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Promiscuous hydrolases/acyltransferases have attracted attention for their ability to efficiently catalyze selective transacylation reactions in water to produce esters, thioesters, amides, carbona...

Western countries’ relations with China are characterised by a dichotomy of partnership and conflict, of rapprochement and demarcation. To date, research lacks longitudinal studies that examine how these economic and political tendencies become manifest in the image of China conveyed by Western media. Taking Germany as an example, this study aims to shed light on the development of China coverage in print media between 2000 and 2019. Following a triangulating mixed-method approach, the results of computational topic1 modelling (N = 55,893) are complemented by semi-standardised interviews with China correspondents. A framing analysis shows that China was depicted as a valuable economic partner until a rivalry frame started to become dominant in 2016/17. This shift was accompanied by a significant increase in media interest., The international communication gazette

A major challenge for the enzymatic synthesis of sugar esters is the low solubility of sugars in anhydrous, often toxic, organic solvents. We overcame this limitation by using acyltransferases for ...

Wir stellen in diesem Aufsatz ein Modell interdisziplinarer Zusammenarbeit zwischen Kommunikationswissenschaft und Methodenwissenschaft (hier: Statistik) vor. Dabeisteht die Frage im Mittelpunkt, wie sich die Kollaboration grundverschiedener Disziplinen uber einen langeren Zeitraum verstetigen lasst. Der agilen Entwicklung von Forschungssoftware, die die fachubergreifende Zusammenarbeit strukturiert, kann hierbei eine zentrale Rolle zukommen. Sie ermoglicht zwei Ebenen der Zusammenarbeit mit verschiedenen Zeithorizonten: auf der einen werden zeitlich begrenzte Projekte umgesetzt, auf der anderen die langerfristige Zusammenarbeit organisiert. Wechselnde Team-Konstellationen und Hierarchien ermoglichen kontinuierlichen Wissensaustausch, die verwendete Programmiersprache ist Grundlage fur die Entstehung einer facherubergreifenden Kommunikation und die Orientierung auf ein gemeinsames Produkt schafft eine Kultur der gemeinsamen Verantwortlichkeit. Um die theoretischen Reflexionen an der Forschungspraxis zu spiegeln, greifen die Autor*innen auf ihre Erfahrungen im Kontext des Dortmund Center fur datenbasierte Medien-Analyse (kurz: DoCMA) zuruck. DoCMA ist deswegen als Fallbeispiel relevant, da Struktur und Organisation hier auf die Erfordernisse der agilen Entwicklung offener Forschungssoftware ausgerichtet wurden.

Olive mill wastewater (OMWW) is produced annually during olive oil extraction and contains most of the health-promoting 3-hydroxytyrosol of the olive fruit. To facilitate its recovery, enzymatic transesterification of hydroxytyrosol (HT) was directly performed in an aqueous system in the presence of ethyl acetate, yielding a 3-hydroxytyrosol acetate rich extract. For this, the promiscuous acyltransferase from Pyrobaculum calidifontis VA1 (PestE) was engineered by rational design. The best mutant for the acetylation of hydroxytyrosol (PestE_I208A_L209F_N288A) was immobilized on EziG

The highly efficient and versatile acyltransferase MsAcT from Mycobacterium smegmatis catalyzes aqueous acyl transfer reactions, enabling applications in environmentally friendly processes and enzy...

