Role of Post-translational Modifications in Alzheimer's Disease

The global burden of Alzheimer's disease (AD) is growing. Valiant efforts to develop clinical candidates for treatment have continuously met with failure. Currently available palliative treatments are temporary and there is a constant need to search for reliable disease pathways, biomarkers and drug targets for developing diagnostic and therapeutic tools to address the unmet medical needs of AD. Challenges in drug-discovery efforts raise further questions about the strategies of current conventional diagnosis; drug design; and understanding of disease pathways, biomarkers and targets. In this context, post-translational modifications (PTMs) regulate protein trafficking, function and degradation, and their in-depth study plays a significant role in the identification of novel biomarkers and drug targets. Aberrant PTMs of disease-relevant proteins could trigger pathological pathways, leading to disease progression. Advancements in proteomics enable the generation of patterns or signatures of such modifications, and thus, provide a versatile platform to develop biomarkers based on PTMs. In addition, understanding and targeting the aberrant PTMs of various proteins provide viable avenues for addressing AD drug-discovery challenges. This review highlights numerous PTMs of proteins relevant to AD and provides an overview of their adverse effects on the protein structure, function and aggregation propensity that contribute to the disease pathology. A critical discussion offers suggestions of methods to develop PTM signatures and interfere with aberrant PTMs to develop viable diagnostic and therapeutic interventions in AD.     

Yield and Quality Characteristics of Rendered Chicken Oil for Biodiesel Production

Whole dead poultry birds obtained from commercial layer farms were assessed for fat in the whole carcass and then dry rendered in three different rendering regimens T₁, T₂ and T₃ (temperature = 120, 130 and 140 °C and shell pressure = 1, 2 and 3 kg/cm² respectively) and the effect on the yield and quality of the rendered chicken oil were studied. The overall fat percentage of the whole dead poultry carcass was 14.55 ± 0.17 % and the fat content of ‘greaves’ was 14.49 ± 0.38 %. In the dry batch rendering trials, the mean overall fat recovery was 24.46 ± 1.19, 26.78 ± 3.14 and 22.42 ± 2.32 % and the overall fat yield was 3.52 ± 1.72, 3.84 ± 0.44 and 3.22 ± 0.33 % of the carcass weight in T₁, T₂ and T₃ respectively. Solvent extraction of fat could recover 96.10 ± 0.14 % of fat from ‘greaves’ which was significantly higher than the mechanical centrifugation method. Among the quality characteristics of the rendered chicken oil (RCO), moisture content ranged from 0.61 % (T₂) to 1.09 % (T₁) and the mean specific gravity was 0.91 at 30 °C. The FFA values of RCO obtained from the T₃ rendering regimen were significantly (p < 0.05) higher than the FFA values of T₂ and T₁. The mean acid value, iodine number, peroxide value, saponification value and unsaponifiable matter present in RCO showed no significant difference. The fatty acid profile and calorific values were studied. The RCO was converted to biodiesel by transesterification and the physico-chemical properties of the biodiesel were studied and compared with the Indian biodiesel specification.     

Theoretical Investigation of Waste Heat Recovery from an IC Engine Using Vapor Absorption Refrigeration System and Thermoelectric Converter

This study proposes the preliminary simulation of a single cylinder spark ignition engine with waste heat recovery system. To harvest waste heat energy from the engine exhaust a thermoelectric generator coupled to a vapor absorption refrigeration (VAR) system was proposed in this simulation work. Parametric simulation of engine, thermoelectric generator and VAR using thermodynamic relations was carried out in MATLAB – Simulink software. An attempt has been made mathematically to integrate engine, thermoelectric generator and VAR system to study the effect of engine load, speed, equivalence ratio on thermoelectric output and coefficient of performance (COP) of a VAR system. In this study, the VAR system runs by taking heat energy from the exhaust gas and the electric power produced by a thermoelectric generator was utilized to run the pump of the refrigeration system. It was found that COP of the absorption refrigeration system depends on engine load, speed and air fuel equivalence ratio. The study also reveals that about 10% to 15% of the total exhaust energy can be harvested using this system.     

Changes in endocrine profile and reproductive organs during puberty in the male marmoset monkey (Callithrix jacchus)

Data on pubertal maturation in male marmoset, a model for human reproduction, are scant and conflicting. We collected data on novel parameters to characterize puberty. Twenty-five marmoset monkeys were assigned to five age groups by weeks (wk): 21 (pre-pubertal), 43 (onset of puberty), 52 (fully pubertal), 70 (mature), and 116 (fully adult). Serum and intratesticular testosterone and pituitary bioactive chorionic gonadotropin (bioCG) were measured. Testicular development was assessed by ultrasonography, histology, and flow cytometry. Three consecutive blood samples revealed extreme fluctuations in testosterone concentrations, suggesting an erratic secretion. Age-related changes in serum testosterone and pituitary bioCG concentrations were observed. Intratesticular androgens (ITAs) showed high fluctuations within groups at all ages and were high in some animals by 21 wk. Unexpectedly, no correlation between pituitary bioCG and serum testosterone or ITAs was found, but these parameters significantly correlated with testicular weight and volume. These observations were consistent a dependence on the testis growth on bioCG. Unfortunately, the low serum levels of bioCG were not measurable in this study. At 43 wk, the animals reached puberty. At 52 wk of age, animals attained maximum body and epididymal weights and qualitatively normal spermatogenesis, but testes continued growing, reaching a maximum of all parameters at 70 wk of age, without further major changes at the age of 116 wk. It is concluded that (1) gonadal activation is evident at wk 21, (2) the male marmoset reaches the pubertal threshold around 43 wk of age, attains qualitative parameters at 52 wk, matures further to sexual maturity at 70 wk, and (3) serum testosterone and ITAs are highly variable without any identifiable correlation with pituitary bioCG.     

