovascular disease and has been associated with hematoma expansion and mortality in patients with primary intracerebral hemorrhage. We aimed to explore whether clinically inapparent liver fibrosis is related to neurological outcome, mortality, and intracranial hemorrhage risk in ischemic stroke patients after mechanical thrombectomy. Methods: We included consecutive patients with anterior circulation large vessel occlusion stroke treated at our center with mechanical thrombectomy between January 2011 and April 2019. Clinical data had been collected prospectively; laboratory data were extracted from our electronic hospital information system. We calculated the Fibrosis-4 index (FIB-4), an established non-invasive liver fibrosis test. The main outcomes were postinterventional intracranial hemorrhage, unfavorable functional status (modified Rankin scale scores of 3–6), and mortality three months post-stroke. Results: In the 460 patients (mean age 69 years, 49.3% female) analyzed, FIB-4 indicated advanced liver fibrosis in 22.6%. Positive FIB-4 was associated with unfavorable neurological outcomes and mortality three months post-stroke, even after correction for co-factors [Odds Ratio (OR) 2.15 for unfavorable outcome in patients with positive FIB-4, 95% confidence interval (CI) 1.21–3.83, p = 0.009, and 2.16 for mortality, 95% CI 1.16–4.03, p = 0.01]. However, FIB-4 was neither related to hemorrhagic transformation nor symptomatic intracranial hemorrhage. Moreover, atrial fibrillation was more frequent in patients with liver fibrosis ( p
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- 2021
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22. Metabolic disease and ABHD6 alter the circulating bis(monoacylglycerol)phosphate profile in mice and humans
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Gernot F. Grabner, Nermeen Fawzy, Maria A. Pribasnig, Markus Trieb, Ulrike Taschler, Michael Holzer, Martina Schweiger, Heimo Wolinski, Dagmar Kolb, Angela Horvath, Rolf Breinbauer, Thomas Rülicke, Roland Rabl, Achim Lass, Vanessa Stadlbauer, Birgit Hutter-Paier, Rudolf E. Stauber, Peter Fickert, Rudolf Zechner, Gunther Marsche, Thomas O. Eichmann, and Robert Zimmermann
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nonalcoholic fatty liver disease ,obesity ,lysosomal storage disorders ,phospholipids ,lysobisphosphatidic acid ,α/β-hydrolase domain-containing 6 ,Biochemistry ,QD415-436 - Abstract
Bis(monoacylglycerol)phosphate (BMP) is a phospholipid that is crucial for lipid degradation and sorting in acidic organelles. Genetic and drug-induced lysosomal storage disorders (LSDs) are associated with increased BMP concentrations in tissues and in the circulation. Data on BMP in disorders other than LSDs, however, are scarce, and key enzymes regulating BMP metabolism remain elusive. Here, we demonstrate that common metabolic disorders and the intracellular BMP hydrolase α/β-hydrolase domain-containing 6 (ABHD6) affect BMP metabolism in mice and humans. In mice, dietary lipid overload strongly affects BMP concentration and FA composition in the liver and plasma, similar to what has been observed in LSDs. Notably, distinct changes in the BMP FA profile enable a clear distinction between lipid overload and drug-induced LSDs. Global deletion of ABHD6 increases circulating BMP concentrations but does not cause LSDs. In humans, nonalcoholic fatty liver disease and liver cirrhosis affect the serum BMP FA composition and concentration. Furthermore, we identified a patient with a loss-of-function mutation in the ABHD6 gene, leading to an altered circulating BMP profile. In conclusion, our results suggest that common metabolic diseases and ABHD6 affect BMP metabolism in mice and humans.
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- 2019
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23. HSD17B13 truncated variant is associated with a mild hepatic phenotype in Wilson’s Disease
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Peter Ferenci, Jan Pfeiffenberger, Albert Friedrich Stättermayer, Rudolf E. Stauber, Claudia Willheim, Karl H. Weiss, Petra Munda-Steindl, Michael Trauner, Michael Schilsky, and Heinz Zoller
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Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Background & Aims: HSD17B13 encodes hydroxysteroid 17-β dehydrogenase 13, a novel liver lipid-droplet associated protein that is involved in the regulation of lipid biosynthetic processes. A protein-truncating HSD17B13 variant (rs72613567) was shown to protect individuals from alcoholic and non-alcoholic liver disease. Since steatosis is a common feature in Wilson’s disease (WD), we aimed to assess whether the HSD17B13 variant modulates the phenotypic presentation and progression of WD. Methods: The HSD17B13:TA (rs72613567) variant was determined by allelic discrimination real-time PCR in 586 patients. The HSD17B13 genotype was correlated with the phenotypic presentation. The age of onset and the type of symptoms at presentation were used as markers of the WD phenotype. Results: The overall HSD17B13:TA allele frequency in patients with WD was 23.3% (273/1,172), not significantly different from the reported minor allele frequency. There was a significantly lower HSD17B13:TA allele frequency in patients with fulminant WD compared to all other phenotypic WD groups (11.0% vs. 24.0%, p
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- 2019
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24. PPMS onset upon adalimumab treatment extends the spectrum of anti-TNF-α therapy-associated demyelinating disorders
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Sinah Engel, Felix Luessi, Aneka Mueller, Rudolf E. Schopf, Frauke Zipp, and Stefan Bittner
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Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Since their introduction in 1999, anti-tumour necrosis factor-α (anti-TNF-α) therapies have been suspected repeatedly to be associated with the occurrence of central nervous system (CNS) demyelinating disorders, including multiple sclerosis (MS). However, recent publications were restricted to descriptions of monophasic demyelinating events or cases of relapsing–remitting MS (RRMS). We here provide the first case report of primary progressive MS (PPMS) onset upon anti-TNF-α therapy as well as a literature review of previously published cases of anti-TNF-α therapy-associated MS onset. The 51-year old male patient was treated with adalimumab due to psoriasis arthritis. About 18 months after treatment initiation, he developed slowly progressing neurological deficits including gait impairment, paraesthesia of the lower limbs, strangury and visual impairment, which led to the discontinuation of adalimumab therapy. Magnetic resonance imaging of the brain and the spinal cord revealed multiple inflammatory lesions and cerebrospinal fluid examination showed slight pleocytosis and positive oligoclonal bands. Thus, PPMS was diagnosed according to the 2017 revision of the McDonald criteria. As PPMS often causes only subtle symptoms in the beginning and early treatment discontinuation of anti-TNF-α therapy seems essential to improve the patient’s outcome, we think that it is important to increase the awareness of slowly progressing neurological deficits as a potential adverse event of anti-TNF-α therapy among all clinicians involved in the initiation and monitoring of these drugs. In addition, the occurrence of both RRMS and progressive MS upon anti-TNF-α therapy might suggest a shared TNF-α-mediated pathophysiological mechanism in the evolution of all MS subtypes.
