This file was created by the TYPO3 extension publications --- Timezone: CEST Creation date: 2025-05-02 Creation time: 21:17:14 --- Number of references 15 article Hadjeras2023 In contrast to extensively studied prokaryotic `small' transcriptomes (encompassing all small noncoding RNAs), small proteomes (here defined as including proteins ≤70 aa) are only now entering the limelight. The absence of a complete small protein catalogue in most prokaryotes precludes our understanding of how these molecules affect physiology. So far, archaeal genomes have not yet been analyzed broadly with a dedicated focus on small proteins. Here, we present a combinatorial approach, integrating experimental data from small protein-optimized mass spectrometry (MS) and ribosome profiling (Ribo-seq), to generate a high confidence inventory of small proteins in the model archaeon Haloferax volcanii. We demonstrate by MS and Ribo-seq that 67% of the 317 annotated small open reading frames (sORFs) are translated under standard growth conditions. Furthermore, annotation-independent analysis of Ribo-seq data showed ribosomal engagement for 47 novel sORFs in intergenic regions. A total of seven of these were also detected by proteomics, in addition to an eighth novel small protein solely identified by MS. We also provide independent experimental evidence in vivo for the translation of 12 sORFs (annotated and novel) using epitope tagging and western blotting, underlining the validity of our identification scheme. Several novel sORFs are conserved in Haloferax species and might have important functions. Based on our findings, we conclude that the small proteome of H. volcanii is larger than previously appreciated, and that combining MS with Ribo-seq is a powerful approach for the discovery of novel small protein coding genes in archaea. 2023 1 01 2633-6693 10.1093/femsml/uqad001 microLife 4 uqad001 https://doi.org/10.1093/femsml/uqad001 Lydia Hadjeras Juergen Bartel Lisa-Katharina Maier Sandra �Ѳ���ß Verena Vogel Sarah L. Svensson Florian Eggenhofer Rick Gelhausen Teresa Mueller Omer S. Alkhnbashi Rolf Backofen Doerte Becher Cynthia M. Sharma Anita Marchfelder article Weixler2022 The bacteriocin nisin is naturally produced by Lactococcus lactis as an inactive prepeptide that is modified posttranslationally resulting in five (methyl-)lanthionine rings characteristic for class Ia bacteriocins. Export and proteolytic cleavage of the leader peptide results in release of active nisin. By targeting the universal peptidoglycan precursor lipid II, nisin has a broad target spectrum including important human pathogens such as Listeria monocytogenes and methicillin-resistant Staphylococcus aureus strains. Industrial nisin production is currently performed using natural producer strains resulting in rather low product purity and limiting its application to preservation of dairy food products. 2022 1 15 1475-2859 10.1186/s12934-022-01739-y Microbial Cell Factories 21 11 1 https://doi.org/10.1186/s12934-022-01739-y Dominik Weixler Max Berghoff Kirill V. Ovchinnikov Sebastian Reich Oliver Goldbeck Gerd M. Seibold Christoph Wittmann Nadav S. Bar Bernhard J. Eikmanns Dzung B. Diep Christian U. Riedel article Heerde2022 Several studies showed that seeding of solutions of monomeric fibril proteins with ex vivo amyloid fibrils accelerated the kinetics of fibril formation in vitro but did not necessarily replicate the seed structure. In this research we use cryo-electron microscopy and other methods to analyze the ability of serum amyloid A (SAA)1.1-derived amyloid fibrils, purified from systemic AA amyloidosis tissue, to seed solutions of recombinant SAA1.1 protein. We show that 98{%} of the seeded fibrils remodel the full fibril structure of the main ex vivo fibril morphology, which we used for seeding, while they are notably different from unseeded in vitro fibrils. The seeded fibrils show a similar proteinase K resistance as ex vivo fibrils and are substantially more stable to proteolytic digestion than unseeded in vitro fibrils. Our data support the view that the fibril morphology contributes to determining proteolytic stability and that pathogenic amyloid fibrils arise from proteolytic selection. 