Das S

References (28)

Title : Environmental impacts of microplastic and role of plastisphere microbes in the biodegradation and upcycling of microplastic - Behera_2023_Chemosphere__138928
Author(s) : Behera S , Das S
Ref : Chemosphere , :138928 , 2023
Abstract : Increasing usage of plastic has led to the deposition of plastic in the environment which later become microplastic, a pollutant of global concern. These polymeric particles affect the ecosystem bestowing toxicity and impede the biogeochemical cycles. Besides, microplastic particles have been known for their role in aggravating the effect of various other environmental pollutants including organic pollutants and heavy metals. These microplastic surfaces are often colonized by the microbial communities also known as "plastisphere microbes" forming biofilms. These microbes include cyanobacteria like Nostoc, Scytonema, etc., and diatoms like Navicula, Cyclotella, etc. Which become the primary colonizer. In addition to the autotrophic microbes, Gammaproteobacteria and Alphaproteobacteria dominate the plastisphere microbial community. These biofilm-forming microbes can efficiently degrade the microplastic in the environment by secreting various catabolic enzymes such as lipase, esterase, hydroxylase, etc. Besides, these microbes have shown great potential for the bioconversion of microplastic to polyhydroxyalkanoates (PHA), an energy efficient and sustainable alternative to the petroleum based plastics. Thus, these microbes can be used for the creation of a circular economy using waste to wealth strategy. This review provides a deeper insight into the distribution, transportation, transformation, and biodegradation of microplastic in the ecosystem. The formation of plastisphere by the biofilm-forming microbes has been described in the article. In addition, the microbial metabolic pathways and genetic regulations involved in the biodegradation have been discussed in detail. The article suggests the microbial bioremediation and upcycling of microplastic along with various other strategies for effectively mitigate the microplastic pollution.
ESTHER : Behera_2023_Chemosphere__138928
PubMedSearch : Behera_2023_Chemosphere__138928
PubMedID: 37211165

Title : Synergistic degradation of Chlorpyrifos by modified solar Photo-Fenton process with bacterial metabolism reduces in vivo biotoxicity in zebrafish (Danio rerio) - Nayak_2023_Sci.Total.Environ__164488
Author(s) : Nayak T , Patel P , Ghosh A , Simnani FZ , Kumari K , Das S , Nandi A , Panda PK , Kaushik NK , Raina V , Verma SK
Ref : Sci Total Environ , :164488 , 2023
Abstract : The extensive use of Chlorpyrifos (CP) as insecticide has raised concern to their hazardous impact on human health and ecosystems. Bioremediation has been proved as one of the key eco-compatible method for reducing these environmental toxicants. This study explores and evaluate the effectiveness of a combined process including solar Photo-Fenton process followed by bacterial degradation using Ochrobactrum sp. CPD-03 for effective CP degradation in wastewater. Moreover, the in vivo molecular biotoxicity of CP and degraded CP has been evaluated with embryonic zebrafish. The solar Photo-Fenton treatment showed CP degradation efficiency of ~42 % in 4 h and ~92 % in 96 h with combined bacterial degradation process. In vivo biotoxicity analysis showed increased survivability of embryonic zebrafish exposed to CP with CPD-03 in water with lesser morphological abnormalities. The mechanistic molecular analysis showed decreased acetylcholinesterase inhibition and GST activity in embryos exposed to CP with CPD-03 for a lesser apoptosis due to influential intrinsic interaction with metabolic proteins. The study advocated to the use of solar Photo-Fenton process followed by bacterial degradation for an efficient ecological degradation of CP for effective reduction of in vivo biotoxicity.
ESTHER : Nayak_2023_Sci.Total.Environ__164488
PubMedSearch : Nayak_2023_Sci.Total.Environ__164488
PubMedID: 37247729

Title : EphH, a unique epoxide hydrolase encoded by Rv3338 is involved in the survival of Mycobacterium tuberculosis under in vitro stress and vacuolar pH-induced changes - Garg_2023_Front.Microbiol_13_1092131
Author(s) : Garg T , Das S , Singh S , Imran M , Mukhopadhyay A , Gupta UD , Chopra S , Dasgupta A
Ref : Front Microbiol , 13 :1092131 , 2023
Abstract : INTRODUCTION: Mycobacterium tuberculosis (Mtb), one of the deadliest human pathogen, has evolved with different strategies of survival inside the host, leading to a chronic state of infection. Phagosomally residing Mtb encounters a variety of stresses, including increasing acidic pH. To better understand the host-pathogen interaction, it is imperative to identify the role of various genes involved in the survivability of Mtb during acidic pH environment. METHODS: Bio-informatic and enzymatic analysis were used to identify Mtb gene, Rv3338, as epoxide hydrolase. Subsequently, CRISPRi knockdown strategy was used to decipher its role for Mtb survival during acidic stress, nutrient starvation and inside macrophages. Confocal microscopy was used to analyse its role in subverting phagosomal acidification within macrophage. RESULTS: The present work describes the characterization of Rv3338 which was previously known to be associated with the aprABC locus induced while encountering acidic stress within the macrophage. Bio-informatic analysis demonstrated its similarity to epoxide hydrolase, which was confirmed by enzymatic assays, thus, renamed EphH. Subsequently, we have deciphered its indispensable role for Mtb in protection from acidic stress by using the CRISPRi knockdown strategy. Our data demonstrated the pH dependent role of EphH for the survival of Mtb during nutrient starvation and in conferring resistance against elevated endogenous ROS levels during stress environment. CONCLUSION: To the best of our knowledge, this is the first report of an EH of Mtb as a crucial protein for bacterial fitness inside the host, a phenomenon central to its pathogenesis.
ESTHER : Garg_2023_Front.Microbiol_13_1092131
PubMedSearch : Garg_2023_Front.Microbiol_13_1092131
PubMedID: 36777032
Gene_locus related to this paper: myctu-MT3441

