Kumar S

References (103)

Title : Lead Identification Through In Silico Studies: Targeting Acetylcholinesterase Enzyme Against Alzheimer's Disease - Agarwal_2024_Cent.Nerv.Syst.Agents.Med.Chem__
Author(s) : Agarwal D , Kumar S , Ambatwar R , Bhanwala N , Chandrakar L , Khatik G
Ref : Cent Nerv Syst Agents Med Chem , : , 2024
Abstract : AIM: In this work, we aimed to acquire the best potential small molecule for Alzheimer's disease (AD) treatment using different models in Biovia Discovery Studio to identify new potential inhibitors of acetylcholinesterase (AChE) via in silico studies. BACKGROUND: The prevalence of cognitive impairment-related neurodegenerative disorders, such as AD, has been observed to escalate rapidly. However, we still know little about the underlying functions, outcome predictors, or intervention targets causing AD. OBJECTIVE: The objective of the study was to optimize and identify the lead compound to target AChE against Alzheimer's disease. METHOD: Different in silico studies were employed, including the pharmacophore model, virtual screening, molecular docking, de novo evolution model, and molecular dynamics. RESULT: The pharmacophoric features of AChE inhibitors were determined by ligand-based pharmacophore models and 3D QSAR pharmacophore generation. Further validation of the best pharmacophore model was done using the cost analysis method, Fischer's randomization method, and test set. The molecules that harmonized the best pharmacophore model with the estimated activity < 1 nM and ADMET parameters were filtered, and 12 molecules were subjected to molecular docking studies to obtain binding energy. 3vsp_EK8_1 secured the highest binding energy of 65.60 kcal/mol. Further optimization led to a 3v_Evo_4 molecule with a better binding energy of 70.17 kcal/mol. The molecule 3v_evo_4 was subjected to 100 ns molecular simulation compared to donepezil, which showed better stability at the binding site. CONCLUSION: A lead compound, 3v_Evo_4 molecule, was identified to inhibit AChE, and it could be further studied to develop as a drug with better efficacy than the existing available drugs for treating AD.
ESTHER : Agarwal_2024_Cent.Nerv.Syst.Agents.Med.Chem__
PubMedSearch : Agarwal_2024_Cent.Nerv.Syst.Agents.Med.Chem__
PubMedID: 38288823

Title : Phylum-level studies of bacterial cutinases for unravelling enzymatic specificity toward PET degradation: an in silico approach - Kumar_2024_Braz.J.Microbiol__
Author(s) : Kumar S , Chaudhary B , Singhal B
Ref : Braz J Microbiol , : , 2024
Abstract : The overwhelming use of PET plastic in various day-to-day activities led to the voluminous increase in PET waste and growing environmental hazards. A plethora of methods have been used that are associated with secondary pollutants. Therefore, microbial degradation of PET provides a sustainable approach due to its versatile metabolic diversity and capacity. The present work highlights the cutinase enzyme's role in PET degradation. This study focuses on the bacterial cutinases homologs screened from 43 reported phylum of bacteria. The reported bacterial cutinases for plastic degradation have been chosen as reference sequences, and 917 sequences have shown homology across the bacterial phyla. The dienelactone hydrolase (DLH) domain was identified for attaining specificity towards PET binding in 196 of 917 sequences. Various computational tools have been used for the physicochemical characterization of 196 sequences. The analysis revealed that most selected sequences are hydrophilic, extracellular, and thermally stable. Based on this analysis, 17 sequences have been further pursued for three-dimensional structure prediction and validation. The molecular docking studies of 17 selected sequences revealed efficient PET binding with the three sequences derived from the phylum Bacteroidota, the lowest binding energy of -5.9 kcal/mol, Armatimonadota, and Nitrososphaerota with -5.8 kcal/mol. The two enzyme sequences retrieved from the phylum Bacteroidota and Armatimonadota are metagenomically derived. Therefore, the present studies concluded that there is a high probability of finding cutinase homologs in various environmental resources that can be further explored for PET degradation.
ESTHER : Kumar_2024_Braz.J.Microbiol__
PubMedSearch : Kumar_2024_Braz.J.Microbiol__
PubMedID: 38750346

Title : Acaricide resistance status of deltamethrin and coumaphos in Hyalomma anatolicum ticks collected from different districts of Haryana - Gupta_2024_Exp.Appl.Acarol__
Author(s) : Gupta S , Sangwan N , Sangwan AK , Kumar A , Maan S , Kumar S
Ref : Exp Appl Acarol , : , 2024
Abstract : To study the acaricide resistance status and possible mechanisms of action in conferring resistance to commonly used acaricides (deltamethrin and coumaphos), Hyalomma anatolicum ticks were collected from 6 dairy farms of Hisar and Charkhi Dadri districts of Haryana. By using standard larval packet test, H. anatolicum tick larvae of Charkhi Dadri isolates were found to be susceptible (100% mortality) to both the acaricides. Level-I resistance against coumaphos was recorded from four isolates, whereas, level-II was observed in only one isolate, collected from Hisar. One isolates (Kaimri) from Hisar also showed level-I resistance against deltamethrin. Biochemically, the ticks having higher values of resistance factor (RF) against coumaphos were found to possess increased enzymatic activity of alpha-esterase, beta-esterase, glutathione-S-transferase (GST) and mono-oxygenase enzymes, whereas, the monoamine oxidase did not show any constant trend. However, the RF showed a statistical significant correlation with GST only. Native PAGE analysis of H. anatolicum ticks revealed the presence of nine types of esterases (EST-1 h to EST-9 h) by using napthyl acetate as substrate. In the inhibitory assay, esterases were found to be inhibited by PMSF, indicating the presence of serine residue at catalytic triad. The partial cds of carboxylesterase and domain II of sodium channel genes were sequenced to determine any proposed mutations in resistant isolates of H. anatolicum ticks, however, no mutations were observed in either gene, indicating that increased expression of detoxification enzymes as a possible mechanism for resistance development, in the current study.
ESTHER : Gupta_2024_Exp.Appl.Acarol__
PubMedSearch : Gupta_2024_Exp.Appl.Acarol__
PubMedID: 38448756

Title : A Review of the Common Neurodegenerative Disorders: Current Therapeutic Approaches and the Potential Role of Bioactive Peptides - Singh_2024_Curr.Protein.Pept.Sci__
Author(s) : Singh K , Gupta JK , Kumar S , Soni U
Ref : Curr Protein Pept Sci , : , 2024
Abstract : Neurodegenerative disorders, which include Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS), represent a significant and growing global health challenge. Current therapies predominantly focus on symptom management rather than altering disease progression. In this review, we discuss the major therapeutic strategies in practice for these disorders, highlighting their limitations. For AD, the mainstay treatments are cholinesterase inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists. For PD, dopamine replacement therapies, including levodopa, are commonly used. HD is managed primarily with symptomatic treatments, and reusable extends survival in ALS. However, none of these therapies halts or substantially slows the neurodegenerative process. In contrast, this review highlights emerging research into bioactive peptides as potential therapeutic agents. These naturally occurring or synthetically designed molecules can interact with specific cellular targets, potentially modulating disease processes. Preclinical studies suggest that bioactive peptides may mitigate oxidative stress, inflammation, and protein misfolding, which are common pathological features in neurodegenerative diseases. Clinical trials using bioactive peptides for neurodegeneration are limited but show promising initial results. For instance, hemiacetal, a gamma-secretase inhibitor peptide, has shown potential in AD by reducing amyloid-beta production, though its development was discontinued due to side effects. Despite these advancements, many challenges remain, including identifying optimal peptides, confirming their mechanisms of action, and overcoming obstacles related to their delivery to the brain. Future research should prioritize the discovery and development of novel bioactive peptides and improve our understanding of their pharmacokinetics and pharmacodynamics. Ultimately, this approach may lead to more effective therapies for neurodegenerative disorders, moving beyond symptom management to potentially modify the course of these devastating diseases.
ESTHER : Singh_2024_Curr.Protein.Pept.Sci__
PubMedSearch : Singh_2024_Curr.Protein.Pept.Sci__
PubMedID: 38561605

Title : Understanding the resistance mechanisms of Rhipicephalus microplus ticks to synthetic pyrethroids and organophosphates in south-west regions of Haryana, North India - Gupta_2023_Pestic.Biochem.Physiol_196_105634
Author(s) : Gupta S , Sangwan N , Sangwan AK , Mann S , Kumar A , Kumar S
Ref : Pestic Biochem Physiol , 196 :105634 , 2023
Abstract : Chemical control of tick infestation on dairy farms in India strongly relies upon the use of synthetic pyrethroids (deltamethrin) and organophosphate (coumaphos) drugs. Therefore, the present manuscript aims to investigate the resistance status of Rhipicephalus microplus ticks against these acaricides. Fully engorged adult R. microplus ticks were randomly collected from 8 dairy farms in North India and evaluated for acaricide resistance by using the Larval Packet Test (LPT). Of these, ticks collected from one and three farms showed the emergence of Level I acaricide resistance against deltamethrin and coumaphos, respectively. Significant positive correlations were found in the enzymatic activity (alpha-esterase, beta-esterase, glutathione-S-transferase, and mono-oxygenase) of R. microplus tick resistant against coumaphos. Native electrophoretogram analysis showed six different types of esterase activity in R. microplus (EST-1b to EST-6b), and EST-5b activity was more predominantly expressed in resistant ticks. Further, inhibitor studies using various esterase inhibitors suggested that EST-5b is a putative acetylcholine-esterase (AchE), and increased expression of one of the AchE might be responsible for the emergence of acaricide resistance. Further, no mutations were detected in the carboxylesterase (G1120A) and domain II S4-5 linker region (C190A) of the sodium channel genes of resistant R. microplus ticks, indicating that increased expression of detoxification enzymes was the probable mechanism for the development of acaricide resistance in the resistant ticks.
ESTHER : Gupta_2023_Pestic.Biochem.Physiol_196_105634
PubMedSearch : Gupta_2023_Pestic.Biochem.Physiol_196_105634
PubMedID: 37945265

Title : Exploiting butyrylcholinesterase inhibitors through a combined 3-D pharmacophore modeling, QSAR, molecular docking, and molecular dynamics investigation - Kumar_2023_RSC.Adv_13_9513
Author(s) : Kumar S , Manoharan A , J J , Abdelgawad MA , Mahdi WA , Alshehri S , Ghoneim MM , Pappachen LK , Zachariah SM , Aneesh TP , Mathew B
Ref : RSC Adv , 13 :9513 , 2023
Abstract : Alzheimer's disease (AD), a neurodegenerative condition associated with ageing, can occur. AD gradually impairs memory and cognitive function, which leads to abnormal behavior, incapacity, and reliance. By 2050, there will likely be 100 million cases of AD in the world's population. Acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibition are significant components of AD treatment. This work developed models using the genetic method multiple linear regression, atom-based, field-based, and 3-D pharmacophore modelling. Due to internal and external validation, all of the models have solid statistical (R (2) > 0.81 and Q (2) > 0.77) underpinnings. From a pre-plated CNS library (6055), we discovered a hit compound using virtual screening on a QSAR model. Through molecular docking, additional hit compounds were investigated (XP mode). Finally, a molecular dynamics simulation revealed that the Molecule5093-4BDS complex was stable (100 ns). Finally, the expected ADME properties for the hit compounds (Molecule5093, Molecule1076, Molecule4412, Molecule1053, and Molecule3344) were found. According to the results of our investigation and the prospective hit compounds, BuChE inhibitors may be used as a treatment for AD.
ESTHER : Kumar_2023_RSC.Adv_13_9513
PubMedSearch : Kumar_2023_RSC.Adv_13_9513
PubMedID: 36968055

Title : Development of quinazolinone and vanillin acrylamide hybrids as multi-target directed ligands against Alzheimer's disease and mechanistic insights into their binding with acetylcholinesterase - Yelamanda_2023_J.Biomol.Struct.Dyn__1
Author(s) : Yelamanda Rao K , Jeelan Basha S , Monika K , Naidu Gajula N , Sivakumar I , Kumar S , Vadde R , Aramati BMR , Subramanyam R , Damu AG
Ref : J Biomol Struct Dyn , :1 , 2023
Abstract : In view of Multi-Target Directed Ligand (MTDL) approach in treating Alzheimer's Disease (AD), a series of novel quinazolinone and vanillin cyanoacetamide based acrylamide derivatives (9a-z) were designed, synthesized, and assessed for their activity against a panel of selected AD targets including acetylcholinesterase (AChE), butyrylcholinesterase (BChE), amyloid beta protein (Abeta), and also 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging and neuroprotective activities. Five of the target analogs 9e, 9h, 9 l, 9t and 9z showed elevated AChE inhibitory activity with IC(50) values of 1.058 +/- 0.06, 1.362 +/- 0.09, 1.434 +/- 0.10, 1.015 +/- 0.10, 1.035 +/- 0.02 microM respectively, high inhibition selectivity against AChE over BChE and good DPPH radical scavenging activity. Enzyme kinetic studies of the potent hybrids in the series disclosed their mixed inhibition approach. Active analogs were found to be non-toxic on SK-N-SH cell lines and have excellent neuroprotective effects against H(2)O(2)-induced cell death. Strong modulating affinities on Abeta aggregation process were observed for most active compounds since; they irretrievably interrupted the morphology of Abeta(42) fibrils, increased the aggregates and declined the Abeta-induced toxicity in neurons. From the fluorescence emission studies, the binding constants (K) were determined as 2.5 +/- 0.021x10(3), 2.7 +/- 0.015x10(3), 3.7 +/- 0.020x10(3), 2.4 +/- 0.013x10(4), and 5.0 +/- 0.033x10(3) M(-1) and binding free energies as -5.82 +/- 0.033, -6.07 +/- 0.042, -6.26 +/- 0.015, -7.71 +/- 0.024, and -6.29 +/- 0.026 kcal M(-1) for complexes of AChE-9e, 9h, 9 l, 9t and 9z, respectively. Moreover, the CD analysis inferred the limited modifications in the AChE secondary structure when it binds to 9e, 9h, 9 l, 9t and 9z. On the basis of docking studies against AChE, the most active congeners were well oriented in the enzyme's active site by interacting with both catalytic active site (CAS) and peripheral anionic site (PAS). In summary, these quinazolinone and vanillin acrylamide hybrid analogs can be used as promising molecular template to further explore their in vivo efficiency in the development of lead compound to treat AD.Communicated by Ramaswamy H. Sarma.
ESTHER : Yelamanda_2023_J.Biomol.Struct.Dyn__1
PubMedSearch : Yelamanda_2023_J.Biomol.Struct.Dyn__1
PubMedID: 37098803

Title : Quantifying PON1 on HDL with nanoparticle-gated electrokinetic membrane sensor for accurate cardiovascular risk assessment - Kumar_2023_Nat.Commun_14_557
Author(s) : Kumar S , Maniya N , Wang C , Senapati S , Chang HC
Ref : Nat Commun , 14 :557 , 2023
Abstract : Cardiovascular disease-related deaths (one-third of global deaths) can be reduced with a simple screening test for better biomarkers than the current lipid and lipoprotein profiles. We propose using a highly atheroprotective subset of HDL with colocalized PON1 (PON1-HDL) for superior cardiovascular risk assessment. However, direct quantification of HDL proteomic subclasses are complicated by the peroxides/antioxidants associated with HDL interfering with redox reactions in enzymatic calorimetric and electrochemical immunoassays. Hence, we developed an enzyme-free Nanoparticle-Gated Electrokinetic Membrane Sensor (NGEMS) platform for quantification of PON1-HDL in plasma within 60 min, with a sub-picomolar limit of detection, 3-4 log dynamic range and without needing sample pretreatment or individual-sample calibration. Using NGEMS, we report our study on human plasma PON1-HDL as a cardiovascular risk marker with AUC~0.99 significantly outperforming others (AUC~0.6-0.8), including cholesterol/triglycerides tests. Validation for a larger cohort can establish PON1-HDL as a biomarker that can potentially reshape cardiovascular landscape.
ESTHER : Kumar_2023_Nat.Commun_14_557
PubMedSearch : Kumar_2023_Nat.Commun_14_557
PubMedID: 36732521

Title : Chemical composition, pesticidal activities and in-silico investigation of Hedychium spicatum Sm. chloroform extract - Rawat_2023_An.Acad.Bras.Cienc_95_e20220964
Author(s) : Rawat A , Prakash OM , Nagarkoti K , Kumar R , Verma AK , Kumar S , Srivastava RM , Latwal M , Pandey G
Ref : An Acad Bras Cienc , 95 :e20220964 , 2023
Abstract : The present study aimed to identify the bioactive constituents in the chloroform extract of H. spicatum rhizomes (HS-RCLE), further evaluated for its in-vitro pesticidal activities validating via molecular docking techniques. GC/MS analysis of HS-RCLE identified 14 compounds contributing 84.1 % of the total composition. The extract was dominated by oxygenated sesquiterpenes (43.1 %) with curcumenone (25.2 %) and coronarin E (14.8 %) as the major compounds. The extract recorded 89.4 % egg hatchability inhibition and 82.6 % immobility of Meloidogyne incognita, 66.7 % insecticidal activity on Spodoptera litura, 100 % phytotoxic activity on Raphanus raphanistrum seeds, and 74.7 % anti-fungal activity on Curvularia lunata at the respective highest dose studied. The biological activities were furthermore validated by using docking studies on certain proteins/enzymes namely acetylcholinesterase (PBD ID: IC2O), carboxylesterase (PDB ID: 1CI8), acetohydroxyacid synthase (PBD ID: 1YHZ) and trihydroxy naphthalene reductase (PBD ID: 3HNR). The bioactivity of the major constituents of the extract was predicted with the help of in silico PASS studies. HS-RCLE was observed to be a viable alternative source of natural pesticidal agents and paves the way for further studies on its mechanistic approaches and field trials to ascertain its pesticidal studies.
ESTHER : Rawat_2023_An.Acad.Bras.Cienc_95_e20220964
PubMedSearch : Rawat_2023_An.Acad.Bras.Cienc_95_e20220964
PubMedID: 37466542

Title : Aducanumab in Alzheimer's disease: A critical update - Ashique_2023_Curr.Med.Chem__
Author(s) : Ashique S , Sirohi E , Kumar S , Rihan M , Mishra N , Bhatt S , Gautam RK , Singh SK , Gupta G , Chellappan DK , Dua K
Ref : Curr Med Chem , : , 2023
Abstract : Alzheimer's disease (AD) is a complex neurological disorder that results in cognitive decline. The incidence rates of AD have been increasing, particularly among individuals 60 years of age or older. In June 2021, the US FDA approved aducanumab, the first humanized monoclonal antibody, as a potential therapeutic option for AD. Clinical trials have shown this drug to effectively target the accumulation of Abeta (beta-amyloid) plaques in the brain, and its effectiveness is dependent on the dosage and duration of treatment. Additionally, aducanumab has been associated with improvements in cognitive function. Biogen, the pharmaceutical company responsible for developing and marketing aducanumab, has positioned it as a potential breakthrough for treating cerebral damage in AD. However, the drug has raised concerns due to its high cost, limitations, and potential side effects. AD is a progressive neurological condition that affects memory, cognitive function, and behaviour. It significantly impacts the quality of life of patients and caregivers and strains healthcare systems. Ongoing research focuses on developing disease-modifying therapies that can halt or slow down AD progression. The pathogenesis of AD involves various molecular cascades and signaling pathways. However, the formation of extracellular amyloid plaques is considered a critical mechanism driving the development and progression of the disease. Aducanumab, as a monoclonal antibody, has shown promising results in inhibiting amyloid plaque formation, which is the primary pathological feature of AD. This review explores the signaling pathways and molecular mechanisms through which aducanumab effectively prevents disease pathogenesis in AD.
ESTHER : Ashique_2023_Curr.Med.Chem__
PubMedSearch : Ashique_2023_Curr.Med.Chem__
PubMedID: 37497712

Title : Y12F mutation in Pseudomonas plecoglossicida S7 lipase enhances its thermal and pH stability for industrial applications: a combination of in silico and in vitro study - Choudhary_2023_World.J.Microbiol.Biotechnol_39_75
Author(s) : Choudhary P , Waseem M , Kumar S , Subbarao N , Srivastava S , Chakdar H
Ref : World J Microbiol Biotechnol , 39 :75 , 2023
Abstract : Appropriate amino acid substitutions are critical for protein engineering to redesign catalytic properties of industrially important enzymes like lipases. The present study aimed for improving the environmental stability of lipase from Pseudomonas plecoglossicida S7 through site-directed mutagenesis driven by computational studies. lipA gene was amplified and sequenced. Both wild type (WT) and mutant type (MT) lipase genes were expressed into the pET SUMO system. The expressed proteins were purified and characterized for pH and thermostability. The lipase gene belonged to subfamily I.1 lipase. Molecular dynamics revealed that Y12F-palmitic acid complex had a greater binding affinity (-6.3 Kcal/mol) than WT (-6.0 Kcal/mol) complex. Interestingly, MDS showed that the binding affinity of WT-complex (-130.314 +/- 15.11 KJ/mol) was more than mutant complex (-108.405 +/- 69.376 KJ/mol) with a marked increase in the electrostatic energy of mutant (-26.969 +/- 12.646 KJ/mol) as compared to WT (-15.082 +/- 13.802 KJ/mol). Y12F mutant yielded 1.27 folds increase in lipase activity at 55s degreesC as compared to the purified WT protein. Also, Y12F mutant showed increased activity (~ 1.2 folds each) at both pH 6 and 10. P. plecoglossicida S7. Y12F mutation altered the kinetic parameters of MT (K(m)- 1.38 mM, V(max)- 22.32 microM/min) as compared to WT (K(m)- 1.52 mM, V(max)- 29.76 microM/min) thus increasing the binding affinity of mutant lipase. Y12F mutant lipase with better pH and thermal stability can be used in biocatalysis.
ESTHER : Choudhary_2023_World.J.Microbiol.Biotechnol_39_75
PubMedSearch : Choudhary_2023_World.J.Microbiol.Biotechnol_39_75
PubMedID: 36637534
Gene_locus related to this paper: psef5-q4kj24

Title : Extraction, isolation, synthesis, and biological evaluation of novel piperic acid derivatives for the treatment of Alzheimer's disease - Kumar_2023_Mol.Divers__
Author(s) : Kumar J , Shankar G , Kumar S , Thomas J , Singh N , Srikrishna S , Satija J , Krishnamurthy S , Modi G , Mishra SK
Ref : Mol Divers , : , 2023
Abstract : In this paper, we developed a series of piperic acid (PA) analogs with the aim of overcoming the limitations associated with the natural products for the management of Alzheimer's disease (AD). A comprehensive SAR study was performed to enhance cholinesterase inhibition of PA. The acetylcholinesterase inhibition and its kinetic data suggested 6j as the lead molecule (AChE IC(50) = 2.13 +/- 0.015 microM, BChE = 28.19 +/- 0.20%), in comparison to PA (AChE = 7.14 +/- 0.98%) which was further selected for various biological studies in AD models. 6j, exhibited interaction with the peripheral anionic site of AChE, BBB permeability (Pe = 7.98), and antioxidant property (% radical scavenging activity = 35.41 +/- 1.09, 2.43 +/- 1.65, for 6j and PA at 20 M[Formula: see text], respectively). The result from the metal chelation study suggests that 6j did not effectively chelate iron. The molecular modeling studies suggested that 6j could effectively interact with Ser293, Phe295, Arg296, and Tyr34 of AChE. In the cell-based cytotoxicity studies, 6j exhibited cytocompatibility at the different tested concentrations. The acute toxicity data on mice suggested that compound 6j had no renal and hepatotoxicity at 500 mg/kg. Moreover, 6j could effectively reverse scopolamine-induced amnesia by improving spatial and cognitive memory in mice. The above results strongly suggest that compound 6j may act as a novel multi-targeted lead for AD therapy.
ESTHER : Kumar_2023_Mol.Divers__
PubMedSearch : Kumar_2023_Mol.Divers__
PubMedID: 37351693

Title : Benzimidazole-derived carbohydrazones as dual monoamine oxidases and acetylcholinesterase inhibitors: design, synthesis, and evaluation - Kumar_2023_J.Biomol.Struct.Dyn__1
Author(s) : Kumar S , Jaiswal S , Gupta SK , Ayyannan SR
Ref : J Biomol Struct Dyn , :1 , 2023
Abstract : A series of novel benzimidazole-derived carbohydrazones was designed, synthesized and evaluated for their dual inhibition potential against monoamine oxidases (MAOs) and acetylcholinesterase (AChE) using multitarget-directed ligand approach (MTDL). The investigated compounds have exhibited moderate to excellent in vitro MAOs/AChE inhibitory activity at micromolar to nanomolar concentrations. Compound 12, 2-(1H-Benzo[d]imidazol-1-yl)-N'-[1-(4-hydroxyphenyl) ethylidene]acetohydrazide has emerged as a lead dual MAO-AChE inhibitor by exhibiting superior multi-target activity profile against MAO-A (IC(50) = 0.067 +/- 0.018 microM), MAO-B (IC(50) = 0.029 +/- 0.005 microM) and AChE (IC(50) = 1.37 +/- 0.026 microM). SAR studies suggest that the site A (hydrophobic ring) and site C (semicarbazone linker) modifications attempted on the semicarbazone-based MTDL resulted in a significant enhancement in the MAO-A/B inhibitory potential and a drastic decrease in the AChE inhibitory activity. Further, molecular docking and dynamics simulation experiments disclosed the possible molecular interactions of inhibitors inside the active site of respective enzymes. Also, computational prediction of drug-likeness and ADME parameters of test compounds revealed their drug-like characteristics.Communicated by Ramaswamy H. Sarma.
ESTHER : Kumar_2023_J.Biomol.Struct.Dyn__1
PubMedSearch : Kumar_2023_J.Biomol.Struct.Dyn__1
PubMedID: 37345530

Title : Targeting DPP4-RBD interactions by sitagliptin and linagliptin delivers a potential host-directed therapy against pan-SARS-CoV-2 infections - Mani_2023_Int.J.Biol.Macromol_245_125444
Author(s) : Mani S , Kaur A , Jakhar K , Kumari G , Sonar S , Kumar A , Das S , Kumar S , Kumar V , Kundu R , Pandey AK , Singh UP , Majumdar T
Ref : Int J Biol Macromol , 245 :125444 , 2023
Abstract : Highly mutated SARS-CoV-2 is known aetiological factor for COVID-19. Here, we have demonstrated that the receptor binding domain (RBD) of the spike protein can interact with human dipeptidyl peptidase 4 (DPP4) to facilitate virus entry, in addition to the usual route of ACE2-RBD binding. Significant number of residues of RBD makes hydrogen bonds and hydrophobic interactions with alpha/beta-hydrolase domain of DPP4. With this observation, we created a strategy to combat COVID-19 by circumventing the catalytic activity of DPP4 using its inhibitors. Sitagliptin, linagliptin or in combination disavowed RBD to establish a heterodimer complex with both DPP4 and ACE2 which is requisite strategy for virus entry into the cells. Both gliptins not only impede DPP4 activity, but also prevent ACE2-RBD interaction, crucial for virus growth. Sitagliptin, and linagliptin alone or in combination have avidity to impede the growth of pan-SARS-CoV-2 variants including original SARS-CoV-2, alpha, beta, delta, and kappa in a dose dependent manner. However, these drugs were unable to alter enzymatic activity of PLpro and Mpro. We conclude that viruses hijack DPP4 for cell invasion via RBD binding. Impeding RBD interaction with both DPP4 and ACE2 selectively by sitagliptin and linagliptin is an potential strategy for efficiently preventing viral replication.
ESTHER : Mani_2023_Int.J.Biol.Macromol_245_125444
PubMedSearch : Mani_2023_Int.J.Biol.Macromol_245_125444
PubMedID: 37385308
Gene_locus related to this paper: human-DPP4

