Biochemical and immunological aspects of protein aggregation in neurodegenerative diseases

Protein aggregation is commonly associated with a large number of neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and other types of pathological conditions. Misfolding and aggregation of a number of peptides and proteins have been found to occur under these conditions. In the present review, some mechanistic features of the events related to the type of structure–function relationships which may define the outcome of the abnormal conditions are discussed. The immunological responses to the aggregates and possible therapeutic strategies for prevention or control of the diseases are also reviewed. Protein aggregation and its effect on human body have become an important issue over the last two decades. Many diseases in human are related to aggregation and misfolding of different kinds of proteins; therefore, diagnosis of causes of the aggregation and their mechanisms which provoke it are important. This review describes the relations between structures and functions of already aggregated proteins, as well as proteins, which only enter initial stages of aggregation. The consequences of aggregations, which provoke many kinds of neurodegenerative disorders, are explained in details and some factors that may influence their severity are described. In addition, the immunologic responses to these aggregates are discussed. Suggestions of plausible therapies of preventing or slowing down the protein condensation diseases are presented.     

Effects of 3D electrodes arrangement in a novel AC electroosmotic micropump: Numerical modeling and experimental validation

To date, a comprehensive systematic optimization framework, capable of accurately predicting an efficient electrode geometry, is not available. Here, different geometries, including 3D step electrodes, have been designed in order to fabricate AC electroosmosis micropumps. It is essential to optimize both geometrical parameters of electrode, such as width and height of steps on each base electrode and their location in one pair, the size of each base electrode (symmetric or asymmetric), the gap of electrode pairs, and nongeometrical parameters such as fluid flow in a channel and electrical characteristics (e.g., frequency and voltage). The governing equations comprising of electric domain and fluid domain have been coupled using finite element method. The developed model was employed to investigate the effect of electrode geometric parameters on electroosmotic slip velocity and its subsequent effect on pressure and flow rate. Numerical simulation indicates that the optimal performance can be achieved using a design with varying step height and displacement, at a given voltage (2.5 V) and frequency (1 kHz). Finally, in order to validate the numerical simulation, the optimal microchip was fabricated using a combination of photolithography, electroplating, and a polydimethylsiloxane microchannel. Our results indicate that our micropump is capable of generating a pressure, velocity, and flow rate of 74.2 Pa, 1.76 mm/s, and 14.8 µl/min, respectively. This result reveals that our proposed geometry outperforms the state-of-the-art micropumps previously reported in the literature by improving the fluid velocity by 32%, with 80% less electrodes per unit length, and whereas the channel length is ∼80% shorter.     

Atropine-selective membrane electrodes and relative selectivity concept

TFPB was introduced as a charged ionophore for atropine selective electrodes. Typical Nernstian responses were found (57.78, 58.95 and 58.41 mV/decade) for PVC-membrane electrodes incorporating NPOE, DOS, and DDP as plasticizers. They exhibited practical linear ranges of 9.1 x 10(-3) - 10(-6), 9.1 x 10(-3) - 10(-6) and 9.1 x 10(-3) - 10(-7) M, respectively. It works in the sub-micro scale of atropine concentrations. The optimum pH-range was 3.18 - 8.97. The selectivity coefficient values were estimated for different organic and inorganic cations. They were interpreted by using the "Relative Selectivity Concept", which was introduced for the first time. The new concept was applied for comparing the selectivity properties of previously reported electrodes. The effect of the presence of ephedrine, caffeine, glucose, Na(+), Ca(2+), and Mg(2+) on the calibration graphs of the electrodes was studied.     

Electrochemical methods for simultaneous determination of trace amounts of dopamine and uric acid using a carbon paste electrode incorporated with multi-wall carbon nanotubes and modified with α-cyclodextrine

In this work, we investigate the electrochemical activity of dopamine (DA) and uric acid (UA) using both a bare and a modified carbon paste electrode as the working electrode, with a platinum wire as the counter electrode and a silver/silver chloride (Ag/AgCl) as the reference electrode. The modified carbon paste electrode consists of multi-walled carbon nanotubes (>95%) treated with α-cyclodextrine, resulting in an electrode that exhibits a significant catalytic effect toward the electro-chemical oxidation of DA in a 0.2-M Britton–Robinson buffer solution (pH 5.0). The peak current increases linearly with the DA concentration within the molar concentration ranges of 2.0 × 10⁻⁶ to 5.0 × 10⁻⁵ M and 5.0 × 10⁻⁵ to 1.9 × 10⁻⁴ M. The detection limit (signal to noise >3) for DA was found to be 1.34 × 10⁻⁷ M, respectively. In this work, voltammetric methods such as cyclic voltammetry, chronoamperometry, chronocuolometry, differential pulse and square wave voltammetry, and linear sweep and hydrodynamic voltammetry were used. Cyclic voltammetry was used to investigate the redox properties of the modified electrode at various scan rates. The diffusion coefficient (D, cm² s⁻¹ = 3.05 × 10⁻⁵) and the kinetic parameters such as the electron transfer coefficient (α = 0.51) and the rate constant (k, cm³ mol⁻¹ s⁻¹ = 1.8 × 10³) for DA were determined using electrochemical approaches. By using differential pulse voltammetry for simultaneous measurements, we obtained two peaks for DA and UA in the same solution, with the peak separation approximately 136 mV. The average recovery was measured at 102.45% for DA injection.     