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- 2020
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25. BASS. XXII. The BASS DR2 AGN Catalog and Data
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Michael J. Koss, Claudio Ricci, Benny Trakhtenbrot, Kyuseok Oh, Jakob S. den Brok, Julian E. Mejía-Restrepo, Daniel Stern, George C. Privon, Ezequiel Treister, Meredith C. Powell, Richard Mushotzky, Franz E. Bauer, Tonima T. Ananna, Mislav Baloković, Rudolf E. Bär, George Becker, Patricia Bessiere, Leonard Burtscher, Turgay Caglar, Enrico Congiu, Phil Evans, Fiona Harrison, Marianne Heida, Kohei Ichikawa, Nikita Kamraj, Isabella Lamperti, Fabio Pacucci, Federica Ricci, Rogério Riffel, Alejandra F. Rojas, Kevin Schawinski, Matthew J. Temple, C. Megan Urry, Sylvain Veilleux, and Jonathan Williams
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X-ray active galactic nuclei ,Active galactic nuclei ,Seyfert galaxies ,X-ray quasars ,X-ray surveys ,Surveys ,Astrophysics ,QB460-466 - Abstract
We present the active galactic nucleus (AGN) catalog and optical spectroscopy for the second data release of the Swift BAT AGN Spectroscopic Survey (BASS DR2). With this DR2 release we provide 1449 optical spectra, of which 1182 are released for the first time, for the 858 hard-X-ray-selected AGNs in the Swift BAT 70-month sample. The majority of the spectra (801/1449, 55%) are newly obtained from Very Large Telescope (VLT)/X-shooter or Palomar/Doublespec. Many of the spectra have both higher resolution ( R > 2500, N ∼ 450) and/or very wide wavelength coverage (3200–10000 Å, N ∼ 600) that are important for a variety of AGN and host galaxy studies. We include newly revised AGN counterparts for the full sample and review important issues for population studies, with 47 AGN redshifts determined for the first time and 790 black hole mass and accretion rate estimates. This release is spectroscopically complete for all AGNs (100%, 858/858), with 99.8% having redshift measurements (857/858) and 96% completion in black hole mass estimates of unbeamed AGNs (722/752). This AGN sample represents a unique census of the brightest hard-X-ray-selected AGNs in the sky, spanning many orders of magnitude in Eddington ratio ( L / L _Edd = 10 ^−5 –100), black hole mass ( M _BH = 10 ^5 –10 ^10 M _⊙ ), and AGN bolometric luminosity ( L _bol = 10 ^40 –10 ^47 erg s ^−1 ).
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- 2022
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26. BASS. XXVI. DR2 Host Galaxy Stellar Velocity Dispersions
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Michael J. Koss, Benny Trakhtenbrot, Claudio Ricci, Kyuseok Oh, Franz E. Bauer, Daniel Stern, Turgay Caglar, Jakob S. den Brok, Richard Mushotzky, Federica Ricci, Julian E. Mejía-Restrepo, Isabella Lamperti, Ezequiel Treister, Rudolf E. Bär, Fiona Harrison, Meredith C. Powell, George C. Privon, Rogério Riffel, Alejandra F. Rojas, Kevin Schawinski, and C. Megan Urry
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Supermassive black holes ,X-ray surveys ,Sky surveys ,X-ray active galactic nuclei ,AGN host galaxies ,Astrophysics ,QB460-466 - Abstract
We present new central stellar velocity dispersions for 484 Sy 1.9 and Sy 2 from the second data release of the Swift/BAT AGN Spectroscopic Survey (BASS DR2). This constitutes the largest study of velocity dispersion measurements in X-ray-selected obscured active galactic nuclei (AGN) with 956 independent measurements of the Ca ii H and K λ 3969, 3934 and Mg I λ 5175 region (3880–5550 Å) and the calcium triplet region (8350–8730 Å) from 642 spectra mainly from VLT/X-Shooter or Palomar/DoubleSpec. Our sample spans velocity dispersions of 40–360 km s ^1 , corresponding to 4–5 orders of magnitude in black hole mass ( M _BH = 10 ^5.5−9.6 M _⊙ ), bolometric luminosity ( L _bol ∼ 10 ^42–46 erg s ^−1 ), and Eddington ratio ( L / L _Edd ∼ 10 ^−5 to 2). For 281 AGN, our data and analysis provide the first published central velocity dispersions, including six AGN with low-mass black holes ( M _BH = 10 ^5.5−6.5 M _⊙ ), discovered thanks to high spectral resolution observations ( σ _inst ∼ 25 km s ^−1 ). The survey represents a significant advance with a nearly complete census of velocity dispersions of hard X-ray–selected obscured AGN with measurements for 99% of nearby AGN ( z < 0.1) outside the Galactic plane (∣ b ∣ > 10°). The BASS AGN have much higher velocity dispersions than the more numerous optically selected narrow-line AGN (i.e., ∼150 versus ∼100 km s ^−1 ) but are not biased toward the highest velocity dispersions of massive ellipticals (i.e., >250 km s ^−1 ). Despite sufficient spectral resolution to resolve the velocity dispersions associated with the bulges of small black holes (∼10 ^4–5 M _⊙ ), we do not find a significant population of super-Eddington AGN. Using estimates of the black hole sphere of influence from velocity dispersion, direct stellar and gas black hole mass measurements could be obtained with existing facilities for more than ∼100 BASS AGN.
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- 2022
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27. BASS. XXV. DR2 Broad-line-based Black Hole Mass Estimates and Biases from Obscuration
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Julian E. Mejía-Restrepo, Benny Trakhtenbrot, Michael J. Koss, Kyuseok Oh, Jakob den Brok, Daniel Stern, Meredith C. Powell, Federica Ricci, Turgay Caglar, Claudio Ricci, Franz E. Bauer, Ezequiel Treister, Fiona A. Harrison, C. M. Urry, Tonima Tasnim Ananna, Daniel Asmus, Roberto J. Assef, Rudolf E. Bär, Patricia S. Bessiere, Leonard Burtscher, Kohei Ichikawa, Darshan Kakkad, Nikita Kamraj, Richard Mushotzky, George C. Privon, Alejandra F. Rojas, Eleonora Sani, Kevin Schawinski, and Sylvain Veilleux
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Active galactic nuclei ,Surveys ,Catalogs ,Supermassive black holes ,X-ray surveys ,M-sigma relation ,Astrophysics ,QB460-466 - Abstract
We present measurements of broad emission lines and virial estimates of supermassive black hole masses ( M _BH ) for a large sample of ultrahard X-ray-selected active galactic nuclei (AGNs) as part of the second data release of the BAT AGN Spectroscopic Survey (BASS/DR2). Our catalog includes M _BH estimates for a total of 689 AGNs, determined from the H α , H β , Mg ii λ 2798, and/or C iv λ 1549 broad emission lines. The core sample includes a total of 512 AGNs drawn from the 70 month Swift/BAT all-sky catalog. We also provide measurements for 177 additional AGNs that are drawn from deeper Swift/BAT survey data. We study the links between M _BH estimates and line-of-sight obscuration measured from X-ray spectral analysis. We find that broad H α emission lines in obscured AGNs ( $\mathrm{log}({N}_{{\rm{H}}}/{\mathrm{cm}}^{-2})\gt 22.0$ ) are on average a factor of ${8.0}_{-2.4}^{+4.1}$ weaker relative to ultrahard X-ray emission and about ${35}_{-12}^{\,+7}$ % narrower than those in unobscured sources (i.e., $\mathrm{log}({N}_{{\rm{H}}}/{\mathrm{cm}}^{-2})\lt 21.5$ ). This indicates that the innermost part of the broad-line region is preferentially absorbed. Consequently, current single-epoch M _BH prescriptions result in severely underestimated (>1 dex) masses for Type 1.9 sources (AGNs with broad H α but no broad H β ) and/or sources with $\mathrm{log}({N}_{{\rm{H}}}/{\mathrm{cm}}^{-2})\gtrsim 22.0$ . We provide simple multiplicative corrections for the observed luminosity and width of the broad H α component ( L [bH α ] and FWHM[bH α ]) in such sources to account for this effect and to (partially) remedy M _BH estimates for Type 1.9 objects. As a key ingredient of BASS/DR2, our work provides the community with the data needed to further study powerful AGNs in the low-redshift universe.