Title : Synthesis and anti-Alzheimer potential of novel alpha-amino phosphonate derivatives and probing their molecular interaction mechanism with acetylcholinesterase - Yelamanda_2023_Eur.J.Med.Chem_253_115288
Author(s) : Yelamanda Rao K , Jeelan Basha S , Monika K , Sreelakshmi M , Sivakumar I , Mallikarjuna G , Yadav RM , Kumar S , Subramanyam R , Damu AG
Ref : Eur Journal of Medicinal Chemistry , 253 :115288 , 2023
Abstract : Pleiotropic interference may be a prerequisite for the efficient limitation of the progression of multi-factorial diseases such as Alzheimer's disease (AD). Concept of designing the single chemical entity acting on two or more targets of interest has potential advantage in AD therapy. In line with this, rational design and synthesis of frame work of hybrids bearing 2,3-disubstituted quinazolinone, vanillin and alpha-amino phosphonate scaffolds (5av) were carried out. A congeneric set of twenty-two synthetic derivatives (5av) were evaluated for their cholinesterase inhibitory, antioxidant, DNA nicking, DNA protection, neuroprotective and Abeta aggregation modulatory activities. Amongst tested activities, the most significant and worth mentioning is that the analogues 5m, 5p and 5u were found to be the most potent, selective, and mixed type inhibitors of EeAChE with IC(50) values of 0.296 +/- 0.030, 0.289 +/- 0.027, and 0.306 +/- 0.028 microM, respectively. Further, the biophysical approaches indicated that the compounds 5m, 5p, and 5u have a strong binding affinity towards AChE. Kinetic and Molecular docking studies have revealed that the most active congeners were well oriented in the AChE active site by interacting with both catalytic active site (CAS) and peripheral anionic site (PAS). A few parameters derived from molecular dynamics (MD) simulation trajectories emphasized the stability of AChE-5p and 5m complexes throughout the 100 ns simulations, and the local conformational changes of the residues of AChE validate the stability of AChE-5p and 5m complexes. Further, these derivatives significantly impacted ABTS radical scavenging capacities and maximal DNA protection activity. Importantly, Thioflavin T (ThT) assay and FE-SEM study demonstrated compounds 5m, 5p and 5u as effective Abeta(1-42) fibril modulators at molecular level by the formation of micro size co-assembled mature structures, thus efficiently abolishing the cytotoxicity of Abeta(1-42). Finally, these active compounds are determined to be non-toxic and highly neuroprotective against H(2)O(2)-induced cell death in SK-N-SH cell lines. Furthermore, in silico ADMET prediction studies have revealed that the targeted analogues satisfied most of the characteristics of CNS acting drugs. These multi-functional efficacies indicated worthiness of these alpha-amino phosphonate derivatives being chosen for further pharmacokinetics, toxicity, and behavioral research to test their potential for AD treatment.
ESTHER : Yelamanda_2023_Eur.J.Med.Chem_253_115288
PubMedSearch : Yelamanda_2023_Eur.J.Med.Chem_253_115288
PubMedID: 37031527

Title : Changing spectrum of acute poisoning in North India: A hospital-based descriptive study - Pannu_2022_Turk.J.Emerg.Med_22_192
Author(s) : Pannu AK , Bhalla A , Vamshi V , Upadhyay MK , Sharma N , Kumar S
Ref : Turk J Emerg Med , 22 :192 , 2022
Abstract : OBJECTIVES: Evaluating local trends and continued monitoring of patterns of acute poisoning are essential for prompt recognition of the toxidromes, the establishment of immediate treatment facilities (e.g., antidote availability), and effective preventive strategies (e.g., governmental regulation on hazardous substances marketing). We aimed to describe the prevalence of the various types of poisoning and associated case fatality in our academic hospital in North India. METHODS: A prospective observational descriptive study was conducted, enrolling patients aged 13 years with acute poisoning for 17 months from December 2016 to December 2017 and from September 2019 to December 2019, for a total of 17 months. RESULTS: Four hundred and two patients were enrolled (median age 28 years; 63.2% males). Majority of the acute poisoning cases resulted from ingestion (n = 391, 97.3%) and the primary intention was most commonly self-harm (n = 314, 78.1%). The major types of poisoning were pesticide (n = 264, 65.7%), drug overdose (n = 77, 19.2%), and corrosive ingestion (n = 31, 7.7%). Pesticides included insecticides (n = 146, 36.3%; cholinesterase inhibitors, n = 91), fungicides (n = 76, 18.9%; all aluminum phosphide), herbicides (n = 22, 5.5%; paraquat, n = 19), and rodenticides (n = 20, 5.0%; coumarin-derived substances, n = 12). Benzodiazepines (n = 33) and opioids (n = 25) were frequent causes of drug overdose. 95.3% (n = 379) received preliminary treatment at the previous health-care center, including gastric lavage (n = 239) and antidotes (n = 73). In-hospital case fatality rate was 17.3% (n = 58). CONCLUSION: Herbicide ingestion and opioid overdose are emerging threats with a gradual decline in organophosphate and aluminum phosphide poisoning. Despite improving management of acute poisoning, the overall case fatality rate remains substantial.
ESTHER : Pannu_2022_Turk.J.Emerg.Med_22_192
PubMedSearch : Pannu_2022_Turk.J.Emerg.Med_22_192
PubMedID: 36353380

Title : Isolation, Characterization, and In Silico Interaction Studies of Bioactive Compounds from Caesalpinia bonducella with Target Proteins Involved in Alzheimer's Disease - Khoba_2022_Appl.Biochem.Biotechnol__
Author(s) : Khoba K , Kumar S , Chatterjee S , Purty RS
Ref : Appl Biochem Biotechnol , : , 2022
Abstract : Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder characterized by memory loss, cognitive deterioration, and neuropsychiatric symptoms. Various drug targets implicated in AD are amyloid beta peptides, cholinesterase enzymes, and anti-amylogenic protein. Medicinal plants derived phytochemical constituents provide a vast pool of diverse compounds as a source of novel drugs. In view of this, the Caesalpinia bonducella seed extract and its active phytoconstituents were used to study the disease-modifying effects in Alzheimer's disease. The present study successfully demonstrated the therapeutic potential of various phytochemicals as it binds to multiple drug targets, resulting in inhibition of acetylcholinesterase (AChE) enzyme, butyrylcholinesterase (BuChE), BACE-1 enzyme, and anti-amylogenic protein as indicated by docking analysis. In conclusion, phytochemicals identified can be used as a suitable lead to developing a molecule that might have multi-targeted directed ligand (MTDL) potential and disease amelioration effects in Alzheimer's disease.
ESTHER : Khoba_2022_Appl.Biochem.Biotechnol__
PubMedSearch : Khoba_2022_Appl.Biochem.Biotechnol__
PubMedID: 35507252

Title : Insecticide susceptibility vis--vis molecular variations in geographical populations of fall armyworm, Spodoptera frugiperda (J.E. smith) in India - Kumar_2022_3.Biotech_12_241
Author(s) : Kumar S , Suby SB , Kumar N , Sekhar JC , Nebapure S , Mahapatro GK
Ref : 3 Biotech , 12 :241 , 2022
Abstract : In an emergency response to the introduction, subsequent detection and rapid spread of the invasive insect pest fall armyworm (FAW), Spodoptera frugiperda (J.E. Smith) in the country, Government of India offered ad-hoc approval for few pesticide molecules namely, emamectin benzoate, spinetoram, chlorantraniliprole, novaluron, thiodicarb, and lambda-cyhalothrin for FAW management in corn crop across the country. Five major maize (corn) growing geographical areas (i.e., Bihar, Delhi, Karnataka, Punjab and Tamil Nadu) were selected during the main crop season of 2020 (Oct-Nov), and sampled for the target-insect populations. The insect populations were lab-reared on maize leaves (15-20 days old); the F(1) generation insects (third instar, 25-30 mg/larva) were subjected to bioassay to determine susceptibility levels of FAW against ad-hoc recommended insecticides. The previously reported target-site molecular variations in the genes ace, encoding acetylcholinesterase (AChE), and vgsc, encoding voltage-gated sodium channel were analyzed. Among the five test-populations, Bihar test-population recorded least susceptibility to all the test-pesticides, whereas the South Indian populations (Karnataka, Tamil Nadu) were found most susceptible. North Indian and South Indian test-insect populations formed two distinct groups in terms of susceptibility levels, speculatively on account of prevailing climatic factors. Being the population with least ace mutation frequency, but with the higher resistance ratio for all the test-pesticides, Bihar insect population implies a bigger role of broad range detoxification machinery than the narrow scope of target site insensitivity. Though, resistance has not developed to the recommended insecticides by FAW, except the case of low-medium resistance development; which is better explained due to behavioural avoidance of synthetic pyrethroid (lambda-cyhalothrin). However, there is no room for complacency. Resistance-monitoring tools such as location/region-specific determination of discriminating diagnostic concentrations/doses for FAW in recommended insecticides are to be devised at the earliest. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-022-03303-2.
ESTHER : Kumar_2022_3.Biotech_12_241
PubMedSearch : Kumar_2022_3.Biotech_12_241
PubMedID: 36032511

Title : A review on structurally diversified synthesized molecules as monoacylglycerol lipase inhibitors and their therapeutic uses - Kashyap_2022_Curr.Drug.Res.Rev__
Author(s) : Kashyap A , Kumar S , Dutt R
Ref : Curr Drug Res Rev , : , 2022
Abstract : Monoacylglycerol is a metabolic key serine hydrolase, engaged in the regulation of signalling network system of endocannabinoids, which is associated with various physiological processes like pain, inflammation, feeding cognition and neurodegenerative diseases like Alzheimer, Parkinson's disease. The monoacylglycerol also found to act as a regulator and the free fatty acid provider in the proliferation of cancer cells, numerous aggressive tumours such as colorectal cancer, neuroblastoma and nasopharyngeal carcinoma. It also played an important role in increasing the concentration of specific lipids derived from free fatty acids like phosphatidic acid, lysophosphatidic acid, sphingosine-1-phosphate and prostaglandin E2. These signalling lipids are associated with cell proliferation, survival, tumour cell migration, contributing to tumour development, maturation and metastases. In the present study here, we are presenting a review on structurally diverse MAGL inhibitors, their development and their evaluation for different pharmacological activities.
ESTHER : Kashyap_2022_Curr.Drug.Res.Rev__
PubMedSearch : Kashyap_2022_Curr.Drug.Res.Rev__
PubMedID: 35232358

Title : Metabolic detoxification and ace-1 target site mutations associated with acetamiprid resistance in Aedes aegypti L - Samal_2022_Front.Physiol_13_988907
Author(s) : Samal RR , Panmei K , Lanbiliu P , Kumar S
Ref : Front Physiol , 13 :988907 , 2022
Abstract : Despite the continuous use of chemical interventions, Aedes-borne diseases remain on the rise. Neonicotinoids are new, safer, and relatively effective pharmacological interventions against mosquitoes. Neonicotinoids interact with the postsynaptic nicotinic acetylcholine receptors (nAChRs) of the insect central nervous system, but the absence of nAChR polymorphism in resistant phenotypes makes their involvement in neonicotinoid resistance uncertain. Thus, an investigation was carried out to understand the role of metabolic detoxification and target site insensitivity in imparting acetamiprid resistance in Aedes aegypti larvae. Studies were conducted on the parent susceptible strain (PS), acetamiprid-larval selected strain for five generations (ACSF-5; 8.83-fold resistance) and 10 generations (ACSF-10; 19.74-fold resistance) of Ae. aegypti. The larval selection raised alpha-esterase and beta-esterase activities by 1.32-fold and 1.34-fold, respectively, in ACSF-10 as compared to PS, while the corresponding glutathione-S-transferase and acetylcholinesterase activity increased by 22.5 and 2%. The ace-1 gene in PS and ACSF-10 showed four mismatches in the 1312-1511 bp region due to mutations in the Y455C codon (tyrosine to cysteine) at the 1367th position (TAC->TGC); I457V codon (isoleucine to valine) at 1372 bp and 1374 bp (ATA->GTG); and R494M codon (arginine to methionine) at 1484 bp (AGG->ATG). The R494M mutation was the novel and dominant type, observed in 70% ACSF-10 population, and has not been reported so far. The studies evidenced the combination of metabolic detoxification and target site mutation in imparting acetamiprid resistance in Ae. aegypti.
ESTHER : Samal_2022_Front.Physiol_13_988907
PubMedSearch : Samal_2022_Front.Physiol_13_988907
PubMedID: 36111159

Title : A novel RP-HPLC method for quantification of cholinesterase activity in human blood: An application for assessing organophosphate and carbamate insecticide exposure - Sinha_2022_PLoS.One_17_e0279287
Author(s) : Sinha SN , Ungarala R , Kumar D , Sangaraju R , Kumar S
Ref : PLoS ONE , 17 :e0279287 , 2022
Abstract : Several methods have been reported to estimate Acetylcholinesterase (AChE) enzyme activity in blood samples. The Ellman assay is the most important among all but with several shortcomings, and there is a need to develop a method which is accurate, sensitive and quick for analyzing AChE. Therefore, we have developed an assay utilizing RP-HPLC with UV detection for the determination of AChE activity. This method measured the conversion of 1-naphthol acetate to 1-naphthol to estimate AChE activity in blood samples. Performance was judged on the basis of reproducibility, sensitivity, accuracy, and the ability to screen enzyme activity within 20minutes. A series of experiments were performed, varying the concentration of blood and substrate, with optimal sensitivity using 50 microM substrate and 10microL blood. The validation parameters such as linearity (R2 of <= 0.9842 for 1-naphthol and <= 0.9897 for 1-naphthol acetate), precision (94.21-96.41%), accuracy (85.2%-99.6% and 82.6%-99.3% for 1-naphthol and 1-naphthol acetate respectively), and robustness were validated according to International Conference on Harmonization (ICH) guidelines. Blood samples were collected from healthy people, farmers exposed to spraying of pesticides, and suicidal patients who ingested pesticides and were hospitalized and were analyzed by the developed method. The AChE level was approximately 21 units/mL compared to 24units/mL in controls, whereas suicidal patients showed the least AChE levels of 1 unit/mL. The employment of this method is recommended for estimating AChE level on various matrices.
ESTHER : Sinha_2022_PLoS.One_17_e0279287
PubMedSearch : Sinha_2022_PLoS.One_17_e0279287
PubMedID: 36584091

Title : Impact of Serum Amylase Level in the Outcome of Acute Organophosphorus Poisoning: 2-Year Cross-Sectional Study at Rural Teaching Hospital - Patil_2022_J.Lab.Physicians_14_1
Author(s) : Patil A , Kumar S , Inamdar A , Acharya S , Wanjari A , Bawankule S , Agrawal S , Sontakke T
Ref : J Lab Physicians , 14 :1 , 2022
Abstract : Introduction : Prompt recognition and aggressive management of acute intoxication due to organophosphorus poisoning are essential to minimize the morbidity and mortality. The present study was undertaken to know the prognosis and outcome of organophosphorus poisoning patients with the estimation of low-cost enzymes like the serum amylase level in a population with financial constraints. Methods : In this cross-sectional study, we had enrolled 100 cases that had a history of exposure to organophosphorus compounds, and the serum amylase level was measured in all the patients. We assessed the outcome of all the patients in the form of discharge, need of ventilators, intensive care unit stay, and death. Results : The mean serum amylase level in discharge patients was 335.40 +/- 192.45, and in the patients who died it was 843.37 +/- 22.60. It was significant to predict the outcome ( t -value 7.07, p -value 0.0001, statistically significant). Conclusion : Serum amylase level shows significant correlation with clinical outcomes in organophosphorus poisoning.
ESTHER : Patil_2022_J.Lab.Physicians_14_1
PubMedSearch : Patil_2022_J.Lab.Physicians_14_1
PubMedID: 36186263

Title : Bergenin ameliorates cognitive deficits and neuropathological alterations in sodium azide-induced experimental dementia - Singla_2022_Front.Pharmacol_13_994018
Author(s) : Singla RK , Dhonchak K , Sodhi RK , Arockia Babu M , Madan J , Madaan R , Kumar S , Sharma R , Shen B
Ref : Front Pharmacol , 13 :994018 , 2022
Abstract : Background: Bergenin, 4-O-methyl gallic acid glucoside, is a bioactive compound found in the cortex of Mallotus japonicus (L.f.) Mll.Arg. along with many other natural resources including that from Bergenia species. The present study delineates the neuroprotective potential of bergenin through the modulation of PPAR-gamma receptors. Method: Dementia was induced in the Wistar rats by intraperitoneal (i.p.) administration of sodium azide (12.5 mg/kg for the first 5 days followed by 10 mg/kg for the next 9 days). The rats were then exposed to the Morris water maze test to assess the effect on cognitive abilities followed by a series of biochemical and histopathological evaluations. Results: Sodium azide-treated rats exhibited a severe deterioration of memory as suggested by poor performance in the spatial learning task in addition to the enhancement of brain acetylcholinesterase potential, oxidative stress, inflammation, and amyloid-beta (Abeta) accumulation. Administration of bergenin to sodium azide-treated rats significantly recovered cognition and related biochemical variations. Further, co-administration of Bisphenol A diglycidyl ether (BADGE), a PPAR-gamma antagonist with bergenin challenged its neuroprotective effects. Conclusions: The findings of our study exhibit that the cognitive restoration potential of bergenin may be attributed to its modulatory effects against cholinesterase, oxidative stress, and inflammatory markers, as well as its neuroprotective actions, thus aligning it as a possible therapy for Alzheimer's disease-related dementia. The study also fortifies the significance of PPAR-gamma receptors in dementia.
ESTHER : Singla_2022_Front.Pharmacol_13_994018
PubMedSearch : Singla_2022_Front.Pharmacol_13_994018
PubMedID: 36249784

Title : Targeting LIPA independent of its lipase activity is a therapeutic strategy in solid tumors via induction of endoplasmic reticulum stress - Liu_2022_Nat.Cancer__
Author(s) : Liu X , Viswanadhapalli S , Kumar S , Lee TK , Moore A , Ma S , Chen L , Hsieh M , Li M , Sareddy GR , Parra K , Blatt EB , Reese TC , Zhao Y , Chang A , Yan H , Xu Z , Pratap UP , Liu Z , Roggero CM , Tan Z , Weintraub ST , Peng Y , Tekmal RR , Arteaga CL , Lippincott-Schwartz J , Vadlamudi RK , Ahn JM , Raj GV
Ref : Nat Cancer , : , 2022
Abstract : Triple-negative breast cancer (TNBC) has a poor clinical outcome, due to a lack of actionable therapeutic targets. Herein we define lysosomal acid lipase A (LIPA) as a viable molecular target in TNBC and identify a stereospecific small molecule (ERX-41) that binds LIPA. ERX-41 induces endoplasmic reticulum (ER) stress resulting in cell death, and this effect is on target as evidenced by specific LIPA mutations providing resistance. Importantly, we demonstrate that ERX-41 activity is independent of LIPA lipase function but dependent on its ER localization. Mechanistically, ERX-41 binding of LIPA decreases expression of multiple ER-resident proteins involved in protein folding. This targeted vulnerability has a large therapeutic window, with no adverse effects either on normal mammary epithelial cells or in mice. Our study implicates a targeted strategy for solid tumors, including breast, brain, pancreatic and ovarian, whereby small, orally bioavailable molecules targeting LIPA block protein folding, induce ER stress and result in tumor cell death.
ESTHER : Liu_2022_Nat.Cancer__
PubMedSearch : Liu_2022_Nat.Cancer__
PubMedID: 35654861
Gene_locus related to this paper: human-LIPA

Title : Mechano-chemical and biological energetics of immobilized enzymes onto functionalized polymers and their applications - Sharma_2022_Bioengineered_13_10518
Author(s) : Sharma T , Xia C , Sharma A , Raizada P , Singh P , Sharma S , Sharma P , Kumar S , Lam S , Nadda AK
Ref : Bioengineered , 13 :10518 , 2022
Abstract : Enzymes of commercial importance, such as lipase, amylase, laccase, phytase, carbonic anhydrase, pectinase, maltase, glucose oxidase etc., show multifunctional features and have been extensively used in several fields including fine chemicals, environmental, pharmaceutical, cosmetics, energy, food industry, agriculture and nutraceutical etc. The deployment of biocatalyst in harsh industrial conditions has some limitations, such as poor stability. These drawbacks can be overcome by immobilizing the enzyme in order to boost the operational stability, catalytic activity along with facilitating the reuse of biocatalyst. Nowadays, functionalized polymers and composites have gained increasing attention as an innovative material for immobilizing the industrially important enzyme. The different types of polymeric materials and composites are pectin, agarose, cellulose, nanofibers, gelatin, and chitosan. The functionalization of these materials enhances the loading capacity of the enzyme by providing more functional groups to the polymeric material and hence enhancing the enzyme immobilization efficiency. However, appropriate coordination among the functionalized polymeric materials and enzymes of interest plays an important role in producing emerging biocatalysts with improved properties. The optimal coordination at a biological, physical, and chemical level is requisite to develop an industrial biocatalyst. Bio-catalysis has become vital aspect in pharmaceutical and chemical industries for synthesis of value-added chemicals. The present review describes the current advances in enzyme immobilization on functionalized polymers and composites. Furthermore, the applications of immobilized enzymes in various sectors including bioremediation, biosensor and biodiesel are also discussed.
ESTHER : Sharma_2022_Bioengineered_13_10518
PubMedSearch : Sharma_2022_Bioengineered_13_10518
PubMedID: 35443858

Title : Forensic toxicological and analytical aspects of carbamate poisoning - A review - Kumar_2022_J.Forensic.Leg.Med_92_102450
Author(s) : Kumar S , Baggi TR , Al-Zughaibi T
Ref : J Forensic Leg Med , 92 :102450 , 2022
Abstract : Pesticides play a pivotal role in modern agricultural practices and effective domestic pest control. Despite their advantages, pesticides pose a great danger to humans and animals due to their toxicity. Pesticides, particularly carbamates, are extensively used all over the world in crop protection and domestic pest control, however, also causing morbidity and mortality on a larger scale, which is of great significance in both clinical and criminal justice management.Carbamates are derived from a carbamic acid (NH(2)COOH) that are commonly used as insecticides. Ethienocarb, Sevin, Carbaryl, Fenoxycarb, Furadan, Carbofuran, Aldicarb, and 2-(1-Methylpropyl) phenyl N-methylcarbamate are examples of insecticides that include the carbamate functional group. By reversibly inactivating the enzyme acetylcholinesterase, these insecticides can induce cholinesterase inhibition poisoning.Chromatographic methods, notably gas and liquid chromatography have traditionally been employed to analyse carbamate pesticides and their metabolites in various matrices. These approaches are employed due to their ability to separate the chemicals contained in a sample; as well as identify and quantify these compounds utilizing advanced detection systems. Aside from these GC and LC conventional methods, other detection and/or hyphenated techniques such as single-quadrupole, ion-trap, triple-quadrupole, or tandem mass spectrometry, have been used in carbamate analysis to provide quick results with excellent sensitivity, precision, and accuracy.The objective of this review is to describe various analytical techniques used to detect and determine carbamate pesticides in various matrices which include urine, blood, and tissues that are commonly encountered in emergency hospital laboratories and forensic science laboratories.
ESTHER : Kumar_2022_J.Forensic.Leg.Med_92_102450
PubMedSearch : Kumar_2022_J.Forensic.Leg.Med_92_102450
PubMedID: 36399917

Title : Exploration of a library of piperonylic acid-derived hydrazones possessing variable aryl functionalities as potent dual cholinesterase and monoamine oxidase inhibitors - Kumar_2022_Mol.Divers__
Author(s) : Kumar VP , Vishnu MS , Kumar S , Jaiswal S , Ayyannan SR
Ref : Mol Divers , : , 2022
Abstract : A library of piperonylic acid-derived hydrazones possessing variable aryl moiety was synthesized and investigated for their multifunctional properties against cholinesterases (ChEs) and monoamine oxidases (MAOs). The in vitro enzymatic assay results revealed that the tested hydrazones have exhibited excellent cholinesterase inhibition profile. Compound 4i, (E)-N'-(2,3-dichlorobenzylidene)benzo[d][1,3]dioxole-5-carbohydrazide showed promising dual inhibitory profile against AChE (0.048 +/- 0.007 M), BChE (0.89 +/- 0.018 M), and MAO-B (0.95 +/- 0.12 M) enzymes. SAR exploration revealed that the truncation of the linker connecting both the aryl binding sites of the semicarbazone scaffold, by one atom, has relatively suppressed the AChE inhibitory potential. Kinetic studies disclosed that the compound 4i reversibly inhibited AChE enzyme in a competitive manner (K(i) = 8.0 +/- 0.076 nM), while it displayed a non-competitive and reversible inhibition profile against MAO-B (K(i) = 9.6 +/- 0.021 M). Moreover, molecular docking studies of synthesized compounds against ChEs and MAOs provided the crucial molecular features that enable their close association and interaction with the target enzymes. All atomistic simulation studies confirmed the stable association of compound 4i within the active sites of AChE and MAO-B. In addition, theoretical ADMET prediction studies demonstrated the acceptable pharmacokinetic profile of the dual inhibitors. In summary, the attempted lead simplification study afforded a potent dual ChE-MAO-B inhibitor compound that merits further investigation.
ESTHER : Kumar_2022_Mol.Divers__
PubMedSearch : Kumar_2022_Mol.Divers__
PubMedID: 36355337

