Ultraviolet Radiation Exposure and its Impacts on Cutaneous Phosphorylation Signaling in Carcinogenesis: Focusing on Protein Tyrosine Phosphatases†

Sunlight exposure is a significant risk factor for UV-induced deteriorating transformations of epidermal homeostasis leading to skin carcinogenesis. The ability of UVB radiation to cause melanoma, as well as basal and squamous cell carcinomas, makes UVB the most harmful among the three known UV ranges. UVB-induced DNA mutations and dysregulation of signaling pathways contribute to skin cancer formation. Among various signaling pathways modulated by UVB, tyrosine phosphorylation signaling which is mediated by the action of protein tyrosine kinases (PTKs) on specific tyrosine residues is highly implicated in photocarcinogenesis. Following UVB irradiation, PTKs get activated and their downstream signaling pathways contribute to photocarcinogenesis by promoting the survival of damaged keratinocytes and increasing cell proliferation. While UVB activates oncogenic signaling pathways, it can also activate tumor suppressive signaling pathways as initial protective mechanisms to maintain epidermal homeostasis. Tyrosine dephosphorylation is one of the protective mechanisms and is mediated by the action of protein tyrosine phosphatases (PTPs). PTP can counteract UVB-mediated PTK activation and downregulate oncogenic signaling pathways. However, PTPs have not been studied extensively in photocarcinogenesis with previous studies regarding their inactivation induced by UVB. This current review will summarize the recent progress in the protective function of PTPs in epidermal photocarcinogenesis.     

Free Superoxide is an Intermediate in the Production of H2O2 by Copper(I)‐Aβ Peptide and O2

Oxidative stress is considered as an important factor and an early event in the etiology of Alzheimer's disease (AD). Cu bound to the peptide amyloid‐β (Aβ) is found in AD brains, and Cu‐Aβ could contribute to this oxidative stress, as it is able to produce in vitro H₂O₂ and HO^. in the presence of oxygen and biological reducing agents such as ascorbate. The mechanism of Cu‐Aβ‐catalyzed H₂O₂ production is however not known, although it was proposed that H₂O₂ is directly formed from O₂ via a 2‐electron process. Here, we implement an electrochemical setup and use the specificity of superoxide dismutase‐1 (SOD1) to show, for the first time, that H₂O₂ production by Cu‐Aβ in the presence of ascorbate occurs mainly via a free O₂^.? intermediate. This finding radically changes the view on the catalytic mechanism of H₂O₂ production by Cu‐Aβ, and opens the possibility that Cu‐Aβ‐catalyzed O₂^.? contributes to oxidative stress in AD, and hence may be of interest.     

The classification of homotopy classes of bounded curvature paths

A bounded curvature path is a continuously differentiable piecewise C² path with bounded absolute curvature that connects two points in the tangent bundle of a surface. In this note we give necessary and sufficient conditions for two bounded curvature paths, defined in the Euclidean plane, to be in the same connected component while keeping the curvature bounded at every stage of the deformation. Following our work in [3], [2] and [4] this work finishes a program started by Lester Dubins in [6] in 1961.     

Monitoring and Targeting the Initial Dimerization Stage of Amyloid Self‐Assembly

Amyloid deposits are pathological hallmark of a large group of human degenerative disorders of unrelated etiologies. While accumulating evidence suggests that early oligomers may account for tissue degeneration, most detection tools do not allow the monitoring of early association events. Here we exploit bimolecular fluorescence complementation analysis to detect and quantify the dimerization of three major amyloidogenic polypeptides; islet amyloid polypeptide, β‐amyloid and α‐synuclein. The constructed systems provided direct visualization of protein‐protein interactions in which only assembled dimers display strong fluorescent signal. Potential inhibitors that interfere with the initial intermolecular interactions of islet amyloid polypeptide were further identified using this system. Moreover, the identified compounds were able to inhibit the aggregation and cytotoxicity of islet amyloid polypeptide, demonstrating the importance of targeting amyloid dimer formation for future drug development.     

Effect of surface charge on the colloidal stability and in vitro uptake of carboxymethyl dextran-coated iron oxide nanoparticles

An easy and novel routine are reported for the preparation of metallic silver nanoparticles (AgNPs) with controlled morphology, using Na⁺–magadiite swelled with hexadecyltrimethylammonium bromide (CTA⁺–magadiite) and a layered aluminophosphate with kanemite-type structure modified with n-dodecylammonium and n-butylammonium (but,dod-AlPO-kan) as hosts. For the preparation of the metallic AgNPs (Ag⁰) in the interlamellar space, the CTA⁺–magadiite and but,dod-AlPO-kan hosts were dispersed in N,N-dimethylformamide (DMF) solution with different AgNO₃ concentrations. DMF acts as reducing agent of Ag⁺ ions leading to nanoparticles with disk-like morphology of magadiite silicate; these were characterized by TEM and UV–Vis spectroscopy. On the other hand, the AgNPs are intercalated in but,dod-AlPO-kan showing spherical-like morphology. The UV–Vis spectra of the nanocomposites based on Ag⁰ and magadiite silicate show bands at 565 nm that can be attributed to Ag⁰ nanodisks. The Ag-but,dod-AlPO-kan-based nanocomposites present a band at 422 nm attributed to the surface plasmon resonance of Ag⁰ nanospheres. The results of transmission electron microscopy agree very well with XRD and UV–Vis analysis, indicating the formation of AgNPs with different morphologies using the two kinds of lamellar materials. The magadiite host has an important role in the synthesis of Ag nanodisks, because it controls the growth of nanoparticles inside the interlayer region with disk-like morphology due the high interlayer interactions of the silicate, leading to the growth of nanoparticles in only two directions (xy plane). On the other hand, when but,dod-AlPO-kan is used a sphere-like morphology is preferred due the best accommodation of AgNPs between the layers of aluminophosphate host.     