2022 1 10 2041-1723 10.1038/s41467-021-27688-5 Nature Communications 13 85 1 https://doi.org/10.1038/s41467-021-27688-5 Thomas Heerde Matthies Rennegarbe Alexander Biedermann Dilan Savran Peter B. Pfeiffer Manuel Hitzenberger Julian Baur Ioana Puscalau-Girtu Martin Zacharias Nadine Schwierz Christian Haupt Marcus Faendrich article LOFT2022 Summary Fasting metabolism and immunity are tightly linked; however, it is largely unknown how immune cells contribute to metabolic homeostasis during fasting in healthy subjects. Here, we combined cell-type-resolved genomics and computational approaches to map crosstalk between hepatocytes and liver macrophages during fasting. We identified the glucocorticoid receptor (GR) as a key driver of fasting-induced reprogramming of the macrophage secretome including fasting-suppressed cytokines and showed that lack of macrophage GR impaired induction of ketogenesis during fasting as well as endotoxemia. Mechanistically, macrophage GR suppressed the expression of tumor necrosis factor (TNF) and promoted nuclear translocation of hepatocyte GR to activate a fat oxidation/ketogenesis-related gene program, cooperatively induced by GR and peroxisome proliferator-activated receptor alpha (PPARα) in hepatocytes. Together, our results demonstrate how resident liver macrophages directly influence ketogenesis in hepatocytes, thereby also outlining a strategy by which the immune system can set the metabolic tone during inflammatory disease and infection. 2022 1550-4131 https://doi.org/10.1016/j.cmet.2022.01.004 Cell Metabolism glucocorticoid receptor, fasting, nuclear receptor, macrophage, liver, hepatocyte, genomics, ketogenesis, transcripional regulation, tumor necrosis factor https://www.sciencedirect.com/science/article/pii/S1550413122000043 Anne Loft Søren Fisker Schmidt Giorgio Caratti Ulrich Stifel Jesper Havelund Revathi Sekar Yun Kwon Alba Sulaj Kan Kau Chow Ana Jimena Alfaro Thomas Schwarzmayr Nikolaj Rittig Mads Svart Foivos-Filippos Tsokanos Adriano Maida Andreas Blutke Annette Feuchtinger Niels ��ø������� Matthias ����ü���� Peter Nawroth Julia ������Ի��ö�徱 Nils J. ��æ�����𳾲��� Anja Zeigerer Jan Tuckermann Stephan Herzig article 10.3389/fmicb.2022.822304 CRISPR-Cas constitutes an adaptive prokaryotic defence system against invasive nucleic acids like viruses and plasmids. Beyond their role in immunity, CRISPR-Cas systems have been shown to closely interact with components of cellular DNA repair pathways, either by regulating their expression or via direct protein-protein contact and enzymatic activity. The integrase Cas1 is usually involved in the adaptation phase of CRISPR-Cas immunity but an additional role in cellular DNA repair pathways has been proposed previously. Here, we analysed the capacity of an archaeal Cas1 from Haloferax volcanii to act upon DNA damage induced by oxidative stress and found that a deletion of the cas1 gene led to reduced survival rates following stress induction. In addition, our results indicate that Cas1 is directly involved in DNA repair as the enzymatically active site of the protein is crucial for growth under oxidative conditions. Based on biochemical assays, we propose a mechanism by which Cas1 plays a similar function to DNA repair protein Fen1 by cleaving branched intermediate structures. The present study broadens our understanding of the functional link between CRISPR-Cas immunity and DNA repair by demonstrating that Cas1 and Fen1 display equivalent roles during archaeal DNA damage repair. 2022 1664-302X 10.3389/fmicb.2022.822304 Frontiers in Microbiology 13 https://www.frontiersin.org/article/10.3389/fmicb.2022.822304 Julia ��ö���ٳ� Victoria Smith ��ö���� Fallmann Sabine ��ö�Ծ��� Tharani Thuraisingam Henning Urlaub Peter F. Stadler Thorsten Allers Frank Hille Anita Marchfelder article stifel_glucocorticoids_2022 Objectives: Glucocorticoids ({GCs}) are one of the most widely prescribed anti-inflammatory drugs. By acting through their cognate receptor, the glucocorticoid receptor ({GR}), {GCs} downregulate the expression of pro-inflammatory genes and upregulate the expression of anti-inflammatory genes. Metabolic pathways have recently been identified as key parts of both the inflammatory activation and anti-inflammatory polarization of macrophages, immune cells responsible for acute inflammation and tissue repair. It is currently unknown whether {GCs} control macrophage metabolism, and if so, to what extent metabolic regulation by {GCs} confers anti-inflammatory activity. Methods: Using transcriptomic and metabolomic profiling of macrophages, we