Search

Demographic change has increased the need for elderly care. Training unemployed workers might be one way to increase the supply of elderly care nurses. This study analyzes the effectiveness of subsidized training for unemployed individuals in the elderly care professions in Germany over 11.5 years. We find that short further training and long retraining courses significantly increase workers' long-term employment. As approximately 25% to 50% of trained nurses have permanent jobs in the care sector, we estimate that approximately 5% of all employed nurses are formerly trained unemployed workers., (© 2019 The Authors Health Economics Published by John Wiley & Sons, Ltd.)

Introduction . Gastrointestinal bleeding represents the main indication for emergency endoscopy (EE). Lately, several hemostatic powders have been released to facilitate EE. Methods . We evaluated all EE in which Hemospray was used as primary or salvage therapy, with regard to short- and long-term hemostasis and complications. Results . We conducted 677 EE in 474 patients (488 examinations in 344 patients were upper GI endoscopies). Hemospray was applied during 35 examinations in 27 patients (19 males), 33 during upper and 2 during lower endoscopy. It was used after previous treatment in 21 examinations (60%) and in 14 (40%) as salvage therapy. Short-term success was reached in 34 of 35 applications (97.1%), while long-term success occurred in 23 applications (65.7%). Similar long-term results were found after primary application (64,3%) or salvage therapy (66,7%). Rebleeding was found in malignant and extended ulcers. One major adverse event (2.8%) occurred with gastric perforation after Hemospray application. Discussion . Hemospray achieved short-term hemostasis in virtually all cases. The long-term effect is mainly determined by the type of bleeding source, but not whether it was applied as first line or salvage therapy. But, even in the failures, patients had benefit from hemodynamic stabilization and consecutive interventions in optimized conditions., Competing Interests: The authors declare that they have no competing interests.

The E-signal is one of five intercellular signals (named A- to E-signal) guiding fruiting body development in Myxococcus xanthus, and it has been shown to be a combination of the branched-chain fatty acid (FA) iso-15 : 0 and the diacylmonoalkyl ether lipid TG1. Developmental mutants HB015 (Δbkd MXAN_4265::kan) and elbD (MXAN_1528::kan) are blocked at different stages of fruiting body and spore formation as they cannot form the required iso-FA or the actual ether lipid, respectively. In order to define the structural basis of the E-signal, different mono- and triglycerides containing ether or ester bonds were synthesized and used for complementation of these mutants. Here, the monoalkylglyceride dl-1-O-(13-methyltetradecyl)glycerol exhibited comparably high levels of complementation in both mutants, restoring fruiting body and spore formation, identifying iso-15 : 0 O-alkylglycerol, part of the natural lipid TG1, as the 'signalophore' of E-signalling.

The largest continuous bacterial nonribosomal peptide synthetase discovered so far is described. It consists of 15 consecutive modules arising from an uninterrupted, fully functional gene in the entomopathogenic bacterium Photorhabdus luminescens. The identification of its cryptic biosynthesis product was achieved by using a combination of genome analysis, promoter exchange, isotopic labeling experiments, and total synthesis of a focused collection of peptide candidates. Although it belongs to the growing class of D-/ L-peptide natural products, the encoded metabolite kolossin A was found to be largely devoid of antibiotic activity and is likely involved in interspecies communication. A stereoisomer of this peculiar natural product displayed high activity against Trypanosoma brucei rhodesiense, a recalcitrant parasite that causes the deadly disease African sleeping sickness., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Exchange of the native promoter to the arabinose-inducible promoter PBAD was established in entomopathogenic bacteria to silence and/or activate gene clusters involved in natural product biosynthesis. This allowed the "on-demand" production of GameXPeptides, xenoamicins, and the blue pigment indigoidine. The gene clusters for the novel "mevalagmapeptides" and the highly toxic xenorhabdins were identified by this approach., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Discovery of new natural products by heterologous expression reaches its limits, especially when specific building blocks are missing in the heterologous host or the production medium. Here, we describe the insect-specific production of the new GameXPeptides E-H (5-8) from Photorhabdus luminescens TTO1, which can be produced heterologously from expression of the GameXPeptide synthetase GxpS only upon supplementation of the production media with the missing building blocks, and thus must be regarded as the true natural products under natural conditions., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Unlabelled: Myxococcus xanthus produces several extracellular signals that guide fruiting body morphogenesis and spore differentiation. Mutants defective in producing a signal may be rescued by codevelopment with wild-type cells or cell fractions containing the signal. In this paper, we identify two molecules that rescue development of the E signal-deficient mutant LS1191 at physiological concentrations, iso15:0 branched-chain fatty acid (FA) and 1-iso15:0-alkyl-2,3-di-iso15:0-acyl glycerol (TG1), a development-specific monoalkyl-diacylglycerol. The physiological concentrations of the bioactive lipids were determined by mass spectrometry from developing wild-type cells using chemically synthesized standards. Synthetic TG1 restored fruiting body morphogenesis and sporulation and activated the expression of the developmentally regulated gene with locus tag MXAN_2146 at physiological concentrations, unlike its nearly identical tri-iso15:0 triacylglycerol (TAG) counterpart, which has an ester linkage instead of an ether linkage. iso15:0 FA restored development at physiological concentrations, unlike palmitic acid, a straight-chain fatty acid. The addition of either lipid stimulates cell shortening, with an 87% decline in membrane surface area, concomitantly with the production of lipid bodies at each cell pole and in the center of the cell. We suggest that cells produce triacylglycerol from membrane phospholipids. Bioactive lipids may be released by programmed cell death (PCD), which claims up to 80% of developing cells, since cells undergoing PCD produce lipid bodies before lysing., Importance: Like mammalian adipose tissue, many of the M. xanthus lipid body lipids are triacylglycerols (TAGs), containing ester-linked fatty acids. In both systems, ester-linked fatty acids are retrieved from TAGs with lipases and consumed by the fatty acid degradation cycle. Both mammals and M. xanthus also produce lipids containing ether-linked fatty alcohols with alkyl or vinyl linkages, such as plasmalogens. Alkyl and vinyl linkages are not hydrolyzed by lipases, and no clear role has emerged for lipids bearing them. For example, plasmalogen deficiency in mice has detrimental consequences to spermatocyte development, myelination, axonal survival, eye development, and long-term survival, though the precise reasons remain elusive. Lipids containing alkyl- and vinyl-linked fatty alcohols are development-specific products in M. xanthus. Here, we show that one of them rescues the development of E signal-producing mutants at physiological concentrations.

