Ageing of alkylthiol-stabilized gold nanoparticles

The ageing of spherical gold nanoparticles having 6-nm-diameter cores and a ligand shell of dodecanethiol is investigated under different storage conditions. Losses caused by agglomeration and changes in optical particle properties are quantified. Changes in colloidal stability are probed by analytical centrifugation in a polar solvent mixture. Chemical changes are detected by elementary analysis of particles and solvent. Fractionation occurs under all storage conditions. Ageing is not uniform but broadens the property distributions of the particles. Small-number statistics in the ligand shell density and the morphological heterogeneity of particles are possible explanations. Washing steps exacerbate ageing, a process that could not be fully reversed by excess ligands. Dry storage is not preferable to storage in solvent. Storage under inert argon atmosphere reduces losses more than all other conditions but could not prevent it entirely

Spinach hexokinase I is located in the outer envelope membrane of plastids

AbstractThe subcellular localization of hexokinase activities in plant cells has been a matter of debate for a long time. We have isolated a hexokinase cDNA fragment from glucose-fed spinach leaves using a differential display reverse transcription-PCR approach. The corresponding cDNA was expressed in Escherichia coli and an antiserum, raised against the recombinant protein, was used in subcellular localization studies. The spinach hexokinase could be localized primarily to the outer envelope membrane of chloroplasts where it is inserted via its N-terminal membrane anchor. We suggest that the chloroplast envelope hexokinase is involved in the energization of glucose export from plastids rather than in the sugar-sensing pathway of the plant cell

Phenotypic consequences of somatic mutations in the ataxia-telangiectasia mutated gene in non-small cell lung cancer

Mutations in the Ataxia-telangiectasia mutated (ATM) gene are frequently found in human cancers, including non-small cell lung cancer (NSCLC). Loss of ATM function confers sensitivity to ionising radiation (IR) and topoisomerase inhibitors and may thus define a subset of cancer patients that could get increased benefit from these therapies. In this study, we evaluated the phenotypic consequences of ATM missense changes reported in seven NSCLC cell lines with regard to radiosensitivity and functionality of ATM signalling. Our data demonstrate that only 2/7 NSCLC cell lines (H1395 and H23) harbouring ATM missense mutations show a functional impairment of ATM signalling following IR-exposure. In these two cell lines, the missense mutations caused a significant reduction in ATM protein levels, impairment of ATM signalling and marked radiosensitivity. Of note, only cell lines with homozygous mutations in the ATM gene showed significant impairment of ATM function. Based on these observations, we developed an immunohistochemistry-based assay to identify patients with loss or reduction of ATM protein expression in a clinical setting. In a set of 137 NSCLC and 154 colorectal cancer specimens we identified tumoral loss of ATM protein expression in 9.5% and 3.9% of cases, respectively, demonstrating the potential utility of this method

Combinatorial omics analysis reveals perturbed lysosomal homeostasis in collagen VII-deficient keratinocytes

The extracellular matrix protein collagen VII is part of the microenvironment of stratified epithelia and critical in organismal homeostasis. Mutations in the encoding gene COL7A1 lead to the skin disorder dystrophic epidermolysis bullosa (DEB), are linked to skin fragility and progressive inflammation-driven fibrosis that facilitates aggressive skin cancer. So far, these changes have been linked to mesenchymal alterations, the epithelial consequences of collagen VII loss remaining under- addressed. As epithelial dysfunction is a principal initiator of fibrosis, we performed a comprehensive transcriptome and proteome profiling of primary human keratinocytes to generate global and detailed images of dysregulated epidermal molecular pathways linked to loss of collagen VII. These revealed downregulation of interaction partners of collagen VII on mRNA and protein level, but also increased abundance of S100 pro- inflammatory proteins in primary DEB keratinocytes. Increased TGF-β signaling due to loss of collagen VII was associated with enhanced activity of lysosomal proteases in both keratinocytes and skin of collagen VII-deficient individuals. Thus, loss of a single structural protein, collagen VII, has extra- and intracellular consequences, resulting in inflammatory processes that enable tissue destabilization and promote keratinocyte- driven, progressive fibrosis

Identification of SARS-CoV-2-induced pathways reveals drug repurposing strategies.

The global outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) necessitates the rapid development of new therapies against coronavirus disease 2019 (COVID-19) infection. Here, we present the identification of 200 approved drugs, appropriate for repurposing against COVID-19. We constructed a SARS-CoV-2-induced protein network, based on disease signatures defined by COVID-19 multiomics datasets, and cross-examined these pathways against approved drugs. This analysis identified 200 drugs predicted to target SARS-CoV-2-induced pathways, 40 of which are already in COVID-19 clinical trials, testifying to the validity of the approach. Using artificial neural network analysis, we classified these 200 drugs into nine distinct pathways, within two overarching mechanisms of action (MoAs): viral replication (126) and immune response (74). Two drugs (proguanil and sulfasalazine) implicated in viral replication were shown to inhibit replication in cell assays. This unbiased and validated analysis opens new avenues for the rapid repurposing of approved drugs into clinical trials

