Pectic Galactan Polysaccharide-Based Gene Delivery System for Targeting Neuroinflammation

Treating neuroinflammation-related injuries and disorders through manipulation of neuroinflammation functions is being heralded as a new therapeutic strategy. In this study, a novel pectic galactan (PG) polysaccharide based gene therapy approach is developed for targeting reactive gliosis in neuroinflammation. Galectin-3 (Gal-3) is a cell protein with a high affinity to β-galactoside sugars and is highly expressed in reactive gliosis. Since PG carries galactans, it can target reactive gliosis via specific carbohydrate interaction between galactan and Gal-3 on the cell membrane, and therefore can be utilized as a carrier for delivering genes to these cells. The carrier is synthesized by modifying quaternary ammonium groups on the PG. The resulting quaternized PG (QPG) is found to form complexes with plasmid DNA with a mean diameter of 100 nm and have the characteristics required for targeted gene therapy. The complexes efficiently condense large amounts of plasmid per particle and successfully bind to Gal-3. The in vivo study shows that the complexes are biocompatible and safe for administration and can selectively transfect reactive glial cells of an induced cortical lesion. The results confirm that this PG-based delivery system is a promising platform for targeting Gal-3 overexpressing neuroinflammation cells for treating neuroinflammation-related injuries and neurodegenerative diseases.     

A simple model for the semicontinuous heterophase polymerization: Ethyl methacrylate as a case example

A simple but comprehensive model considering homogeneous and micellar nucleation, coagulation, entry of radicals to particles and to micelles and radicals' exit from particles, is presented. The model is validated, in a starved semicontinuous heterophase polymerization of ethyl methacrylate, at three monomer addition rates. The model accurately describes the overall and instantaneous conversion, the average particle density and diameter, and the number and weight average molar masses evolutions over time. It is found that even though the average number of radicals is much smaller than 0.5, the system is not 0-1. An empirical function was used to describe the gel effect. The homogeneous nucleation was the prevailing mechanism for particle formation and large exit rates of radicals were observed. POLYM. ENG. SCI., 60: 223–232, 2019. © 2019 Society of Plastics Engineers     

市场观察:向H.264过渡将推动视频IC快速增长

数字视频编码和解码芯片目前需求量很大.在未来几年里,这种芯片的市场将更加强劲地增长.推动这个市场增长的因素有三个:一个是全球范围的从模拟电视向数字电视的过渡,这种过渡将刺激数字接收机和基础设施设备的需求;另一个因素是手机、便携式播放机和汽车内的移动视频功能日益流行;第三个因素是数字视频标准的持续发展将推动对提供高性能芯片的新需求.     

Acrylonitrile-based copolymers: Synthesis,characterization, and formation of ultrafiltration membranes utilized for the immobilization of proteins

Various high molecular weight copolymers of acrylonitrile and a vinyl comonomer containing an aryl amine, a pyridine, or an aliphatic hydroxyl group were synthesized via slurry polymerization techniques so as to contain from 1 to 15 mol % functional comonomer. The comonomer content was quantitated by ultraviolet absorbance, base titration of acid polymer salts, and/or relative chemical reactivity with trichloro-s-triazine. Thin films were cast from copolymer solutions, coagulated into unsupported ultrafiltration membrances, and characterized with respect to both water permeability and pore size distribution. Analysis by size exclusion chromatography of the membrane permeate of a pool of dextran fractions yielded a continuous distribution curve for membrane pore size over the range 1.5 to 70 nm. The ultrafiltration membranes were used for protein immobilization after appropriate chemical activation. The three distinct types of functional copolymers gave comparable results for α-chymotrypsin, with protein weight loadings of 6–12% and 40–65% retention of enzymatic specific activity.     

Future directions for the Agency for Health Care Policy and Research

The Agency for Health Care Policy and Research (AHCPR) plays a leading role in health services research. Research efforts to develop practice guidelines, outcomes research, and computer applications have led to improvements in the delivery of care and reduced health care costs. These efforts aid consumers, providers, purchasers, and policy makers in health care decision making. This article cites numerous examples of AHCPR's efforts to increase quality of care and reduce costs.     

