The Role of System-Specific Molecular Chaperones in the Maturation of Molybdoenzymes in Bacteria

Biogenesis of prokaryotic molybdoenzymes is a complex process with the final step representing the insertion of a matured molybdenum cofactor (Moco) into a folded apoenzyme. Usually, specific chaperones of the XdhC family are required for the maturation of molybdoenzymes of the xanthine oxidase family in bacteria. Enzymes of the xanthine oxidase family are characterized to contain an equatorial sulfur ligand at the molybdenum center of Moco. This sulfur ligand is inserted into Moco while bound to the XdhC-like protein and before its insertion into the target enzyme. In addition, enzymes of the xanthine oxidase family bind either the molybdopterin (Mo-MPT) form of Moco or the modified molybdopterin cytosine dinucleotide cofactor (MCD). In both cases, only the matured cofactor is inserted by a proofreading process of XdhC. The roles of these specific XdhC-like chaperones during the biogenesis of enzymes of the xanthine oxidase family in bacteria are described

Predicting chemical environments of bacteria from receptor signaling

Sensory systems have evolved to respond to input stimuli of certain statistical properties, and to reliably transmit this information through biochemical pathways. Hence, for an experimentally well-characterized sensory system, one ought to be able to extract valuable information about the statistics of the stimuli. Based on dose-response curves from in vivo fluorescence resonance energy transfer (FRET) experiments of the bacterial chemotaxis sensory system, we predict the chemical gradients chemotactic Escherichia coli cells typically encounter in their natural environment. To predict average gradients cells experience, we revaluate the phenomenological Weber's law and its generalizations to the Weber-Fechner law and fold-change detection. To obtain full distributions of gradients we use information theory and simulations, considering limitations of information transmission from both cell-external and internal noise. We identify broad distributions of exponential gradients, which lead to log-normal stimuli and maximal drift velocity. Our results thus provide a first step towards deciphering the chemical nature of complex, experimentally inaccessible cellular microenvironments, such as the human intestine.Comment: DG and GM contributed equally to this wor

Exponential signaling gain at the receptor level enhances signal-to-noise ratio in bacterial chemotaxis

Peer reviewedPublisher PD

Atlas : examining the wider context of assistive robotics

We examine the proposition of a stationary assistive robot arm in the kitchen. Based on a preliminary business plan and with the aim of generating engineering requirements, a multi-disciplinary project was established to examine the wider ramifications of such assistive technology in the household, in a Swiss context, in the fields of health and social wellbeing. Additionally the engineering aspects as well as the business aspects were examined. We detail both the individual methodologies used in this study, the results achieved and discuss the results in a wider context

Crabs, scallops, fish, and more: barcoding the marine fauna of the North Sea

Background: During the last years, the effectiveness of DNA barcoding for animal species identification has been proven in many studies, analyzing both vertebrate and invertebrate taxa. In terms of marine organisms, however, most barcoding studies typically focus on economically relevant species, for example, fish, as well asonthedocumentationof hotspots of species diversity, for example, tropical coral reefs or regions of the almost unexplored deep sea regions. In contrast to this, species diversity of “well-known” habitats is nearly neglected. As part of our running project we started to build up a comprehensive DNA barcode library for the metazoan taxa of the North Sea, one of the most extensively studied ecosystems of the world. The North Sea is characterized by a highamountof anthropogenic pressure such as intensive fishing and ship traffic as well as offshore installations. Environmental parameters (e.g., depth, sediment characteristics, temperature, and salinity) of this semi-enclosed shelf sea follow a distinct pattern: high seasonal fluctuations can be observed in southern areas, but low fluctuations are given in the northern regions. This heterogeneity is also displayed in macrobenthic community structures, with a lower number of species in the shallow southern parts (i.e., the German Bight) and more species in the central and northern North Sea. In addition to this, species with a typical Mediterranean-Lusitanean distribution are also known to occur in parts of the North Sea where oceanic influences prevail. Results: Our barcode library includes a broad variety of taxa, including typical taxa of marine barcoding studies, for example, fish or decapod crustaceans. Our on-growing library also includes groups that are often ignored as cnidarians, parasitic crustaceans, echinoderms, mollusks, pantopods, polychaets, and others. In total, our library includes more than 4200 DNA barcodes of more than 600 species at the moment. By using the Barcode of Life Data Systems (BOLD), unique BINs were identified for more than 90% of the analyzed species. Significance: Our data represent a first step towards the establishment of a comprehensive DNA barcode library of the Metazoa of the North Sea. Despite the fact that various taxa are still missing or are currently underrepresented, our results clearly underline the usefulness of DNA barcodes to discriminate the vast majority of the analyzed species. It should be also kept in mind that the benefits of DNA barcoding are not restricted to taxonomic or systematic research only. The rise of modern high-throughput sequencing technologies will change biomonitoring applications and surveys significantly in the coming years. Following this, reference datasets such as ours will become essential for a correct identification of specimens sequenced as part of a metabarcoding study. This is especially true for the North Sea, a marine region that has been massively affected by cargo ship traffic, the exploitation of oil and gas resources, offshore wind parks, and in particular extensive long-term fisheries

The Influence of Microbial Metabolites in the Gastrointestinal Microenvironment on Anticancer Immunity

