Huntingtin Co-Isolates with Small Extracellular Vesicles from Blood Plasma of TgHD and KI-HD Pig Models of Huntington’s Disease and Human Blood Plasma

(1) Background: Huntington’s disease (HD) is rare incurable hereditary neurodegenerative disorder caused by CAG repeat expansion in the gene coding for the protein huntingtin (HTT). Mutated huntingtin (mHTT) undergoes fragmentation and accumulation, affecting cellular functions and leading to neuronal cell death. Porcine models of HD are used in preclinical testing of currently emerging disease modifying therapies. Such therapies are aimed at reducing mHTT expression, postpone the disease onset, slow down the progression, and point out the need of biomarkers to monitor disease development and therapy efficacy. Recently, extracellular vesicles (EVs), particularly exosomes, gained attention as possible carriers of disease biomarkers. We aimed to characterize HTT and mHTT forms/fragments in blood plasma derived EVs in transgenic (TgHD) and knock-in (KI-HD) porcine models, as well as in HD patients’ plasma. (2) Methods: Small EVs were isolated by ultracentrifugation and HTT forms were visualized by western blotting. (3) Results: The full length 360 kDa HTT co-isolated with EVs from both the pig model and HD patient plasma. In addition, a ~70 kDa mutant HTT fragment was specific for TgHD pigs. Elevated total huntingtin levels in EVs from plasma of HD groups compared to controls were observed in both pig models and HD patients, however only in TgHD were they significant (p = 0.02). (4) Conclusions: Our study represents a valuable initial step towards the characterization of EV content in the search for HD biomarkers.     

Polycyclic Aromatic Hydrocarbon Biomarkers of Internal Exposure in U.S. Army Soldiers Serving in Kuwait in 1991

Biomarkers of exposure were applied to a cohort of U.S. Army soldiers who were deployed to Kuwait and Saudi Arabia in 1991 in the aftermath of the Persian Gulf War. The U.S. Army Environmental Hygiene Agency (currently the U.S Army Center for Health Promotion and Preventive Medicine) monitored air and soil for ambient PAHs. In addition, a group of 61 soldiers kept diaries of daily activities. These soldiers provided blood and urine samples in June in Germany before deployment to Kuwait, in August after 8 weeks in Kuwait, and in October, one month after the return to Germany. DNA, prepared from white blood cells, was assayed for PAH-DNA adducts by immunoassay and bulky aromatic adducts by ³²P-postlabeling. Urinary 1-hydroxypyrene-glucuronide (1-OH-PG) was determined by synchronous fluorescence spectrometry. Contrary to expectations, environmental monitoring showed low ambient PAH levels in the areas where these soldiers were working in Kuwait. In addition, literature values for ambient PAH monitoring in Germany in 1990 suggest that the soldiers may have been exposed to higher levels of ambient PAHs in Germany than in Kuwait. Blood cell DNA adduct levels were lowest in Kuwait and increased significantly after the return to Germany. Also, urinary 1-OH-PG levels were lowest in Kuwait and highest in Germany. This study demonstrates modulations in PAH exposure biomarker levels that appear to correlate with ambient PAH exposure.     

Variability of Escherichia coli Concentrations in an Urban Watershed in Texas

In this study, daily Escherichia coli measurements at six locations in an urban watershed in Houston, were undertaken over a period of 12 weeks, and were analyzed using time series and fractal analyses. The time series analysis revealed that the E. coli data series were nonrandom in nature and were characterized by a lack of periodicity. Shorter E. coli time series data sets (on the order of 10 days or less) exhibited a fractal structure, suggesting that micro scale time series may be fractal in nature in urban environments, a finding that has significant implications for bacteriological water quality monitoring. Although stormflow E. coli concentrations were significantly higher than baseflow levels, the range of variability in E. coli concentrations both during dry and wet weather conditions was comparable, indicating the residual impacts of rain events on bayou water quality. While other studies in the literature have shown that afternoon E. coli levels were lower than morning levels, the results from this study demonstrate the complexity of this phenomenon and its dependence on flow, turbidity, total suspended solids, temperature and the location/land use of the monitoring point (upstream or downstream and rural/urban). Spatial variability was highly correlated to land use with key differences between grassland and urban uses: urbanized sites exhibited higher overall E. coli concentrations, experienced rebound in E. coli levels during and after a rain event, exhibited no correlations between total suspended solids and E. coli, and exhibited less daily variability in bacteria concentrations.     

Effect of annealing treatment of PC60BM layer on inverted perovskite solar cells

Journal of Materials Science: Materials in Electronics - The optimization of perovskite interfaces is an effective method to boost the device efficiency. In this review, we have reported an...     

Platinum(II) phenanthroimidazoles for targeting telomeric G-quadruplexes

A rationally designed progression of phenanthroimidazole platinum(II) complexes were examined for their ability to target telomere-derived intramolecular G-quadruplex DNA. Through the use of circular dichroism, fluorescence displacement assays, and molecular modeling we show that these complexes template and stabilize G-quadruplexes from sequences based on the human telomeric repeat (TTAGGG)(n). The greatest stabilization was observed for the p-chlorophenyl derivative 6((G4)DC(50) =0.31 μM). We also show that the G-quadruplex binding complexes are able to inhibit telomerase activity through a modified telomerase repeat amplification protocol (TRAP-LIG assay). Preliminary cell studies show that complex 6 is preferentially cytotoxic toward cancer over normal cell lines, indicating its potential use in cancer therapy.     

