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https://www.readbyqxmd.com/read/28644885/organic-anion-transporting-polypeptide-1b3-can-form-homo-and-hetero-oligomers
#1
Yuchen Zhang, Kelli H Boxberger, Bruno Hagenbuch
OATP1B3 is a 12 transmembrane domain protein expressed at the basolateral membrane of human hepatocytes where it mediates the uptake of numerous drugs and endogenous compounds. Previous western blot results suggest the formation of OATP1B3 multimers. In order to better understand the function of OATP1B3 under normal physiological conditions, we investigated its oligomerization status. We transiently transfected OATP1B3 with a C-terminal His-, FLAG- or HA-tag in HEK293 cells and used co-immunoprecipitation and a Proximity Ligation Assay to detect interactions between the different constructs...
2017: PloS One
https://www.readbyqxmd.com/read/28644501/stabilizing-amyloid-%C3%AE-peptide-by-the-n-terminus-capture-is-capable-of-preventing-and-eliminating-amyloid-%C3%AE-oligomers
#2
Gesi Wen, Daoyuan Chen, Wenjing Qin, Binhua Zhou, Youqiao Wang, Ziyi Liu, Jun Du, Qiang Zhou, Junmin Quan, Xianzhang Bu
Elimination of amyloid-β (Aβ) oligomers remains challenging. We describe here a novel strategy to prevent and eliminate the Aβ oligomers from either the early aggregation or the fibril dissolution pathway by targeting the flexible N-terminus, but not the widely investigated hydrophobic segment, with a rationally designed cyclopeptide.
June 23, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28643168/self-aggregation-of-synthetic-zinc-methyl-20-substituted-3-hydroxymethyl-pyropheophorbides-as-models-of-bacteriochlorophyll-c
#3
Ayaka Wada, Hitoshi Tamiaki
Zinc 3-hydroxymethyl-13(1)-oxo-chlorins bearing a variety of primary alkyl groups at the 20-position were prepared as models of bacteriochlorophyll-c by chemical modification of naturally occurring chlorophyll-a. The synthetic chlorophyll-a derivatives self-aggregated in an aqueous Triton X-100 solution to afford large oligomers whose Soret and Qy bands were red-shifted and broadened, compared with the bands of their monomers in tetrahydrofuran. The oligomeric bands are similar to those of bacteriochlorophyll-c self-aggregates in chlorosomes, the main light-harvesting antennae of photosynthetic green bacteria...
June 22, 2017: Photosynthesis Research
https://www.readbyqxmd.com/read/28642346/detergent-induced-self-assembly-and-controllable-photosensitizer-activity-of-diester-phenylene-ethynylenes
#4
Patrick L Donabedian, Matthew N Creyer, Florencia A Monge, Kirk S Schanze, Eva Y Chi, David G Whitten
Photodynamic therapy, in which malignant tissue is killed by targeted light exposure following administration of a photosensitizer, can be a valuable treatment modality but currently relies on passive transport and local irradiation to avoid off-target oxidation. We present a system of excited-state control for truly local delivery of singlet oxygen. An anionic phenylene ethynylene oligomer is initially quenched by water, producing minimal fluorescence and no measurable singlet oxygen generation. When presented with a binding partner, in this case an oppositely charged surfactant, changes in solvent microenvironment result in fluorescence unquenching, restoration of intersystem crossing to the triplet state, and singlet oxygen generation, as assayed by transient absorption spectroscopy and chemical trapping...
June 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28642302/residual-erythropoiesis-protects-against-myocardial-hemosiderosis-in-transfusion-dependent-thalassemia-by-lowering-labile-plasma-iron-via-transient-generation-of-apotransferrin
#5
Maciej W Garbowski, Patricia Evans, Evangelia Vlachodimitropoulou, Robert Hider, John B Porter
Cardiosiderosis is a leading cause of mortality in transfusion-dependent thalassemias. Plasma non-transferrin-bound iron and its redox-active component, labile plasma iron, are key sources of iron loading in cardiosiderosis. Risk factors were identified in 73 patients with or without cardiosiderosis. Soluble transferrin receptor-1 levels were significantly lower in patients with cardiosiderosis (odds ratio 21). This risk increased when transfusion-iron loading rates exceeded the erythroid transferrin uptake rate (derived from soluble transferrin receptor-1) by >0...
