Protein disulfide isomerase acts as an injury response signal that enhances fibrin generation via tissue factor activation

The activation of initiator protein tissue factor (TF) is likely to be a crucial step in the blood coagulation process, which leads to fibrin formation. The stimuli responsible for inducing TF activation are largely undefined. Here we show that the oxidoreductase protein disulfide isomerase (PDI) directly promotes TF-dependent fibrin production during thrombus formation in vivo. After endothelial denudation of mouse carotid arteries, PDI was released at the injury site from adherent platelets and disrupted vessel wall cells. Inhibition of PDI decreased TF-triggered fibrin formation in different in vivo murine models of thrombus formation, as determined by intravital fluorescence microscopy. PDI infusion increased — and, under conditions of decreased platelet adhesion, PDI inhibition reduced — fibrin generation at the injury site, indicating that PDI can directly initiate blood coagulation. In vitro, human platelet–secreted PDI contributed to the activation of cryptic TF on microvesicles (microparticles). Mass spectrometry analyses indicated that part of the extracellular cysteine 209 of TF was constitutively glutathionylated. Mixed disulfide formation contributed to maintaining TF in a state of low functionality. We propose that reduced PDI activates TF by isomerization of a mixed disulfide and a free thiol to an intramolecular disulfide. Our findings suggest that disulfide isomerases can act as injury response signals that trigger the activation of fibrin formation following vessel injury

TransGeoTherm - Erdwärmepotenzial in der Neiße-Region

Die Broschüre gibt einen Überblick über die Ergebnisse des EU-Projektes TransGeoTherm. Im Projekt wurde ein grenzüberschreitendes 3D-Modell entwickelt, das den geologischen Untergrund der Neiße-Region darstellt. Mit dem 3D-Modell wurden geothermische Potenzialkarten berechnet. Damit steht erstmals für diese Region ein Hilfsmittel für die qualifizierte Planung geothermischer Anlagen zur Verfügung. Der Abschlussbericht richtet sich an Bürger, Unternehmen, Behörden und Institutionen, die sich mit der Erdwärmenutzung befassen

Der Geologische Dienst in Sachsen: Festband zum Jubiläum 150 Jahre Landesgeologie

Der Geologische Dienst von Sachsen feiert im Jahr 2022 sein 150-jähriges Jubiläum – am 6. April 1872 wurde die Geologische Landesuntersuchung im Königreich Sachsen gegründet. Auf 153 Seiten der Reihe „Geoprofil“ werden Einblicke in die Arbeit des Geologischen Dienstes im LfULG, seinen Aufgaben und die Dienste als zuständige Fachbehörde gegeben. Die elf Einzelbeiträge zeigen die aktuellen Herausforderungen und Chancen, die sich aus den Themenbereichen Umwelt, Naturschutz und Geologie für Sachsen stellen. Im Einzelnen geht es in den Beiträgen um die sächsische Rohstoffstrategie, die Suche nach einem Endlagerstandort für radioaktive Abfälle, Erdwärme, Hydrogeologie, die Eisenbahn Neubaustrecke Dresden – Prag, Naturgefahren, das geowissenschaftliche Archiv, Träger öffentlicher Belange (TöB), Geoparks und einen Blick in die 150 jährige Geschichte. Redaktionsschluss: 30.11.202

Murine CD4+ T Cell Responses Are Inhibited by Cytotoxic T Cell-Mediated Killing of Dendritic Cells and Are Restored by Antigen Transfer

Cytotoxic T lymphocytes (CTL) provide protection against pathogens and tumors. In addition, experiments in mouse models have shown that CTL can also kill antigen-presenting dendritic cells (DC), reducing their ability to activate primary and secondary CD8+ T cell responses. In contrast, the effects of CTL-mediated killing on CD4+ T cell responses have not been fully investigated. Here we use adoptive transfer of TCR transgenic T cells and DC immunization to show that specific CTL significantly inhibited CD4+ T cell proliferation induced by DC loaded with peptide or low concentrations of protein antigen. In contrast, CTL had little effect on CD4+ T cell proliferation induced by DC loaded with high protein concentrations or expressing antigen endogenously, even if these DC were efficiently killed and failed to accumulate in the lymph node (LN). Residual CD4+ T cell proliferation was due to the transfer of antigen from carrier DC to host APC, and predominantly involved skin DC populations. Importantly, the proliferating CD4+ T cells also developed into IFN-γ producing memory cells, a property normally requiring direct presentation by activated DC. Thus, CTL-mediated DC killing can inhibit CD4+ T cell proliferation, with the extent of inhibition being determined by the form and amount of antigen used to load DC. In the presence of high antigen concentrations, antigen transfer to host DC enables the generation of CD4+ T cell responses regardless of DC killing, and suggests mechanisms whereby CD4+ T cell responses can be amplified

Synopse virologischer Analysen im Nationalen Referenzzentrum für Influenzaviren während der COVID-19-Pandemie

Das Nationale Referenzzentrum für Influenzaviren gewinnt durch die fortlaufende Untersuchung von Proben aus den Sentinelpraxen der Arbeitsgemeinschaft Influenza einen umfassenden Überblick über die zirkulierenden respiratorischen Erreger in Deutschland. Dazu gehören neben SARS-CoV-2 und den Influenzaviren auch das Respiratorische Synzytialvirus, Parainfluenzaviren, humane Metapneumoviren, humane saisonale Coronaviren und humane Rhinoviren. Die Analyseergebnisse von 15.660 Sentinelproben sowie weiteren Isolaten im Zeitraum von Kalenderwoche 5/2020 bis 21/2022 werden im Epidemiologischen Bulletin 22/2022 vorgestellt. Beschrieben werden außerdem die Zirkulation respiratorischer Erreger im Vergleich zu vorpandemischen Saisons, die molekulare Charakterisierung und phylogenetische Analysen, die Überprüfung der Passgenauigkeit der eingesetzten Influenzaimpfstoffe und die Resistenzprüfung von Influenzaviren

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Household transmissibility and other characteristics of seasonal oseltamivir-resistant influenza A(H1N1) viruses, Germany, 2007-8

During the influenza season 2007-8, the proportion of seasonal influenza A(H1N1) viruses resistant to the neuraminidase inhibitor oseltamivir increased worldwide. We conducted an investigation to compare patients infected with oseltamivir-resistant (ose-R) and oseltamivir- susceptible (ose-S) influenza A(H1N1) viruses regarding risk factors for resistance and the capability to transmit in the household setting. Within a cohort of 396 laboratory confirmed influenza patients from sentinel physicians we conducted a nested casecontrol study among patients infected with A(H1N1). Thirty patients in the cohort were infected with influenza B, none with influenza A(H3N2) and 366 with A(H1N1). Of the 366 A(H1N1) viruses 52 (14%) were ose-R. Demographic characteristics, oseltamivir exposure, travel history and outcome were not significantly different between ose-S and ose-R patients. Among 133 households in the nested case-control study, secondary household attack rates in households with ose-R cases and households with ose-S cases were similar (23 versus 26%; p-value=0.54). Ose-R household status and occurrence of secondary cases were associated with an odds ratio of 0.85 (95% confidence interval 0.38-1.88). We conclude that seasonal ose-R influenza A(H1N1) viruses have transmitted well in the household setting