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- 2022
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28. BASS. XXIV. The BASS DR2 Spectroscopic Line Measurements and AGN Demographics
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Kyuseok Oh, Michael J. Koss, Yoshihiro Ueda, Daniel Stern, Claudio Ricci, Benny Trakhtenbrot, Meredith C. Powell, Jakob S. den Brok, Isabella Lamperti, Richard Mushotzky, Federica Ricci, Rudolf E. Bär, Alejandra F. Rojas, Kohei Ichikawa, Rogério Riffel, Ezequiel Treister, Fiona Harrison, C. Megan Urry, Franz E. Bauer, and Kevin Schawinski
- Subjects
Supermassive black holes ,Active galactic nuclei ,X-ray active galactic nuclei ,AGN host galaxies ,Quasars ,Astrophysics ,QB460-466 - Abstract
We present the second catalog and data release of optical spectral line measurements and active galactic nucleus (AGN) demographics of the BAT AGN Spectroscopic Survey, which focuses on the Swift-BAT hard X-ray detected AGNs. We use spectra from dedicated campaigns and publicly available archives to investigate spectral properties of most of the AGNs listed in the 70 month Swift-BAT all-sky catalog; specifically, 743 of the 746 unbeamed and unlensed AGNs (99.6%). We find a good correspondence between the optical emission line widths and the hydrogen column density distributions using the X-ray spectra, with a clear dichotomy of AGN types for N _H = 10 ^22 cm ^−2 . Based on optical emission-line diagnostics, we show that 48%–75% of BAT AGNs are classified as Seyfert, depending on the choice of emission lines used in the diagnostics. The fraction of objects with upper limits on line emission varies from 6% to 20%. Roughly 4% of the BAT AGNs have lines too weak to be placed on the most commonly used diagnostic diagram, [O iii ] λ 5007/H β versus [N ii ] λ 6584/H α , despite the high signal-to-noise ratio of their spectra. This value increases to 35% in the [O iii ] λ 5007/[O ii ] λ 3727 diagram, owing to difficulties in line detection. Compared to optically selected narrow-line AGNs in the Sloan Digital Sky Survey, the BAT narrow-line AGNs have a higher rate of reddening/extinction, with H α /H β > 5 (∼36%), indicating that hard X-ray selection more effectively detects obscured AGNs from the underlying AGN population. Finally, we present a subpopulation of AGNs that feature complex broad lines (34%, 250/743) or double-peaked narrow emission lines (2%, 17/743).
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- 2022
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29. Autophagy and Endoplasmic Reticulum Stress during Onset and Progression of Arrhythmogenic Cardiomyopathy
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Mark Pitsch, Sebastian Kant, Corinna Mytzka, Rudolf E. Leube, and Claudia A. Krusche
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ARVC ,arrhythmogenic cardiomyopathy ,desmoglein ,autophagy ,ER stress ,Chop ,Cytology ,QH573-671 - Abstract
Arrhythmogenic cardiomyopathy (AC) is a heritable, potentially lethal disease without a causal therapy. AC is characterized by focal cardiomyocyte death followed by inflammation and progressive formation of connective tissue. The pathomechanisms leading to structural disease onset and progression, however, are not fully elucidated. Recent studies revealed that dysregulation of autophagy and endoplasmic/sarcoplasmic reticulum (ER/SR) stress plays an important role in cardiac pathophysiology. We therefore examined the temporal and spatial expression patterns of autophagy and ER/SR stress indicators in murine AC models by qRT-PCR, immunohistochemistry, in situ hybridization and electron microscopy. Cardiomyocytes overexpressing the autophagy markers LC3 and SQSTM1/p62 and containing prominent autophagic vacuoles were detected next to regions of inflammation and fibrosis during onset and chronic disease progression. mRNAs of the ER stress markers Chop and sXbp1 were elevated in both ventricles at disease onset. During chronic disease progression Chop mRNA was upregulated in right ventricles. In addition, reduced Ryr2 mRNA expression together with often drastically enlarged ER/SR cisternae further indicated SR dysfunction during this disease phase. Our observations support the hypothesis that locally altered autophagy and enhanced ER/SR stress play a role in AC pathogenesis both at the onset and during chronic progression.
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- 2021
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30. How Mechanical Forces Change the Human Endometrium during the Menstrual Cycle in Preparation for Embryo Implantation
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Anna K. Sternberg, Volker U. Buck, Irmgard Classen-Linke, and Rudolf E. Leube
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mechanobiology ,endometrial epithelium ,embryo ,endometrial crosstalk ,adhesion ,cytoskeleton ,Cytology ,QH573-671 - Abstract
The human endometrium is characterized by exceptional plasticity, as evidenced by rapid growth and differentiation during the menstrual cycle and fast tissue remodeling during early pregnancy. Past work has rarely addressed the role of cellular mechanics in these processes. It is becoming increasingly clear that sensing and responding to mechanical forces are as significant for cell behavior as biochemical signaling. Here, we provide an overview of experimental evidence and concepts that illustrate how mechanical forces influence endometrial cell behavior during the hormone-driven menstrual cycle and prepare the endometrium for embryo implantation. Given the fundamental species differences during implantation, we restrict the review to the human situation. Novel technologies and devices such as 3D multifrequency magnetic resonance elastography, atomic force microscopy, organ-on-a-chip microfluidic systems, stem-cell-derived organoid formation, and complex 3D co-culture systems have propelled the understanding how endometrial receptivity and blastocyst implantation are regulated in the human uterus. Accumulating evidence has shown that junctional adhesion, cytoskeletal rearrangement, and extracellular matrix stiffness affect the local force balance that regulates endometrial differentiation and blastocyst invasion. A focus of this review is on the hormonal regulation of endometrial epithelial cell mechanics. We discuss potential implications for embryo implantation.
