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.     

Raman microprobe investigation of the calcium phosphate phases of three commercially available plasma-flame-sprayed hydroxyapatite-coated dental implants

The purpose of the current study was to evaluate the crystallographic properties of three commercially plasma-flame-sprayed hydroxyapatite (HAp) coatings on dental implants. For this purpose a Raman microprobe (MOLE U1000) was used. No preparation of the surfaces was necessary to examine the thin ceramic surface layers. Microspectra (5 µm) and macrospectra (100 µm) have been measured and compared to the spectra of crystalline and amorphous HAp as well as to the spectra of tricalciumphosphate. All implants showed spectra that were more like that of the amorphous phase of HAp than any of the other examined reference materials. However, the implant spectra exhibited an extra band that as yet has not been identified. This band is probably indicative of some structure within the sprayed amorphous phase. Such structural effects would result either directly from quenching from the plasma state or by incorporation of titanium into the lattice during plasma treatment.     

Optimizing depth resolution in confocal Raman microscopy: a comparison of metallurgical, dry corrected, and oil immersion objectives

Spherical aberration is probably the most important factor limiting the practical performance of a confocal Raman microscope. This paper suggests some simple samples that can be readily fabricated in any laboratory to test the performance of a confocal Raman microscope under realistic operating conditions (i.e., a deeply buried interface, rather than the often-selected alternative of a bare silicon wafer or a thin film in air). The samples chosen were silicon wafers buried beneath transparent polymeric or glass overlayers, and a polymer laminate buried beneath a cover glass. These samples were used to compare the performance of three types of objectives (metallurgical, oil immersion, and dry corrected) in terms of depth resolution and signal throughput. The oil immersion objective gave the best depth resolution and intensity, followed by a dry corrected (60x, 0.9 numerical aperture) objective. The 100x metallurgical objective was the worst choice, with degradations of approximately 5x and 8x in the depth resolution and signal from a silicon wafer, comparing a bare wafer with one buried under a 150 microm cover glass. In particular, the high signal level obtained makes the immersion objective an attractive choice. Results from the buried laminate were even more impressive; a 30x improvement in spectral contrast was obtained using the oil immersion objective to analyze a thin (19 microm) coating on a PET substrate, buried beneath a 150 microm cover glass, compared with the metallurgical objective.     

Detection of multiple disease indicators by an autonomous biomolecular computer

The promise of biomolecular computers is their ability to interact with naturally occurring biomolecules, enabling in the future the development of context-dependent programmable drugs. Here we show a context-sensing mechanism of a biomolecular automaton that can simultaneously sense different types of molecules, allowing future integration of biomedical knowledge on a broad range of molecular disease symptoms in the decision of a biomolecular computer to release a drug molecule.     

Valuating privacy

In several experimental auctions, participants put a dollar value on private information before revealing it to a group. An analysis of results show that a trait's desirability in relation to the group played a key role in the amount people demanded to publicize private information. Because people can easily obtain, aggregate, and disperse personal data electronically, privacy is a central concern in the information age. This concern is clear in relation to financial data and genetic information, both of which can lead to identity abuse and discrimination. However, other relatively harmless information can also be abused, including a person's gender, salary, age, marital status, or shopping preferences. What's unclear is whether it's the fear of such abuse that actually causes people's stated hesitance to reveal their data. Our hypothesis - and the motivation for our study - is that people reveal information when they feel that they're somewhat typical or positively atypical compared to the target group. To test this hypothesis, we conducted experiments that elicit the value people place on their private data. We found, with great significance (more than 95 percent statistical confidence) that a linear relationship exists between an individual's belief about a trait and the value he or she places on it. That is, the less desirable the trait, the greater the price a person demands for releasing the information. Furthermore, we found that small deviations in a socially positive direction are associated with a lower asking price.     

Assessment of insulin resistance by a <Superscript>13</Superscript>C glucose breath test: a new tool for early diagnosis and follow-up of high-risk patients

Background/Aims

Insulin resistance (IR) plays an important role in the pathogenesis of diabetes and non-alcoholic fatty liver disease (NAFLD). Current methods for insulin resistance detection are cumbersome, or not sensitive enough for early detection and follow-up. The BreathID^® system can continuously analyse breath samples in real-time at the point-of-care. Here we determined the efficacy of the BreathID^® using the ¹³C-Glucose breath test (GBT) for evaluation of insulin resistance.

Methods

Twenty healthy volunteers were orally administered 75 mg of ¹³C-glucose 1-¹³C. An oral glucose tolerance test (OGTT) was performed immediately; followed by serum glucose and insulin level determinations using GBT. GBT and OGTT were repeated following exercise, which alters insulin resistance levels.

Results

Within-subject correlations of GBT parameters with serum glucose and serum insulin levels were high. Before and after exercise, between-subjects correlations were high between the relative insulin levels and the % dose recoveries at 90 min (PDR 90), and the cumulative PDRs at 60 min (CPDR 60). Pairwise correlations were identified between pre-exercise Homeostasis Model Assessment (HOMA) IR at 90 min and PDR 90; HOMA B (for beta cell function) 120 and CPDR 30; HOMA IR 60 and peak time post-exercise; and HOMA B 150 with PDR 150.

Conclusions

The non-invasive real-time BreathID^® GBT reliably assesses changes in liver glucose metabolism, and the degree of insulin resistance. It may serve as a non-invasive tool for early diagnosis and follow up of patients in high-risk groups.