Myrciaria dubia, a plant native to the Amazon region, stands out as a fruit rich in vitamin C and other metabolites with nutritional potential. We evaluated the antioxidant, genotoxic and antigenotoxic potential of M. dubia juice on blood cells of mice after acute, subacute and chronic treatments. Flavonoids and vitamin C present in the fruit of M. dubia were quantified. In vitro antioxidant activity was evaluated by DPPH assay. Blood samples were collected for analysis after treatment, and the alkaline comet assay was used to analyze the genotoxic and antigenotoxic activity (ex vivo analysis using H(2)O(2)). The amount of vitamin C per 100mL of M. dubia was 52.5mg. DPPH assay showed an antioxidant potential of the fruit. No M. dubia concentration tested exerted any genotoxic effect on mice blood cells. In the ex vivo test, the juice demonstrated antigenotoxic effect, and acute treatment produced the most significant results. After the treatments, there was no evidence of toxicity or death. In conclusion, our data show that M. dubia juice has antigenotoxic and antioxidant activities, though with no genotoxicity for blood cells. Nevertheless, more in-depth studies should be conducted to assess the safety of this fruit for human consumption., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Structure elucidation of natural products including the absolute configuration is a complex task that involves different analytical methods like mass spectrometry, NMR spectroscopy, and chemical derivation, which are usually performed after the isolation of the compound of interest. Here, a combination of stable isotope labeling of Photorhabdus and Xenorhabdus strains and their transaminase mutants followed by detailed MS analysis enabled the structure elucidation of novel cyclopeptides named GameXPeptides including their absolute configuration in crude extracts without their actual isolation., (Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Myxobacteria are soil-dwelling bacteria notable for several unique behavioral features, such as cellular movement by gliding and the formation of multicellular fruiting bodies. More recently they have gained recognition as producers of several unique polyketide and nonribosomal polypeptide metabolites with potential therapeutic value. The biosynthesis of these compounds often involves highly unusual mechanisms including the formation of the chloro-hydroxy-styryl moiety of the chondrochloren antibiotic produced by Chondromyces crocatus Cm c5. Here it is shown that the final product of the chondrochloren megasynthetase is the novel natural product pre-chondrochloren, a carboxylated and saturated derivative of chondrochloren. This compound was isolated from strains harboring mutants of a hypothetical oxidative decarboxylase (CndG) identified in the chondrochloren gene cluster. CndG was heterologously expressed in Escherichia coli and shown to be an FAD-dependent oxidative decarboxylase. Biochemical characterization of the protein was achieved using the intermediate described above as the substrate and yielded chondrochloren by oxidative decarboxylation. It was also demonstrated that the CndG post-assembly line modification of pre-chondrochloren is essential for the biological activity of chondrochloren.

Investigation of the DNA repair process performed by the spore photoproduct (SP) lyase repair enzyme is strongly hampered by the lack of defined substrates needed for detailed enzymatic studies. The problem is particularly severe because the repair enzyme belongs to the class of strongly oxygen-sensitive radical (S)-adenosylmethionine (SAM) enzymes, which are notoriously difficult to handle. We report the synthesis of the spore photoproduct analogues 1 a and 1 b, which have open backbones and are diastereoisomers. In order to solve the problem of stereochemical assignment, two further derivatives 2 a and 2 b with closed backbones were prepared. The key step of the synthesis of 2 a/b is a metathesis-based macrocyclization that strongly increases the conformational rigidity of the synthetic spore photoproduct derivatives. NOESY experiments of the cyclic isomers furnished a clear cross-peak pattern that allowed the unequivocal assignment of the stereochemistry. The results were transferred to the data for isomers 1 a and 1 b, which were subsequently used for enzymatic-repair studies. These studies were performed with the novel spore photoproduct lyase repair enzyme from Geobacillus stearothermophilus. The studies showed an accordance with a recent investigation performed by us with the spore photoproduct lyase from Bacillus subtilis, in that only the S isomer 1 a is recognized and repaired. The ability to prepare a defined functioning substrate now paves the way for detailed enzymatic studies of the SP-lyase lesion recognition and repair process.