Tunable ultrabroadband hybrid THz emitter combining a spintronic THz source and a GaSe crystal

Linear terahertz time-domain spectroscopy (THz-TDS) is a sensitive probe for material characterization including thickness measurements of thin layers. These applications critically rely on a sufficiently large bandwidth, which is not straightforwardly available in typical THz-TDS systems. Here, we introduce a hybrid THz-emitter concept based on a spintronic THz emitter that is deposited onto a thin freestanding GaSe nonlinear crystal. By tuning the parameters of this hybrid emitter, we generate an ultrabroadband spectrum covering the full range from 1 to 40 THz without any gaps at high spectral amplitudes, resulting in ultrashort THz-pulse durations of only 32 fs. Finally, we demonstrate the straightforward tunability of the carrier-envelope phase from unipolar or bipolar THz pulses with ultrashort duration

Synergistic Antitumour Properties of viscumTT in Alveolar Rhabdomyosarcoma

Aqueous mistletoe extracts from the European mistletoe (Viscum album) contain mainly mistletoe lectins and viscotoxins as cytotoxic compounds. Lipophilic triterpene acids, which do not occur in conventional mistletoe preparations, were solubilised with β-cyclodextrins. The combination of an aqueous extract (viscum) and a triterpene-containing extract (TT) recreated a whole mistletoe extract (viscumTT). These extracts were tested on rhabdomyosarcoma in vitro, ex vivo, and in vivo with regard to anticancer effects. Viscum and viscumTT inhibited cell proliferation and induced apoptosis effectively in a dose- dependent manner in vitro and ex vivo, whereas TT showed only moderate inhibitory effects. viscumTT proved to be more effective than the single extracts and displayed a synergistic effect in vitro and a stronger effect in vivo. viscumTT induced apoptosis via the extrinsic and intrinsic pathways, evidenced by the loss of mitochondrial membrane potential and activation of CASP8 and CASP9. CASP10 inhibitor inhibited apoptosis effectively, emphasising the importance of CASP10 in viscumTT-induced apoptosis. Additionally, viscumTT changed the ratio of apoptosis-associated proteins by downregulation of antiapoptotic proteins such as XIAP and BIRC5, thus shifting the balance towards apoptosis. viscumTT effectively reduced tumour volume in patient- derived xenografts in vivo and may be considered a promising substance for rhabdomyosarcoma therapy

Crystal Structure of the Hydroxyquinol 1,2-Dioxygenase from Nocardioides simplex 3E, a Key Enzyme Involved in Polychlorinated Aromatics Biodegradation

Hydroxyquinol 1,2-dioxygenase (1,2-HQD) catalyzes the ring cleavage of hydroxyquinol (1,2,4-trihydroxybenzene), a central intermediate in the degradation of aromatic compounds including a variety of particularly recalcitrant polychloro- and nitroaromatic pollutants. We report here the primary sequence determination and the analysis of the crystal structure of the 1,2-HQD from Nocardioides simplex 3E solved at 1.75 A resolution using the multiple wavelength anomalous dispersion of the two catalytic irons (1 Fe/293 amino acids). The catalytic Fe(III) coordination polyhedron composed by the side chains of Tyr164, Tyr197, His221, and His223 resembles that of the other known intradiol-cleaving dioxygenases, but several of the tertiary structure features are notably different. One of the most distinctive characteristics of the present structure is the extensive openings and consequent exposure to solvent of the upper part of the catalytic cavity arranged to favor the binding of hydroxyquinols but not catechols. A co-crystallized benzoate-like molecule is also found bound to the metal center forming a distinctive hydrogen bond network as observed previously also in 4-chlorocatechol 1,2-dioxygenase from Rhodococcus opacus 1CP. This is the first structure of an intradiol dioxygenase specialized in hydroxyquinol ring cleavage to be investigated in detail

"Wissenschaft fürs Wohnzimmer" – two years of interactive, scientific livestreams weekly on YouTube