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 : Role of multi-targeted bioactive natural molecules and their derivatives in the treatment of Alzheimer's disease: an insight into structure-activity relationship - Halder_2022_J.Biomol.Struct.Dyn__1
Author(s) : Halder D , Das S , R SJ , Joseph A
Ref : J Biomol Struct Dyn , :1 , 2022
Abstract : Alzheimer's disease (AD) is a complex neurodegenerative disorder involving cognitive dysfunction like short-term memory and behavioral changes as the disease progresses due to other unaltered physiological factors. The solution for this problem is Multi-targeted Drugs (MTDs), which can affect multiple determinants to realize the multifunctional effects. Acetylcholinesterase (AChE) inhibitors donepezil, rivastigmine, galantamine, and N-methyl-D-aspartate (NMDA) receptor antagonist memantine are FDA-approved drugs used to treat AD symptomatically. The key objective of this review is to understand multitargeted bioactive natural molecules that could be considered as leads for further development as effective drugs for treating AD, along with understanding its pharmacology and structure-activity relationship (SAR). Understanding the molecular mechanism of the AD pathophysiology, the role of existing drugs, treatment of AD via amyloid beta (Abeta) plaque, and neurofibrillary tangle (NFT) inhibition by natural bioactive molecules were also discussed in the review. The current quest and recent advancements with natural bioactive compounds like physostigmine, resveratrol, curcumin, and catechins, along with the study of in silico SAR, were reported in the present study. This review summarises the structural properties required for bioactive natural molecules to show anti-Alzheimer's activity by emphasizing on SAR of several bioactive natural molecules targeting various AD pathologies, their key molecular interactions that are critical for target specificity, their role as multitargeted ligands, used with adjunctive therapy for AD followed by related US patents granted recently. This article highlights the significance of the structural features of natural bioactive molecules in the treatment of AD and establishes a connection between them.Communicated by Ramaswamy H. Sarma.
ESTHER : Halder_2022_J.Biomol.Struct.Dyn__1
PubMedSearch : Halder_2022_J.Biomol.Struct.Dyn__1
PubMedID: 36579430

Title : Nanonization of a chemically synthesized flavone HMDF (3-hydroxy-3',4'-methylenedioxyflavone) by entrapping within calcium phosphate nanoparticle (CPNP) and exploring its anti-oxidant role on neural cells in vitro and zebra fish in vivo - Patra_2021_Nanotechnology__
Author(s) : Patra M , Banik M , Bandyopadhyay P , Dutta D , Mukherjee R , Das S , Begum NA , Basu T
Ref : Nanotechnology , : , 2021
Abstract : HMDF was reported to be synthesized chemically to generate a modified flavone of potent antioxidant activity with significant neuro-pharmacological property. In this study, HMDF was nanonized by entrapping within CPNP. HMDF-CPNPs were of i) size 25nm, ii) zeta potential (-) [22+/-3]mV and iii) entrapment efficiency 67%. HMDF-CPNP, but not HMDF alone, inhibited in vitro activity of acetylcholinesterase enzyme to break down major neurotransmitter compound acetylcholine. Moreover, nanonized HMDF had more anti-oxidant activity than bulk HMDF, as observed from their ability to protect mouse neural cells (neuro-2A) from oxidative damage, caused by H2O2 exposure, at the levels of cell viability, intracellular reactive oxygen species (ROS), mitochondrial membrane potential, cell cycle stages, nuclear integrity and neural connectivity. In vivo study on Zebra-fish larvae (Denio rerio) also demonstrated that H2O2-mediated larval death was checked by HMDF-CPNP treatment. Results, therefore, suggest that HMDF-CPNP may be developed as a potential antioxidant, particularly as neuro-protectant.
ESTHER : Patra_2021_Nanotechnology__
PubMedSearch : Patra_2021_Nanotechnology__
PubMedID: 33588381
Gene_locus related to this paper: danre-ACHE

Title : An atomistic view of solvent-free protein liquids: the case of Lipase A - Behera_2021_Phys.Chem.Chem.Phys_23_7302
Author(s) : Behera S , Das S , Balasubramanian S
Ref : Phys Chem Chem Phys , 23 :7302 , 2021
Abstract : Solvent-free enzymes hold the promise of being able to deliver higher activity at elevated temperatures by virtue of them being not limited by the boiling point of the solvent. They have been realized in the liquid phase through a polymer surfactant coating on the protein surface. However, a clear understanding of intermolecular interactions, structure, dynamics, and the behaviour of the minuscule amount of water present in the solvent-free protein liquid is essential to enhance the activity of these biofluids. Using atomistic molecular dynamics simulations, we demonstrate that the scaled spatial correlations between proteins in the hybrid liquid phase of Lipase A enzymes are comparable to the inter-particle correlations in a noble gas fluid. The hydrophilic region of the surfactants forms a coronal layer around each enzyme which percolates throughout the liquid, while the hydrophobic parts are present as disjointed clusters. Inter-surfactant interactions, determined to be attractive and in the range of -200 to -300 kcal mol(-1), stabilize the liquid state. While the protein retains its native state conformational dynamics in the solvent-free form, the fluxionality of its side chains is much reduced; at 333 K, the latter is found to be equivalent to that of the enzyme in an aqueous solution at 249 K. Despite the sluggishness of the solvent-free enzyme, some water molecules exhibit high mobility and transit between enzymes primarily via the interspersed hydrophilic regions. These microscopic insights offer ideas to improve substrate diffusion in the liquid to enable the enhancement of catalytic activity.
ESTHER : Behera_2021_Phys.Chem.Chem.Phys_23_7302
PubMedSearch : Behera_2021_Phys.Chem.Chem.Phys_23_7302
PubMedID: 33876090