International audience; Biocatalytic transesterification is commonly carried out employing lipases in anhydrous organic solvents since hydrolases usually prefer hydrolysis over acyl transfer in bulk water. However, some promiscuous acyltransferases can catalyze acylation in an aqueous solution. In this study, a rational design was performed to enhance the acyltransferase selectivity and substrate scope of the Pyrobaculum calidifontis VA1 esterase (PestE). PestE wild type and variants were applied for the acylation of monoterpene alcohols. The mutant PestE_I208A is selective for (–)-menthyl acetate (E-Value = 55). Highly active acyltransferases were designed, allowing for complete conversion of (–)-citronellol to citronellyl acetate. Additionally, carvacrol was acetylated but with lower conversions. To the best of our knowledge, this is the first example of the biocatalytic acylation of a phenolic alcohol in bulk water. In addition, a high citronellol conversion of 92% was achieved with the more environmentally friendly and inexpensive acyl donor ethyl acetate using PestE_N288F as a catalyst. PestE_N288F exhibits good acyl transfer activity in an aqueous medium and low hydrolysis activity at the same time. Thus, our study demonstrates an alternative synthetic strategy for acylation of compounds without organic solvents.

Right-wing media have been growing in terms of readership and impact in recent years. However, comparative analyses that gauge linkages between mainstream and right-wing media in Europe are virtually missing. We pursued an algorithm-based topic-modelling analysis of 11,420 articles concerning the question of whether reporting of the leading German right-wing newspaper Junge Freiheit differed from that of mainstream media outlets in the context of the refugee crisis of 201516. The results strongly support this notion. They show a clear-cut dichotomy with mainstream media on one side and Junge Freiheit on the other. A time lag could be found, pointing to a reporting pattern that positioned Junge Freiheit relative to the journalistic and political mainstream. Thus, Junge Freiheit can be characterised as a reactive alternative media outlet that is prone to populism: it stresses the national dimension of the crisis, embraces the positions of the right-wing party Alternative fr Deutschland (AfD) and largely neglects complex international, and particularly European, implications.

Biradicals were applied as molecular switches to control chemical reactions that involve the activation of small molecules. The mechanism was studied by experimental and computational methods., Molecular switches are molecules that can reversibly be shifted between at least two stable states with different physical and chemical properties, making them interesting for application as chemical sensors or molecular machines. We recently discovered that five-membered, cyclic biradicals based on group 15 elements are efficient and robust photochemical switches that can be activated by red light. The quantum yield of the photo-isomerization is as high as 24.6%, and the thermal equilibration of the photo-activation product proceeds rapidly at ambient temperature. The fully reversible process was studied by experimental and high-level ab initio techniques. We could further demonstrate that the biradical character could be completely turned on and off, so the system could be applied to control chemical equilibria that involve activation products of the cyclic biradicals.

The Wehrl entropy is an entropy associated to the Husimi quasi-probability distribution. We discuss how it can be used to formulate entropic uncertainty relations and for a quantification of entanglement in continuous variables. We show that the Wehrl-Lieb inequality is closer to equality than the usual Bia{\l}ynicki-Birula and Mycielski entropic uncertainty relation almost everywhere. Furthermore, we show how a Wehrl mutual information can be used to obtain a measurable perfect witness for pure state bipartite entanglement, which additionally provides a lower bound on the entanglement entropy., Comment: 15 pages, 3 figures

SummaryαB-crystallin (ABC) is a human small heat shock protein that is strongly linked to Alzheimer’s disease (AD). In vitro, it can inhibit the aggregation and amyloid formation of a range of proteins including Aβ(1-40), a primary component of AD amyloid plaques. Despite the strong links, the mechanism by which ABC inhibits amyloid formation has remained elusive, in part due to the notorious irreproducibility of aggregation assays involving preparations of Aβ-peptides of native sequence. Here, we present a recombinant expression protocol to produce native Aβ(1-40), devoid of any modifications or exogenous residues, with yields up to 4 mg/L E. coli. This material provides highly reproducible aggregation kinetics and, by varying the solution conditions, we obtain either highly ordered amyloid fibrils or more disordered aggregates. Addition of ABC slows the aggregation of Aβ(1-40), and interferes specifically with the formation of ordered amyloid fibrils, favouring instead the more disordered aggregates. Solution-state NMR spectroscopy reveals that the interaction of ABC with Aβ(1-40) depends on the specific aggregate morphology. These results provide mechanistic insight into how ABC inhibits the formation of amyloid fibrils.HighlightsProtocol for production of native recombinant Aβ(1-40)Amyloid formation under physiological conditions is highly reproducibleBoth ordered fibrils and disordered aggregates can be reliably formedαB-crystallin specifically inhibits amyloid fibril assembling, favouring disordered aggregateseTOC blurbMüller et al. introduce a protocol for the highly reproducible production of amyloid from native Aβ(1-40) and determine that the human chaperone ABC specifically destabilises them in favour of disordered aggregates. NMR shows that ABC can distinguish between aggregate morphologies.Graphical Abstract