Title : Genus Rauvolfia: A review of its ethnopharmacology, phytochemistry, quality control\/quality assurance, pharmacological activities and clinical evidence - Kumar_2022_J.Ethnopharmacol__115327
Author(s) : Kumar S , Kumari D , Singh B
Ref : J Ethnopharmacol , :115327 , 2022
Abstract : ETHNOPHARMACOLOGICAL RELEVANCE: The plants are from the genus Rauvolfia Plum. ex L. (Apocynaceae), which is represented by 74 species with many synonyms, and distributed worldwide, especially in the Asian, and African continents. Traditionally, some of them are used for the treatment of various disorders related to the central nervous system (CNS), cardiovascular diseases (CVD), and as an antidote due to the presence of monoterpene indole alkaloids (MIAs) such as ajmaline (144), ajmalicine (164) serpentine (182), yohimbine (190) and reserpine (214). AIM: The present review provides comprehensive summarization and critical analysis of the traditional to modern applications of Rauvolfia species, and the major focus was to include traditional uses, phytochemistry, quality control, pharmacological properties, as well as clinical evidence that may be useful in the drug discovery process. MATERIALS AND METHODS: Information related to traditional uses, chemical constituents, separation techniques/analytical methods, and pharmacological properties of the genus Rauvolfia were obtained using electronic databases such as Web of Science, Scopus, SciFinder, PubMed, PubChem, ChemSpider, and Google Scholar between the years 1949-2021. The scientific name of the species and its synonyms were checked with the information of The Plant List. RESULTS: A total of seventeen Rauvolfia species have been traditionally explored for various therapeutic applications, out of which the roots of R. serpentina and R. vomitoria are used most commonly for the treatment of many diseases. About 287 alkaloids, seven terpenoids, nine flavonoids, and four phenolic acids have been reported in different parts of the forty-three species. Quality control (QC)/quality assurance (QA) of extracts/herbal formulations of Rauvolfia species was analyzed by qualitative and quantitative methods based on the major MIAs such as compounds 144, 164, 182, 190, and 214 using HPTLC, HPLC, and HPLC-MS. The various extracts of different plant parts of thirteen Rauvolfia species are explored for their pharmacological properties such as antimicrobial, antioxidant, antiprotozoal, antitrypanosomal, antipsychotic, cardioprotective, cholinesterase inhibitory, and hepatoprotective. Of which, clinical trials of herbal formulations/extracts of R. serpentina and MIAs have been reported for CVD, CNS, antihypertensive therapy, antidiabetic effects, and psoriasis therapy, while the extracts and phytoconstituents of remaining Rauvolfia species are predominantly significant, owning them to be additional attention for further investigation under clinical trials and QC/QA. CONCLUSION: The present communication has provided a comprehensive, systematic, and critically analyzed vision into the traditional uses, phytochemistry, and modern therapeutic applications of the genus Rauvolfia are validated by scientific evidence. In addition, different plant parts from this genus, especially raw and finished herbal products of the roots of R. serpentina have been demonstrated for the QC/QA.
ESTHER : Kumar_2022_J.Ethnopharmacol__115327
PubMedSearch : Kumar_2022_J.Ethnopharmacol__115327
PubMedID: 35504505

Title : Discovery of new phenyl sulfonyl-pyrimidine carboxylate derivatives as the potential multi-target drugs with effective anti-Alzheimer's action: Design, synthesis, crystal structure and in-vitro biological evaluation - Manzoor_2021_Eur.J.Med.Chem_215_113224
Author(s) : Manzoor S , Prajapati SK , Majumdar S , Raza K , Gabr MT , Kumar S , Pal K , Rashid H , Krishnamurthy S , Hoda N
Ref : Eur Journal of Medicinal Chemistry , 215 :113224 , 2021
Abstract : Alzheimer's disease (AD) is multifactorial, progressive neurodegeneration with impaired behavioural and cognitive functions. The multitarget-directed ligand (MTDL) strategies are promising paradigm in drug development, potentially leading to new possible therapy options for complex AD. Herein, a series of novel MTDLs phenylsulfonyl-pyrimidine carboxylate (BS-1 to BS-24) derivatives were designed and synthesized for AD treatment. All the synthesized compounds were validated by (1)HNMR, (13)CNMR, HRMS, and BS-19 were structurally validated by X-Ray single diffraction analysis. To evaluate the plausible binding affinity of designed compounds, molecular docking study was performed, and the result revealed their significant interaction with active sites of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The synthesized compounds displayed moderate to excellent in vitro enzyme inhibitory activity against AChE and BuChE at nanomolar (nM) concentration. Among 24 compounds (BS-1 to BS-24), the optimal compounds (BS-10 and BS-22) displayed potential inhibition against AChE; IC(50) = 47.33 +/- 0.02 nM and 51.36 +/- 0.04 nM and moderate inhibition against BuChE; IC(50) = 159.43 +/- 0.72 nM and 153.3 +/- 0.74 nM respectively. In the enzyme kinetics study, the compound BS-10 displayed non-competitive inhibition of AChE with Ki = 8 nM. Respective compounds BS-10 and BS-22 inhibited AChE-induced Abeta(1-42) aggregation in thioflavin T-assay at 10 microM and 20 microM, but BS-10 at 10 microM and 20 microM concentrations are found more potent than BS-22. In addition, the aggregation properties were determined by the dynamic light scattering (DLS) and was found that BS-10 and BS-22 could significantly inhibit self-induced as well as AChE-induced Abeta(1-42) aggregation. The effect of compounds (BS-10 and BS-22) on the viability of MC65 neuroblastoma cells and their capability to cross the blood-brain barrier (BBB) in PAMPA-BBB were further studied. Further, in silico approach was applied to analyze physicochemical and pharmacokinetics properties of the designed compounds via the SwissADME and PreADMET server. Hence, the novel phenylsulfonyl-pyrimidine carboxylate derivatives can act as promising leads in the development of AChE inhibitors and Abeta disaggregator for the treatment of AD.
ESTHER : Manzoor_2021_Eur.J.Med.Chem_215_113224
PubMedSearch : Manzoor_2021_Eur.J.Med.Chem_215_113224
PubMedID: 33582578

Title : Comparative susceptibility of Rhipicephalus microplus collected from the northern state of India to coumaphos, malathion, deltamethrin, ivermectin, and fipronil - Bisht_2021_Trop.Anim.Health.Prod_53_460
Author(s) : Bisht N , Kumar S , Sharma AK , Nandi A , Singh K , Fular A , Nagar G , Ghosh S
Ref : Trop Anim Health Prod , 53 :460 , 2021
Abstract : The chemical-based tick management method is gradually losing its clutch due to the establishment of resistant ticks. For development of region-specific tick management strategies, the present study was aimed to evaluate the comparative resistance profile of Rhipicephalus microplus isolates collected from seven districts of Uttar Pradesh, a northern state of India. Comparative analysis of the dose-response data using adult immersion test (AIT) against coumaphos, malathion, deltamethrin, ivermectin, and fipronil revealed that all the isolates were resistant to discriminating concentration of deltamethrin having LC(50) of 295.12-436.52 ppm with a resistance ratio of 22.02-32.58. An emerging low level of ivermectin resistance (resistance ratio, RR(50) = 1.03-2.26) with LC(50) in the range of 22.39-48.98 ppm was found across the isolates. The coumaphos was highly effective against all except Amethi (AMT) isolate. Similarly, malathion was efficacious against most of the isolates except Pratapgarh (PRT) and Sultanpur (SUL) isolates showing LC(50) of 5128.61 and 5623.41 ppm, respectively. All the isolates were responsive to fipronil. Comparative detoxifying enzymes profiles revealed a significant correlation between the increased activity of esterase and deltamethrin resistance. The GST activity was 51.2% correlated with RR(50) of malathion while esterase activity was significantly correlated (68.9%) with RR(50) of coumaphos. No correlation between the ivermectin resistance and enzyme activity was established. Multiple sequence analysis of S4-5 linker region of the sodium channel gene of all the isolates revealed a point mutation at 190th position (C190A) which is associated with deltamethrin resistance. The possible tick management strategies in this part of the country are discussed.
ESTHER : Bisht_2021_Trop.Anim.Health.Prod_53_460
PubMedSearch : Bisht_2021_Trop.Anim.Health.Prod_53_460
PubMedID: 34542704

Title : Five-Decade Update on Chemopreventive and Other Pharmacological Potential of Kurarinone: a Natural Flavanone - Kumar_2021_Front.Pharmacol_12_737137
Author(s) : Kumar S , Prajapati KS , Shuaib M , Kushwaha PP , Tuli HS , Singh AK
Ref : Front Pharmacol , 12 :737137 , 2021
Abstract : In the present article we present an update on the role of chemoprevention and other pharmacological activities reported on kurarinone, a natural flavanone (from 1970 to 2021). To the best of our knowledge this is the first and exhaustive review of kurarinone. The literature was obtained from different search engine platforms including PubMed. Kurarinone possesses anticancer potential against cervical, lung (non-small and small), hepatic, esophageal, breast, gastric, cervical, and prostate cancer cells. In vivo anticancer potential of kurarinone has been extensively studied in lungs (non-small and small) using experimental xenograft models. In in vitro anticancer studies, kurarinone showed IC(50) in the range of 2-62 microM while in vivo efficacy was studied in the range of 20-500 mg/kg body weight of the experimental organism. The phytochemical showed higher selectivity toward cancer cells in comparison to respective normal cells. kurarinone inhibits cell cycle progression in G2/M and Sub-G1 phase in a cancer-specific context. It induces apoptosis in cancer cells by modulating molecular players involved in apoptosis/anti-apoptotic processes such as NF-kappaB, caspase 3/8/9/12, Bcl2, Bcl-XL, etc. The phytochemical inhibits metastasis in cancer cells by modulating the protein expression of Vimentin, N-cadherin, E-cadherin, MMP2, MMP3, and MMP9. It produces a cytostatic effect by modulating p21, p27, Cyclin D1, and Cyclin A proteins in cancer cells. Kurarinone possesses stress-mediated anticancer activity and modulates STAT3 and Akt pathways. Besides, the literature showed that kurarinone possesses anti-inflammatory, anti-drug resistance, anti-microbial (fungal, yeast, bacteria, and Coronavirus), channel and transporter modulation, neuroprotection, and estrogenic activities as well as tyrosinase/diacylglycerol acyltransferase/glucosidase/aldose reductase/human carboxylesterases 2 inhibitory potential. Kurarinone also showed therapeutic potential in the clinical study. Further, we also discussed the isolation, bioavailability, metabolism, and toxicity of Kurarinone in experimental models.
ESTHER : Kumar_2021_Front.Pharmacol_12_737137
PubMedSearch : Kumar_2021_Front.Pharmacol_12_737137
PubMedID: 34646138

Title : Integrated 3D-QSAR, molecular docking, and molecular dynamics simulation studies on 1,2,3-triazole based derivatives for designing new acetylcholinesterase inhibitors - El Khatabi_2021_Turk.J.Chem_45_647
Author(s) : El Khatabi K , Aanouz I , El-Mernissi R , Singh AK , Ajana MA , Lakhlifi T , Kumar S , Bouachrine M
Ref : Turk J Chem , 45 :647 , 2021
Abstract : Alzheimer's disease (AD) is a multifactorial and polygenic disease. It is the most prevalent reason for dementia in the aging population. A dataset of twenty-six 1,2,3-triazole-based derivatives previously synthetized and evaluated for acetylcholinesterase inhibitory activity were subjected to the three-dimensional quantitative structure-activity relationship (3D-QSAR) study. Good predictability was achieved for comparative molecular field analysis (CoMFA) (Q(2) = 0.604, R(2) = 0.863, r(ext) (2) = 0.701) and comparative molecular similarity indices analysis (CoMSIA) (Q(2) = 0.606, R(2) = 0.854, r(ext) (2) = 0.647). The molecular features characteristics provided by the 3D-QSAR contour plots were quite useful for designing and improving the activity of acetylcholinesterase of this class. Based on these findings, a new series of 1,2,3-triazole based derivatives were designed, among which compound A1 with the highest predictive activity was subjected to detailed molecular docking and compared to the most active compound. The selected compounds were further subjected to 20 ns molecular dynamics (MD) simulations to study the comparative conformation dynamics of the protein after ligand binding, revealing promising results for the designed molecule. Therefore, this study could provide worthy guidance for further experimental analysis of highly effective acetylcholinesterase inhibitors.
ESTHER : El Khatabi_2021_Turk.J.Chem_45_647
PubMedSearch : El Khatabi_2021_Turk.J.Chem_45_647
PubMedID: 34385858

Title : Characterization of deltamethrin, cypermethrin, coumaphos and ivermectin resistance in populations of Rhipicephalus microplus in India and efficacy of an antitick natural formulation prepared from Ageratum conyzoides - Kumar_2021_Ticks.Tick.Borne.Dis_12_101818
Author(s) : Kumar S , Sharma AK , Kumar B , Shakya M , Patel JA , Bisht N , Chigure GM , Singh K , Kumar R , Srivastava S , Rawat P , Ghosh S
Ref : Ticks Tick Borne Dis , 12 :101818 , 2021
Abstract : Rhipicephalus microplus is posing a serious threat to productive animal husbandry. Excessive use of synthetic chemicals in tick management has led to the development of resistant tick populations. Characterization of resistance to deltamethrin, cypermethrin, coumaphos and ivermectin in ticks is necessary to develop a suitable and sustainable control strategy. Based on adult immersion test and larval packet test, the resistance ratios (RR(50)) for adults and larvae of R. microplus populations from two Indian states ranged from 3.8 to 19.4 and 1.35-25.0 against deltamethrin, 0.061-26.3 and 0.22-19.2 against cypermethrin, and 0.2-9.5 and 0.01-3.1 against coumaphos, respectively, were recorded. Moreover, the RR(50) for adults ranged from 0.212 to 3.87 against ivermectin. The RR(50) for different acaricides was significantly (p<0.01) correlated with esterases, Glutathione S-transferase and monooxygenase activity. A point mutation at the 190th position of the domain II S4-5 linker region of the sodium channel gene in synthetic pyrethroids (SP) resistant populations was also detected. An antitick natural formulation prepared from the plant Azeratum conyzoides and containing two major compounds, Precocene-I (7methoxy-2, 2-dimethyl 2H-chromene) and Precocene II (6, 7-dimethoxy-2, 2-dimethyl- 3-chromene), was developed and tested against the resistant ticks. The LC(50) values of the natural formulation against the resistant populations were in the range of 4.31-5.33% irrespective of their RR(50) values. Multi-acaricide resistant populations of R. microplus are established in India and the A. conyzoides based natural formulation can be used for its management.
ESTHER : Kumar_2021_Ticks.Tick.Borne.Dis_12_101818
PubMedSearch : Kumar_2021_Ticks.Tick.Borne.Dis_12_101818
PubMedID: 34537543

Title : A review on ferulic acid and analogs based scaffolds for the management of Alzheimer's disease - Singh_2021_Eur.J.Med.Chem_215_113278
Author(s) : Singh YP , Rai H , Singh G , Singh GK , Mishra S , Kumar S , Srikrishna S , Modi G
Ref : Eur Journal of Medicinal Chemistry , 215 :113278 , 2021
Abstract : Alzheimer's disease (AD) is an age-related multifactorial neurodegenerative disorder characterized by severe central cholinergic neuronal loss, gradually contributing to cognitive dysfunction and impaired motor activity, resulting in the brain's cell death at the later stages of AD. Although the etiology of AD is not well understood, however, several factors such as oxidative stress, deposition of amyloid-beta (Abeta) peptides to form Abeta plaques, intraneuronal accumulation of hyperphosphorylated tau protein, and low level of acetylcholine are thought to play a major role in the pathogenesis of AD. There is practically no drug for AD treatment that can address the basic factors responsible for the neurodegeneration and slow down the disease progression. The currently available therapies for AD in the market focus on providing only symptomatic relief without addressing the aforesaid basic factors responsible for the neurodegeneration. Ferulic acid (FA) is a phenol derivative from natural sources and serves as a potential pharmacophore that exerts multiple pharmacological properties such as antioxidant, neuroprotection, Abeta aggregation modulation, and anti-inflammatory. Several FA based hybrid analogs are under investigation as a multi-target directed ligand (MTDLs) to develop novel hybrid compounds for the treatment of AD. In the present review article, we are focused on the critical pathogenic factors responsible for the onset of AD followed by the developments of FA pharmacophore-based hybrids compounds as a novel multifunctional therapeutic agent to address the limitations associated with available treatment for AD. The rationale behind the development of these compounds and their pharmacological activities in particular to their ChE inhibition (ChEI), neuroprotection, antioxidant property, Abeta aggregation modulation, and metal chelation ability, are discussed in detail. We have also discussed the discovery of caffeic and cinnamic acids based MTDLs for AD. This review paper provides an in-depth insight into the research progress and current status of these novel therapeutics in AD and prospects for developing a druggable molecule with desired pharmacological affinity and reduced toxicity for the management of AD.
ESTHER : Singh_2021_Eur.J.Med.Chem_215_113278
PubMedSearch : Singh_2021_Eur.J.Med.Chem_215_113278
PubMedID: 33662757

Title : A Broad Temperature Active Lipase Purified From a Psychrotrophic Bacterium of Sikkim Himalaya With Potential Application in Detergent Formulation - Kumar_2020_Front.Bioeng.Biotechnol_8_642
Author(s) : Kumar A , Mukhia S , Kumar N , Acharya V , Kumar S , Kumar R
Ref : Front Bioeng Biotechnol , 8 :642 , 2020
Abstract : Bacterial lipases with activity spanning over a broad temperature and substrate range have several industrial applications. An efficient enzyme-producing bacterium Chryseobacterium polytrichastri ERMR1:04, previously reported from Sikkim Himalaya, was explored for purification and characterization of cold-adapted lipase. Optimum lipase production was observed in 1% (v/v) rice bran oil, pH 7 at 20degC. Size exclusion and hydrophobic interaction chromatography purified the enzyme up to 21.3-fold predicting it to be a hexameric protein of 250 kDa, with 39.8 kDa monomeric unit. MALDI-TOF-MS analysis of the purified lipase showed maximum similarity with alpha/beta hydrolase (lipase superfamily). Biochemical characterization of the purified enzyme revealed optimum pH (8.0), temperature (37degC) and activity over a temperature range of 5-65degC. The tested metals (except Cu(2+) and Fe(2+)) enhanced the enzyme activity and it was tolerant to 5% (v/v) methanol and isopropanol. The Km and Vmax values were determined as 0.104 mM and 3.58 U/mg, respectively for p-nitrophenyl palmitate. Bioinformatics analysis also supported in vitro findings by predicting enzyme's broad temperature and substrate specificity. The compatibility of the purified lipase with regular commercial detergents, coupled with its versatile temperature and substrate range, renders the given enzyme a promising biocatalyst for potential detergent formulations.
ESTHER : Kumar_2020_Front.Bioeng.Biotechnol_8_642
PubMedSearch : Kumar_2020_Front.Bioeng.Biotechnol_8_642
PubMedID: 32671041

Title : Scopoletin: Antiamyloidogenic, Anticholinesterase, and Neuroprotective Potential of a Natural Compound Present in Argyreia speciosa Roots by In Vitro and In Silico Study - Kashyap_2020_Neurosci.Insights_15_2633105520937693
Author(s) : Kashyap P , Ram H , Shukla SD , Kumar S
Ref : Neurosci Insights , 15 :2633105520937693 , 2020
Abstract : Alzheimer's disease (AD) is characterized by depositions of amyloid beta (Abeta) peptides aggregates resulting in plaques formation in the central nervous system (CNS). This study evaluates the disease-modifying potential of scopoletin against multiple factors associated with AD such as cholinesterase enzymes, Abeta peptides, and neuroprotective properties against Abeta- and H(2)O(2)-induced cytotoxicity under in vitro conditions. Scopoletin was identified and quantified using UPLC-QTOF (ultra-high performance liquid chromatography-quadrupole time-of-flight) and high-performance liquid chromatography (HPLC), respectively. The antiamyloidogenic potential was evaluated by thioflavin T and congo red binding assay. Inhibition of key enzymes, that is, acetylcholinesterase and butyrylcholinesterase, was investigated by Ellman's assay. UPLC-QTOF analysis showed that most abundant phytoconstituent present in Argyreia speciosa hydroalcoholic root extract was scopoletin followed by festuclavine and ergometrine. Scopoletin was further quantified using novel reverse phase (RP)-HPLC method developed in this study. The neuroprotective potential of scopoletin was found to be 69% against Abeta42-induced neurotoxicity and 73% against H(2)O(2)-induced cytotoxicity in PC12 cell culture at 40 muM final concentration. At the same concentration, scopoletin inhibited Abeta42 fibril formation up to 57%. The IC(50) concentration for AChE and BuChE enzyme inhibition by scopoletin was 5.34 and 9.11 muM, respectively. The antiaggregation and enzyme inhibition results were complemented with strong molecular interactions of scopoletin with target proteins validated by in silico molecular docking analysis. Based on this study, it can be concluded that scopoletin can be used as a lead for amelioration of symptoms and disease-modifying effects in AD.
ESTHER : Kashyap_2020_Neurosci.Insights_15_2633105520937693
PubMedSearch : Kashyap_2020_Neurosci.Insights_15_2633105520937693
PubMedID: 32671342

Title : Synthesis of novel 4-methylthiocoumarin and comparison with conventional coumarin derivative as a multi-target-directed ligand in Alzheimer's disease - Kumar_2020_3.Biotech_10_509
Author(s) : Kumar S , Tyagi YK , Kumar M
Ref : 3 Biotech , 10 :509 , 2020
Abstract : Alzheimer's disease (AD) is a multifactorial disorder characterized by cognitive deficit and memory loss. The pathological feature of the disease involves beta-amyloid senile plaques, reduced levels of acetylcholine neurotransmitter, oxidative stress and neurofibrillary tangles formation within the brain of AD patients. The present study aims to screen the inhibitory activity of newly synthesized and existing novel 4-methylthiocoumarin derivative against acetylcholinesterase, butyrylcholinesterase, BACE1, beta-amyloid aggregation and oxidative stress involved in the AD pathogenesis. The in vitro assays used in this study were Ellman's assay, FRET assays, Thioflavin T, transmission electron microscopy, circular dichroism, FRAP, and TEAC. Molecular docking and dynamics studies were performed to correlate the results. C3 and C7 (thiocoumarin derivatives) were found to be the most potent inhibitors of acetylcholinesterase (IC(50)-5.63 muM) and butyrylcholinesterase (IC(50)-3.40 muM) using Ellman's assays. Enzyme kinetic studies showed that C3 and C7 compounds followed by the mixed mode of inhibition using LB plot. C3 also moderately inhibited the BACE1 using FRET assay. C3 inhibited the fibrillization of beta-amyloid peptides in a concentration-dependent manner as observed by Thioflavin T, TEM studies and Circular dichroism data. Molecular modeling studies were performed to understand the probable mode of binding of C3 and C7 in the binding pocket of acetylcholinesterase, butyrylcholinesterase, BACE1 and amyloid beta peptides. This indicates the important role of hydrophobic interactions between C3 and acetylcholinesterase. C3 also exhibited significant antioxidant potential by FRAP and TEAC assays. Hence, C3 might serve as a promising lead for developing novel multi target-directed ligand for the treatment of AD.
ESTHER : Kumar_2020_3.Biotech_10_509
PubMedSearch : Kumar_2020_3.Biotech_10_509
PubMedID: 33184595

Title : A multi-biomarker approach using integrated biomarker response to assess the effect of pH on triclosan toxicity in Pangasianodon hypophthalmus (Sauvage, 1878) - Paul_2020_Environ.Pollut_260_114001
Author(s) : Paul T , Kumar S , Shukla SP , Pal P , Kumar K , Poojary N , Biswal A , Mishra A
Ref : Environ Pollut , 260 :114001 , 2020
Abstract : Application of biomarkers is an effective approach for a better understanding of varying toxicity in aquatic organisms during the seasonal and diurnal changes in the natural environment. This report describes the toxicity of sub-lethal concentrations of triclosan (TCS) at different pH (6.5, 7.5 and 8.5) based on selected biomarkers related to oxidative stress, metabolism and genotoxicity in Pangasianodon hypophthalmus. The 96 h LC50 of TCS for P. hypophthalmus was lower at pH 6.5 when compared to higher pH. The sub-lethal concentration of TCS exhibited a significant decrease in hematological parameters related to complete blood counts except for total leukocyte count (TLC), mean cell haemoglobin concentration (MCHC) and red cell distribution width (RDW). Multivariate data analysis showed a significant interaction of TCS and pH in metabolizing enzymes like glutamic oxaloacetate transaminase (GOT), glutamic pyruvic transaminase (GPT), Lactate dehydrogenase (LDH), antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT) and glutathione-s-transferase (GST) and neurotransmitter enzyme acetylcholinesterase (AChE). A significant increase in DNA damage and micronuclei frequency in liver and blood cells of TCS exposed fish at pH 6.5 indicate that the TCS exposure has pronounced effects on genetic materials. The findings of present study establish that enzymes like SOD, LDH, GOT, AChE, DNA damage and micronuclei frequency can be successfully deployed as biomarkers for the assessment of toxicity of TCS in fish.
ESTHER : Paul_2020_Environ.Pollut_260_114001
PubMedSearch : Paul_2020_Environ.Pollut_260_114001
PubMedID: 32041020

Title : Inhibition of BACE1, MAO-B, cholinesterase enzymes, and anti-amyloidogenic potential of selected natural phytoconstituents: Multi-target-directed ligand approach - Chowdhury_2020_J.Food.Biochem__e13571
Author(s) : Chowdhury S , Kumar S
Ref : J Food Biochem , :e13571 , 2020
Abstract : Alzheimer's disease (AD) is a neurodegenerative disorder, and multiple factors are involved in disease progression. This is why there is an urgent need to develop novel molecules with multi-target-directed ligands (MTDLs) potential. The current study explores the active phytoconstituents from traditionally used medicinal spices, namely piperine, cinnamaldehyde, eugenol, cuminaldehyde, and alpha-terpinyl acetate for the inhibition of beta-secretase, monoamine oxidase, cholinesterase enzymes, anti-aggregation of amyloid beta (Abeta) fibrils, and their protective effect against hydrogen peroxide (H(2) O(2) ) and Abeta-induced toxicity. Eugenol showed inhibitory activity against MAO-B enzyme, free radical scavenging activity, and anti-aggregation activity against Abeta peptides than other phytoconstituents. It also demonstrated a significant cytoprotective effect against H(2) O(2) -induced oxidative stress and Abeta-induced cytotoxicity in pheochromocytoma (PC) 12 cells. A molecular docking study of eugenol showed interactions with active site residue of the target enzymes. The study successfully demonstrated that eugenol could have an MTDLs potential better than synthesized drugs used in the treatment of AD. PRACTICAL APPLICATIONS: The present study demonstrated multi-target-directed ligand potential of eugenol and can be developed to treat complex diseases like Alzheimer's. Eugenol can bind to different Alzheimer's targets such as beta-secretase (BACE1), Monoamine oxidase B (MAO-B), Cholinesterase's, and amyloid beta(1-42) fibrils and might have a disease-modifying potential. The other natural phytoconstituents such as piperine, cinnamaldehyde, cuminaldehyde, and alpha-terpinyl acetate also demonstrated MTDL potential could also be used for developing novel molecules for disease-modifying effect. It also protects against oxidative stress.
ESTHER : Chowdhury_2020_J.Food.Biochem__e13571
PubMedSearch : Chowdhury_2020_J.Food.Biochem__e13571
PubMedID: 33249607