Title : Nanonization of a chemically synthesized flavone HMDF (3-hydroxy-3',4'-methylenedioxyflavone) by entrapping within calcium phosphate nanoparticles and exploring its antioxidant role on neural cells in vitro and zebrafish in vivo - Patra_2021_Nanotechnology_32_235101
Author(s) : Patra M , Banik M , Bandopadhyay P , Dutta D , Mukherjee R , Das S , Begum NA , Basu T
Ref : Nanotechnology , 32 :235101 , 2021
Abstract : The chemical synthesis of 3-hydroxy-3',4'-methylenedioxyflavone (HMDF) was reported to generate a modified flavone of potent antioxidant activity with significant neuropharmacological properties. In this study, HMDF was nanonized by entrapping within calcium phosphate nanoparticles (CPNPs). HMDF-CPNPs were of (i) size 25 nm, (ii) zeta potential (-) [22 +/- 3] mV and (iii) entrapment efficiency 67%. HMDF-CPNPs, but not HMDF alone, inhibited the in vitro activity of acetylcholinesterase enzymes to break down the major neurotransmitter compound acetylcholine. Moreover, nanonized HMDF had more antioxidant activity than bulk HMDF, as observed from its ability to protect mouse neural (N2A) cells from oxidative damage caused by H(2)O(2) exposure at the levels of cell viability, intracellular reactive oxygen species, mitochondrial membrane potential, cell cycle stages, nuclear integrity and neural connectivity. An in vivo study on zebrafish larvae (Denio rerio) also demonstrated that H(2)O(2)-mediated larval death was checked by HMDF-CPNP treatment. These results, therefore, suggest that HMDF-CPNPs may be developed as a potential antioxidant, particularly as a neuroprotectant.
ESTHER : Patra_2021_Nanotechnology_32_235101
PubMedSearch : Patra_2021_Nanotechnology_32_235101
PubMedID: 33724928

Title : Neurodegenerative Pathways in Alzheimer's Disease: A Review - Ramachandran_2021_Curr.Neuropharmacol_19_679
Author(s) : Ramachandran AK , Das S , Joseph A , Shenoy GG , Alex AT , Mudgal J
Ref : Curr Neuropharmacol , 19 :679 , 2021
Abstract : Alzheimer's disease (AD) is a complex neurodegenerative disease that leads to insidious deterioration of brain functions and is considered the sixth leading cause of death in the world. Alzheimer's patients suffer from memory loss, cognitive deficit and behavioral changes; thus, they eventually follow a low-quality life. AD is considered as a multifactorial disorder involving different neuropathological mechanisms. Recent research has identified more than 20 pathological factors that are promoting disease progression. Three significant hypotheses are said to be the root cause of disease pathology, which include acetylcholine deficit, the formation of amyloid-beta senile plaques and tau protein hyperphosphorylation. Apart from these crucial factors, pathological factors such as apolipoprotein E (APOE), glycogen synthase kinase 3beta, notch signaling pathway, Wnt signaling pathway, etc., are considered to play a role in the advancement of AD and therefore could be used as targets for drug discovery and development. As of today, there is no complete cure or effective disease altering therapies for AD. The current therapy is assuring only symptomatic relief from the disease, and progressive loss of efficacy for these symptomatic treatments warrants the discovery of newer drugs by exploring these novel drug targets. A comprehensive understanding of these therapeutic targets and their neuropathological role in AD is necessary to identify novel molecules for the treatment of AD rationally.
ESTHER : Ramachandran_2021_Curr.Neuropharmacol_19_679
PubMedSearch : Ramachandran_2021_Curr.Neuropharmacol_19_679
PubMedID: 32851951

Title : Pharmacological and pharmacognostical valuation of Canna indica leaves extract by quantifying safety profile and neuroprotective potential - Chigurupati_2021_Saudi.J.Biol.Sci_28_5579
Author(s) : Chigurupati S , Abdul Rahman Alharbi N , Sharma AK , Alhowail A , Vardharajula VR , Vijayabalan S , Das S , Kauser F , Amin E
Ref : Saudi J Biol Sci , 28 :5579 , 2021
Abstract : The current study primarily focused on the pharmacognostical and phytochemical screening of Canna indica and further analyzing the leaves extract for toxicological profile and neuroprotective potential. The microscopic, dry powder properties of the leaf material and phytochemical, physicochemical analysis was evaluated for pharmacognostical assessment. Dry leaves of C. indica were extracted using methanol and then further studied for both in vitro and in vivo toxicological study. The acute toxicity was measured by estimating the antioxidant defense system and anatomical impairment in the rat's organs. Also, the neuroprotective activity of the plant extract was assessed using anticholinesterase enzymatic inhibitory assay. The extract was found to be hemocompatible and showed absences of induction of behavioural changes. Likewise, no changes were seen on the anatomical structure of the rat's organs. The methanolic extract portrayed a significant upsurge in the reduced glutathione level and showed a comparable acetylcholinesterase inhibition in a dosedependent manner with an IC50 value of 14.53 microg/mL compared to the standard Donepezil with an IC50 value of 13.31 microg/mL. C. indica has compelling pharmacognostical characteristics, good safety reports, and significant antioxidant as well as the neuroprotective potential that shows great potential for its further in-depth research for pharmacological use.
ESTHER : Chigurupati_2021_Saudi.J.Biol.Sci_28_5579
PubMedSearch : Chigurupati_2021_Saudi.J.Biol.Sci_28_5579
PubMedID: 34588868

Title : Acetylcholinesterase and antioxidant responses in freshwater teleost, Channa punctata exposed to chlorpyrifos and urea - Deb_2020_Comp.Biochem.Physiol.C.Toxicol.Pharmacol_240_108912
Author(s) : Deb N , Das S
Ref : Comparative Biochemistry & Physiology C Toxicol Pharmacol , 240 :108912 , 2020
Abstract : We aimed to understand the toxic effects of two crop protecting agents, organophosphate pesticide, chlorpyrifos (CPF) and fertilizer, urea (U), and their binary mixtures at sublethal concentrations for 28-d in a freshwater fish Channa punctata with a battery of biochemical biomarkers in gill and liver. The study has practical value as such mixtures, so often present together in water in the agro-intensive areas, might be predicted to cause cocktail effects. Both CPF and U inhibited AChE, augmented SOD, CAT, GPx activities, and caused lipid peroxidation and depletion in tissue macromolecules in a concentration and duration-dependent manner. While U alone had less severe effects compared to CPF treatments, complex interactions were observed for three combination doses (1CPF + 1U, 2CPF + 1U, 1CPF + 2U). In their mutual effects, antagonism prevailed over other interactions when CPF and U were in equal proportion in the mixture, while synergism was observed for AchE and key antioxidant enzymes when more U was in the mixture. The present study concluded that urea in water bodies might impart adverse effects in combination with pesticides in non-target aquatic organisms such as fish, and there should be a restriction in its excessive usage.
ESTHER : Deb_2020_Comp.Biochem.Physiol.C.Toxicol.Pharmacol_240_108912
PubMedSearch : Deb_2020_Comp.Biochem.Physiol.C.Toxicol.Pharmacol_240_108912
PubMedID: 33059086

