Polythionine and gold nanostar-based impedimetric aptasensor for label-free detection of α-synuclein oligomers

Journal of Applied Electrochemistry - The neurotoxicity of α-synuclein oligomers (α-syno) could cause Parkinson’s disease (PD) which is an irreversible neurodegenerative disease. In...     

Mechanisms of dimer and trimer formation from ultraviolet-irradiated α-tocopherol

α-Tocopherol (α-TH) undergoes ultraviolet (UV)-induced photooxidation on the surface of mouse skin to produce a dihydroxydimer, a spirodimer, and trimers as the major products. To study the photochemistry involved, we UV-irradiated α-TH in a thin film on a glass petri dish. Photooxidation yielded a mixture of dihydroxydimer, spirodimer, and trimers. In the time-course studies, the dihydroxydimer accumulated and then was further oxidized, whereas the spirodimer and trimers accumulated more gradually. Reaction of two tocopheroxyl radicals forms the dihydroxydimer, whereas the spirodimer may be formed either by photooxidation of α-TH to an orthoquinone methide (o-QM) followed by a Diels-Alder reaction or by photooxidation of α-TH to the dihydroxydimer, followed by two-electron oxidation. Irradiation of a mixture of d ₁₀-labeled and unlabeled (d ₀) dihydroxydimer produced a mixture of labeled and unlabeled spirodimers as detected by positive atmospheric pressure chemical ionization-mass spectrometry. The absence of mixed label spirodimers among products indicated that direct oxidation of the dihydroxydimer is a facile route to the spirodimer and is probably the major spirodimer-forming reaction in α-TH photooxidations. Trimer formation from the dihydroxydimer and the spirodimer was observed, however, and requires an o-QM intermediate. Photooxidation of d ₁₀-labeled and unlabeled (d ₀) dihydroxydimers yielded mixed isotopomers of the trimer products, thus demonstrating that the dihydroxydimer and spirodimers underwent conversion to o-QM intermediates. Photochemical conversion of α-TH to UV-absorbing dimer and trimer products may contribute to photoprotection by topically applied α-TH.     

Effects of α- and γ-tocopherols on formation of hydroperoxides and two decomposition products from methyl linoleate

The antioxidant effects of α-and γ-tocopherols (at 0, 10, 100, 500, and 1000 ppm) were evaluated in a model system based on the autoxidation of methyl linoleate in bulk for 4 d at 40°C. Samples were collected every 24 h and analyzed for the 9 cis,trans, 9 trans,trans, 13 cis,trans, and 13 trans,trans isomers of hydroperoxide, hydroxy, and ketodiene oxidation products by high-performance liquid chromatography. Results showed that both α- and γ-tocopherols are effective hydrogen donors as evidenced by their abilities to inhibit the formation of hydroperoxides, hydroxy compounds, and ketodienes and the cis,trans to trans,trans isomerization of hydroperoxides. Compared with γ-tocopherol, α-tocopherol was a more efficient antioxidant at very low concentrations (10 ppm) but a less efficient antioxidant at the high concentrations (100–1000 ppm). This paradoxical behavior is explained on the basis of differences in ease of hydrogen donation between the two tocopherol homologs. Although α-tocopherol shows some loss of efficiency with increasing concentration, it is not a prooxidant when compared to the control void of antioxidants.     

Bioorthogonal surface modified α-TCP-based bone filler for enhancement of apatite formation and bioactivity

The aim of the present study was to investigate the effect of click chemistry reactants on morphology and physico-chemical properties of alpha tricalcium phosphate (α-TCP)-based powders. The powders were synthesized by solid-state reaction. The powders were modified with azide and cycloalkyne to form triazole as a consequence of reactions of these molecules. The presence of the band related to the triazole ring and the click molecules in powder structure was confirmed by Fourier transform infrared (FTIR) and Liquid chromatography- mass spectroscopy (LC-MS) analyses. Based on scanning electron microscopy (SEM) observations, the modified powder exhibited a different microstructure and morphology of apatite precipitates after one day and 7 days of soaking in distilled water and SBF solution, respectively, with respect to unmodified powder. According to the acellular in vitro test, X-ray diffraction (XRD) patterns represented triple characteristic peaks of hydroxyapatite (HA) in modified powder compared with control. Besides, the tendency of conversion of α-TCP to HA is more enhanced for modified powder as well. The SEM analysis depicted the plate-like and needle-like morphology of HA on the surface of modified and control powders, respectively. Since plate-like morphology of HA enhances bone generation and is found in trabecular bone, therefore, a future design can be considered for triazole-modified α-TCP-based fillers as good candidates for bone substitute application.     

