Now showing items 21-40 of 4086

    • PD-L1 Checkpoint Inhibition Narrows the Antigen-Specific T Cell Receptor Repertoire in Chronic Lymphocytic Choriomeningitis Virus Infection.

      Klein, S; Ghersi, D; Manns, M P; Prinz, I; Cornberg, M; Kraft, A R M (American Society for Microbiology, 2020-08-31)
      Checkpoint inhibitors are effective in restoring exhausted CD8+ T cell responses in persistent viral infections or tumors. Several compounds are in clinical use for different malignancies, but trials in patients with chronic viral infections have also been conducted. In a mouse model of persistent lymphocytic choriomeningitis virus (LCMV) infection, it was shown that checkpoint inhibitor treatment increased T cell proliferation and functionality, but its influence on the antigen-specific T cell receptor (TCR) repertoire is unknown. NP396-specific CD8+ T cells dominate during acute LCMV infection and are predominantly exhausted during chronic infection. Next-generation sequencing of NP396-specific TCRs showed that exhaustion corresponds with a significantly reduced NP396-specific TCR repertoire diversity: Shannon indices of 4 in immunized mice to 2.6 in persistently infected mice. Anti-PD-L1 treatment during persistent LCMV infection restored NP396-specific T cell responses and reduced viral titers. Nevertheless, anti-PD-L1-treated mice showed an even more narrowed TCR repertoire, with reduced TCR diversity compared to that of persistently infected control mice (Shannon indices of 2.1 and 2.6, respectively). Interestingly, anti-PD-L1 treatment-induced narrowing of the TCR repertoire negatively correlates with functional and physical restoration of the antigen-specific T cell response. Further, we found that private, hyperexpanded TCR clonotypes dominated the T cell response after anti-PD-L1 treatment. Although being private, these top clonotypes from anti-PD-L1-treated mice revealed a more closely related CDR3 motif than those of top clonotypes from persistently infected control mice. In conclusion, although targeting the PD-1/PD-L1 pathway reinvigorates exhausted CD8+ T cells, it fails to restore T cell repertoire diversity.IMPORTANCE Checkpoint inhibitors are effective immunotherapeutics to restore cancer- and virus-induced exhausted CD8+ T cells, by enhancing the quality and survival of immune responses. Although checkpoint inhibitors are already used as therapy against various cancers, not much is known about their multifaceted impact on the exhausted CD8+ T cell receptor (TCR) repertoire. This report describes for the first time the evolvement of an exhausted antigen-specific CD8+ TCR repertoire under checkpoint inhibitor treatment. By using a well-established virus model, we were able to show major shifts toward oligoclonality of the CD8+ TCR repertoire response against a massively exhausted lymphocytic choriomeningitis virus (LCMV) epitope. While supporting viral control in the LCMV model, oligoclonality and more private of TCR repertoires may impact future pathogenic challenges and may promote viral escape. Our results may explain the ongoing problems of viral escapes, unpredictable autoimmunity, and heterogeneous responses appearing as adverse effects of checkpoint inhibitor treatments.
    • A minimal modeling framework of radiation and immune system synergy to assist radiotherapy planning.

      Montaseri, Ghazal; Alfonso, Juan Carlos López; Hatzikirou, Haralampos; Meyer-Hermann, Michael (Elsevier, 2020-02-07)
    • Cows selected for divergent mastitis susceptibility display a differential liver transcriptome profile after experimental Staphylococcus aureus mammary gland inoculation.

      Heimes, A; Brodhagen, J; Weikard, R; Becker, D; Meyerholz, M M; Petzl, W; Zerbe, H; Schuberth, H-J; Hoedemaker, M; Schmicke, M; et al. (Elsevier, 2020-04-16)
      Infection and inflammation of the mammary gland, and especially prevention of mastitis, are still major challenges for the dairy industry. Different approaches have been tried to reduce the incidence of mastitis. Genetic selection of cows with lower susceptibility to mastitis promises sustainable success in this regard. Bos taurus autosome (BTA) 18, particularly the region between 43 and 59 Mb, harbors quantitative trait loci (QTL) for somatic cell score, a surrogate trait for mastitis susceptibility. Scrutinizing the molecular bases hereof, we challenged udders from half-sib heifers having inherited either favorable paternal haplotypes for somatic cell score (Q) or unfavorable haplotypes (q) with the Staphylococcus aureus pathogen. RNA sequencing was used for an in-depth analysis of challenge- related alterations in the hepatic transcriptome. Liver exerts highly relevant immune functions aside from being the key metabolic organ. Hence, a holistic approach focusing on the liver enabled us to identify challenge-related and genotype-dependent differentially expressed genes and underlying regulatory networks. In response to the S. aureus challenge, we found that heifers with Q haplotypes displayed more activated immune genes and pathways after S. aureus challenge compared with their q half-sibs. Furthermore, we found a significant enrichment of differentially expressed loci in the genomic target region on BTA18, suggesting the existence of a regionally acting regulatory element with effects on a variety of genes in this region.
    • A Probabilistic Cohort-Component Model for Population Forecasting – The Case of Germany