1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine as a substrate of cytochrome P450 2D6: allosteric effects of NADPH-cytochrome P450 reductase

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a neurotoxin that produces Parkinsonism symptoms in man, has been examined as a substrate of recombinant human cytochrome P450 2D6. When cumene hydroperoxide is used as an oxygen and electron donor, a single product is formed, identified as 4-phenyl-1,2,3,6-tetrahydropyridine. The K(m) for formation of this product (130 microM) is in agreement with the dissociation constants for MPTP binding to the enzyme determined by optical and nuclear magnetic resonance (NMR) spectroscopy. When the reaction is carried out with nicotinamide adenine dinucleotide phosphate (reduced) (NADPH) and recombinant human NADPH-cytochrome P450 reductase, a second product, identified as 1-methyl-4-(4'-hydroxyphenyl)-1,2,3,6-tetrahydropyridine, is formed in addition to 4-phenyl-1,2,3,6-tetrahydropyridine. The K(m) values for formation of these two products are 19 microM and 120 microM, respectively. Paramagnetic relaxation experiments have been used to measure distances between the protons of bound MPTP and the heme iron, and these have been used to construct models for the position and orientation of MPTP in the active site. For the cytochrome alone, a single mode of binding was observed, with the N-methyl close to the heme iron in a position appropriate for the observed N-demethylation reaction. In the presence of the reductase, the data were not consistent with a single mode of binding but could be explained by the existence of two alternative orientations of MPTP in the active site. One of these, characterized by a dissociation constant of 150 microM, is essentially identical to that observed in the absence of the reductase. In the second, which has a K(d) of 25 microM, the MPTP is oriented so that the aromatic ring is close to the heme iron, in a position appropriate for p-hydroxylation leading to the formation of the product seen only in the presence of the reductase. In the case of codeine, another substrate for cytochrome P450 2D6, the addition of reductase had no effect on the nature of the product formed, the dissociation constant, or the orientation in the binding site. These observations show that NADPH-cytochrome P450 reductase has an allosteric effect on the active site of cytochrome P450 2D6 that affects the binding of some substrates but not others.     

Purification and partial characterization of 76 kDa transglutaminase in the egg envelope (chorion) of rainbow trout, Oncorhynchus mykiss

Transglutaminase (TGase), responsible for crosslinking between proteins, is known to be localized exclusively in the egg envelope (chorion) of rainbow trout, Oncorhynchus mykiss, and probably participates in the post-fertilization chorion hardening. We purified the TGase from unfertilized egg chorions by sequential chromatography using SP-Sepharose, Q-Sepharose, and TSK-gel G3000SWXL columns. The purified enzyme was a monomeric protein having the molecular mass of 76 kDa. It promoted incorporation of monodansyl-cadaverine into chorion protein and catalyzed the polymerization of chorion subunit proteins. The effect of various reagents suggested that the chorion TGase is a Ca2+-dependent SH-enzyme similar to the well-characterized TGases of various animals. The highest activity was observed at pH 6.0. The amines examined in the present study inhibited the TGase activity of the purified enzyme. However, they did not necessarily cause effective inhibition of its activity. These properties of the chorion TGase were essentially consistent with our previous observations on polymerization of chorion proteins, resulting in chorion hardening. We compared the amino acid composition of the purified TGase with those of the previously characterized TGases of fishes, such as chum salmon and red sea bream. The results suggest that the chorion 76 kDa TGase is not homologous with those liver TGases in terms of amino acid composition.     

Fetus-in-fetu with malignant recurrence

Fetus-in-fetu is an unusual condition in which a vertebrate fetus is enclosed within the abdomen of another fetus. These occurrences are usually benign. This report describes an instance of malignant recurrence after resection of a fetus-in-fetu.