Effect of filler characteristics on radiopacity of experimental nanocomposite series*

This study evaluated the radiopacity of experimental nanocomposites and compared the values to those of human’s enamel and dentin. Three disc-shape (6 mm diameter × 1 mm thickness) specimens of each eleven nanocomposite series based on different filler particle size formulations (range of 100–1500 nm) and two shapes (spherical and irregular) were prepared in a split Teflon mold. After irradiation by a halogen light, the series were digitally radiographed (Kodak Unit imaging) along with 99.5% Aluminum step-wedge. The radiographic density in Mean Gray Values were measured, and then converted into Al (Aluminum) equivalent (mm). The data were analyzed by one-way ANOVA, Tukey’s HSD post hoc test and independent t-test (α = 0.05). The radiopacity values varied among the nanocomposite series (p < 0.05). The highest mean Al equivalent was recorded in bi-modal irregular-shape series, I-450/1000 (RZD 111) (2.74 ± 0.41) followed by monomodal irregular-shape, I-450 (RZD 103) (2.31 ± 0.43). The lowest value was expressed by monomodal spherical-shape larger size filler series, S-1000 (RZD 105) (0.12 ± 0.02). The irregular-shape series showed more radiopacities than the spherical-shape series in a range equivalent to those of enamel and dentin. The regression analysis demonstrated a decrease in the radiopacity values with increasing filler particle size of both spherical and irregular-shape monomodal series. The shape and composition of nanofillers have an effect on radiopacity of the experimental series.     

Modeling Escherichia Coli and Its Sources in an Urban Bayou with Hydrologic Simulation Program—FORTRAN

Bacterial levels in Buffalo Bayou in Houston commonly exceed contact recreation standards. Potential sources of bacteria include wastewater treatment plants, sanitary sewer overflows, septic systems, wet and dry nonpoint-source discharges via direct runoff and pipes, direct deposition, and sediment. A water-quality model in the Hydrologic Simulation Program—FORTRAN (HSPF) was calibrated and validated for hydrology, sediment, and Escherichia coli and subsequently used to evaluate the impacts of the bacterial sources in the watershed. In addition, simple estimates of bacterial loads were calculated along with source evaluations from load duration curves. Load reductions based upon the simple estimates indicated that water-quality standards were met by reducing dry-weather indicator bacterial loads by 69% and wet-weather loads by 98%. When these load reductions were implemented in the HSPF model, however, standards were not met under dry-weather conditions. Residual nonpoint-source loading was found to cause the discrepancy between simple load estimate calculations and the developed water-quality model. This paper demonstrates that runoff can play a significant role in maintaining high levels of bacteria under all flow conditions and that understanding the temporal variations in bacterial source loading is critical to ensure that load reductions will achieve water-quality standards.     

Ultra-structural characterization of enamel–resin interface using FIB-TEM technology

This study evaluated the enamel–resin interface of three adhesive resins (ARs) by a transmission electron microscope (TEM) after milling with focused ion beam (FIB). Simple Class-I cavities (0.5?mm within enamel depth, 4?mm length, and 2?mm width) were prepared on human caries-free molars. The enamel of two groups was conditioned by one-step self-etch bonding system (Scotchbond^?/Single Bond Universal [SBU], and Xeno V^®+ [XV⁺]), while the enamel of the third group was etched by phosphoric acid, and then treated by two-step self-priming etch-rinse system (Prime&Bond^® NT [PBNT]). The application of the adhesive systems was carried out according to their respective manufacturer’s instructions. The cavities were restored by a nanofill resin composite (Filtek^? Z350 XT Universal; 3?M ESPE) in one bulk-fill, and cured for 40?s at 550?mW/cm² by a halogen light (Optilux 501, Demetron/Kerr, Danbury, USA). The specimens were milled by FIB into 100?nm thickness slices, and then observed under TEM. The transmission electron micrographs showed an adequate adhesion of both two-step etch-rinse (PBNT) and one-step self-etch (SBU) to enamel surface. The deeply etched enamel prisms were impregnated by the etch-rinse PBNT adhesive. A relatively inadequate adhesion associated with some areas of bond degradation underneath the hybrid layer and within the adhesive was noted for the XV⁺ AR. Apart from the mild acidic adhesives of one-step self-etch and two-step etch-rinse investigated, the highly hydrophilic and acidic water-based one-step self-etch adhesive (XV⁺) proved to be less effective enamel bond by ultra-structural characterization technique using FIB-TEM.     

The Synthesis and in vivo Evaluation of 2′,2′‐Difluoro KRN7000

The synthesis of 2′,2′‐difluoro KRN7000 is described. In vivo evaluation demonstrates that this fluorinated glycolipid induces CD1d‐dependent TCR activation of NKT cells, with a bias towards Th2 cytokine production.