This is the institutional Repository of the Helmholtz Centre for Infection Research in Braunschweig/Germany (HZI), the Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Saarbrücken/Germany, the TWINCORE Zentrum für Exprerimentelle und Klinische Infektionsforschung, Hannover/Germany,Helmholtz-Institut für RNA-basierte Infektionsforschung (HIRI), Würzburg/Germany, Braunschweig Integrated Centre for Systems biology (BRICS), Centre for Structural Systems Biology (CSSB) the Study Centre Hannover, Hannover/Germany and the Centre for Individualised Infection Medicine (CiiM).

 

  • An extended catalogue of tandem alternative splice sites in human tissue transcriptomes.

    Mironov, Aleksei; Denisov, Stepan; Gress, Alexander; Kalinina, Olga V; Pervouchine, Dmitri D; HIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany. (PLOS, 2021-04-07)
    Tandem alternative splice sites (TASS) is a special class of alternative splicing events that are characterized by a close tandem arrangement of splice sites. Most TASS lack functional characterization and are believed to arise from splicing noise. Based on the RNA-seq data from the Genotype Tissue Expression project, we present an extended catalogue of TASS in healthy human tissues and analyze their tissue-specific expression. The expression of TASS is usually dominated by one major splice site (maSS), while the expression of minor splice sites (miSS) is at least an order of magnitude lower. Among 46k miSS with sufficient read support, 9k (20%) are significantly expressed above the expected noise level, and among them 2.5k are expressed tissue-specifically. We found significant correlations between tissue-specific expression of RNA-binding proteins (RBP), tissue-specific expression of miSS, and miSS response to RBP inactivation by shRNA. In combination with RBP profiling by eCLIP, this allowed prediction of novel cases of tissue-specific splicing regulation including a miSS in QKI mRNA that is likely regulated by PTBP1. The analysis of human primary cell transcriptomes suggested that both tissue-specific and cell-type-specific factors contribute to the regulation of miSS expression. More than 20% of tissue-specific miSS affect structured protein regions and may adjust protein-protein interactions or modify the stability of the protein core. The significantly expressed miSS evolve under the same selection pressure as maSS, while other miSS lack signatures of evolutionary selection and conservation. Using mixture models, we estimated that not more than 15% of maSS and not more than 54% of tissue-specific miSS are noisy, while the proportion of noisy splice sites among non-significantly expressed miSS is above 63%.
  • Fucosylated lipid nanocarriers loaded with antibiotics efficiently inhibit mycobacterial propagation in human myeloid cells.

    Durán, Verónica; Grabski, Elena; Hozsa, Constantin; Becker, Jennifer; Yasar, Hanzey; Monteiro, João T; Costa, Bibiana; Koller, Nicole; Lueder, Yvonne; Wiegmann, Bettina; et al. (Elsevier, 2021-04-16)
    Antibiotic treatment of tuberculosis (TB) is complex, lengthy, and can be associated with various adverse effects. As a result, patient compliance often is poor, thus further enhancing the risk of selecting multi-drug resistant bacteria. Macrophage mannose receptor (MMR)-positive alveolar macrophages (AM) constitute a niche in which Mycobacterium tuberculosis replicates and survives. Therefore, we encapsulated levofloxacin in lipid nanocarriers functionalized with fucosyl residues that interact with the MMR. Indeed, such nanocarriers preferentially targeted MMR-positive myeloid cells, and in particular, AM. Intracellularly, fucosylated lipid nanocarriers favorably delivered their payload into endosomal compartments, where mycobacteria reside. In an in vitro setting using infected human primary macrophages as well as dendritic cells, the encapsulated antibiotic cleared the pathogen more efficiently than free levofloxacin. In conclusion, our results point towards carbohydrate-functionalized nanocarriers as a promising tool for improving TB treatment by targeted delivery of antibiotics.
  • How to publish a new fungal species, or name, version 3.0.