Synthesis of a novel lipopeptide with α-melanocyte-stimulating hormone peptide ligand and its effect on liposome stability

Introduction of liposomes into target cells is important for drug delivery systems. For this purpose, the surface of the liposome is equipped with ligand peptides, which may bind to specific receptors on the cell membrane. An artificial novel lipopeptide (MSH-C4A2) containing the α-melanocyte-stimulating hormone (α-MSH) sequence and two long alkyl chains was designed and synthesized, and the liposome, composed of egg phosphatidylcholine (EPC) and MSH-C4A2, was prepared. The stability of the liposome was estimated by measuring calcein leakage from the liposome inner phase. The stability of the liposome decreased upon addition of MSH-A4C2, which seemed to be attributable to the amphiphilic property of the peptide moiety (α-MSH) of MSH-A2C4. The stability was, however, recovered fairly well upon addition of cholesterol (Ch) or phosphatidylglycerol (PG). It was concluded therefore that the ternary system, MSH-C4A2/Ch/EPC or MSH-C4A2/PG/EPC, is suitable for preparing the functional liposome.     

Role of B2O3 in formation of mullite from kaolinite and α-Al2O3 mixtures

Abstract

The microstructure, phase constitution, and physical properties of mullite bodies prepared from α-Al₂O₃- kaolin mixtures with added B₂O₃ were investigated. Densification was found to be enhanced with small additions of B₂O₃. The results indicate that 0.5 wt-% B₂O₃ increases the content and growth rate of the mullite. It was found to be the optimum addition with respect to densification and resulting properties.     

Dissecting the role of single regions of an IAPP mimic and IAPP in inhibition of Aβ40 amyloid formation and cytotoxicity

Alzheimer's disease (AD) and type 2 diabetes (T2D) are linked to the self-association of β-amyloid peptide (Aβ) and islet amyloid polypeptide (IAPP), respectively. We have shown that IAPP-GI, a soluble IAPP analogue and mimic of nonamyloidogenic and nontoxic IAPP, binds Aβ with high affinity and blocks its cytotoxic self-assembly and fibrillogenesis. We have also shown that IAPP and Aβ interact with each other into nonfibrillar and nontoxic heterocomplexes that suppress cytotoxic self-association by both polypeptides. The Aβ-IAPP interaction might thus be a molecular link between AD and T2D. We studied the role of individual IAPP-GI and IAPP regions in their inhibitory function on Aβ40 self-association and cytotoxicity. We found that the presence of the two hot-spot regions of the Aβ-IAPP interaction interface in IAPP(8-28) is not sufficient for inhibitory function and that, in addition to IAPP(8-28), the presence of the N-terminal region IAPP(1-7) is absolutely required. By contrast, the C-terminal region, IAPP(30-37), is not required although its presence together with IAPP(1-7) in IAPP-GI results in a marked enhancement of the inhibitory effect as compared to IAPP(1-28)-GI. We suggest that the inhibitory effect of IAPP-GI and IAPP on Aβ40 fibrillogenesis and cell toxicity is mediated primarily by interactions involving the hot regions of the Aβ-IAPP interaction interface and the N terminus of IAPP while a concerted and likely structure-stabilizing action of the N- and C-terminal IAPP regions potentiates this effect. These results identify important molecular determinants of the amyloid suppressing function of the Aβ40-IAPP interaction and could contribute to the design of novel inhibitors of Aβ40 aggregation and cell degeneration.     

