Highly Stretchable Free-Standing Poly(acrylic acid)-<i>block</i>-poly(vinyl alcohol) Films Obtained from Cobalt-Mediated Radical Polymerization

The block copolymers of poly­(acrylic acid)-<i>b</i>-poly­(vinyl alcohol) (PAA-<i>b</i>-PVA) were obtained from the hydrolysis of poly­(methyl acrylate)-<i>b</i>-poly­(vinyl acetate) (PMA-<i>b</i>-PVAc), which was synthesized by cobalt-mediated radical polymerization (CMRP) using the cobalt­(II) porphyrin complex (Co^II(TMP)) as the mediator. The mechanical properties of the PAA-<i>b</i>-PVA free-standing films could be tuned by the pH of the aqueous solution used to cast the films. The block copolymer films showed a much higher tensile strain and fractural tensile strength than the films prepared from the blends of PAA and PVA homopolymers. FTIR and morphological characterizations suggested that the tensile properties of the films were governed by both the hydrogen bonding between PVA and PAA that led to interpolymer complexation and the phase-separated morphology. For a given type of material, the greater extent of interpolymer complexation attained at lower solution pH led to the film with better tensile properties. The difference in the length scale of phase separation was responsible for the large difference in the tensile properties between block copolymer and blend films, where the characteristic nanostructure formed in the block copolymer prescribed a considerably larger amount of interface which enhanced the tensile properties significantly

Additional files 3: Figure S3. of Increased tauopathy drives microglia-mediated clearance of beta-amyloid

Changes in tau pathology correlate closely with alterations in TNFα and IL-2. (A) Further demonstrating the shift in cytokines that occurs in T5x mice, IL-6 and TNFα exhibit a bimodal distribution, with high levels of TNF α but low levels of IL-6 in T5x mice (green) versus low TNFα and high IL-6 in WT (purple), Thy-Tau22 (blue), and 5xfAD (red) mice. (B) TNFα and IL-2 expression are very closely correlated (R2 = 0.925) especially in T5x mice (green), illustrating a strong concordance between these two pro-inflammatory cytokines. Both soluble (C) and insoluble (D) measures of cortical PHF-1 tau correlate well with cortical TNFα levels. Likewise, soluble (E) and insoluble (F) measures of PHF-1 tau also correlate closely with IL-2 expression. (PDF 920 kb

Additional files 6: Figure S6. of Increased tauopathy drives microglia-mediated clearance of beta-amyloid

The combination of Aβ and Tau pathology leads to reductions in hippocampal β3-tubulin. (A-D) To determine whether T5x mice begin to exhibit early signs of neurodegeneration, dendritic architecture was examined by β3-tubulin immunolabeling of all four genotypes. (E-G) Quantification of β3-tubulin revealed a significant reduction in T5x mice compared to WT and transgenic littermates within the pyramidal cell layer (E; p < 0.05), stratum radiatum (F; p < 0.05), and molecular layer (G; WT, Tau p < 0.05; 5x p = 0.27) of the hippocampus. Data are represented as mean ± SEM of optical density (O.D.), n ≥ 8 mice/group. * Indicates p < 0.05 for both ANOVA and Fisher’s protected least-significant difference (PLSD) post hoc tests with significance versus all other groups, whereas *over a bar indicates significance between 2 or 3 particular groups. Scale Bar = 100 μm in A-D, 30 μm in H-J, and 10 μm in K. (PDF 3896 kb

Mollugo pentaphylla L.

原著和名: [記載なし]科名: ザクロソウ科 = Molluginaceae採集地: タイ ラヨーン海岸 (タイ国 チャンタブリ ラヨン海岸)採集日: 1984/11/4採集者: 萩庭丈壽整理番号: JH050339国立科学博物館整理番号: TNS-VS-999312備考: Nijsiri同

Azetidine and Piperidine Carbamates as Efficient, Covalent Inhibitors of Monoacylglycerol Lipase

Monoacylglycerol lipase (MAGL) is the main enzyme responsible for degradation of the endocannabinoid 2-arachidonoylglycerol (2-AG) in the CNS. MAGL catalyzes the conversion of 2-AG to arachidonic acid (AA), a precursor to the proinflammatory eicosannoids such as prostaglandins. Herein we describe highly efficient MAGL inhibitors, identified through a parallel medicinal chemistry approach that highlighted the improved efficiency of azetidine and piperidine-derived carbamates. The discovery and optimization of 3-substituted azetidine carbamate irreversible inhibitors of MAGL were aided by the generation of inhibitor-bound MAGL crystal structures. Compound <b>6</b>, a highly efficient and selective MAGL inhibitor against recombinant enzyme and in a cellular context, was tested in vivo and shown to elevate central 2-AG levels at a 10 mg/kg dose