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572 results match your criteria: "Paul-Ehrlich Institute[Affiliation]"
Nucleic Acids Res
December 2024
Department of Physics and Optical Science, University of North Carolina at Charlotte, 9201 University City Blvd., Charlotte, NC 28223, USA.
DNA transposons have emerged as promising tools in both gene therapy and functional genomics. In particular, the Sleeping Beauty (SB) DNA transposon has advanced into clinical trials due to its ability to stably integrate DNA sequences of choice into eukaryotic genomes. The efficiency of the DNA transposon system depends on the interaction between the transposon DNA and the transposase enzyme that facilitates gene transfer.
View Article and Find Full Text PDFCell Mol Life Sci
December 2024
Institute of Molecular Health Sciences, Department of Biology, ETH Zürich, Otto-Stern-Weg 7, Zürich, 8093, Switzerland.
The development of antiviral strategies is a key task of biomedical research, but broad-spectrum virus inhibitors are scarce. Here we show that fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitors reduce infection of several cell types with DNA and RNA viruses by blocking early stages of infection, but not viral cell association. Unexpectedly, their antiviral activity was largely independent of FGFR kinase inhibition.
View Article and Find Full Text PDFJ Microsc
November 2024
Department of Microscopy of Pathogens, Paul Ehrlich Institute, Langen, Germany.
In this short and popular review, we summarise some of our findings analysing the replication cycles of large DNA viruses using scanning transmission electron tomography (STEM tomography) that we applied in the laboratory of Paul Walther. It is also a tribute to a very kind and expert scientist, who recently retired. Transmission electron microscopy (TEM), in particular cryo-EM, has benefited tremendously from recent developments in instrumentation.
View Article and Find Full Text PDFStem Cell Res
December 2024
Goethe University, Department of Pediatrics, Division for Stem Cell Transplantation and Immunology, Frankfurt/Main, Germany.
Leukocyte Adhesion Deficiency Type I (LAD I) is a rare inborn error of immunity caused by mutations in the ITGB2 gene coding for β2-integrin CD18 on the surface of leukocytes. Affected patients display severe clinical manifestations with life threatening infections and inflammatory complications due to an impaired ability of leukocytes to transmigrate from the blood vessel to the tissue. Here we describe the generation of eight induced pluripotent stem cell lines from two patients with LAD I and mutations in the ITGB2 gene.
View Article and Find Full Text PDFTrends Pharmacol Sci
November 2024
Division of Immunology, Paul-Ehrlich-Institute, Federal Institute for Vaccines and Biomedicines, Langen, 63225, Hesse, Germany.
Nitro-fatty acids (NO-FAs) are endogenous pleiotropic lipid mediators regarded as promising drug candidates for treating inflammatory and fibrotic diseases. Over the past two decades, the anti-inflammatory and cytoprotective actions of NO-FAs and several molecular targets have been identified. More recently, preclinical studies have demonstrated their potential as prospective cancer therapeutics with favorable safety and tumor-selective profiles.
View Article and Find Full Text PDFMol Ther
October 2024
Institute of Clinical Immunology, University of Leipzig, Leipzig, Germany; Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany. Electronic address:
Allergy
September 2024
Institute of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
Background: In contrast to sublingual immunotherapy (SLIT) with recombinant Mal d 1 (rMal d 1-SLIT), SLIT with rBet v 1 (rBet v 1-SLIT) induced Mal d 1-cross-reactive antibodies without IgE-blocking activity. To elucidate whether the development of cross-protective IgG responses depends on the degree of molecular identity of allergens we compared the cross-reactivity, cross-blocking activity, and affinity of SLIT-induced antibodies with allergens of varying amino acid sequence identities to Bet v 1 and Mal d 1, namely Cor a 1.04 (hazelnut), Pru av 1 (cherry), and Dau c 1 (carrot).
View Article and Find Full Text PDFJ Virol
September 2024
Department of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, California, USA.
Unlabelled: Some negative-sense RNA viruses, including measles virus (MeV), share the characteristic that during their infection cycle, cytoplasmic inclusion bodies (IBs) are formed where components of the viral replication machinery are concentrated. As a foci of viral replication, how IBs act to enhance the efficiency of infection by affecting virus-host interactions remains an important topic of investigation. We previously established that upon MeV infection, the epigenetic host protein, WD repeat-containing protein 5 (WDR5), translocates to cytoplasmic viral IBs and facilitates MeV replication.
View Article and Find Full Text PDFmBio
September 2024
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, USA.
