Oxidoreductases on their way to industrial biotransformations

Fungi produce heme-containing peroxidases and peroxygenases, flavin-containing oxidases and dehydrogenases, and different copper-containing oxidoreductases involved in the biodegradation of lignin and other recalcitrant compounds. Heme peroxidases comprise the classical ligninolytic peroxidases and the new dye-decolorizing peroxidases, while heme peroxygenases belong to a still largely unexplored superfamily of heme-thiolate proteins. Nevertheless, basidiomycete unspecific peroxygenases have the highest biotechnological interest due to their ability to catalyze a variety of regio- and stereo-selective monooxygenation reactions with H2O2 as the source of oxygen and final electron acceptor. Flavo-oxidases are involved in both lignin and cellulose decay generating H2O2 that activates peroxidases and generates hydroxyl radical. The group of copper oxidoreductases also includes other H2O2 generating enzymes - copper-radical oxidases - together with classical laccases that are the oxidoreductases with the largest number of reported applications to date. However, the recently described lytic polysaccharide monooxygenases have attracted the highest attention among copper oxidoreductases, since they are capable of oxidatively breaking down crystalline cellulose, the disintegration of which is still a major bottleneck in lignocellulose biorefineries, along with lignin degradation. Interestingly, some flavin-containing dehydrogenases also play a key role in cellulose breakdown by directly/indirectly "fueling" electrons for polysaccharide monooxygenase activation. Many of the above oxidoreductases have been engineered, combining rational and computational design with directed evolution, to attain the selectivity, catalytic efficiency and stability properties required for their industrial utilization. Indeed, using ad hoc software and current computational capabilities, it is now possible to predict substrate access to the active site in biophysical simulations, and electron transfer efficiency in biochemical simulations, reducing in orders of magnitude the time of experimental work in oxidoreductase screening and engineering. What has been set out above is illustrated by a series of remarkable oxyfunctionalization and oxidation reactions developed in the frame of an intersectorial and multidisciplinary European RTD project. The optimized reactions include enzymatic synthesis of 1-naphthol, 25-hydroxyvitamin D3, drug metabolites, furandicarboxylic acid, indigo and other dyes, and conductive polyaniline, terminal oxygenation of alkanes, biomass delignification and lignin oxidation, among others. These successful case stories demonstrate the unexploited potential of oxidoreductases in medium and large-scale biotransformations

Histone deacetylase inhibitors suppress mechanical stress-induced expression of RUNX-2 and ADAMTS-5 through the inhibition of the MAPK signaling pathway in cultured human chondrocytes

Objective: To investigate the inhibitory effects and the regulatory mechanisms of histone deacetylase (HDAC) inhibitors on mechanical stress-induced gene expression of runt-related transcription factor (RUNX)-2 and a disintegrin and metalloproteinase with thrombospondin motif (ADAMTS)-5 in human chondrocytes. Methods: Human chondrocytes were seeded in stretch chambers at a concentration of 5 x 10(4) cells/chamber. Cells were pre-incubated with or without HDAC inhibitors (MS-275 or trichostatin A; TSA) for 12 h, followed by uniaxial cyclic tensile strain (CTS) (0.5 Hz, 10% elongation), which was applied for 30 min using the ST-140-10 system (STREX, Osaka, Japan). Total RNA was extracted and the expression of RUNX-2, ADAMTS-5, matrix metalloproteinase (MMP)-3, and MMP-13 at the mRNA and protein levels were examined by real-time polymerase chain reaction (PCR) and immunocytochemistry, respectively. The activation of diverse mitogen-activated protein kinase (MAPK) pathways with or without HDAC inhibitors during CTS was examined by western blotting. Results: HDAC inhibitors (TSA: 10 nM, MS-275: 100 nM) suppressed CTS-induced expression of RUNX-2, ADAMTS-5, and MMP-3 at both the mRNA and protein levels within 1 h. CTS-induced activation of p38 MAPK (p38), extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (INK) MAPKs was downregulated by both HDAC inhibitors. Conclusion: The CTS-induced expression of RUNX-2 and ADAMTS-5 was suppressed by HDAC inhibitors via the inhibition of the MAPK pathway activation in human chondrocytes. The results of the current study suggested a novel therapeutic role for HDAC inhibitors against degenerative joint disease such as osteoarthritis

Have Atmospheric Cerenkov Telescopes Observed Dark Matter?

