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Queuosine (Q) is a hypermodified RNA nucleoside that is found in tRNAHis, tRNAAsn, tRNATyr, and tRNAAsp. It is located at the wobble position of the tRNA anticodon loop, where it can interact with U as well as C bases located at the respective position of the corresponding mRNA codons. In tRNATyr and tRNAAsp of higher eukaryotes, including humans, the Q base is for yet unknown reasons further modified by the addition of a galactose and a mannose sugar, respectively. The reason for this additional modification, and how the sugar modification is orchestrated with Q formation and insertion, is unknown. Here, we report a total synthesis of the hypermodified nucleoside galactosyl‐queuosine (galQ). The availability of the compound enabled us to study the absolute levels of the Q‐family nucleosides in six different organs of newborn and adult mice, and also in human cytosolic tRNA. Our synthesis now paves the way to a more detailed analysis of the biological function of the Q‐nucleoside family., The first total synthesis of the hypermodified RNA nucleoside galactosyl‐queuosine (galQ) was achieved. Moreover, the distribution of this nucleoside as well as mannosyl‐queuosine and queuosine was determined in tissues of newborn and adult mice, and in human cytosolic tRNAs.

Queuosine (Q) is a structurally complex, non‐canonical RNA nucleoside. It is present in many eukaryotic and bacterial species, where it is part of the anticodon loop of certain tRNAs. In higher vertebrates, including humans, two further modified queuosine-derivatives exist ‐ galactosyl‐ (galQ) and mannosyl-queuosine (manQ). The function of these low abundant hypermodified RNA nucleosides remains unknown. While the structure of galQ was elucidated and confirmed by total synthesis, the reported structure of manQ still awaits confirmation. By combining total synthesis and LC-MS-co-injection experiments, together with a metabolic feeding study of labelled hexoses, we show here that the natural compound manQ isolated from mouse liver deviates from the literature-reported structure. Our data show that manQ features an α‐allyl connectivity of its sugar moiety. The yet unidentified glycosylases that attach galactose and mannose to the Q‐base therefore have a maximally different constitutional connectivity preference. Knowing the correct structure of manQ will now pave the way towards further elucidation of its biological function., Mannosyl-queuosine (manQ) is a non-canonical RNA nucleoside present in the anticodon loop of certain tRNAs. Here, the authors use a combination of total synthesis and mass spectrometry to contradict the literature-reported structure and show that manQ features an alpha-allyl connectivity of its mannose moiety.

Hepatic steatosis is a very common response to liver injury and often attributed to metabolic disorders. Prior studies have demonstrated the efficacy of a biotechnologically produced oyster mushroom (Pleurotus sajor-caju, PSC) in alleviating hepatic steatosis in obese Zucker rats. This study aims to elucidate molecular events underlying the anti-steatotic effects of PSC. Tandem mass tag (TMT) peptide labeling coupled with LC-MS/MS/MS was used to quantify and compare proteins in the livers of lean Zucker rats fed a control diet (LC), obese Zucker rats fed the same control diet (OC) and obese Zucker rats fed the control diet supplemented with 5% PSC (OPSC) for 4 weeks. Using this technique 3128 proteins could be quantified, out of which 108 were differentially abundant between the OPSC and OC group. Functional enrichment analysis of the up-regulated proteins showed that these proteins were mainly involved in metabolic processes, while the down-regulated proteins were involved in inflammatory processes. Results from proteomic analysis were successfully validated for two up-regulated (carbonic anhydrase 3, regucalcin) and two down-regulated (cadherin-17, ceruloplasmin) proteins by means of immunoblotting.