Title : Quercetin-induced amelioration of deltamethrin stress in freshwater teleost, Channa punctata: Multiple biomarker analysis - Bhattacharjee_2019_Comp.Biochem.Physiol.C.Toxicol.Pharmacol__108626
Author(s) : Bhattacharjee P , Borah A , Das S
Ref : Comparative Biochemistry & Physiology C Toxicol Pharmacol , :108626 , 2019
Abstract : We aimed to ascertain whether ubiquitous plant-based polyphenolic flavonoid compound quercetin (Q) was capable of alleviating deltamethrin (DM) stress in a freshwater teleost, Channa punctata, with emphasis on levels of acetylcholinesterase (AChE), reduced glutathione (GSH), glutathione-S-transferase (GST), DNA/RNA contents and hematological parameters. We measured these parameters in various tissues of fish at 7 and 21days of exposure to DM doses (0.03 and 0.15muLL(-1)), Q (0.14gL(-1)) and their combinations (0.03muLDML(-1)+0.14gQL(-1) and 0.15muLDML(-1)+0.14gQL(-1)). Both the DM doses altered blood parameters, lowered DNA/RNA contents, AchE activities, GSH levels and augmented GST activities as a mark of neurotoxicity and oxidative stress in fish tissues. We found that 0.14gL(-1) Q ameliorated oxidative stress and AchE inhibitory effects, recovered DM-induced nucleic acid damage and alterations in blood parameters, with some tissue specificity and duration-dependent manner. Thus, the results indicated that Q was capable of neuroprotection and enhancing the function of antioxidants in fish, which could be predicted to be useful for providing better protection to fish under aquaculture settings with improved Q-rich diets. Through this study with multiple biomarkers in several tissues of fish, valuable information for devising better strategies regarding pesticide risk assessment was obtained and it was recognized that an appropriate dose of Q was essential for its better functioning.
ESTHER : Bhattacharjee_2019_Comp.Biochem.Physiol.C.Toxicol.Pharmacol__108626
PubMedSearch : Bhattacharjee_2019_Comp.Biochem.Physiol.C.Toxicol.Pharmacol__108626
PubMedID: 31648051

Title : Flavanone glycosides inhibit beta-site amyloid precursor protein cleaving enzyme 1 and cholinesterase and reduce Abeta aggregation in the amyloidogenic pathway - Ali_2019_Chem.Biol.Interact_309_108707
Author(s) : Ali MY , Jannat S , Edraki N , Das S , Chang WK , Kim HC , Park SK , Chang MS
Ref : Chemico-Biological Interactions , 309 :108707 , 2019
Abstract : Alzheimer's disease (AD) is a slow but progressive neurodegenerative disease. One of the pathological hallmarks of AD is the progressive accumulation of beta-amyloid (Abeta) in the form of senile plaques, and Abeta insult to neuronal cells has been identified as one of the major causes of AD onset. In the present study, we investigated the anti-AD potential of four flavonoids, naringenin, didymin, prunin, and poncirin, by evaluating their ability to inhibit acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and beta-site amyloid precursor protein cleaving enzyme 1 (BACE1). All four flavonoids displayed promising inhibitory activity against AChE, BChE, and BACE1. Structure-activity relationships suggested that glycosylation of naringenin at sugar moieties, and at different positions of the glycosidic linkage, might be closely associated with anti-AD potential. Kinetic and docking studies showed the lowest binding energy and highest affinity for the mixed, competitive, and non-competitive type inhibitors didymin, prunin, and poncirin. Hydrophobic interactions and the number of hydrogen bonds determined the strength of the protein-inhibitor interaction. We also examined the neuroprotective mechanisms by which flavonoids act against Abeta25-35-induced toxicity in PC12cells. Exposure of PC12cells to 10muMAbeta25-35 for 24h resulted in a significant decrease in cell viability. In addition, pretreatment of PC12cells with different concentrations of flavonoids for 1h significantly reversed the effects of Abeta. Furthermore, treatment with the most active flavonoid, didymin, significantly reduced BACE1, APPsbeta, and C99 expression levels in a dose-dependent manner, without affecting amyloid precursor protein (APP) levels in the amyloidogenic pathway. Together, our results indicate that flavonoids, and in particular didymin, exhibit inhibitory activity in vitro, and may be useful in the development of therapeutic modalities for the treatment of AD.
ESTHER : Ali_2019_Chem.Biol.Interact_309_108707
PubMedSearch : Ali_2019_Chem.Biol.Interact_309_108707
PubMedID: 31194956