Two ground-based experiments have recently independently detected TeV $\gamma$-rays from the direction of the Galactic center. The observations made by the VERITAS and CANGAROO collaborations are unexpected, although not impossible to interpret in terms of astrophysical sources. Here we examine in detail whether the observed $\gamma$-rays may arise from the more exotic alternative of annihilations of dark matter particles clustered in the center of the Galaxy.Comment: 19 pages, 7 figure

Advances in tenascin-C biology

Tenascin-C is an extracellular matrix glycoprotein that is specifically and transiently expressed upon tissue injury. Upon tissue damage, tenascin-C plays a multitude of different roles that mediate both inflammatory and fibrotic processes to enable effective tissue repair. In the last decade, emerging evidence has demonstrated a vital role for tenascin-C in cardiac and arterial injury, tumor angiogenesis and metastasis, as well as in modulating stem cell behavior. Here we highlight the molecular mechanisms by which tenascin-C mediates these effects and discuss the implications of mis-regulated tenascin-C expression in driving disease pathology

Was kann man vom Leben im Altenheim noch erwarten? - "Lebensqualität" im Fokus des Qualitätsaudits

Lebensqualität – ein wichtiger Outcome-Faktor der Langzeitpflege - Neuanlage und psychometrische Testung eines konzeptgestützten Audit-Fragebogens, der Lebensqualitätsindex (LQ-Index), zur Beurteilung der Berücksichtigung der individuellen Lebensqualitätsaspekte im Pflegeprozess auch für Klienten mit eingeschränkter Kommunikationsfähigkeit Methode: Aus der Gesamtheit von 1128 Bewohnern (N=1128) in 8 Altenheimen wurde eine nach Pflegestufen geschichtete Zufallsstichprobe von insgesamt 209 Bewohnern (n=209) gezogen, und deren individuellen LQ-Aspekte mit dem SEIQoL-DW bzw. bei kommunikativen Einschränkungen mit der LQ-Index-Informationssammlung erhoben. Die neuen Prüfitems des LQ-Index wurden validiert durch die Paralleltestung mit dem Referenzstandard SEIQoL-DW, eine Itemblockanalyse, die Erhebung der Interrater-Reliabilität (Kappa) und eine strukturierte Expertenbewertung nach der kognitiven-Interview-Methode. Ergebnisse: Das SEIQoL-Interview konnte nur bei 18 (8,61 % ) vollständig und valide durchgeführt, der LQ-Index bei allen 209 Probanden valide erhoben werden. Die psychometrische Testung und die Expertenbewertung weisen auf eine hohe Praktikabilität, Zuverlässigkeit, Validität und Objektivität des Instruments hin. Diskussion: Es liegt ein praktikables und valides Instrument zur Beurteilung der Berücksichtigung der individuellen Lebensqualität im Pflegeprozess auch für Klienten in kommunikativ schwierigen Situationen für die Praxis vor.von Astrid Dorothea Herold-Majumda

Organizational culture empowering nurses an residents in nursing homes.<strong></strong>

Purpose. If nurses should respect resident´s autonomy, nurses themselves must experience empowerment and respect for their own autonomy in the work environment. The purpose of this study is to get a deeper understanding of nurses’ perception of their own empowerment in the organization’s culture during an intervention program for strengthening autonomy. Design/methodology/approach. Guided semi-structured interviews and moderated group discussions were conducted before and after the intervention. A structured and evaluative content analysis of the text material were performed. Findings. In total 73 nurses and nurse aids working at frontline with the residents were voluntarily included into the study. New categories for nurses’ perceived empowerment and organizational culture could be derived from the text material. Originality/value. The study’s results deliver a theoretical model with a sophisticated system of categories for organizational culture as perceived by nurses that can be used for further qualitative and quantitative research and for a sustainable organization development.&nbsp

Kulturelle Achtsamkeit und Wissensbasierung in der klinisch‐pflegerischen Fallbeurteilung. Entwicklung und Evaluation eines kooperativen Lehr‐Lernkonzeptes zwischen Hochschule und Klinik im Rahmen des QualiFIVE Programms im dualen Bachelorstudiengang Pflege ; Ergebnisse der Begleitstudie CANDo: Cultural Awareness and Evidence in Nursing Diagnosis 2015‐2017

Bericht über eine wissenschaftliche Begleitstudie mit Mixed‐Method Design zur Evaluation eines kooperativen Lehr‐Lernkonzeptes zwischen Hochschule und Klini