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- 2021
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31. Addressing Profiles of Systemic Inflammation Across the Different Clinical Phenotypes of Acutely Decompensated Cirrhosis
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Jonel Trebicka, Alex Amoros, Carla Pitarch, Esther Titos, José Alcaraz-Quiles, Robert Schierwagen, Carmen Deulofeu, Javier Fernandez-Gomez, Salvatore Piano, Paolo Caraceni, Karl Oettl, Elsa Sola, Wim Laleman, Jane McNaughtan, Rajeshwar P. Mookerjee, Minneke J. Coenraad, Tania Welzel, Christian Steib, Rita Garcia, Thierry Gustot, Miguel A. Rodriguez Gandia, Rafael Bañares, Agustin Albillos, Stefan Zeuzem, Victor Vargas, Faouzi Saliba, Frederic Nevens, Carlo Alessandria, Andrea de Gottardi, Heinz Zoller, Pere Ginès, Tilman Sauerbruch, Alexander Gerbes, Rudolf E. Stauber, Mauro Bernardi, Paolo Angeli, Marco Pavesi, Richard Moreau, Joan Clària, Rajiv Jalan, and Vicente Arroyo
- Subjects
acute decompensation ,cirrhosis ,signature ,ACLF ,organ failure ,organ dysfunction ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Background: Patients with acutely decompensated cirrhosis (AD) may or may not develop acute-on-chronic liver failure (ACLF). ACLF is characterized by high-grade systemic inflammation, organ failures (OF) and high short-term mortality. Although patients with AD cirrhosis exhibit distinct clinical phenotypes at baseline, they have low short-term mortality, unless ACLF develops during follow-up. Because little is known about the association of profile of systemic inflammation with clinical phenotypes of patients with AD cirrhosis, we aimed to investigate a battery of markers of systemic inflammation in these patients.Methods: Upon hospital admission baseline plasma levels of 15 markers (cytokines, chemokines, and oxidized albumin) were measured in 40 healthy controls, 39 compensated cirrhosis, 342 AD cirrhosis, and 161 ACLF. According to EASL-CLIF criteria, AD cirrhosis was divided into three distinct clinical phenotypes (AD-1: Creatinine
- Published
- 2019
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32. A bright triple transient that vanished within 50 minutes
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Solano, Enrique, Marcy, Geoffrey W., Villarroel, Beatriz, Geier, Stefan, Streblyanska, Alina, Lombardi, Gianluca, Bär, Rudolf E., and Andruk, Vitaly N.
- Subjects
Astrophysics - Solar and Stellar Astrophysics - Abstract
We report on three optically bright, ~15th mag, point-sources within 10 arcsec of each other that vanished within 1 hour, based on two consecutive exposures at Palomar Observatory on 1952 July 19 (POSS I Red and Blue). The three point-sources have continued to be absent in telescope exposures during 71 years with detection thresholds of ~21st mag. We obtained two deep exposures with the 10.4-m Gran Telescopio Canarias on 25 and 27 April 2023 in r and g-band, both reaching magnitude 25.5 (3-sigma). The three point-sources are still absent, implying they have dimmed by more than 10 magnitudes within an hour. When bright in 1952, the most isolated transient source has a profile nearly the same as comparison stars, implying the sources are sub-arcsec in angular size and they exhibit no elongation due to movement. This triple transient has observed properties similar to other cases where groups of transients ("multiple transients") have appeared and vanished in a small region within a plate exposure. The explanation for these three transients and the previously reported cases remains unclear. Models involving background objects that are optically luminous for less than one hour coupled with foreground gravitational lensing seem plausible. If so, a significant population of massive objects with structure serving as the lenses, to produce three images, are required to explain the hundreds of sub-hour transients., Comment: 9 pages, 7 figures. Submitted to MNRAS
- Published
- 2023
33. Hemidesmosome-Related Keratin Filament Bundling and Nucleation
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Marcin Moch and Rudolf E. Leube
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keratin intermediate filament ,hemidesmosome ,focal adhesion ,actin ,microtubule ,integrin beta 4 ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
The epithelial cytoskeleton encompasses actin filaments, microtubules, and keratin intermediate filaments. They are interconnected and attached to the extracellular matrix via focal adhesions and hemidesmosomes. To study their interplay, we inhibited actin and tubulin polymerization in the human keratinocyte cell line HaCaT by latrunculin B and nocodazole, respectively. Using immunocytochemistry and time-lapse imaging of living cells, we found that inhibition of actin and tubulin polymerization alone or in combination induced keratin network re-organization albeit differently in each situation. Keratin filament network retraction towards the nucleus and formation of bundled and radial keratin filaments was most pronounced in latrunculin-B treated cells but less in doubly-treated cells and not detectable in the presence of nocodazole alone. Hemidesmosomal keratin filament anchorage was maintained in each instance, whereas focal adhesions were disassembled in the absence of actin filaments. Simultaneous inhibition of actin and tubulin polymerization, therefore, allowed us to dissect hemidesmosome-specific functions for keratin network properties. These included not only anchorage of keratin filament bundles but also nucleation of keratin filaments, which was also observed in migrating cells. The findings highlight the fundamental role of hemidesmosomal adhesion for keratin network formation and organization independent of other cytoskeletal filaments pointing to a unique mechanobiological function.
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- 2021
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34. Identification of a Novel Link between the Intermediate Filament Organizer IFO-1 and Cholesterol Metabolism in the Caenorhabditis elegans Intestine
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Richard A. Coch, Florian Geisler, Andrea Annibal, Adam Antebi, and Rudolf E. Leube
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intestine ,Caenorhabditis elegans ,endotube ,cytoskeleton ,intermediate filament ,nuclear hormone receptor ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
The intestine is an organ essential to organismal nutrient absorption, metabolic control, barrier function and immunoprotection. The Caenorhabditis elegans intestine consists of 20 cells harboring a dense intermediate filament network positioned below the apical plasma membrane that forms a junction-anchored sheath around the intestinal lumen. This evolutionarily conserved arrangement provides mechanical and overall stress-protection, and it serves as an important model for deciphering the role of intestinal architecture in metazoan biology. We recently reported that the loss-of-function mutation of the intestinal intermediate filament organizer IFO-1 perturbs this architecture, leading to reduced body size and reproduction. Here, we demonstrate that the IFO-1 mutation dramatically affects cholesterol metabolism. Mutants showed an increased sensitivity to cholesterol depletion, reduced cholesterol uptake, and cholesterol transfer to the gonads, which is also observed in worms completely lacking an intermediate filament network. Accordingly, we found striking similarities to transcriptome and lipidome profiles of a nuclear hormone receptor (NHR)-8 mutant. NHR-8 is homologous to mammalian LXR (liver X receptor) that serves as a sterol sensor and transcriptional regulator of lipid metabolism. Remarkably, increasing exogenous cholesterol partially rescues the developmental retardation in IFO-1 mutants. Our results uncover a novel link of the intestinal intermediate filament cytoskeleton to cholesterol metabolism that contributes to compromised growth and reproduction.
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- 2020
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35. Changes in the Intestinal Microbiome during a Multispecies Probiotic Intervention in Compensated Cirrhosis
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Angela Horvath, Marija Durdevic, Bettina Leber, Katharina di Vora, Florian Rainer, Elisabeth Krones, Philipp Douschan, Walter Spindelboeck, Franziska Durchschein, Gernot Zollner, Rudolf E. Stauber, Peter Fickert, Philipp Stiegler, and Vanessa Stadlbauer
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gastrointestinal microbiome ,RNA ,ribosomal ,16S ,cirrhosis ,probiotics ,Nutrition. Foods and food supply ,TX341-641 - Abstract
Probiotics have been used in trials to therapeutically modulate the gut microbiome and have shown beneficial effects in cirrhosis. However, their effect on the microbiome of cirrhosis patients is not fully understood yet. Here, we tested the effects of a multispecies probiotic on microbiome composition in compensated cirrhosis. The gut microbiome composition of 58 patients with compensated cirrhosis from a randomized controlled trial who received a daily dose of multispecies probiotics or placebo for six months was analysed by 16S rRNA gene sequencing. Microbiome composition of patients who received probiotics was enriched with probiotic strains and the abundance of Faecalibacterium prausnitzii, Syntrophococcus sucromutans, Bacteroides vulgatus, Alistipes shahii and a Prevotella species was increased in the probiotic group compared to the placebo group. Patients who had microbiome changes in response to probiotic treatment also showed a significant increase in neopterin and a significant decrease in faecal zonulin levels after intervention, which was not observed in placebo-treated patients or patients with unchanged microbiome compositions. In conclusion, multispecies probiotics may enrich the microbiome of compensated cirrhotic patients with probiotic bacteria during a six-month intervention and beneficially change the residential microbiome and gut barrier function.
