Polyglutamine-Specific Gold Nanoparticle Complex Alleviates Mutant Huntingtin-Induced Toxicity.

Huntington's disease (HD) belongs to protein misfolding disorders associated with polyglutamine (polyQ)-rich mutant huntingtin (mHtt) protein inclusions. Currently, it is indicated that the aggregation of polyQ-rich mHtt participates in neuronal toxicity and dysfunction. Here, we designed and synthesized a polyglutamine-specific gold nanoparticle (AuNP) complex, which specifically targeted mHtt and alleviated its toxicity. The polyglutamine-specific AuNPs were prepared by decorating the surface of AuNPs with an amphiphilic peptide (JLD1) consisting of both polyglutamine-binding sequences and negatively charged sequences. By applying the polyQ aggregation model system, we demonstrated that AuNPs-JLD1 dissociated the fibrillary aggregates from the polyQ peptide and reduced its ß-sheet content in a concentration-dependent manner. By further integrating polyethyleneimine (PEI) onto AuNPs-JLD1, we generated a complex (AuNPs-JLD1-PEI). We showed that this complex could penetrate cells, bind to cytosolic mHtt proteins, dissociate mHtt inclusions, reduce mHtt oligomers, and ameliorate mHtt-induced toxicity. AuNPs-JLD1-PEI was also able to be transported to the brain and improved the functional deterioration in the HD Drosophila larva model. Our results revealed the feasibility of combining AuNPs, JLD1s, and cell-penetrating polymers against mHtt protein aggregation and oligomerization, which hinted on the early therapeutic strategies against HD.

Insight into the Ionizing Surface Potential Method and Aqueous Sodium Halide Surfaces.

Complementing the microscopic picture of the surface structure of electrolyte solutions set out by previous theoretical and experimental studies, the ionizing surface potential technique offers a unique approach to quantifying the impact of aqueous inorganic ions upon the interfacial electric field of the air-aqueous interface. In this Feature Article, we review the vulnerability of theoretical and empirically derived χwater values as a normative reference for aqueous ion surface potentials. Instead, we recognize and evaluate aqueous ion surface potentials relative to well-known ionic surfactants cetyltrimethylammonium bromide (CTAB) and sodium dodecyl sulfate (SDS). Additionally, we also explore factors that impact the magnitude of the measured surface potentials using the ionizing method, particularly in the type of reference electrode and ionizing gas environment. With potential measurements of sodium halide solutions, we show that iodide has a dominant effect on the air-aqueous electric field. Compared to chloride and bromide, iodide is directly observed with a net negatively charged surface electric field at all salt concentrations measured (0.2 to 3.0 mol/kg water). Also, above the 2 M region, bromide is observed with a net negatively charged surface. Although several scenarios contribute to this effect, it is most likely due to the surface enrichment of bromide and iodide. While the results of this study are pertinent to determining the specific interfacial reactivity of aqueous halides, these anions seldom transpire as single-halide systems in the natural environment. Therefore, we also provide an outlook on future research concerning surface potential methods and more complex aqueous electrolyte systems.

Thermodynamic Signatures of the Origin of Anti-Hofmeister Selectivity for Phosphate at Aqueous Interfaces.

The selectivities and driving forces governing phosphate recognition by charged receptors at prevalent aqueous interfaces is unexplored relative to the many studies in homogeneous solutions. Here we report on electrostatic binding versus hydrogen-bond-assisted electrostatic binding of phosphate (H2PO4-) for two important receptor classes in the unique microenvironment of the air-water interface. We find that the methylated ammonium receptor (U-Ammo+) is dominated by electrostatic binding to phosphate anions and fails to be selective for phosphate binding over chloride, whereas the highly phosphate-selective guanidinium receptor (U-Guan+) provides synergistic hydrogen-bonding and electrostatic interactions. Apparent binding constants were evaluated in situ for U-Ammo+ and U-Guan+ using temperature-controlled infrared reflection-absorption spectroscopy with Langmuir-type fitting. Thermodynamic quantities showed enthalpically driven binding affinities of U-Guan+ and U-Ammo+ receptors (ΔH°b = -71 (±9) kJ/mol and ΔH°b = -155 (±13) kJ/mol, respectively). U-Guan+ revealed a nearly fourfold smaller entropic barrier to binding (ΔS°b = -132 (±34) J/mol K) than the U-Ammo+ receptor (ΔS°b = -440 (±45) J/mol K), attributed to hydration differences. The larger entropic penalty for the U-Ammo+ receptor is correlated with a molecular expansion shown in surface pressure-area isotherms, whereas the smaller entropic penalty of the U-Guan+ receptor conversely correlated with no expansion. The U-Guan+ receptor also revealed anti-Hofmeister selectivity for phosphate over chloride, while the non-hydrogen-bonding U-Ammo+ receptor followed Hofmeister selectivity. Our results indicate that hydrogen bonding is an integral chemical design element for achieving anti-Hofmeister selectivity for phosphate.

