Lah is a transmembrane protein and requires Spa10 for stable positioning of Woronin bodies at the septal pore of Aspergillus fumigatus

Woronin bodies are specialized, fungal-specific organelles that enable an immediate closure of septal pores after injury to protect hyphae from excessive cytoplasmic bleeding. In most Ascomycetes, Woronin bodies are tethered at the septal pore by so-called Lah proteins. Using the pathogenic mold Aspergillus fumigatus as a model organism, we show that the C-terminal 288 amino acids of Lah (LahC(288)) bind to the rim of the septal pore. LahC(288) essentially consists of a membrane spanning region and a putative extracellular domain, which are both required for the targeting to the septum. In an A. fumigatus rho4 deletion mutant that has a severe defect in septum formation, LahC(288) is recruited to spot-like structures in or at the lateral membrane. This suggests that LahC is recruited before Rho4 starts to govern the septation process. Accordingly, we found that in wild type hyphae Lah is bound before a cross-wall emerges and thus enables a tethering of Woronin bodies at the site of the newly formed septum. Finally, we identified Spa10, a member of a recently described family of septal poreassociated proteins, as a first protein that directly or indirectly interacts with LahC to allow a stable positioning of Woronin bodies at the mature septum

An Ontology for Designing Models of Epidemics

Models of epidemics allow decision makers to explore the consequences of different interventions. The Models of Infectious Disease Agent Study (MIDAS) project has been collecting studies, models, data supporting the models, and publications providing historical evidence about epidemics.
An ontology has been developed for MIDAS to support the collection, documentation, and dissemination of models. It uses relations to link taxonomies (including a subset of the infectious disease ontology) that define the scope of its models and supporting documentation.
The ontology is used to aid in the navigation process that is part of the user interface for identifying which studies and publications are available in the MIDAS repository (MREP) that are consistent with the many parameters associated with a particular study. 
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Heme Oxygenase, Inflammation, and Fibrosis: The Good, the Bad, and the Ugly?

Upon injury, prolonged inflammation and oxidative stress may cause pathological wound healing and fibrosis, leading to formation of excessive scar tissue. Fibrogenesis can occur in most organs and tissues and may ultimately lead to organ dysfunction and failure. The underlying mechanisms of pathological wound healing still remain unclear, and are considered to be multifactorial, but so far, no efficient anti-fibrotic therapies exist. Extra- and intracellular levels of free heme may be increased in a variety of pathological conditions due to release from hemoproteins. Free heme possesses pro-inflammatory and oxidative properties, and may act as a danger signal. Effects of free heme may be counteracted by heme-binding proteins or by heme degradation. Heme is degraded by heme oxygenase (HO) that exists as two isoforms: inducible HO-1 and constitutively expressed HO-2. HO generates the effector molecules biliverdin/bilirubin, carbon monoxide, and free iron/ferritin. HO deficiency in mouse and man leads to exaggerated inflammation following mild insults, and accumulating epidemiological and preclinical studies support the widely recognized notion of the cytoprotective, anti-oxidative, and anti-inflammatory effects of the activity of the HO system and its effector molecules. In this review, we address the potential effects of targeted HO-1 induction or administration of HO-effector molecules as therapeutic targets in fibrotic conditions to counteract inflammatory and oxidative insults. This is exemplified by various clinically relevant conditions, such as hypertrophic scarring, chronic inflammatory liver disease, chronic pancreatitis, and chronic graft rejection in transplantation

Visible-Light-Mediated Charge Transfer Enables C−C Bond Formation with Traceless Acceptor Groups

The development and application of traceless acceptor groups in photochemical C−C bond formation is described. This strategy was enabled by the photoexcitation of electron donor–acceptor (EDA) complexes with visible light. The traceless acceptors, which were readily prepared from amino acid and peptide feedstocks, could be used to alkylate a wide range of heteroarene and enamine donors under metal- and peroxide-free conditions. The crucial role of the EDA complexes in the mechanism of these reactions was explored through combined experimental and computational studies