Title : Ajmalicine and Reserpine: Indole Alkaloids as Multi-Target Directed Ligands Towards Factors Implicated in Alzheimer's Disease - Kashyap_2020_Molecules_25_
Author(s) : Kashyap P , Kalaiselvan V , Kumar R , Kumar S
Ref : Molecules , 25 : , 2020
Abstract : Alzheimer's disease (AD) is a multifactorial disorder characterized by exponential loss of memory and cognitive deficit involving several disease modifying targets (amyloid beta, beta-secretase, monoaminoxidase-B, and cholinesterase). The present study explores multi-target directed ligand approach using secondary metabolite reserpine (RES) and ajmalicine (AJM) obtained from Rauwolfia serpentina roots. Novel LCMS and HPLC methods were developed for identification and quantification of reserpine and ajmalicine. In vitro enzyme inhibition assays were performed to evaluate anti-cholinesterase, beta-site amyloid cleaving enzyme (BACE-1) inhibition and monoamine oxidase-B (MAO-B) inhibition, further analyzed with in silico analysis. Anti-amyloidogenic potential was studied using anti-aggregation studies along with TEM and circular dichroism (CD) analysis. In vitro neuroprotective potential against Abeta toxicity and anti-oxidative stress was demonstrated using PC12 cell cultures. Reserpine is a more potent dual cholinesterase inhibitor than ajmalicine (IC50 values of 1.7 muM (AChE) and 2.8 muM (BuChE)). The anti-aggregation activity of reserpine (68%) was more than ajmalicine (56%). Both compounds demonstrated neuroprotective activity against Abeta42 (92%) and H2O2 (93%) induced toxicity in PC12 cells against controls. Phytocompounds also inhibited MAO-B and BACE-1 enzymes in concentration dependent manner. Molecular docking studies indicated the strong binding of compounds to the catalytic site of targets. This novel study demonstrated that reserpine and ajmalicine as a multi-target directed ligand that have disease modifying potential for amelioration of AD.
ESTHER : Kashyap_2020_Molecules_25_
PubMedSearch : Kashyap_2020_Molecules_25_
PubMedID: 32244635

Title : Effect of temperature on triclosan toxicity in Pangasianodon hypophthalmus (Sauvage, 1878): Hematology, biochemistry and genotoxicity evaluation - Paul_2019_Sci.Total.Environ_668_104
Author(s) : Paul T , Shukla SP , Kumar K , Poojary N , Kumar S
Ref : Sci Total Environ , 668 :104 , 2019
Abstract : The rising level of triclosan (TCS) in aquatic environment is raising concerns and in this context, evaluation of toxicity towards aquatic organisms under varying environmental conditions, especially temperature, is a pre-requisite for a better understanding of the toxic effects on specific metabolic processes. In this report, the mechanistic physiological responses of fish towards varying concentration of TCS at graded temperature were evaluated. The static renewal acute test was performed, and 96h median lethal concentration (LC50) of TCS for Pangasianodon hypophthalmus was estimated and the values were 848.33, 1181.94 and 1356.96mugL(-1) at 25, 30 and 35 degrees C respectively. The chronic study was performed for 30days at 1/5th and 1/10th concentration of the estimated LC50 of TCS at 25, 30 and 35 degrees C respectively. The chronic effects resulted in significant decrease in total erythrocyte count (TEC), hemoglobin (Hb), packed cell volume (PCV), mean corpuscular hemoglobin (MCH) and mean cell volume (MCV), while a significant increase in total leukocyte count (TLC), mean corpuscular hemoglobin concentration (MCHC) and red cell distribution width (RDW) was observed in TCS exposed groups at 25-35 degrees C. Further, a significant increase in activity of transaminase enzymes, lactate dehydrogenase (LDH) and antioxidant enzymes (superoxide dismutase) (SOD) and catalase (CAT) except glutathione-S-transferase (GST) in liver and acetylcholinesterase (AChE) in brain of the TCS exposed fish was recorded in all the above temperature range. Severe damage of DNA in nucleus of blood and liver cells, and high micronuclei frequency (MNi) was noticed in TCS exposed groups at 25 degrees C. The report provides convincing evidence for the effect of temperature on TCS toxicity. The findings will help in gaining a better insight into the change in toxicity of TCS in a natural environment where diurnal variations in temperature may be crucial in determining the overall extent of toxicity.
ESTHER : Paul_2019_Sci.Total.Environ_668_104
PubMedSearch : Paul_2019_Sci.Total.Environ_668_104
PubMedID: 30852190

Title : Sarsasapogenin: A steroidal saponin from Asparagus racemosus as multi target directed ligand in Alzheimer's Disease - Kashyap_2019_Steroids__108529
Author(s) : Kashyap P , Muthusamy K , Niranjan M , Trikha S , Kumar S
Ref : Steroids , :108529 , 2019
Abstract : Alzheimer's Disease (AD) is multi-factorial disorder characterized by impaired memory and cognition deficit. AD is characterized by impaired cholinergic transmission, extracellular amyloid beta deposits , neurofibillary tangles and oxidative stress. A multi-target directed ligand (MTDL) approach is required to devise a therapeutic strategy against AD. In the present study, Asparagus racemosus aqueous extract was chosen, as it possess abundant medicinal properties including nootropic effect mentioned in ancient Ayurvedic texts. Moreover, its secondary metabolite sarsasapogenin (SRS) was also selected for this multi-target study for the very first time. The current study demonstrated that sarsasapogenin significantly inhibits key enzymes involved in pathogenesis of AD which are acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), BACE1 and MAO-B in a concentration dependent manner. SRS also exhibited anti-amyloidogenic, anti-oxidant and neuroprotective effects by in vitro studies. The IC50 values of SRS is 7.7muM and 23.4muM for AChE and BuChE respectively. SRS also significantly inhibited Abeta42 fibrilisation up to 68% at 40muM concentration as compared to control. TEM visualization showed Abeta aggregates as short and scattered fibril clearly indicating SRS significantly inhibited peptide nucleation and fibril formation. Furthermore, the SRS was found to exert neuroprotective effect on PC12 cells against Abeta42 and H2O2-mediated cytotoxicity. The cell survival was 62% and 69% against Abeta42 and H2O2-mediated cytotoxicity, respectively. SRS also inhibited monoaminoxidase-B (MAO-B) and BACE1 enzymes in concentration dependent manner. Molecular docking studies indicated that SRS binds to the catalytic sites of multiple targets (AChE, BuChE, Abeta42, BACE1, and MAO-B) in a significant manner that might having disease-modifying effects. Thus SRS is acting as suitable lead and can be utilised as MTDL compound for factors implicated in AD.
ESTHER : Kashyap_2019_Steroids__108529
PubMedSearch : Kashyap_2019_Steroids__108529
PubMedID: 31672628

Title : Dual Inhibition of DPP-4 and Cholinesterase Enzymes by the Phytoconstituents of the Ethanolic Extract of Prosopis cineraria Pods: Therapeutic Implications for the Treatment of Diabetes-associated Neurological Impairments - Ram_2019_Curr.Alzheimer.Res_16_1230
Author(s) : Ram H , Jaipal N , Kumar P , Deka P , Kumar S , Kashyap P , Singh BP , Alqarawi AA , Hashem A , Tabassum B , Abd Allah EF
Ref : Curr Alzheimer Res , 16 :1230 , 2019
Abstract : BACKGROUND: Insulin resistance causes decreased uptake of glucose which promotes the susceptibility of type 2 associated neurological impairments. METHODS: The study was aimed to evaluate the inhibition potential of the ethanolic extract of Prosopis cineraria (EPC) pods against DPP-4 and cholinesterase enzymes by in-vitro, in-vivo and in-silico assessments. The present study consists of in vivo studies on a diabetes-induced rat model by HOMA (Homeostasis model assessment) and related parameters, in vitro studies through the DPP-4 enzyme assay and cholinesterase assays using Ellman's reaction. The in-silico studies were conducted by the molecular docking of Cinerin C with targeted enzymes. The phytochemical characterization of the extract was demonstrated through LCMS studies. The antioxidant studies on the extract were performed by FRAP and TEAC assays. RESULTS: The extract showed 64.8% maximum inhibition of DPP-4, 34.91% inhibition of AChE and 74.35% inhibition of BuChE. The antioxidant capacity of the extract was observed to be 847.81+/-16.25muM Fe2+ equivalent in the FRAP assay and 0.40 +/- 0.08 mmol/l of Trolox equivalent in the TEAC assay. The in vivo study showed competent glycaemic control against significant HOMA IR (1.5), HOMA % beta (26.5) and HOMA % S (68.8) as well as pancreatic cell mass proliferation. The insilico analysis also revealed positive interactions of Cinerin C with targeted enzymes (DPP4 and cholinesterase). CONCLUSION: It can be concluded that the phytoconstituents of Prosopis cineraria pod extract can be significantly considered in neuropharmacology to resolve insulin resistance-induced neurological complications as it showed inhibition against DPP-4, AChE and BuChE target enzymes.
ESTHER : Ram_2019_Curr.Alzheimer.Res_16_1230
PubMedSearch : Ram_2019_Curr.Alzheimer.Res_16_1230
PubMedID: 31797759

Title : Experimental and Computational Evaluation of Piperonylic Acid Derived Hydrazones Bearing Isatin Moieties as Dual Inhibitors of Cholinesterases and Monoamine Oxidases - Vishnu_2019_ChemMedChem_14_1359
Author(s) : Vishnu MS , Pavankumar V , Kumar S , Raja AS
Ref : ChemMedChem , 14 :1359 , 2019
Abstract : A set of piperonylic acid derived hydrazones with variable isatin moieties was synthesized and evaluated for their inhibitory activity against the enzymes acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and monoamine oxidases A and B (MAO-A/B). The results of in vitro studies revealed IC50 values in the micromolar range, with the majority of the compounds showing selectivity for the MAO-B isoform. N-[2-Oxo-1-(prop-2-ynyl)indolin-3-ylidene]benzo[d][1,3]dioxole-5-carbohydrazide (3) was identified as a lead AChE inhibitor with IC50 =0.052+/-0.006 mum. N-[(3E)-5-chloro-2-oxo-2,3-dihydro-1H-indol-3-ylidene]-2H-1,3-benzodioxole-5-carb ohydrazide (2) was the lead MAO-B inhibitor with IC50 =0.034+/-0.007 mum, and showed 50 times greater selectivity for MAO-B over MAO-A. The kinetic studies revealed that compounds 2 and 3 displayed competitive and reversible inhibition of AChE and MAO-B, respectively. The molecular docking studies revealed the significance of hydrophobic interactions in the active site pocket of the enzymes under investigation. Further optimization studies might lead to the development of potential neurotherapeutic agents.
ESTHER : Vishnu_2019_ChemMedChem_14_1359
PubMedSearch : Vishnu_2019_ChemMedChem_14_1359
PubMedID: 31177620

Title : Enteric RET inhibition attenuates gastrointestinal secretion and motility via cholinergic signaling in rat colonic mucosal preparations - Russell_2018_Neurogastroenterol.Motil__e13479
Author(s) : Russell JP , Mohammadi E , Ligon C , Latorre R , Johnson AC , Hoang B , Krull D , Ho MW , Eidam HS , DeMartino MP , Cheung M , Oliff AI , Kumar S , Greenwood-Van Meerveld B
Ref : Neurogastroenterol Motil , :e13479 , 2018
Abstract : BACKGROUND: The expression of RET in the developing enteric nervous system (ENS) suggests that RET may contribute to adult intestinal function. ENS cholinergic nerves play a critical role in the control of colonic function through the release of acetylcholine (ACh). In the current study, we hypothesized that a RET-mediated mechanism may regulate colonic ion transport and motility through modulation of cholinergic nerves. METHODS: The effect of RET inhibition on active ion transport was assessed electrophysiologically in rat colonic tissue mounted in Ussing chambers via measurements of short circuit current (Isc) upon electrical field stimulation (EFS) or pharmacologically with cholinergic agonists utilizing a gastrointestinal (GI)-restricted RET inhibitor. We assessed the effect of the RET inhibitor on propulsive motility via quantification of fecal pellet output (FPO) induced by the acetylcholinesterase inhibitor neostigmine. KEY RESULTS: We found that enteric ganglia co-expressed RET and choline acetyltransferase (ChAT) transcripts. In vitro, the RET kinase inhibitor GSK3179106 attenuated the mean increase in Isc induced by either EFS or carbachol but not bethanechol. In vivo, GSK3179106 significantly reduced the prokinetic effect of neostigmine. CONCLUSION AND INFERENCES: Our findings provide evidence that RET-mediated mechanisms regulate colonic function by maintaining cholinergic neuronal function and enabling ACh-evoked chloride secretion and motility. We suggest that modulating the cholinergic control of the colon via a RET inhibitor may represent a novel target for the treatment of intestinal disorders associated with increased secretion and accelerated GI transit such as irritable bowel syndrome with diarrhea (IBS-D).
ESTHER : Russell_2018_Neurogastroenterol.Motil__e13479
PubMedSearch : Russell_2018_Neurogastroenterol.Motil__e13479
PubMedID: 30311722

Title : Triclosan toxicity alters behavioral and hematological parameters and vital antioxidant and neurological enzymes in Pangasianodon hypophthalmus (Sauvage, 1878) - Sahu_2018_Aquat.Toxicol_202_145
Author(s) : Sahu VK , Karmakar S , Kumar S , Shukla SP , Kumar K
Ref : Aquat Toxicol , 202 :145 , 2018
Abstract : Triclosan and its metabolites are detected in a diverse aquatic environment and are major concerns for various aquatic organisms. The present study investigated the impact of acute and sub-lethal exposure of triclosan on behaviour, activities of acetylcholinesterase and selected antioxidant enzymes, haematological and serum gas-electrolyte parameters of Pangasianodon hypophthalmus. The 96h LC50 of triclosan for P. hypophthalmus was estimated as 1458mugL(-1). Further, sub-lethal triclosan exposure to 1/15th (97mugL(-1)), 1/10th (145mugL(-1)) and 1/5th (291mugL(-1)) of 96h LC50 concentration for a period of 45 days lead to decrease in total erythrocyte count, haemoglobin content and packed cell volume of blood while total leukocyte count increased significantly (p<0.05) as compared to control. A concentration-dependent increase in the serum chloride and decrease in partial pressure of oxygen in blood serum was noted on 45th day. An increased activity of catalase and superoxide dismutase in gill and liver tissues and inhibition of acetylcholinesterase activity in brain was observed on 15th, 30th and 45th day of exposure which was dependent on both - concentration of triclosan and duration of exposure. A significant high activity of glutathione-S-transferase in gill and liver tissue was observed in triclosan exposed groups in comparison to control during the experimental period. The study shows that long-term sub-lethal exposure of triclosan to fish can lead to several physiological alterations such as enzymatic scavenging of oxygen radicals and the normal neurological functions mediated by the enzyme acetylcholinesterase. With increasing anthropogenic activity, the study provides a convincing evidence for the necessity of a regulated use and safer disposal of triclosan to the environment.
ESTHER : Sahu_2018_Aquat.Toxicol_202_145
PubMedSearch : Sahu_2018_Aquat.Toxicol_202_145
PubMedID: 30031254

Title : Leukocyte count: A reliable marker for the severity of organophosphate intoxication? - Kumar_2018_J.Lab.Physicians_10_185
Author(s) : Kumar S , Agrawal S , Raisinghani N , Khan S
Ref : J Lab Physicians , 10 :185 , 2018
Abstract : INTRODUCTION: Organophosphorus poisoning (OPP) is a major public health problem in developing countries like India. Leukocyte count is a simple and inexpensive test, and elevated count is associated with acute inflammation and increased oxidative stress-like OPP. This study was done to correlate the severity of acute OPP with leukocyte count and also to assess the prognosis. MATERIALS AND METHODS: A prospective, observational clinical study was done on 80 patients suspected of OPP of age >15 years admitted to emergency unit at a tertiary rural teaching health-care center of Central India. Serum cholinesterase level and leukocyte count were estimated at the time of admission in all patients and severity of OPP was assessed according to Peradeniya organophosphorus poisoning (POP) scale. RESULTS: The mean age of the patients was 33.52 years (standard deviation [SD] 11.62) in males and 27.30 years (SD 7.33) in females. Among them, 57 (71.25%) were males and 23 (28.75%) were females. The severity of poisoning was directly correlated with serum cholinesterase level (P = 0.0001). Leukocyte count had a sensitivity of 60%, specificity of 76%, and negative predictive value of 85% if counts were more than 12,000 and 30% sensitivity, 95% specificity, and 80% negative predictive value if counts were more than 15,000 in predicting mortality in patients with OPP. CONCLUSION: Leukocyte count levels on admission can be used a prognostic marker in patients with OP poisoning.
ESTHER : Kumar_2018_J.Lab.Physicians_10_185
PubMedSearch : Kumar_2018_J.Lab.Physicians_10_185
PubMedID: 29692585

Title : Molecular mechanism of synthetic pyrethroid and organophosphate resistance in field isolates of Rhipicephalus microplus tick collected from a northern state of India - Nagar_2018_Exp.Appl.Acarol_75_319
Author(s) : Nagar G , Sharma AK , Kumar S , Saravanan BC , Kumar R , Gupta S , Ghosh S
Ref : Exp Appl Acarol , 75 :319 , 2018
Abstract : The frequently used chemical control method to manage Rhipicephalus microplus is limited by the emergence of resistance populations. Understanding of resistance mechanisms is essential to develop strategy for sustainable management. The present study was focused on working out the molecular mechanisms of resistance against synthetic pyrethroids (SPs) and organophosphates (OPs) in field isolates of R. microplus collected from six districts of Uttar Pradesh, India. Adult immersion test with discriminating concentrations (AIT-DC) was used to determine resistance status of isolates to SPs (deltamethrin, cypermethrin) and OPs (diazinon, coumaphos). All the six isolates were found resistant to SPs with resistance factor (RF) of 2.9-58.6 and to one of the OP compounds, diazinon having RF of 3.5-13.7 but susceptible to coumaphos (RF < 1.4). Three R. microplus genes, viz. para-sodium channel domain II S4-5 linker, carboxylesterase (372 bp) and acetylcholinesterase 2 (1692 bp) were sequenced and compared with respective sequences of reference susceptible IVRI-I, reference OP resistant population (IVRI-III), IVRI-IV and multi-acaricide resistant population (IVRI-V) of R. microplus. A C190A mutation in the domain II S4-5 linker region of sodium channel gene leading to L64I amino acid substitution was detected in all six isolates. The G1120A mutation in the carboxylesterase gene could not be detected in any isolate. Five nucleotide substitutions viz., G138A, G889A, T1090A, C1234T and G1403A were identified in the acetylcholinesterase 2 gene leading to four amino acid substitutions. The findings of the study corroborate the role of mutation in sodium channel and acetylcholinesterase 2 genes in SP and OP resistance in this part of India.
ESTHER : Nagar_2018_Exp.Appl.Acarol_75_319
PubMedSearch : Nagar_2018_Exp.Appl.Acarol_75_319
PubMedID: 29846851
Gene_locus related to this paper: boomi-ACHE2

Title : Establishment of a multi-acaricide resistant reference tick strain (IVRI-V) of Rhipicephalus microplus - Fular_2018_Ticks.Tick.Borne.Dis_9_1184
Author(s) : Fular A , Sharma AK , Kumar S , Nagar G , Chigure G , Ray DD , Ghosh S
Ref : Ticks Tick Borne Dis , 9 :1184 , 2018
Abstract : Tick-borne diseases is a global threat and tick resistance to commonly used acaricides is a growing problem, thus calling for improved resistance monitoring tools. To aid in monitoring of resistance in field tick populations, a resistant colony of Rhipicephalus microplus was characterized with the aim to establish a reference multi-acaricide resistant tick strain. Using a standardized adult immersion test, the Lethal Concentration(LC)50 values for deltamethrin, cypermethrin, fenvalerate and diazinon against the laboratory selected resistant tick (LSRT) strain were determined as 306.7ppm, 2776.9ppm, 30262.1ppm and 9458.7ppm. Relative to the susceptible IVRI-I tick strain, the LSRT strain showed 4.78- and 5.84-fold increases in activity of esterases, a 6-fold increase for monooxygenases and a 2.24 fold increase for glutathione S-transferase. In the acetylcholinesterase 2 gene, 22 single nucleotide polymorphisms (SNPs) were identified in the LSRT strain. Four of these SNPs lead to amino acid substitutions and were consistently found in resistant field populations in India. A C190A mutation in the domain II S4-5 linker region of sodium channel gene resulting in a L64I amino acid substitution was recorded in the LSRT strain. Monitorable indicators for the maintenance of the strain, designated as the reference IVRI-V tick strain and representing the first established multi-acaricide resistant tick strain in India, were identified.
ESTHER : Fular_2018_Ticks.Tick.Borne.Dis_9_1184
PubMedSearch : Fular_2018_Ticks.Tick.Borne.Dis_9_1184
PubMedID: 29730262

Title : Sequential drug treatment algorithm for agitation and aggression in Alzheimer's and mixed dementia - Davies_2018_J.Psychopharmacol__269881117744996
Author(s) : Davies SJ , Burhan AM , Kim D , Gerretsen P , Graff-Guerrero A , Woo VL , Kumar S , Colman S , Pollock BG , Mulsant BH , Rajji TK
Ref : J Psychopharmacol , :269881117744996 , 2018
Abstract : INTRODUCTION: Behavioural and psychological symptoms of dementia (BPSD) include agitation and aggression in people with dementia. BPSD is common on inpatient psychogeriatric units and may prevent individuals from living at home or in residential/nursing home settings. Several drugs and non-pharmacological treatments have been shown to be effective in reducing behavioural and psychological symptoms of dementia. Algorithmic treatment may address the challenge of synthesizing this evidence-based knowledge. METHODS: A multidisciplinary team created evidence-based algorithms for the treatment of behavioural and psychological symptoms of dementia. We present drug treatment algorithms for agitation and aggression associated with Alzheimer's and mixed Alzheimer's/vascular dementia. Drugs were appraised by psychiatrists based on strength of evidence of efficacy, time to onset of clinical effect, tolerability, ease of use, and efficacy for indications other than behavioural and psychological symptoms of dementia. RESULTS: After baseline assessment and discontinuation of potentially exacerbating medications, sequential trials are recommended with risperidone, aripiprazole or quetiapine, carbamazepine, citalopram, gabapentin, and prazosin. Titration schedules are proposed, with adjustments for frailty. Additional guidance is given on use of electroconvulsive therapy, optimization of existing cholinesterase inhibitors/memantine, and use of pro re nata medications. CONCLUSION: This algorithm-based approach for drug treatment of agitation/aggression in Alzheimer's/mixed dementia has been implemented in several Canadian Hospital Inpatient Units. Impact should be assessed in future research.
ESTHER : Davies_2018_J.Psychopharmacol__269881117744996
PubMedSearch : Davies_2018_J.Psychopharmacol__269881117744996
PubMedID: 29338602

Title : Arsenic-induced oxidative stress, cholinesterase activity in the brain of Swiss albino mice, and its amelioration by antioxidants Vitamin E and Coenzyme Q10 - Sharma_2018_Environ.Sci.Pollut.Res.Int_25_23946
Author(s) : Sharma A , Kshetrimayum C , Sadhu HG , Kumar S
Ref : Environ Sci Pollut Res Int , 25 :23946 , 2018
Abstract : Arsenic toxicity becomes one of the major public health issues in several countries. Chronic and acute exposure to arsenic has been reported to be toxic to various systems of the human body and also observed in controlled experimental studies. The study was conducted to evaluate the neurotoxic effect of arsenic in Swiss albino mice and its amelioration by Vitamin E, Coenzyme Q10 and their combination. Swiss albino mice were treated with arsenic of 136 ppm for 15 days. The daily dose is 1/3 of LD 50 (acute) reported dose of arsenic. Thereafter, the animals were maintained either on drinking water or treated with Vitamin E (50 mg/kg bwt), Coenzyme Q10 (10 mg/kg bwt), and their combination by i.p.daily for 15 days. After the treatment, animals were sacrificed. The weight of the brain was marginally lower (ns), in arsenic-treated group as compared to control and antioxidant-protected groups. The LPO (lipid peroxidation) level was higher in arsenic-treated group, and this elevation was checked to some extent by the selected antioxidants which were statistically significant in combination of antioxidant-protected group. A significant reduction was found in GSH (reduced glutathione) level in the brain of arsenic-treated mice whereas GSH level was considerably higher in antioxidant-protected groups. Further, total thiol and total protein level were lower in arsenic-treated group. However, total thiol was significantly higher in antioxidant-protected groups. CAT (catalase) activity was significantly lower while SOD (superoxide dismutase) activity was marginally lowered in arsenic-treated group, and it was slightly higher in antioxidant-protected groups. Further, reduction in AChE (acetylcholinesterase) and BChE (butyrylcholinesterase) and motor coordination activity were also observed in arsenic-treated groups. Whereas, a higher AChE, BChE, and motor coordination activity was observed in antioxidant-protected group. These data indicate a positive role of selected antioxidant against the toxicity of arsenic in the brain of mice.
ESTHER : Sharma_2018_Environ.Sci.Pollut.Res.Int_25_23946
PubMedSearch : Sharma_2018_Environ.Sci.Pollut.Res.Int_25_23946
PubMedID: 29948670

Title : Characterization and establishment of a reference deltamethrin and cypermethrin resistant tick line (IVRI-IV) of Rhipicephalus (Boophilus) microplus - Ghosh_2017_Pestic.Biochem.Physiol_138_66
Author(s) : Ghosh S , Gupta S , Ajith Kumar KG , Sharma AK , Kumar S , Nagar G , Kumar R , Paul S , Fular A , Chigure G , Nandi A , Manjunathachar HV , Mohammad A , Verma MR , Saravanan BC , Ray D
Ref : Pestic Biochem Physiol , 138 :66 , 2017
Abstract : The problem of ticks and tick borne diseases is a global threat and growing reports of resistance to commonly used insecticides further aggravated the condition and demands for country specific resistance monitoring tools and possible solutions of the problem. Establishment of standard reference is prerequisite for development of monitoring tools. For studying possible role of different mechanisms involved in development of resistance in Rhipicephalus (Boophilus) microplus population and to develop newer drug to manage the problem of resistance, a deltamethrin exposed and selected tick colony, referred to as IVRI-IV, was characterized using reference susceptible IVRI-I tick line as control. The RF values of IVRI-IV ticks against deltamethrin, cypermethrin and diazinon were determined as 194.0, 26.6, 2.86, respectively, against adults. The esterase enzyme ratios of 2.60 and 5.83 was observed using alpha-naphthyl and beta-naphthyl acetate while glutathione S-transferase (GST) ratio was 3.77. Comparative analysis of IVRI-I and IVRI-IV carboxylesterase gene sequences revealed 13 synonymous and 5 non synonymous mutations, reported for the first time. The C190A mutation in the domain II S4-5 linker region of sodium channel gene leading to leucine to isoleucine (L64I) amino acid substitution was also detected in the IVRI-IV population. In the present study, monitorable indicators for the maintenance of the reference IVRI-IV colony, the first established deltamethrin and cypermethrin resistant tick line of India, were identified.
ESTHER : Ghosh_2017_Pestic.Biochem.Physiol_138_66
PubMedSearch : Ghosh_2017_Pestic.Biochem.Physiol_138_66
PubMedID: 28456306