Certain hydrolases preferentially catalyze acyl transfer over hydrolysis in an aqueous environment. However, the molecular and structural reasons for this phenomenon are still unclear. Herein, we provide evidence that acyltransferase activity in esterases highly correlates with the hydrophobicity of the substrate‐binding pocket. A hydrophobicity scoring system developed in this work allows accurate prediction of promiscuous acyltransferase activity solely from the amino acid sequence of the cap domain. This concept was experimentally verified by systematic investigation of several homologous esterases, leading to the discovery of five novel promiscuous acyltransferases. We also developed a simple yet versatile colorimetric assay for rapid characterization of novel acyltransferases. This study demonstrates that promiscuous acyltransferase activity is not as rare as previously thought and provides access to a vast number of novel acyltransferases with diverse substrate specificity and potential applications., What's the score? Promiscuous acyltransferase activity of esterases strongly correlates with active‐site hydrophobicity. A hydrophobicity scoring concept was developed that enables the accurate prediction of promiscuous acyltransferase activity simply from the amino acid sequence of the enzyme cap domain.

In der Formula Student, einem Konstruktionswettbewerb fur Studenten, gewinnt das Thema Leichtbau immer mehr an Bedeutung. Mit geringerer Masse sind die konstruierten Rennwagen wettkampftauglicher. Daher bietet sich das Selektive Laserstrahlschmelzens an, um fur den Anwendungsfall optimierte Geometrien zu erzeugen, welche mit herkommlichen Fertigungsverfahren nicht herstellbar sind. Eine geringe Teilezahl innerhalb von Baugruppen ist dabei vorteilhaft, um den Fertigungs- und Montageaufwand gering zu halten. In diesem Beitrag wird eine Methode zur Teilezahlreduktion, unter Anwendung der Funktionsintegration, entwickelt. Diese wird beispielhaft an der Pedalerie eines Formula Student Rennwagens durchgefuhrt. Basierend auf dieser Auswahl wird eine neue Geometrie ermittelt und mit Hilfe der Topologieoptimierung in iterativen Schritten das Gewicht optimiert. Die Geometrie wird mittels einer FE-Analyse validiert und das fertige Modell aus der Aluminiumlegierung ALSI10Mg gefertigt.

Die Anwendung digitaler Methoden bietet die Chance, Kommunikationswissenschaften und Okonomik enger zu verknupfen. So besteht in der Konjunktur- und der Finanzmarktforschung seit einigen Jahren ein wachsendes Interesse an der Einbeziehung von Medieninhalten, allerdings meist ohne Ruckgriff auf die Kommunikationswissenschaften. Dieser Beitrag gibt einen Uberblick uber Ansatze zur Einbeziehung von Medieninhalten in der Wirtschaftsforschung und stellt einen neuen, multidimensionalen Indikator vor, der wirtschaftspolitische Unsicherheit auf der Grundlage des Topic-Modelling-Verfahrens Latent Dirichlet Allocation (LDA) misst: den Uncertainty Perception Indicator (UPI). Auf dieser Basis zeigen wir, wie sich der in der Okonomik populare Begriff des „Narrativs“ operationalisieren und mit dem kommunikationswissenschaftlichen Konzept des Frames verknupfen lasst.

