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.     

Butyrate and Propionate Restore the Cytokine and House Dust Mite Compromised Barrier Function of Human Bronchial Airway Epithelial Cells

Barrier dysfunction of airway epithelium contributes to the development of allergies, airway hyper-responsiveness and immunological respiratory diseases. Short-chain fatty acids (SCFA) enhance and restore the barrier function of the intestinal epithelium. This study investigated whether acetate, propionate and butyrate enhance the integrity of bronchial epithelial cells. Differentiating human bronchial epithelial cells (16HBE) grown on transwells were exposed to butyrate, propionate and acetate while trans-epithelial electrical resistance was monitored over time. Restorative effects of SCFA were investigated by subsequent incubation of cells with IL-4, IL-13 or house dust mite extract and SCFA. SCFA effects on IL-4-induced cytokine production and the expression of zonula occludens-1 (ZO-1) and Mitogen-activated protein kinases (MAPK) signalling pathways were investigated by ELISA and Western blot assays. Propionate and butyrate enhanced the barrier function of differentiating 16HBE cells and induced complete recovery of the barrier function after exposure to the above-mentioned stimuli. Butyrate decreased IL-4-induced IL-6 production. IL-4 decreased ZO-1 protein expression and induced phosphorylation of extracellular signal-regulated protein kinases 1/2 (ERK1/2) and c-Jun N-terminal kinases (JNK) in 16HBE cells, both of which could be restored by SCFA. SCFA showed prophylactic and restorative effects on airway epithelial barrier function, which might be induced by increased ZO-1 expression.     

Human DDX17 Unwinds Rift Valley Fever Virus Non-Coding RNAs

Rift Valley fever virus (RVFV) is a mosquito-transmitted virus from the Bunyaviridae family that causes high rates of mortality and morbidity in humans and ruminant animals. Previous studies indicated that DEAD-box helicase 17 (DDX17) restricts RVFV replication by recognizing two primary non-coding RNAs in the S-segment of the genome: the intergenic region (IGR) and 5′ non-coding region (NCR). However, we lack molecular insights into the direct binding of DDX17 with RVFV non-coding RNAs and information on the unwinding of both non-coding RNAs by DDX17. Therefore, we performed an extensive biophysical analysis of the DDX17 helicase domain (DDX17_135–555) and RVFV non-coding RNAs, IGR and 5’ NCR. The homogeneity studies using analytical ultracentrifugation indicated that DDX17_135–555, IGR, and 5’ NCR are pure. Next, we performed small-angle X-ray scattering (SAXS) experiments, which suggested that DDX17 and both RNAs are homogenous as well. SAXS analysis also demonstrated that DDX17 is globular to an extent, whereas the RNAs adopt an extended conformation in solution. Subsequently, microscale thermophoresis (MST) experiments were performed to investigate the direct binding of DDX17 to the non-coding RNAs. The MST experiments demonstrated that DDX17 binds with the IGR and 5’ NCR with a dissociation constant of 5.77 ± 0.15 µM and 9.85 ± 0.11 µM, respectively. As DDX17_135–555 is an RNA helicase, we next determined if it could unwind IGR and NCR. We developed a helicase assay using MST and fluorescently-labeled oligos, which suggested DDX17_135–555 can unwind both RNAs. Overall, our study provides direct evidence of DDX17_135–555 interacting with and unwinding RVFV non-coding regions.     

Intrinsic carrier multiplication in layered Bi2O2Se avalanche photodiodes with gain bandwidth product exceeding 1 GHz

Emerging layered semiconductors present multiple advantages for optoelectronic technologies including high carrier mobilities, strong light-matter interactions, and tunable optical absorption and emission. Here, metal-semiconductor-metal avalanche photodiodes (APDs) are fabricated from Bi₂O₂Se crystals, which consist of electrostatically bound [Bi₂O₂]²⁺ and [Se]²⁻ layers. The resulting APDs possess an intrinsic carrier multiplication factor up to 400 at 7 K with a responsivity gain exceeding 3,000 A/W and bandwidth of ~ 400 kHz at a visible wavelength of 515.6 nm, ultimately resulting in a gain bandwidth product exceeding 1 GHz. Due to exceptionally low dark currents, Bi₂O₂Se APDs also yield high detectivities up to 4.6 × 10¹⁴ Jones. A systematic analysis of the photocurrent temperature and bias dependence reveals that the carrier multiplication process in Bi₂O₂Se APDs is consistent with a reverse biased Schottky diode model with a barrier height of ~ 44 meV, in contrast to the charge trapping extrinsic gain mechanism that dominates most layered semiconductor phototransistors. In this manner, layered Bi₂O₂Se APDs provide a unique platform that can be exploited in a diverse range of high-performance photodetector applications.

     

Manual patient transfers: factors that influence decisions and kinematic strategies employed by nursing aides

While extensive literature has characterised factors that influence the acceptable mass of ‘boxes’ during MMH tasks, less is known about these factors when moving ‘people’ in healthcare settings. This study examined factors that influence decisions/approaches employed during manual patient transfers. Sixteen nursing aides manually-transferred a standardised ‘patient’; patient mass was adjusted (using a weight vest) to determine a maximum acceptable patient mass for this task (mass_max). Grip strength was the only worker characteristic significantly associated with mass_max (r?=?0.48). Older worker age was associated with smaller peak trunk flexion (r?= ?0.58) and shoulder abduction (r?= ?0.59), and greater trunk axial twist (r?=?0.52). Workers emphasised that patient characteristics (e.g. physical/cognitive status) influenced their decisions when performing transfers. These findings extend previous literature by suggesting that grip strength is a useful predictor of perceived work capacity, older workers adapt protective postural strategies during patient transfers and worker-patient dynamics are crucial during this high-risk occupational task.

Practitioner Summary: This study examined manual patient transfers performed by nursing aides. Worker grip strength (but not age or size) was associated with perceptions of maximum acceptable patient mass. Kinematic changes suggested more conservative strategies used by older workers. Workers emphasised that patient characteristics substantially influenced their decisions when performing transfer tasks.     

A lakewide survey of Asian clam (Corbicula fluminea) distribution at warmwater discharges in Lake Michigan

The Asian clam Corbicula fluminea is among the most prolific aquatic invaders in the world; but in colder mid-latitude areas, like the Laurentian Great Lakes, their population expansion has likely been limited by poor overwinter survival. In these areas, Asian clams are typically found in thermal refugia like warmwater discharges from industrial facilities. We sought to identify the current extent of Asian clam populations in Lake Michigan and waters immediately adjacent to it, specifically at locations most likely to harbor overwintering populations – industrial warmwater discharges. During April–May 2017, we surveyed 17 locations around Lake Michigan. Evidence of Asian clam populations was found at four sites, though live specimens (n?=?3) were only found at the Indiana Harbor Ship Canal in East Chicago, IN. Shells or fragments of shells were found at Green Bay, WI, Waukegan, IL, and Port Sheldon, MI. Our findings indicate that although Asian clams are present in Lake Michigan, they are relatively rare, and remain isolated to a few small pockets of over-wintering habitat.