Web 2.0-Anwendungen in den Kommunen des Landes Sachsen-Anhalt

Der vorliegende Bericht ist das Ergebnis eines einjährigen Studienprojekts am Fachbereich Verwaltungswissenschaften der Hochschule Harz, in dem der derzeitige Einsatz und die potenziellen Einsatzmöglichkeiten von Web 2.0-Anwendungen in den Kommunen des Landes Sachsen-Anhalts untersucht wurden. Im Rahmen des Projekts wurden alle 134 Kommunen des Landes in einem Online-Survey befragt, darüber hinaus wurden in drei Kommunen vertie-fende Interviews durchgeführt und einzelne Aspekte der Web 2.0-Nutzung in einem Online-Forum mit Verwaltungsbeschäftigten und weiteren Expertinnen und Experten diskutiert. Insgesamt ist festzustellen, dass bislang nur ein Bruchteil der Kommunen in Sachsen-Anhalt - wir gehen von maximal 25% aus - Web 2.0-Anwendungen nutzt. Am Stärksten werden bis-lang offene, privatwirtschaftlich betriebene soziale Netzwerke, wie zum Beispiel Facebook, eingesetzt. Auf Basis der vorliegenden Ergebnisse muss bezweifelt werden, dass Kommunen von der Nutzung konventioneller sozialer Netzwerke grundsätzlich in einem Maß profitieren können, das den notwendigen Aufwand rechtfertigen würde. Kommunen, die entsprechende Anwen-dungen nutzen, sehen zwar zumindest teilweise einen Mehrwert. Die Argumente sind aber überwiegend sehr subjektiv. Die Nutzung konventioneller sozialer Netzwerke, wie zum Beispiel Facebook, kann daher nicht pauschal empfohlen werden. Dagegen liegt mit sogenannten Anliegenmanagementsystemen ein Beispiel für eine spezifisch von Kommunen nutzbare Web 2.0-Anwendung vor, aus dem auch Konsequenzen für weiter-führende Nutzungsformen und Neuentwicklungen gezogen werden können. Spezifisch für kommunale Verwaltungen entwickelte, kooperativ implementiert und genutzte Anwendungen, die eine elektronische Kollaboration zwischen Verwaltungen und Stakeholdern in Kernprozes-sen der Kommunalverwaltung ermöglichen, scheinen eine durchaus erfolgsversprechende Option. Neben einer thematischen Erweiterung auf allgemeine und alltägliche Themen der Interaktion von Bürgerinnen und Bürgern mit der kommunalen Verwaltung müssen auch die kooperativen Strukturen zur Entwicklung und zum Betrieb entsprechender Lösungen noch weiter entwickelt werden

Finanzmärkte, Unternehmungen, Informationen: Ergebnisse des Projektes im Wintersemester 2015/2016

Der vorliegende Beitrag der Wirtschaftswissenschaftlichen Schriften ist ein Sammelband, der die Beiträge der Studierenden des 2. Fachsemesters im Masterstudiengang General Management aus dem Wintersemester 2015/2016 umfasst. Die Einzelbeiträge wurden in einer zwei Monate dauernden Projektarbeit im Herbst 2015 erarbeitet und im Januar 2016 präsentiert. Der diesjährige Themenschwerpunkt lag auf dem Bereich "Banken", jedoch fanden auch andere Bereiche Eingang in das Spektrum der Arbeiten. Das Besondere dieser Ausarbeitungen liegt darin, dass sie in Form eines journalistischen Artikels aufgebaut sind und die Autoren die Aufgabe hatten, eine auch für Nichtfachleute geeignete Form der Darstellung zu finden. Besonderer Wert wurde auch auf einen gut lesbaren Schreibstil und die Vielfalt der Gestaltungsformen gelegt. Die Arbeiten liegen hier in der Originalversion vor und wurden nicht redigiert. Die Fakten wurden nach bestem Wissen ermittelt, jedoch besteht kein Anspruch auf Vollständigkeit

Emissions from a modern log wood masonry heater and wood pellet boiler : Composition and biological impact on air-liquid interface exposed human lung cancer cells

The consumption of wood fuel is markedly increasing in developing and industrialized countries. Known side effects of wood smoke inhalation manifest in proinflammatory signaling, oxidative stress, DNA damage and hence increased cancer risk. In this study, the composition and acute biological impact of emissions of state-of-the-art wood combustion compliances: masonry heater (MH) and pellet boiler (PB) were investigated. Therefore A549 cells were exposed to emission aerosols in an automated air-liquid interface exposure station followed by cytotoxicity, transcriptome and proteome analyses. In parallel, aerosols were subjected to a chemical and physical haracterization. Compared to PB, the MH combustion at the same dilution ratio resulted in a 3-fold higher particle mass concentration (PM2.5) and deposited dose (PB: 27 $\pm$ 2 ng/cm2, MH; 73 $\pm$ 12 ng/cm2). Additionally, the MH aerosol displayed a substantially larger concentration of aldehydes, polycyclic aromatic hydrocarbons (PAH) or oxidized PAH. Gene ontology analysis of transcriptome of A549 cells exposed to MH emissions revealed the activation of proinflammatory response and key signaling cascades MAP kinase and JAK-STAT. Furthermore, CYP1A1, an essential enzyme in PAH metabolism, was induced. PB combustion aerosol activated the proinflammatory marker IL6 and different transport processes. The proteomics data uncovered induction of DNA damage-associated proteins in response to PB and DNA doublestrand break processing proteins in response to MH emissions. Taking together, the MH produces emissions with a higher particle dose and more toxic compounds while causing only mild biological responses. This finding points to a significant mitigating effect of antioxidative compounds in MH wood smoke