    Aime, M Catherine; Miller, Andrew N; Aoki, Takayuki; Bensch, Konstanze; Cai, Lei; Crous, Pedro W; Hawksworth, David L; Hyde, Kevin D; Kirk, Paul M; Lücking, Robert; et al. (BMC, 2021-05-03)
    It is now a decade since The International Commission on the Taxonomy of Fungi (ICTF) produced an overview of requirements and best practices for describing a new fungal species. In the meantime the International Code of Nomenclature for algae, fungi, and plants (ICNafp) has changed from its former name (the International Code of Botanical Nomenclature) and introduced new formal requirements for valid publication of species scientific names, including the separation of provisions specific to Fungi and organisms treated as fungi in a new Chapter F. Equally transformative have been changes in the data collection, data dissemination, and analytical tools available to mycologists. This paper provides an updated and expanded discussion of current publication requirements along with best practices for the description of new fungal species and publication of new names and for improving accessibility of their associated metadata that have developed over the last 10 years. Additionally, we provide: (1) model papers for different fungal groups and circumstances; (2) a checklist to simplify meeting (i) the requirements of the ICNafp to ensure the effective, valid and legitimate publication of names of new taxa, and (ii) minimally accepted standards for description; and, (3) templates for preparing standardized species descriptions.
  • Glutathione Metabolism Contributes to the Induction of Trained Immunity.

    Ferreira, Anaisa V; Koeken, Valerie A C M; Matzaraki, Vasiliki; Kostidis, Sarantos; Alarcon-Barrera, Juan Carlos; de Bree, L Charlotte J; Moorlag, Simone J C F M; Mourits, Vera P; Novakovic, Boris; Giera, Martin A; et al. (MDPI, 2021-04-21)
    The innate immune system displays heterologous memory characteristics, which are characterized by stronger responses to a secondary challenge. This phenomenon termed trained immunity relies on epigenetic and metabolic rewiring of innate immune cells. As reactive oxygen species (ROS) production has been associated with the trained immunity phenotype, we hypothesized that the increased ROS levels and the main intracellular redox molecule glutathione play a role in the induction of trained immunity. Here we show that pharmacological inhibition of ROS in an in vitro model of trained immunity did not influence cell responsiveness; the modulation of glutathione levels reduced pro-inflammatory cytokine production in human monocytes. Single nucleotide polymorphisms (SNPs) in genes involved in glutathione metabolism were found to be associated with changes in pro-inflammatory cytokine production capacity upon trained immunity. Also, plasma glutathione concentrations were positively associated with ex vivo IL-1β production, a biomarker of trained immunity, produced by monocytes of BCG-vaccinated individuals. In conclusion, glutathione metabolism is involved in the induction of trained immunity, and future studies are warranted to explore its functional consequences in human diseases.
  • Respiratory viral infections and associated neurological manifestations

    Hosseini, Shirin; Michaelsen-Preusse, Kristin; Korte, Martin; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (Walter de Gruyter GmbH, 2021-03-29)
    Respiratory viruses as a major threat to human and animal health today are still a leading cause of worldwide severe pandemics. Although the primary target tissue of these viruses is the lung, they can induce immediate or delayed neuropathological manifestations in humans and animals. Already after the Spanish flu (1918/20) evidence accumulated that neurological diseases can be induced by respiratory viral infections as some patients showed parkinsonism, seizures, or dementia. In the recent outbreak of COVID-19 as well patients suffered from headache, dizziness, nausea, or reduced sense of smell and taste suggesting that SARS-CoV2 may affect the central nervous system (CNS). It was shown that different respiratory viral infections can lead to deleterious complications in the CNS by a direct invasion of the virus into the brain and/or indirect pathways via proinflammatory cytokine expression. Therefore, we will discuss in this review mechanisms how the most prevalent respiratory viruses including influenza and coronaviruses in humans can exert long-lasting detrimental effects on the CNS and possible links to the development of neurodegenerative diseases as an enduring consequence.

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