Nemerteans (ribbon worms) employ toxins to subdue their prey, but research thus far has focused on the small-molecule components of mucus secretions and few protein toxins have been characterized. We carried out a preliminary proteotranscriptomic analysis of putative toxins produced by the hoplonemertean Amphiporus lactifloreus (Hoplonemertea, Amphiporidae). No variants were found of known nemertean-specific toxin proteins (neurotoxins, cytotoxins, parbolysins or nemertides) but several toxin-like transcripts were discovered, expressed strongly in the proboscis, including putative metalloproteinases and sequences resembling sea anemone actitoxins, crown-of-thorn sea star plancitoxins, and multiple classes of inhibitor cystine knot/knottin family proteins. Some of these products were also directly identified in the mucus proteome, supporting their preliminary identification as secreted toxin components. Two new nemertean-typical toxin candidates could be described and we re named U-nemertotoxin-1 and U-nemertotoxin-2. Our findings provide insight into the largely overlooked venom system of nemerteans and support a hypothesis in which the nemertean proboscis evolved in several steps from a flesh-melting organ in scavenging nemerteans to a flesh-melting and toxin-secreting venom apparatus in hunting hoplonemerteans.

An updated taxonomic review of freshwater Annelida found in the Neotropical and Antarctic Regions is presented in this chapter. This chapter provides dichotomous identification keys to Polychaeta, Clitellata, and Aphanoneura. Also included are current limits to identification of various annelids, a description of terms needed to identify taxa, and methods for preparing and identifying species. Additional information on annelids can be found in Volume I (“Ecology and General Biology”) of this book series (Thorp & Rogers, 2015, Elsevier).

Gold-catalyzed reactions of 3-silyloxy-1,4-enynes with alcohols afford primary, secondary, and tertiary pent-2-en-4-ynyl ethers in moderate to excellent yields. The substitution proceeds with high regioselectivity. An initial cyclization providing five-membered carbocycles instead was not observed under the reaction conditions. Control experiments show that these reactions are also catalyzed by Bronsted- and Lewis-acids, although scope and yields are markedly reduced.

Gold-catalyzed reactions of 3-silyloxy-1,5-enynes in the presence of sterically demanding alcohols afford 4-acylcyclopentenes. The cascade process most likely proceeds through a 6-endo-dig carbocyclization and subsequent pinacol-type rearrangement. Studies that define scope and limitations of the cyclization–migration strategy are also described. An alternative cascade yields highly substituted aryls through an unprecedented cyclization–fragmentation pathway.

A combination of gold(I) complexes and amine bases catalyzes the 5-exo-dig cyclization of formyl alkynes. This direct alpha-functionalization of aldehydes with unactivated alkynes does not involve the use of preformed enol equivalents.

PTEN-induced kinase1 (PINK1) acts at multiple levels topromote mitochondrial health, including regulatory influence on ATP-synthesis, protein quality control, apoptosis, mitochondrialtransport, and destiny. PINK1 mutations are linked to Parkinsondisease (PD) and mostly result in loss of kinase activity. But themolecular events responsible for neuronal death as well as thephysiological targets and regulators of PINK1 are still a matter ofdebate. We will discuss recent progress revealing the cellularfunctions of the cytosolic pool of PINK1 in mitochondrialtrafficking and neuronal differentiation. Regulation of PINK1signaling occurs by mitochondrial processing to truncated formsof PINK1, differentially targeted to several subcellular compart-ments. The first identified activating kinase of PINK1 is MAP/microtubule affinity regulating kinase2 (MARK2), which phospho-rylates T313, a frequent mutation site linked to PD. Kinases of theMARK2 family perform diverse functions in neuronal polarity,transport, migration, and neurodegeneration such as Alzheimerdisease (AD); in particular they regulate the interactions betweenmicrotubules and microtubule-associated proteins such as tau. ThisMARK-PINK kinase signaling axis might provide a link betweenneurodegenerative processes in AD and PD and opens novelpossibilities of targeting pathological signaling processes. – Sup-ported by MPG, DZNE, KNDD (BMBF)

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Starting from the same compounds, two unprecedented domino reactions are performed leading to either bicyclic 2,3-dihydrofurans or furylbutanals.