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- 2020
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36. BASS XXXV. The $M_\rm{BH}$-$\sigma_\rm{\star}$ Relation of 105-Month Swift-BAT Type 1 AGNs
- Author
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Caglar, Turgay, Koss, Michael J., Burtscher, Leonard, Trakhtenbrot, Benny, Erdim, M. Kiyami, Mejía-Restrepo, Julian E., Ricci, Federica, Powell, Meredith C., Ricci, Claudio, Mushotzky, Richard, Bauer, Franz E., Ananna, Tonima T., Bär, Rudolf E., Brandl, Bernhard, Brinchmann, Jarle, Harrison, Fiona, Ichikawa, Kohei, Kakkad, Darshan, Oh, Kyuseok, Riffel, Rogério, Sartori, Lia F., Smith, Krista L., Stern, Daniel, and Urry, C. Megan
- Subjects
Astrophysics - Astrophysics of Galaxies - Abstract
We present two independent measurements of stellar velocity dispersions ( $\sigma_\rm{\star}$ ) from the Ca\,H+K \& Mg\,\textsc{i} region (3880--5550~\AA) and the Calcium Triplet region (CaT, 8350--8750~\AA) for 173 hard X-ray-selected Type 1 AGNs ($z \leq$ 0.08) from the 105-month Swift-BAT catalog. We construct one of the largest samples of local Type 1 AGNs that have both single-epoch (SE) 'virial' black hole mass ($M_\rm{BH}$) estimates and $\sigma_\rm{\star}$ measurements obtained from high spectral resolution data, allowing us to test the usage of such methods for SMBH studies. We find that the two independent $\sigma_\rm{\star}$ measurements are highly consistent with each other, with an average offset of only $0.002\pm0.001$ dex. Comparing $M_\rm{BH}$ estimates based on broad emission lines and stellar velocity dispersion measurements, we find that the former is systematically lower by $\approx$0.12 dex. Consequently, Eddington ratios estimated through broad-line $M_\rm{BH}$ determinations are similarly biased (but in the opposite way). We argue that the discrepancy is driven by extinction in the broad-line region (BLR). We also find an anti-correlation between the offset from the $M_\rm{BH}$ - $\sigma_\rm{\star}$ relation and the Eddington ratio. Our sample of Type 1 AGNs shows a shallower $M_\rm{BH}$ - $\sigma_\rm{\star}$ relation (with a power law exponent of $\approx$3.5) compared with that of inactive galaxies (with a power-law exponent of $\approx$4.5), confirming earlier results obtained from smaller samples., Comment: Accepted by the ApJ
- Published
- 2023
37. SAT-129 Sub-optimal global public health policies and strategies to combat hepatocellular carcinoma
- Author
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Diaz, Luis Antonio, Norero, Blanca, Corsi, Oscar, Ayares, Gustavo, Idalsoaga, Francisco, García, Sergio, Vázquez, Valeria, Lacalle, Lucas, Lazo, Mariana, Ferreccio, Catterina, Mendizabal, Manuel, Piñero, Federico, Martinez, Edmundo, Ijeoma, Ifeorah, Louvet, Alexandre, Piano, Salvatore, Cortez-Pinto, Helena, Wong, Vincent Wai-Sun, Kulkarni, Anand, Cotter, Thomas, Brahmania, Mayur, roblero, Juan Pablo, Dirchwolf, Melisa, Pollarsky, Florencia, George, Jacob, Stauber, Rudolf E, Francque, Sven, Guerra, Patricia, Oliveira, Claudia, Araujo, Roberta, Álvares-da-Silva, Mario, Blaise, Nkegoum, Abraldes, Juan G, Zheng, Ming-Hua, Toro, Luis, Restrepo, Juan Carlos, Ramirez, Wagner, Grgurević, Ivica, Infante, Mirtha, Mbendi, Charles, Carrera, Enrique, Kassas, Mohamed El, Mahmoud, Abdelmajeed, Tesfaye, Yonas Gedamu, Tadesse, Sewale Anagaw, Akalu, Tiruwork Fekadu, Desalegn, Hailemichael, Allaire, Manon, Patrizia, Carrieri, Schattenberg, Jörn, Aguyire, Joan, Micah, Eileen Akonobea, Tachi, Kenneth, Cardona, Katherine Emilia Maldonado, Sanchez, Abel, Sánchez, Marco, Björnsson, Einar S, Iavarone, Massimo, Okamoto, Ryuichi, Some, Fatuma, Hellani, Mohammad Fadel, Gonzalez, Veronica Enith Prado, Chávez-Tapia, Norberto Carlos, Méndez-Sánchez, Nahum, Mucumbi, Sheila Constância Mabote, Ugiagbe, Rose Ashinedu, Akande, Kolawole, Nwoko, Chinenye, Ezenkwa, Uchenna Simon, Okoye, Ifeoma Joy, Hamid, Saeed Sadiq, Quezada, Julissa Lombardo, Girala, Marcos, Padilla, P Martin, Diaz-Ferrer, Javier, Tagle, Martin, Kukla, Michał, Odeghe, Emuobor, wemimo, Rasheed mumini, Reis, Daniela, Mozgovoi, Sergei, Ismail, Mona, Koller, Tomas, Spearman, Wendy, Elhassan, Moawia, Stal, Per, Pazi, Swaleh, Ocanit, Anthony, Masson, Steven, Dunn, Winston, Kamath, Patrick S, Singal, Ashwani, Debes, Jose, Reig, María, Loomba, Rohit, Bataller, Ramon, Lazarus, Jeffrey, Arrese, Marco, and Arab, Juan Pablo
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Biomedical and Clinical Sciences ,Clinical Sciences ,Public Health and Health Services ,Gastroenterology & Hepatology ,Clinical sciences - Published
- 2023
38. Effects of Plectin Depletion on Keratin Network Dynamics and Organization.
- Author
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Marcin Moch, Reinhard Windoffer, Nicole Schwarz, Raphaela Pohl, Andreas Omenzetter, Uwe Schnakenberg, Fabian Herb, Kraisorn Chaisaowong, Dorit Merhof, Lena Ramms, Gloria Fabris, Bernd Hoffmann, Rudolf Merkel, and Rudolf E Leube
- Subjects
Medicine ,Science - Abstract
The keratin intermediate filament cytoskeleton protects epithelial cells against various types of stress and is involved in fundamental cellular processes such as signaling, differentiation and organelle trafficking. These functions rely on the cell type-specific arrangement and plasticity of the keratin system. It has been suggested that these properties are regulated by a complex cycle of assembly and disassembly. The exact mechanisms responsible for the underlying molecular processes, however, have not been clarified. Accumulating evidence implicates the cytolinker plectin in various aspects of the keratin cycle, i.e., by acting as a stabilizing anchor at hemidesmosomal adhesion sites and the nucleus, by affecting keratin bundling and branching and by linkage of keratins to actin filament and microtubule dynamics. In the present study we tested these hypotheses. To this end, plectin was downregulated by shRNA in vulvar carcinoma-derived A431 cells. As expected, integrin β4- and BPAG-1-positive hemidesmosomal structures were strongly reduced and cytosolic actin stress fibers were increased. In addition, integrins α3 and β1 were reduced. The experiments furthermore showed that loss of plectin led to a reduction in keratin filament branch length but did not alter overall mechanical properties as assessed by indentation analyses using atomic force microscopy and by displacement analyses of cytoplasmic superparamagnetic beads using magnetic tweezers. An increase in keratin movement was observed in plectin-depleted cells as was the case in control cells lacking hemidesmosome-like structures. Yet, keratin turnover was not significantly affected. We conclude that plectin alone is not needed for keratin assembly and disassembly and that other mechanisms exist to guarantee proper keratin cycling under steady state conditions in cultured single cells.