Synthesis and anticancer activity of some new pyridine derivatives

Different substituents were introduced in positions 2 and 6 of 2,6 diaminopyridine in order to obtain new heterocyclic compounds. A new series of aza pyridine, imidazopyridine, benzodiazepine, indole, pyrimidine, and benzimidazole heterocyclic derivatives were synthesized in good yields. The anticancer activities of some of the new compounds were evaluated against liver cancer cell line HEPG2. Compounds 3, 4, 10, 11, 12, and 17 showed the highest activity when compared to 5-flurouracil (5-FU) and doxorubicin (DOX) chemotherapy.     

Fe3O4@SiO2‐imid‐PMAn Magnetic Porous Nanosphere as Reusable Catalyst for Synthesis of Polysubstituted Quinolines under Solvent‐free Conditions

In this research, a facile one‐pot synthesis of poly‐substituted quinoline derivatives has been demonstrated by using 2‐aminobenzophenones and ethylacetoacetate or ketones in the presence of Fe₃O₄@SiO₂‐imid‐PMAⁿ and Fe₃O₄@SiO₂‐imid‐PMA^b nanoparticles as green and reusable catalysts under solvent‐free conditions. The reaction proceeds efficiently in excellent yields and in a state of excellent purity. The nanocatalysts can be recycled and reused for at least four times without noticeably decreasing in catalytic activity.     

Hydrodynamic Characteristics and Adsorption Particularity of Nanobiological Feedstock Along the Bed Height in a Novel Chromatography Column

Expanded bed adsorption (EBA) is a practical method for the separation of nanoparticulates. In order to analysis the local hydrodynamic and adsorption behavior of nanoparticle (NP)-based biological feedstock, a modified Nano Biotechnology Group EBA column with a 26-mm inner diameter was used to withdraw liquid from different axial positions of the column. Fabricated egg albumin (EA) NPs with an average size of 70 nm were employed as a model system and viral size/charge mimic to assess the relationship between hydrodynamic and adsorption performance of NPs at the different column regions. The effects of influential factors, including flow velocity and initial concentration of NPs, on NP hydrodynamic behavior and adsorption kinetics along the bed height were investigated. NP hydrodynamic studies confirmed that non-uniform behavior dominated the system and a decreasing trend of liquid mixing/dispersion with increase of bed height was observed in this column. The results demonstrated an increase in the mixing/dispersion at certain bed heights with the increase in both the velocity and feed initial concentration. Breakthrough curves were measured at various column points to determine the adsorption performance [dynamic binding capacity (DBC) and yield] in different bed positions/zones. Yield and DBC of NPs were improved along the bed height, whereas liquid velocity had the opposite effect. Increasing the initial concentration of NPs enhanced only the DBC. Separation of EA NPs under optimal conditions was 87 %, which is an excellent result for a one-pass frontal chromatography method.

     

A nanostructured ion-imprinted polymer for the selective extraction and preconcentration of ultra-trace quantities of nickel ions

We describe a nanostructured ion-imprinted polymer (IIP) for the selective preconcentration of Ni(II) ions. It was obtained by bulk polymerization from 2-vinylpyridine (the functional monomer), ethylene glycol dimethacrylate (the cross-linker), 2,2′-azobisisobutyronitrile (the initiator), alizarin red S (the nickel-binding ligand), and nickel (the template ion) in acetonitrile solution. The IIP particles were characterized by elemental analysis, X-ray diffraction, Fourier transform IR spectroscopy, thermogravimetric and differential thermal analysis, and by scanning electron microscopy. Imprinted Ni(II) ions were removed from the polymeric structure using 5 % HCl as the eluting solvent. The material is capable of selectively binding Ni(II) from solutions at pH values between (pH 8.0 being best). Both the sorption and desorption process occur within 5 min. The maximum sorbent capacity of the ion imprinted polymer is 73 mg g^?1. Following desorption, Ni(II) was determined by FAAS, with relative standard deviation and limit of detection of 3.4 % and 0.15 ng mL^?1, respectively. The method was applied to the determination of nickel in certified reference materials (soil and polymetallic gold ore), fish, vegetables, river sediments, and river water.

Tetravalent arc-transitive graphs of order twice a product of two primes

In this article a complete classification of tetravalent arc-transitive graphs of order twice a product of two primes is given.     

Cayley’s hyperdeterminant: A combinatorial approach via representation theory

Cayley’s hyperdeterminant is a homogeneous polynomial of degree 4 in the 8 entries of a $2\times 2\times 2$ array. It is the simplest (nonconstant) polynomial which is invariant under changes of basis in three directions. We use elementary facts about representations of the 3-dimensional simple Lie algebra $\mathfrak{s}{l}_2(\mathbb{C})$ to reduce the problem of finding the invariant polynomials for a $2\times 2\times 2$ array to a combinatorial problem on the enumeration of $2\times 2\times 2$ arrays with non-negative integer entries. We then apply results from linear algebra to obtain a new proof that Cayley’s hyperdeterminant generates all the invariants. In the last section we discuss the application of our methods to general multidimensional arrays.