Title : Green-synthesized CdS nano-pesticides: Toxicity on young instars of malaria vectors and impact on enzymatic activities of the non-target mud crab Scylla serrata - Sujitha_2017_Aquat.Toxicol_188_100
Author(s) : Sujitha V , Murugan K , Dinesh D , Pandiyan A , Aruliah R , Hwang JS , Kalimuthu K , Panneerselvam C , Higuchi A , Aziz AT , Kumar S , Alarfaj AA , Vaseeharan B , Canale A , Benelli G
Ref : Aquat Toxicol , 188 :100 , 2017
Abstract : Currently, nano-formulated mosquito larvicides have been widely proposed to control young instars of malaria vector populations. However, the fate of nanoparticles in the aquatic environment is scarcely known, with special reference to the impact of nanoparticles on enzymatic activity of non-target aquatic invertebrates. In this study, we synthesized CdS nanoparticles using a green protocol relying on the cheap extract of Valoniopsis pachynema algae. CdS nanoparticles showed high toxicity on young instars of the malaria vectors Anopheles stephensi and A. sundaicus. The antimalarial activity of the nano-synthesized product against chloroquine-resistant (CQ-r) Plasmodium falciparum parasites was investigated. From a non-target perspective, we focused on the impact of this novel nano-pesticide on antioxidant enzymes acetylcholinesterase (AChE) and glutathione S-transferase (GST) activities of the mud crab Scylla serrata. The characterization of nanomaterials was carried out by UV-vis and FTIR spectroscopy, as well as SEM and XRD analyses. In mosquitocidal assays, LC50 of V. pachynema-synthesized CdS nanoparticles on A. stephensi ranged from 16.856 (larva I), to 30.301mug/ml (pupa), while for An. sundaicus they ranged from 13.584 to 22.496mug/ml. The antiplasmodial activity of V. pachynema extract and CdS nanoparticles was evaluated against CQ-r and CQ-sensitive (CQ-s) strains of Plasmodium falciparum. IC50 of V. pachynema extract was 58.1mug/ml (CQ-s) and 71.46mug/ml (CQ-r), while nano-CdS IC50 was 76.14mug/ml (CQ-s) and 89.21mug/ml (CQ-r). In enzymatic assays, S. serrata crabs were exposed to sub-lethal concentrations, i.e. 4, 6 and 8mug/ml of CdS nanoparticles, assessing changes in GST and AChE activity after 16days. We observed significantly higher activity of GST, if compared to the control, during the whole experiment period. In addition, a single treatment with CdS nanoparticles led to a significant decrease in AChE activity over time. The toxicity of CdS nanoparticles and Cd ions in aqueous solution was also assessed in mud crabs, showing higher toxicity of aqueous Cd ions if compared to nano-CdS. Overall, our results underlined the efficacy of green-synthesized CdS nanoparticles in malaria vector control, outlining also significant impacts on the enzymatic activity of non-target aquatic organisms, with special reference to mud crabs.
ESTHER : Sujitha_2017_Aquat.Toxicol_188_100
PubMedSearch : Sujitha_2017_Aquat.Toxicol_188_100
PubMedID: 28482328

Title : Graft copolymerization of acrylamide on chitosan-co-chitin and its application for immobilization of Aspergillus sp. RL2Ct cutinase - Kumari_2017_Bioorg.Chem_70_34
Author(s) : Kumari V , Kumar S , Kaur I , Bhalla TC
Ref : Bioorg Chem , 70 :34 , 2017
Abstract : The synthesis of chitosan (Chs) and chitin (Chi) copolymer and grafting of acrylamide (AAm) onto the synthesized copolymer have been carried out by chemical methods. The grafted copolymer was characterized by FTIR, SEM and XRD. The extracellular cutinase of Aspergillus sp. RL2Ct (E.C. was purified to 4.46 fold with 16.1% yield using acetone precipitation and DEAE sepharose ion exchange chromatography. It was immobilized by adsorption on the grafted copolymer. The immobilized enzyme was found to be more stable then the free enzyme and has a good binding efficiency (78.8%) with the grafted copolymer. The kinetic parameters KM and Vmax for free and immobilized cutinase were found to be 0.55mM and 1410mumolmin-1mg-1 protein, 2.99mM and 996mumolmin-1mg-1 protein, respectively. The immobilized cutinase was recycled 64 times without considerable loss of activity. The matrix (Chs-co-Chi-g-poly(AAm)) prepared and cutinase immobilized on the matrix have potential applications in enzyme immobilization and organic synthesis respectively.
ESTHER : Kumari_2017_Bioorg.Chem_70_34
PubMedSearch : Kumari_2017_Bioorg.Chem_70_34
PubMedID: 27866660

Title : In silico repurposing of antipsychotic drugs for Alzheimer's disease - Kumar_2017_BMC.Neurosci_18_76
Author(s) : Kumar S , Chowdhury S
Ref : BMC Neurosci , 18 :76 , 2017
Abstract : BACKGROUND: Alzheimer's disease (AD) is the most prevalent form of dementia and represents one of the highest unmet requirements in medicine today. There is shortage of novel molecules entering into market because of poor pharmacokinetic properties and safety issues. Drug repurposing offers an opportunity to reinvigorate the slowing drug discovery process by finding new uses for existing drugs. The major advantage of the drug repurposing approach is that the safety issues are already investigated in the clinical trials and the drugs are commercially available in the marketplace. As this approach provides an effective solution to hasten the process of providing new alternative drugs for AD, the current study shows the molecular interaction of already known antipsychotic drugs with the different protein targets implicated in AD using in silico studies. RESULT: A computational method based on ligand-protein interaction was adopted in present study to explore potential antipsychotic drugs for the treatment of AD. The screening of approximately 150 antipsychotic drugs was performed on five major protein targets (AChE, BuChE, BACE 1, MAO and NMDA) by molecular docking. In this study, for each protein target, the best drug was identified on the basis of dock score and glide energy. The top hits were then compared with the already known inhibitor of the respective proteins. Some of the drugs showed relatively better docking score and binding energies as compared to the already known inhibitors of the respective targets. Molecular descriptors like molecular weight, number of hydrogen bond donors, acceptors, predicted octanol/water partition coefficient and percentage human oral absorption were also analysed to determine the in silico ADME properties of these drugs and all were found in the acceptable range and follows Lipinski's rule. CONCLUSION: The present study have led to unravel the potential of leading antipsychotic drugs such as pimozide, bromperidol, melperone, anisoperidone, benperidol and anisopirol against multiple targets associated with AD. Benperidol was found to be the best candidate drug interacting with different target proteins involved in AD.
ESTHER : Kumar_2017_BMC.Neurosci_18_76
PubMedSearch : Kumar_2017_BMC.Neurosci_18_76
PubMedID: 29078760

Title : Acetamide Derivatives of Chromen-2-ones as Potent Cholinesterase Inhibitors - Prasad_2017_Arch.Pharm.(Weinheim)_350_
Author(s) : Prasad S , Kumar B , Kumar S , Chand K , Kamble SS , Gautam HK , Sharma SK
Ref : Arch Pharm (Weinheim) , 350 : , 2017
Abstract : Alzheimer's disease (AD), a neurodegenerative disorder, is a serious medical issue worldwide with drastic social consequences. Inhibition of cholinesterase is one of the rational and effective approaches to retard the symptoms of AD and, hence, consistent efforts are being made to develop efficient anti-cholinesterase agents. In pursuit of this, a series of 19 acetamide derivatives of chromen-2-ones were synthesized and evaluated for their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory potential. All the synthesized compounds exhibited significant anti-AChE and anti-BChE activity, with IC50 values in the range of 0.24-10.19 muM and 0.64-30.08 muM, respectively, using donepezil hydrochloride as the standard. Out of 19 compounds screened, 3 compounds, viz. 22, 40, and 43, caused 50% inhibition of AChE at 0.24, 0.25, and 0.25 muM, respectively. A kinetic study revealed them to be mixed-type inhibitors, binding with both the CAS and PAS sites of AChE. The above-selected compounds were found to be effective inhibitors of AChE-induced and self-mediated Abeta1-42 aggregation. ADMET predictions demonstrated that these compounds may possess suitable blood-brain barrier (BBB) permeability. Hemolytic assay results revealed that these compounds did not lyse human RBCs up to a thousand times of their IC50 value. MTT assays performed for the shortlisted compounds showed them to be negligibly toxic after 24 h of treatment with the SH-SY5Y neuroblastoma cells. These results provide insights for further optimization of the scaffolds for designing the next generation of compounds as lead cholinesterase inhibitors.
ESTHER : Prasad_2017_Arch.Pharm.(Weinheim)_350_
PubMedSearch : Prasad_2017_Arch.Pharm.(Weinheim)_350_
PubMedID: 28699213

Title : Esterase mediated resistance in deltamethrin resistant reference tick colony of Rhipicephalus (Boophilus) microplus - Gupta_2016_Exp.Appl.Acarol_69_239
Author(s) : Gupta S , Ajith Kumar KG , Sharma AK , Nagar G , Kumar S , Saravanan BC , Ravikumar G , Ghosh S
Ref : Exp Appl Acarol , 69 :239 , 2016
Abstract : Monitoring of acaricide resistance is considered as one of the important facets of integrated tick management. In an attempt of development of resistance monitoring indicators, in the present study two reference tick lines of Rhipicephalus (Boophilus) microplus maintained in the Entomology laboratory, Indian Veterinary Research Institute (IVRI), Izatnagar, India, were studied to determine the possible contributing factors involved in development of resistance to deltamethrin. Electrophoretic profiling of esterase enzymes detected high activities of EST-1 in reference resistant tick colony designated as IVRI-IV whereas it was not detectable in reference susceptible IVRI-I line of R. (B.) microplus. Esterases were further characterized as carboxylesterase or acetylcholinesterase based on inhibitor study using PMSF, eserine sulphate, malathion, TPP and copper sulphate. It was concluded that an acetylcholinesterase, EST-1, possibly plays an important role for development of deltamethrin resistance in IVRI-IV colony of R. (B.) microplus.
ESTHER : Gupta_2016_Exp.Appl.Acarol_69_239
PubMedSearch : Gupta_2016_Exp.Appl.Acarol_69_239
PubMedID: 26979585

Title : In vitro anti-acetylcholinesterase activity of an aqueous extract of Unicaria tomentosa and in silico study of its active constituents - Chowdhury_2016_Bioinformation_12_112
Author(s) : Chowdhury S , Shivani , Kumar S
Ref : Bioinformation , 12 :112 , 2016
Abstract : Depletion of acetylcholine in the central nervous system (CNS) is responsible for memory loss and cognition deficit. Enzyme acetylcholinesterase (AChE) is responsible for destruction of acetylcholine (Ach) in the brain. Many herbal plant extracts have been investigated for their potential use in the treatment of Alzheimer's disease (AD) by inhibiting AChE and upregulating the levels of Ach. The current study investigated the anti-acetylcholinesterase (AChE) activity of an aqueous extract of Unicaria tomentosa bark which has not been reported so far in the literature. The in vitro study of an aqueous extract of U. tomentosa showed maximum inhibition of 76.2+/-0.002 % at 0.4mg/ml of final concentration with an IC50 = 0.112 mg/ml. The mechanism of inhibition was elucidated by kinetic study which showed mixed type of inhibition, this might be due to the presence of various phytoconstituents such as oxindole alkaloids present in an aqueous extract. Based on molecular structure of phytoconstituents obtained from U. tomentosa known from the relevant literature, in-silico molecular docking study was performed against AChE protein to validate the results.
ESTHER : Chowdhury_2016_Bioinformation_12_112
PubMedSearch : Chowdhury_2016_Bioinformation_12_112
PubMedID: 28149044

Title : Hit to lead optimization of a series of N-[4-(1,3-benzothiazol-2-yl)phenyl]acetamides as monoacylglycerol lipase inhibitors with potential anticancer activity - Afzal_2016_Eur.J.Med.Chem_121_318
Author(s) : Afzal O , Akhtar MS , Kumar S , Ali MR , Jaggi M , Bawa S
Ref : Eur Journal of Medicinal Chemistry , 121 :318 , 2016
Abstract : A total of thirty five new N-[4-(1,3-benzothiazol-2-yl)phenyl]acetamide derivatives were synthesized and structures of all the compounds were confirmed on the basis of elemental analysis and collective use of IR, (1)H NMR, (13)C NMR and mass spectral data. Compounds were tested for their ability to inhibit human monoacylglycerol lipase (hMAGL) enzyme. Eight compounds 4, 19-21, 24-26, and 34 reduced the hMAGL activity less than 50% at 100 nM concentrations. The halogen substituted aniline derivatives 20, 21 and 24-26 were found to be most active among all the synthesized compounds having IC50 value in the range of 6.5-9 nM. Twenty five compounds were selected by NCI, USA for one dose anticancer screening. Compound 21 (NSC: 780167) and 24 (NSC: 780168) fulfilled prearranged doorstep growth inhibition criteria and further selected for NCI full panel five dose assay at 10-fold dilutions of five different concentrations (0.01, 0.1, 1, 10 and 100 muM). Both the compounds 21 and 24 were found to be most active against MCF7 and MDA-MB-468 breast cancer cell lines. The GI50 value of 32.5 nM (MCF7) and 23.8 nM (MDA-MB-468) was observed for compound 21. Compound 24 showed GI50 values of 37.1 nM against MCF7 breast cancer cell line and 25.1 nM against MDA-MB-468 breast cancer cell line.
ESTHER : Afzal_2016_Eur.J.Med.Chem_121_318
PubMedSearch : Afzal_2016_Eur.J.Med.Chem_121_318
PubMedID: 27267002

Title : Dual inhibition of acetylcholinesterase and butyrylcholinesterase enzymes by allicin - Kumar_2015_Indian.J.Pharmacol_47_444
Author(s) : Kumar S
Ref : Indian J Pharmacol , 47 :444 , 2015
Abstract : OBJECTIVES: The brain of mammals contains two major form of cholinesterase enzymes, acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The dual inhibition of these enzymes is considered as a promising strategy for the treatment of neurological disorder such as Alzheimer's disease (AD), senile dementia, ataxia, and myasthenia gravis. The present study was undertaken to explore the anticholinesterase inhibition property of allicin. MATERIALS AND
METHODS: An assessment of cholinesterase inhibition was carried out by Ellman's assay.
RESULTS: The present study demonstrates allicin, a major ingredient of crushed garlic (Allium sativum L.) inhibited both AChE and BuChE enzymes in a concentration-dependent manner. For allicin, the IC50 concentration was 0.01 mg/mL (61.62 muM) for AChE and 0.05 +/- 0.018 mg/mL (308.12 muM) for BuChE enzymes.
CONCLUSIONS: Allicin shows a potential to ameliorate the decline of cognitive function and memory loss associated with AD by inhibiting cholinesterase enzymes and upregulate the levels of acetylcholine (ACh) in the brain. It can be used as a new lead to target AChE and BuChE to upregulate the level of ACh which will be useful in alleviating the symptoms associated with AD.
ESTHER : Kumar_2015_Indian.J.Pharmacol_47_444
PubMedSearch : Kumar_2015_Indian.J.Pharmacol_47_444
PubMedID: 26288480

Title : Evidence of salicylic acid pathway with EDS1 and PAD4 proteins by molecular dynamics simulation for grape improvement - Tandon_2015_J.Biomol.Struct.Dyn_33_2180
Author(s) : Tandon G , Jaiswal S , Iquebal MA , Kumar S , Kaur S , Rai A , Kumar D
Ref : J Biomol Struct Dyn , 33 :2180 , 2015
Abstract : Biotic stress is a major cause of heavy loss in grape productivity. In order to develop biotic stress-resistant grape varieties, the key defense genes along with its pathway have to be deciphered. In angiosperm plants, lipase-like protein phytoalexin deficient 4 (PAD4) is well known to be essential for systemic resistance against biotic stress. PAD4 functions together with its interacting partner protein enhanced disease susceptibility 1 (EDS1) to promote salicylic acid (SA)-dependent and SA-independent defense pathway. Existence and structure of key protein of systemic resistance EDS1 and PAD4 are not known in grapes. Before SA pathway studies are taken in grape, molecular evidence of EDS1: PAD4 complex is to be established. To establish this, EDS1 protein sequence was retrieved from NCBI and homologous PAD4 protein was generated using Arabidopsis thaliana as template and conserved domains were confirmed. In this study, computational methods were used to model EDS1 and PAD4 and simulated the interactions of EDS1 and PAD4. Since no structural details of the proteins were available, homology modeling was employed to construct three-dimensional structures. Further, molecular dynamic simulations were performed to study the dynamic behavior of the EDS1 and PAD4. The modeled proteins were validated and subjected to molecular docking analysis. Molecular evidence of stable complex of EDS1:PAD4 in grape supporting SA defense pathway in response to biotic stress is reported in this study. If SA defense pathway genes are explored, then markers of genes involved can play pivotal role in grape variety development especially against biotic stress leading to higher productivity.
ESTHER : Tandon_2015_J.Biomol.Struct.Dyn_33_2180
PubMedSearch : Tandon_2015_J.Biomol.Struct.Dyn_33_2180
PubMedID: 25483988

Title : Survey of acaricides resistance status of Rhipiciphalus (Boophilus) microplus collected from selected places of Bihar, an eastern state of India - Ghosh_2015_Ticks.Tick.Borne.Dis_6_668
Author(s) : Ghosh S , Kumar R , Nagar G , Kumar S , Sharma AK , Srivastava A , Ajith Kumar KG , Saravanan BC
Ref : Ticks Tick Borne Dis , 6 :668 , 2015
Abstract : Monitoring acaricide resistance in field ticks and use of suitable managemental practices are essential for controlling tick populations infesting animals. In the present study, the acaricide resistance status in Rhipicephalus (Boophilus) microplus ticks infesting cattle and buffaloes of five districts located in the eastern Indian state, Bihar were characterized using three data sets (AIT, Biochemical assays and gene sequences). Adult immersion test (AIT) was adopted using seven field isolates and their resistance factor (RF) was determined. Six isolates (DNP, MUZ, BEG, VSH, DRB and SUL) were found resistant to both deltamethrin and diazinon and except VSH all were resistant to cypermethrin. One isolate (PTN) was susceptible with a RF below 1.5. To understand the possible mode of resistance development, targeted enzymes and gene sequences of the para sodium channel and achetylcholinesterase 2 (AChE2) were analyzed. The esterase, monooxygenase and glutathione-S-transferase (GST) activity of reference susceptible IVRI-I line was determined as 2.47+/-0.007nmol/min/mg protein, 0.089+/-0.0016nmol/mg of protein and 0.0439+/-0.0003nmol/mg/min respectively, which increased significantly in the resistant field isolates. However, except esterases, the fold increase of monooxygenase (1.14-2.27 times) and GST (0.82-1.53 times) activities were not very high. A cytosine (C) to adenine (A) nucleotide substitution (CTC to ATC) at position 190 in domain II S4-5 linker region was detected only in one isolate (SUL) having RF of 34.9 and in the reference deltamethrin resistant line (IVRI-IV). However, the T2134A mutation was not detected in domain IIIS6 transmembrane segment of resistant isolates and also in reference IVRI-IV line despite of varying degree of resistance. The flumethrin specific G215T and the recently identified T170C mutations were also absent in domain II sequences under study. Four novel amino acid substitutions in AChE2 gene of field isolates and in organophosphate (OP) resistant reference IVRI-III line were identified which can possibly have a role in resistance development.
ESTHER : Ghosh_2015_Ticks.Tick.Borne.Dis_6_668
PubMedSearch : Ghosh_2015_Ticks.Tick.Borne.Dis_6_668
PubMedID: 26117183
Gene_locus related to this paper: boomi-ACHE2

Title : Docking based virtual screening and molecular dynamics study to identify potential monoacylglycerol lipase inhibitors - Afzal_2014_Bioorg.Med.Chem.Lett_24_3986
Author(s) : Afzal O , Kumar S , Kumar R , Firoz A , Jaggi M , Bawa S
Ref : Bioorganic & Medicinal Chemistry Lett , 24 :3986 , 2014
Abstract : Monoacylglycerol lipase (MAGL) is one of the key enzymes of the endocannabinoid system (ECS). It hydrolyzes one of the major endocannabinoid, 2-arachidonoylglycerol (2-AG), an endogenous full agonist at G protein coupled cannabinoid receptors CB1 and CB2. Numerous studies showed that MGL inhibitors are potentially useful for the treatment of pain, inflammation, cancer and CNS disorders. These provocative findings suggested that pharmacological inhibition of MAGL function may confer significant therapeutic benefits. In this study, we presented hybrid ligand and structure-based approaches to obtain a novel set of virtual leads as MAGL inhibitors. The constraints used in this study, were Glide score, binding free energy estimates and ADME properties to screen the ZINC database, containing approximately 21 million compounds. A total of seven virtual hits were obtained, which showed significant binding affinity towards MAGL protein. Ligand, ZINC24092691 was employed in complex form with the protein MAGL, for molecular dynamics simulation study, because of its excellent glide score, binding free energy and ADME properties. The RMSD of ZINC24092691 was observed to stay at 0.1nm (1A) in most of the trajectories, which further confirmed its ability to inhibit the protein MAGL. The hits were then evaluated for their ability to inhibit human MAGL. The compound ZINC24092691 displayed the noteworthy inhibitory activity reducing MAGL activity to 21.15% at 100nM concentration, with an IC50 value of 10nM.
ESTHER : Afzal_2014_Bioorg.Med.Chem.Lett_24_3986
PubMedSearch : Afzal_2014_Bioorg.Med.Chem.Lett_24_3986
PubMedID: 25011912

Title : Whole-genome sequencing of the snub-nosed monkey provides insights into folivory and evolutionary history - Zhou_2014_Nat.Genet_46_1303
Author(s) : Zhou X , Wang B , Pan Q , Zhang J , Kumar S , Sun X , Liu Z , Pan H , Lin Y , Liu G , Zhan W , Li M , Ren B , Ma X , Ruan H , Cheng C , Wang D , Shi F , Hui Y , Tao Y , Zhang C , Zhu P , Xiang Z , Jiang W , Chang J , Wang H , Cao Z , Jiang Z , Li B , Yang G , Roos C , Garber PA , Bruford MW , Li R
Ref : Nat Genet , 46 :1303 , 2014
Abstract : Colobines are a unique group of Old World monkeys that principally eat leaves and seeds rather than fruits and insects. We report the sequencing at 146x coverage, de novo assembly and analyses of the genome of a male golden snub-nosed monkey (Rhinopithecus roxellana) and resequencing at 30x coverage of three related species (Rhinopithecus bieti, Rhinopithecus brelichi and Rhinopithecus strykeri). Comparative analyses showed that Asian colobines have an enhanced ability to derive energy from fatty acids and to degrade xenobiotics. We found evidence for functional evolution in the colobine RNASE1 gene, encoding a key secretory RNase that digests the high concentrations of bacterial RNA derived from symbiotic microflora. Demographic reconstructions indicated that the profile of ancient effective population sizes for R. roxellana more closely resembles that of giant panda rather than its congeners. These findings offer new insights into the dietary adaptations and evolutionary history of colobine primates.
ESTHER : Zhou_2014_Nat.Genet_46_1303
PubMedSearch : Zhou_2014_Nat.Genet_46_1303
PubMedID: 25362486
Gene_locus related to this paper: rhibe-a0a2k6jtl7 , rhibe-ACHE , rhibe-a0a2k6k3y7 , rhibe-a0a2k6k493 , rhibe-a0a2k6lev4 , rhibe-a0a2k6lfa5 , rhibe-a0a2k6m6k8 , rhiro-a0a2k6p1u8 , rhiro-a0a2k6q1t8 , rhiro-a0a2k6q1w3 , rhibe-a0a2k6n5t9 , rhibe-a0a2k6ju46 , rhibe-a0a2k6kt48 , rhibe-a0a2k6llm5 , rhibe-a0a2k6lnt5 , rhiro-a0a2k6qzp6 , rhiro-a0a2k6q4a6 , rhibe-a0a2k6kn93 , rhibe-a0a2k6lm22 , rhibe-a0a2k6jwp8 , rhiro-a0a2k6qun2 , rhiro-a0a2k6nj56 , rhiro-a0a2k6n885 , rhiro-a0a2k6nnj4 , rhiro-a0a2k6n7n5 , rhibe-a0a2k6jvz4 , rhiro-a0a2k6nfk9 , rhiro-a0a2k6qjv0 , rhibe-a0a2k6jn19 , rhibe-a0a2k6k333 , rhibe-a0a2k6mff5

Title : Draft Genome Sequence of the Type Species of the Genus Citrobacter, Citrobacter freundii MTCC 1658 - Kumar_2013_Genome.Announc_1_e00120
Author(s) : Kumar S , Kaur C , Kimura K , Takeo M , Raghava GP , Mayilraj S
Ref : Genome Announc , 1 :e00120 , 2013
Abstract : We report the 5.0-Mb genome sequence of the type species of the genus Citrobacter, Citrobacter freundii strain MTCC 1658, isolated from canal water. This draft genome sequence of C. freundii strain MTCC 1658(T) consists of 5,001,265 bp with a G+C content of 51.61%, 4,691 protein-coding genes, 70 tRNAs, and 10 rRNAs.
ESTHER : Kumar_2013_Genome.Announc_1_e00120
PubMedSearch : Kumar_2013_Genome.Announc_1_e00120
PubMedID: 23405287
Gene_locus related to this paper: citk8-y1948 , citfr-k8qr28

Title : Draft Genome Sequence of Rhodococcus qingshengii Strain BKS 20-40 - Bala_2013_Genome.Announc_1_e0012813
Author(s) : Bala M , Kumar S , Raghava GP , Mayilraj S
Ref : Genome Announc , 1 :e0012813 , 2013
Abstract : We report the 5.8-Mb genome sequence of Rhodococcus qingshengii strain BKS 20-40, isolated from a palm tree rhizosphere soil sample from Bhitarkanika National Park, Odisha, India. The strain is capable of degrading cholesterol moiety. The draft genome of strain BKS 20-40 consists of 6,601,618 bp, with 62.4% G+C content.
ESTHER : Bala_2013_Genome.Announc_1_e0012813
PubMedSearch : Bala_2013_Genome.Announc_1_e0012813
PubMedID: 23538906
Gene_locus related to this paper: rhoe4-c0zm95 , rhoe4-c0zm96 , rhoe4-c0znd3 , rhoe4-c0ztz7 , rhoe4-c1a280 , rhoer-c3jfu1 , rhoer-c3jen1