Title : Physical interaction between nuclear accumulated CC-NB-ARC-LRR protein and WRKY64 promotes EDS1 dependent Fusarium wilt resistance in chickpea - Chakraborty_2018_Plant.Sci_276_111
Author(s) : Chakraborty J , Priya P , Dastidar SG , Das S
Ref : Plant Sci , 276 :111 , 2018
Abstract : Fusarium wilt is one of the most serious diseases affecting chickpea (Cicer arietinum L.). Here, we identified a putative Resistance Gene Analog (CaRGA) from chickpea, encoding a coiled-coil (CC) nucleotide-binding oligomerization domain (NB-ARC) containing leucine-rich repeat (LRR) protein (CC-NLR protein) that confers resistance against Fusarium oxysporum f. sp. ciceri race1 (Foc1). Over-expression and silencing of CaRGA in chickpea resulted in enhanced resistance and hyper-susceptibility, respectively against Foc1. Furthermore, defense response to Foc1 depends on CC-NLR interaction with WRKY64 transcription factor. CaRGA mediated wilt resistance largely compromised when WRKY64 was silenced. We also determined in planta intramolecular interactions and self-association of chickpea CC-NLR protein. The study shows CC domain suppressing auto-activation of the full-length CC-NLR protein in the absence of pathogen through self-inhibitory intramolecular interaction with NB-ARC domain, which is attenuated by self-interactions to LRR domain. Chickpea CC-NLR protein forms homocomplexes and then interacts with WRKY64. CC-NLR protein further phosphorylates WRKY64 thereby, ubiquitination and proteasome mediated degradation are protected. Phosphorylated WRKY64 with increased stability binds to EDS1 promoter and stimulates its transcription that induces in planta ectopic cell-death. The detailed analysis of CC-NLR and WRKY interactions provide a better understanding of the immune regulation by NLR proteins under biotic stresses.
ESTHER : Chakraborty_2018_Plant.Sci_276_111
PubMedSearch : Chakraborty_2018_Plant.Sci_276_111
PubMedID: 30348309

Title : Prediction of Anti-Alzheimer's Activity of Flavonoids Targeting Acetylcholinesterase in silico - Das_2017_Phytochem.Anal_28_324
Author(s) : Das S , Laskar MA , Sarker SD , Choudhury MD , Choudhury PR , Mitra A , Jamil S , Lathiff SMA , Abdullah SA , Basar N , Nahar L , Talukdar AD
Ref : Phytochem Anal , 28 :324 , 2017
Abstract : INTRODUCTION: Prenylated and pyrano-flavonoids of the genus Artocarpus J. R. Forster & G. Forster are well known for their acetylcholinesterase (AChE) inhibitory, anti-cholinergic, anti-inflammatory, anti-microbial, anti-oxidant, anti-proliferative and tyrosinase inhibitory activities. Some of these compounds have also been shown to be effective against Alzheimer's disease. OBJECTIVE: The aim of the in silico study was to establish protocols to predict the most effective flavonoid from prenylated and pyrano-flavonoid classes for AChE inhibition linking to the potential treatment of Alzheimer's disease. METHODOLOGY: Three flavonoids isolated from Artocarpus anisophyllus Miq. were selected for the study. With these compounds, Lipinski filter, ADME/Tox screening, molecular docking and quantitative structure-activity relationship (QSAR) were performed in silico. In vitro activity was evaluated by bioactivity staining based on the Ellman's method.
RESULTS: In the Lipinski filter and ADME/Tox screening, all test compounds produced positive results, but in the target fishing, only one flavonoid could successfully target AChE. Molecular docking was performed on this flavonoid, and this compound gained the score as -13.5762. From the QSAR analysis the IC50 was found to be 1659.59 nM. Again, 100 derivatives were generated from the parent compound and docking was performed. The derivative compound 20 was the best scorer, i.e. -31.6392 and IC50 was predicted as 6.025 nM. CONCLUSION: Results indicated that flavonoids could be efficient inhibitors of AChE and thus, could be useful in the management of Alzheimer's disease. Copyright (c) 2017 John Wiley & Sons, Ltd.
ESTHER : Das_2017_Phytochem.Anal_28_324
PubMedSearch : Das_2017_Phytochem.Anal_28_324
PubMedID: 28168765

Title : Multi-targeting Strategies for Alzheimer's Disease Therapeutics: Pros and Cons - Das_2017_Curr.Top.Med.Chem_17_3017
Author(s) : Das S , Basu S
Ref : Curr Top Med Chem , 17 :3017 , 2017
Abstract : Alzheimer's Disease (AD) is a single major cause of dementia in middle to old age individuals involving several different etiopathological mechanisms that are yet to be properly characterized. Major invariant and characteristic features consist of the progressive cerebral deposition of the Amyloid beta-protein (Abeta) and the neurofibrillary degeneration through Neurofibrillary Tangles (NFT) formed by hyperphosphorylation of the tau proteins in the regions of the brain that deal with memory and cognition. There are at least five subgroups of AD that can be identified by determining Cerebrospinal Fluid (CSF) levels of Abeta1-42, tau and ubiquitin. This multifactorial nature of the disease thus demands promising approaches for the development of rational disease-modifying drugs. A large number of agents have been discovered against individual targets but the success rate is very low and the number of compounds progressing to regulatory review is among the lowest found in any therapeutic area. A very promising modern approach solicits the design of Multi-Target-Directed Ligands (MTDLs) based on the "one molecule multiple targets" paradigm that has been specifically adopted for the treatment of disorders with complex pathological mechanisms. AD is one such disorder in which MTDL has found applicability. This review aims at providing an overview of the research carried out in discovering more efficient treatment against AD using MTDL, with a goal to ascertain safer drugs.
ESTHER : Das_2017_Curr.Top.Med.Chem_17_3017
PubMedSearch : Das_2017_Curr.Top.Med.Chem_17_3017
PubMedID: 28685694