identified {GC}-controlled pathways involved in metabolism, especially in mitochondrial function. Results: Metabolic analyses revealed that {GCs} repress glycolysis in inflammatory myeloid cells and promote tricarboxylic acid ({TCA}) cycle flux, promoting succinate metabolism and preventing intracellular accumulation of succinate. Inhibition of {ATP} synthase attenuated {GC}-induced transcriptional changes, likely through stalling of {TCA} cycle anaplerosis. We further identified a glycolytic regulatory transcription factor, {HIF}1a, as regulated by {GCs}, and as a key regulator of {GC} responsiveness during inflammatory challenge. Conclusions: Our findings link metabolism to gene regulation by {GCs} in macrophages. Ó 2021 The Author(s). Published by Elsevier {GmbH}. This is an open access article under the {CC} {BY} license (http://creativecommons.org/licenses/by/4.0/). 2022 22128778 10.1016/j.molmet.2021.101424 57 101424 https://linkinghub.elsevier.com/retrieve/pii/S2212877821002829 Ulrich Stifel Eva-Maria Wolfschmitt Josef Vogt Ulrich Wachter Daniel Tews Melanie Hogg Fabian Zink Nora Maria Koll Sandra Winning ��é���� Mounier ��é��é�徱���ٱ� Chazaud Peter Radermacher Pamela Fischer-Posovszky Giorgio Caratti Jan Tuckermann article https://doi.org/10.1111/plb.13384 Abstract Drought events may increase the likelihood that the plant water transport system becomes interrupted by embolism. Yet our knowledge about the temporal frequency of xylem embolism in the field is frequently lacking, as it requires detailed, long-term measurements. We measured xylem embolism resistance and midday xylem water potentials during the consecutive summers of 2019 and 2020 to estimate maximum levels of embolism in leaf and stem xylem of ten temperate angiosperm tree species. We also studied vessel and pit membrane characteristics based on light and electron microscopy to corroborate potential differences in embolism resistance between leaves and stems. Apart from A. pseudoplatanus and Q. petraea, eight species experienced minimum xylem water potentials that were close to or below those required to initiate embolism. Water potentials corresponding to ca. 12% loss of hydraulic conductivity (PLC) could occur in six species, while considerable levels of embolism around 50% PLC were limited to B. pendula and C. avellana. There was a general agreement in embolism resistance between stems and leaves, with leaves being equally or more resistant than stems. Also, xylem embolism resistance was significantly correlated to intervessel pit membrane thickness (TPM) for stems, but not to vessel diameter and total intervessel pit membrane surface area of a vessel. Our data indicate that low amounts of embolism occur in most species during moderate summer drought, and that considerable levels of embolism are uncommon. Moreover, our experimental and TPM data show that leaf xylem is generally no more vulnerable than stem xylem. 2022 https://doi.org/10.1111/plb.13384 Plant Biology n/a n/a Hydraulic safety margin, pit characteristics, summer drought, vulnerability segmentation, xylem embolism resistance, xylem anatomy https://onlinelibrary.wiley.com/doi/abs/10.1111/plb.13384 X. Guan K.-F. Cao L. Pereira L. Kaack S. A. M. McAdam S. Jansen article doi:10.1126/scisignal.abm4452 Mutations that activate members of the RAS family of GTPases are associated with various cancers and drive tumor growth. The glucocorticoid receptor (GR), a member of the nuclear receptor family, has been proposed to interact with and inhibit the activation of components of the PI3K-AKT and MAPK pathways downstream of RAS. In the absence of activating ligands, we found that GR was present in cytoplasmic KRAS-containing complexes and inhibited the activation of wild-type and oncogenic KRAS in mouse embryonic fibroblasts and human lung cancer A549 cells. The DNA binding domain of GR was involved in the interaction with KRAS, but GR-dependent inhibition of RAS activation did not depend on the nuclear translocation of GR. The addition of ligand released GR-dependent inhibition of RAS, AKT, the MAPK p38, and the MAPKK MEK. CRISPR-Cas9–mediated deletion of GR in A549 cells enhanced tumor growth in xenografts in mice. Patient samples of non–small cell lung carcinomas showed lower expression of NR3C1, the gene encoding GR, compared to adjacent normal tissues and lower NR3C1 expression correlated with a worse disease