      Vanella, Patrizio; Deschermeier, Philipp (Springer Science and Business Media LLC, 2020-01-02)
    • Naive- and Memory-like CD21 B Cell Subsets Share Core Phenotypic and Signaling Characteristics in Systemic Autoimmune Disorders.

      Freudenhammer, Mirjam; Voll, Reinhard E; Binder, Sebastian C; Keller, Baerbel; Warnatz, Klaus (2020-09-09)
      An expansion of CD21low B cells has been described in a variety of diseases associated with persistent immune stimulation as in chronic infection, immunodeficiency, or autoimmunity. Different developmental stages of CD21low B cells have been highlighted in specific diseases; however, a systematic comparison of distribution, phenotype, and signaling capacity of these populations has not yet been performed to delineate the pivotal character of this unusual B cell population. Screening of more than 200 patients with autoimmune disease demonstrated that the prevalence of patients with expanded CD21low B cells varies between diseases. The expansion was frequent in patients with systemic lupus erythematosus, in which it correlated to relative B cell lymphopenia and duration of disease. Different proportions of distinct developmental stages of CD21low B cells co-occur in nearly all patients with autoimmune disease. Although in most patients, naive-like and CD27- switched memory B cells were the most prominent CD21low subpopulations, there was no detectable association of the pattern with the underlying disease. Despite their distinct developmental stage, all CD21low B cells share a common core phenotype including the increased expression of inhibitory receptors, associated with an elevated constitutive phosphorylation of proximal signaling molecules downstream of the BCR but impaired Ca2+ mobilization and NF-κB activation after BCR stimulation. Further, this was accompanied by impaired upregulation of CD69, although CD86 upregulation was preserved. Beyond maturation-associated differences, the common core characteristics of all CD21low B cell populations suggests either a common ancestry or a shared sustained imprint by the environment they originated in.
    • C19orf66 is an interferon-induced inhibitor of HCV replication that restricts formation of the viral replication organelle.

      Kinast, Volker; Plociennikowska, Agnieszka; Anggakusuma; Bracht, Thilo; Todt, Daniel; Brown, Richard J P; Boldanova, Tujana; Zhang, Yudi; Brüggemann, Yannick; Friesland, Martina; et al. (Elsevier, 2020-04-12)
    • Contiguous Quaternary Carbons: A Selection of Total Syntheses.

      Eggert, Alina; Etling, Christoph; Lübken, Dennis; Saxarra, Marius; Kalesse, Markus (2020-08-24)
      Contiguous quaternary carbons in terpene natural products remain a major challenge in total synthesis. Synthetic strategies to overcome this challenge will be a pivotal prerequisite to the medicinal application of natural products and their analogs or derivatives. In this review, we cover syntheses of natural products that exhibit a dense assembly of quaternary carbons and whose syntheses were uncompleted until recently. While discussing their syntheses, we not only cover the most recent total syntheses but also provide an update on the status quo of modern syntheses of complex natural products. Herein, we review (±)-canataxpropellane, (+)-waihoensene, (-)-illisimonin A and (±)-11-O-debenzoyltashironin as prominent examples of natural products bearing contiguous quaternary carbons.
    • Characteristics of Genome of Bacillus velezensis ONU 553 Strain Isolated from the Bottom Sediments of the Black Sea

      Shtenikov, M.D.; Ostapchuk, A.M.; Vasylieva, N.Y.; Luzhetskyy, A.M.; Rückert, C.; Kalinowski, J.; Ivanytsia, V.О. (National Academy of Sciences of Ukraine (Co. LTD Ukrinformnauka), 2020-06-17)
    • The Quantitative Proteome of the Cement and Adhesive Gland of the Pedunculate Barnacle, pollicipes pollicipes.

