The major enzyme responsible for the hydrolytic breakdown of the neurotransmitter acetylcholine (ACh) is acetylcholinesterase (AChE). Acetylcholinesterase inhibitors (AChEIs) are the most prescribed ...class of medications for the treatment of Alzheimer's disease (AD) and dementia. The limitations of available therapy, like side effects, drug tolerance, and inefficacy in halting disease progression, drive the need for better, more efficacious, and safer drugs. In this study, a series of fourteen novel chalcone-coumarin derivatives (8a-n) were designed, synthesized and characterized by spectral techniques like FT-IR, NMR, and HR-MS. Subsequently, the synthesized compounds were tested for their ability to inhibit acetylcholinesterase (AChE) activity by Ellman's method. All tested compounds showed AChE inhibition with IC
50
value ranging from 0.201 ± 0.008 to 1.047 ± 0.043 μM. Hybrid 8d having chloro substitution on ring-B of the chalcone scaffold showed relatively better potency, with IC
50
value of 0.201 ± 0.008 μM compared to other members of the series. The reference drug, galantamine, exhibited an IC
50
at 1.142 ± 0.027 μM. Computational studies revealed that designed compounds bind to the peripheral anionic site (PAS), the catalytic active site (CAS), and the mid-gorge site of AChE. Putative binding modes, ligand-enzyme interactions, and stability of the best active compound are studied using molecular docking, followed by molecular dynamics (MD) simulations. The cytotoxicity of the synthesised derivatives was determined using the MTT test at three concentrations (100 g/mL, 500 g/mL, and 1 mg/mL). None of the chemicals had a significant effect on the body at the highest dose of 1 mg/mL.
Communicated by Ramaswamy H. Sarma
Cowpea aphid, Aphis craccivora Koch is one of the important pests of legumes. It is a cosmopolitan and polyphagous pest causing 30-35% damage to vegetable crops globally. Chemical control of this ...pest is not only expensive but also has deleterious effects on human health, environment and non-target organisms. Biological control is one of the most important components of integrated pest management to achieve eco-friendly and sustainable management of crop pests. Coccinellid predator, Coccinella transversalis Fab. is an efficient predator known for its appetite on cowpea aphid under vegetable ecosystem. With this background, we conducted a study on biology, morphometric and functional response of C. transversalis on cowpea aphid under laboratory conditions (27±1°C and 65±5% RH) at Biological Control Lab, ICAR-Indian Agricultural Research Institute, New Delhi, during 2016-17. Type of functional response was determined through polynomial logistic regression of proportion of prey consumption to the density of prey. Functional response parameters were obtained by fitting the data to the Holling's and Roger's equations. Total life span of male and female was ranged from 47-64 and 60-71 days, with a mean of 56±6.2 and 66±3.9 days, respectively. Both male and female of C. transversalis were found to exhibit Type II functional response. Female has showed high attack rate (1.99±0.141) compared to male (1.90±0.088) with maximum prey consumption of 84.41 and 80.51 aphids/day, respectively. Handling time obtained for males (0.0124 day) was higher than females (0.0118 day).
Background
The long‐term consequences of adolescent alcohol abuse that persist into adulthood are poorly understood and have not been widely investigated. We have shown that intermittent exposure to ...alcohol during adolescence decreased the amplitude of GABAA receptor (GABAAR)‐mediated tonic currents in hippocampal dentate granule cells in adulthood. The aim of this study was to investigate the enduring effects of chronic intermittent alcohol exposure during adolescence or adulthood on the expression of hippocampal GABAARs.
Methods
We used a previously characterized tissue fractionation method to isolate detergent resistant membranes and soluble fractions, followed by Western blots to measure GABAAR protein expression. We also measured mRNA levels of GABAAR subunits using quantitative real‐time polymerase chain reaction.
Results
Although the protein levels of α1‐, α4‐, and δ‐GABAAR subunits remained stable between postnatal day (PD) 30 (early adolescence) and PD71 (adulthood), the α5‐GABAAR subunit was reduced across that period. In rats that were subjected to adolescent intermittent ethanol (AIE) exposure between PD30 and PD46, there was a significant reduction in the protein levels of the δ‐GABAAR, in the absence of any changes in mRNA levels, at 48 hours and 26 days after the last ethanol (EtOH) exposure. Protein levels of the α4‐GABAAR subunit were significantly reduced, but mRNA levels were increased, 26 days (but not 48 hours) after the last AIE exposure. Protein levels of α5‐GABAAR were not changed by AIE, but mRNA levels were reduced at 48 hours but normalized 26 days after AIE. In contrast to the effects of AIE, chronic intermittent ethanol (CIE) exposure during adulthood had no effect on expression of any of the GABAAR subunits examined.
Conclusions
AIE produced both short‐ and long‐term alterations of GABAAR subunits mRNA and protein expression in the hippocampus, whereas CIE produced no long‐lasting effects on those measures. The observed reduction of protein levels of the δ‐GABAAR, specifically, is consistent with previously reported altered hippocampal GABAAR‐mediated electrophysiological responses after AIE. The absence of effects of CIE underscores the emerging view of adolescence as a time of distinctive vulnerability to the enduring effects of repeated EtOH exposure.