Mehr als nur Rohstofflieferant

Mit der Transformation zu einer biobasierten Wirtschaft bieten sich auch über die Rohstoffbereitstellung hinaus Entwicklungsmöglichkeiten für den ländlichen Raum. Diese in einer nachhaltigen Art und Weise zu fördern, ist eine Zukunftsaufgabe von Politik, Wirtschaft, Wissenschaft und Zivilgesellschaft

Approaching the Secrets of N-Glycosylation in Aspergillus fumigatus: Characterization of the AfOch1 Protein

The mannosyltransferase Och1 is the key enzyme for synthesis of elaborated protein N-glycans in yeast. In filamentous fungi genes implicated in outer chain formation are present, but their function is unclear. In this study we have analyzed the Och1 protein of Aspergillus fumigatus. We provide first evidence that poly-mannosylated N-glycans exist in A. fumigatus and that their synthesis requires AfOch1 activity. This implies that AfOch1 plays a similar role as S. cerevisiae ScOch1 in the initiation of an N-glycan outer chain. A Δafoch1 mutant showed normal growth under standard and various stress conditions including elevated temperature, cell wall and oxidative stress. However, sporulation of this mutant was dramatically reduced in the presence of high calcium concentrations, suggesting that certain proteins engaged in sporulation require N-glycan outer chains to be fully functional. A characteristic feature of AfOch1 and Och1 homologues from other filamentous fungi is a signal peptide that clearly distinguishes them from their yeast counterparts. However, this difference does not appear to have consequences for its localization in the Golgi. Replacing the signal peptide of AfOch1 by a membrane anchor had no impact on its ability to complement the sporulation defect of the Δafoch1 strain. The mutant triggered a normal cytokine response in infected murine macrophages, arguing against a role of outer chains as relevant Aspergillus pathogen associated molecular patterns. Infection experiments provided no evidence for attenuation in virulence; in fact, according to our data the Δafoch1 mutant may even be slightly more virulent than the control strains

Continuous face authentication scheme for mobile devices with tracking and liveness detection

We present a novel scheme for continuous face authentication using mobile device cameras that addresses the issue of spoof attacks and attack windows in state-of-the-art approaches. Our scheme authenticates a user based on extracted facial features. However, unlike other schemes that periodically re-authenticate a user, our scheme tracks the authenticated face and only attempts re-authentication when the authenticated face is lost. This allows our scheme to eliminate attack windows that exist in schemes authenticating periodically and immediately recognise impostor usage. We also introduce a robust liveness detection component to our scheme that can detect printed faces and face videos. We describe how the addition of liveness detection enhances the robustness of our scheme against spoof attacks, improving on state-of-the-art approaches that lack this capability. Furthermore, we create the first dataset of facial videos collected from mobile devices during different real-world activities (walking, sitting and standing) such that our results reflect realistic scenarios. Our dataset therefore allows us to give new insight into the impact of user activity on facial recognition. Our dataset also includes spoofed facial videos for liveness testing. We use our dataset alongside two benchmark datasets for our experiments. We show and discuss how our scheme improves on existing continuous face authentication approaches and efficiently enhances device security

Kosten, Nutzen, Erlöse bei der Renaturierung von Gewässern: Ermittlung und ökonomische Analyse der Kosten, Nutzen und Erlöse bei der Renaturierung von Gewässern im ländlichen Raum: Projekt ElmaR II – Kosten, Nutzen, Erlöse: Abschlussbericht