      Domínguez-Pérez, Dany; Almeida, Daniela; Wissing, Josef; Machado, André M; Jänsch, Lothar; Castro, Luís Filipe; Antunes, Agostinho; Vasconcelos, Vitor; Campos, Alexandre; Cunha, Isabel (MDPI, 2020-04-05)
      Adhesive secretion has a fundamental role in barnacles' survival, keeping them in an adequate position on the substrate under a variety of hydrologic regimes. It arouses special interest for industrial applications, such as antifouling strategies, underwater industrial and surgical glues, and dental composites. This study was focused on the goose barnacle Pollicipes pollicipes adhesion system, a species that lives in the Eastern Atlantic strongly exposed intertidal rocky shores and cliffs. The protein composition of P. pollicipes cement multicomplex and cement gland was quantitatively studied using a label-free LC-MS high-throughput proteomic analysis, searched against a custom transcriptome-derived database. Overall, 11,755 peptide sequences were identified in the gland while 2880 peptide sequences were detected in the cement, clustered in 1616 and 1568 protein groups, respectively. The gland proteome was dominated by proteins of the muscle, cytoskeleton, and some uncharacterized proteins, while the cement was, for the first time, reported to be composed by nearly 50% of proteins that are not canonical cement proteins, mainly unannotated proteins, chemical cues, and protease inhibitors, among others. Bulk adhesive proteins accounted for one-third of the cement proteome, with CP52k being the most abundant. Some unannotated proteins highly expressed in the proteomes, as well as at the transcriptomic level, showed similar physicochemical properties to the known surface-coupling barnacle adhesive proteins while the function of the others remains to be discovered. New quantitative and qualitative clues are provided to understand the diversity and function of proteins in the cement of stalked barnacles, contributing to the whole adhesion model in Cirripedia.
    • Non-Typeable Invade Choroid Plexus Epithelial Cells in a Polar Fashion.

      Wegele, Christian; Stump-Guthier, Carolin; Moroniak, Selina; Weiss, Christel; Rohde, Manfred; Ishikawa, Hiroshi; Schroten, Horst; Schwerk, Christian; Karremann, Michael; Borkowski, Julia (MDPI, 2020-08-10)
      Non-typeable Haemophilus influenzae (NTHI) is a pathogen of the human respiratory tract causing the majority of invasive H. influenzae infections. Severe invasive infections such as septicemia and meningitis occur rarely, but the lack of a protecting vaccine and the increasing antibiotic resistance of NTHI impede treatment and emphasize its relevance as a potential meningitis causing pathogen. Meningitis results from pathogens crossing blood-brain barriers and invading the immune privileged central nervous system (CNS). In this study, we addressed the potential of NTHI to enter the brain by invading cells of the choroid plexus (CP) prior to meningeal inflammation to enlighten NTHI pathophysiological mechanisms. A cell culture model of human CP epithelial cells, which form the blood-cerebrospinal fluid barrier (BCSFB) in vivo, was used to analyze adhesion and invasion by immunofluorescence and electron microscopy. NTHI invade CP cells in vitro in a polar fashion from the blood-facing side. Furthermore, NTHI invasion rates are increased compared to encapsulated HiB and HiF strains. Fimbriae occurrence attenuated adhesion and invasion. Thus, our findings underline the role of the BCSFB as a potential entry port for NTHI into the brain and provide strong evidence for a function of the CP during NTHI invasion into the CNS during the course of meningitis.
    • The Microbiome of Seagrass Leaves Can Be Dominated by Planctomycetes.

      Kohn, Timo; Rast, Patrick; Kallscheuer, Nicolai; Wiegand, Sandra; Boedeker, Christian; Jetten, Mike S M; Jeske, Olga; Vollmers, John; Kaster, Anne-Kristin; Rohde, Manfred; et al. (Frontiers, 2020-07-10)
      Seagrass meadows are ubiquitous, fragile and endangered marine habitats, which serve as fish breeding grounds, stabilize ocean floor substrates, retain nutrients and serve as important carbon sinks, counteracting climate change. In the Mediterranean Sea, seagrass meadows are mostly formed by the slow-growing endemic plant Posidonia oceanica (Neptune grass), which is endangered by global warming and recreational motorboating. Despite its importance, surprisingly little is known about the leaf surface microbiome of P. oceanica. Using amplicon sequencing, we here show that species belonging to the phylum Planctomycetes can dominate the biofilms of young and aged P. oceanica leaves. Application of selective cultivation techniques allowed for the isolation of two novel planctomycetal strains belonging to two yet uncharacterized genera.
    • Fingolimod Modulates Dendritic Architecture in a BDNF-Dependent Manner.

