Ca2+/calmodulin-dependent kinase II mediates simultaneous enhancement of gap-junctional conductance and glutamatergic transmission

While chemical synapses are very plastic and modifiable by defined activity patterns, gap junctions, which mediate electrical transmission, have been classically perceived as passive intercellular channels. Excitatory transmission between auditory afferents and the goldfish Mauthner cell is mediated by coexisting gap junctions and glutamatergic synapses. Although an increased intracellular Ca2+ concentration is expected to reduce gap junctional conductance, both components of the synaptic response were instead enhanced by postsynaptic increases in Ca2+ concentration, produced by patterned synaptic activity or intradendritic Ca2+ injections. The synaptically induced potentiations were blocked by intradendritic injection of KN-93, a Ca2+/calmodulin-dependent kinase (CaM-K) inhibitor, or CaM-KIINtide, a potent and specific peptide inhibitor of CaM-KII, whereas the responses were potentiated by injection of an activated form of CaM-KII. The striking similarities of the mechanisms reported here with those proposed for long-term potentiation of mammalian glutamatergic synapses suggest that gap junctions are also similarly regulated and indicate a primary role for CaM-KII in shaping and regulating interneuronal communication, regardless of its modality.     

Metal Ion Promiscuity and Structure of 2,3-Dihydroxybenzoic Acid Decarboxylase of Aspergillus oryzae

Broad substrate tolerance and excellent regioselectivity, as well as independence from sensitive cofactors have established benzoic acid decarboxylases from microbial sources as efficient biocatalysts. Robustness under process conditions makes them particularly attractive for preparative-scale applications. The divalent metal-dependent enzymes are capable of catalyzing the reversible non-oxidative (de)carboxylation of a variety of electron-rich (hetero)aromatic substrates analogously to the chemical Kolbe-Schmitt reaction. Elemental mass spectrometry supported by crystal structure elucidation and quantum chemical calculations verified the presence of a catalytically relevant Mg²⁺ complexed in the active site of 2,3-dihydroxybenoic acid decarboxylase from Aspergillus oryzae (2,3-DHBD_Ao). This unique example with respect to the nature of the metal is in contrast to mechanistically related decarboxylases, which generally have Zn²⁺ or Mn²⁺ as the catalytically active metal.     

Manufacture and characterization of acid-coagulated fresh cheese made from casein concentrates obtained by acid diafiltration

This study aimed to investigate the production of acid-coagulated fresh cheese by using slightly acid diafiltered (DF) microfiltered (MF) casein concentrates (8% protein). Three different acidifying agents were tested during DF: carbon dioxide, lactic acid, and citric acid. Fresh cheese was manufactured using acid-DF casein concentrates, or casein concentrates DF with just water, and compared with cheese manufactured using MF casein concentrates without DF. The fresh cheeses were characterized for composition, rheological, and sensorial properties. Acid-DF casein concentrates improved acidification kinetics during cheesemaking and reduced casein leakage to cheese whey, compared with cheese from regular MF casein concentrate. Among the rheological properties investigated in this study, the storage modulus of the fresh cheese was higher when DF of the casein concentrate was performed with nonacidified DF water or when DF water was acidified with citric acid. However, fresh cheese made from casein concentrate diafiltered with DF water acidified by citric acid was most liked in a sensory ranking test.     

Nitrile as Activating Group in the Asymmetric Bioreduction of β‐Cyanoacrylic Acids Catalyzed by Ene‐Reductases

Asymmetric bioreduction of an (E)‐β‐cyano‐2,4‐dienoic acid derivative by ene‐reductases allowed a shortened access to a precursor of pregabalin [(S)‐3‐(aminomethyl)‐5‐methylhexanoic acid] possessing the desired configuration in up to 94% conversion and >99% ee. Deuterium labelling studies showed that the nitrile moiety was the preferred activating/anchor group in the active site of the enzyme over the carboxylic acid or the corresponding methyl ester.

     

A Complexity Framework for Studying Disaster Response Management

Guided by complexity theory, in this article, we argue that a complex understanding of disaster response management can be achieved by making multiple, transparent and modest interpretations. We suggest an analytical framework in which multiple system interpretations are constructed, all based on explicit analytical choices according to three aspects: (1) system dimension, (2) system scope and (3) system resolution. We apply the framework to a major Swedish forest fire and conclude that direction and coordination as system properties, emerging at a macro level, are the result of interplay between various patterns of influences. These patterns, we argue, can be constructed and analysed through a complexity framework allowing for the construction, and contrasting, of multiple system interpretations.     

