@article{vonKriesWeissFalkenhorstetal.2011, author = {von Kries, R{\"u}diger and Weiss, Susanne and Falkenhorst, Gerhard and Wirth, Stephan and Kaiser, Petra and Huppertz, Hans-Iko and Tenenbaum, Tobias and Schroten, Horst and Streng, Andrea and Liese, Johannes and Shai, Sonu and Niehues, Tim and Girschick, Hermann and Kuscher, Ellen and Sauerbrey, Axel and Peters, Jochen and Wirsing von Koenig, Carl Heinz and R{\"u}ckinger, Simon and Hampl, Walter and Michel, Detlef and Mertens, Thomas}, title = {Post-Pandemic Seroprevalence of Pandemic Influenza A (H1N1) 2009 Infection (Swine Flu) among Children < 18 Years in Germany}, series = {PLoS ONE}, volume = {6}, journal = {PLoS ONE}, number = {9}, doi = {10.1371/journal.pone.0023955}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-141698}, pages = {e23955}, year = {2011}, abstract = {Background: We determined antibodies to the pandemic influenza A (H1N1) 2009 virus in children to assess: the incidence of (H1N1) 2009 infections in the 2009/2010 season in Germany, the proportion of subclinical infections and to compare titers in vaccinated and infected children. Methodology/Principal Findings: Eight pediatric hospitals distributed over Germany prospectively provided sera from in-or outpatients aged 1 to 17 years from April 1(st) to July 31(st) 2010. Vaccination history, recall of infections and sociodemographic factors were ascertained. Antibody titers were measured with a sensitive and specific in-house hemagglutination inhibition test (HIT) and compared to age-matched sera collected during 6 months before the onset of the pandemic in Germany. We analyzed 1420 post-pandemic and 300 pre-pandemic sera. Among unvaccinated children aged 1-4 and 5-17 years the prevalence of HI titers (>= 1:10) was 27.1\% (95\% CI: 23.5-31.3) and 53.5\% (95\% CI: 50.9-56.2) compared to 1.7\% and 5.5\%, respectively, for pre-pandemic sera, accounting for a serologically determined incidence of influenza A (H1N1) 2009 during the season 2009/2010 of 25,4\% (95\% CI : 19.3-30.5) in children aged 1-4 years and 48.0\% (95\% CI: 42.6-52.0) in 5-17 year old children. Of children with HI titers >= 1: 10, 25.5\% (95\% CI: 22.5-28.8) reported no history of any infectious disease since June 2009. Among vaccinated children, 92\% (95\%-CI: 87.0-96.6) of the 5-17 year old but only 47.8\% (95\%-CI: 33.5-66.5) of the 1-4 year old children exhibited HI titers against influenza A virus (H1N1) 2009. Conclusion: Serologically determined incidence of influenza A (H1N1) 2009 infections in children indicates high infection rates with older children (5-17 years) infected twice as often as younger children. In about a quarter of the children with HI titers after the season 2009/2010 subclinical infections must be assumed. Low HI titers in young children after vaccination with the AS03(B)-adjuvanted split virion vaccine need further scrutiny.}, language = {en} } @techreport{MuellerSchererLorenzenAmmeretal.2022, author = {M{\"u}ller, J{\"o}rg and Scherer-Lorenzen, Michael and Ammer, Christian and Eisenhauer, Nico and Seidel, Dominik and Schuldt, Bernhard and Biedermann, Peter and Schmitt, Thomas and K{\"u}nzer, Claudia and Wegmann, Martin and Cesarz, Simone and Peters, Marcell and Feldhaar, Heike and Steffan-Dewenter, Ingolf and Claßen, Alice and B{\"a}ssler, Claus and von Oheimb, Goddert and Fichtner, Andreas and Thorn, Simon and Weisser, Wolfgang}, title = {BETA-FOR: Erh{\"o}hung der strukturellen Diversit{\"a}t zwischen Waldbest{\"a}nden zur Erh{\"o}hung der Multidiversit{\"a}t und Multifunktionalit{\"a}t in Produktionsw{\"a}ldern. Antragstext f{\"u}r die DFG Forschungsgruppe FOR 5375}, doi = {10.25972/OPUS-29084}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-290849}, pages = {210}, year = {2022}, abstract = {Der in j{\"u}ngster Zeit beobachtete kontinuierliche Verlust der β-Diversit{\"a}t in {\"O}kosystemen deutet auf homogene Gemeinschaften auf Landschaftsebene hin, was haupts{\"a}chlich auf die steigende Landnutzungsintensit{\"a}t zur{\"u}ckgef{\"u}hrt wird. Biologische Vielfalt ist mit zahlreichen Funktionen und der Stabilit{\"a}t von {\"O}kosystemen verkn{\"u}pft. Es ist daher zu erwarten, dass eine abnehmende β-Diversit{\"a}t auch die Multifunktionalit{\"a}t verringert. Wir kombinieren hier Fachwissen aus der Forstwissenschaft, der {\"O}kologie, der Fernerkundung, der chemischen {\"O}kologie und der Statistik in einem gemeinschaftlichen und experimentellen β-Diversit{\"a}tsdesign, um einerseits die Auswirkungen der Homogenisierung zu