June 22, 2017: Haematologica
https://www.readbyqxmd.com/read/28642151/the-role-of-the-lb-structural-loop-and-its-interactions-with-the-pdz-domain-of-the-human-htra3-protease
#6
Tomasz Wenta, Przemysław Glaza, Mirosław Jarząb, Urszula Zarzecka, Dorota Żurawa-Janicka, Adam Lesner, Joanna Skórko-Glonek, Barbara Lipińska
Human HtrA3 protease is a proapoptotic protein, involved in embryo implantation and oncogenesis. In stress conditions the protease is activated by removal of its N-terminal domain. The activated form, ΔN-HtrA3L is a homotrimer composed of the protease (PD) and PDZ domains. The LB structural loop of the PD is longer by six amino acid residues than its counterparts of other human HtrA proteins and interacts with the PDZ in a way not observed in other known HtrA structures. By size exclusion chromatography of the ΔN-HtrA3L mutated variants we found that removal of the additional LB loop residues caused a complete loss of the proper trimeric structure while impairing their interactions with the PDZ domain decreased the amount of the trimers...
June 19, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28642038/functional-characterization-of-21-allelic-variants-of-dihydropyrimidinase
#7
Eiji Hishinuma, Fumika Akai, Yoko Narita, Masamitsu Maekawa, Hiroaki Yamaguchi, Nariyasu Mano, Akifumi Oda, Noriyasu Hirasawa, Masahiro Hiratsuka
Dihydropyrimidinase (DHP, EC 3.5.2.2), encoded by the gene DPYS, is the second enzyme in the catabolic pathway of pyrimidine and of fluoropyrimidine drugs such as 5-fluorouracil, which are commonly used in anticancer treatment; DHP catalyzes the hydrolytic ring opening of dihydrouracil and dihydro-5-fluorouracil. DPYS mutations are known to contribute to interindividual variations in the toxicity of fluoropyrimidine drugs, but the functional characterization of DHP allelic variants remains inadequate. In this study, in vitro analysis was performed on 22 allelic variants of DHP by transiently expressing wild-type DHP and 21 DHP variants in 293FT cells and characterizing their enzymatic activities by using dihydrouracil and dihydro-5-fluorouracil as substrates...
June 19, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28641562/structural-characterization-of-amyloid-%C3%AE-17-42-dimer-by-potential-of-mean-force-analysis-insights-from-molecular-dynamics-simulations
#8
Mary Dutta, Rajkalyan Chutia, Venkata Satish Kumar Mattaparthi
Recent experiments with Amyloid β1-42 peptide have indicated that the initial dimerization of Aβ1-42 monomers to form amyloid dimers stand out as a key event in the generation of toxic oligomers. However, the structural characterization of Aβ1-42 dimer at the atomistic level and the dimerization mechanism by which Aβ1-42 peptides co-aggregate still remains not clear. In the present study, the process of Aβ17-42 peptide dimerization which is known to play an important role in the plaque formation was evaluated in terms of potential of mean force, which provided free energies along the reaction coordinates...
June 20, 2017: Protein and Peptide Letters
https://www.readbyqxmd.com/read/28641441/the-closo-si12c12-molecule-from-cluster-to-crystal-effects-of-hydrogenation-and-oligomerization-on-excited-states
#9
Xiaofeng F Duan, Larry W Burggraf
Excited state properties of chain and cyclic oligomers of closo-Si12C12 moieties are calculated using time-dependent density functional theory methods. Ultraviolet, visible, and near-infrared photo-absorption properties are described for oligomers that form by linking closo-Si12C12 monomer moieties through Si-Si bonds. Natural transition orbitals for electron and hole states of stationary-state excitons in oligomers were compared to understand how exciton states are influenced by oligomer structure. Depending on the structure, some prominent excited states have large electron-hole charge separation while others do not; some exhibit exciton delocalization while others do not...
June 21, 2017: Journal of Chemical Physics
https://www.readbyqxmd.com/read/28641440/accurate-excitation-energies-of-molecules-and-oligomers-from-a-semilocal-density-functional
#10
Guocai Tian, Yuxiang Mo, Jianmin Tao
Excitation energy plays an important role in energy conversion, biological processes, and optical devices. In this work, we apply the Tao-Mo (TM) nonempirical meta-generalized gradient approximation and the combination TMTPSS (TMx + TPSSc), with TPSSc being the correlation part of the original TPSS (Tao-Perdew-Staroverov-Scuseria) to study excitation energies of small molecules and oligomers. Our test set consists of 17 molecules with 134 total excited states, including singlet, triplet, valence, and Rydberg excited states...