outcome. These results suggest that glucocorticoids prevent the ability of GR to limit tumor growth by inhibiting RAS activation, which has potential implications for the use of glucocorticoids in patients with cancer. In its unliganded state, the glucocorticoid receptor inhibits RAS activation. The glucocorticoid receptor (GR) is a nuclear hormone receptor that localizes to the cytoplasm in the absence of activating ligands. Caratti et al. found that GR interacted with cytoplasmic complexes containing the small GTPase RAS and the RAS-activating kinase RAF1 in mouse embryonic fibroblasts and human lung cancer A549 cells. The genetic loss of GR or the ligand-induced nuclear translocation of GR increased the activation of RAS and RAS-dependent mitogenic signaling, stimulated cell proliferation in vitro, and promoted the growth of A549 xenografts in mice. These effects on RAS activation did not depend on GR transcriptional activity. Thus, in addition to controlling transcriptional programs that regulate cell growth, GR also limits the activation of RAS through a nongenomic mechanism. 2022 10.1126/scisignal.abm4452 Science Signaling 15 eabm4452 726 Bozhena Caratti Giorgio Caratti Kristina Breitenecker Melanie Engler Naser Kazemitash Rebecca Traut Rainer Wittig Emilio Casanova Mohammad Reza Ahmadian Herwig P. Moll Ion Cristian Cirstea article Radamaker2021 Systemic AL amyloidosis is a rare disease that is caused by the misfolding of immunoglobulin light chains (LCs). Potential drivers of amyloid formation in this disease are post-translational modifications (PTMs) and the mutational changes that are inserted into the LCs by somatic hypermutation. Here we present the cryo electron microscopy (cryo-EM) structure of an ex vivo $\lambda$1-AL amyloid fibril whose deposits disrupt the ordered cardiomyocyte structure in the heart. The fibril protein contains six mutational changes compared to the germ line and three PTMs (disulfide bond, N-glycosylation and pyroglutamylation). Our data imply that the disulfide bond, glycosylation and mutational changes contribute to determining the fibril protein fold and help to generate a fibril morphology that is able to withstand proteolytic degradation inside the body. 2021 11 05 2041-1723 10.1038/s41467-021-26553-9 Nature Communications 12 6434 1 https://doi.org/10.1038/s41467-021-26553-9 Lynn Radamaker Sara Karimi-Farsijani Giada Andreotti Julian Baur Sarah Schreiner Natalie Berghaus Raoul Motika Christian Haupt Volker Schmidt Stefanie Huhn Ute Hegenbart Stefan O. Schoenland Sebastian Wiese Marcus Faendrich article article 2021 11 10.1128/Spectrum.01525-21 Microbiology Spectrum 9 Luis ��í��ܱ��-�� Kelly Speer Kerstin Wilhelm Nancy Simmons Rodrigo �ѱ������í�� Simone Sommer Marco Tschapka article Goldbeck2021 Bacteriocins are antimicrobial peptides produced by bacteria to inhibit competitors in their natural environments. Some of these peptides have emerged as commercial food preservatives and, due to the rapid increase in antibiotic resistant bacteria, are also discussed as interesting alternatives to antibiotics for therapeutic purposes. Currently, commercial bacteriocins are produced exclusively with natural producer organisms on complex substrates and are sold as semi-purified preparations or crude fermentates. To allow clinical application, efficacy of production and purity of the product need to be improved. This can be achieved by shifting production to recombinant microorganisms. Here, we identify Corynebacterium glutamicum as a suitable production host for the bacteriocin pediocin PA-1. C. glutamicum CR099 shows resistance to high concentrations of pediocin PA-1 and the bacteriocin was not inactivated when spiked into growing cultures of this bacterium. Recombinant C. glutamicum expressing a synthetic pedACDCgl operon releases a compound that has potent antimicrobial activity against Listeria monocytogenes and Listeria innocua and matches size and mass:charge ratio of commercial pediocin PA-1. Fermentations in shake flasks and bioreactors suggest that low levels of dissolved oxygen are favorable for production of pediocin. Under these conditions, however, reduced activity of the TCA cycle resulted in decreased availability of the important pediocin precursor l-asparagine suggesting options for further improvement. Overall, we demonstrate that C. glutamicum is a suitable host for recombinant production of bacteriocins of the pediocin family. 