Die Umsetzung von Maßnahmen zur Renaturierung von Gewässern geht mit zahlreichen planerischen und finanziellen Herausforderungen einher. Will man dies erfolgreich vor Ort mit den Flächeneigentümern/-nutzern, Kommunen, etc. gestalten, sind u.a. Kosten-Nutzen-Betrachtungen notwendig. Am Beispiel der Anlage von gewässerschonenden Bewirtschaftungsformen (z. B. Agrarholzsysteme) wird dargestellt. dass die Verbesserung ökologischer Zustände an Gewässern auch Wirkungen auf regionale Wertschöpfungsketten entfalten können. Ausführungen zum (Umwelt-)Nutzen von Gewässerrenaturierungen und zum Einsatz möglicher Förder- und Finanzierungsinstrumentarien runden die Studie ab. Die Veröffentlichung richtet sich an Flächeneigentümer, Flächenbewirtschafter, Kommunen, politische Entscheidungsträger und fachlich interessierte Bürger. Redaktionsschluss: 30.06.202

Diannexin Protects against Renal Ischemia Reperfusion Injury and Targets Phosphatidylserines in Ischemic Tissue

Renal ischemia/reperfusion injury (IRI) frequently complicates shock, renal transplantation and cardiac and aortic surgery, and has prognostic significance. The translocation of phosphatidylserines to cell surfaces is an important pro-inflammatory signal for cell-stress after IRI. We hypothesized that shielding of exposed phosphatidylserines by the annexin A5 (ANXA5) homodimer Diannexin protects against renal IRI. Protective effects of Diannexin on the kidney were studied in a mouse model of mild renal IRI. Diannexin treatment before renal IRI decreased proximal tubule damage and leukocyte influx, decreased transcription and expression of renal injury markers Neutrophil Gelatinase Associated Lipocalin and Kidney Injury Molecule-1 and improved renal function. A mouse model of ischemic hind limb exercise was used to assess Diannexin biodistribution and targeting. When comparing its biodistribution and elimination to ANXA5, Diannexin was found to have a distinct distribution pattern and longer blood half-life. Diannexin targeted specifically to the ischemic muscle and its affinity exceeded that of ANXA5. Targeting of both proteins was inhibited by pre-treatment with unlabeled ANXA5, suggesting that Diannexin targets specifically to ischemic tissues via phosphatidylserine-binding. This study emphasizes the importance of phosphatidylserine translocation in the pathophysiology of IRI. We show for the first time that Diannexin protects against renal IRI, making it a promising therapeutic tool to prevent IRI in a clinical setting. Our results indicate that Diannexin is a potential new imaging agent for the study of phosphatidylserine-exposing organs in vivo

Erythropoietin Attenuates Pulmonary Vascular Remodeling in Experimental Pulmonary Arterial Hypertension through Interplay between Endothelial Progenitor Cells and Heme Oxygenase

BackgroundPulmonary arterial hypertension (PAH) is a pulmonary vascular disease with a high mortality, characterized by typical angio-proliferative lesions. Erythropoietin (EPO) attenuates pulmonary vascular remodeling in PAH. We postulated that EPO acts through mobilization of endothelial progenitor cells (EPCs) and activation of the cytoprotective enzyme heme oxygenase-1 (HO1).MethodsRats with flow-associated PAH, resembling pediatric PAH, were treated with HO-1 inducer EPO in the presence or absence of the selective HO-activity-inhibitor tin-mesoporphyrin (SnMP). HO-activity, circulating EPCs and pulmonary vascular lesions were assessed after 3 weeks.ResultsIn PAH-rats, circulating EPCs were decreased and HO-activity was increased compared to control. EPO-treatment restored circulating EPCs and improved pulmonary vascular remodeling, as shown by a reduced wall thickness and occlusion rate of the intra-acinar vessels. Inhibition of HO-activity with SnMP aggravated PAH. Moreover, SnMP treatment abrogated EPO-induced amelioration of pulmonary vascular remodeling, while surprisingly further increasing circulating EPCs as compared with EPO alone.ConclusionsIn experimental PAH, EPO treatment restored the number of circulating EPC’s to control level, improved pulmonary vascular remodeling, and showed important interplay with HO-activity. Inhibition of increased HO-activity in PAH-rats exacerbated progression of pulmonary vascular remodeling, despite the presence of restored numbers of circulating EPC’s. We suggest that both EPO-induced HO1 and EPCs are promising targets to ameliorate the pulmonary vasculature in PAH