June 21, 2017: Journal of Chemical Physics
https://www.readbyqxmd.com/read/28639641/incorporation-of-click-chemistry-glycomimetics-dramatically-alters-triple-helix-stability-in-an-adiponectin-model-peptide
#11
Katherine R Lutteroth, Paul W R Harris, Tom H Wright, Harveen Kaur, Kevin Sparrow, Sung-Hyun Yang, Garth J S Cooper, Margaret A Brimble
Adiponectin (Adpn) has been shown to be a possible therapeutic for Type II diabetes, however the production of a therapeutic version of Adpn has proved to be challenging. Biological studies have highlighted the importance of the glycosylated lysine residues for the formation of bioactive high molecular weight oligomers of Adpn. Through the use of 'click' glycopeptide mimetics, we investigated the role of glycosylated lysine and serine residues for the formation of triple helical structures of the collagenous domain of Adpn, in the context of a collagen model peptide scaffold...
June 22, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28637350/structural-peculiarities-of-ion-conductive-organic-inorganic-polymer-composites-based-on-aliphatic-epoxy-resin-and-salt-of-lithium-perchlorate
#12
Liubov Matkovska, Maksym Iurzhenko, Yevgen Mamunya, Igor Tkachenko, Valeriy Demchenko, Volodymyr Synyuk, Andriy Shadrin, Gisele Boiteux
The article is concerned with hybrid amorphous polymers synthesized basing on epoxy oligomer of diglycide aliphatic ester of polyethylene glycol that was cured by polyethylene polyamine and lithium perchlorate salt. Structural peculiarities of organic-inorganic polymer composites were studied by differential scanning calorimetry, wide-angle X-ray spectra, infrared spectroscopic, scanning electron microscopy, elemental analysis, and transmission and reflective optical microscopy. On the one hand, the results showed that the introduction of LiClO4 salt into epoxy polymer leads to formation of the coordinative metal-polymer complexes of donor-acceptor type between central Li(+) ion and ligand...
December 2017: Nanoscale Research Letters
https://www.readbyqxmd.com/read/28636776/facile-synthesis-and-chain-length-dependent-optical-and-structural-properties-of-diketopyrrolopyrrole-based-oligomers
#13
Satish Patil, Tushita Mukhopadhyay, Boregowda Puttaraju, Palas Roy, Jyotishman Dasgupta, Andreas Meyer
Here we report the synthesis, optical properties and solid-state packing of monodisperse oligomers of DPP up to five repeating units. Optical properties of DPP-oligomers in solution and solid state were investigated by a combination of steady-state, and transient spectroscopy. Transient absorption spectroscopy and time-correlated single photon counting (TCSPC) measurements show that the fluorescence lifetime decreases with increase in the oligomer size from monomer to trimer, thereby reaching saturation for pentameric DPP oligomer...
June 21, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28636332/new-insights-into-the-wavelength-dependence-of-maldi-mass-spectrometry
#14
Marcel Niehaus, Andreas Schnapp, Annika Koch, Jens Soltwisch, Klaus Dreisewerd
The interplay between the wavelength of the laser and the absorption profile of the matrix constitutes a crucial factor in matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS). Numerous studies have shown that typically best analytical results are obtained if the laser wavelength matches the UV absorption band of the matrix in the solid state well. However, many powerful matrices exhibit peak absorptions which differ notably from the standard MALDI laser wavelengths of 337, 349, and 355 nm, respectively...
June 21, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28635170/alginate-oligosaccharides-modify-hyphal-infiltration-of-candida-albicans-in-an-in-vitro-model-of-invasive-human-candidosis
#15
Manon F Pritchard, Alison Jack, Lydia C Powell, Hina Sadh, Philip D Rye, Katja E Hill, David W Thomas
AIMS: A novel alginate oligomer (OligoG CF-5/20) has been shown to potentiate antifungal therapy against a range of fungal pathogens. The current study assessed the effect of this oligomer on in vitro virulence factor expression and epithelial invasion by Candida species. METHODS AND RESULTS: Plate substrate assays and epithelial models were used to assess Candida albicans (CCUG 39343 and ATCC 90028) invasion, in conjunction with confocal laser-scanning microscopy and histochemistry...