      Patnaik, Abhisarika; Spiombi, Eleonora; Frasca, Angelisa; Landsberger, Nicoletta; Zagrebelsky, Marta; Korte, Martin (MDPI, 2020-04-27)
      The brain-derived neurotrophic factor (BDNF) plays crucial roles in both the developing and mature brain. Moreover, alterations in BDNF levels are correlated with the cognitive impairment observed in several neurological diseases. Among the different therapeutic strategies developed to improve endogenous BDNF levels is the administration of the BDNF-inducing drug Fingolimod, an agonist of the sphingosine-1-phosphate receptor. Fingolimod treatment was shown to rescue diverse symptoms associated with several neurological conditions (i.e., Alzheimer disease, Rett syndrome). However, the cellular mechanisms through which Fingolimod mediates its BDNF-dependent therapeutic effects remain unclear. We show that Fingolimod regulates the dendritic architecture, dendritic spine density and morphology of healthy mature primary hippocampal neurons. Moreover, the application of Fingolimod upregulates the expression of activity-related proteins c-Fos and pERK1/2 in these cells. Importantly, we show that BDNF release is required for these actions of Fingolimod. As alterations in neuronal structure underlie cognitive impairment, we tested whether Fingolimod application might prevent the abnormalities in neuronal structure typical of two neurodevelopmental disorders, namely Rett syndrome and Cdk5 deficiency disorder. We found a significant rescue in the neurite architecture of developing cortical neurons from Mecp2 and Cdkl5 mutant mice. Our study provides insights into understanding the BDNF-dependent therapeutic actions of Fingolimod.
    • From the Cradle to the Grave of an Infection: Host-Pathogen Interaction Visualized by Intravital Microscopy.

      Handschuh, Juliane; Amore, Jonas; Müller, Andreas J (Wiley, 2019-11-27)
      During infections, interactions between host immune cells and the pathogen occur in distinct anatomical locations and along defined time scales. This can best be assessed in the physiological context of an infection in the living tissue. Consequently, intravital imaging has enabled us to dissect the critical phases and events throughout an infection in real time in living tissues. Specifically, advances in visualizing specific cell types and individual pathogens permitted tracking the early events of tissue invasion of the pathogen, cellular interactions involved in the induction of the immune response as well the events implicated in clearance of the infection. In this respect, two vantage points have evolved since the initial employment of this technique in the field of infection biology. On the one hand, strategies acquired by the pathogen to establish within the host and circumvent or evade the immune defenses have been elucidated. On the other hand, analyzing infections from the immune system’s perspective has led to insights into the dynamic cellular interactions that are involved in the initial recognition of the pathogen, immune induction as well as effector function delivery and immunopathology. Furthermore, an increasing interest in probing functional parameters in vivo has emerged, such as the analysis of pathogen reactivity to stress conditions imposed by the host organism in order to mediate clearance upon pathogen encounter. Here, we give an overview on recent intravital microscopy findings of hostpathogen interactions along the course of an infection, from both the immune system’s and pathogen’s perspectives. We also discuss recent developments and future perspectives in extracting intravital information beyond the localization of pathogens and their interaction with immune cells. Such reporter systems on the pathogen’s physiological state and immune cell functions may prove useful in dissecting the functional dynamics of hostpathogen interactions.
    • Fibrosis and Immune Cell Infiltration Are Separate Events Regulated by Cell-Specific Receptor Notch3 Expression.

      Brandt, Sabine; Ballhause, Tobias M; Bernhardt, Anja; Becker, Annika; Salaru, Delia; Le-Deffge, Hien Minh; Fehr, Alexander; Fu, Yan; Philipsen, Lars; Djudjaj, Sonja; et al. (2020-08-28)
      Kidney injuries that result in chronic inflammation initiate crosstalk between stressed resident cells and infiltrating immune cells. In animal models, whole-body receptor Notch3 deficiency protects from leukocyte infiltration and organ fibrosis. However, the relative contribution of Notch3 expression in tissue versus infiltrating immune cells is unknown.
    • Dynamics of Cardiac Neutrophil Diversity in Murine Myocardial Infarction.