bewerten und andererseits Konzepte zu entwickeln, um negative Auswirkungen durch Homogenisierung in W{\"a}ldern r{\"u}ckg{\"a}ngig zu machen. Konkret werden wir uns mit der Frage besch{\"a}ftigen, ob die Verbesserung der strukturellen β-Komplexit{\"a}t (ESBC) in W{\"a}ldern durch Waldbau oder nat{\"u}rliche St{\"o}rungen die Biodiversit{\"a}t und Multifunktionalit{\"a}t in ehemals homogenen Produktionsw{\"a}ldern erh{\"o}hen kann. Unser Ansatz wird m{\"o}gliche Mechanismen hinter den beobachteten Homogenisierungs-Diversit{\"a}ts-Beziehungen identifizieren und zeigen, wie sich diese auf die Multifunktionalit{\"a}t auswirken. An elf Standorten in ganz Deutschland haben wir dazu zwei Waldbest{\"a}nde als zwei kleine "Waldlandschaften" ausgew{\"a}hlt. In einem dieser beiden Best{\"a}nde haben wir ESBC (Enhancement of Structural Beta Complexity)-Behandlungen durchgef{\"u}hrt. Im zweiten, dem Kontrollbestand, werden wir die gleich Anzahl 50x50m Parzellen ohne ESBC einrichten. Auf allen Parzellen werden wir 18 taxonomische Artengruppen aller trophischer Ebenen und 21 {\"O}kosystemfunktionen, einschließlich der wichtigsten Funktionen in W{\"a}ldern der gem{\"a}ßigten Zonen, messen. Der statistische Rahmen wird eine umfassende Analyse der Biodiversit{\"a}t erm{\"o}glichen, indem verschiedenen Aspekte (taxonomische, funktionelle und phylogenetische Vielfalt) auf verschiedenen Skalenebenen (α-, β-, γ-Diversit{\"a}t) quantifiziert werden. Um die Gesamtdiversit{\"a}t zu kombinieren, werden wir das Konzept der Multidiversit{\"a}t auf die 18 Taxa anwenden. Wir werden neue Ans{\"a}tze zur Quantifizierung und Aufteilung der Multifunktionalit{\"a}t auf α- und β-Skalen verwenden und entwickeln. Durch die experimentelle Beschreibung des Zusammenhangs zwischen β-Diversit{\"a}t und Multifunktionalit{\"a}t in einer Reallandschaft wird unsere Forschung einen neuen Weg einschlagen. Dar{\"u}ber hinaus werden wir dazu beitragen, verbesserte Leitlinien f{\"u}r waldbauliche Konzepte und f{\"u}r das Management nat{\"u}rlicher St{\"o}rungen zu entwickeln, um Homogenisierungseffekte der Vergangenheit umzukehren.}, subject = {Wald{\"o}kosystem}, language = {en} } @article{SchlegelPetersDooseetal.2019, author = {Schlegel, Jan and Peters, Simon and Doose, S{\"o}ren and Schubert-Unkmeir, Alexandra and Sauer, Markus}, title = {Super-resolution microscopy reveals local accumulation of plasma membrane gangliosides at Neisseria meningitidis Invasion Sites}, series = {Frontiers in Cell and Developmental Biology}, volume = {7}, journal = {Frontiers in Cell and Developmental Biology}, number = {194}, doi = {10.3389/fcell.2019.00194}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-201639}, year = {2019}, abstract = {Neisseria meningitidis (meningococcus) is a Gram-negative bacterium responsible for epidemic meningitis and sepsis worldwide. A critical step in the development of meningitis is the interaction of bacteria with cells forming the blood-cerebrospinal fluid barrier, which requires tight adhesion of the pathogen to highly specialized brain endothelial cells. Two endothelial receptors, CD147 and the β2-adrenergic receptor, have been found to be sequentially recruited by meningococci involving the interaction with type IV pilus. Despite the identification of cellular key players in bacterial adhesion the detailed mechanism of invasion is still poorly understood. Here, we investigated cellular dynamics and mobility of the type IV pilus receptor CD147 upon treatment with pili enriched fractions and specific antibodies directed against two extracellular Ig-like domains in living human brain microvascular endothelial cells. Modulation of CD147 mobility after ligand binding revealed by single-molecule tracking experiments demonstrates receptor activation and indicates plasma membrane rearrangements. Exploiting the binding of Shiga (STxB) and Cholera toxin B (CTxB) subunits to the two native plasma membrane sphingolipids globotriaosylceramide (Gb3) and raft-associated monosialotetrahexosylganglioside GM1, respectively, we investigated their involvement in bacterial invasion by super-resolution microscopy. Structured illumination microscopy (SIM) and direct stochastic optical reconstruction microscopy (dSTORM) unraveled accumulation and coating of meningococci with GM1 upon cellular uptake. Blocking of CTxB binding sites did not impair bacterial adhesion but dramatically reduced bacterial invasion efficiency. In addition, cell cycle arrest in G1 phase induced by serum starvation led to an overall increase of GM1 molecules in the plasma membrane and consequently also in bacterial invasion efficiency. Our results will help to understand downstream signaling events after initial type IV pilus-host cell interactions and thus have general impact on the development of new therapeutics targeting key molecules involved in infection.