- Published
- 2016
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39. Triple Therapy with First Generation Protease Inhibitors for Hepatitis C Markedly Impairs Function of Neutrophil Granulocytes.
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Walter Spindelboeck, Angela Horvath, Monika Tawdrous, Bianca Schmerböck, Gabriele Zettel, Andreas Posch, Andrea Streit, Petra Jurse, Sandra Lemesch, Martin Horn, Gerit Wuensch, Philipp Stiegler, Rudolf E Stauber, Bettina Leber, and Vanessa Stadlbauer
- Subjects
Medicine ,Science - Abstract
First-generation HCV protease inhibitors represent a milestone in antiviral therapy for chronic hepatitis C infection (CHC), but substantially increased rates of viral clearance are offset by increased rates of infection and infection-associated deaths, especially of patients with advanced liver disease. We aimed to assess whether first generation protease inhibitors interfere with neutrophil function. We included 108 consecutive, retrospective CHC patients and 44 consecutive, prospective CHC patients who were treated with peginterferon and ribavirin with or without protease inhibitors according to the guidelines in the period of November 2012 to June 2015. 33 healthy volunteers served as controls. Infection data were evaluated in all patients. Neutrophil phagocytosis, oxidative burst, elastase and diamine oxidase levels during 12 weeks of triple (n = 23) or dual therapy (n = 21) were studied in the prospective part. In the retro- and prospective cohorts patients experiencing clinically relevant infections were significantly more frequent during protease inhibitor therapy (31% and 26%) than during therapy with peginterferon and ribavirin (13% and 0%). Neutrophil phagocytosis decreased to 40% of baseline with addition of protease inhibitors to P/R but recovered 6 months after end of treatment. Protease inhibitors also seemed to reduce serum elastase levels but did not impact on gut permeability. Impaired neutrophil function during triple therapy with first generation HCV protease inhibitors may explain the high infection rate associated to these treatments and be of relevance for treatment success and patient survival.
- Published
- 2016
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40. Keratin dynamics: modeling the interplay between turnover and transport.
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Stéphanie Portet, Anotida Madzvamuse, Andy Chung, Rudolf E Leube, and Reinhard Windoffer
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Medicine ,Science - Abstract
Keratin are among the most abundant proteins in epithelial cells. Functions of the keratin network in cells are shaped by their dynamical organization. Using a collection of experimentally-driven mathematical models, different hypotheses for the turnover and transport of the keratin material in epithelial cells are tested. The interplay between turnover and transport and their effects on the keratin organization in cells are hence investigated by combining mathematical modeling and experimental data. Amongst the collection of mathematical models considered, a best model strongly supported by experimental data is identified. Fundamental to this approach is the fact that optimal parameter values associated with the best fit for each model are established. The best candidate among the best fits is characterized by the disassembly of the assembled keratin material in the perinuclear region and an active transport of the assembled keratin. Our study shows that an active transport of the assembled keratin is required to explain the experimentally observed keratin organization.
- Published
- 2015
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41. BASS XXVI: DR2 Host Galaxy Stellar Velocity Dispersions
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Koss, Michael J., Trakhtenbrot, Benny, Ricci, Claudio, Oh, Kyuseok, Bauer, Franz E., Stern, Daniel, Caglar, Turgay, Brok, Jakob S. den, Mushotzky, Richard, Ricci, Federica, Mejia-Restrepo, Julian E., Lamperti, Isabella, Treister, Ezequiel, Bar, Rudolf E., Harrison, Fiona, Powell, Meredith C., Privon, George C., Riffel, Rogerio, Rojas, Alejandra F., Schawinski, Kevin, and Urry, C. Megan
- Subjects
Astrophysics - Astrophysics of Galaxies ,Astrophysics - High Energy Astrophysical Phenomena - Abstract
We present new central stellar velocity dispersions for 484 Sy 1.9 and Sy 2 from the second data release of the Swift/BAT AGN Spectroscopic Survey (BASS DR2). This constitutes the largest study of velocity dispersion measurements in X-ray selected, obscured AGN with 956 independent measurements of the Ca H+K and Mg b region (3880-5550A) and the Ca triplet region (8350-8730A) from 642 spectra mainly from VLT/Xshooter or Palomar/DoubleSpec. Our sample spans velocity dispersions of 40-360 km/s, corresponding to 4-5 orders of magnitude in black holes mass (MBH=10^5.5-9.6 Msun), bolometric luminosity (LBol~10^{42-46 ergs/s), and Eddington ratio (L/Ledd~10^{-5}-2). For 281 AGN, our data provide the first published central velocity dispersions, including 6 AGN with low mass black holes (MBH=10^5.5-6.5 Msun), discovered thanks to our high spectral resolution observations (sigma~25 km/s). The survey represents a significant advance with a nearly complete census of hard-X-ray selected obscured AGN with measurements for 99% of nearby AGN (z<0.1) outside the Galactic plane. The BASS AGN have higher velocity dispersions than the more numerous optically selected narrow line AGN (i.e., ~150 vs. ~100 km/s), but are not biased towards the highest velocity dispersions of massive ellipticals (i.e., >250 km/s). Despite sufficient spectral resolution to resolve the velocity dispersions associated with the bulges of small black holes (~10^4-5 Msun), we do not find a significant population of super-Eddington AGN. Using estimates of the black hole sphere of influence, direct stellar and gas black hole mass measurements could be obtained with existing facilities for more than ~100 BASS AGN., Comment: 32 pages, 16 figures, 8 tables, published in ApJS as part of BASS DR2 special issue
- Published
- 2022
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- View/download PDF
42. BASS XXII: The BASS DR2 AGN Catalog and Data
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Koss, Michael J., Ricci, Claudio, Trakhtenbrot, Benny, Oh, Kyuseok, Brok, Jakob S. den, Mejia-Restrepo, Julian E., Stern, Daniel, Privon, George C., Treister, Ezequiel, Powell, Meredith C., Mushotzky, Richard, Bauer, Franz E., Ananna, Tonima T., Balokovic, Mislav, Bar, Rudolf E., Becker, George, Bessiere, Patricia, Burtscher, Leonard, Caglar, Turgay, Congiu, Enrico, Evans, Phil, Harrison, Fiona, Heida, Marianne, Ichikawa, Kohei, Kamraj, Nikita, Lamperti, Isabella, Pacucci, Fabio, Ricci, Federica, Riffel, Rogerio, Rojas, Alejandra F., Schawinski, Kevin, Temple, Matthew, Urry, C. Megan, Veilleux, Sylvain, and Williams, Jonathan
- Subjects
Astrophysics - Astrophysics of Galaxies ,Astrophysics - High Energy Astrophysical Phenomena - Abstract
We present the AGN catalog and optical spectroscopy for the second data release of the Swift BAT AGN Spectroscopic Survey (BASS DR2). With this DR2 release we provide 1425 optical spectra, of which 1181 are released for the first time, for the 858 hard X-ray selected AGN in the Swift BAT 70-month sample. The majority of the spectra (813/1425, 57%) are newly obtained from VLT/Xshooter or Palomar/Doublespec. Many of the spectra have both higher resolution (R>2500, N~450) and/or very wide wavelength coverage (3200-10000 A, N~600) that are important for a variety of AGN and host galaxy studies. We include newly revised AGN counterparts for the full sample and review important issues for population studies, with 44 AGN redshifts determined for the first time and 780 black hole mass and accretion rate estimates. This release is spectroscopically complete for all AGN (100%, 858/858) with 99.8% having redshift measurements (857/858) and 96% completion in black hole mass estimates of unbeamed AGN (outside the Galactic plane). This AGN sample represents a unique census of the brightest hard X-ray selected AGN in the sky, spanning many orders of magnitude in Eddington ratio (Ledd=10^-5-100), black hole mass (MBH=10^5-10^10 Msun), and AGN bolometric luminosity (Lbol=10^40-10^47 ergs/s)., Comment: 34 pages, 11 figures, 15 tables, published in ApJS as part of BASS DR2 special issue
- Published
- 2022
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43. Is there a background population of high-albedo objects in geosynchronous orbits around Earth?