Recently there has been a surge of interest in adopting deep neural networks (DNNs) for solving the optimal power flow (OPF) problem in power systems. Computing optimal generation dispatch decisions ...using a trained DNN takes significantly less time when compared to conventional optimization solvers. However, a major drawback of existing work is that the machine learning models are trained for a specific system topology. Hence, the DNN predictions are only useful as long as the system topology remains unchanged. Changes to the system topology (initiated by the system operator) would require retraining the DNN, which incurs significant training overhead and requires an extensive amount of training data (corresponding to the new system topology). To overcome this drawback, we propose a DNN-based OPF predictor that is trained using a meta-learning (MTL) approach. The key idea behind this approach is to find a common initialization vector that enables fast training for any system topology. The developed OPF-predictor is validated through simulations using benchmark IEEE bus systems. The results show that the MTL approach achieves significant training speed-ups and requires only a few gradient steps with a few data samples to achieve high OPF prediction accuracy and outperforms other pretraining techniques.
This paper develops a hybrid genetic algorithm for production and distribution problems in multi-factory supply chain models. Supply chain problems usually may involve multi-criterion ...decision-making, for example operating cost, service level, resources utilization, etc. These criteria are numerous and interrelated. To organize them, analytic hierarchy process (AHP) will be utilized. It provides a systematic approach for decision makers to assign weightings and relate them. Meanwhile, genetic algorithms (GAs) will be utilized to determine jobs allocation into suitable production plants. Genetic operators adopted to improve the genetic search algorithm will be introduced and discussed. Finally, a hypothetical production–distribution problem will be solved by the proposed algorithm. The optimization results show that it is reliable and robust.
multocida contain various surface-associated antigens that could be used as a target for both therapeutics as well as diagnostics. The current study was planned to select ligands using Ph.D.-12 phage ...display library. This library was amplified and subjected to the alternate selection/subtraction methodology of biopanning using the suspension method in which alternate rounds of positive selection against P. multocida and negative selection against Haemophilus influenzae and Actinobacillus lignieresii were performed. After completing biopanning, out of 48 selected phages, 16 clonal phages were selected for indirect phage ELISA to check their binding efficiency with P. multocida. Out of these 16, five clonal phages bound their target with high intensity giving higher OD values at 450 nm and their binding efficiency was compared with closely related Actinobacillus lignieresii and Hemophilus influenzae using 107 pfu/ml at 450 nm wavelength which was found to be less against these bacteria.
An increasing cost of production, declining factor productivity and sustainability in rice–wheat cropping system are forcing the Indian farmers to shift from conventional tillage (CT) practice to ...conservational tillage (CA) practice for crop cultivation. With all the numerous advantage of CA practice, weed is a major concern restricting the farm productivity and profitability. To evaluate various tillage and weed management practices in rice–wheat cropping system of Central India, a study was carried out at farmers field. An integrated approach of weed management with
Sesbania
co-culture with rice followed by tank-mix application of bispyribac-Na + 2,4-
d
effectively reduced the total weed density and dry biomass accumulation and simultaneously increased the rice grain yield and farmers income, whereas, in case of wheat, as compared to CT practice, CA gave ~ 11% higher grain yield by restricting the growth of weeds. The weed density and dry weight were effectively diminished with pre-mix application of mesosulfuron + idosulfuron in wheat, and this pre-mix combination has also significantly increased the wheat grain yield over farmers practice. As compared to sole application, tank-mix or pre-mix application of different herbicides with varied target group of weeds controlled various weed species in a single application. The total system yield of rice–wheat cropping system with CA practice (6.27 t/ha) was higher as compared to CT practice (5.97 t/ha). The sustainable yield index, farmers profit and B:C ratio of the rice–wheat cropping system were in upper side by adopting the CA practice as compared to existing farmers (CT) practice.
A 35-year-old male bodybuilder was found to have a hepatocellular carcinoma (HCC) arising in a pre-existing hepatic adenoma following recreational anabolic steroid use. Given the widespread use of ...recreational anabolic steroids, another potentially life-threatening complication is highlighted in addition to the more commonly recognised hepatic adenoma. Malignant transformation to HCC from a pre-existing hepatic adenoma confirmed by immunohistochemical study has previously not been reported in athletes taking anabolic steroids. Further studies using screening programmes to identify high-risk individuals are recommended.
Damage to human skin due to ultraviolet light from the sun (photoaging) and damage occurring as a consequence of the passage of time (chronologic or natural aging) are considered to be distinct ...entities. Photoaging is caused in part by damage to skin connective tissue by increased elaboration of collagen-degrading matrix metalloproteinases, and by reduced collagen synthesis. As matrix metalloproteinase levels are known to rise in fibroblasts as a function of age, and as oxidant stress is believed to underlie changes associated with both photoaging and natural aging, we determined whether natural skin aging, like photoaging, gives rise to increased matrix metalloproteinases and reduced collagen synthesis. In addition, we determined whether topical vitamin A (retinol) could stimulate new collagen deposition in sun-protected aged skin, as it does in photoaged skin. Sun-protected skin samples were obtained from 72 individuals in four age groups: 18-29 y, 30-59 y, 60-79 y, and 80+ y. Histologic and cellular markers of connective tissue abnormalities were significantly elevated in the 60-79 y and 80+ y groups, compared with the two younger age groups. Increased matrix metalloproteinase levels and decreased collagen synthesis/expression were associated with this connective tissue damage. In a separate group of 53 individuals (80+ y of age), topical application of 1% vitamin A for 7 d increased fibroblast growth and collagen synthesis, and concomitantly reduced the levels of matrix-degrading matrix metalloproteinases. Our findings indicate that naturally aged, sun-protected skin and photoaged skin share important molecular features including connective tissue damage, elevated matrix metalloproteinase levels, and reduced collagen production. In addition, vitamin A treatment reduces matrix metalloproteinase expression and stimulates collagen synthesis in naturally aged, sun-protected skin, as it does in photoaged skin.
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