Iron(III) Speciation Observed at Aqueous and Glycerol Surfaces: Vibrational Sum Frequency and X-ray.

Aqueous solutions of FeCl3 have been widely studied to shed light on a number of processes from dissolution, mineralization, biology, electrocatalysis, corrosion, to microbial biomineralization. Yet there are little to no molecular level studies of the air-liquid FeCl3 interface. Here, both aqueous and glycerol FeCl3 solution surfaces are investigated with polarized vibrational sum frequency generation (SFG) spectroscopy. We also present the first ever extreme ultraviolet reflection-absorption (XUV-RA) spectroscopy measurements of solvated ions and complexes at a solution interface, and observe with both X-ray photoelectron spectroscopy (XPS) and XUV-RA the existence of Fe(III) at the surface and in the near surface regions of glycerol FeCl3 solutions, where glycerol is used as a high vacuum compatible proxy for water. XPS showed Cl- and Fe(III) species with significant Fe(III) interfacial enrichment. In aqueous solutions, an electrical double layer (EDL) of Cl- and Fe(III) species at 0.5 m FeCl3 concentration is observed as evidenced from an enhancement of molecular ordering of water dipoles, consistent with the observed behavior at the glycerol surface. At higher concentrations in water, the EDL appears to be substantially repressed, indicative of further Fe(III) complex enrichment and dominance of a centrosymmetric Fe(III) species that is surface active. In addition, a significant vibrational red-shift of the dangling OH from the water molecules that straddle the air-water interface reveals that the second solvation shell of the surface active Fe(III) complex permeates the topmost layer of the aqueous interface.

Increased Adult Aedes aegypti and Culex quinquefasciatus (Diptera: Culicidae) Abundance in a Dengue Transmission Hotspot, Compared to a Coldspot, within Kaohsiung City, Taiwan.

The assumption that vector abundance differences might drive spatial and temporal heterogeneities in vector-borne disease transmission is common, though data supporting it is scarce. Here, we present data from two common mosquito species Aedes aegypti (Linnaeus) and Culex quinquefasciatus Say, biweekly sampled as adults, from March 2016 through December 2017, with BG-sentinel traps in two neighboring districts of Kaohsiung City (KC), Taiwan. One district has historically been a dengue transmission hotspot (Sanmin), and the other a coldspot (Nanzih). We collected a total 41,027 mosquitoes, and we found that average mosquito abundance (mean ± S.D.) was higher in Sanmin (Ae. aegypti: 9.03 ± 1.46; Cx. quinquefasciatus: 142.57 ± 14.38) than Nanzih (Ae. aegypti: 6.21 ± 0.47; Cx. quinquefasciatus: 63.37 ± 8.71) during the study period. In both districts, Ae. aegypti and Cx. quinquefasciatus population dynamics were sensitive to changes in temperature, the most platykurtic environmental variable at KC during the study period, a pattern predicted by Schmalhausen's law, which states that organisms are more sensitive to small changes in environmental variables whose average value is more uncertain than its extremes. Our results also suggest that differences in Ae. aegypti abundance might be responsible for spatial differences in dengue transmission at KC. Our comparative approach, where we also observed a significant increment in the abundance of Cx. quinquefasciatus in the dengue transmission hotspot, suggests this area might be more likely to experience outbreaks of other vector borne diseases and should become a primary focus for vector surveillance and control.

Epidemiological Characteristics and Space-Time Analysis of the 2015 Dengue Outbreak in the Metropolitan Region of Tainan City, Taiwan.