Science communication is becoming increasingly important to connect academia and society, and to counteract fake news among climate change deniers. Online video platforms, such as YouTube, offer great potential for low-threshold communication of scientific knowledge to the general public. In April 2020 a diverse group of researchers from the Alfred Wegener Institute Helmholtz Centre for Polar and Marine Research launched the YouTube channel "Wissenschaft fürs Wohnzimmer" (translated to "Sitting Room Science") to stream scientific talks about climate change and biodiversity every Thursday evening. Here we report on the numbers and diversity of content, viewers, and presenters from 2 years and 100 episodes of weekly livestreams. Presented topics encompass all areas of polar research, social issues related to climate change, and new technologies to deal with the changing world and climate ahead. We show that constant engagement by a group of co-hosts, and presenters from all topics, career stages, and genders enable a continuous growth of views and subscriptions, i.e. impact. After 783 days the channel gained 30,251 views and 828 subscribers and hosted well-known scientists while enabling especially early career researchers to improve their outreach and media skills. We show that interactive and science-related videos, both live and on-demand, within a pleasant atmosphere, can be produced voluntarily while maintaining high quality. We further discuss challenges and possible improvements for the future. Our experiences may help other researchers to conduct meaningful scientific outreach and to push borders of existing formats with the overall aim of developing a better understanding of climate change and our planet

Verglichende Ökobilanz zweier Fahrzeugkomponenten aus unterschiedlichen Werkstoffen und Herstellungsprozessen

Unternehmen sind mehr und mehr dem globalen Wettbewerb, strengeren gesetzlichen Regelungen und veränderten Kundenbedürfnissen ausgesetzt. Durch eine Neuausrichtung des Unternehmens auf Stakeholder-Management können sich Entscheidungsträger an veränderte Marktbedingungen anpassen. Der vorliegende Beitrag ist ein Leitfaden zum Stakeholder-Management der gemeinsam mit Nachhaltigkeitsexperten von PricewaterhouseCoopers entwickelt wurde. Er besteht aus den Schritten (i) Strategisch Denken, (ii) Analyse und Priorisierung der Stakeholder und ihrer Ansprüche, (iii) Aufbau von Kapazitäten zum Stakeholder-Management, (iv) Stakeholder-Kommunikation sowie (v) Kommunikation und Lernen. Der vorliegende Leitfaden ist der erste, der explizit die Bedürfnisse von kleinen und mittleren Unternehmen und Familienunternehmen einbezieht. Obwohl diese Unternehmen oft explizit oder implizit Stakeholder-Management in ihrer Unternehmensphilosophie verankert haben, fehlen häufig strukturierte Ansätze und Management-Tools hierfür. Dieser Leitfaden gibt Managern in kleinen und mittleren Unternehmen sowie Familienunternehmen eine praktische Handhabe für ihr Stakeholder-Management.Firms are facing more global competition, more stringent regulation and a faster change of customer needs. Managers can adapt to changed market dynamics with increased stakeholder management. Together with sustainability experts from Pricewaterhouse Coopers we develop a guideline for stakeholder management consisting of the steps (i) think strategically, (ii) analysis and prioritization of stakeholders and their stakes (iii) capacity building for stakeholder management (iv) stakeholder information (v) communication and learning. It builds on Freeman (1984) and defines stakeholder as “any group or individual who can affect or can be affected by the achievement of anorganisation’s objectives”. The proposed stakeholder guideline is the first, which fulfils the needs of small and medium sized enterprises and family owned businesses. While these companies often have explicitly or implicitly embodied stakeholder management corporate philosophy, structured approaches and management tools are still missing. Our guideline givesmanagers in small and medium sized enterprises and family owned businesses a practical tool for stakeholder management

Epidemiologie, prevence a léčba kolorektálního karcinomu dle dostupných českých a mezinárodních dat

