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.     

TOF-SIMS imaging of chlorhexidine-digluconate transport in frozen hydrated biofilms of the fungus Candida albicans

The diffusion of the anti-microbial chlorhexidine digluconate (CHG) has been studied in C. albicans biofilms by time-of-flight secondary-ion mass spectrometry (TOF-SIMS). C. albicans has been shown to become resistant to common anti-microbial agents, including CHG, when growing as a biofilm. Mass transport resistance within biofilms has commonly been suggested as a resistance mechanism, but measurement of transport for most anti-microbial agents in biofilms has proven extremely difficult because of the heterogeneity of the biofilms and the difficulty in detecting these agents within an intact biofilm. In this study, TOF-SIMS has been used to study the transport of CHG and glucose in a frozen hydrated biofilm. The TOF-SIMS images reveal a progression of CHG from the top of the biofilm to its base with time. Images suggest that there are channels within the biofilm and show preferential binding of CHG to cellular components of the biofilm. Additionally, both living and dead cells can be identified in the TOF-SIMS images by the sequestration of K⁺ and the presence of cell markers. This study demonstrates that TOF-SIMS has the unique potential to simultaneously observe the presence of an antimicrobial agent, concentration of nutrients, and the viability of the cell population.     

Deconvolution methods for mitigation of transverse blurring in optical coherence tomography.

Imaging resolution in optical coherence tomography (OCT) is a key determinant for acquiring clinically useful optical biopsies of tissues. In contrast to light or confocal microscopy, the axial and transverse resolutions in OCT are independent and each can be analyzed individually. A method for mitigating transverse blurring and the apparent loss of transverse resolution in OCT by means of Gaussian beam deconvolution is presented. Such a method provides better representation of a specimen by using known physical parameters of a lens. To implement this method, deconvolution algorithms based on a focal-dependent kernel are investigated. First, the direct inverse problem is investigated using two types of regularization, truncated singular value decomposition, and Tikhonov. Second, an iterative expectation maximization algorithm, the Richardson-Lucy algorithm, with a beam-width-dependent iteration scheme is developed. A dynamically iterative Richardson-Lucy algorithm can reduce transverse blurring by providing an improvement in the transverse point-spread-function for sparse scattering samples in regions up to two times larger than the confocal region of the lens. These deblurring improvements inside and outside of the confocal region, which are validated experimentally, are possible without introducing new optical imaging hardware or acquiring multiple images of the same specimen. Implementation of this method in sparse scattering specimens, such as engineered tissues, has the potential to improve cellular detection and categorization.     

High transverse momentum Ξ baryon correlations in p+p collisions at √s=200 GeV

Angular correlations between produced high-p _TΞ^? baryons and unidentified charged and neutral particles are observed in high-tower triggered (on a large electromagnetic energy deposit) √s=200 GeV p+p collisions. This trigger favors events with higher average multiplicity than those in minimum bias. These events are likely to contain jets. The average multiplicity of a high-tower triggered event is similar to that of a minimum bias event containing a Ξ baryon, which implies that Ξ baryons are likely to be produced in jets. Ξ^? <p _T> is higher in the triggered data then in the minimum bias sample.     

PHYTOCHROME MEDIATION OF UREDOSPORE GERMINATION IN THE FUNGUS PUCCINIA GRAMINIS

Abstract—Applying criteria used for higher plants, phytochrome mediation of uredospore germination in the stem-rust fungus, Puccinia graminis f. sp. tritici (Eriks & Henn) Guyot is established. A 1 min red irradiation at 660 nm promotes uredospore germination and this potentiation of promotion is photoreversible by a 1 min far-red irradiation at 730 nm.     

A hexacyclic ent-trachylobane diterpenoid possessing an oxetane ring from Mitrephora glabra

[chemical reaction: see text]. Three new ent-trachylobane diterpenoids (1-3) were isolated and structures elucidated from Mitrephora glabra Scheff. (Annonaceae). Mitrephorone A (1) possesses a hexacyclic ring system with adjacent ketone moieties and an oxetane ring, both of which are unprecedented among trachylobanes. All compounds were evaluated for cytotoxicity against a panel of cancer cells, where 1 displayed the most potent and broadest activity, and against a battery of antimicrobial assays, where all compounds were approximately equipotent.     

Picrylamino-substituted heterocycles. VI. Pyrimidines

The condensation of various aminopyrimidines with picryl chloride and picryl fluoride has been investigated as part of our continuing effort in the field of picrylamino-substituted heterocycles. Most of the aminopyrimidines that can tautomerize reacted with picryl fluoride to form picryl derivatives of their imino forms, but they gave picrylamino derivatives when they condensed with picryl chloride.     

Baylis-Hillman mechanism: a new interpretation in aprotic solvents

Using reaction rate data collected in aprotic solvents, we have determined that the Baylis-Hillman rate-determining step is second order in aldehyde and first order in DABCO and acrylate. On the basis of these data, we have proposed a new mechanism involving a hemiacetal intermediate. The proposed mechanism was then supported using two different kinetic isotope experiments.