Inhibition of lipase from rice (Oryza sativa) by diethyl-p-nitrophenyl phosphate

The inhibition of rice bran lipase (RBL) by diethyl-p-nitrophenyl phosphate was studied with reference to kinetics, nature of inhibition and also elucidate the effect of the inhibitor on the structure—function of the enzyme. Enzyme activity measurements shows that the inhibitor is more effective at 0.050 mM concentration of diethyl-p-nitrophenyl phosphate and the activity is 50% at this level of inhibitor concentration. The affinity of substrate for the enzyme was observed by the increase in the velocity of the reaction with increase in the substrate concentrations and double reciprocal plot indicates that the inhibition followed a competitive in nature and inhibition constant K _i is found to be 0.016 mM at pH 7.0. The decrease in apparent thermal denaturation temperature to 4 °C compared to control indicates the destabilization of enzyme in the presence of inhibitor. Fluorescence spectral measurements suggests that pronounced quenching of fluorescence intensity of RBL occurs at higher concentrations of diethyl-p-nitrophenyl phosphate and ‘K _a’ value was found to be 2.4 × 10⁴ M⁻¹ with free energy change ΔG^o—26 kJ/mol at 30 °C suggesting strong binding between the enzyme and the inhibitor with microenvironmental changes occur at the active site or in the neighbourhood of active site. The far UV-CD data suggest that there is no significant changes in the conformation of the enzyme as a result of binding of diethyl-p-nitrophenyl phosphate. These results indicate that diethyl-p-nitrophenyl phosphate is a inhibitor of RBL and binds to the enzyme in brining about inhibition without any structural alterations.     

Classical and Differential Thermal Analysis Studies of the Glass-Ceramic Transformation in a YSiAlON Glass

Nucleation and crystallization studies were conducted on a YSiAlON glass that contained 17 equiv.% nitrogen (7.5 at.%) by using a two-stage nucleation-and-growth treatment. Classical and differential thermal analysis (DTA) techniques were both used to study the crystallization process, to ensure that the optimum heat-treatment schedule that yielded a fine microstructure and minimum residual glass was applied. The optimum nucleation and crystallization temperatures were determined from DTA traces that were recorded from isothermal heat treatments at different nucleating temperatures, ranging between T _g - 40°C and T _g+ 100°C for 1 h and crystal-growth temperatures in the range of 1170°-1310°C for 0.5 h, respectively. The activation energy for the crystallization process was determined, based on the analysis of the variation of peak temperature at five different heating rates. Specimens heat treated in a tube furnace under nitrogen gas were subjected to microscopical investigation, and results showed variations in the volume fraction of crystalline phases and crystal size with nucleation temperature. The nucleation temperature, T _g+ 40°C (1025°C), which corresponded to the maximum volume fraction of crystalline phases and minimum crystal size, was consistent with the optimum nucleation temperature, T _g+ 35°C (1020°C), as determined from DTA. The time and temperature of nucleation and crystal growth dictated the nature and size of the crystalline phases. Properties such as hardness and density were assessed and correlated to the nucleation temperature. The influence of sample specific surface on the devitrification mechanisms was estimated, and bulk nucleation was observed to be the dominant nucleation mechanism.     

Synthesis,structural and luminescence properties of near white light emitting Dy-doped Y2CaZnO5 nanophosphor for solid state lighting

Novel near white light emitting Y₂CaZnO₅ (YCZ) nanocrystalline powders doped with Dy³⁺ ions were synthesized via the citrate gel combustion method. The structure of the compound is found to be triclinic with a particle size in the range of 20–30 nm. Luminescence properties have been characterized using photoluminescence (PL), excitation spectra and decay time measurements. The PL spectra have shown a broad blue band due to ⁴F_9/2→⁶H_15/2 transition and sharp yellow band corresponding to ⁴F_9/2→⁶H_13/2 transition of Dy³⁺ ions. From the concentration dependent PL studies, the optimum concentration of Dy³⁺ ions in YCZ is found to be 1.0 mol%, where intense near white light emission was observed. The Dy³⁺:YCZ nanophosphor has shown relatively better white color properties than the reported Dy³⁺:Y₂O₃ nanophosphor. The yellow to blue intensity ratios, CIE chromaticity coordinates and correlated color temperature studies have shown the possibility of using this compound for white light emission.     

A delay and energy aware coordination mechanism for WSAN

In this paper, a delay and energy aware coordination mechanism (DEACM) has been devised for wireless sensor–actor networks. In DEACM, a two‐level hierarchical K‐hop clustering mechanism is used to organize the sensors and actors for communication. In the first level, sensors form a K‐hop cluster using actors as cluster heads, and sink is made as the cluster head in the second level to form a cluster among actors. Sensor nodes, which are 1‐hop away from the actors, also called as relay nodes are elected as backup cluster head (BCH) based on the residual energy and node degree. BCH collects the data from sensors when an actor is away to perform actions in the affected area. The scheme is evaluated through exhaustive simulation in NS2 along with other existing schemes. Different parameters like average event waiting time, event reliability, and average energy dissipation are compared, varying the number of sensors, actors, and data transfer rate. In general, it is observed that the proposed DEACM outperforms other existing schemes. Copyright © 2016 John Wiley & Sons, Ltd.     

RESRES: The story behind the paper “Research in software engineering: An analysis of the literature”

This article is a background report describing a comprehensive study of research in the three computing disciplines Computer Science, Software Engineering, and Information Systems. Findings relate to research topics, approaches, methods, reference disciplines, and levels of analysis. The article informally describes the process used and the research products produced.