Nádory tlustého střeva a konečníku patří mezi nejčastější onkologické diagnózy. V České republice je každoročně nově diagnostikováno téměř 8 500 pacientů s kolorektálním karcinomem a přibližně 3 900 osob tomuto onemocnění každým rokem podlehne. Celková prevalence přesáhne v roce 2012 hranici 55 000 osob. Společenské, etické i ekonomické důsledky vyplývající z takto vysoké zátěže jsou zřejmé. Publikace „Epidemiologie, prevence a léčba kolorektálního karcinomu dle dostupných českých a mezinárodních dat“ přináší ucelený přehled epidemiologické a léčebné zátěže české populace touto chorobou a věnuje se krátkodobým a dlouhodobým predikcím dalšího vývoje. Situace je rovněž hodnocena v mezinárodním srovnání, neboť v hodnotách incidence a mortality kolorektálního karcinomu obsazuje ČR přední příčky evropských i světových statistik. Z mezinárodních studií však také vyplývá pozitivní poznatek, že většině nádorů tlustého střeva a konečníku lze předejít účinnou prevencí. Kromě primární prevence je zde hlavním nástrojem organizovaný populační screening, který je založen na testech krvácení do stolice a na kolonoskopii. Otázkám prevence a výsledkům screeningu kolorektálního karcinomu jsou v publikaci věnovány zvláštní kapitoly. Ačkoli nejnovější data dokládají rostoucí výkonnost českého screeningu, celkově dosažené pokrytí populace bohužel stále není dostatečné. To platí pro včasný záchyt kolorektálního karcinomu obecně, neboť v ČR je setrvale téměř 50 % nových onemocnění diagnostikováno v pokročilých klinických stadiích, a tedy s výrazně sníženou šancí na vyléčení nebo dlouhodobé přežití pacienta. Publikace rovněž hodnotí přežití dosahované u českých pacientů jakožto zásadní ukazatel výsledků léčebné péče, u kterého v posledních 15 letech zaznamenáváme statisticky významné zlepšení. Pravděpodobnost 5letého relativního přežití je u včasně diagnostikovaného kolorektálního karcinomu v klinickém stadiu i vyšší než 88%. Tato čísla opět potvrzují nutnost účinné prevence a posílení screeningu tohoto preventabilního onemocnění. V tomto směru má publikace ambici informovat odbornou i laickou veřejnost, a proto věnuje značný prostor přehledu dostupných informačních zdrojů.The book aims to inform expert and general public about epidemiology of colorectal carcinoma in the Czech Republic and priorities resulting from high population burden for prevention, diagnostics, and treatment of this severe disease. A number of invited experts assess selected information sources that representatively describe performance and quality of preventive programmes and results of CRC treatment in the Czech Republic

The Metaproteomics Initiative: a coordinated approach for propelling the functional characterization of microbiomes

publishedVersio

Functional consequences of microbial shifts in the human gastrointestinal tract linked to antibiotic treatment and obesity

The microbiomes in the gastrointestinal tract (GIT) of individuals receiving antibiotics and those in obese subjects undergo compositional shifts, the metabolic effects and linkages of which are not clearly understood. Herein, we set to gain insight into these effects, particularly with regard to carbohydrate metabolism, and to contribute to unravel the underlying mechanisms and consequences for health conditions. We measured the activity level of GIT carbohydrate-active enzymes toward 23 distinct sugars in adults patients (n = 2) receiving 14-d β-lactam therapy and in obese (n = 7) and lean (n = 5) adolescents. We observed that both 14 d antibiotic-treated and obese subjects showed higher and less balanced sugar anabolic capacities, with 40% carbohydrates being preferentially processed as compared with non-treated and lean patients. Metaproteome-wide metabolic reconstructions confirmed that the impaired utilization of sugars propagated throughout the pentose phosphate metabolism, which had adverse consequences for the metabolic status of the GIT microbiota. The results point to an age-independent positive association between GIT glycosidase activity and the body mass index, fasting blood glucose and insulin resistance (r2 ≥ 0.95). Moreover, antibiotics altered the active fraction of enzymes controlling the thickness, composition and consistency of the mucin glycans. Our data and analyses provide biochemical insights into the effects of antibiotic usage on the dynamics of the GIT microbiota and pin-point presumptive links to obesity. The knowledge and the hypotheses generated herein lay a foundation for subsequent, systematic research that will be paramount for the design of “smart” dietary and therapeutic interventions to modulate host-microbe metabolic co-regulation in intestinal homeostasis