}, language = {en} } @article{PetersFohmannRudeletal.2021, author = {Peters, Simon and Fohmann, Ingo and Rudel, Thomas and Schubert-Unkmeir, Alexandra}, title = {A Comprehensive Review on the Interplay between Neisseria spp. and Host Sphingolipid Metabolites}, series = {Cells}, volume = {10}, journal = {Cells}, number = {11}, issn = {2073-4409}, doi = {10.3390/cells10113201}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-250203}, year = {2021}, abstract = {Sphingolipids represent a class of structural related lipids involved in membrane biology and various cellular processes including cell growth, apoptosis, inflammation and migration. Over the past decade, sphingolipids have become the focus of intensive studies regarding their involvement in infectious diseases. Pathogens can manipulate the sphingolipid metabolism resulting in cell membrane reorganization and receptor recruitment to facilitate their entry. They may recruit specific host sphingolipid metabolites to establish a favorable niche for intracellular survival and proliferation. In contrast, some sphingolipid metabolites can also act as a first line defense against bacteria based on their antimicrobial activity. In this review, we will focus on the strategies employed by pathogenic Neisseria spp. to modulate the sphingolipid metabolism and hijack the sphingolipid balance in the host to promote cellular colonization, invasion and intracellular survival. Novel techniques and innovative approaches will be highlighted that allow imaging of sphingolipid derivatives in the host cell as well as in the pathogen.}, language = {en} } @phdthesis{Peters2021, author = {Peters, Simon}, title = {The impact of sphingolipids on \(Neisseria\) \(meningitidis\) and their role in meningococcal pathogenicity}, doi = {10.25972/OPUS-22623}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-226233}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2021}, abstract = {The obligate human pathogen Neisseria meningitidis is a major cause of sepsis and meningitis worldwide. It affects mainly toddlers and infants and is responsible for thousands of deaths each year. In this study, different aspects of the importance of sphingolipids in meningococcal pathogenicity were investigated. In a first step, the acid sphingomyelinase (ASM), which degrades membrane sphingomyelin to ceramide, was studied in the context of meningococcal infection. A requirement for ASM surface activity is its translocation from the lysosomal compartment to the cell surface, a process that is currently poorly understood. This study used various approaches, including classical invasion and adherence assays, flow cytometry, and classical and super resolution immunofluorescence microscopy (dSTORM). The results showed that the live, highly piliated N. meningitidis strain 8013/12 induced calcium-dependent ASM translocation in human brain microvascular endothelial cells (HBMEC). Furthermore, it promoted the formation of ceramide-rich platforms (CRPs). In addition, ASM translocation and CRP formation were observed after treating the cells with pili-enriched fractions derived from the same strain. The importance for N. meningitidis to utilize this pathway was shown by the inhibition of the calcium-dependent ASM translocation, which greatly decreased the number of invasive bacteria. I also investigated the importance of the glycosphingolipids GM1 and Gb3. The results showed that GM1, but not Gb3, plays an important role in the ability of N. meningitidis to invade HBMEC. By combining dSTORM imaging and microbiological approaches, we demonstrated that GM1 accumulated prolifically around bacteria during the infection, and that this interaction seemed essential for meningococcal invasion. Sphingolipids are not only known for their beneficial effect on pathogens. Sphingoid bases, including sphingosine, are known for their antimicrobial activity. In the last part of this study, a novel correlative light and electron microscopy approach was established in the combination with click chemistry to precisely localize azido-functionalized sphingolipids in N. meningitidis. The result showed a distinct concentration-dependent localization in either the outer membrane (low concentration) or accumulated in the cytosol (high concentration). This pattern was confirmed by mass spectrometry on separated membrane fractions. Our data provide a first insight into the underlying mechanism of antimicrobial sphingolipids.