Molecular basis of cross-interactions between Aβ and Tau protofibrils probed by molecular simulations

Amyloid β-protein(Aβ) and Tau, two common pathogenic proteins associated with Alzheimer’s disease(AD), cross-interact, and thus co-assemble into hybrid aggregates. However, molecular mechanism of the cross-interactions remains unclear. To explore the issue, docking and molecular dynamics(MD) simulations were coupled to study the cross-interactions between Aβ pentamer and Tau pentamer. Four stable hybrid decamer conformations including double layer, single layer, block, and part-in were obtained ...     

The influence of passivation and photovoltaic properties of α-Si:H coverage on silicon nanowire array solar cells

Silicon nanowire (SiNW) arrays for radial p-n junction solar cells offer potential advantages of light trapping effects and quick charge collection. Nevertheless, lower open circuit voltages (V_oc) lead to lower energy conversion efficiencies. In such cases, the performance of the solar cells depends critically on the quality of the SiNW interfaces. In this study, SiNW core-shell solar cells have been fabricated by growing crystalline silicon (c-Si) nanowires via the metal-assisted chemical etching method and by depositing hydrogenated amorphous silicon (α-Si:H) via the plasma-enhanced chemical vapor deposition (PECVD) method. The influence of deposition parameters on the coverage and, consequently, the passivation and photovoltaic properties of α-Si:H layers on SiNW solar cells have been analyzed.     

Synthesis of α-SiC/α-SiAlON composites by spark plasma sintering: Phase formation and microstructures development

α-SiC/α-SiAlON composites with 80 wt% α-SiC (6H phase) were fabricated by spark plasma sintering at 1800-2000 °C in a 0.6 atm nitrogen atmosphere. The effects of the temperatures on the phase development, microstructures and mechanical properties were investigated. The results showed the Si₃N₄, AlN, Al₂O₃, and Y₂O₃ particles were isolated by the 6H-SiC to prevent α-SiAlON formation at 1800 °C. The Si₃N₄ decomposed at 1900 °C and above, thus added Si in the phase compositions. The α-SiC grains grew anisotropic in the sintering liquids at 1800 °C and 1900 °C, forming the self-reinforcing microstructures, and accordingly increased the flexural strength and fracture toughness. In cooling down immediately after the temperature reached 2000 °C, a transitory hold at 1700 °C transformed the 6H-SiC into the 3C polytype in 30 s. The electric current was suspected of activating this polytype transformation.     

Amyloid cross-seeding between Aβ and hIAPP in relation to the pathogenesis of Alzheimer and type 2 diabetes

Amyloid cross-seeding of different amyloid proteins is considered as a highly possible mechanism for exacerbating the transmissible pathogenesis of protein misfolding disease(PMDs) and for explaining a molecular link between different PMDs, including Alzheimer disease(AD) and type 2 diabetes(T2D),AD and Parkinson disease(PD), and AD and prion disease.Among them, AD and T2D are the most prevalent PMDs, affecting millions of people globally, while Aβ and hIAPP are the causative peptides responsible for AD and T2D, respectively.Increasing clinical and epidemiological evidences lead to a hypothesis that the cross-seeding of Aβ and hIAPP is more biologically responsible for a pathological link between AD and T2D.In this review, we particularly focus on(i) the most recent and important findings of amyloid cross-seeding between Aβ and h IAPP from in vitro, in vivo, and in silico studies,(ii) a mechanistic role of structural compatibility and sequence similarity of amyloid proteins(beyond Aβ and hIAPP)in amyloid cross-seeding, and(iii) several current challenges and future research directions in this lessstudied field.Review of amyloid cross-seeding hopefully provides some mechanistic understanding of amyloidogenesis and inspires more efforts for the better design of next-generation drugs/strategies to treat different PMDs simultaneously.     