Anaerobic Microbial Degradation of Hydrocarbons: From Enzymatic Reactions to the Environment

Hydrocarbons are abundant in anoxic environments and pose biochemical challenges to their anaerobic degradation by microorganisms. Within the framework of the Priority Program 1319, investigations funded by the Deutsche Forschungsgemeinschaft on the anaerobic microbial degradation of hydrocarbons ranged from isolation and enrichment of hitherto unknown hydrocarbon-degrading anaerobic microorganisms, discovery of novel reactions, detailed studies of enzyme mechanisms and structures to process-oriented in situ studies. Selected highlights from this program are collected in this synopsis, with more detailed information provided by theme-focused reviews of the special topic issue on 'Anaerobic biodegradation of hydrocarbons' [this issue, pp. 1-244]. The interdisciplinary character of the program, involving microbiologists, biochemists, organic chemists and environmental scientists, is best exemplified by the studies on alkyl-/arylalkylsuccinate synthases. Here, research topics ranged from in-depth mechanistic studies of archetypical toluene-activating benzylsuccinate synthase, substrate-specific phylogenetic clustering of alkyl-/arylalkylsuccinate synthases (toluene plus xylenes, p-cymene, p-cresol, 2-methylnaphthalene, n-alkanes), stereochemical and co-metabolic insights into n-alkane-activating (methylalkyl) succinate synthases to the discovery of bacterial groups previously unknown to possess alkyl-/arylalkylsuccinate synthases by means of functional gene markers and in situ field studies enabled by state-of-the-art stable isotope probing and fractionation approaches. Other topics are Mo-cofactor-dependent dehydrogenases performing O-2-independent hydroxylation of hydrocarbons and alkyl side chains (ethylbenzene, p-cymene, cholesterol, n-hexadecane), degradation of p-alkylated benzoates and toluenes, glycyl radical-bearing 4-hydroxyphenylacetate decarboxylase, novel types of carboxylation reactions (for acetophenone, acetone, and potentially also benzene and naphthalene), W-cofactor-containing enzymes for reductive dearomatization of benzoyl-CoA (class II benzoyl-CoA reductase) in obligate anaerobes and addition of water to acetylene, fermentative formation of cyclohexanecarboxylate from benzoate, and methanogenic degradation of hydrocarbons

Glacial meltwater effects on the carbon cycle of Scoresby Sund (Greenland), the world's largest fjord system

Climate change induced mass loss of the Greenland Ice Sheet increases the amount of meltwater, which is mainly released into the numerous fjords along the coast of Greenland. Due to its low salinity and high silt load, meltwater can profoundly affect the biogeochemical cycling of carbon. We visited the world’s largest fjord system, Scoresby Sund at the eastern coast of Greenland, and its northernmost branch, Nordvestfjord, in the summer of 2016 for investigating biogeochemical carbon cycling. The data reveal that meltwater limited the productivity by inhibiting the resupply of nutrients to the surface and by shadowing the upper part of the water column by the introduction of silts. These silts, though, increased the export of organic carbon to depth by ballasting the sinking organic particles. While the region close to the fjord entrance was influenced by shelf waters, the water column within Nordvestfjord was significantly modulated by meltwater input from a number of marine- and land-terminating glaciers. Our results show that there was a clear gradient from a productive system with efficient remineralization at the mouth of the fjord to a less productive system with a high carbon export towards the inner fjord parts. These results imply that Scoresby Sund can be seen as a hotspot of carbon burial