In-situ ionic liquid-dispersive liquid-liquid microextraction method to determine endocrine disrupting phenols in seawaters and industrial effluents

We have evaluated an in-situ ionic liquid-dispersive liquid-liquid microextraction procedure for the determination of six endocrine disrupting phenols in seawaters and industrial effluents using HPLC. The optimized method requires 38???L of the water-soluble ionic liquid 1-butyl-3-methylimidazolium chloride, and 5?mL of seawater or industrial effluent. After appropriate work-up, a drop (~10???L) of an ionic liquid is formed that contains the analytes of interest. It is diluted with acetonitrile and injected into the HPLC system. This procedure is accomplished without heating or cooling the solutions. The method is characterized by (a) average relative recoveries of 90.2%, (b) enrichment factors ranging from 140 to 989, and (c) precisions (expressed as relative standard deviations) of less than 11% when using a spiking level of 10?ng?mL^?1. The limits of detection range from 0.8?ng?mL^?1 for 4-cumylphenol to 4.8?ng?mL^?1 for bisphenol-A.

Headspace-single drop microextraction (HS-SDME) in combination with high-performance liquid chromatography (HPLC) to evaluate the content of alkyl- and methoxy-phenolic compounds in biomass smoke

The content of ten phenolic compounds present in four different biomass smoke materials: rock rose (Cistus monpelienisis), prickly pear (Opuntia ficus indica), pine needles (Pinus canariensis), and almonds skin (Prunus dulcis), have been evaluated. The sampling method mainly consisted of a trap alkaline solution to solubilize the phenols, and was optimized by an experimental design. Average sampling efficiencies of 78.1% and an average precision value of 10.6% (as relative standard deviation, RSD), were obtained for the selected group of phenols. The trapped phenolates were further analyzed by a headspace-single drop microextraction (HS-SDME) procedure, in combination with high-performance liquid chromatography (HPLC) with UV detection. The optimum variables for the HS-SDME method were: 1-decanol as extractant solvent, 3.5 μL of microdrop volume, 2 mL of sample volume, a pH value of 2, saturation of NaCl, an extraction temperature of 60 °C, and an extraction time of 25 min. The optimized HS-SDME method presented detection limits ranging from 0.35 to 5.8 μg mL⁻¹, RSD values ranging from 0.7 to 7.4%, and an average relative recovery (RR) of 99.8% and an average standard deviation of 5.2. The average content of phenolic compounds in the biomass materials studied were 70, 161, 206 and 252 mg kg⁻¹ of biomass for prickly pear, almonds skin, rock rose, and pine needles, respectively. The main components of the smokes were vanillin, phenol and methoxyphenols, in all smoking materials studied.     

Multiparametric automated system for sulfate,nitrite and nitrate monitoring in drinking water and wastewater based on sequential injection analysis

An automated monitoring system for sulfate, nitrite and nitrate based on sequential injection analysis (SIA) was developed. For nitrite determination the modified Griess-Ilosvay method was used, whereas nitrate was previously reduced to nitrite using a cadmium column followed by nitrite determination. A turbidimetric method was carried out in order to determine sulfate. The results showed that the proposed SIA monitoring system constitutes an effective approach for nitrite, nitrate and sulfate determination since it is able to determine levels required by international agencies that regulate these parameters in water. Detection limits of 0.0207 mg N L^? 1, 0.0022 mg N L^? 1 and 3 mg SO₄^2? L^? 1 were obtained for nitrate, nitrite and sulfate, respectively. The developed method offers also typical characteristics of the multicommutated systems, as portability, low reagents consumption and the subsequently minimization of waste generation. The proposed system was successfully applied to drinking water and wastewater samples and validated with a certified river water sample (ION-96.3, LGC Standards).     

Real-time NMR characterization of structure and dynamics in a transiently populated protein folding intermediate

Recent advances in NMR spectroscopy and the availability of high magnetic field strengths now offer the possibility to record real-time 3D NMR spectra of short-lived protein states, e.g., states that become transiently populated during protein folding. Here we present a strategy for obtaining sequential NMR assignments as well as atom-resolved information on structural and dynamic features within a folding intermediate of the amyloidogenic protein β2-microglobulin that has a half-lifetime of only 20 min.     

The simplex dispersion ordering and its application to the evaluation of human corneal endothelia

A multivariate dispersion ordering based on random simplices is proposed in this paper. Given a R^d-valued random vector, we consider two random simplices determined by the convex hulls of two independent random samples of sizes d+1 of the vector. By means of the stochastic comparison of the Hausdorff distances between such simplices, a multivariate dispersion ordering is introduced. Main properties of the new ordering are studied. Relationships with other dispersion orderings are considered, placing emphasis on the univariate version. Some statistical tests for the new order are proposed. An application of such ordering to the clinical evaluation of human corneal endothelia is provided. Different analyses are included using an image database of human corneal endothelia.