SCREENING OF COMPETITIVE INHIBITOR OF HEPARAN SULFATE IN JAPANESE ENCEPHALITIS

ABSTRACTObjective: Japanese encephalitis virus (JEV) causes central nervous system inflammatory disease Japanese encephalitis (JE), which is mainly causedin children below 15 years of age. On an estimate, there are around 3 billion people at the risk and the disease is continuously spreading globally. TheJEV belongs to Flavivirdiae family and has RNA genome. JEV envelope protein domain III (D-III) binds to the Heparan sulfate present on the cell surfaceand initiates the infection which causes the disease in children.Methods: The drug discovery and development process has become more quantitative and much more computational in recent years. In this study,comparative molecular docking studies of 200 zinc database compounds and Heparan sulfate were done with D-III of JEV using Autodock 4.2 and theresults were analyzed on the basis of binding energy, inhibition constant, and number of hydrogen bonds. The results were also analyzed by studyingthe absorption, distribution, metabolism, and excretion (ADME-T) properties of the compounds using admetSAR server.Results: Best three lead molecules zinc_8964844 zinc_8964845, zinc_12660861 were chosen based on the binding energy, inhibition constant andADME properties among a set of 200 ligands that can act as the competitive inhibitor of the Heparan sulfate, which presents on the surface of the hostcell and mediates the attachment and binding of the virus to the host cell.Conclusion: These compounds can act as the competitive inhibitor of the Heparan sulfate and they can be validated further as a drug for the treatment of JE.Keywords: Japanese encephalitis, Domain-III, Heparan sulfate, Autodock, Autodock, Absorption, Distribution, Metabolism, Excretion

IDENTIFICATION OF INHIBITORS OF DENGUE VIRUS (DENV1, DENV2 AND DENV3) NS2B/ NS3 SERINE PROTEASE: A MOLICULAR DOCKING AND SIMULATION APPROACH

 Dengue is one of the fatal diseases, which are becoming a global health burden from few decades. Dengue fever, dengue hemorrhagic fever anddengue shock syndrome, caused by dengue virus (DENV), which completes its life cycle in mosquito i.e. Aedes aegyti, and human (DENV), and infectabout various individuals every year. The objective of this study is to find a potent inhibitor of DENV (DENV1, DENV2 and DENV3). In the presentstudy, NS2b/NS3 serine protease complex in targeted for the screening of the suitable inhibitors for DENV (DENV1, DENV2 and DENV 3). Therefore,the NS2b/NS3 serine protease complex structures were retrieved from the RCSB Protein Databank. The unliganded protein structures were docked,and best three selected and analyzed. A molecular dynamic simulation is also performed to investigate the conformational and positional changesof ligand that provide insights into the binding stability. It was observed that three of screened compounds have the maximum potential against theprotein. The analysis was performed on the basis of scoring and binding ability and one of them indicated minimum energy score with high numberof interactions with active site residues and the simulation study revealed that this selected ligand could efficiently bind to the NS2b/NS3 protease.These findings conclude that this selected ligand could be a promising inhibitor of all three serotypes of DENV as drug targets.Keywords: Dengue virus, Aedes aegyti, Flaviviridae, Serine protease, Docking

Studies on variability, heritability and genetic advance for yield and yield contributing characters in french bean (Phaseolus vulgaris L.) germplasm under tarai region of Uttarakhand

Seventy four French bean germplasms were evaluated for twenty two quantitative traits to study the genetic variability, heritability and genetic advance during Jan-Feb in G.B. Pant University of Agriculture and Technology, Pantnagar. Significant differences were observed among all genotypes. Higher genotypic and phenotypic coefficient of variability were observed for plant height, seed yield per plant, pod yield per plant, pod yield per hectare, number of pods per cluster, number of pods per plant and 100 seed weight (42.45% and 43.30%, 39.72% and 42.34%, 27.59% and 32.12%, 27.59% and 32.12%, 25.01% and 28.14%, 24.56% and 26.76% and 22.65% and 22.96% respectively). High heritability coupled with high genetic advance over mean were observed for plant height, seed yield per plant, pod yield per plant, pod yield per hectare, number of pods per plant, 100 seed weight, number of pods per cluster, leaf length, single pod weight, pod diameter, pod length, number of pod clusters per plant, leaf width, seed length, number of seeds per pod and seed width (96.34% and 85.73%, 88.03% and 76.77%, 73.80% and 48.83%, 73.80% and 48.83%, 84.20% and 46.42%, 97.34% and 46.04%, 45.78% and 78.96%, 38.88% and 89.58%, 38.21% and 92.70%, 92.69% and 35.45%, 90.13% and 34.48%, 32.47% and 79.39%, 28.03% and 79.60%, 26.92% and 99.04%, 56.27% and 24.85%, and 97.82% and 24.01% respectively) indicate predominance additive gene action. Thus, there is ample scope for improving these characters through direct selection