June 21, 2017: Journal of Applied Microbiology
https://www.readbyqxmd.com/read/28634239/the-dual-activity-responsible-for-the-elongation-and-branching-of-%C3%AE-1-3-glucan-in-the-fungal-cell-wall
#16
Vishukumar Aimanianda, Catherine Simenel, Cecile Garnaud, Cecile Clavaud, Rui Tada, Lise Barbin, Isabelle Mouyna, Christoph Heddergott, Laura Popolo, Yoshikazu Ohya, Muriel Delepierre, Jean-Paul Latge
β-(1,3)-Glucan, the major fungal cell wall component, ramifies through β-(1,6)-glycosidic linkages, which facilitates its binding with other cell wall components contributing to proper cell wall assembly. Using Saccharomyces cerevisiae as a model, we developed a protocol to quantify β-(1,6)-branching on β-(1,3)-glucan. Permeabilized S. cerevisiae and radiolabeled substrate UDP-((14)C)glucose allowed us to determine branching kinetics. A screening aimed at identifying deletion mutants with reduced branching among them revealed only two, the bgl2Δ and gas1Δ mutants, showing 15% and 70% reductions in the branching, respectively, compared to the wild-type strain...
June 20, 2017: MBio
https://www.readbyqxmd.com/read/28633548/polyquaternium-mediated-delivery-of-morpholino-oligonucleotides-for-exon-skipping-in-vitro-and-in-mdx-mice
#17
Mingxing Wang, Bo Wu, Sapana N Shah, Peijuan Lu, Qilong Lu
Antisense oligonucleotide therapy for Duchenne muscular dystrophy has shown great potential in preclinical and clinical trials, but its therapeutic applications are still limited due to inefficient delivery. In this study, we investigated a few polyquaterniums (PQs) with different size and composition for their potential to improve delivery performance of an antisense phosphorodiamidate morpholino oligomer (PMO) both in vitro and in vivo. The results showed that Luviquat(TM) series, especially PQ-1 and PQ-3, promoted the exon-skipping efficiency comparable to Endoporter-mediated PMO delivery in vitro...
November 2017: Drug Delivery
https://www.readbyqxmd.com/read/28632947/pimozide-reduces-toxic-forms-of-tau-in-tauc3-mice-via-ampk-mediated-autophagy
#18
YoungDoo Kim, Eun Il Jeong, Jihoon Nah, Seung-Min Yoo, WonJae Lee, Youbin Kim, Seowon Moon, Se-Hoon Hong, Yong-Keun Jung
In neurodegenerative diseases like Alzheimer's disease (AD), tau is hyperphosphorylated and forms aggregates and neurofibrillary tangles in affected neurons. Autophagy is critical to clear the aggregates of disease-associated proteins and is often altered in patients and animal models of AD. Because mTOR (mechanistic target of rapamycin) negatively regulates autophagy and is hyperactive in the brains of patients with AD, mTOR is an attractive therapeutic target for AD. However, pharmacological strategies to increase autophagy by targeting mTOR inhibition cause various side effects...
June 20, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28632757/molecular-mechanism-of-drp1-assembly-studied-in-vitro-by-cryo-electron-microscopy
#19
Kaustuv Basu, Driss Lajoie, Tristan Aumentado-Armstrong, Jin Chen, Roman I Koning, Blaise Bossy, Mihnea Bostina, Attila Sik, Ella Bossy-Wetzel, Isabelle Rouiller
Mitochondria are dynamic organelles that continually adapt their morphology by fusion and fission events. An imbalance between fusion and fission has been linked to major neurodegenerative diseases, including Huntington's, Alzheimer's, and Parkinson's diseases. A member of the Dynamin superfamily, dynamin-related protein 1 (DRP1), a dynamin-related GTPase, is required for mitochondrial membrane fission. Self-assembly of DRP1 into oligomers in a GTP-dependent manner likely drives the division process. We show here that DRP1 self-assembles in two ways: i) in the presence of the non-hydrolysable GTP analog GMP-PNP into spiral-like structures of ~36 nm diameter; and ii) in the presence of GTP into rings composed of 13-18 monomers...
2017: PloS One
https://www.readbyqxmd.com/read/28630966/%C3%AE-iminobodipy-oligomers-facilely-accessible-%C3%AF-conjugated-luminescent-bodipy-arrays
#20
Mizuho Tsuchiya, Ryota Sakamoto, Masaki Shimada, Yoshinori Yamanoi, Yohei Hattori, Kunihisa Sugimoto, Eiji Nishibori, Hiroshi Nishihara
Imine-linked BODIPY oligomers show fluorescence quantum yields of up to 0.93. The azine linker may mediate π-conjugation that extends over six BODIPY units with redshifts up to 125 nm. BODIPYs are immobilized on silica gel through heterogeneous imine-bond formation, being fluorescent and robust.
June 20, 2017: Chemical Communications: Chem Comm
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