2021 11 01 1096-7176 Metabolic Engineering 68 34-45 Corynebacterium glutamicum; Bacteriocin; Pediocin; Recombinant production; Rational design; Antimicrobial peptide; Oxygen limitation; Listeria sp https://www.sciencedirect.com/science/article/pii/S1096717621001415 Oliver Goldbeck Dominique N. Desef Kirill V. Ovchinnikov Fernando Perez-Garcia Jens Christmann Peter Sinner Peter Crauwels Dominik Weixler Peng Cao Judith Becker Michael Kohlstedt Julian Kager Bernhard J. Eikmanns Gerd M. Seibold Christoph Herwig Christoph Wittmann Nadav S. Bar Dzung B. Diep Christian U. Riedel article article 2021 11 10.1371/journal.ppat.1009675 PLOS Pathogens 17 e1009675 B. Montero Wasim Uddin Nina Schwensow Mark Gillingham Rakotomalala Ratovonamana S. Rakotondranary Victor Corman Christian Drosten ��ö���� Ganzhorn Simone Sommer unknown 2021 11 10.22541/au.163590446.60539987/v1 Ana Carranco Mark Gillingham Kerstin Wilhelm �Ѳ���í�� Torres Simone Sommer David Romo article https://doi.org/10.1002/2211-5463.13350 The energy-saving strategy of Djungarian hamsters (Phodopus sungorus, Cricetidae) to overcome harsh environmental conditions comprises of behavioral, morphological, and physiological adjustments, including spontaneous daily torpor, a metabolic downstate. These acclimatizations are triggered by short photoperiod and orchestrated by the hypothalamus. Key mechanisms of long-term photoperiodic acclimatizations have partly been described, but specific mechanisms that acutely control torpor remain incomplete. Here, we performed comparative transcriptome analysis on hypothalamus of normometabolic hamsters in their summer- and winter-like state to enable us to identify changes in gene expression during photoperiodic acclimations. Comparing nontorpid and torpid hamsters may also be able to pin down mechanisms relevant for torpor control. A de novo assembled transcriptome of the hypothalamus was generated from hamsters acclimated to long photoperiod or to short photoperiod. The hamsters were sampled either during long photoperiod normothermia, short photoperiod normothermia, or short photoperiod-induced spontaneous torpor with a body temperature of 24.6 ± 1.0 °C, or. The mRNA-seq analysis revealed that 32 and 759 genes were differentially expressed during photoperiod or torpor, respectively. Biological processes were not enriched during photoperiodic acclimatization but were during torpor, where transcriptional and metabolic processes were reinforced. Most extremely regulated genes (those genes with |log2(FC)| > 2.0 and padj < 0.05 of a pairwise group comparison) underpinned the role of known key players in photoperiodic comparison, but these genes exhibit adaptive and protective adjustments during torpor. Targeted analyses of genes from potentially involved hypothalamic systems identified gene regulation of previously described torpor-relevant systems and a potential involvement of glucose transport. 2021 https://doi.org/10.1002/2211-5463.13350 FEBS Open Bio n/a n/a RNA-Seq, gene expression, metabolism, hypothermia, Siberian hamster, Phodopus sungorus https://febs.onlinelibrary.wiley.com/doi/abs/10.1002/2211-5463.13350 Elena Haugg Janus Borner Victoria Diedrich Annika Herwig article WILFERT2021107506 The OneHealth approach aims to further our understanding of the drivers of human, animal and environmental health, and, ultimately, to improve them by combining approaches and knowledge from medicine, biology and fields beyond. Wild and managed bees are essential pollinators of crops and wild flowers. Their health thus directly impacts on human and environmental health. At the same time, these bee species represent highly amenable and relevant model organisms for a OneHealth approach that aims to study fundamental epidemiological questions. In this review, we focus on how infectious diseases of wild and managed bees can be used as a OneHealth model system, informing fundamental questions on ecological immunology and disease transmission, while addressing how this knowledge can be used to tackle the issues facing pollinator health. 2021 0022-2011 https://doi.org/10.1016/j.jip.2020.107506 Journal of Invertebrate Pathology 186 107506 Bee, OneHealth, Social immunity, Disease transmission, Vector, Virulence https://www.sciencedirect.com/science/article/pii/S0022201120302123 Lena Wilfert Mark J.F. Brown Vincent Doublet