Title : The Mycobacterium phlei Genome: Expectations and Surprises - Das_2016_Genome.Biol.Evol_8_975
Author(s) : Das S , Pettersson BM , Behra PR , Ramesh M , Dasgupta S , Bhattacharya A , Kirsebom LA
Ref : Genome Biol Evol , 8 :975 , 2016
Abstract : Mycobacterium phlei, a nontuberculosis mycobacterial species, was first described in 1898-1899. We present the complete genome sequence for theM. phlei CCUG21000(T)type strain and the draft genomes for four additional strains. The genome size for all five is 5.3 Mb with 69.4% Guanine-Cytosine content. This is approximately 0.35 Mbp smaller than the previously reported M. phlei RIVM draft genome. The size difference is attributed partly to large bacteriophage sequence fragments in theM. phlei RIVM genome. Comparative analysis revealed the following: 1) A CRISPR system similar to Type 1E (cas3) in M. phlei RIVM; 2) genes involved in polyamine metabolism and transport (potAD,potF) that are absent in other mycobacteria, and 3) strain-specific variations in the number of sigma-factor genes. Moreover,M. phlei has as many as 82 mce(mammalian cell entry) homologs and many of the horizontally acquired genes in M. phlei are present in other environmental bacteria including mycobacteria that share similar habitat. Phylogenetic analysis based on 693 Mycobacterium core genes present in all complete mycobacterial genomes suggested that its closest neighbor is Mycobacterium smegmatis JS623 and Mycobacterium rhodesiae NBB3, while it is more distant toM. smegmatis mc2 155.
ESTHER : Das_2016_Genome.Biol.Evol_8_975
PubMedSearch : Das_2016_Genome.Biol.Evol_8_975
PubMedID: 26941228
Gene_locus related to this paper: mycph-a0a139v4t0

Title : Molecular Mechanism behind Solvent Concentration-Dependent Optimal Activity of Thermomyces lanuginosus Lipase in a Biocompatible Ionic Liquid: Interfacial Activation through Arginine Switch - Das_2016_J.Phys.Chem.B_120_11720
Author(s) : Das S , Karmakar T , Balasubramanian S
Ref : J Phys Chem B , 120 :11720 , 2016
Abstract : Thermomyces lanuginosus lipase (TLL) is an industrially significant catalyst for the production of biodiesel due to its operability over a wide range of pH's and temperatures. Molecular dynamics simulations of TLL in aqueous solutions of a biocompatible ionic liquid (IL), cholinium glycinate (ChGly), have been carried out to investigate the microscopic reasons for the experimentally observed enhancement in the activity of TLL upon addition of a room temperature IL (RTIL), especially at an optimal concentration. Eight different TLL systems, in both their open and closed forms, at various concentrations of the RTIL in water have been studied. A special orientation of the lid residue, W89, in the closed form, which enables an optimal substrate-binding rate, has been identified, which can be probed via fluorescence spectroscopy. The flipping and consequent exposure of W89 in the open form of TLL induce a change in the lid helicity and orientation in such a way that residue R84 from the front lid hinge gets trapped around a particular region in all systems except at a 0.5 M IL concentration. At that concentration, R84 exhibits considerable fluxionality and moves back and forth via a water channel that is formed because of the chaotropic nature of the cholinium cation. Arginine switch is well established to be the primary signature of interfacial activation of TLL, which is observed here at an optimal IL concentration (0.5 M) without the use of a substrate or surfactant. The present work can pave the way for development of a broader platform for understanding lipases and their application in environment-friendly catalysis.
ESTHER : Das_2016_J.Phys.Chem.B_120_11720
PubMedSearch : Das_2016_J.Phys.Chem.B_120_11720
PubMedID: 27779408

Title : Characterization of Three Mycobacterium spp. with Potential Use in Bioremediation by Genome Sequencing and Comparative Genomics - Das_2015_Genome.Biol.Evol_7_1871
Author(s) : Das S , Pettersson BM , Behra PR , Ramesh M , Dasgupta S , Bhattacharya A , Kirsebom LA
Ref : Genome Biol Evol , 7 :1871 , 2015
Abstract : We provide the genome sequences of the type strains of the polychlorophenol-degrading Mycobacterium chlorophenolicum (DSM43826), the degrader of chlorinated aliphatics Mycobacterium chubuense (DSM44219) and Mycobacterium obuense (DSM44075) that has been tested for use in cancer immunotherapy. The genome sizes of M. chlorophenolicum, M. chubuense, and M. obuense are 6.93, 5.95, and 5.58 Mb with GC-contents of 68.4%, 69.2%, and 67.9%, respectively. Comparative genomic analysis revealed that 3,254 genes are common and we predicted approximately 250 genes acquired through horizontal gene transfer from different sources including proteobacteria. The data also showed that the biodegrading Mycobacterium spp. NBB4, also referred to as M. chubuense NBB4, is distantly related to the M. chubuense type strain and should be considered as a separate species, we suggest it to be named Mycobacterium ethylenense NBB4. Among different categories we identified genes with potential roles in: biodegradation of aromatic compounds and copper homeostasis. These are the first nonpathogenic Mycobacterium spp. found harboring genes involved in copper homeostasis. These findings would therefore provide insight into the role of this group of Mycobacterium spp. in bioremediation as well as the evolution of copper homeostasis within the Mycobacterium genus.
ESTHER : Das_2015_Genome.Biol.Evol_7_1871
PubMedSearch : Das_2015_Genome.Biol.Evol_7_1871
PubMedID: 26079817
Gene_locus related to this paper: 9myco-a0a099cjp1 , 9myco-a0a0j6vre4 , 9myco-a0a0j6w0u2 , 9myco-a0a0j6yty5 , 9myco-a0a0j6w1z8 , 9myco-a0a0j6w9j0

Title : Diversity in protein domain superfamilies - Das_2015_Curr.Opin.Genet.Dev_35_40
Author(s) : Das S , Dawson NL , Orengo CA
Ref : Curr Opin Genet Dev , 35 :40 , 2015
Abstract : Whilst approximately 93% of domain superfamilies appear to be relatively structurally and functionally conserved based on the available data from the CATH-Gene3D domain classification resource, the remainder are much more diverse. In this review, we consider how domains in some of the most ubiquitous and promiscuous superfamilies have evolved, in particular the plasticity in their functional sites and surfaces which expands the repertoire of molecules they interact with and actions performed on them. To what extent can we identify a core function for these superfamilies which would allow us to develop a 'domain grammar of function' whereby a protein's biological role can be proposed from its constituent domains? Clearly the first step is to understand the extent to which these components vary and how changes in their molecular make-up modifies function.
ESTHER : Das_2015_Curr.Opin.Genet.Dev_35_40
PubMedSearch : Das_2015_Curr.Opin.Genet.Dev_35_40
PubMedID: 26451979

