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.     

Dietary Alcohol and Fat Differentially Affect Plasma Cholesteryl Ester Transfer Activity and Triglycerides in Normo- and Hypertriglyceridemic Subjects

Moderate alcohol consumption is associated with increased plasma high-density lipoprotein (HDL)-cholesterol concentrations and reduced risk for cardiovascular disease. Plasma cholesteryl ester transfer activity (CETA) mediates the exchange of HDL-cholesteryl ester (CE) for the triacylglycerol (TAG) of very-low-density lipoproteins. We compared the effects of oral challenges of Alcohol, saturated fat (SAT), and (Alcohol + SAT) on plasma CETA, cholesterol, nonesterified fatty acids (NEFA), and TAG among normo-triglyceridemic (NTG) and mildly hypertriglyceridemic (HTG) volunteers having a range of plasma TAG concentrations. The major changes were (1) CETA increased more after ingestion of SAT and (Alcohol + SAT) in the HTG group versus the NTG group; (2) after all three challenges, elevation of plasma TAG concentration persisted longer in the HTG versus NTG group. Plasma cholesterol was not affected by the three dietary challenges, while Alcohol increased NEFA more in the HTG group than the NTG group. Plasma TAG best predicted plasma CETA, suggesting that intestinally derived lipoproteins are acceptors of HDL-CE. Unexpectedly, ingestion of (Alcohol + SAT) reduced the strength of the correlation between plasma TAG and CETA, that is the effects of (SAT and Alcohol) on plasma CETA are not synergistic nor additive but rather mutually suppressive. The alcohol-mediated inhibition of CE-transfer to chylomicrons maintains a higher plasma HDL-cholesterol concentration, which is athero-protective, although the suppressive metabolite underlying this correlation could be acetate, the terminal alcohol metabolite, other factors, including CETA inhibitors, are also likely important.     

Elevated temperature impact on performance of Low Temperature Co-fired Ceramic dielectrics

The need for electronics to operate at temperatures of 200°C and above continues to grow. These applications include avionics, aerospace, automotive, downhole drilling, mining, and many others. To satisfy this demand, a significant amount of research and development has been conducted. Despite the efforts, the number of new electronic components designed specifically for high-temperature operation is still relatively limited. In Low Temperature Co-fired Ceramic (LTCC) packages, LTCC materials are generally used as the host media for a number of pre-fabricated semiconductor components. As a result, reliability of the entire LTCC package largely depends on the performance of the least robust component. Ferro A6M-E and Ferro L8 are the two well-established and recognized LTCC dielectrics widely used for mid and high frequency LTCC applications, including several high reliability aerospace and defense applications that require demanding Mil-Spec qualifications. This study is our first attempt to characterize and understand basic high-temperature dielectric properties of these two commercial LTCC materials. The secondary objective is to initiate a dialogue in attempt to establish reliability requirements for LTCC packages dedicated for high-temperature operation.     

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.     

Current and future water issues in the Oldman River Basin of Alberta, Canada.

Long-term trends in alpine and prairie snow pack accumulation and melt are affecting streamflow within the Oldman River Basin in southern Alberta, Canada. Unchecked rural and urban development also has contributed to changes in water quality, including enhanced microbial populations and increased waterborne pathogen occurrence. In this study we look at changing environment within the Oldman River Basin and its impact on water quality and quantity. The cumulative effects include a decline in net water supplies, and declining quality resulting in increased risk of disease. Our data indicates that decreases in the rate of flow of water can result in sedimentation of bacterial contaminants within the water column. Water for ecosystems, urban consumption, recreation and distribution through irrigation is often drawn from waterholding facilities such as dams and weirs, and concern must be expressed over the potential for contaminate build-up and disproportionate potential of these structures to pose a risk to human and animal health. With disruption of natural flow rates for water resulting from environmental change such as global warming and/or human intervention, increased attention needs to be paid to use of best management practices to protect source water supplies.