Nanomechanical properties of α-synuclein amyloid fibrils: a comparative study by nanoindentation,harmonic force microscopy,and Peakforce QNM

We report on the use of three different atomic force spectroscopy modalities to determine the nanomechanical properties of amyloid fibrils of the human α-synuclein protein. α-Synuclein forms fibrillar nanostructures of approximately 10 nm diameter and lengths ranging from 100 nm to several microns, which have been associated with Parkinson's disease. Atomic force microscopy (AFM) has been used to image the morphology of these protein fibrils deposited on a flat surface. For nanomechanical measurements, we used single-point nanoindentation, in which the AFM tip as the indenter is moved vertically to the fibril surface and back while the force is being recorded. We also used two recently developed AFM surface property mapping techniques: Harmonic force microscopy (HarmoniX) and Peakforce QNM. These modalities allow extraction of mechanical parameters of the surface with a lateral resolution and speed comparable to tapping-mode AFM imaging. Based on this phenomenological study, the elastic moduli of the α-synuclein fibrils determined using these three different modalities are within the range 1.3-2.1 GPa. We discuss the relative merits of these three methods for the determination of the elastic properties of protein fibrils, particularly considering the differences and difficulties of each method.     

Hydroformylation of Alkynyl Sulfides: A Stereo- and Regioselective Route to α-Sulfenyl Acroleins

The rhodium-catalyzed hydroformylation of alkynyl sulfides at 40 °C under 5 bars of syngas is described. The method gives access to α-sulfenyl acroleins with α/β regioselectivities up to 89/11 and is applicable to alkyl or aryl substituted substrates. It is effective even on more complex substrates, such as cysteine and cholesterol derivatives. To demonstrate the synthetic potential of the obtained products, (Z)-3-cyclohexyl-2-methylsulfenyl acrolein was selected as an example and its sulfur atom selectively oxidized to the corresponding sulfoxide or sulfone. Acid-promoted (Z) to (E) isomerization of the double bond occurred during oxidation. The three obtained sulfenyl-, sulfinyl-, and sulfonyl-functionalized acroleins have been then used as dienophiles to access cyclohexene carbaldehydes.     

The effect of α-linolenic acid and linoleic acid on the growth and development of formula-fed infants: A systematic review and meta-analysis of randomized controlled trials

This systematic review and meta-analysis aimed to evaluate the effect of modifying 18-carbon PUFA [18-C PUFA: α-linolenic acid (ALA, 18∶3n−3) and linoleic acid (LA, 18∶2n−6)] in the diets of term and preterm infants on DHA (22∶6n−3) status, growth, and developmental outcomes. Only randomized controlled trials (RCT) involving formula-fed term and preterm infants, in which the 18-C PUFA composition of the formula was changed and growth or developmental outcomes were measured, were included. Differences were presented as control (standard formula) and treatment (18-C PUFA-supplemented formula). Primary analyses for term infants were 4 and 12 mon and for preterm infants 37–42 and 57 wk postmenstrual age. Five RCT involving term infants and three RCT involving preterm infants were included in the systematic review. Infants fed ALA-supplemented formula had significantly higher plasma and erythrocyte phospholipid DHA levels than control infants. There was no effect of ALA supplementation on the growth of preterm infants. In term infants, ALA supplementation was associated with increased weight and length at 12 mon, which was at least 4 mon after the end of dietary intervention. Developmental indices of term infants did not differ between groups. There was a transient improvement in the retinal function of preterm infants fed ALA-supplemented diets compared with controls. The findings suggest that ALA-supplemented diets improve the DHA status of infants. Further studies are needed to provide convincing evidence regarding the effects of ALA supplementation of formula on infant growth and development.     

Peptide Array on Cellulose Support—A Screening Tool to Identify Peptides with Dipeptidyl-Peptidase IV Inhibitory Activity within the Sequence of α-Lactalbumin