A study of thrombocytopenia in malaria and its prognostic significance

Background:Malaria is one of the most common infectious diseases of tropics, affecting 300-500 million people and causing over 1 million deaths each year in the world. Malaria is a multisystem infection and can be associated with many complications. Thrombocytopenia is the most common hematological complication of malaria, but association of thrombocytopenia with different types of malaria and its prognostic implications in context with severity of low platelet count has not been evaluated in many of previous studies. Objectives of the study was to study the incidence, correlation of severity and prognostic significance of thrombocytopenia in malaria.Methods: A total of 100 cases were included in the study and identified positive for malaria parasites on peripheral smear examination with conventional microscopy and /or by rapid diagnostic test.Results: Present study includes 100 patient with malaria from which 78% were males and 22% were females. Most of the patients were suffering from P. vivax malaria (65%), and rest suffered from P. falciparum malaria (32%) and mixed infection (03%). Incidence of thrombocytopenia was 79%, of which mild, moderate and severe thrombocytopenia was 35.44%, 41.77% and 22.78% respectively. Complicated and uncomplicated malaria cases were 22.79% and 77.21% respectively.Conclusion: Clinical bleeding in severe malaria is not a common feature and occurred in 5.5% of individuals with severe disease. Unnecessary platelet transfusion is not required for mild to moderate degree of thrombocytopenia in malaria patients which further avoids an unnecessary cost burden in the poor group of patients.

A Comparative Study of Architecture and Quality of Sleep among Juvenile Myoclonic Epilepsy Patients and Healthy Individuals Attending Tertiary Care Hospital in Central India

Background and Objective: Primary sleep disorders are common in patients with epilepsy. Seizures, epileptiform discharges, and antiepileptic drugs alter the sleep architecture of patients with juvenile myoclonic epilepsy (JME). We evaluated sleep architecture and its quality in these patients. Materials and Methods: Thirty patients with JME (11 men and 19 women with mean age of 21.10 ± 4.55 years) and 30 healthy controls underwent overnight polysomnography (PSG). Sleep quality and daytime sleepiness were assessed using Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS), respectively. Results: Myoclonus and generalized tonic-clonic seizures (GTCS) were present in all patients with JME, while absence seizures were in 13.3%. Sleep deprivation was the most frequent precipitating factor for seizures (56.6%) followed by fatigue, sound, and photic stimulation. Patients with JME reported a statistically significant drop in sleep efficiency (P<0.001) with prolonged sleep onset latency (P<0.001). There was prolongation in the N1 stage of non-rapid eye movement (NREM) sleep (P=0.002), and reduction in the N2 stage of NREM (P<0.001) and rapid eye movement (REM) sleep (P<0.001). The median PSQI score was higher in patients with JME, suggesting poor sleep quality (P<0.001), and the daytime sleepiness was not different as indicated by the similar median ESS score (P=0.033). Conclusion: Our results suggest a significant alteration in the sleep architecture of patients with JME with reduced sleep efficiency and poor sleep quality. The possible role of the disease itself is suggested for these alterations as a simi-lar trend was also observed in drug naïve patients

Breeding tomato (Solanum lycopersicum L.) for resistance to biotic and abiotic stresses

Tomato (Solanum lycopersicum L.) is an important vegetable crop cultivated in the tropical and sub-tropical regions of the world. Low productivity in India is due to occurrence of both biotic and abiotic stresses. Among the biotic stresses, tomato leaf curl disease, bacterial wilt, early blight and Groundnut Bud Necrosis Virus disease have become serious production constraints causing considerable yield loss in the major tomato growing areas of the country. Adoption of multiple disease resistant varieties or F1 hybrids would be the most appropriate way to address these diseases. At ICAR-IIHR, Bengaluru systematic breeding strategies were employed to pyramid genes for resistance to early blight, bacterial wilt and tomato leaf curl diseases and to develop advanced breeding lines&amp; F1 hybrids with triple disease resistance. Stable source of resistance to early blight and bi-partite begomo-virus (Tomato Leaf Curl New Delhi Virus) has been identified in Solanum habrochaites LA-1777. Validation with molecular markers linked to tomato leaf curl virus resistance revealed that LA-1777 carryTy2 and other putative resistant genes. Several high yielding dual purpose hybrids were also developed for fresh market and processing with high level of resistance to multiple diseases. Cherry tomato lines have also been bred for high TSS, total carotenoids, total phenols, flavonoids, vitamin C, acidity and lycopene content. IIHR-249-1, IIHR-2101 (Solanum habrochaites LA-1777), IIHR- 2866 and IIHR-2864 recorded high values for quality parameters like total carotenoids, lycopene, vitamin C, total phenols, flavonoids and TSS. Drought tolerant root stock has been developed by an interspecific cross between S. habrochaites LA-1777 and S. lycopersicum (15 SB SB). Resistant sources have also been identified against Tuta absoluta, a serious insect pest reported from major tomato growing areas in the country in recent time. High temperature tolerant breeding lines are in pipe line

