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Lunn, David J.,Seo, Sungbaek,Lee, Sang‐,Ho,Zerdan, Raghida Bou,Mattson, Kaila M.,Treat, Nicolas J.,McGrath, Alaina J.,Gutekunst, Will R.,Lawrence, Jimmy,Abdilla, Allison,Anastasaki, Athina,Knigh John WileySons, Inc. 2019 Journal of polymer science Part A, Polymer chemist Vol.57 No.6
<P><B>ABSTRACT</B></P><P>The synthesis and systematic comparison of a comprehensive library of well‐defined polymer architectures based on poly(acrylic acid) is reported. Through the development of new synthetic methodologies, linear, single branched, precision‐branched comb, and star polymers were prepared and their performance as dispersants was evaluated. The ability to accurately control chain lengths and branch points allows the subtle interplay between structure and dispersant performance to be defined and affords critical insights into the design of improved polymeric additives for coating formulations. The general industrial relevance of ionic polymers and branched macromolecular architectures supports these design rules for a wide range of other applications and materials, including as additives for personal care products and in water treatment. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. <B>2019</B>, <I>57</I>, 716–725</P>
Morin attenuates tau hyperphosphorylation by inhibiting GSK3β
Gong, E.J.,Park, H.R.,Kim, M.E.,Piao, S.,Lee, E.,Jo, D.G.,Chung, H.Y.,Ha, N.C.,Mattson, M.P.,Lee, J. Blackwell Science ; Academic Press 2011 Neurobiology of disease Vol.44 No.2
Alzheimer's disease (AD) is the major form of age-related dementia and is characterized by progressive cognitive impairment, the accumulation of extracellular amyloid β-peptide (Aβ), and intracellular hyperphosphorylated tau aggregates in affected brain regions. Tau hyperphosphorylation and accumulation in neurofibrillary tangles is strongly correlated with cognitive deficits, and is apparently a critical event in the dementia process because mutations in tau can cause a tangle-only form of dementia called frontotemporal lobe dementia. Among kinases that phosphorylate tau, glycogen synthase kinase 3β (GSK3β) is strongly implicated in AD pathogenesis. In the present study, we established an ELISA to screen for agents that inhibit GSK3β activity and found that the flavonoid morin effectively inhibited GSK3β activity and blocked GSK3β-induced tau phosphorylation in vitro. In addition, morin attenuated Aβ-induced tau phosphorylation and protected human neuroblastoma cells against Aβ cytotoxicity. Furthermore, treatment of 3xTg-AD mice with morin resulted in reductions in tau hyperphosphorylation and paired helical filament-like immunoreactivity in hippocampal neurons. Morin is a novel inhibitor of GSK3β that can reduce tau pathology in vivo and may have potential as a therapeutic agent in tauopathies.
Cheng, Y.L.,Park, J.S.,Manzanero, S.,Choi, Y.,Baik, S.H.,Okun, E.,Gelderblom, M.,Fann, D.Y.W.,Magnus, T.,Launikonis, B.S.,Mattson, M.P.,Sobey, C.G.,Jo, D.G.,Arumugam, T.V. Blackwell Science ; Academic Press 2014 Neurobiology of disease Vol.62 No.-
Recent findings suggest that Notch-1 signaling contributes to neuronal death in ischemic stroke, but the underlying mechanisms are unknown. Hypoxia inducible factor-1α (HIF-1α), a global regulator of cellular responses to hypoxia, can interact with Notch and modulate its signaling during hypoxic stress. Here we show that Notch signaling interacts with the HIF-1α pathway in the process of ischemic neuronal death. We found that a chemical inhibitor of the Notch-activating enzyme, γ-secretase, and a HIF-1α inhibitor, protect cultured cortical neurons against ischemic stress, and combined inhibition of Notch-1 and HIF-1α further decreased neuronal death. HIF-1α and Notch intracellular domain (NICD) are co-expressed in the neuronal nucleus, and co-immunoprecipitated in cultured neurons and in brain tissue from mice subjected to focal ischemic stroke. Overexpression of NICD and HIF-1α in cultured human neural cells enhanced cell death under ischemia-like conditions, and a HIF-1α inhibitor rescued the cells. RNA interference-mediated depletion of endogenous NICD and HIF-1α also decreased cell death under ischemia-like conditions. Finally, mice treated with inhibitors of γ-secretase and HIF-1α exhibited improved outcome after focal ischemic stroke, with combined treatment being superior to individual treatments. Additional findings suggest that the NICD and HIF-1α collaborate to engage pro-inflammatory and apoptotic signaling pathways in stroke.
Critical Role of Mullite-type Oxides’ Surface Chemistry on Catalytic NO Oxidation Performance
Thampy, Sampreetha,Ashburn, Nickolas,Dillon, Sean,Liu, Chengfa,Xiong, Ka,Mattson, Eric C.,Zheng, Yongping,Chabal, Yves J.,Cho, Kyeongjae,Hsu, Julia W. P. American Chemical Society 2019 The Journal of Physical Chemistry Part C Vol.123 No.9
<P>By combining low energy ion scattering spectroscopy and density functional theory calculation, we study the surface composition and surface formation energy of AMn<SUB>2</SUB>O<SUB>5</SUB> (A = Sm, Bi) mullite-type oxides synthesized by different methods and their effects on NO catalytic performance. It is well-known that hydrothermal (HT) synthesis at low temperatures produces materials with higher specific surface areas (SSAs) compared with those synthesized by coprecipitation (CP) and high-temperature calcination; however, it is less clear how synthesis methods affect surface chemistry. We find that the NO oxidation performance of SmMn<SUB>2</SUB>O<SUB>5</SUB>-HT does not match the SSA increase when compared to the lower SSA SmMn<SUB>2</SUB>O<SUB>5</SUB>-CP. Combined experimental and theoretical investigation reveals that SmMn<SUB>2</SUB>O<SUB>5</SUB>-HT includes a higher fraction of inactive Sm-terminated surfaces, which explains its lower than expected activity. However, the surface chemistry change depends strongly on the A-site element. The exposed surfaces of BiMn<SUB>2</SUB>O<SUB>5</SUB>-CP are predominantly terminated by Bi and exhibit a very low activity, while BiMn<SUB>2</SUB>O<SUB>5</SUB>-HT contains active Mn-terminated surfaces. This study shows that catalytic performance is determined predominantly by surface chemistry, which depends critically on the A-site element and synthesis method and less by physical surface area.</P> [FIG OMISSION]</BR>