Title : Treatment of dementia with herbs: A short review - Tang_2013_Clin.Ter_164_43
Author(s) : Tang CT , Belani LK , Das S , Jaafar MZ
Ref : Clin Ter , 164 :43 , 2013
Abstract : Dementia is a common symptom observed in many psychiatric and neurodegenerative diseases. Alzheimer's disease is the most common form of senile dementia seen in the general population. Multiple factors like oxidative stress, apoptosis, mitochondrial dysfunction and inflammation may be related to the neurodegenerative states. Many drugs like cholinesterase have been used for treatment but the progression of the disease still poses a challenge to the clinician. During recent times, herbs have gained much popularity as supplements because of the cost effectiveness, easy availability and fewer side effects. Early diagnosis and proper treatment may help in the prevention of mortality and morbidity concerned with any neurodegenerative disease. Understanding the cellular and molecular biology of the mode of the action of herbal products may be beneficial for researchers and clinicians. The present review article attempts to look into the potential herbal extracts which may act as an antioxidant in combating dementia. Clin Ter 2013; 164(1):43-46. doi: 10.7417/CT.2013.1511.
ESTHER : Tang_2013_Clin.Ter_164_43
PubMedSearch : Tang_2013_Clin.Ter_164_43
PubMedID: 23455743

Title : Repeated polyploidization of Gossypium genomes and the evolution of spinnable cotton fibres - Paterson_2012_Nature_492_423
Author(s) : Paterson AH , Wendel JF , Gundlach H , Guo H , Jenkins J , Jin D , Llewellyn D , Showmaker KC , Shu S , Udall J , Yoo MJ , Byers R , Chen W , Doron-Faigenboim A , Duke MV , Gong L , Grimwood J , Grover C , Grupp K , Hu G , Lee TH , Li J , Lin L , Liu T , Marler BS , Page JT , Roberts AW , Romanel E , Sanders WS , Szadkowski E , Tan X , Tang H , Xu C , Wang J , Wang Z , Zhang D , Zhang L , Ashrafi H , Bedon F , Bowers JE , Brubaker CL , Chee PW , Das S , Gingle AR , Haigler CH , Harker D , Hoffmann LV , Hovav R , Jones DC , Lemke C , Mansoor S , ur Rahman M , Rainville LN , Rambani A , Reddy UK , Rong JK , Saranga Y , Scheffler BE , Scheffler JA , Stelly DM , Triplett BA , Van Deynze A , Vaslin MF , Waghmare VN , Walford SA , Wright RJ , Zaki EA , Zhang T , Dennis ES , Mayer KF , Peterson DG , Rokhsar DS , Wang X , Schmutz J
Ref : Nature , 492 :423 , 2012
Abstract : Polyploidy often confers emergent properties, such as the higher fibre productivity and quality of tetraploid cottons than diploid cottons bred for the same environments. Here we show that an abrupt five- to sixfold ploidy increase approximately 60 million years (Myr) ago, and allopolyploidy reuniting divergent Gossypium genomes approximately 1-2 Myr ago, conferred about 30-36-fold duplication of ancestral angiosperm (flowering plant) genes in elite cottons (Gossypium hirsutum and Gossypium barbadense), genetic complexity equalled only by Brassica among sequenced angiosperms. Nascent fibre evolution, before allopolyploidy, is elucidated by comparison of spinnable-fibred Gossypium herbaceum A and non-spinnable Gossypium longicalyx F genomes to one another and the outgroup D genome of non-spinnable Gossypium raimondii. The sequence of a G. hirsutum A(t)D(t) (in which 't' indicates tetraploid) cultivar reveals many non-reciprocal DNA exchanges between subgenomes that may have contributed to phenotypic innovation and/or other emergent properties such as ecological adaptation by polyploids. Most DNA-level novelty in G. hirsutum recombines alleles from the D-genome progenitor native to its New World habitat and the Old World A-genome progenitor in which spinnable fibre evolved. Coordinated expression changes in proximal groups of functionally distinct genes, including a nuclear mitochondrial DNA block, may account for clusters of cotton-fibre quantitative trait loci affecting diverse traits. Opportunities abound for dissecting emergent properties of other polyploids, particularly angiosperms, by comparison to diploid progenitors and outgroups.
ESTHER : Paterson_2012_Nature_492_423
PubMedSearch : Paterson_2012_Nature_492_423
PubMedID: 23257886
Gene_locus related to this paper: gosra-a0a0d2qg22 , gosra-a0a0d2w3z1 , gosra-a0a0d2uuz7 , gosra-a0a0d2rxs2 , gosra-a0a0d2sdk0 , gosra-a0a0d2tng2 , gosra-a0a0d2twz7 , gosra-a0a0d2vdc5 , gosra-a0a0d2vj24 , gosra-a0a0d2sr31 , goshi-a0a1u8knd1 , goshi-a0a1u8nhw9 , goshi-a0a1u8kis4 , gosra-a0a0d2pul0 , gosra-a0a0d2p3f2 , gosra-a0a0d2ril5 , gosra-a0a0d2s7d5 , gosra-a0a0d2t9b3 , gosra-a0a0d2tw88 , gosra-a0a0d2umz5 , gosra-a0a0d2pzd7 , gosra-a0a0d2scu7 , gosra-a0a0d2vcx6

