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.     

Biological evaluation of two anomeric glucose analogues iodinated in position 6

Two anomeric analogues of glucose labelled with 123 iodine in position 6, proposed as tracers of glucose transport in vivo, have been synthesized: alpha- and beta-methyl-6-deoxy-6-iodo-D-glucopyranoside (alpha MDIG and beta MDIG). The aim of this study was to determine whether these molecules interact with the glucose transporter and whether they could be used as tracers of glucose transport in vivo. The biodistribution of alpha MDIG and beta MDIG was studied in the mouse in vivo. To determine if these two anomers enter the cell via the glucose transporter, their uptake was measured in isolated perfused rat hearts, in human erythrocytes in suspension, and in cardiomyocytes of neonatal rat in culture. Both alpha MDIG and beta MDIG had similar repartitions in the mouse: myocardial uptake averaged 7% of the injected dose/g of organ at 2 min postinjection and alpha MDIG competed with D-glucose to enter the cells. Insulin produced a 123% increase of its uptake in isolated perfused rat hearts and a 100% increase in cardiomyocytes of neonatal rat in culture. alpha MDIG uptake was lowered in the presence of glucose transport inhibitors in each experimental model. An interaction between beta MDIG and glucose transporters was observed only in human erythrocytes in suspension. Only alpha MDIG interacts with the glucose transporter, and thus could be used to estimate glucose transport in vivo.     

Non-pinched, minimum energy distillation designs

Non-pinched, minimum energy solutions are important class of distillation designs that offer the potential advantage of a better trade-off between capital investment and operating costs. In this paper, two important tasks associated with non-pinched distillation designs are studied. Thus the novel contributions of this work to the literature are

(1) A comprehensive methodology for finding non-pinched minimum energy designs.

(2) Understanding of the reasons for the existence of non-pinched distillation designs.

It is shown that the recent shortest stripping line distance approach of Lucia et al. [Lucia, A., Amale, A. and Taylor, R., 2007, Distillation pinch points and more. Comput Chem Eng, available on-line] is capable of systematically and reliably finding non-pinched, minimum energy distillation designs. In addition, we provide an understanding of the reasons behind the existence of non-pinched designs, which include trajectories that follow unstable branches of a pinch point curve in azeotropic systems, the inherent looping structure of trajectories in hydrocarbon separations, and the presence of ancillary constraints in multi-unit processes like extraction/distillation. Several distillation examples are studied and many numerical results and geometric illustrations are presented that show the shortest stripping line distance methodology is indeed a powerful and systematic tool for computing non-pinched, minimum energy designs and that support the underlying reason we provide for the existence of non-pinched designs.     

A Neural Network Model of Caenorhabditis Elegans: The Circuit of Touch Sensitivity

The paper presents a neural network model of the touch sensitivity circuit of the nematode Caenorhabditis elegans. We describe a serie of simulations in which neural networks are trained, using a genetic algorithm, to reproduce the habituation of the nematode's touch sensitive behavior. A lesion study of the network allows to make a direct comparison between the fine functioning of the model and the data collected in real organisms. The model accords well with the known neurobiological data and it suggests some hypotheses about the functioning of the neural circuit and of single neurons.