Identification of Natural Products as Potential Pharmacological Chaperones for Protein Misfolding Diseases

Defective protein folding and accumulation of misfolded proteins is associated with neurodegenerative, cardiovascular, secretory, and metabolic disorders. Efforts are being made to identify small-molecule modulators or structural-correctors for conformationally destabilized proteins implicated in various protein aggregation diseases. Using a metastable-reporter-based primary screen, we evaluated pharmacological chaperone activity of a diverse class of natural products. We found that a flavonoid glycoside ( C-10 , chrysoeriol-7-O-β-D-glucopyranoside) stabilizes metastable proteins, prevents its aggregation, and remodels the oligomers into protease-sensitive species. Data was corroborated with additional secondary screen with disease-specific pathogenic protein. In vitro and cell-based experiments showed that C-10 inhibits α-synuclein aggregation which is implicated in synucleinopathies-related neurodegeneration. C-10 interferes in its structural transition into β-sheeted fibrils and mitigates α-synuclein aggregation-associated cytotoxic effects. Computational modeling suggests that C-10 binds to unique sites in α-synuclein which may interfere in its aggregation amplification. These findings open an avenue for comprehensive SAR development for flavonoid glycosides as pharmacological chaperones for metastable and aggregation-prone proteins implicated in protein conformational diseases.     

Remote sensing and GIS for locating favourable zones of lead-zinc-copper mineralization in Rajpura-Dariba area,Rajasthan, India

This paper reports the results of a pilot study carried out in RajpuraDariba area, Rajasthan, for locating favourable zones of lead-zinc-copper (Pb-Zn-Cu) mineralization using remote sensing, Geographical Information System (GIS) and geostatistical modelling techniques. Remotely sensed data, both aerial and satellite, were used to update the existing geological map. ATLAS GIS software and multivariate geostatistical techniques were used to analyse and integrate different types of geological and geophysical datasets. The Favourability Index (FI) maps prepared during this study show the occurrence of three favourable zones for Pb-Zn-Cu mineralization. They are: (i) around and north of Rawan ka Khera; (ii) isolated spots between Ruppura and Bhupalsagar; and (iii) north of Dhani. Selective geochemical sampling and resistivity profiling carried out in these favourable zones indicated the presence of geochemical anomalies (anomalous concentrations of Zn and Cu) and low/moderate resistivity zones, respectively. Recent drilling carried out by the Department of Mines and Geology (DMG), Rajasthan, at about 2.5 km north of Rawan ka Khera (one of the predicted favourable zones) indicated evidence of Cu mineralization at a depth of about 70 m.     

Synthesis,Structural, and Magnetic Properties of Nanocrystalline Ti 0.95Co0.05O2-Diluted Magnetic Semiconductors

With a view to investigate the influence of nanometric size on the structural, surface, and magnetic properties of nanocrystalline Ti_0.95Co_0.05O₂-diluted magnetic semiconductors, prepared by a novel simple controllable peroxide-assisted reflux chemical route followed by annealing at different temperatures, a systematic investigation has been undertaken. Structural characterizations such as X-ray diffraction followed by Rietveld refinement, electron diffraction pattern, Fourier transform infrared, Raman scattering, and X-ray photoelectron spectroscopy (XPS) measurements have shown anatase phase formation in nanocrystalline Ti_0.95Co_0.05O₂ without any additional impurity phases. The modified reflux chemical route was effective in obtaining pure phase Ti_0.95Co_0.05O₂ nanoparticles. Surface morphological investigations by using transmission electron microscopy and atomic force microscopy measurements showed the predominant effect of random distribution of nanoparticles on the aggregation behavior and local microstructural changes. The deconvoluted XPS core level Co 2p spectral study manifested the oxidation state of Co as + 2 and is found to be stable with varying particle size and annealing temperature. The ferromagnetic behavior was investigated by vibrating sample magnetometer, magnetic force microscopy, and electron spin resonance measurements. These magnetization studies showed all the samples are ferromagnetic at room temperature without any magnetic clusters. The correlation between structure, surface condition of the nanoparticles and local electronic interactions, and magnetization of the samples was analyzed and explored the origin of ferromagnetism.     

Specialty Fats Enriched with Behenic and Medium Chain Fatty Acids from Palm Stearin by Lipase Acidolysis

Structured lipids containing behenic and medium chain (MC) fatty acids were prepared from palm stearin using 1,3-specific lipase-catalyzed acidolysis. Incorporation of MC and behenic acids was affected by proportion of substrate, type of fatty acids, reaction time, addition of water and quantity of lipase. It was found that incorporation of caproic acid was less compared to other longer chain fatty acids. Caprylic, capric and behenic acids shared similar incorporation (up to 32 %), which increased with the amount of fatty acids added and the time of reaction. The incorporation of these acids increased with addition of 1 % moisture and the increasing amount of enzyme from 5 to 10 % at the beginning of the reaction. Incorporating behenic and MC fatty acids, reduced palmitic and oleic acids considerably from palm stearin, the extent being the same as those incorporated. However, the reduction of linoleic acid was marginal. The solid fats content of the modified palm stearin containing MC and behenic acids were reduced at all temperatures due to a reduction in higher molecular weight triglycerides and an increasing proportion of lower chain triglycerides. The modified products of palm stearin with added capric and behenic acids were similar to commercial bakery shortenings and those with added capric acid were like salad or cooking oils or butter in melting characteristics.     

Optimization of tensile properties thermoplastic blends from soy and biodegradable polyesters: Taguchi design of experiments approach

Soy meal-based biodegradable blends were prepared by melt extrusion process. The effects of denaturants, i.e., urea and sodium sulfite and plasticizer (glycerol) and polyester type (polybutylene succinate, polycaprolactone, polybutylene adipate terephthalate) on tensile strength and elongation at break were investigated using a Taguchi experimental design approach. The results showed that the sodium sulfite had little or no effect on final properties of the blends. Also, biodegradable polyester type had significant effect on the tensile strength and elongation at break of the blends prepared. The predicted values and experimental were found to be in tune with each other. The chemical structure and morphology of the optimum sample was probed by FT-IR spectroscopy and scanning electron microscopy (SEM). Also, the results provided an insight into how important the plasticization and destructurization of soy protein to obtain the blends with desired mechanical properties.     

Influence of Grain Boundary Complexion on Deformation Mechanism of High Temperature Bending Creep Process of Cu Bicrystal

Despite of substantial advancement, the effect of grain boundary (GB) complexions on high temperature creep deformation process has not been fully understood. In this paper, we have studied the high temperature bending creep deformation of copper bicrystal with various GB complexions under different loads using molecular dynamics simulation. It has been found that specimen with normal kite GB complexion have better creep resistance properties when subjected to comparatively lower applied load. In case of monolayer Zr segregation, a drastic decrease in creep strength as well as creep plasticity is observed due to inhibition of GB migration. On the other hand, deviation between creep properties for specimen with split-kite GB complexion and split-kite bilayer Zr segregation GB complexion is minimal. Enhanced creep plasticity is observed in case of split-kite bilayer Zr segregation GB complexion, which is due to formation of interpenetrating icosahedral clusters in the necking region. Fracture in specimen with monolayer Zr segregation GB complexion has occurred by means of slip phenomenon at lower deformation load whereas amorphization and necking is observed at higher deformation load. In case of specimen with bilayer Zr segregation GB complexion, it is found that fracture has occurred through amorphization and necking at all deformation loads due to higher GB thickness.