Myricetin: A Naturally Occurring Regulator of Metal-Induced Amyloid-β Aggregation and Neurotoxicity

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Recent Development of Bifunctional Small Molecules to Study Metal-Amyloid-β Species in Alzheimer's Disease

Alzheimer's disease (AD) is a multifactorial neurodegenerative disease related to the deposition of aggregated amyloid-β (Aβ) peptides in the brain. It has been proposed that metal ion dyshomeostasis and miscompartmentalization contribute to AD progression, especially as metal ions (e.g., Cu(II) and Zn(II)) found in Aβ plaques of the diseased brain can bind to Aβ and be linked to aggregation and neurotoxicity. The role of metal ions in AD pathogenesis, however, is uncertain. To accelerate understanding in this area and contribute to therapeutic development, recent efforts to devise suitable chemical reagents that can target metal ions associated with Aβ have been made using rational structure-based design that combines two functions (metal chelation and Aβ interaction) in the same molecule. This paper presents bifunctional compounds developed by two different design strategies (linkage or incorporation) and discusses progress in their applications as chemical tools and/or potential therapeutics

Cyclometalated Iridium(III) Complexes with Deoxyribose Substituents

Fundamental study of enzymatic nucleoside transport suffers for lack of optical probes that can be tracked noninvasively. Nucleoside transporters are integral membrane glycoproteins that mediate the salvage of nucleosides and their passage across cell membranes. The substrate recognition site is the deoxyribose sugar, often with little distinction among nucleobases. Reported here are nucleoside analogues in which emissive, cyclometalated iridium(III) complexes are “clicked” to C-1 of deoxyribose in place of canonical nucleobases. The resulting complexes show visible luminescence at room temperature and 77 K with microsecond-length triplet lifetimes. A representative complex is crystallographically characterized. Transport and luminescence are demonstrated in cultured human carcinoma (KB3-1) cells

Tin doped indium oxide core-TiO <inf>2</inf> shell nanowires on stainless steel mesh for flexible photoelectrochemical cells

Photoanode architecture is built on highly conductive tin doped indium oxide (ITO) nanowires (NWs) on a flexible stainless steel mesh (SSM). ITO nanowires were coated with the atomic layer deposition grown TiO 2 layer and the photoelectrochemical performance of the stainless steel mesh based photoanode were examined as a function of wire-length and shell-thickness. The photoanode consisting of 20 m-long nanowire core and 36 nm thick shell increased the photocurrent of the testing cell by 4 times, compared to a reference cell. This enhanced photochemical activity is attributed to higher light harvesting efficiency of nanowire arrays and suppressed charge recombination of core-shell structure. © 2012 American Institute of Physics

Effects of cyclic adenosine monophosphate modulators on maturation and quality of vitrified-warmed germinal vesicle stage mouse oocytes

Background It is still one of the unresolved issues if germinal vesicle stage (GV) oocytes can be successfully cryopreserved for fertility preservation and matured in vitro without damage after warming. Several studies have reported that the addition of cyclic adenosine monophosphate (cAMP) modulators to in vitro maturation (IVM) media improved the developmental potency of mature oocytes though vitrification itself provokes cAMP depletion. We evaluated whether the addition of cAMP modulators after GV oocytes retrieval before vitrification enhances maturation and developmental capability after warming of GV oocytes. Methods Retrieved GV oocytes of mice were divided into cumulus-oocyte complexes (COCs) and denuded oocytes (DOs). Then, GV oocytes were cultured with or without dibutyryl-cAMP (dbcAMP, cAMP analog) and 3-isobutyl-l-methylxanthine (phosphodiesterase inhibitor) during the pre-vitrification period for 30 min. Results One hour after warming, the ratio of oocytes that stayed in the intact GV stage was significantly higher in groups treated with cAMP modulators. After 18 h of IVM, the percentage of maturation was significantly higher in the COC group treated with dbcAMP. The expression of F-actin, which is involved in meiotic spindle migration and chromosomal translocation, is likewise increased in this group. However, there was no difference in chromosome and spindle organization integrity or developmental competence between the MII oocytes of all groups. Conclusions Increasing the intracellular cAMP level before vitrification of the GV oocytes maintained the cell cycle arrest, and this process may facilitate oocyte maturation after IVM by preventing cryodamage and synchronizing maturation between nuclear and cytoplasmic components. The role of cumulus cells seems to be essential for this mechanism.This work was supported by the grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI18C1999 and HI18C0081), supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (grant number: NRF-2017R1C1B2003897), and supported by the grant from the Seoul National University Bundang Hospital (SNUBH) Research Fund (grant number: 02–2014-022)

Microscopic origins of the surface exciton photoluminescence peak in ZnO nanostructures

We report photoluminescence (PL) studies of the surface exciton peak in ZnO nanostructures at ∼3.367 eV aimed at elucidation of the nature and origin of the emission and its relationship to the nanostructure morphology. PL spectra in conjunction with localized voltage application in high vacuum and different gas atmospheres show a consistent variation (and recovery), allowing an association of the PL to a bound excitonic transition at the ZnO surface, which is modified by an adsorbate. PL studies of samples treated by plasma and of samples exposed to UV light under high vacuum conditions, both well-known processes for desorption of surface adsorbed oxygen, show no consistent effects on the surface exciton peak indicating the lack of involvement of oxygen species. X-ray photoelectron spectroscopy data strongly suggest involvement of adsorbed OH species. X-ray diffraction, scanning, and transmission electronmicroscopy data are presented also, and the relationship of the surface exciton peak to the nanostructure morphology is discussed

Mono-anionic phosphopeptides produced by unexpected histidine alkylation exhibit high plk1 polo-box domain-binding affinities and enhanced antiproliferative effects in hela cells

Binding of polo-like kinase 1 (Plk1) polo-box domains (PBDs) to phosphothreonine (pThr)/phosphoserine (pSer)-containing sequences is critical for the proper function of Plk1. Although high-affinity synthetic pThr-containing peptides provide starting points for developing PBD-directed inhibitors, to date the efficacy of such peptides in whole cell assays has been poor. This potentially reflects limited cell membrane permeability arising, in part, from the di-anionic nature of the phosphoryl group or its mimetics. In our current article we report the unanticipated on-resin N(τ)-alkylation of histidine residues already bearing a N(π)- alkyl group. This resulted in cationic imidazolium-containing pThr peptides, several of which exhibit single-digit nanomolar PBD-binding affinities in extracellular assays and improved antimitotic efficacies in intact cells. We enhanced the cellular efficacies of these peptides further by applying bio-reversible pivaloyloxymethyl (POM) phosphoryl protection. New structural insights presented in our current study, including the potential utility of intramolecular charge masking, may be useful for the further development of PBD-binding peptides and peptide mimetics.National Institutes of Health (U.S.) (Grants ES015339 and GM104047