Title : Draft Genome Sequence of Rhodococcus triatomae Strain BKS 15-14 - Kumar_2013_Genome.Announc_1_e0012913
Author(s) : Kumar S , Bala M , Raghava GP , Mayilraj S
Ref : Genome Announc , 1 :e0012913 , 2013
Abstract : We report the 5.8-Mb genome sequence of Rhodococcus triatomae BKS 15-14, isolated from an ant hill soil sample, collected from Bhitarkanika Mangrove Reserve Forest, Odisha, India. The draft genome of strain BKS 15-14 consists of 5,824,349 bp, with a G+C content of 69%, 5,387 protein-coding genes, and 57 RNAs.
ESTHER : Kumar_2013_Genome.Announc_1_e0012913
PubMedSearch : Kumar_2013_Genome.Announc_1_e0012913
PubMedID: 23538907
Gene_locus related to this paper: 9noca-m2wff8 , 9noca-m2xi22 , 9noca-m2wzc3 , 9noca-m2wgw2 , 9noca-m2vj79 , 9noca-m2wkp1 , 9noca-m2xbi7 , 9noca-m2wka4 , 9noca-m2wtp6 , 9noca-m2x572

Title : Draft Genome Sequence of Rhodococcus ruber Strain BKS 20-38 - Bala_2013_Genome.Announc_1_e0013913
Author(s) : Bala M , Kumar S , Raghava GP , Mayilraj S
Ref : Genome Announc , 1 :e0013913 , 2013
Abstract : We report the 6.1-Mb genome sequence of Rhodococcus ruber strain BKS 20-38, isolated from the palm tree rhizosphere soil of Bhitarkanika National Park, Odhisha, India. The draft genome sequence of strain BKS 20-38 consists of 6,126,900 bp, with a G+C content of 69.72%, 5,716 protein-coding genes, and 49 RNAs.
ESTHER : Bala_2013_Genome.Announc_1_e0013913
PubMedSearch : Bala_2013_Genome.Announc_1_e0013913
PubMedID: 23558535
Gene_locus related to this paper: 9noca-m3a1c7 , 9noca-m2zch2 , 9noca-m2z3g5 , 9noca-m2xl64 , 9noca-a0a098bi38

Title : Association of microsomal epoxide hydrolase exon 3 Tyr113His and exon 4 His139Arg polymorphisms with gastric cancer in India - Ghoshal_2013_Indian.J.Gastroenterol_32_246
Author(s) : Ghoshal U , Kumar S , Jaiswal V , Tripathi S , Mittal B , Ghoshal UC
Ref : Indian J Gastroenterol , 32 :246 , 2013
Abstract : BACKGROUND: Microsomal epoxide hydrolase, an important phase II xenobiotic enzyme, exhibits polymorphisms at exon 3 (Tyr113His [T/C]) and exon 4 (His139Arg [A/G]), which modulate enzyme activity; this may affect susceptibility to cancers. We studied association between these polymorphisms and gastric cancer (GC).
METHODS: In a prospective study, 77 patients with GC, 50 with peptic ulcer, and 160 healthy controls (HC) were genotyped for exon 3 (PCR-RFLP followed by sequencing) and exon 4 (PCR-RFLP). Helicobacter pylori was considered to be present if two of three tests (histology, rapid urease test, and IgG antibody) were positive.
RESULTS: Tyr113His and His139Arg genotypes and haplotypes were comparable among groups. 113His carriers were commoner among H. pylori-negative patients with GC than HC (p-value = 0.019, odds ratio (OR) = 2.5, 95 % confidence interval (CI) = 1.2-5.4). Haplotype combination of exons 3 and 4 113Tyr-139Arg (TA) were associated with higher and reduced risk in patients with GC than HC in presence and absence of H. pylori (25 % vs. 11 %; p-value = 0.033, OR = 2.61, 95 % CI = 1.08-6.3 and 11.6 % vs. 28.7 %; p-value = 0.004, OR = 0.33, 95 % CI = 0.15-0.7, respectively).
CONCLUSIONS: Though 113Tyr-139Arg was associated with GC in presence of H. pylori, in its absence, it appeared to be protective. Exon 3, 113His, however, was associated with GC even in absence of H. pylori infection.
ESTHER : Ghoshal_2013_Indian.J.Gastroenterol_32_246
PubMedSearch : Ghoshal_2013_Indian.J.Gastroenterol_32_246
PubMedID: 23580125

Title : Draft Genome Sequence of Acinetobacter baumannii Strain MSP4-16 - Singh_2013_Genome.Announc_1_e0013713
Author(s) : Singh NK , Kumar S , Raghava GP , Mayilraj S
Ref : Genome Announc , 1 :e0013713 , 2013
Abstract : We report the 4.0-Mb draft genome sequence of Acinetobacter baumannii strain MSP4-16, isolated from a mangrove soil sample from Parangipettai (11 degrees 30'N, 79 degrees 47'E), Tamil Nadu, India. The draft genome sequence of strain MSP4-16 consists of 3,944,542 bp, with a G+C content of 39%, 5,387 protein coding genes, and 69 RNAs.
ESTHER : Singh_2013_Genome.Announc_1_e0013713
PubMedSearch : Singh_2013_Genome.Announc_1_e0013713
PubMedID: 23558533
Gene_locus related to this paper: aciba-f5iht4 , aciba-a0a009wzt4

Title : Draft Genome Sequence of the 2-Chloro-4-Nitrophenol-Degrading Bacterium Arthrobacter sp. Strain SJCon - Vikram_2013_Genome.Announc_1_e00058
Author(s) : Vikram S , Kumar S , Vaidya B , Pinnaka AK , Raghava GP
Ref : Genome Announc , 1 :e00058 , 2013
Abstract : We report the 4.39-Mb draft genome sequence of the 2-chloro-4-nitrophenol-degrading bacterium Arthrobacter sp. strain SJCon, isolated from a pesticide-contaminated site. The draft genome sequence of strain SJCon will be helpful in studying the genetic pathways involved in the degradation of several aromatic compounds.
ESTHER : Vikram_2013_Genome.Announc_1_e00058
PubMedSearch : Vikram_2013_Genome.Announc_1_e00058
PubMedID: 23516196
Gene_locus related to this paper: 9micc-l8ttr4 , 9micc-l8tn08 , 9micc-l8tr39 , 9micc-l8tp83 , 9micc-l8thf1

Title : Draft Genome Sequence of Streptomyces gancidicus Strain BKS 13-15 - Kumar_2013_Genome.Announc_1_e00150
Author(s) : Kumar S , Kaur N , Singh NK , Raghava GP , Mayilraj S
Ref : Genome Announc , 1 :e00150 , 2013
Abstract : We report the 7.3-Mbp genome sequence of Streptomyces gancidicus strain BKS 13-15, isolated from mangrove sediment samples collected from the Bhitar Kanika Mangrove Reserve Forest, Odissha, India. The draft genome of strain Streptomyces gancidicus strain BKS 13-15 consists of 7,300,479 bp with 72.6% G+C content, 6,631 protein-coding genes, and 71 RNAs.
ESTHER : Kumar_2013_Genome.Announc_1_e00150
PubMedSearch : Kumar_2013_Genome.Announc_1_e00150
PubMedID: 23599292
Gene_locus related to this paper: 9acto-m3dym6 , 9acto-m3ccc9 , 9acto-m3cr51 , 9acto-m3dhl5

Title : Anti-obesity effects of galangin, a pancreatic lipase inhibitor in cafeteria diet fed female rats - Kumar_2013_Pharm.Biol_51_607
Author(s) : Kumar S , Alagawadi KR
Ref : Pharm Biol , 51 :607 , 2013
Abstract : Abstract Context: Alpinia galanga Willd (Zingiberaceae) (AG) is a rhizomatous herb widely cultivated in shady regions of Malaysia, India, Indochina and Indonesia. It is used in southern India as a domestic remedy for the treatment of rheumatoid arthritis, cough, asthma, obesity, diabetes, etc. It was reported to have anti-obesity, hypoglycemic, hypolipidemic and antioxidant properties. Objective: A flavonol glycoside, galangin, was isolated from AG rhizomes. Based on its in vitro pancreatic lipase inhibitory effect, the study was further aimed to clarify whether galangin prevented obesity induced in female rats by feeding cafeteria diet (CD) for 6 weeks. Materials and methods: The in vitro pancreatic lipase inhibitory effect of galangin was determined by measuring the release of oleic acid from triolein. For in vivo experiments, female albino rats were fed CD with or without 50 mg/kg galangin for 6 weeks. Body weight and food intake was measured at weekly intervals. On day 42, serum lipids levels were estimated and then the weight of liver and parametrial adipose tissue (PAT) was determined. The liver lipid peroxidation and triglyceride (TG) content was also estimated. Results: The IC50 value of galangin for pancreatic lipase was 48.20 mg/mL. Galangin produced inhibition of increased body weight, energy intake and PAT weight induced by CD. In addition, galangin produced a significant decrease in serum lipids, liver weight, lipid peroxidation and accumulation of hepatic TGs. Conclusion: Galangin present in AG rhizomes produces anti-obesity effects in CD-fed rats; this may be mediated through its pancreatic lipase inhibitory, hypolipidemic and antioxidant activities.
ESTHER : Kumar_2013_Pharm.Biol_51_607
PubMedSearch : Kumar_2013_Pharm.Biol_51_607
PubMedID: 23363068

Title : Draft Genome Sequence of Amycolatopsis decaplanina Strain DSM 44594T - Kaur_2013_Genome.Announc_1_e0013813
Author(s) : Kaur N , Kumar S , Bala M , Raghava GP , Mayilraj S
Ref : Genome Announc , 1 :e0013813 , 2013
Abstract : We report the 8.5-Mb genome sequence of Amycolatopsis decaplanina strain DSM 44594(T), isolated from a soil sample from India. The draft genome of strain DSM 44594(T) consists of 8,533,276 bp with a 68.6% G+C content, 7,899 protein-coding genes, and 57 RNAs.
ESTHER : Kaur_2013_Genome.Announc_1_e0013813
PubMedSearch : Kaur_2013_Genome.Announc_1_e0013813
PubMedID: 23558534
Gene_locus related to this paper: 9pseu-m2y2s7 , 9pseu-m2y2c6 , 9pseu-m2zt97 , 9pseu-m2y9w0 , 9pseu-m2z3i8 , amyor-r4t1x8 , 9pseu-m2xss2 , 9pseu-m2yta0

Title : Genome Sequence of the Indian Bison Type Biotype of Mycobacterium avium subsp. paratuberculosis Strain S5 - Singh_2013_Genome.Announc_1_e00005
Author(s) : Singh SV , Kumar N , Singh SN , Bhattacharya T , Sohal JS , Singh PK , Singh AV , Singh B , Chaubey KK , Gupta S , Sharma N , Kumar S , Raghava GP
Ref : Genome Announc , 1 : , 2013
Abstract : We report the 4.79-Mb genome sequence of the "Indian Bison Type" biotype of Mycobacterium avium subsp. paratuberculosis strain S5, isolated from a terminally sick Jamunapari goat at the CIRG (Central Institute for Research on Goats) farm in India. This draft genome will help in studying novelties of this biotype, which is widely distributed in animals and human beings in India.
ESTHER : Singh_2013_Genome.Announc_1_e00005
PubMedSearch : Singh_2013_Genome.Announc_1_e00005
PubMedID: 23469332
Gene_locus related to this paper: mycav-DHMA , mycav-Q73T09 , mycpa-MAP2689c

Title : Genome Sequence of Non-O1 Vibrio cholerae PS15 - Kumar_2013_Genome.Announc_1_E00227
Author(s) : Kumar S , Lindquist IE , Sundararajan A , Rajanna C , Floyd JT , Smith KP , Andersen JL , He G , Ayers RM , Johnson JA , Werdann JJ , Sandoval AA , Mojica NM , Schilkey FD , Mudge J , Varela MF
Ref : Genome Announc , 1 :E00227 , 2013
Abstract : The draft genome sequence of a non-O1 Vibrio cholerae strain, PS15, organized into 3,512 open reading frames within a 3.9-Mb genome, was determined. The PS15 genome sequence will allow for the study of the evolution of virulence and environmental adaptation in V. cholerae.
ESTHER : Kumar_2013_Genome.Announc_1_E00227
PubMedSearch : Kumar_2013_Genome.Announc_1_E00227
PubMedID: 23409261
Gene_locus related to this paper: vibch-y1892

Title : Genome sequence of the halotolerant bacterium Imtechella halotolerans K1T - Kumar_2012_J.Bacteriol_194_3731
Author(s) : Kumar S , Vikram S , Subramanian S , Raghava GP , Pinnaka AK
Ref : Journal of Bacteriology , 194 :3731 , 2012
Abstract : We report the 3.087-Mb genome sequence of Imtechella halotolerans K1(T), isolated from an estuarine water sample collected from Kochi, Kerala, India. Strain K1 was recently reported as a novel genus of the family Flavobacteriaceae.
ESTHER : Kumar_2012_J.Bacteriol_194_3731
PubMedSearch : Kumar_2012_J.Bacteriol_194_3731
PubMedID: 22740661
Gene_locus related to this paper: 9flao-i0wf68 , 9flao-i0we86

Title : Draft genome sequence of the nitrophenol-degrading actinomycete Rhodococcus imtechensis RKJ300 - Vikram_2012_J.Bacteriol_194_3543
Author(s) : Vikram S , Kumar S , Subramanian S , Raghava GP
Ref : Journal of Bacteriology , 194 :3543 , 2012
Abstract : We report the 8.231-Mb genome sequence of Rhodococcus imtechensis RKJ300, isolated from pesticide-contaminated soil in Punjab, India. The genome sequence of the strain RKJ300 will be helpful in exploring the molecular pathways involved in the degradation of nitrophenols.
ESTHER : Vikram_2012_J.Bacteriol_194_3543
PubMedSearch : Vikram_2012_J.Bacteriol_194_3543
PubMedID: 22689233
Gene_locus related to this paper: rhoop-pcaL , rhosr-q0sgc8 , rhosr-q0sh74 , rhoob-c1b934 , rhosr-q0sab7 , 9noca-i0wah3 , rhoob-c1asm3 , 9noca-i0wkn6 , 9noca-i0wm39 , rhoop-k8x8c5

Title : Acaricide resistance status in Indian isolates of Hyalomma anatolicum - Shyma_2012_Exp.Appl.Acarol_58_471
Author(s) : Shyma KP , Kumar S , Sharma AK , Ray DD , Ghosh S
Ref : Exp Appl Acarol , 58 :471 , 2012
Abstract : The multi host tick, Hyalomma anatolicum, is the commonest Hyalomma species in India and cattle serves as the main host of this species. A study to evaluate the acaricide resistance of H. anatolicum to deltamethrin, cypermethrin and diazinon was conducted in 20 areas located in three agro climatic regions known to have abundance of the species. Results obtained by the "larval packet test" (LPT) showed a low grade resistance (level-I, RF <5) in the tick species to both deltamethrin and cypermethrin in 10 areas and higher grade resistance (level-II, RF <25) to deltamethrin in one area, where intensive use of synthetic pyrethroids are practiced for tick control. Low grade resistance to diazinon (level I) was recorded in six areas where organophosphates compounds are extensively used for agricultural practices allowing increased exposure of the moulting instars of the ticks to these chemicals. Biochemical analysis of the samples suggested involvement of esterase and alterations of acetylcholinesterase in the resistance mechanisms.
ESTHER : Shyma_2012_Exp.Appl.Acarol_58_471
PubMedSearch : Shyma_2012_Exp.Appl.Acarol_58_471
PubMedID: 22760859

Title : Silencing of germline-expressed genes by DNA elimination in somatic cells - Wang_2012_Dev.Cell_23_1072
Author(s) : Wang J , Mitreva M , Berriman M , Thorne A , Magrini V , Koutsovoulos G , Kumar S , Blaxter ML , Davis RE
Ref : Dev Cell , 23 :1072 , 2012
Abstract : Chromatin diminution is the programmed elimination of specific DNA sequences during development. It occurs in diverse species, but the function(s) of diminution and the specificity of sequence loss remain largely unknown. Diminution in the nematode Ascaris suum occurs during early embryonic cleavages and leads to the loss of germline genome sequences and the formation of a distinct genome in somatic cells. We found that approximately 43 Mb ( approximately 13%) of genome sequence is eliminated in A. suum somatic cells, including approximately 12.7 Mb of unique sequence. The eliminated sequences and location of the DNA breaks are the same in all somatic lineages from a single individual and between different individuals. At least 685 genes are eliminated. These genes are preferentially expressed in the germline and during early embryogenesis. We propose that diminution is a mechanism of germline gene regulation that specifically removes a large number of genes involved in gametogenesis and early embryogenesis.
ESTHER : Wang_2012_Dev.Cell_23_1072
PubMedSearch : Wang_2012_Dev.Cell_23_1072
PubMedID: 23123092
Gene_locus related to this paper: ascsu-f1kr69 , ascsu-f1kxs8 , ascsu-f1ky57 , ascsu-f1kze8 , ascsu-f1kzv8 , ascsu-f1kzx8 , ascsu-f1l0a5 , ascsu-f1l0j3 , ascsu-f1l0s5 , ascsu-f1l1m9 , ascsu-f1l2e5 , ascsu-f1l3k2 , ascsu-f1l7s2 , ascsu-f1l145 , ascsu-u1mei8 , ascsu-u1ns34 , ascsu-u1nb30 , ascsu-f1kzg5 , ascsu-u1ntf1 , ascsu-u1nx87 , ascsu-f1l5f0 , ascsu-f1l6n2

Title : Genome sequence of the nitroaromatic compound-degrading Bacterium Burkholderia sp. strain SJ98 - Kumar_2012_J.Bacteriol_194_3286
Author(s) : Kumar S , Vikram S , Raghava GP
Ref : Journal of Bacteriology , 194 :3286 , 2012
Abstract : We report the 7.85-Mb genome sequence of Burkholderia sp. strain SJ98, isolated from agricultural fields of Assam, India. The draft genome of this strain will be helpful in studying the genetic pathways involved in the degradation of aromatic compounds.
ESTHER : Kumar_2012_J.Bacteriol_194_3286
PubMedSearch : Kumar_2012_J.Bacteriol_194_3286
PubMedID: 22628512
Gene_locus related to this paper: burp8-b2jub2 , 9burk-k8rk89 , 9burk-a0a069nn99 , 9burk-k8rkm7 , 9burk-k8qzg6

Title : Gene expression and phosphoprotein profile of certain key neuronal signaling proteins following soman intoxication - RamaRao_2011_Toxicology_290_195
Author(s) : Ramarao G , Bhattacharya BK , Kumar S , Waghmare CK
Ref : Toxicology , 290 :195 , 2011
Abstract : Nerve agents irreversibly inhibit acetylcholinesterase (AChE), leading to cholinergic crisis and death at acute exposure levels. The complexity, delayed onset, and persistent nature of nerve agent induced CNS effects need to be elucidated to block their multiple effects. In the present study gene expression and phosphoprotein profile of certain key neuronal proteins were studied after soman exposure. Quantitative real time PCR analysis of c-Fos, Bax, CREB and caspase 3 genes in the hippocampus, cortex and cerebellum showed that only c-Fos and Bax mRNA expression was increased significantly. Western blot analysis also confirmed the induction of c-Fos at early time points both at 0.5 and 1.0 LD(50) dose of soman exposure. Acute soman exposure caused perturbations in the phosphorylation status of ERK, JNK, p38 MAPK, CREB, c-Jun and NF-kappaB in all the three brain regions. The primary target for soman toxicity, AChE was inhibited in blood and brain up to 90%. Therapeutic treatment comprising of HI-6, atropine and diazepam has completely protected animals from death and reactivated soman inhibited AChE up to 40% in the plasma and RBC. This therapeutic regime also reduced soman induced Bax expression to near control levels, but could not reverse the soman induced changes in c-Fos expression and phosphorylation levels completely. Results suggest that exposure to soman caused persistent changes in these key brain proteins, which could lead to the development of complex neurotoxic effects and there is an urgent need for development of better drugs to stop multiple effects of nerve agents poisoning.
ESTHER : RamaRao_2011_Toxicology_290_195
PubMedSearch : RamaRao_2011_Toxicology_290_195
PubMedID: 21971501

Title : DPP-IV inhibition enhances the antilipolytic action of NPY in human adipose tissue - Kos_2009_Diabetes.Obes.Metab_11_285
Author(s) : Kos K , Baker AR , Jernas M , Harte AL , Clapham JC , O'Hare JP , Carlsson L , Kumar S , McTernan PG
Ref : Diabetes Obes Metab , 11 :285 , 2009
Abstract : CONTEXT: Dipeptidyl peptidase IV (DPP-IV) inactivates the incretin hormone glucagon-like peptide. It can also affect the orexigenic hormone neuropeptide Y (NPY(1-36)) which is truncated by DPP-IV to NPY(3-36), as a consequence NPY's affinity changes from receptor Y1, which mediates the antilipolytic function of NPY, to other NPY receptors. Little is known whether DPP-IV inhibitors for the treatment of type 2 diabetic (T2DM) patients could influence these pathways. AIMS: To investigate the in vitro effects of NPY with DPP-IV inhibition in isolated abdominal subcutaneous (AbdSc) adipocytes on fat metabolism, and assessment of NPY receptor and DPP-IV expression in adipose tissue (AT). METHODS: Ex vivo human AT was taken from women undergoing elective surgery (body mass index: 27.5 (mean +/- s.d.) +/- 5 kg/m2, age: 43.7 +/- 10 years, n = 36). Isolated AbdSc adipocytes were treated with human recombinant (rh)NPY (1-100 nM) with and without DPP-IV inhibitor (1 M); glycerol release and tissue distribution of DPP-IV, Y1 and Y5 messenger RNA (mRNA) were measured and compared between lean and obese subjects. RESULTS AND CONCLUSION: rhNPY reduced glycerol release, an effect that was further enhanced by co-incubation with a DPP-IV inhibitor [control: 224 (mean +/- s.e.) +/- 37 micromol/l; NPY, 100 nM: 161 +/- 27 micromol/l**; NPY 100 nM/DPP-IV inhibitor, 1 M: 127 +/- 14 micromol/l**; **p < 0.01, n = 14]. DPP-IV was expressed in AbdSc AT and omental AT with relative DPP-IV mRNA expression lower in AbdSc AT taken from obese [77 +/- 6 signal units (SU)] vs. lean subjects (186 +/- 29 SU*, n = 10). Y1 was predominantly expressed in fat and present in all fat depots but higher in obese subjects, particularly the AbdSc AT-depot (obese: 1944 +/- 111 SU vs. lean: 711 +/- 112 SU**, n = 10). NPY appears to be regulated by AT-derived DPP-IV. DPP-IV inhibitors augment the antilipolytic effect of NPY in AT. Further studies are required to show whether this explains the lack of weight loss in T2DM patients treated with DPP-IV inhibitors.
ESTHER : Kos_2009_Diabetes.Obes.Metab_11_285
PubMedSearch : Kos_2009_Diabetes.Obes.Metab_11_285
PubMedID: 19175376

Title : Discovery of a highly potent, selective, and bioavailable soluble epoxide hydrolase inhibitor with excellent ex vivo target engagement - Shen_2009_J.Med.Chem_52_5009
Author(s) : Shen HC , Ding FX , Wang S , Deng Q , Zhang X , Chen Y , Zhou G , Xu S , Chen HS , Tong X , Tong V , Mitra K , Kumar S , Tsai C , Stevenson AS , Pai LY , Alonso-Galicia M , Chen X , Soisson SM , Roy S , Zhang B , Tata JR , Berger JP , Colletti SL
Ref : Journal of Medicinal Chemistry , 52 :5009 , 2009
Abstract : 4-Substituted piperidine-derived trisubstituted ureas are reported as highly potent and selective inhibitors for sEH. The SAR outlines approaches to improve activity against sEH and reduce ion channel and CYP liability. With minimal off-target activity and a good PK profile, the benchmark 2d exhibited remarkable in vitro and ex vivo target engagement. The eutomer entA-2d also elicited vasodilation effect in rat mesenteric artery.
ESTHER : Shen_2009_J.Med.Chem_52_5009
PubMedSearch : Shen_2009_J.Med.Chem_52_5009
PubMedID: 19645482

Title : The complete genome of Teredinibacter turnerae T7901: an intracellular endosymbiont of marine wood-boring bivalves (shipworms) - Yang_2009_PLoS.One_4_e6085
Author(s) : Yang JC , Madupu R , Durkin AS , Ekborg NA , Pedamallu CS , Hostetler JB , Radune D , Toms BS , Henrissat B , Coutinho PM , Schwarz S , Field L , Trindade-Silva AE , Soares CA , Elshahawi S , Hanora A , Schmidt EW , Haygood MG , Posfai J , Benner J , Madinger C , Nove J , Anton B , Chaudhary K , Foster J , Holman A , Kumar S , Lessard PA , Luyten YA , Slatko B , Wood N , Wu B , Teplitski M , Mougous JD , Ward N , Eisen JA , Badger JH , Distel DL
Ref : PLoS ONE , 4 :e6085 , 2009
Abstract : Here we report the complete genome sequence of Teredinibacter turnerae T7901. T. turnerae is a marine gamma proteobacterium that occurs as an intracellular endosymbiont in the gills of wood-boring marine bivalves of the family Teredinidae (shipworms). This species is the sole cultivated member of an endosymbiotic consortium thought to provide the host with enzymes, including cellulases and nitrogenase, critical for digestion of wood and supplementation of the host's nitrogen-deficient diet. T. turnerae is closely related to the free-living marine polysaccharide degrading bacterium Saccharophagus degradans str. 2-40 and to as yet uncultivated endosymbionts with which it coexists in shipworm cells. Like S. degradans, the T. turnerae genome encodes a large number of enzymes predicted to be involved in complex polysaccharide degradation (>100). However, unlike S. degradans, which degrades a broad spectrum (>10 classes) of complex plant, fungal and algal polysaccharides, T. turnerae primarily encodes enzymes associated with deconstruction of terrestrial woody plant material. Also unlike S. degradans and many other eubacteria, T. turnerae dedicates a large proportion of its genome to genes predicted to function in secondary metabolism. Despite its intracellular niche, the T. turnerae genome lacks many features associated with obligate intracellular existence (e.g. reduced genome size, reduced %G+C, loss of genes of core metabolism) and displays evidence of adaptations common to free-living bacteria (e.g. defense against bacteriophage infection). These results suggest that T. turnerae is likely a facultative intracellular ensosymbiont whose niche presently includes, or recently included, free-living existence. As such, the T. turnerae genome provides insights into the range of genomic adaptations associated with intracellular endosymbiosis as well as enzymatic mechanisms relevant to the recycling of plant materials in marine environments and the production of cellulose-derived biofuels.
ESTHER : Yang_2009_PLoS.One_4_e6085
PubMedSearch : Yang_2009_PLoS.One_4_e6085
PubMedID: 19568419
Gene_locus related to this paper: tertt-c5bif5 , tertt-c5bkb0 , tertt-c5bkv2 , tertt-c5bmq4 , tertt-c5bmw5 , tertt-c5bmx1 , tertt-c5bmz8 , tertt-c5bn23 , tertt-c5bn62 , tertt-c5bpb2 , tertt-c5bpu2 , tertt-c5bru8 , tertt-c5btp6 , tertt-c5buc2 , tertt-metx , tertt-c5br42 , tertt-c5bpt0 , tertt-c5btk3