Self-propagating β-sheet-rich fibrillar protein aggregates, amyloid fibers, are often associated with cellular dysfunction and disease. Distinct amyloid conformations dictate different physiological consequences, such as cellular toxicity. However, the origin of the diversity of amyloid conformation remains unknown. Here, we suggest that altered conformational equilibrium in natively disordered monomeric proteins leads to the adaptation of alternate amyloid conformations that have different phenotypic effects. We performed a comprehensive high-resolution structural analysis of Sup35NM, an N-terminal fragment of the Sup35 yeast prion protein, and found that monomeric Sup35NM harbored latent local compact structures despite its overall disordered conformation. When the hidden local microstructures were relaxed by genetic mutations or solvent conditions, Sup35NM adopted a strikingly different amyloid conformation, which redirected chaperone-mediated fiber fragmentation and modulated prion strain phenotypes. Thus, dynamic conformational fluctuations in natively disordered monomeric proteins represent a posttranslational mechanism for diversification of aggregate structures and cellular phenotypes.

Populism is increasingly turning against globalization, thereby threatening the stability of the international order. In the vast debate about the causes of the current backlash many factors have been discussed, without explicitly analyzing the role of the media. This paper strives to fill this gap. It focuses on the interaction between politics, economics, and the media in the context of globalization-related issues. In applying a media economic framework it shows that the rise of populism can be interpreted as the consequence of rational choices of different groups of players. The result is a spiral of noise of ever more extreme anti-globalist rhetoric and policies.

In seinem Beitrag „So wie Muller reden nur Dogmatiker“ gibt Henrik Muller in Form eines Werkstattberichts Einblicke in die Entstehung seiner wochentliche Kolumne „Mullers Memo“ bei Spiegel Online, die in den Jahren 2017 und 2018 bei rund der Halfte der Texte sechsstellige Leserzahlen erreichte. Dabei erlautert er nicht nur Prozesse und Schwerpunkte der Themenfindung, sondern auch welche Ziele er als Journalist verfolgt sowie welche redaktionellen Arbeitsschritte bis zum Erscheinen eines Artikels hinter den Kulissen durchlaufen werden. Des Weiteren geht er darauf ein, welche (konstruktiven und reflektierten) Debatten sich unter den Lesern in einem Online-Forum entwickeln konnen und wie er als Autor mit personlicher Kritik und polemischen Kommentaren umgeht. Wissenschaftler sind Mullers Einschatzung nach gehalten, sich an gesellschaftlichen Diskursen zu beteiligen: „Wissenschaftler, die aus offentlichen Geldern bezahlt werden, haben die Aufgabe, sich gegenuber der Offentlichkeit zu erklaren. Sie sollten an politischen Debatten teilnehmen, weil sie zur Versachlichung und Aufklarung beitragen konnen. Sich kontroversen Diskussionen zu stellen, hilft ubrigens auch bei der Scharfung der eigenen Argumente“.

Nature Communications 10(1), 1717 (2019). doi:10.1038/s41467-019-09326-3, MET, the product of the c-MET proto-oncogene, and its ligand hepatocyte growth factor/scatter factor (HGF/SF) control survival, proliferation and migration during development and tissue regeneration. HGF/SF-MET signaling is equally crucial for growth and metastasis of a variety of human tumors, but resistance to small-molecule inhibitors of MET kinase develops rapidly and therapeutic antibody targeting remains challenging. We made use of the designed ankyrin repeat protein (DARPin) technology to develop an alternative approach for inhibiting MET. We generated a collection of MET-binding DARPins covering epitopes in the extracellular MET domains and created comprehensive sets of bi-paratopic fusion proteins. This new class of molecules efficiently inhibited MET kinase activity and downstream signaling, caused receptor downregulation and strongly inhibited the proliferation of MET-dependent gastric carcinoma cells carrying MET locus amplifications. MET-specific bi-paratopic DARPins may represent a novel and potent strategy for therapeutic targeting of MET and other receptors, and this study has elucidated their mode of action., Published by Nature Publishing Group UK, [London]