Risikobasierter Ansatz zur Bewertung der Robustheit von Bauwerken

Ziel des vorliegenden Beitrages ist es, einen Überblick über die aktuellen Entwicklungen im Bereich der Bewertung und der Quantifizierung der Robustheit von Bauwerken zu geben. In diesem Sinne ist eine Zusammenstellung von Ansätzen und Ergebnissen aktueller Veröffentlichungen enthalten. Ein umfassender entscheidungstheoretischer Ansatz für die Berechnung und das Management der Robustheit wird vorgestellt. Dieser beinhaltet die Definition der Robustheit als eine Qualität eines Systems, welches das Bauwerk beinhaltet, d. h. eine Qualität, die auf der Grundlage einer Risikoanalyse bewertet werden kann. Um eine umfassende Risikoanalyse zu ermöglichen, wird ein szenarienbasierter Modellansatz eingeführt, welcher zwei Arten von Konsequenzen im System unterscheidet: direkte Konsequenzen (in Verbindung mit Schäden einzelner Komponenten des Systems) und indirekte Konsequenzen (in Verbindung mit einem Versagen des Systems). Die Definition des Systems spielt deshalb für die Risikoanalyse eine wichtige Rolle, und es wird diskutiert, wie die Robustheit für verschiedene Definitionen zu unterschiedlichen Ergebnissen und Erkenntnissen im Sinne des Managements der Integrität des Bauwerks im gesamten Lebenszyklus unter Berücksichtigung seiner Funktionalität führt. Weiterhin werden wichtige Aspekte der Standardisierung der Robustheitsanalyse, wie auch Anforderungen an die Robustheit, diskutiert und Vorschläge zum Umgang mit diesen Aspekten unterbreitet. Auf der Grundlage der vorgestellten Ansätze zur Berechnung der Robustheit eines Bauwerks wird beschrieben, wie Entscheidungen in Bezug auf den Entwurf, die Zustandsbewertung, auf Inspektionen und Wartung sowie in Bezug auf die Überwachung von Bauwerken, in Hinblick auf das Management der Risiken in allen Phasen des Lebenszyklus, optimiert werden können. Risk based approach for the assessment of the robustness of structures. The present paper serves as an overview of recent developments by the author on the assessment and quantification of robustness of structures; the paper aims in this sense not to present any new results but collects approaches and results from previous publications. A general decision theoretical approach to the assessment and management of structural robustness is outlined. Structural robustness is introduced as a quality of the system comprising the structure; a quality which can be assessed by means of risk assessments. To facilitate an appropriate risk assessment for structural systems a scenario based model approach is outlined which differentiates consequences into two different types: direct (related to damages to individual components) and indirect (related to collapse failures). The definition of the “structural system” thus plays an important role in the risk assessment and it is discussed how the robustness assessed according to different definitions of the structural system will lead to different results and insights of relevance for the lifecycle management of the structural integrity. Furthermore, the important aspects of standardization of robustness assessments as well as requirements to robustness are discussed and suggestions for the treatment of these are proposed. Based on the presented approach to the assessment of structural robustness it is outlined how decisions on design, condition assessment, inspection and maintenance as well as monitoring activities for structures can be optimized for the purpose of managing structural risks over all phases of the life‐cycle of structures.     

Non‐Racemic Halohydrins via Biocatalytic Hydrogen‐Transfer Reduction of Halo‐Ketones and One‐Pot Cascade Reaction to Enantiopure Epoxides

Biocatalytic hydrogen‐transfer reduction of α‐chloro‐ketones furnished non‐racemic chlorohydrins by employing either Rhodococcus ruber as lyophilized cell catalyst or an alcohol dehydrogenase preparation from Pseudomonas fluorescens DSM 50106 (PF‐ADH). For all substrates investigated, Rhodococcus ruber gave strictly the “Prelog” product, whereas PF‐ADH showed scattered stereopreference. One possibility for a follow‐up reaction of halohydrins is the ring closure to the corresponding epoxide. A novel “one pot‐one step strategy” was employed to obtain the enantiopure epoxide from the α‐chloro‐ketone in a cascade like fashion at pH>12 involving biocatalytic hydrogen transfer reduction and in situ chemo‐catalyzed ring closure.