65 research outputs found
Vergleichende Analyse von thermisch modifizierter und nativer Fichte bei Beanspruchung quer zur Faserrichtung
Diversity in Functional Organization of Class I and Class II Biotin Protein Ligase
The cell envelope of Mycobacterium tuberculosis
(M.tuberculosis) is composed of a variety of lipids
including mycolic acids, sulpholipids, lipoarabinomannans, etc., which impart
rigidity crucial for its survival and pathogenesis. Acyl CoA carboxylase (ACC)
provides malonyl-CoA and methylmalonyl-CoA, committed precursors for fatty acid
and essential for mycolic acid synthesis respectively. Biotin Protein Ligase
(BPL/BirA) activates apo-biotin carboxyl carrier protein (BCCP) by biotinylating
it to an active holo-BCCP. A minimal peptide (Schatz), an efficient substrate
for Escherichia coli BirA, failed to serve as substrate for
M. tuberculosis Biotin Protein Ligase
(MtBPL). MtBPL specifically biotinylates
homologous BCCP domain, MtBCCP87, but not
EcBCCP87. This is a unique feature of
MtBPL as EcBirA lacks such a stringent
substrate specificity. This feature is also reflected in the lack of
self/promiscuous biotinylation by MtBPL. The N-terminus/HTH
domain of EcBirA has the self-biotinable lysine residue that is
inhibited in the presence of Schatz peptide, a peptide designed to act as a
universal acceptor for EcBirA. This suggests that when biotin
is limiting, EcBirA preferentially catalyzes, biotinylation of
BCCP over self-biotinylation. R118G mutant of EcBirA showed
enhanced self and promiscuous biotinylation but its homologue, R69A
MtBPL did not exhibit these properties. The catalytic
domain of MtBPL was characterized further by limited
proteolysis. Holo-MtBPL is protected from proteolysis by
biotinyl-5′ AMP, an intermediate of MtBPL catalyzed
reaction. In contrast, apo-MtBPL is completely digested by
trypsin within 20 min of co-incubation. Substrate selectivity and inability to
promote self biotinylation are exquisite features of MtBPL and
are a consequence of the unique molecular mechanism of an enzyme adapted for the
high turnover of fatty acid biosynthesis
Quantitative Detection and Biological Propagation of Scrapie Seeding Activity In Vitro Facilitate Use of Prions as Model Pathogens for Disinfection
Prions are pathogens with an unusually high tolerance to inactivation and constitute a complex challenge to the re-processing of surgical instruments. On the other hand, however, they provide an informative paradigm which has been exploited successfully for the development of novel broad-range disinfectants simultaneously active also against bacteria, viruses and fungi. Here we report on the development of a methodological platform that further facilitates the use of scrapie prions as model pathogens for disinfection. We used specifically adapted serial protein misfolding cyclic amplification (PMCA) for the quantitative detection, on steel wires providing model carriers for decontamination, of 263K scrapie seeding activity converting normal protease-sensitive into abnormal protease-resistant prion protein. Reference steel wires carrying defined amounts of scrapie infectivity were used for assay calibration, while scrapie-contaminated test steel wires were subjected to fifteen different procedures for disinfection that yielded scrapie titre reductions of ≤101- to ≥105.5-fold. As confirmed by titration in hamsters the residual scrapie infectivity on test wires could be reliably deduced for all examined disinfection procedures, from our quantitative seeding activity assay. Furthermore, we found that scrapie seeding activity present in 263K hamster brain homogenate or multiplied by PMCA of scrapie-contaminated steel wires both triggered accumulation of protease-resistant prion protein and was further propagated in a novel cell assay for 263K scrapie prions, i.e., cerebral glial cell cultures from hamsters. The findings from our PMCA- and glial cell culture assays revealed scrapie seeding activity as a biochemically and biologically replicative principle in vitro, with the former being quantitatively linked to prion infectivity detected on steel wires in vivo. When combined, our in vitro assays provide an alternative to titrations of biological scrapie infectivity in animals that substantially facilitates the use of prions as potentially highly indicative test agents in the search for novel broad-range disinfectants
Genome-wide association study identifies susceptibility loci for acute myeloid leukemia
Acute myeloid leukemia (AML) is a hematological malignancy with an undefined heritable risk. Here we perform a meta-analysis of three genome-wide association studies, with replication in a fourth study, incorporating a total of 4018 AML cases and 10488 controls. We identify a genome-wide significant risk locus for AML at 11q13.2 (rs4930561; P = 2.15 × 10^{-8}; KMT5B). We also identify a genome-wide significant risk locus for the cytogenetically normal AML sub-group (N = 1287) at 6p21.32 (rs3916765; P = 1.51 × 10^{−10}; HLA). Our results inform on AML etiology and identify putative functional genes operating in histone methylation (KMT5B) and immune function (HLA)
Mehr als nur Dämmung. Zusatznutzen von Dämmstoffen aus nachwachsenden Rohstoffen. Einsatz biopolymerbasierter Flammschutzmittel
In sechs Arbeitsbereichen forschen zwölf Forschungseinrichtungen interdisziplinär, die Anwendbarkeit von NawaRo-Dämmstoffen signifikant zu erhöhen. Unter der Koordination des Fraunhofer WKI beteilgen sich Industriepartner und Fachverbände an ganzheitlichen Lösungen. Dabei stehen Themen wie Brandschutz und Glimmverhalten, Schallschutz, Wärmeschutz, Nachhaltigkeitsbewertung, Feuchteschutz sowie Emission im Fokus. Un in der Herstellung, Verarbeitung und Anwendung weitere Umweltaspekte zu berücksichtigen, wird im Teilvorhaben der Einsatz von Flammschutzmittel und Glimmhemmer auf Stärkebasis untersucht
Continuously produced paper honeycomb sandwich panels for furniture applications
status: publishe
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