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Chemical and mechanistic analysis of photodynamic inhibition of Alzheimer's β-amyloid aggregation
Ahn, Minkoo,Lee, Byung Il,Chia, Sean,Habchi, Johnny,Kumita, Janet R.,Vendruscolo, Michele,Dobson, Christopher M.,Park, Chan Beum The Royal Society of Chemistry 2019 Chemical communications Vol.55 No.8
<P>The self-assembly of the beta-amyloid peptide (Aβ) into amyloid aggregates is a central phenomenon associated with Alzheimer's disease. Here, we report chemical modifications of key amino acid residues of Aβ42 (Y10, H13, H14, and M35) by photoexcited thioflavin-T (ThT), a fluorescent probe of amyloid structure. The quantitative chemical kinetics analysis shows that the oxidized monomer species does not self-assemble, nor perturb the aggregation kinetics of non-oxidized Aβ42.</P>
Koo, Bon-Chul,McKee, Christopher F.,Suh, Kyung-Won,Moon, Dae-Sik,Onaka, Takashi,Burton, Michael G.,Hiramatsu, Masaaki,Bessell, Michael S.,Gaensler, B. M.,Kim, Hyun-Jeong,Lee, Jae-Joon,Jeong, Woong-Seo IOP Publishing 2011 The Astrophysical journal Vol.732 No.1
<P>We report new mid-infrared (MIR) observations of the remarkable object IRAS 15099-5856 using the space telescopes AKARI and Spitzer, which demonstrate the presence of prominent crystalline silicate emission in this bright source. IRAS 15099-5856 has a complex morphology with a bright central compact source (IRS1) surrounded by knots, spurs, and several extended (similar to 4') arc-like filaments. The source is seen only at >= 10 mu m. The Spitzer mid-infrared spectrum of IRS1 shows prominent emission features from Mg-rich crystalline silicates, strong [Ne II] 12.81 mu m, and several other faint ionic lines. We model the MIR spectrum as thermal emission from dust and compare with the Herbig Be star HD 100546 and the luminous blue variable R71, which show very similar MIR spectra. Molecular line observations reveal two molecular clouds around the source, but no associated dense molecular cores. We suggest that IRS1 is heated by UV radiation from the adjacent O star Muzzio 10 and that its crystalline silicates most likely originated in a mass outflow from the progenitor of the supernova remnant (SNR) MSH 15-52. IRS1, which is embedded in the SNR, could have been shielded from the SN blast wave if the progenitor was in a close binary system with Muzzio 10. If MSH 15-52 is a remnant of Type Ib/c supernova (SN Ib/c), as has been previously proposed, this would confirm the binary model for SN Ib/c. IRS1 and the associated structures may be the relics of massive star death, as shaped by the supernova explosion, the pulsar wind, and the intense ionizing radiation of the embedded O star.</P>
Deering-Rice, Cassandra E,Johansen, Mark E,Roberts, Jessica K,Thomas, Karen C,Romero, Erin G,Lee, Jeewoo,Yost, Garold S,Veranth, John M,Reilly, Christopher A American Society for Pharmacology and Experimental 2012 Molecular pharmacology Vol.81 No.3
<P>Environmental particulate matter (PM) pollutants adversely affect human health, but the molecular basis is poorly understood. The ion channel transient receptor potential vanilloid-1 (TRPV1) has been implicated as a sensor for environmental PM and a mediator of adverse events in the respiratory tract. The objectives of this study were to determine whether TRPV1 can distinguish chemically and physically unique PM that represents important sources of air pollution; to elucidate the molecular basis of TRPV1 activation by PM; and to ascertain the contributions of TRPV1 to human lung cell and mouse lung tissue responses exposed to an insoluble PM agonist, coal fly ash (CFA1). The major findings of this study are that TRPV1 is activated by some, but not all of the prototype PM materials evaluated, with rank-ordered responses of CFA1 > diesel exhaust PM > crystalline silica; TRP melastatin-8 is also robustly activated by CFA1, whereas other TRP channels expressed by airway sensory neurons and lung epithelial cells that may also be activated by CFA1, including TRPs ankyrin 1 (A1), canonical 4α (C4α), M2, V2, V3, and V4, were either slightly (TRPA1) or not activated by CFA1; activation of TRPV1 by CFA1 occurs via cell surface interactions between the solid components of CFA1 and specific amino acid residues of TRPV1 that are localized in the putative pore-loop region; and activation of TRPV1 by CFA1 is not exclusive in mouse lungs but represents a pathway by which CFA1 affects the expression of selected genes in lung epithelial cells and airway tissue.</P>
Production of tunable nanomaterials using hierarchically assembled bacteriophages
Lee, Ju Hun,Warner, Christopher M,Jin, Hyo-Eon,Barnes, Eftihia,Poda, Aimee R,Perkins, Edward J,Lee, Seung-Wuk Nature Publishing Group 2017 NATURE PROTOCOLS -ELECTRONIC EDITION- Vol.12 No.9