The metropolitan region of Tainan City in southern Taiwan experienced a dengue outbreak in 2015. This manuscript describes basic epidemiological features of this outbreak and uses spatial and temporal analysis tools to understand the spread of dengue during the outbreak. The analysis found that, independently of gender, dengue incidence rate increased with age, and proportionally affected more males below the age of 40 years but females above the age of 40 years. A spatial scan statistic was applied to detect clusters of disease transmission. The scan statistic found that dengue spread in a north-south diffusion direction, which is across the North, West-Central and South districts of Tainan City. Spatial regression models were used to quantify factors associated with transmission. This analysis indicated that neighborhoods with high proportions of residential area (or low wetland cover) were associated with dengue transmission. However, these association patterns were non-linear. The findings presented here can help Taiwanese public health agencies to understand the fundamental epidemiological characteristics and diffusion patterns of the 2015 dengue outbreak in Tainan City. This type of information is fundamental for policy making to prevent future uncontrolled dengue outbreaks, given that results from this study suggest that control interventions should be emphasized in the North and West-Central districts of Tainan city, in areas with a moderate percentage of residential land cover.

Formation of hollow and mesoporous structures in single-crystalline microcrystals of metal-organic frameworks via double-solvent mediated overgrowth.

The creation of hierarchical porosity in metal-organic frameworks (MOFs) could benefit various applications of MOFs such as gas storage and separation. Having single-crystalline microcrystals instead of poly-crystalline composites is critical for these potential applications of MOFs with hierarchical porosity. We developed a room temperature synthetic method to generate uniform hollow and mesoporous zeolitic imidazolate framework-8 (ZIF-8) microcrystals with a single-crystalline structure via overgrowing a ZIF-8 shell in methanol solution on a ZIF-8 core with water adsorbed in the pores. The cavities formed as a result of the different solvent micro-environment. This double-solvent mediated overgrowth method could be applied to prepare other MOFs with hierarchical porosity.

Electrochemically induced surface metal migration in well-defined core-shell nanoparticles and its general influence on electrocatalytic reactions.

Bimetallic nanoparticle catalysts provide enhanced activity, as combining metals allows tuning of electronic and geometric structure, but the enhancement may vary during the reaction because the nanoparticles can undergo metal migration under catalytic reaction conditions. Using cyclic voltammetry to track the surface composition over time, we carried out a detailed study of metal migration in a well-defined model Au-Pd core-shell nanocatalyst. When subjected to electrochemical conditions, Au migration from the core to the shell was observed. The effect of Pd shell thickness and electrolyte identity on the extent of migration was studied. Migration of metals during catalytic ethanol oxidation was found to alter the particle's surface composition and electronic structure, enhancing the core-shell particles' activity. We show that metal migration in core-shell nanoparticles is a phenomenon common to numerous electrochemical systems and must be considered when studying electrochemical catalysis.

Effects of surfactants on the purple membrane and bacteriorhodopsin: solubilization or aggregation?

Using steady-state spectroscopic and zeta potential methods, we have unraveled the interaction of the purple membrane (PM) and bacteriorhodopsin (bR) with various surfactants below their critical micelle concentrations. We found that the charged hydrophilic heads of ionic surfactants play a role in perturbing the structure and conformation of PM and bR and that ionic surfactants of opposite charges cause opposing effects. Specifically, the addition of a low concentration (0.2 mM) of the cationic surfactant cetyl trimethylammonium bromide (CTAB) is capable of neutralizing the negatively charged lipids on the PM surface via electrostatic forces. This results in increased hydrophobicity of PM that leads to the aggregation of PM. In contrast, denaturation of PM and bR was observed when the anionic surfactant sodium dodecyl sulfate (SDS) was added to the PM suspensions. The attachment of SDS to the PM surface increases the solubility of PM and causes a loose crystalline structure. As the SDS concentration is increased to more than 3 mM, the secondary structure of the constituents of bR is significantly distorted, and the protonated Schiff base is hydrolyzed to form free retinal. The addition of the neutral surfactant diethylene glycol mono-n-hexyl ether (C6E2) does not significantly influence the PM and bR, meaning most of their original properties are preserved. We conclude that the addition of surfactants might cause the aggregation or solubilization of the membrane protein, depending on the signs of the charged hydrophilic heads of the surfactants and the charges of the membrane protein surface. Aggregation results when the surfactant and protein have opposite charges, whereas solubilization results when the surfactant and protein have the same charge.