In humans, sterile alpha motif (SAM) domain- and histidine-aspartic acid (HD) domain-containing protein 1 (SAMHD1) is a dNTPase enzyme that prevents HIV-1 infection in non-cycling cells, such as differentiated THP-1 cells and human primary macrophages. Although phosphorylation of threonine 592 (T592) in SAMHD1 is recognized as the primary regulator of the ability to prevent HIV-1 infection, the contributions of SAMHD1 acetylation to this ability remain unknown. Mass spectrometry analysis of SAMHD1 proteins derived from cycling and non-cycling THP-1 cells, primary cycling B cells, and primary macrophages revealed that SAMHD1 is preferentially acetylated at lysine residues 354, 494, and 580 (K354, K494, and K580).
View Article and Find Full Text PDFLiver Int
October 2024
Department of Gastroenterology and Hepatology, University Hospital Frankfurt, Frankfurt, Germany.
Background: The hepatitis B e antigen (HBeAg)-negative infection Phase 3 is characterized by no or minimal signs of hepatic inflammation and the absence of hepatic fibrosis. However, underlying molecular mechanisms leading to this benign phenotype are poorly understood.
Methods: Genotype A, B and D HBeAg-negative patient isolates with precore mutation G1896A from Phase 3 were analysed in comparison with respective HBeAg-positive rescue mutant and HBeAg-positive wild-type reference genomes regarding differences in viral replication, morphogenesis, infectivity and impact on NF-E2-related factor 2 (Nrf2)/antioxidant response element (ARE)-dependent gene expression and cellular kinome.
Allergy
October 2024
Department of Dermatology, University Hospital Münster, University of Münster, Münster, Germany.
Background: Approximately 70% of individuals allergic to birch pollen (Bet v 1.01 [Bet]) develop a secondary food allergy (e.g.
View Article and Find Full Text PDFHeliyon
July 2024
Institute of Pharmaceutical Chemistry, Philipps University Marburg, 35032, Marburg, Germany.
Pateamines, derived from the sponge , function as inhibitors of the RNA helicase eIF4A and exhibit promising antiviral and anticancer properties. eIF4A plays a pivotal role in unwinding stable RNA structures within the 5'-UTR of selected mRNAs, facilitating the binding of the 43S preinitiation complex during translation initiation. Pateamines function by clamping RNA substrates onto the eIF4A surface, effectively preventing eIF4A from carrying out the unwinding step.
View Article and Find Full Text PDFJ Virol
August 2024
Division of Veterinary Medicine, Paul-Ehrlich-Institute, Langen, Germany.
PLoS Negl Trop Dis
June 2024
Department for Molecular and Medical Virology, Ruhr University Bochum, Bochum, Germany.
Despite continued outbreaks of yellow fever virus (YFV) in endemic regions, data on its environmental stability or guidelines for its effective inactivation is limited. Here, we evaluated the susceptibility of the YFV 17D vaccine strain to inactivation by ethanol, 2-propanol, World Health Organization (WHO)-recommended hand rub formulations I and II, as well as surface disinfectants. In addition, two pathogenic strains were tested to compare inactivation kinetics by WHO-recommended hand rub formulations I and II.
View Article and Find Full Text PDFJ Virol
July 2024
Division of Virology, Paul Ehrlich Institute, Langen, Germany.
Unlabelled: Hepatitis E virus (HEV) poses a global threat, which currently remains understudied in terms of host interactions. Epidermal growth factor receptor (EGFR) plays multifaceted roles in viral pathogenesis, impacting host-cell entry, viral replication, and host-defense modulation. On the one hand, EGFR signaling emerged as a major driver in innate immunity; on the other hand, a crosstalk between HEV and EGFR requires deeper analysis.
View Article and Find Full Text PDFArch Toxicol
July 2024
Department of Toxicology, Leibniz Research Centre for Working Environment and Human Factors (IfADo), Ardeystrasse 67, 44139, Dortmund, Germany.
Since 2006, the responsible regulatory bodies have proposed five health-based guidance values (HBGV) for bisphenol A (BPA) that differ by a factor of 250,000. This range of HBGVs covers a considerable part of the range from highly toxic to relatively non-toxic substances. As such heterogeneity of regulatory opinions is a challenge not only for scientific risk assessment but also for all stakeholders, the Senate Commission on Food Safety (SKLM) of the German Research Foundation (DFG) analyzed the reasons for the current discrepancy and used this example to suggest improvements for the process of HBGV recommendations.
View Article and Find Full Text PDFMethods Mol Biol
May 2024
Division of Veterinary Medicine, Paul-Ehrlich-Institute, Langen, Germany.