- Author
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Villarroel, Beatriz, Solano, Enrique, Guergouri, Hichem, Streblyanska, Alina, Mattsson, Lars, Bär, Rudolf E., Mimouni, Jamal, Geier, Stefan, Gupta, Alok C., Okororie, Vanessa, Laggoune, Khaoula, Shultz, Matthew E., Freitas Jr., Robert A., and Ward, Martin J.
- Subjects
Astrophysics - Earth and Planetary Astrophysics ,Astrophysics - Instrumentation and Methods for Astrophysics - Abstract
Old, digitized astronomical images taken before the human spacefaring age offer a unique view of the sky devoid of known artificial satellites. In this paper, we have carried out the first optical searches ever for non-terrestrial artifacts near the Earth following the method proposed in Villarroel et al. (2022). We use images contained in the First Palomar Sky Survey to search for simultaneous (during a plate exposure time) transients that in addition to being point-like, are aligned. We provide a shortlist of the most promising candidates of aligned transients, that must be examined with the help of a microscope to separate celestial sources from plate defects with coincidentally star-like brightness profiles. We further explore one possible, but not unique, interpretation in terms of fast reflections off high-albedo objects in geosynchronous orbits around Earth. If a future study rules out each multiple transient candidate, the estimated surface density becomes an upper limit of $<10^{-9}$ objects km$^{-2}$ non-terrestrial artifacts in geosynchronous orbits around Earth. Finally, we conclude that observations and analysis of multiple, simultaneously appearing and vanishing light sources on the sky merit serious further attention, regardless of their origin., Comment: Submitted to Astronomical Journal
- Published
- 2022
44. BASS XXV: DR2 Broad-line Based Black Hole Mass Estimates and Biases from Obscuration
- Author
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Mejıa-Restrepo, Julian E., Trakhtenbrot, Benny, Koss, Michael J., Oh, Kyuseok, Brok, Jakob den, Stern, Daniel, Powell, Meredith C., Ricci, Federica, Caglar, Turgay, Ricci, Claudio, Bauer, Franz E., Treister, Ezequiel, Harrison, Fiona A., Urry, C. M., Ananna, Tonima Tasnim, Asmus, Daniel, Assef, Roberto J., Bar, Rudolf E., Bessiere, Patricia S., Burtscher, Leonard, Ichikawa, Kohei, Kakkad, Darshan, Kamraj, Nikita, Mushotzky, Richard, Privon, George C., Rojas, Alejandra F., Sani, Eleonora, Schawinski, Kevin, and Veilleux, Sylvain
- Subjects
Astrophysics - Astrophysics of Galaxies - Abstract
We present measurements of broad emission lines and virial estimates of supermassive black hole masses ($M_{BH}$) for a large sample of ultra-hard X-ray selected active galactic nuclei (AGNs) as part of the second data release of the BAT AGN Spectroscopic Survey (BASS/DR2). Our catalog includes $M_{BH}$ estimates for a total 689 AGNs, determined from the H$\alpha$, H$\beta$, $MgII\lambda2798$, and/or $CIV\lambda1549$ broad emission lines. The core sample includes a total of 512 AGNs drawn from the 70-month Swift/BAT all-sky catalog. We also provide measurements for 177 additional AGNs that are drawn from deeper Swift/BAT survey data. We study the links between $M_{BH}$ estimates and line-of-sight obscuration measured from X-ray spectral analysis. We find that broad H$\alpha$ emission lines in obscured AGNs ($\log (N_{\rm H}/{\rm cm}^{-2})> 22.0$) are on average a factor of $8.0_{-2.4}^{+4.1}$ weaker, relative to ultra-hard X-ray emission, and about $35_{-12}^{~+7}$\% narrower than in unobscured sources (i.e., $\log (N_{\rm H}/{\rm cm}^{-2}) < 21.5$). This indicates that the innermost part of the broad-line region is preferentially absorbed. Consequently, current single-epoch $M_{BH}$ prescriptions result in severely underestimated ($>$1 dex) masses for Type 1.9 sources (AGNs with broad H$\alpha$ but no broad H$\beta$) and/or sources with $\log (N_{\rm H}/{\rm cm}^{-2}) > 22.0$. We provide simple multiplicative corrections for the observed luminosity and width of the broad H$\alpha$ component ($L[{\rm b}{\rm H}\alpha]$ and FWHM[bH$\alpha$]) in such sources to account for this effect, and to (partially) remedy $M_{BH}$ estimates for Type 1.9 objects. As key ingredient of BASS/DR2, our work provides the community with the data needed to further study powerful AGNs in the low-redshift Universe., Comment: published in ApJS
- Published
- 2022
- Full Text
- View/download PDF
45. BASS XXIV: The BASS DR2 Spectroscopic Line Measurements and AGN Demographics
- Author
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Oh, Kyuseok, Koss, Michael J., Ueda, Yoshihiro, Stern, Daniel, Ricci, Claudio, Trakhtenbrot, Benny, Powell, Meredith C., Brok, Jakob S. Den, Lamperti, Isabella, Mushotzky, Richard, Ricci, Federica, Bär, Rudolf E., Rojas, Alejandra F., Ichikawa, Kohei, Riffel, Rogerio, Treister, Ezequiel, Harrison, Fiona, Urry, C. Megan, Bauer, Franz E., and Schawinski, Kevin
- Subjects
Astrophysics - Astrophysics of Galaxies - Abstract
We present the second catalog and data release of optical spectral line measurements and AGN demographics of the BAT AGN Spectroscopic Survey, which focuses on the of Swift-BAT hard X-ray detected AGNs. We use spectra from dedicated campaigns and publicly available archives to investigate spectral properties of most of the AGNs listed in the 70-month Swift-BAT all-sky catalog; specifically, 743 of the 746 unbeamed and unlensed AGNs (99.6%). We find a good correspondence between the optical emission line widths and the hydrogen column density distributions using the X-ray spectra, with a clear dichotomy of AGN types for NH = 10^22 cm-2. Based on optical emission-line diagnostics, we show that 48%-75% of BAT AGNs are classified as Seyfert, depending on the choice of emission lines used in the diagnostics. The fraction of objects with upper limits on line emission varies from 6% to 20%. Roughly 4% of the BAT AGNs have lines too weak to be placed on the most commonly used diagnostic diagram, [O III]{\lambda}5007/H\b{eta} versus [N II]{\lambda}6584/H{\alpha}, despite the high signal-to-noise ratio (S/N) of their spectra. This value increases to 35% in the [O III]{\lambda}5007/[O II]{\lambda}3727 diagram, owing to difficulties in line detection. Compared to optically-selected narrow-line AGNs in the Sloan Digital Sky Survey, the BAT narrow-line AGNs have a higher rate of reddening/extinction, with H{\alpha}/H\b{eta} > 5 (~ 36%), indicating that hard X-ray selection more effectively detects obscured AGNs from the underlying AGN population. Finally, we present a subpopulation of AGNs that feature complex broad-lines (34%, 250/743) or double-peaked narrow emission lines (2%, 17/743)., Comment: 30 pages, 17 figures, 11 tables, accepted for publication in ApJS; part of BASS DR2 special issue
- Published
- 2022
- Full Text
- View/download PDF
46. Pleuro-Pulmonary Nocardiosis as Opportunistic Infection in a Patient with Chronic Hepatitis C under Combination Treatment with Pegylated Interferon, Ribavirin, and Boceprevir
- Author
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Csilla Putz-Bankuti, Harald H. Kessler, Thomas Valentin, Eva Leitner, Emina Talakic, Helmut Schoellnast, Peter Fickert, Guenter J. Krejs, and Rudolf E. Stauber
- Subjects
Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Nocardiosis is an infrequent but serious pulmonary infection caused by Gram-positive aerobic actinomycetes. In this paper, we report on a 48-year-old patient with pleuropulmonary nocardiosis and cirrhosis due to chronic hepatitis C virus infection treated with triple antiviral treatment complicated by prolonged neutropenia.