Europa muss sich entscheiden, ob es die gewachsene Zusammenarbeit vertiefen oder aber reduzieren will. Unter Ökonomen dominiert Skepsis. Viele würden das Euro-Rad am liebsten zurückdrehen. Was dagegen fehlt, ist eine plausible Vision, wie es vorangehen könnte. Kernelemente sollten finanzielle Ausgleichszahlungen zwischen den Ländern der EU sowie die demokratische Legitimierung durch ein 'echtes' Europäisches Parlament sein, das mit Budgetrechten - insbesondere der Kompetenz zur Besteuerung von Kapital - ausgestattet wird. The European Union is approaching a point where it has to decide between two options: deepening political integration or reducing it. Economists tend to be sceptical. Many would prefer to reduce the scale of integration while returning more competences to member states. The debate, though, lacks a plausible vision for the path forward. Every stable currency union needs some kind of transfer mechanism. Once this notion is accepted, the installation of a 'real' European Parliament with the power to raise taxes, particularly on capital income, should be considered.

Der Beitrag thematisiert eine Abgrenzung des wirtschaftspolitischen Journalismus gegenuber den ubrigen Spielarten des Wirtschaftsjournalismus. Dieser ist nicht auf spezifische Zielgruppen fokussiert, wirtschaftspolitische Journalismus ist breit angelegt. Es ist Aufgabe des wirtschaftspolitischen Journalismus, narrative Brucken zu bauen, um die okonomische Realitat verstandlich zu machen. Er betrachtet Entwicklungen vor dem Hintergrund gesamtwirtschaftlicher Zusammenhange und nimmt somit eine systemische Perspektive ein. Erlautert werden die Funktionen des wirtschaftspolitischen Journalismus fur Wirtschaft und Politik. Es wird ein theoretisch fundiertes Selbstverstandnis des wirtschaftspolitischen Journalismus skizziert.

As a basis for the further development of a wall-function approach, the SETCOM (Separate Effect test for Condensation Modeling) facility is operated at Forschungszentrum Julich to gain an insight into the turbulent heat and mass transfer in the boundary layer during wall condensation. This data was applied on the one hand for a detailed validation of a resolved boundary layer (low-Re) CFD approach. On the other hand, the data has been post processed following the classical scaling approach based on the friction or shear velocity uτ (i.e. u+ − y+ or T+ − y+). It became obvious that a single dimensionless parameter y+, which is a kind of Reynolds number, is not sufficient for describing flows including near wall buoyancy and wall normal mass transfer. For this reason, two additional new dimensionless parameters, the dimensionless gravity force and the dimensionless heat flux have been introduced to describe the wall boundary conditions by 3D surfaces instead of a 1D analytical correlation. These characteristic 3D maps, which are based on a combination of detailed experimental data and validated CFD results, are implemented numerically efficient for u+, T+, YS+ and turbulence (ηt via ω) by means of a non-equilibrium factor and an approximation by radial basis functions into an existing U-RANS model. Following a detailed discussion of the model derivation and implementation, the paper is concluded with exemplary discussion of current model assessment results.

Solution-state NMR spectroscopy remains the primary method for characterising synthetic supramolecular assemblies. Yet, in their NMR spectra, relaxation interference effects can significantly alter peak intensities hindering interpretation. Here, we present a simple experiment for synthetic chemists to analyse this effect, allowing interpretation of these distorted spectra and validation of spectral assignments. We apply this experiment to synthetic porphyrin oligomers with molecular weights approaching those of protein domains (10 kDa). Our experiment provides a simple means to gain additional structural and dynamical information that will become increasingly useful as chemists create larger molecular architectures.