}, subject = {Neisseria meningitidis}, language = {en} } @article{PetersKaiserFinketal.2021, author = {Peters, Simon and Kaiser, Lena and Fink, Julian and Schumacher, Fabian and Perschin, Veronika and Schlegel, Jan and Sauer, Markus and Stigloher, Christian and Kleuser, Burkhard and Seibel, Juergen and Schubert-Unkmeir, Alexandra}, title = {Click-correlative light and electron microscopy (click-AT-CLEM) for imaging and tracking azido-functionalized sphingolipids in bacteria}, series = {Scientific Reports}, volume = {11}, journal = {Scientific Reports}, number = {1}, doi = {10.1038/s41598-021-83813-w}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-259147}, pages = {4300}, year = {2021}, abstract = {Sphingolipids, including ceramides, are a diverse group of structurally related lipids composed of a sphingoid base backbone coupled to a fatty acid side chain and modified terminal hydroxyl group. Recently, it has been shown that sphingolipids show antimicrobial activity against a broad range of pathogenic microorganisms. The antimicrobial mechanism, however, remains so far elusive. Here, we introduce 'click-AT-CLEM', a labeling technique for correlated light and electron microscopy (CLEM) based on the super-resolution array tomography (srAT) approach and bio-orthogonal click chemistry for imaging of azido-tagged sphingolipids to directly visualize their interaction with the model Gram-negative bacterium Neisseria meningitidis at subcellular level. We observed ultrastructural damage of bacteria and disruption of the bacterial outer membrane induced by two azido-modified sphingolipids by scanning electron microscopy and transmission electron microscopy. Click-AT-CLEM imaging and mass spectrometry clearly revealed efficient incorporation of azido-tagged sphingolipids into the outer membrane of Gram-negative bacteria as underlying cause of their antimicrobial activity.}, language = {en} } @article{MagesShojaaKohletal.2021, author = {Mages, Michelle and Shojaa, Mahdieh and Kohl, Matthias and Stengel, Simon von and Becker, Clemens and Gosch, Markus and Jakob, Franz and Kerschan-Schindl, Katharina and Kladny, Bernd and Kl{\"o}ckner, Nicole and Lange, Uwe and Middeldorf, Stefan and Peters, Stefan and Schoene, Daniel and Sieber, Cornel C. and Tholen, Reina and Thomasius, Friederike E. and Uder, Michael and Kemmler, Wolfgang}, title = {Exercise effects on Bone Mineral Density in men}, series = {Nutrients}, volume = {13}, journal = {Nutrients}, number = {12}, issn = {2072-6643}, doi = {10.3390/nu13124244}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-250247}, year = {2021}, abstract = {In contrast to postmenopausal women, evidence for a favorable effect of exercise on Bone Mineral Density (BMD) is still limited for men. This might be due to the paucity of studies, but also to the great variety of participants and study characteristics that may dilute study results. The aim of the present systematic review and meta-analysis was to evaluate the effect of exercise on BMD changes with rational eligibility criteria. A comprehensive search of six electronic databases up to 15 March 2021 was conducted. Briefly, controlled trials ≥6 months that determined changes in areal BMD in men >18 years old, with no apparent diseases or pharmacological therapy that relevantly affect bone metabolism, were included. BMD changes (standardized mean differences: SMD) of the lumbar spine (LS) and femoral neck (FN) were considered as outcomes. Twelve studies with 16 exercise and 12 control groups were identified. The pooled estimate of random-effect analysis was SMD = 0.38, 95\%-CI: 0.14-0.61 and SMD = 0.25, 95\%-CI: 0.00-0.49, for LS and FN, respectively. Heterogeneity between the trials was low-moderate. Funnel plots and rank and regression correlation tests indicate evidence for small study publication bias for LS but not FN-BMD. Subgroup analyses that focus on study length, type of exercise and methodologic quality revealed no significant difference between each of the three categories. In summary, we provided further evidence for a low but significant effect of exercise on BMD in men. However, we are currently unable to give even rough exercise recommendations for male cohorts.}, language = {en} }