Two cats, two paths: two novel domino reactions starting from 6-hydroxy-2-alkyl-2-alkynylcyclohexanones have been discovered. While redox-neutral platinum catalysis gives rise to furans through a sequence of cyclization, 1,2-shift, and Grob fragmentation, oxidative copper catalysis provides an entry to bicyclic 2,3-dihydrofurans. Upon cyclization and oxidation, an unusual benzilic acid rearrangement can take place in this case.

BACKGROUND: Deregulation of the protein kinase MARK has been linked to Alzheimer disease. - RESULTS: Mark-specific inhibitors and a biosensor are identified. - CONCLUSION: The inhibitors and the biosensor are tools to provide new insights into the role of MARK during polarity establishment and maintenance of neurons. - SIGNIFICANCE: The inhibitors might possess therapeutic potential by interfering with abnormal Tau phosphorylation in Alzheimer disease. Protein kinases of the microtubule affinity regulating kinase (MARK)/Par-1 family play important roles in the establishment of cellular polarity, cell cycle control, and intracellular signal transduction. Disturbance of their function is linked to cancer and brain diseases, e.g. lissencephaly and Alzheimer disease. To understand the biological role of MARK family kinases, we searched for specific inhibitors and a biosensor for MARK activity. A screen of the ChemBioNet library containing ∼18,000 substances yielded several compounds with inhibitory activity in the low micromolar range and capable of inhibiting MARK activity in cultured cells and primary neurons, as judged by MARK-dependent phosphorylation of microtubule-associated proteins and its consequences for microtubule integrity. Four of the compounds share a 9-oxo-9H-acridin-10-yl structure as a basis that will serve as a lead for optimization of inhibition efficiency. To test these inhibitors, we developed a cellular biosensor for MARK activity based on a MARK target sequence attached to the 14-3-3 scaffold protein and linked to enhanced cyan or teal and yellow fluorescent protein as FRET donor and acceptor pairs. Transfection of the teal/yellow fluorescent protein sensor into neurons and imaging by fluorescence lifetime imaging revealed that MARK was particularly active in the axons and growth cones of differentiating neurons.

The paper discusses collaboration and cooperation in supply networks and presents a planning mechanism whose assumptions are motivated by the automotive industry. The mechanism called Dynamic Supply Loops (DSL) is decentralized, warrants local planning autonomy and works with a relatively simple information exchange protocol between immediate partners in a supply chain. By balancing the benefit of cooperation between the partners, DSL also provides incentive to give up local optima against a globally more beneficial solution. DSL is open to embed standard planning techniques and novel incentive schemes alike. Simulation results on a multi-echelon multi-period model show that DSL outperforms traditional upstream planning and facilitates channel coordination.

Gold-catalyzed reactions of 3-silyloxy-1,4-enynes with alcohols afford primary, secondary, and tertiary pent-2-en-4-ynyl ethers in moderate to excellent yields. The substitution proceeds with high regioselectivity. An initial cyclization providing five-membered carbocycles instead was not observed under the reaction conditions. Control experiments show that these reactions are also catalyzed by Bronsted- and Lewis-acids, although scope and yields are markedly reduced.

Gold-catalyzed reactions of 3-silyloxy-1,5-enynes in the presence of sterically demanding alcohols afford 4-acylcyclopentenes. The cascade process most likely proceeds through a 6-endo-dig carbocyclization and subsequent pinacol-type rearrangement. Studies that define scope and limitations of the cyclization–migration strategy are also described. An alternative cascade yields highly substituted aryls through an unprecedented cyclization–fragmentation pathway.

A combination of gold(I) complexes and amine bases catalyzes the 5-exo-dig cyclization of formyl alkynes. This direct alpha-functionalization of aldehydes with unactivated alkynes does not involve the use of preformed enol equivalents.

Die Software OOPUS WEB stellt eine Plattform für individualisierte Produktionsplanung und -steuerung für Unternehmen der Serienfertigung dar. Um die Integration dieser Software in die Daten- und Prozesslandschaft von Unternehmen bestmöglich zu unterstützen, bedarf es einer Schnittstelle zu SAP ERP. Diese Schnittstelle wurde auf Basis des SAP Java Connectors umgesetzt.