STEM CELLS: AN APPROACH FOR TREATMENT OF ATHEROSCLEROSIS

The contribution of stem cells to control atherosclerosis progression and vascular remodeling after injury in humans is established; however, many details are still unknown. The success with stem cell therapies in the treatment of hematological disorders over the past four decades enhanced our understanding of the physiology of vascular remodeling and motivated towards regenerative medicine and therapeutic restoration of the damaged organ. Stem cells isolated from bone marrow are currently being tested for their therapeutic potential in a variety of clinical conditions including cardiovascular injury, kidney failure, cancer, neurological, and bone disorders. The main focus of this review paper is to reveal the role of different types of stem cells such as embryonic stem cell, adult stem cell, smooth muscle progenitor cells, endothelial progenitor cells, mesenchymal stem cells, and vascular smooth muscle cells and find out possibility to use them for the treatment of atherosclerosis as well as to reduce atheroma formation

ESTIMATION OF MICROBIAL POPULATION IN SOME CONFECTIONARY PRODUCTS

ABSTRACT Microbial analysis is essential part of food safety. Confidence in the safety and integrity of the food supply is an important requirement for consumers. For the evaluation we used following confectionary items such as Dairy milk, Jam, Jelly, biscuit (Parle-G, Priya gold, and Britannia). For microbiological test all sample were used in triplate form. Specific media were used for identification of different microbes (Yeast, Mould, Bacteria). For the identification and microbial analysis TPC, PDA, Macconkey media were used and for confirmation of gram positive bacteria gram staining have done. Number of gram positive seen in jelly and Mould was seen in biscuit. Aim of our studies were compare specified confectionary product and find out the amount of microbes found in all confectionary products and also compare all on the basis of microbes presence in all confectionary products

VIRTUAL SCREENING AND ADMET ANALYSIS FOR IDENTIFICATION OF INHIBITORS AGAINST ACETYLCHOLINESTERASE ASSOCIATED WITH ALZHEIMER'S DISEASE

Objective: Alzheimer's disease a progressive neurodegenerative disorder characterized by oxidative stress, amyloid β deposition and due to low level of neurotransmitter acetylcholine in the brain. the reduction of acetylcholine in the brain is due to enhance activity of acetyl cholinesterase enzyme. This study is done to find out the possible inhibiters of acetyl cholinesterase. In lieu of that, the present study focus on to find possible analogs of known drug Rivastigmine. Methods: Protein for study is retrieved through protein databank (PDB ID - 1B41) and constrains was removed using Swiss-pdbviewer. Analogs for docking were chosen from zinc database and docking was performed using Autodock 4.2, after docking ADME analysis and toxicity were done against the possible inhibitors. Results: Out of fifty analogs chosen for docking only nine analogs showed minimum binding energy and good RMS value, out of that analogs two with id ZINC00004413 and ZINC967938 shows good results so they were chosen for ADME analysis and toxicity prediction. Conclusion: The possible analogs obtained after study can be further used for study and preparation of novel drug against Alzheimer's disease

Influence of Organic Manure and Inorganic Fertilizers on Growth and Yield of Radish (Raphanus sativus L.) in Gird Region of Madhya Pradesh, India

A field experiment was conducted to study the effect of organic manure and inorganic fertilizers on growth and yield of Radish (Raphanus sativus L.) in Grid region of Madhya Pradesh as factorial based on the randomized block design(RBD) with three replication and&nbsp; Ten treatments viz., T1-(100% NPK through inorganic sources), T2-(100% NPK through Farm Yard manure (16t/ha)), T3-(100% NPK through Vermicompost (12t/ha)), T4-(100% NPK through Poultry Manure (9.48t/ha)), T5-(75% NPK+25%N through FYM), T6-(75% NPK+25% N through Vermicompost), T7-(75% NPK+25% N through Poultry manure), T8-(50% NPK+50% N through FYM), T9-(50% NPK+50% N through Vermicompost), T10-(50% NPK+50% N through Poultry manure) were made up of singlevariety Ivory white the experiment was planted in the CRC-II, School of agriculture, ITM University Gwalior. At all of the periodic crop growth phases except at 15 DAS, T6 showed significant plant height and leaf count increases across crop phases. T5, T6 had maximum heights; T3, T10 had minimum. T5, T6, T8 displayed the highest leaf counts; T1 the least. Leaf lengths followed a similar trend, with T8, T6 having the longest; T1 the shortest. Overall, T6 exhibited prominent growth in both height and leaf attributes, while T1 consistently showed the lowest values throughout all stages and measurements. The conventional practices T6 had significant positive influence on yield and yield attributing parameters, viz; root length (35.05cm), weight of whole plant (418.91g), initial fresh weight of roots (355.54g) but initial fresh weight of leaves (72.52g) in recorded in treatment T2, root diameter (50.61mm), girth of root (12.3cm), dry weight of leaves (13.49g) measured in T2, dry weight of root (102.19g), root yield per plot (21.33kg), root yield per hectare (319.98qha-1). Conclusion-: Economically the application of 75% NPK+25% N through vermicompost gave maximum net return (Rs. 262553.80) and BC ratio (3.94)