      Vafadarnejad, Ehsan; Rizzo, Giuseppe; Krampert, Laura; Arampatzi, Panagiota; Arias-Loza, Anahi-Paula; Nazzal, Yara; Rizakou, Anna; Knochenhauer, Tim; Bandi, Sourish Reddy; Nugroho, Vallery Audy; et al. (2020-08-19)
      We employed single-cell transcriptomics combined with cell surface epitope detection by sequencing to investigate temporal neutrophil diversity in the blood and heart after murine myocardial infarction. At day 1, 3, and 5 after infarction, cardiac Ly6G+ (lymphocyte antigen 6G) neutrophils could be delineated into 6 distinct clusters with specific time-dependent patterning and proportions. At day 1, neutrophils were characterized by a gene expression profile proximal to bone marrow neutrophils (Cd177, Lcn2, Fpr1), and putative activity of transcriptional regulators involved in hypoxic response (Hif1a) and emergency granulopoiesis (Cebpb). At 3 and 5 days, 2 major subsets of Siglecfhi (enriched for eg, Icam1 and Tnf) and Siglecflow (Slpi, Ifitm1) neutrophils were found. Cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) analysis in blood and heart revealed that while circulating neutrophils undergo a process of aging characterized by loss of surface CD62L and upregulation of Cxcr4, heart infiltrating neutrophils acquired a unique SiglecFhi signature. SiglecFhi neutrophils were absent from the bone marrow and spleen, indicating local acquisition of the SiglecFhi signature. Reducing the influx of blood neutrophils by anti-Ly6G treatment increased proportions of cardiac SiglecFhi neutrophils, suggesting accumulation of locally aged neutrophils. Computational analysis of ligand/receptor interactions revealed putative pathways mediating neutrophil to macrophage communication in the myocardium. Finally, SiglecFhi neutrophils were also found in atherosclerotic vessels, revealing that they arise across distinct contexts of cardiovascular inflammation.
    • An Overview of Population Projections—Methodological Concepts, International Data Availability, and Use Cases

      Vanella, Patrizio; Deschermeier, Philipp; Wilke, Christina B. (MDPI AG, 2020-09-02)
      Population projections serve various actors at subnational, national, and international levels as a quantitative basis for political and economic decision-making. Usually, the users are no experts in statistics or forecasting and therefore lack the methodological and demographic background to completely understand methods and limitations behind the projections they use to inform further analysis. Our contribution primarily targets that readership. Therefore, we give a brief overview of di erent approaches to population projection and discuss their respective advantages and disadvantages, alongside practical problems in population data and forecasting. Fundamental di erences between deterministic and stochastic approaches are discussed, with special emphasis on the advantages of stochastic approaches. Next to selected projection data available to the public, we show central areas of application of population projections, with an emphasis on Germany
    • Inhibition of Type IV Secretion Activity and Growth of by Cisplatin and Other Platinum Complexes.

      Lettl, Clara; Schindele, Franziska; Testolin, Giambattista; Bär, Alexander; Rehm, Tobias; Brönstrup, Mark; Schobert, Rainer; Bilitewski, Ursula; Haas, Rainer; Fischer, Wolfgang (Frontiers, 2020-12-18)
      Type IV secretion systems are protein secretion machineries that are frequently used by pathogenic bacteria to inject their virulence factors into target cells of their respective hosts. In the case of the human gastric pathogen Helicobacter pylori, the cytotoxin-associated gene (Cag) type IV secretion system is considered a major cause for severe disease, such as gastric cancer, and thus constitutes an attractive target for specific treatment options against H. pylori infections. Here, we have used a Cag type IV secretion reporter assay for screening a repurposing compound library for inhibitors targeting this system. We found that the antitumor agent cisplatin, a platinum coordination complex that kills target cells by formation of DNA crosslinks, is a potent inhibitor of the Cag type IV secretion system. Strikingly, we found that this inhibitory activity of cisplatin depends on a ligand exchange reaction which incorporates a solvent molecule (dimethylsulfoxide) into the complex, a modification which is known to be deleterious for DNA crosslinking, and for its anticancer activity. We extended our analysis to several analogous platinum complexes containing N-heterocyclic carbene, as well as DMSO or other ligands, and found varying inhibitory activities toward the Cag system which were not congruent with their DNA-binding properties, suggesting that protein interactions may cause the inhibitory effect. Inhibition experiments under varying conditions revealed effects on adherence and bacterial viability as well, and showed that the type IV secretion-inhibitory capacity of platinum complexes can be inactivated by sulfur-containing reagents and in complex bacterial growth media. Taken together, our results demonstrate DNA binding-independent inhibitory effects of cisplatin and other platinum complexes against different H. pylori processes including type IV secretion.
    • Differential DNA methylation in bronchial biopsies between persistent asthma and asthma in remission.