The inhibition of the enzyme dipeptidyl-peptidase IV (DPP-IV) is an effective pharmacotherapeutic approach for the management of type 2 diabetes. Recent findings have suggested that dietary proteins, including bovine α-lactalbumin, could be precursors of peptides able to inhibit DPP-IV. However, information on the location of active peptide sequences within the proteins is far from being comprehensive. Moreover, the traditional approach to identify bioactive peptides from foods can be tedious and long. Therefore, the objective of this study was to use peptide arrays to screen α-lactalbumin-derived peptides for their interaction with DPP-IV. Deca-peptides spanning the entire α-lactalbumin sequence, with a frame shift of 1 amino acid between successive sequences, were synthesized on cellulose membranes using “SPOT” technology, and their binding to and inhibition of DPP-IV was studied. Among the 114 α-lactalbumin-derived decamers investigated, the peptides ⁶⁰WCKDDQNPHS⁶⁹ (αK_i = 76 µM), ¹⁰⁵LAHKALCSEK¹¹⁴ (K_i = 217 µM) and ¹¹⁰LCSEKLDQWL¹¹⁹ (K_i = 217 µM) were among the strongest DPP-IV inhibitors. While the SPOT- and traditionally-synthesized peptides showed consistent trends in DPP-IV inhibitory activity, the cellulose-bound peptides’ binding behavior was not correlated to their ability to inhibit the enzyme. This research showed, for the first time, that peptide arrays are useful screening tools to identify DPP-IV inhibitory peptides from dietary proteins.     

Modification of the rate of formation and surface area of ettringite by polycarboxylate ether superplasticizers during early C3A–CaSO4 hydration

Early C₃A–CaSO₄ hydration was studied in the presence of various amounts of two polycarboxylate ether superplasticizers differing in their grafting degree. Hydration and surface area developments were investigated by in-situ NMR relaxometry coupled with BET and DSC during the first 2 h after mixing. This study enables a quantitative comparison of the amount and the specific surface area of the ettringite precipitated along the C₃A–CaSO₄ hydration with or without PCE. The main effect of PCE is to strongly increase ettringite specific area for a variable period. These effects are clearly dependent on the PCE charge and dosage and are reduced when using delayed addition. In this context the NMR relaxometry technique is of particular interest because of its high sensitivity to ettringite and furthermore this in-situ method does not need preliminary preparation likely to damage structure or modify particle arrangement.     

A quantum‐chemical study of the formation mechanism and nature of tert‐butyl carbenium ions in 100% sulfuric acid

Ab initio quantum‐chemical calculations reveal that the interaction of isobutene with H₃SO ₄ ⁺ ions produced by self‐dissociation of sulfuric acid occurs virtually without an activation barrier, whereas the reactions involving neutral species of sulfuric acid are characterized by considerable activation barriers: 14.9 kcal/mol at the MP2(full)/6‐31+G*//6-31+G* level and 16.9 kcal/mol^-1 at the MP2(full)/6‐31+G*//3‐21+G* level. It is also concluded that the species resulting from interaction of isobutane with H₃SO ₄ ⁺ ions of protonated tert‐butyl sulfuric acid are ion‐molecular complexes which should be considered as tert‐butyl carbenium ions weakly solvated by H₂SO₄ molecules. Although the concentration of these species in concentrated sulfuric acid is very low, presumably, they play a role of active intermediates in isobutene conversions catalyzed by sulfuric acid. This revised version was published online in July 2006 with corrections to the Cover Date.     

Combination of Aβ Secretion and Oxidative Stress in an Alzheimer-Like Cell Line Leads to the Over-Expression of the Nucleotide Excision Repair Proteins DDB2 and XPC

Repair of oxidative DNA damage, particularly Base Excision Repair (BER), impairment is often associated with Alzheimer’s disease pathology. Here, we aimed at investigating the complete Nucleotide Excision Repair (NER), a DNA repair pathway involved in the removal of bulky DNA adducts, status in an Alzheimer-like cell line. The level of DNA damage was quantified using mass spectrometry, NER gene expression was assessed by qPCR, and the NER protein activity was analysed through a modified version of the COMET assay. Interestingly, we found that in the presence of the Amyloid β peptide (Aβ), NER factors were upregulated at the mRNA level and that NER capacities were also specifically increased following oxidative stress. Surprisingly, NER capacities were not differentially improved following a typical NER-triggering of ultraviolet C (UVC) stress. Oxidative stress generates a differential and specific DNA damage response in the presence of Aβ. We hypothesized that the release of NER components such as DNA damage binding protein 2 (DDB2) and Xeroderma Pigmentosum complementation group C protein (XPC) following oxidative stress might putatively involve their apoptotic role rather than DNA repair function.