Title : Genotoxicity assessment of acute exposure of chlorpyrifos to freshwater fish Channa punctatus (Bloch) using micronucleus assay and alkaline single-cell gel electrophoresis - Ali_2008_Chemosphere_71_1823
Author(s) : Ali D , Nagpure NS , Kumar S , Kumar R , Kushwaha B
Ref : Chemosphere , 71 :1823 , 2008
Abstract : Chlorpyrifos (O,O-diethyl O-3,5,6-trichloro-2-pyridylphosphorothioate) is one of the organophosphate pesticides widely used in agricultural practices throughout world and irreversible inhibitor of cholinesterase in all animal species. Limited efforts have been made to study acute genotoxic effects of chlorpyrifos (CPF) in different tissues of fish using genotoxic biomarkers. Therefore, the present investigation was aimed to study the induction of DNA damage by CPF in freshwater teleost fish Channapunctatus using micronucleus assay (MN assay) and alkaline single-cell gel electrophoresis (comet assay). The value of LC(50) - 96 h of CPF was determined as 811.98 microgl(-1) for C. punctatus, in a semi-static system and on the basis of LC(50) value three acute concentrations viz., 203, 406 and 609 microgl(-1) were determined. The fishes were exposed to the different concentrations of CPF for 96 h and samplings were done at regular intervals for assessment of the MN frequencies and DNA damage. In general, significant effects (P<0.01) from both concentrations and time of exposure were observed in exposed fishes. It was found that the micronucleus induction was highest on 96 h at all concentrations in the peripheral blood. Similar trend was observed for the DNA damage measured in terms of the percentage of tail DNA in the lymphocyte and gill cells. This study explored the combined use of micronucleus assay and comet assay for in vivo laboratory studies using fresh water fish for screening the genotoxic potential of xenobiotics.
ESTHER : Ali_2008_Chemosphere_71_1823
PubMedSearch : Ali_2008_Chemosphere_71_1823
PubMedID: 18359502

Title : Evolution of genes and genomes on the Drosophila phylogeny - Clark_2007_Nature_450_203
Author(s) : Clark AG , Eisen MB , Smith DR , Bergman CM , Oliver B , Markow TA , Kaufman TC , Kellis M , Gelbart W , Iyer VN , Pollard DA , Sackton TB , Larracuente AM , Singh ND , Abad JP , Abt DN , Adryan B , Aguade M , Akashi H , Anderson WW , Aquadro CF , Ardell DH , Arguello R , Artieri CG , Barbash DA , Barker D , Barsanti P , Batterham P , Batzoglou S , Begun D , Bhutkar A , Blanco E , Bosak SA , Bradley RK , Brand AD , Brent MR , Brooks AN , Brown RH , Butlin RK , Caggese C , Calvi BR , Bernardo de Carvalho A , Caspi A , Castrezana S , Celniker SE , Chang JL , Chapple C , Chatterji S , Chinwalla A , Civetta A , Clifton SW , Comeron JM , Costello JC , Coyne JA , Daub J , David RG , Delcher AL , Delehaunty K , Do CB , Ebling H , Edwards K , Eickbush T , Evans JD , Filipski A , Findeiss S , Freyhult E , Fulton L , Fulton R , Garcia AC , Gardiner A , Garfield DA , Garvin BE , Gibson G , Gilbert D , Gnerre S , Godfrey J , Good R , Gotea V , Gravely B , Greenberg AJ , Griffiths-Jones S , Gross S , Guigo R , Gustafson EA , Haerty W , Hahn MW , Halligan DL , Halpern AL , Halter GM , Han MV , Heger A , Hillier L , Hinrichs AS , Holmes I , Hoskins RA , Hubisz MJ , Hultmark D , Huntley MA , Jaffe DB , Jagadeeshan S , Jeck WR , Johnson J , Jones CD , Jordan WC , Karpen GH , Kataoka E , Keightley PD , Kheradpour P , Kirkness EF , Koerich LB , Kristiansen K , Kudrna D , Kulathinal RJ , Kumar S , Kwok R , Lander E , Langley CH , Lapoint R , Lazzaro BP , Lee SJ , Levesque L , Li R , Lin CF , Lin MF , Lindblad-Toh K , Llopart A , Long M , Low L , Lozovsky E , Lu J , Luo M , Machado CA , Makalowski W , Marzo M , Matsuda M , Matzkin L , McAllister B , McBride CS , McKernan B , McKernan K , Mendez-Lago M , Minx P , Mollenhauer MU , Montooth K , Mount SM , Mu X , Myers E , Negre B , Newfeld S , Nielsen R , Noor MA , O'Grady P , Pachter L , Papaceit M , Parisi MJ , Parisi M , Parts L , Pedersen JS , Pesole G , Phillippy AM , Ponting CP , Pop M , Porcelli D , Powell JR , Prohaska S , Pruitt K , Puig M , Quesneville H , Ram KR , Rand D , Rasmussen MD , Reed LK , Reenan R , Reily A , Remington KA , Rieger TT , Ritchie MG , Robin C , Rogers YH , Rohde C , Rozas J , Rubenfield MJ , Ruiz A , Russo S , Salzberg SL , Sanchez-Gracia A , Saranga DJ , Sato H , Schaeffer SW , Schatz MC , Schlenke T , Schwartz R , Segarra C , Singh RS , Sirot L , Sirota M , Sisneros NB , Smith CD , Smith TF , Spieth J , Stage DE , Stark A , Stephan W , Strausberg RL , Strempel S , Sturgill D , Sutton G , Sutton GG , Tao W , Teichmann S , Tobari YN , Tomimura Y , Tsolas JM , Valente VL , Venter E , Venter JC , Vicario S , Vieira FG , Vilella AJ , Villasante A , Walenz B , Wang J , Wasserman M , Watts T , Wilson D , Wilson RK , Wing RA , Wolfner MF , Wong A , Wong GK , Wu CI , Wu G , Yamamoto D , Yang HP , Yang SP , Yorke JA , Yoshida K , Zdobnov E , Zhang P , Zhang Y , Zimin AV , Baldwin J , Abdouelleil A , Abdulkadir J , Abebe A , Abera B , Abreu J , Acer SC , Aftuck L , Alexander A , An P , Anderson E , Anderson S , Arachi H , Azer M , Bachantsang P , Barry A , Bayul T , Berlin A , Bessette D , Bloom T , Blye J , Boguslavskiy L , Bonnet C , Boukhgalter B , Bourzgui I , Brown A , Cahill P , Channer S , Cheshatsang Y , Chuda L , Citroen M , Collymore A , Cooke P , Costello M , D'Aco K , Daza R , De Haan G , DeGray S , DeMaso C , Dhargay N , Dooley K , Dooley E , Doricent M , Dorje P , Dorjee K , Dupes A , Elong R , Falk J , Farina A , Faro S , Ferguson D , Fisher S , Foley CD , Franke A , Friedrich D , Gadbois L , Gearin G , Gearin CR , Giannoukos G , Goode T , Graham J , Grandbois E , Grewal S , Gyaltsen K , Hafez N , Hagos B , Hall J , Henson C , Hollinger A , Honan T , Huard MD , Hughes L , Hurhula B , Husby ME , Kamat A , Kanga B , Kashin S , Khazanovich D , Kisner P , Lance K , Lara M , Lee W , Lennon N , Letendre F , LeVine R , Lipovsky A , Liu X , Liu J , Liu S , Lokyitsang T , Lokyitsang Y , Lubonja R , Lui A , Macdonald P , Magnisalis V , Maru K , Matthews C , McCusker W , McDonough S , Mehta T , Meldrim J , Meneus L , Mihai O , Mihalev A , Mihova T , Mittelman R , Mlenga V , Montmayeur A , Mulrain L , Navidi A , Naylor J , Negash T , Nguyen T , Nguyen N , Nicol R , Norbu C , Norbu N , Novod N , O'Neill B , Osman S , Markiewicz E , Oyono OL , Patti C , Phunkhang P , Pierre F , Priest M , Raghuraman S , Rege F , Reyes R , Rise C , Rogov P , Ross K , Ryan E , Settipalli S , Shea T , Sherpa N , Shi L , Shih D , Sparrow T , Spaulding J , Stalker J , Stange-Thomann N , Stavropoulos S , Stone C , Strader C , Tesfaye S , Thomson T , Thoulutsang Y , Thoulutsang D , Topham K , Topping I , Tsamla T , Vassiliev H , Vo A , Wangchuk T , Wangdi T , Weiand M , Wilkinson J , Wilson A , Yadav S , Young G , Yu Q , Zembek L , Zhong D , Zimmer A , Zwirko Z , Alvarez P , Brockman W , Butler J , Chin C , Grabherr M , Kleber M , Mauceli E , MacCallum I
Ref : Nature , 450 :203 , 2007
Abstract : Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.
ESTHER : Clark_2007_Nature_450_203
PubMedSearch : Clark_2007_Nature_450_203
PubMedID: 17994087
Gene_locus related to this paper: droan-ACHE , droan-b3lx10 , droan-b3lx75 , droan-b3lxv7 , droan-b3ly87 , droan-b3lyh4 , droan-b3lyh5 , droan-b3lyh7 , droan-b3lyh9 , droan-b3lyi0 , droan-b3lyi2 , droan-b3lyi3 , droan-b3lyi4 , droan-b3lyj8 , droan-b3lyj9 , droan-b3lyx4 , droan-b3lyx5 , droan-b3lyx6 , droan-b3lyx7 , droan-b3lyx9 , droan-b3lz72 , droan-b3m1x3 , droan-b3m2d4 , droan-b3m3d9 , droan-b3m4e3 , droan-b3m5w1 , droan-b3m6i7 , droan-b3m7v2 , droan-b3m9a5 , droan-b3m9f4 , droan-b3m9p3 , droan-b3m254 , droan-b3m259 , droan-b3m260 , droan-b3m262 , droan-b3m524 , droan-b3m635 , droan-b3m845 , droan-b3m846 , droan-b3md01 , droan-b3mdh7 , droan-b3mdm6 , droan-b3mdw8 , droan-b3mee1 , droan-b3mf47 , droan-b3mf48 , droan-b3mg94 , droan-b3mgk2 , droan-b3mgn6 , droan-b3mii3 , droan-b3mjk2 , droan-b3mjk3 , droan-b3mjk4 , droan-b3mjk5 , droan-b3mjl2 , droan-b3mjl4 , droan-b3mjl7 , droan-b3mjl9 , droan-b3mjm8 , droan-b3mjm9 , droan-b3mjs6 , droan-b3mkr0 , droan-b3ml20 , droan-b3mly4 , droan-b3mly5 , droan-b3mly6 , droan-b3mmm8 , droan-b3mnb5 , droan-b3mny9 , droan-b3mtj5 , droan-b3muw4 , droan-b3muw8 , droan-b3n0e7 , droan-b3n2j7 , droan-b3n247 , droan-c5idb2 , droer-ACHE , droer-b3n5c7 , droer-b3n5d0 , droer-b3n5d8 , droer-b3n5d9 , droer-b3n5t7 , droer-b3n5y4 , droer-b3n7d2 , droer-b3n7d3 , droer-b3n7d4 , droer-b3n7k8 , droer-b3n8e4 , droer-b3n8f7 , droer-b3n8f8 , droer-b3n9e1 , droer-b3n319 , droer-b3n547 , droer-b3n549 , droer-b3n558 , droer-b3n560 , droer-b3n577 , droer-b3n612 , droer-b3nar5 , droer-b3nb91 , droer-b3nct9 , droer-b3nd53 , droer-b3ndh9 , droer-b3ndq8 , droer-b3ne66 , droer-b3ne67 , droer-b3ne97 , droer-b3nfk3 , droer-b3nfq9 , droer-b3nim7 , droer-b3nkn2 , droer-b3nm11 , droer-b3nmh4 , droer-b3nmy2 , droer-b3npx2 , droer-b3npx3 , droer-b3nq76 , droer-b3nqg9 , droer-b3nqm8 , droer-b3nr28 , droer-b3nrd3 , droer-b3nst4 , droer-b3nwa7 , droer-b3nyp5.1 , droer-b3nyp5.2 , droer-b3nyp6 , droer-b3nyp7 , droer-b3nyp8 , droer-b3nyp9 , droer-b3nyq3 , droer-b3nz06 , droer-b3nz14 , droer-b3nzj0 , droer-b3p0c0 , droer-b3p0c1 , droer-b3p0c2 , droer-b3p2x6 , droer-b3p2x7 , droer-b3p2x9 , droer-b3p2y1 , droer-b3p2y2 , droer-b3p6d4 , droer-b3p6d5 , droer-b3p6w3 , droer-b3p7b4 , droer-b3p7h9 , droer-b3p152 , droer-b3p486 , droer-b3p487 , droer-b3p488 , droer-b3p489 , droer-EST6 , droer-q670j5 , drogr-ACHE , drogr-b4iwp3 , drogr-b4iww3 , drogr-b4iwy3 , drogr-b4ixf7 , drogr-b4ixh4 , drogr-b4iyz5 , drogr-b4j2s2 , drogr-b4j2u8 , drogr-b4j3u1 , drogr-b4j3v3 , drogr-b4j4g7 , drogr-b4j4x9 , drogr-b4j6e6 , drogr-b4j9c9 , drogr-b4j9y4 , drogr-b4j156 , drogr-b4j384 , drogr-b4j605 , drogr-b4j685 , drogr-b4ja76 , drogr-b4jay5 , drogr-b4jcf0 , drogr-b4jcf1 , drogr-b4jdg6 , drogr-b4jdg7 , drogr-b4jdh6 , drogr-b4jdz1 , drogr-b4jdz2 , drogr-b4jdz4 , drogr-b4je66 , drogr-b4je79 , drogr-b4je82 , drogr-b4je88 , drogr-b4je89 , drogr-b4je90 , drogr-b4je91 , drogr-b4jf76 , drogr-b4jf79 , drogr-b4jf80 , drogr-b4jf81 , drogr-b4jf82 , drogr-b4jf83 , drogr-b4jf84 , drogr-b4jf85 , drogr-b4jf87 , drogr-b4jf91 , drogr-b4jf92 , drogr-b4jg66 , drogr-b4jgh0 , drogr-b4jgh1 , drogr-b4jgr9 , drogr-b4ji67 , drogr-b4jls2 , drogr-b4jnh9 , drogr-b4jpc6 , drogr-b4jpq3 , drogr-b4jpx9 , drogr-b4jql2 , drogr-b4jrh5 , drogr-b4jsb2 , drogr-b4jth3 , drogr-b4jti1 , drogr-b4jul5 , drogr-b4jur4 , drogr-b4jvh3 , drogr-b4jz00 , drogr-b4jz03 , drogr-b4jz04 , drogr-b4jz05 , drogr-b4jzh2 , drogr-b4k0u2 , drogr-b4k2r1 , drogr-b4k234 , drogr-b4k235 , drome-BEM46 , drome-CG3734 , drome-CG9953 , drome-CG11626 , drome-GH02439 , dromo-ACHE , dromo-b4k6a7 , dromo-b4k6a8 , dromo-b4k6q8 , dromo-b4k6q9 , dromo-b4k6r1 , dromo-b4k6r3 , dromo-b4k6r4 , dromo-b4k6r5 , dromo-b4k6r6 , dromo-b4k6r7 , dromo-b4k6r8 , dromo-b4k6r9 , dromo-b4k6s0 , dromo-b4k6s1 , dromo-b4k6s2 , dromo-b4k9c7 , dromo-b4k9d3 , dromo-b4k571 , dromo-b4k721 , dromo-b4ka74 , dromo-b4ka89 , dromo-b4kaj4 , dromo-b4kc20 , dromo-b4kcl2 , dromo-b4kcl3 , dromo-b4kd55.1 , dromo-b4kd55.2 , dromo-b4kd56 , dromo-b4kd57 , dromo-b4kde1 , dromo-b4kdg2 , dromo-b4kdh4 , dromo-b4kdh5 , dromo-b4kdh6 , dromo-A0A0Q9XDF2 , dromo-b4kdh8.1 , dromo-b4kdh8.2 , dromo-b4kg04 , dromo-b4kg05 , dromo-b4kg06 , dromo-b4kg16 , dromo-b4kg44 , dromo-b4kg90 , dromo-b4kh20 , dromo-b4kh21 , dromo-b4kht7 , dromo-b4kid3 , dromo-b4kik0 , dromo-b4kjx0 , dromo-b4kki1 , dromo-b4kkp6 , dromo-b4kkp8 , dromo-b4kkq8 , dromo-b4kkr0 , dromo-b4kkr3 , dromo-b4kkr4 , dromo-b4kks0 , dromo-b4kks1 , dromo-b4kks2 , dromo-b4kla1 , dromo-b4klv8 , dromo-b4knt4 , dromo-b4kp08 , dromo-b4kp16 , dromo-b4kqa6 , dromo-b4kqa7 , dromo-b4kqa8 , dromo-b4kqh1 , dromo-b4kst4 , dromo-b4ksy6 , dromo-b4kt84 , dromo-b4ktf5 , dromo-b4ktf6 , dromo-b4kvl3 , dromo-b4kvw2 , dromo-b4kwv4 , dromo-b4kwv5 , dromo-b4kxz6 , dromo-b4ky12 , dromo-b4ky36 , dromo-b4ky44 , dromo-b4kzu7 , dromo-b4l0n8 , dromo-b4l4u5 , dromo-b4l6l9 , dromo-b4l084 , drope-ACHE , drope-b4g3s6 , drope-b4g4p7 , drope-b4g6v4 , drope-b4g8m0 , drope-b4g8n6 , drope-b4g8n7 , drope-b4g9p2 , drope-b4g815 , drope-b4g816 , drope-b4gat7 , drope-b4gav5 , drope-b4gb05 , drope-b4gc08 , drope-b4gcr3 , drope-b4gdk2 , drope-b4gdl9 , drope-b4gdv9 , drope-b4gei8 , drope-b4gei9 , drope-b4gej0 , drope-b4ghz9 , drope-b4gj62 , drope-b4gj64 , drope-b4gj74 , drope-b4gkf4 , drope-b4gkv2 , drope-b4gky9 , drope-b4gl76 , drope-b4glf3 , drope-b4gmt3 , drope-b4gmt7 , drope-b4gmt9 , drope-b4gmu2 , drope-b4gmu3 , drope-b4gmu4 , drope-b4gmu5 , drope-b4gmu6 , drope-b4gmu7 , drope-b4gmv1 , drope-b4gn08 , drope-b4gpa7 , drope-b4gq13 , drope-b4grh7 , drope-b4gsf9 , drope-b4gsw4 , drope-b4gsw5 , drope-b4gsx2 , drope-b4gsx7 , drope-b4gsy6 , drope-b4gsy7 , drope-b4guj8 , drope-b4gw36 , drope-b4gzc2 , drope-b4gzc6 , drope-b4gzc7 , drope-b4h4p9 , drope-b4h5l3 , drope-b4h6a0 , drope-b4h6a8 , drope-b4h6a9 , drope-b4h6b0 , drope-b4h7m7 , drope-b4h462 , drope-b4h601 , drope-b4h602 , drope-b4hay1 , drope-b4hb18 , drope-est5a , drope-est5b , drope-est5c , drops-ACHE , drops-b5dhd2 , drops-b5dk96 , drops-b5dpe3 , drops-b5drp9 , drops-b5dwa7 , drops-b5dwa8 , drops-b5dz85 , drops-b5dz86 , drops-est5a , drops-est5b , drops-q29bq2 , drops-q29dd7 , drops-q29ew0 , drops-q291d5 , drops-q291e8 , drops-q293n1 , drops-q293n4 , drops-q293n5 , drops-q293n6 , drops-q294n6 , drops-q294n7 , drops-q294n9 , drops-q294p4 , drose-b4he97 , drose-b4hfu2 , drose-b4hg54 , drose-b4hga0 , drose-b4hgu9 , drose-b4hgv0 , drose-b4hgv3 , drose-b4hgv4 , drose-b4hhm8 , drose-b4hhs6 , drose-b4hie4 , drose-b4him9 , drose-b4hk63 , drose-b4hkj5 , drose-b4hr07 , drose-b4hr81 , drose-b4hre7 , drose-b4hs13 , drose-b4hsj9 , drose-b4hsk0 , drose-b4hsm8 , drose-b4hvr5 , drose-b4hwr7 , drose-b4hwr8 , drose-b4hwr9 , drose-b4hws6 , drose-b4hws7 , drose-b4hwt0 , drose-b4hwt2 , drose-b4hwu1 , drose-b4hwu2 , drose-b4hxs9 , drose-b4hxu4 , drose-b4hxz1 , drose-b4hyp8 , drose-b4hyp9 , drose-b4hyq0 , drose-b4hyz4 , drose-b4hyz5 , drose-b4i1k8 , drose-b4i2f3 , drose-b4i2w5 , drose-b4i4u3 , drose-b4i4u7 , drose-b4i4u9 , drose-b4i4v0 , drose-b4i4v1 , drose-b4i4v4 , drose-b4i4v5 , drose-b4i4v6 , drose-b4i4v7 , drose-b4i4v8 , drose-b4i4w0 , drose-b4i7s6 , drose-b4i133 , drose-b4i857 , drose-b4iam7 , drose-b4iam9 , drose-b4iaq6 , drose-b4icf6 , drose-b4icf7 , drose-b4id80 , drose-b4ifc5 , drose-b4ihv9 , drose-b4iie9 , drose-b4ilj8 , drose-b4in13 , drose-b4inj9 , drosi-ACHE , drosi-aes04a , drosi-b4nsh8 , drosi-b4q3d7 , drosi-b4q4w5 , drosi-b4q4y7 , drosi-b4q6h6 , drosi-b4q7u2 , drosi-b4q7u3 , drosi-b4q9c6 , drosi-b4q9c7 , drosi-b4q9d3 , drosi-b4q9d4 , drosi-b4q9r0 , drosi-b4q9r1 , drosi-b4q9r3 , drosi-b4q9s2 , drosi-b4q9s3 , drosi-b4q429 , drosi-b4q530 , drosi-b4q734 , drosi-b4q782 , drosi-b4q783 , drosi-b4q942 , drosi-b4qet1 , drosi-b4qfv6 , drosi-b4qge5 , drosi-b4qgh5 , drosi-b4qgs5 , drosi-b4qhf3 , drosi-b4qhf4 , drosi-b4qhi5 , drosi-b4qjr2 , drosi-b4qjr3 , drosi-b4qjv6 , drosi-b4qk23 , drosi-b4qk51 , drosi-b4qlt1 , drosi-b4qlz9 , drosi-b4qmn9 , drosi-b4qrq7 , drosi-b4qs01 , drosi-b4qs57 , drosi-b4qs82 , drosi-b4qs83 , drosi-b4qs84 , drosi-b4qs85 , drosi-b4qs86 , drosi-b4qsq1 , drosi-b4quk6 , drosi-b4qvg5 , drosi-b4qvg6 , drosi-b4qzn2 , drosi-b4qzn3 , drosi-b4qzn5 , drosi-b4qzn7 , drosi-b4qzn8 , drosi-b4qzp2 , drosi-b4qzp3 , drosi-b4qzp4 , drosi-b4qzp5 , drosi-b4qzp6 , drosi-b4qzp7 , drosi-b4r1a4 , drosi-b4r025 , drosi-b4r207 , drosi-b4r662 , drosi-este6 , drosi-q670k8 , drovi-ACHE , drovi-b4lev2 , drovi-b4lf33 , drovi-b4lf51 , drovi-b4lg54 , drovi-b4lg72 , drovi-b4lgc6 , drovi-b4lgd5 , drovi-b4lgg0 , drovi-b4lgk5 , drovi-b4lgn2 , drovi-b4lh17 , drovi-b4lh18 , drovi-b4lk43 , drovi-b4ll59 , drovi-b4ll60 , drovi-b4llm5 , drovi-b4lln3 , drovi-b4lmk4 , drovi-b4lmp0 , drovi-b4lnr4 , drovi-b4lp47 , drovi-b4lpd0 , drovi-b4lps0 , drovi-b4lqc6 , drovi-b4lr00 , drovi-b4lrp6 , drovi-b4lrw2 , drovi-b4lse7 , drovi-b4lse9 , drovi-b4lsf0 , drovi-b4lsn0 , drovi-b4lsq5 , drovi-b4lt32 , drovi-b4ltr1 , drovi-b4lui7 , drovi-b4lui9 , drovi-b4luj8 , drovi-b4luk0 , drovi-b4luk3 , drovi-b4luk8 , drovi-b4luk9 , drovi-b4lul0 , drovi-b4lve2 , drovi-b4lxi9 , drovi-b4lxj8 , drovi-b4lyf3 , drovi-b4lyq2 , drovi-b4lyq3 , drovi-b4lz07 , drovi-b4lz13 , drovi-b4lz14 , drovi-b4lz15 , drovi-b4m0j7 , drovi-b4m0s0 , drovi-b4m2b6 , drovi-b4m4h7 , drovi-b4m4h8 , drovi-b4m4i0 , drovi-b4m4i2 , drovi-b4m4i3.A , drovi-b4m4i3.B , drovi-b4m4i4 , drovi-b4m4i5 , drovi-b4m4i6 , drovi-b4m4i7 , drovi-b4m4i8 , drovi-b4m4i9 , drovi-b4m4j2 , drovi-b4m5a0 , drovi-b4m5a1 , drovi-b4m5a2 , drovi-b4m6b9 , drovi-b4m7k9 , drovi-b4m9g9 , drovi-b4m9h0 , drovi-b4m564 , drovi-b4m599 , drovi-b4m918 , drovi-b4mb87 , drovi-b4mc71 , drovi-b4mfa4 , drowi-ACHE , drowi-b4mjb9 , drowi-b4mkt7 , drowi-b4mlc1 , drowi-b4mp68 , drowi-b4mqe9 , drowi-b4mqf0.2 , drowi-b4mqf1 , drowi-b4mqf3 , drowi-b4mqf4 , drowi-b4mqf5 , drowi-b4mqq6 , drowi-b4mrd1 , drowi-b4mrk3 , drowi-b4mtl5 , drowi-b4mug2 , drowi-b4muj8 , drowi-b4mv18 , drowi-b4mw32 , drowi-b4mw85 , drowi-b4mwp2 , drowi-b4mwp6 , drowi-b4mwq5 , drowi-b4mwr0 , drowi-b4mwr8 , drowi-b4mwr9 , drowi-b4mwt1 , drowi-b4mwz7 , drowi-b4mxn5 , drowi-b4my54 , drowi-b4myg1 , drowi-b4myh5 , drowi-b4n0d4 , drowi-b4n1a7 , drowi-b4n1c8 , drowi-b4n3s9 , drowi-b4n3x7 , drowi-b4n4x9 , drowi-b4n4y0 , drowi-b4n6m1 , drowi-b4n6n0 , drowi-b4n6n7 , drowi-b4n6u6 , drowi-b4n7s6 , drowi-b4n7s7 , drowi-b4n7s8 , drowi-b4n899.1 , drowi-b4n8a1 , drowi-b4n8a2 , drowi-b4n8a3 , drowi-b4n8a4 , drowi-b4n8a9 , drowi-b4n023 , drowi-b4n075 , drowi-b4n543 , drowi-b4n888 , drowi-b4n889 , drowi-b4n891 , drowi-b4n893 , drowi-b4n895 , drowi-b4n897 , drowi-b4n898 , drowi-b4n899.2 , drowi-b4nae3 , drowi-b4ner8 , drowi-b4ng76 , drowi-b4nga7 , drowi-b4ngb5 , drowi-b4nhz9 , drowi-b4nj18 , drowi-b4nj19 , drowi-b4nja7 , drowi-b4nja8 , drowi-b4nja9 , drowi-b4njk8 , drowi-b4nkc8 , drowi-b4nky0 , drowi-b4nl36 , drowi-b4nm27 , drowi-b4nn59 , drowi-b4nnc1 , drowi-b4nng1 , drowi-b4nng2 , droya-ACHE , droya-aes04 , droya-b4itg2 , droya-b4itg6 , droya-b4itu9 , droya-b4iuv4 , droya-b4iuv5 , droya-b4nxe6 , droya-b4nxg5 , droya-b4nxg6 , droya-b4nxg8 , droya-b4nxw4 , droya-b4ny57 , droya-b4ny58 , droya-b4ny86 , droya-b4nzz8 , droya-b4p0b5 , droya-b4p0q9 , droya-b4p0r0 , droya-b4p0r7 , droya-b4p0r8 , droya-b4p0r9 , droya-b4p0s0 , droya-b4p0s2 , droya-b4p0t0 , droya-b4p0t1 , droya-b4p3h4 , droya-b4p3x8 , droya-b4p5g8 , droya-b4p6c9 , droya-b4p6l9 , droya-b4p6r1 , droya-b4p6r2 , droya-b4p7u4 , droya-b4p8w7 , droya-b4p023 , droya-b4p241 , droya-b4p774 , droya-b4pat9 , droya-b4pbl1 , droya-b4pd22 , droya-b4pd70 , droya-b4pdm8 , droya-b4pet9 , droya-b4pff9 , droya-b4pga7 , droya-b4pgu0 , droya-b4pig3 , droya-b4pjt8 , droya-b4pka2 , droya-b4plh2 , droya-b4pma3 , droya-b4pmv3 , droya-b4pmv4 , droya-b4pmv5 , droya-b4pn92 , droya-b4pp65 , droya-b4ppc5 , droya-b4ppc6 , droya-b4ppc7 , droya-b4ppc8 , droya-b4pq03 , droya-b4prg6B , droya-b4prg9 , droya-b4prh3 , droya-b4prh4 , droya-b4prh6 , droya-b4prh7 , droya-b4psz8 , droya-b4psz9 , droya-b4pv22 , droya-b4q0g5 , droya-b4q246 , droya-EST6 , droya-q71d76 , drowi-b4n7m9 , drope-b4gkk1 , droer-b3n5s3 , drose-b4i1w5 , drowi-a0a0q9x0t3 , drogr-b4jvm7 , dromo-b4ku70 , drovi-b4mcn9 , drovi-b4lty2 , drogr-b4jdu1 , drovi-a0a0q9wiq8 , dromo-b4kf70 , drosi-b2zi86 , droya-b4p2y4 , drose-b2zic5 , droer-b3n895