<P>Large-scale fabrication of precisely defined nanostructures with tunable functions is critical to the exploitation of nanoscience and nanotechnology for production of electronic devices, energy generators, biosensors, and bionanomedicines. Although self-assembly processes have been developed to exploit biological molecules for functional materials, the resulting nanostructures and functions are still very limited, and scalable synthesis is far from being realized. Recently, we have established a bacteriophage-based biomimetic process, called 'self-templating assembly'. We used bacteriophage as a nanofiber model system to exploit its liquid crystalline structure for the creation of diverse hierarchically organized structures. We have also demonstrated that genetic modification of functional peptides of bacteriophage results in structures that can be used as soft and hard tissue-regenerating materials, biosensors, and energy-generating materials. Here, we describe a comprehensive protocol to perform genetic engineering of phage, liter-scale amplification, purification, and self-templating assembly, and suggest approaches for characterizing hierarchical phage nanostructures using optical microscopy, atomic-force microscopy (AFM), and scanning electron microscopy (SESEM). We also discuss sources of contamination, common mistakes during the fabrication process, and quality-control measures to ensure reproducible material production. The protocol takes similar to 8-10 d to complete.</P>
Lee, Sunho,Kim, Changhoon,Ann, Jihyae,Thorat, Shivaji A.,Kim, Eunhye,Park, Jongmi,Choi, Sun,Blumberg, Peter M.,Frank-Foltyn, Robert,Bahrenberg, Gregor,Stockhausen, Hannelore,Christoph, Thomas,Lee, Jee Pergamon Press 2017 Bioorganic & medicinal chemistry letters Vol.27 No.18
<P><B>Abstract</B></P> <P>A series of 1-substituted 3-(<I>t</I>-butyl/trifluoromethyl)pyrazole C-region analogues of 2-(3-fluoro-4-methylsulfonamidophenyl)propanamides were investigated for <I>h</I>TRPV1 antagonism. The structure activity relationship indicated that the 3-chlorophenyl group at the 1-position of pyrazole was the optimized hydrophobic group for antagonistic potency and the activity was stereospecific to the <I>S</I>-configuration, providing exceptionally potent antagonists <B>13<I>S</I> </B> and <B>16<I>S</I> </B> with <I>K<SUB>i(CAP)</SUB> </I> =0.1nM. Particularly significant, <B>13<I>S</I> </B> exhibited antagonism selective for capsaicin and NADA and not for low pH or elevated temperature. Both compounds also proved to be very potent antagonists for <I>r</I>TRPV1, blocking <I>in vivo</I> the hypothermic action of capsaicin, consistent with their <I>in vitro</I> mechanism. The docking study of compounds <B>13<I>S</I> </B> and <B>16<I>S</I> </B> in our <I>h</I>TRPV1 homology model indicated that the binding modes differed somewhat, with that of <B>13<I>S</I> </B> more closely resembling that of <B>GRT12360</B>.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>
Lee, Hye-Soon,Lee, Annette T.,Criswell, Lindsey A.,Seldin, Michael F.,Amos, Christopher I.,Carulli, John P.,Navarrete, Cristina,Remmers, Elaine F.,Kastner, Daniel L.,Plenge, Robert M.,Li, Wentian,Greg Springer (Biomed Central Ltd.) 2008 Molecular Medicine Vol.14 No.5
<P>Recent evidence suggests that additional risk loci for RA are present in the major histocompatibility complex (MHC), independent of the class II HLA-DRB1 locus. We have now tested a total of 1,769 SNPs across 7.5Mb of the MHC located from 6p22.2 (26.03 Mb) to 6p21.32 (33.59 Mb) derived from the Illumina 550K Beadchip (Illumina, San Diego, CA, USA). For an initial analysis in the whole dataset (869 RA CCP + cases, 1,193 controls), the strongest association signal was observed in markers near the HLA-DRB1 locus, with additional evidence for association extending out into the Class I HLA region. To avoid confounding that may arise due to linkage disequilibrium with DRB1 alleles, we analyzed a subset of the data by matching cases and controls by DRB1 genotype (both alleles matched 1:1), yielding a set of 372 cases with 372 controls. This analysis revealed the presence of at least two regions of association with RA in the Class I region, independent of DRB1 genotype. SNP alleles found on the conserved A1-B8-DR3 (8.1) haplotype show the strongest evidence of positive association (P ~ 0.00005) clustered in the region around the HLA-C locus. In addition, we identified risk alleles that are not present on the 8.1 haplotype, with maximal association signals (P ~ 0.001-0.0027) located near the ZNF311 locus. This latter association is enriched in DRB1*0404 individuals. Finally, several additional association signals were found in the extreme centromeric portion of the MHC, in regions containing the DOB1, TAP2, DPB1, and COL11A2 genes. These data emphasize that further analysis of the MHC is likely to reveal genetic risk factors for rheumatoid arthritis that are independent of the DRB1 shared epitope alleles.</P>