The gastrointestinal (GI) tumour microenvironment is characterised by its unique colonisation with bacteria that are estimated to match the total number of cells in our body. It is becoming increasingly clear that the microbiome and its metabolites are important orchestrators of local and systemic immune responses, anticancer immunity and the host response to cancer therapy. Apart from their role as an energy source, metabolites have been shown to modulate inflammation, immune cell function and cancer cell survival. The polarisation of immune cell subsets by microbial metabolites towards either pro- or antitumorigenic functions strongly affects cancer progression and outcomes. In this chapter, we will discuss the link between microbial metabolites in the GI tumour microenvironment, anticancer immune responses and cancer progression

An acoustically-driven biochip - Impact of flow on the cell-association of targeted drug carriers

The interaction of targeted drug carriers with epithelial and endothelial barriers in vivo is largely determined by the dynamics of the body fluids. To simulate these conditions in binding assays, a fully biocompatible in vitro model was developed which can accurately mimic a wide range of physiological flow conditions on a thumbnail-format cell-chip. This acoustically-driven microfluidic system was used to study the interaction characteristics of protein-coated particles with cells. Poly(D,L-lactide-co-glycolide) (PLGA) microparticles (2.86 {\pm} 0.95 {\mu}m) were conjugated with wheat germ agglutinin (WGA-MP, cytoadhesive protein) or bovine serum albumin (BSA-MP, nonspecific protein) and their binding to epithelial cell monolayers was investigated under stationary and flow conditions. While mean numbers of 1500 {\pm} 307 mm-2 WGA-MP and 94 {\pm} 64 mm-2 BSA-MP respectively were detected to be cell-bound in the stationary setup, incubation at increasing flow velocities increasingly antagonized the attachment of both types of surface-modified particles. However, while binding of BSA-MP was totally inhibited by flow, grafting with WGA resulted in a pronounced anchoring effect. This was indicated by a mean number of 747 {\pm} 241 mm-2 and 104 {\pm} 44 mm-2 attached particles at shear rates of 0.2 s-1 and 1 s-1 respectively. Due to the compactness of the fluidic chip which favours parallelization, this setup represents a highly promising approach towards a screening platform for the performance of drug delivery vehicles under physiological flow conditions. In this regard, the flow-chip is expected to provide substantial information for the successful design and development of targeted micro- and nanoparticulate drug carrier systems.Comment: 19 page

Стратегия развития организационной культуры как фактор эффективности деятельности организации

В работе были рассмотрены функции и элементы организационной культуры и её влияние на эффективность деятельности организации. В результате исследования были предложены рекомендации и мероприятия по совершенствованию организационной культуры.The word considered the functions and elements of organizational culture and its influence on the effectiveness of the organization. As a result of the study, recommendations and measures were proposed to improve the organizational culture

Perspektive der Leistungserbringer - Modul 4 des Projekts "Evaluation von Leistungen zur Teilhabe behinderter Menschen am Arbeitsleben - Abschlussbericht"

Der Abschlussbericht zum Projektmodul "Perspektive der Leistungserbringer" betrachtet den Prozess der beruflichen Rehabilitation aus Sicht der Leistungserbringer. Dabei wird ein gemischt-methodisches Forschungsdesign verwendet. Im Rahmen des Berichts werden die Leistungserbringer näher charakterisiert und interne sowie externe Organisationsprozesse dargestellt. Des Weiteren wird die Zusammenarbeit mit der Bundesagentur für Arbeit und mit den Betrieben näher beleuchtet. Schließlich werden aktuelle Herausforderungen der Leistungserbringer betrachtet und unterschiedliche Definitionen von Maßnahmeerfolg.The report "Perspectives of Rehabilitation Providers" looks at the organization of the process of occupational rehabilitation from the perspective of rehabilitation providers using a mixed-methods approach. It presents main characteristics of providers and the internal and external organization of the rehabilitation process. Furthermore, main aspects of the joint work of rehabilitation providers with the Federal Employment Agency and employers are discussed. Finally, main provider-specific challenges and approaches to define successful rehabilitation are provided

Increased IL-10-producing regulatory T cells are characteristic of severe cases of COVID-19.

OBJECTIVES: The pandemic spread of the coronavirus SARS-CoV-2 is due, in part, to the immunological properties of the host-virus interaction. The clinical presentation varies from individual to individual, with asymptomatic carriers, mild-to-moderate-presenting patients and severely affected patients. Variation in immune response to SARS-CoV-2 may underlie this clinical variation. METHODS: Using a high-dimensional systems immunology platform, we have analysed the peripheral blood compartment of 6 healthy individuals, 23 mild-to-moderate and 20 severe COVID-19 patients. RESULTS: We identify distinct immunological signatures in the peripheral blood of the mild-to-moderate and severe COVID-19 patients, including T-cell lymphopenia, more consistent with peripheral hypo- than hyper-immune activation. Unique to the severe COVID-19 cases was a large increase in the proportion of IL-10-secreting regulatory T cells, a lineage known to possess anti-inflammatory properties in the lung. CONCLUSION: As IL-10-secreting regulatory T cells are known to possess anti-inflammatory properties in the lung, their proportional increase could contribute to a more severe COVID-19 phenotype. We openly provide annotated data (https://flowrepository.org/experiments/2713) with clinical correlates as a systems immunology resource for the COVID-19 research community