Title : Draft genome of the filarial nematode parasite Brugia malayi - Ghedin_2007_Science_317_1756
Author(s) : Ghedin E , Wang S , Spiro D , Caler E , Zhao Q , Crabtree J , Allen JE , Delcher AL , Guiliano DB , Miranda-Saavedra D , Angiuoli SV , Creasy T , Amedeo P , Haas B , El-Sayed NM , Wortman JR , Feldblyum T , Tallon L , Schatz M , Shumway M , Koo H , Salzberg SL , Schobel S , Pertea M , Pop M , White O , Barton GJ , Carlow CK , Crawford MJ , Daub J , Dimmic MW , Estes CF , Foster JM , Ganatra M , Gregory WF , Johnson NM , Jin J , Komuniecki R , Korf I , Kumar S , Laney S , Li BW , Li W , Lindblom TH , Lustigman S , Ma D , Maina CV , Martin DM , McCarter JP , McReynolds L , Mitreva M , Nutman TB , Parkinson J , Peregrin-Alvarez JM , Poole C , Ren Q , Saunders L , Sluder AE , Smith K , Stanke M , Unnasch TR , Ware J , Wei AD , Weil G , Williams DJ , Zhang Y , Williams SA , Fraser-Liggett C , Slatko B , Blaxter ML , Scott AL
Ref : Science , 317 :1756 , 2007
Abstract : Parasitic nematodes that cause elephantiasis and river blindness threaten hundreds of millions of people in the developing world. We have sequenced the approximately 90 megabase (Mb) genome of the human filarial parasite Brugia malayi and predict approximately 11,500 protein coding genes in 71 Mb of robustly assembled sequence. Comparative analysis with the free-living, model nematode Caenorhabditis elegans revealed that, despite these genes having maintained little conservation of local synteny during approximately 350 million years of evolution, they largely remain in linkage on chromosomal units. More than 100 conserved operons were identified. Analysis of the predicted proteome provides evidence for adaptations of B. malayi to niches in its human and vector hosts and insights into the molecular basis of a mutualistic relationship with its Wolbachia endosymbiont. These findings offer a foundation for rational drug design.
ESTHER : Ghedin_2007_Science_317_1756
PubMedSearch : Ghedin_2007_Science_317_1756
PubMedID: 17885136
Gene_locus related to this paper: bruma-a8ndk6 , bruma-a8njt8 , bruma-a8nl88 , bruma-a8npi4 , bruma-a8npi6 , bruma-a8p6g9 , bruma-a8pah3 , bruma-a8pc38 , bruma-a8pek5 , bruma-a8piq4 , bruma-a8pnw8 , bruma-a8psu4 , bruma-a8pte1 , bruma-a8q606 , bruma-a8q632 , bruma-a8q937 , bruma-a8qav5 , bruma-a8qbd9 , bruma-a8qgj6 , bruma-a8qh78 , bruma-a8q143 , bruma-a0a024mej5 , bruma-a0a0k0jju9 , bruma-a0a0i9n517

Title : Adjuncts to caudal blockade in children -
Author(s) : Mahajan R , Batra YK , Kumar S
Ref : British Journal of Anaesthesia , 96 :401 , 2006
PubMedID: 16526100

Title : Production of alkaline lipase by Corynebacterium paurometabolum, MTCC 6841 isolated from Lake Naukuchiatal, Uttaranchal State, India - Joshi_2006_Curr.Microbiol_52_354
Author(s) : Joshi GK , Kumar S , Tripathi BN , Sharma V
Ref : Curr Microbiol , 52 :354 , 2006
Abstract : A moderately psychrophilic bacterium Corynebacterium paurometabolum MTCC 6841 (gram positive, short rod type) producing extracellular alkaline lipase was isolated from Lake Naukuchiatal, Uttaranchal, India. The bacterium was able to grow within a broad range of pH (5-10). Soyabean oil and olive oil served as the best carbon sources for lipase production. The bacterium preferred inorganic nitrogenous compounds, NaNO3 and KNO3, over organic nitrogenous compound for its growth. Maximum lipase production occurred at 25 degrees C and 8.5 pH. The enzyme activity was found to be maximum at the same values of temperature and pH. The enzyme was reasonably stable in the presence of various organic solvents. No significant effect of Ca+, Cu++, Fe++, Na+, K+, Mg++, Mn+, NH4+, Co++ ions over enzyme activity was detected. Treatment with EDTA reduced the activity to nearly one half.
ESTHER : Joshi_2006_Curr.Microbiol_52_354
PubMedSearch : Joshi_2006_Curr.Microbiol_52_354
PubMedID: 16604420

Title : The Wolbachia genome of Brugia malayi: endosymbiont evolution within a human pathogenic nematode - Foster_2005_PLoS.Biol_3_e121
Author(s) : Foster J , Ganatra M , Kamal I , Ware J , Makarova K , Ivanova N , Bhattacharyya A , Kapatral V , Kumar S , Posfai J , Vincze T , Ingram J , Moran L , Lapidus A , Omelchenko M , Kyrpides N , Ghedin E , Wang S , Goltsman E , Joukov V , Ostrovskaya O , Tsukerman K , Mazur M , Comb D , Koonin E , Slatko B
Ref : PLoS Biol , 3 :e121 , 2005
Abstract : Complete genome DNA sequence and analysis is presented for Wolbachia, the obligate alpha-proteobacterial endosymbiont required for fertility and survival of the human filarial parasitic nematode Brugia malayi. Although, quantitatively, the genome is even more degraded than those of closely related Rickettsia species, Wolbachia has retained more intact metabolic pathways. The ability to provide riboflavin, flavin adenine dinucleotide, heme, and nucleotides is likely to be Wolbachia's principal contribution to the mutualistic relationship, whereas the host nematode likely supplies amino acids required for Wolbachia growth. Genome comparison of the Wolbachia endosymbiont of B. malayi (wBm) with the Wolbachia endosymbiont of Drosophila melanogaster (wMel) shows that they share similar metabolic trends, although their genomes show a high degree of genome shuffling. In contrast to wMel, wBm contains no prophage and has a reduced level of repeated DNA. Both Wolbachia have lost a considerable number of membrane biogenesis genes that apparently make them unable to synthesize lipid A, the usual component of proteobacterial membranes. However, differences in their peptidoglycan structures may reflect the mutualistic lifestyle of wBm in contrast to the parasitic lifestyle of wMel. The smaller genome size of wBm, relative to wMel, may reflect the loss of genes required for infecting host cells and avoiding host defense systems. Analysis of this first sequenced endosymbiont genome from a filarial nematode provides insight into endosymbiont evolution and additionally provides new potential targets for elimination of cutaneous and lymphatic human filarial disease.
ESTHER : Foster_2005_PLoS.Biol_3_e121
PubMedSearch : Foster_2005_PLoS.Biol_3_e121
PubMedID: 15780005
Gene_locus related to this paper: woltr-q5gs90 , woltr-q5gtr0

Title : Potent and selective proline derived dipeptidyl peptidase IV inhibitors - Edmondson_2004_Bioorg.Med.Chem.Lett_14_5151
Author(s) : Edmondson SD , Mastracchio A , Beconi M , Colwell LF, Jr. , Habulihaz B , He H , Kumar S , Leiting B , Lyons KA , Mao A , Marsilio F , Patel RA , Wu JK , Zhu L , Thornberry NA , Weber AE , Parmee ER
Ref : Bioorganic & Medicinal Chemistry Lett , 14 :5151 , 2004
Abstract : In-house screening of the Merck sample collection identified proline derived homophenylalanine 3 as a DPP-IV inhibitor with modest potency (DPP-IV IC50=1.9 microM). Optimization of 3 led to compound 37, which is among the most potent and selective DPP-IV inhibitors discovered to date.
ESTHER : Edmondson_2004_Bioorg.Med.Chem.Lett_14_5151
PubMedSearch : Edmondson_2004_Bioorg.Med.Chem.Lett_14_5151
PubMedID: 15380217

Title : Memantine: pharmacological properties and clinical uses - Kumar_2004_Neurol.India_52_307
Author(s) : Kumar S
Ref : Neurol India , 52 :307 , 2004
Abstract : Memantine is a relatively new drug specially developed for use in moderate-to-severe dementia. It is an uncompetitive N-methyl-D-aspartate receptor antagonist and reduces glutamatergic excitotoxicity. Though Alzheimer's disease (AD) is the commonest cause of dementia in the world, there is no "cure" available for the same. Cholinesterase inhibitors such as donepezil and rivastigmine have been shown to provide symptomatic relief in patients with AD but have no effect on disease progression or survival. Moreover, they are not helpful in more severe stages of dementia. Memantine has been shown to cause modest improvement in clinical symptoms in severe stages of AD and may retard the disease progression. Moreover, it has been shown to be useful in various forms of dementia including AD, vascular dementia and Wernicke-Korsakoff psychosis. It is also the first drug to cause complete disappearance of pendular nystagmus due to multiple sclerosis. The current review focuses on the pharmacological properties of memantine and examines the recent evidence in favor of memantine.
ESTHER : Kumar_2004_Neurol.India_52_307
PubMedSearch : Kumar_2004_Neurol.India_52_307
PubMedID: 15472417

Title : Clinical characteristics of organophosphate-induced delayed polyneuropathy -
Author(s) : Kumar S
Ref : Neurol India , 52 :128 , 2004
PubMedID: 15069267

Title : Comparative metabolism of chrysene and 5-methylchrysene by rat and rainbow trout liver microsomes - Shappell_2003_Toxicol.Sci_72_260
Author(s) : Shappell NW , Carlino-MacDonald U , Amin S , Kumar S , Sikka HC
Ref : Toxicol Sci , 72 :260 , 2003
Abstract : We have investigated the metabolism of chrysene (CHR) and 5-methychyrsene (5-MeCHR) by Shasta rainbow trout (Oncorhyncus mykiss) and Long Evans rat liver microsomes to assess the effect of a non-benzo ring methyl substituent on the reactions involved in the metabolism of polycyclic aromatic hydrocarbons (PAHs). Trout as well as rat liver microsomes metabolized both CHR and 5-MeCHR at essentially similar rates, indicating that the methyl substituent does not alter the substrate specificity of the cytochrome P450(s) involved in the metabolism of the two PAHs. Dihydrodiols were the major CHR metabolites formed by both trout and rat liver microsomes, whereas the trout liver microsomes formed a considerably higher proportion of 5-MeCHR phenols compared to diols, indicating that 5-methyl substitution alters the substrate specificity of trout microsomal epoxide hydrolase for 5-MeCHR epoxides. Unlike trout liver microsomes, rat liver microsomes formed a much greater proportion of 5-MeCHR diols compared to 5-MeCHR phenols, suggesting that 5-MeCHR epoxides are better substrates for the microsomal epoxide hydrolase present in rat liver than for the enzyme in trout liver. Both trout and rat liver microsomes are more efficient at attacking the bay-region bond versus the non-bay-region double bond in chrysene. In contrast the reverse is true in the case of 5-MeCHR, indicating that a non-benzo ring methyl substituent alters the regioselectivity of the enzymes involved in the oxidative metabolism of PAHs.
ESTHER : Shappell_2003_Toxicol.Sci_72_260
PubMedSearch : Shappell_2003_Toxicol.Sci_72_260
PubMedID: 12655039

Title : Comparative account of certain enzymes in the serum of homo-iothermal vertebrates subjected to production of myocardial infarction by isoproterenol hydrochloride - Gaur_2003_J.Environ.Biol_24_483
Author(s) : Gaur M , Kumar S
Ref : J Environ Biol , 24 :483 , 2003
Abstract : Myocardial infarction was produced by subcutaneous administration of isoproterenol hydrochloride (85 mg/kg b.w. for two consecutive days). The myocardial damage was proved by observing increase in the activity of SGOT and SGPT in serum whereas AChE activity was inhibited by increasing Km, without affecting Vmax. The inhibition of AChE and inhibitory kinetic may be useful in the diagnosis and management of salvage of myocardium.
ESTHER : Gaur_2003_J.Environ.Biol_24_483
PubMedSearch : Gaur_2003_J.Environ.Biol_24_483
PubMedID: 15248667

Title : Effect of DDVP on the histology and AChE kinetics of heart muscles of Rattus norvegicus - Parveen_2001_J.Environ.Biol_22_257
Author(s) : Parveen M , Kumar S
Ref : J Environ Biol , 22 :257 , 2001
Abstract : The LD50 of DDVP (Dichloro, dimethyl vinyl phosphate) for Rattus norvegicus was 21.4 mg/kg. b.w. The two sub lethal doses 1 and 3 mg/kg showed many histopathological changes in the working heart muscles and also showed significant necrosis in this S-A node, A-V node and bunble of His of the cardiac conducting system. These sublethal doses of the OP pesticide caused a significant inhibition of AChE. The maximum inhibition was noticed at the highest dose. The enhanced inhibitory constant Km and ACh contents in the heart muscles with the increase of dose showed inhibition of enzyme. The constant Vmax showed competitive nature of inhibition. A significant inhibition of AChE (69%) indicated that DDVP is a strong inhibitor of enzyme in heart.
ESTHER : Parveen_2001_J.Environ.Biol_22_257
PubMedSearch : Parveen_2001_J.Environ.Biol_22_257
PubMedID: 12018594

Title : Aluminium-induced biphasic effect - Kumar_1999_Med.Hypotheses_52_557
Author(s) : Kumar S
Ref : Med Hypotheses , 52 :557 , 1999
Abstract : Increased bioavailability of aluminium has raised concerns about the toxic effect of aluminium. The cholinotoxic effect of aluminium is already well established. The biological response of an organism following exposure to a chemical may be biphasic. Although aluminium-induced biphasic change has been reported in diverse organ systems, the biphasic effect on cholinergic system has received less attention. In vitro and in vivo studies have demonstrated an aluminium-induced biphasic effect on the marker enzyme of cholinergic system, acetylcholinesterase. The biphasic effect of aluminium on the acetylcholinesterase enzyme activity may be due to the direct neurotoxic effect of the metal and the level of aluminium accumulated. Among various hypotheses, peroxidation-induced changes in the structure of membrane following aluminium accumulation seems to explain the biphasic effect of aluminium on acetylcholinesterase activity.
ESTHER : Kumar_1999_Med.Hypotheses_52_557
PubMedSearch : Kumar_1999_Med.Hypotheses_52_557
PubMedID: 10459838

Title : The proximate carcinogen trans-3,4-dihydroxy-3,4-dihydro-dibenz[c,h]acridine is oxidized stereoselectively and regioselectively by cytochrome 1A1, epoxide hydrolase and hepatic microsomes from 3-methylcholanthrene-treated rats - Adams_1999_Chem.Biol.Interact_122_117
Author(s) : Adams JD, Jr. , Sayer JM , Chadha A , Shirai N , Lehr RE , Kumar S , Jerina DM
Ref : Chemico-Biological Interactions , 122 :117 , 1999
Abstract : Metabolism of the proximate carcinogen trans-3,4-dihydroxy-3,4-dihydrodibenz[c,h]acridine has been examined with rat liver enzymes. The dihydrodiol is metabolized at a rate of 2.4 nmol/nmol of cytochrome P450 1A1/min with microsomes from 3-methylcholanthrene-treated rats, a rate more than 10-fold higher than that observed with microsomes from control or phenobarbital-treated rats. Major metabolises consisted of a diastereomeric pair of bis-dihydrodiols (68-83%), where the new dihydrodiol group has been introduced at the 8,9-position, tetraols derived from bay region 3,4-diol-1,2-epoxides (15-23%), and a small amount of a phenolic dihydrodiol(s) where the new hydroxy group is at the 8,9-position of the substrate. A highly purified monooxygenase system reconstituted with cytochrome P450 1A1 and epoxide hydrolase (17 nmol of metabolites/nmol of cytochrome P450 1A1/min) gave a metabolite profile very similar to that observed with liver microsomes from 3-methylcholanthrene-treated rats. Study of the stereoselectivity of these microsomes established that the (+)-(3S,4S)-dihydrodiol gave mainly the diol epoxide-1 diastereomer, in which the benzylic 4-hydroxyl group and epoxide oxygen are cis. The (-)-(3R,4R)-dihydrodiol gave mainly diol epoxide-2 where these same groups are trans. The major enantiomers of the diastereomeric bis-dihydrodiols are shown to have the same absolute configuration at the 8,9-position. Correlations of circular dichroism spectra suggest this configuration to be (8R,9R). The (8R,9S)-oxide may be their common precursor.
ESTHER : Adams_1999_Chem.Biol.Interact_122_117
PubMedSearch : Adams_1999_Chem.Biol.Interact_122_117
PubMedID: 10528997

Title : A molecular timescale for vertebrate evolution - Kumar_1998_Nature_392_917
Author(s) : Kumar S , Hedges SB
Ref : Nature , 392 :917 , 1998
Abstract : A timescale is necessary for estimating rates of molecular and morphological change in organisms and for interpreting patterns of macroevolution and biogeography. Traditionally, these times have been obtained from the fossil record, where the earliest representatives of two lineages establish a minimum time of divergence of these lineages. The clock-like accumulation of sequence differences in some genes provides an alternative method by which the mean divergence time can be estimated. Estimates from single genes may have large statistical errors, but multiple genes can be studied to obtain a more reliable estimate of divergence time. However, until recently, the number of genes available for estimation of divergence time has been limited. Here we present divergence-time estimates for mammalian orders and major lineages of vertebrates, from an analysis of 658 nuclear genes. The molecular times agree with most early (Palaeozoic) and late (Cenozoic) fossil-based times, but indicate major gaps in the Mesozoic fossil record. At least five lineages of placental mammals arose more than 100 million years ago, and most of the modern orders seem to have diversified before the Cretaceous/Tertiary extinction of the dinosaurs.
ESTHER : Kumar_1998_Nature_392_917
PubMedSearch : Kumar_1998_Nature_392_917
PubMedID: 9582070

Title : Biphasic effect of aluminium on cholinergic enzyme of rat brain - Kumar_1998_Neurosci.Lett_248_121
Author(s) : Kumar S
Ref : Neuroscience Letters , 248 :121 , 1998
Abstract : The cholinotoxic effect of aluminium has been widely reported. In vitro aluminium has a biphasic effect on acetylcholinesterase activity. The present study analyses its in vivo effect in brain regions. Rats were exposed to aluminium chloride by the oral route at a dose of 320 mg/kg body weight for shorter (4 and 14 days) and longer (60 days) duration. Acetylcholinesterase activity in olfactory bulb, striatum and hypothalamus brain regions increased after 4 and 14 days and decreased after 60 days of aluminium exposure. Aluminium level in the brain regions studied increased significantly. No significant change in body weight of rats exposed to aluminium was found. The biphasic change in acetylcholinesterase activity may be due to slow accumulation of aluminium in the brain regions and its effect on the enzyme.
ESTHER : Kumar_1998_Neurosci.Lett_248_121
PubMedSearch : Kumar_1998_Neurosci.Lett_248_121
PubMedID: 9654357

Title : Serum paraoxonase activity, concentration, and phenotype distribution in diabetes mellitus and its relationship to serum lipids and lipoproteins - Abbott_1995_Arterioscler.Thromb.Vasc.Biol_15_1812
Author(s) : Abbott CA , Mackness MI , Kumar S , Boulton AJ , Durrington PN
Ref : Arterioscler Thromb Vasc Biol , 15 :1812 , 1995
Abstract : Human serum paraoxonase is physically associated with HDL and has been implicated in the detoxification of organophosphates and possibly in the prevention of LDL lipid peroxidation. We investigated the serum activity and concentration of paraoxonase in 78 patients with type 1 diabetes mellitus, 92 with type 2 diabetes, and 82 nondiabetic control subjects. Paraoxonase activity was generally lower in diabetics than in control subjects. This decrease was unrelated to differences in paraoxonase phenotype distribution or its serum concentration. Rather, the difference in paraoxonase activity was explained by its specific activity, which was lower in diabetics, indicating either the presence of a circulating inhibitor or disturbance of the interaction of paraoxonase with HDL affecting its activity. Paraoxonase specific activity was lowest in patients with peripheral neuropathy, suggesting an association of paraoxonase with neuropathy. In control subjects but not patients with diabetes, paraoxonase correlated with HDL cholesterol and apolipoprotein A-1. Our results indicate that the low paraoxonase activity in diabetes is due to decreased specific activity. In other studies low serum paraoxonase activity has been associated with increased susceptibility to atherosclerosis, and the present results also suggest an association with peripheral neuropathy, which could be due to reduced capacity to detoxify lipid peroxides in diabetes.
ESTHER : Abbott_1995_Arterioscler.Thromb.Vasc.Biol_15_1812
PubMedSearch : Abbott_1995_Arterioscler.Thromb.Vasc.Biol_15_1812
PubMedID: 7583560

Title : Relationship between serum butyrylcholinesterase activity, hypertriglyceridaemia and insulin sensitivity in diabetes mellitus - Abbott_1993_Clin.Sci_85_77
Author(s) : Abbott CA , Mackness MI , Kumar S , Olukoga AO , Gordon C , Arrol S , Bhatnagar D , Boulton AJ , Durrington PN
Ref : Clinical Science , 85 :77 , 1993
Abstract : 1. The activity of serum butyrylcholinesterase ('pseudocholinesterase', EC3.1.1.8) was investigated in 56 patients with type 1 diabetes mellitus, 51 patients with type 2 diabetes mellitus and 101 healthy control subjects. 2. Butyrylcholinesterase activity was significantly elevated in both type 1 (8.10 +/- 3.35 units/ml) and type 2 (7.22 +/- 1.95 units/ml) diabetes compared with the control subjects (4.23 +/- 1.89 units/ml) (P < 0.001). 3. In the patients with type 1 and type 2 diabetes, serum butyrylcholinesterase activity was correlated with log serum fasting triacylglycerol concentration (r = 0.41 and r = 0.43, respectively, P < 0.001). In the type 2 population serum butyrylcholinesterase activity was also correlated with insulin sensitivity (r = -0.51, P < 0.001). 4. Serum butyrylcholinesterase activity was unrelated to age, gender, serum gamma-glutamyltranspeptidase activity, body mass index, or treatment for diabetes in both the diabetic populations. 5. In 37 non-diabetic patients with butyrylcholinesterase deficiency serum triacylglycerol levels were in the normal range. 6. These results are consistent with the view that butyrylcholinesterase may have a role in the altered lipoprotein metabolism in hypertriglyceridaemia associated with insulin insensitivity or insulin deficiency in diabetes mellitus.
ESTHER : Abbott_1993_Clin.Sci_85_77
PubMedSearch : Abbott_1993_Clin.Sci_85_77
PubMedID: 8149699