- Published
- 2013
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47. Intermediate Filaments and Polarization in the Intestinal Epithelium
- Author
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Richard A. Coch and Rudolf E. Leube
- Subjects
keratin ,cytokeratin ,endotube ,brush border ,C. elegans apical junction ,desmosome ,γ-tubulin ring complex ,atypical protein kinase C ,PAR proteins ,Cytology ,QH573-671 - Abstract
The cytoplasmic intermediate filament cytoskeleton provides a tissue-specific three-dimensional scaffolding with unique context-dependent organizational features. This is particularly apparent in the intestinal epithelium, in which the intermediate filament network is localized below the apical terminal web region and is anchored to the apical junction complex. This arrangement is conserved from the nematode Caenorhabditis elegans to humans. The review summarizes compositional, morphological and functional features of the polarized intermediate filament cytoskeleton in intestinal cells of nematodes and mammals. We emphasize the cross talk of intermediate filaments with the actin- and tubulin-based cytoskeleton. Possible links of the intermediate filament system to the distribution of apical membrane proteins and the cell polarity complex are highlighted. Finally, we discuss how these properties relate to the establishment and maintenance of polarity in the intestine.
- Published
- 2016
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- View/download PDF
48. Intermediate Filaments as Organizers of Cellular Space: How They Affect Mitochondrial Structure and Function
- Author
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Nicole Schwarz and Rudolf E. Leube
- Subjects
mitochondrion ,mitochondria-associated membrane ,intermediate filament ,neurofilament ,desmin ,keratin ,vimentin ,Cytology ,QH573-671 - Abstract
Intermediate filaments together with actin filaments and microtubules form the cytoskeleton, which is a complex and highly dynamic 3D network. Intermediate filaments are the major mechanical stress protectors but also affect cell growth, differentiation, signal transduction, and migration. Using intermediate filament-mitochondrial crosstalk as a prominent example, this review emphasizes the importance of intermediate filaments as crucial organizers of cytoplasmic space to support these functions. We summarize observations in different mammalian cell types which demonstrate how intermediate filaments influence mitochondrial morphology, subcellular localization, and function through direct and indirect interactions and how perturbations of these interactions may lead to human diseases.
- Published
- 2016
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49. Epithelial Intermediate Filaments: Guardians against Microbial Infection?
- Author
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Florian Geisler and Rudolf E. Leube
- Subjects
epithelium ,keratin ,barrier ,pathogen ,virus ,bacterium ,parasite ,Caenorhabditis elegans ,Cytology ,QH573-671 - Abstract
Intermediate filaments are abundant cytoskeletal components of epithelial tissues. They have been implicated in overall stress protection. A hitherto poorly investigated area of research is the function of intermediate filaments as a barrier to microbial infection. This review summarizes the accumulating knowledge about this interaction. It first emphasizes the unique spatial organization of the keratin intermediate filament cytoskeleton in different epithelial tissues to protect the organism against microbial insults. We then present examples of direct interaction between viral, bacterial, and parasitic proteins and the intermediate filament system and describe how this affects the microbe-host interaction by modulating the epithelial cytoskeleton, the progression of infection, and host response. These observations not only provide novel insights into the dynamics and function of intermediate filaments but also indicate future avenues to combat microbial infection.
- Published
- 2016
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50. Effects of Vitamin D Supplementation on Serum 25-Hydroxyvitamin D Concentrations in Cirrhotic Patients: A Randomized Controlled Trial
- Author
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Stefan Pilz, Csilla Putz-Bankuti, Martin Gaksch, Walter Spindelboeck, Marius Haselberger, Florian Rainer, Andreas Posch, Philipp Kreuzer, Tatjana Stojakovic, Vanessa Stadlbauer, Barbara Obermayer-Pietsch, and Rudolf E. Stauber
- Subjects
vitamin D ,RCT ,supplementation ,intervention ,liver ,Nutrition. Foods and food supply ,TX341-641 - Abstract
Background: The liver is crucial for 25-hydroxyvitamin D (25(OH)D) metabolism, and vitamin D deficiency is highly prevalent in patients with cirrhosis and predicts adverse outcomes. We aimed to evaluate whether vitamin D supplementation in patients with cirrhosis is effective in increasing 25(OH)D serum concentrations. Secondary outcome measures included liver function tests (aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyltransferase (GGT), and alkaline phosphatase (AP)), albumin, International Normalized Ratio (INR), bilirubin, the liver fibrosis marker hyaluronic acid, and parameters of mineral metabolism including parathyroid hormone (PTH). Methods: This is a double-center, double-blind, placebo-controlled study conducted from December 2013 to May 2014 at the Medical University of Graz, and the hospital Hoergas-Enzenbach, Austria. We enrolled 36 consecutive patients with cirrhosis and 25(OH)D concentrations below 30 ng/mL. Study participants were randomly allocated to receive either 2800 International Units of vitamin D3 per day as oily drops (n = 18) or placebo (n = 18) for 8 weeks. Results: Thirty-three study participants (mean (SD) age: 60 (9) years; 21% females; 25(OH)D: 15.6 (7.4) ng/mL) completed the trial. The mean treatment effect (95% CI) for 25(OH)D was 15.2 (8.0 to 22.4) ng/mL (p < 0.001). There was no significant effect on any secondary outcome. Conclusions: In this randomized controlled trial, vitamin D supplementation increases 25(OH)D serum concentrations, even in cirrhotic patients.
- Published
- 2016
- Full Text
- View/download PDF
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