Hougaardgoode8396

Halogenated natural products (HNPs) show a wide range of interesting biological activities. A chemistry-guided screening using a software tool dedicated to identifying halogenated compounds in HPLC-MS data indicated the presence of several yet uncharacterised HNPs in an extract of the cyanobacterium Fischerella ambigua (Näg.) Gomont 108b. Three new natural products, tjipanazoles K, L, and M, were isolated from this strain together with the known tjipanazoles D and I. Taking into account the structures of all tjipanazole derivatives detected in this strain, reanalysis of the tjipanazole biosynthetic gene cluster allowed us to propose a biosynthetic pathway for the tjipanazoles. As the isolated tjipanazoles show structural similarity to arcyriaflavin A, an inhibitor of the clinically relevant multidrug-transporter ABCG2 overexpressed by different cancer cell lines, the isolated compounds were tested for ABCG2 inhibitory activity. Only tjipanazole K showed appreciable transporter inhibition, whereas the compounds lacking the pyrrolo[3,4-c] ring or featuring additional chloro substituents were found to be much less active. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.The display of complex proteins on the surface of cells is of great importance for protein engineering and other fields of biotechnology. We here describe a modular approach, where the membrane anchor protein Lpp-OmpA and a protein of interest (passenger) are expressed independently as genetically fused SpyCatcher and SpyTag units and assembled in situ by post-translational coupling. Using fluorescent proteins, we first demonstrate that this strategy allows for instalment of the construct on the surface of E. coli cells. The scope of our approach was then demonstrated by using three different functional enzymes, the stereoselective ketoreductase Gre2p, the homotetrameric glucose 1-dehydrogenase GDH and the bulky heme and diflavin containing cytochrome P450 BM3 (BM3). In all cases the SpyCatcher-SpyTag method enabled the generation of functional whole-cell biocatalysts, even for the bulky BM3 which could not be displayed by conventional fusion with Lpp-OmpA. Furthermore, by using a GDH variant carrying an internal SpyTag, the system could be used to display an enzyme with unmodified N- and C-termini. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.OBJECTIVE Sjӧgren's syndrome (SS) patients have an increased risk to develop malignant B-cell lymphoma, particularly mucosa-associated lymphoid tissue (MALT) lymphoma. Previously, we have shown that a proportion of salivary gland MALT lymphomas express somatically hypermutated IgM with strong homology to stereotypic rheumatoid factors (RFs). In a larger cohort of SS-associated MALT lymphomas, we here more firmly assess the frequency of RF reactivity and the significance of the somatic IGV mutations for RF reactivity. METHODS We have analyzed the B-cell antigen receptors (BCRs) of 16 SS-associated MALT lymphomas and produced soluble recombinant IgM of 12 of them, including of a lymphoma fitting in a novel IGHV3-30-encoded stereotypic IGHV subset. Of 4 MALT lymphoma antibodies, the somatically mutated IGHV and IGKV were reverted to germline configurations. Their RF activity and affinity were determined by ELISA and surface plasmon resonance. RESULTS Nine of the 12 IgM antibodies (75%) displayed strong mono-reactive RF activity. E7766 research buy Reversion of IGHV and IGKV mutations to germline configuration resulted in significantly lower affinities for IgG of 3 of 4 antibodies. In stereotypic IGHV3-7/IGKV3-15-encoded RFs, we identified a recurrent replacement mutation in IGKV3-15-CDR3 that is pivotal for the affinity for IgG-Fc. CONCLUSION SS-associated MALT lymphoma in majority express somatically mutated BCRs selected for mono-reactive, high-affinity binding of IgG-Fc. Our data underscore the notion that soluble IgG, most likely in immune complexes in inflamed tissues, is the principal autoantigen in the pathogenesis of a variety of B-cell lymphomas, in particular of SS-associated MALT lymphoma. This article is protected by copyright. All rights reserved.A 56-year-old woman with a previous history for a dermatomyositis/scleroderma overlap with positive PM-Scl 75/100 kDa was admitted due to a severe myopathy flare. Her disease had been characterized by Raynaud's phenomenon, extensive calcinosis cutis, mild interstitial lung disease, creatine kinase elevation and proximal muscle weakness. This article is protected by copyright. All rights reserved.Dr. Arend was born in Utica, New York on August 24, 1937 and grew up exploring, hunting, and fishing the lakes and forests of the Adirondacks in upstate New York. He received his Bachelor of Arts degree (Cum Laude and Phi Beta Kappa) from Williams College. During his career, Dr. Arend often sought out younger individuals who shared the same undergraduate education and experiences to recount the importance of that particular humanistic experience, where knowledge, curiosity, critical thinking, empathy and service were emphasized. This article is protected by copyright. All rights reserved.A proof-of-principle prototype of volumetric three-dimensional (3D) displaying system is herein demonstrated by harnessing the photo-activated phosphorescence of two long-lived phosphorescent metal-porphyrins in dimethyl sulfoxide (DMSO), a photochemically deoxygenating solvent. The first phosphorescent sensitizer, Pt(TPBP), absorbs the light-beam of 635 nm and the sensitized singlet oxygen is scavenged by DMSO. The second phosphorescent emitter, Pt(OEP), absorbs the light-beam of 532 nm and visibly phosphoresces only in the deoxygenated zone generated by the first sensitizer. The phosphorescent voxels, 3D images, and animations are well-defined by the intersections of the 635 and 532 nm light-beams that are programmable by tuning of excitation power densities, the beam shapes and kinetics. As a pivotal selection rule for the phosphorescent molecular couple used in this 3D displaying system, their absorptions and emissions must be orthogonal to each other, so that they can be excited and addressed independently. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.