Flavonoids are an interesting group of natural products ubiquitously present in human diet. Their consumption has been associated with various and differing beneficial health effects. However, several flavonoids have been reported to inhibit the breast cancer resistance protein (BCRP) encoded by the ABCG2 gene. Thus, the consumption of flavonoids with high inhibitory activity could change pharmacokinetics and drug levels of drugs that are BCRP substrates. In cancer patients receiving chemotherapy an increased intake of such flavonoids could lead to adverse effects. We investigated a structurally diverse set of flavonoids, including derivatives with a rare C-methylated structure that were isolated from plants used in traditional medicine. The flavones retusin and ayanin were found to be highly potent inhibitors of BCRP, showing only slightly less potency than Ko143, the most potent ABCG2 inhibitor known so far. The activity data were analyzed by 2D and 3D QSAR analyses and the results revealed the impact of the different substituents at the various positions of the flavonoid core on activity. Additionally, a lateral 2D QSAR analysis of data collected from the literature was performed aiming to derive more general information about the influence of distinct structural features on the inhibitory potency of flavonoids. The comparative QSAR analyses led to a consistent picture of the effects of the different substituents at various positions of the flavone backbone. The following structural features were found to contribute positively to BCRP inhibition: a hydroxyl group in position 5, double bond between position 2 and 3, and a methoxy group in position 3. The exchange of a 3-methoxy group by an OH-group acting also as a hydrogen bond donor, resulted in decrease in activity underlining the potential role of the hydrogen bond acceptor 3-OCH(3) for the interaction with BCRP.

We report the details of the total synthesis of natural and non-natural jatropha-5,12-dienes. The successful tactic for the assembly of the strained trans-bicyclo[10.3.0]pentadecane scaffold employed a B-alkyl Suzuki-Miyaura cross-coupling for the formation of the C5/C6 double bond and a ring-closing metathesis for the construction of the C12/C13 double bond. The key step of the synthesis of the cyclopentane fragment, an uncatalyzed intramolecular carbonyl-ene reaction, was studied computationally by DFT calculations. The members of the ensemble of synthetic natural and non-natural jatrophanes were subsequently examined as modulators for the ABCB1, ABCG2, and ABCC1 efflux proteins, which are associated with multidrug resistance in cancer chemotherapy.

From our modulator library an interesting inhibitor of breast cancer resistance protein (BCRP) was identified. Due to its high inhibitory potency, this compound may serve as a promising novel lead for the design of new and potent modulators. This adds a new structural class to the few known highly active BCRP inhibitors.

The development of new modulators possessing high efficacy, low toxicity and high selectivity is a pivotal approach to overcoming P-glycoprotein (P-gp) mediated multidrug resistance (MDR) in tumour cells. In this study 39 compounds are presented which have been synthesized and pharmacologically investigated in our laboratory. Similarly to the potent 3rd generation MDR modulator tariquidar (XR9576) the compounds contain a tetrahydroisoquinoline-ethyl-phenylamine substructure that, in contrast to XR9576, is connected to a smaller hydrophobic part, thus leading to molecules of lower molecular weight. The connection between the tetrahydroisoquinoline-ethyl-phenylamine substructure and the hydrophobic part was achieved through four different types of linkers: amide, urea, amide-ether and amide-styryl. A number of structural modifications in the hydrophobic part were created. The calcein AM assay served as test system to determine the P-gp transport inhibitory potencies of the compounds. For the amide linker derivatives a structure-activity relationship analysis was performed outlining which structural modifications contributed to the inhibitory potency. The compounds containing a bicyclic hydrophobic part with a particular substituent in a specific orientation were identified as the most potent amide derivatives. Among the urea derivatives the compounds with highest inhibitory potency possessed an ortho-nitro substituent. The conformational analysis revealed that this position enables the formation of a hydrogen bond to the urea linker thus stabilizing the conformation. Regarding the amide-styryl derivatives the elongation of the amide linker seemed to be most decisive for the observed increase in activity. The most promising candidate in the whole library possess an amide-ether linker and an ortho-nitro substituent in the hydrophobic part. This compound inhibites P-gp slightly less than tariquidar and can serve as a lead structure for new potent P-gp modulators.