Canine distemper virus (CDV) is a highly contagious pathogen within the morbillivirus genus infecting a wide range of different carnivore species. The virus shares most biological features with other closely related morbilliviruses, including clinical signs, tissue tropism, and replication cycle in the respective host organisms.In the laboratory environment, experimental infections of ferrets with CDV were established as a potent surrogate model for the analysis of several aspects of the biology of the human morbillivirus, measles virus (MeV).
View Article and Find Full Text PDFMethods Mol Biol
May 2024
Division of Veterinary Medicine, Paul-Ehrlich-Institute, Langen, Germany.
Copy-back defective interfering RNAs are major contaminants of viral stock preparations of morbilliviruses and other negative strand RNA viruses. They are hybrid molecules of positive sense antigenome and negative sense genome. They possess perfectly complementary ends allowing the formation of extremely stable double-stranded RNA panhandle structures.
View Article and Find Full Text PDFBiofabrication
May 2024
Department for Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany.
Ensuring the safety of parenteral drugs before injection into patients is of utmost importance. New regulations around the globe and the need to refrain from using animals however, have highlighted the need for new cell sources to be used in next-generation bioassays to detect the entire spectrum of possible contaminating pyrogens. Given the current drawbacks of the Monocyte-Activation-Test (MAT) with respect to the use of primary peripheral blood mono-nuclear cells or the use of monocytic cell lines, we here demonstrate the manufacturing of sensor monocytes/macrophages from human induced pluripotent stem cells (iMonoMac), which are fully defined and superior to current cell products.
View Article and Find Full Text PDFAntiviral Res
June 2024
Department of Virology, Paul-Ehrlich-Institute, Paul-Ehrlich-Straße 51-59, D63225, Langen, Germany. Electronic address:
Zoonoses such as ZIKV and SARS-CoV-2 pose a severe risk to global health. There is urgent need for broad antiviral strategies based on host-targets filling gaps between pathogen emergence and availability of therapeutic or preventive strategies. Significant reduction of pathogen titers decreases spread of infections and thereby ensures health systems not being overloaded and public life to continue.
View Article and Find Full Text PDFJ Virol
May 2024
Division of Virology, Paul Ehrlich Institute, Langen, Germany.
Chronic hepatitis B virus (HBV) infections are strongly associated with liver cirrhosis, inflammation, and hepatocellular carcinoma. In this context, the viral HBx protein is considered as a major factor influencing HBV-associated pathogenesis through deregulation of multiple cellular signaling pathways and is therefore a potential target for prognostic and therapeutic applications. However, HBV-associated pathogenesis differs significantly between genotypes, with the relevant factors and in particular the contribution of the genetic diversity of HBx being largely unknown.
View Article and Find Full Text PDFPediatrics
May 2024
Institute of Virology, Faculty of Medicine and University Hospital Cologne.
Background And Objectives: Test-to-stay concepts apply serial testing of children in daycare after exposure to SARS-CoV-2 without use of quarantine. This study aims to assess the safety of a test-to-stay screening in daycare facilities.
Methods: 714 daycare facilities and approximately 50 000 children ≤6 years in Cologne, Germany participated in a SARS-CoV-2 Pool-polymerase chain reaction (PCR) screening from March 2021 to April 2022.
Br J Clin Pharmacol
May 2024
Spanish Agency of Medicines and Medical Devices, Madrid, Spain.
Great advances have been made in the knowledge of development and regulatory approval of medicinal product containing genetically modified cells. Although a guideline has been available in the EU since 2012, the current updated version provides a useful guide to developers and professionals involved in the regulatory process of these medicines. This article presents the main issues communicated in that guidance, the regulators' insights and a commentary from the academic developers' point of view.
View Article and Find Full Text PDFPharmeur Bio Sci Notes
March 2024
Paul-Ehrlich-Institute, Paul-Ehrlich-Strasse 51-59, D-63225 Langen, Germany.
In 2010, the reporting of thrombotic adverse events for one subcutaneous and certain intravenous immunoglobulins (IGs) raised some concerns. In Europe, regulatory bodies rapidly revised compendial specifications for therapeutic IGs to ensure they do not exhibit thrombogenic (procoagulant) activity (PCA). At the global level, a working group (GWG) was launched with the aim of assessing PCA measurement methods and limits, considering results obtained by human IG manufacturers during in-process controls.
View Article and Find Full Text PDFLancet Reg Health Eur
March 2024
Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden.
Background: Investigating outcomes of hospitalised COVID-19 patients throughout the pandemic is crucial to understand the impact of different SARS-CoV-2 variants. We compared 28-day in-hospital mortality of Wild-type, Alpha, Delta, and Omicron variant infections. Whether the difference in risk by variant varied by age was also evaluated.
View Article and Find Full Text PDF