      Vermeulen, Cornelis J; Xu, Cheng-Jian; Vonk, Judith M; Ten Hacken, Nick H T; Timens, Wim; Heijink, Irene H; Nawijn, Martijn C; Boekhoudt, Jeunard; van Oosterhout, Antoon J; Affleck, Karen; et al. (2020-02-06)
      Approximately 40% of asthmatics experience remission of asthma symptoms. A better understanding of biological pathways leading to asthma remission may provide insight into new therapeutic targets for asthma. As an important mechanism of gene regulation, investigation of DNA methylation provides a promising approach. Our objective was to identify differences in epigenome wide DNA methylation levels in bronchial biopsies between subjects with asthma remission and subjects with persistent asthma or healthy controls.We analysed differential DNA methylation in bronchial biopsies from 26 subjects with persistent asthma, 39 remission subjects and 70 healthy controls, using the limma package. The comb-p tool was used to identify differentially methylated regions. DNA methylation of CpG-sites was associated to expression of nearby genes from the same biopsies to understand function.Four CpG-sites and 42 regions were differentially methylated between persistent asthma and remission. DNA methylation at two sites was correlated i n cis with gene expression at ACKR2 and DGKQ Between remission subjects and healthy controls 1163 CpG-sites and 328 regions were differentially methylated. DNA methylation was associated with expression of a set of genes expressed in ciliated epithelium.CpGs differentially methylated between remission and persistent asthma identify genetic loci associated with resolution of inflammation and airway responsiveness. Despite the absence of symptoms, remission subjects have a DNA methylation profile that is distinct from that of healthy controls, partly due to changes in cellular composition, with a higher gene expression signal related to ciliated epithelium in remission versus healthy controls.
    • Ribavirin for Hepatitis E Virus Infection After Organ Transplantation: A Large European Retrospective Multicenter Study.

      Kamar, Nassim; Abravanel, Florence; Behrendt, Patrick; Hofmann, Jörg; Pageaux, Georges Phillippe; Barbet, Christelle; Moal, Valérie; Couzi, Lionel; Horvatits, Thomas; De Man, Robert A; et al. (2020-09-01)
      Background. Ribavirin is currently recommended for treating chronic hepatitis E virus (HEV) infection. This retrospective European multicenter study aimed to assess the sustained virological response (SVR) in a large cohort of solid organ transplant (SOT) recipients with chronic HEV infection treated with ribavirin monotherapy (N = 255), to identify the predictive factors for SVR, and to evaluate the impact of HEV RNA mutations on virological response. Methods. Data from 255 SOT recipients with chronic HEV infection from 30 European centers were analyzed. Ribavirin was given at the median dose of 600 (range, 29–1200) mg/day (mean, 8.6 ± 3.6 mg/kg/day) for a median duration of 3 (range, 0.25–18) months. Results. After a first course of ribavirin, the SVR rate was 81.2%. It increased to 89.8% when some patients were offered a second course of ribavirin. An increased lymphocyte count at the initiation of therapy was a predictive factor for SVR, while poor hematological tolerance of ribavirin requiring its dose reduction (28%) and blood transfusion (15.7%) were associated with more relapse after ribavirin cessation. Pretreatment HEV polymerase mutations and de novo mutations under ribavirin did not have a negative impact on HEV clearance. Anemia was the main adverse event. Conclusions. This large-scale retrospective study confirms that ribavirin is highly efficient for treating chronic HEV infection in SOT recipients and shows that the predominant HEV RNA polymerase mutations found in this study do not affect the rate of HEV clearance.
    • Development and validation of the Simulator of the Canine Intestinal Microbial Ecosystem (SCIME)1.

      Duysburgh, Cindy; Ossieur, Wendy P; De Paepe, Kim; Van den Abbeele, Pieter; Vichez-Vargas, Ramiro; Vital, Marius; Pieper, Dietmar H; Van De Wiele, Tom; Hesta, Myriam; Possemiers, Sam; et al. (2020-01)