Title : Neuregulin effect on quantal content dissociated from effect on miniature endplate potential amplitude - Mann_2006_J.Neurophysiol_96_671
Author(s) : Mann MA , Das S , Zhang J , Wagner M , Fischbach GD
Ref : Journal of Neurophysiology , 96 :671 , 2006
Abstract : Members of the neuregulin family of signaling proteins increase transcription of acetylcholine receptor (AChR) subunit genes in muscle fibers and the number of AChRs in the muscle membrane. In adult mice heterozygous for targeted deletion of type I neuregulins (Ig-NRG(+/-)), postsynaptic AChR density was decreased and transmitter release was increased. We examined the relationship between functional AChR density and ACh release in postnatal day 7 (P7), P14, and adult NRG-deficient mice. Here we report that changes in postsynaptic sensitivity and transmitter release are not temporally coupled during postnatal development in Ig-NRG-deficient mice. Although miniature endplate potential (MEPP) amplitude was decreased compared with control in P7 Ig-NRG(+/-) mice, quantum content was not increased. Quantum content was increased in adult heterozygotes despite normal MEPP amplitudes. Thus, during postnatal maturation, both quantal size and quantum content were influenced by decreased Ig-NRG expression, although the effects were dissociated in time.
ESTHER : Mann_2006_J.Neurophysiol_96_671
PubMedSearch : Mann_2006_J.Neurophysiol_96_671
PubMedID: 16835362

Title : Pharmacogenetic analysis of interindividual irinotecan (CPT-11) pharmacokinetic (PK) variability: Evidence for a functional variant of ABCC2 - Innocenti_2004_J.Clin.Oncol_22_2010
Author(s) : Innocenti F , Undevia SD , Chen PX , Das S , Ramirez J , Dolan ME , Relling MV , Kroetz DL , Ratain MJ
Ref : J Clin Oncol , 22 :2010 , 2004
Abstract : 2010 Background: CPT-11 is oxidized to inactivated metabolites (including APC) by CYP3A enzymes and activated to SN-38 by carboxylesterase-2 (CES-2). SN-38 is inactivated to it glucuronide (SN-38G) by UGT1A1 and UGT1A9. Other enzymes and ABC transporters are involved in pathways of CPT-11 disposition. We had previously measured the plasma PK of patients treated with CPT-11 and analyzed the correlation with UGT1A1 variants. This study aims to generate hypotheses regarding the phenotypic effects of variation in other drug metabolizing and transporter genes.
METHODS: CPT-11, SN-38, and SN-38G AUCs were measured after a 350 mg/m2 IV dose in 64 adults with refractory solid tumors as part of a pharmacogenetic study. Genotyping of common variants (q>0.10) was performed for the following genes (number of variants in parenthesis): CES-2 (n=2), ABCC1 (n=7), ABCC2 (n=6), and ABCB1 (n=8). CYP3A4*1B, CYP3A5*3, UGT1A9 -11810T/9T and HNF1 79A>C were also typed.
RESULTS: The synonymous 3972T>C variant in ABCC2 was correlated with CPT-11 AUC (p=0.02), APC AUC (p<0.0001) and APC/CPT-11 AUC ratios (p<0.0001, ANOVA). For SN-38 and SN-38G AUC, the correlation with 3972T>C was analyzed in the subset of patients with 6/6 and 6/7 UGT1A1 genotype (n=54) to minimize the confounding effect of 7/7. SN-38G and SN-38G/SN-38 AUC ratios were correlated with 3972T>C (p<=0.001, ANOVA). No significant correlation was observed between SN-38 AUC and 3972T>C (p=0.9). Other gene variants showed either no or borderline statistical significance in the ANOVA test. The TT 3972 genotype was associated with higher AUC of CPT-11 (p=0.02), APC and SN-38G (both p<0.0001, t test) compared to CT+CC patients. The frequencies of CC, CT, and TT genotypes were 0.44, 0.44, and 0.13, respectively.
CONCLUSIONS: This study identifies 3972T>C as a variant potentially affecting ABCC2 activity and suggests that ABCC2 may have a significant impact on CPT-11 clearance. These results also suggest that APC may be a substrate for ABCC2. The phenotypic effect of 3972T>C was previously unknown and further studies will test its biological function and clinical relevance. No significant financial relationships to disclose.
ESTHER : Innocenti_2004_J.Clin.Oncol_22_2010
PubMedSearch : Innocenti_2004_J.Clin.Oncol_22_2010
PubMedID: 28015612

Title : In vitro studies of the effects of HAART drugs and excipients on activity of digestive enzymes - Wignot_2004_Pharm.Res_21_420
Author(s) : Wignot TM , Stewart RP , Schray KJ , Das S , Sipos T
Ref : Pharm Res , 21 :420 , 2004
Abstract : PURPOSE: Side effects of diarrhea and steatorrhea diminish the therapeutic value of highly active antiretroviral therapy (HAART). We report in vitro studies of the effect of HAART drugs on the activity of pancrelipase, trypsin, and enterokinase and restoration of activity by subsequent addition of excess pancrelipase or colipase.
METHODS: Commercial formulations of sixteen HAART drug formulations with solvent and four excipients were mixed with substrate. Activity of pancrelipase was recorded after addition of the enzyme; restoration of activity was monitored after addition of excess pancrelipase or colipase to the reaction mixture.
RESULTS: Five protease inhibitors (Agenerase solution, Agenerase capsules, Norvir, Viracept, Kaletra, and Fortovase) and the excipient TPGS (d-alpha-tocopheryl polyethylene glycol 1000 succinate) inhibited lipase significantly at or below physiological concentrations. Neither nucleoside reverse transcriptase inhibitors nor non-nucleoside reverse transcriptase inhibitors showed significant lipase inhibition at physiological levels. Addition of excess pancrelipase to the medium completely reversed inhibition by Agenerase, Fortovase, Norvir, and TPGS and reactivated lipase; it diminished inhibition by Kaletra and Viracept but did not completely restore activity. Addition of colipase reversed inhibition by Agenerase solution, Agenerase capsules, and TPGS; inhibition by Kaletra and Fortovase recovered slightly. No compounds tested inhibited trypsin or enterokinase.
CONCLUSIONS: These results justify evaluating protocols involving coadministration of buffered pancrelipase with protease inhibitors to reduce or eliminate diarrhea and steatorrhea in individuals being treated for HIV.
ESTHER : Wignot_2004_Pharm.Res_21_420
PubMedSearch : Wignot_2004_Pharm.Res_21_420
PubMedID: 15070091

Title : Determination and analysis of single nucleotide polymorphisms and haplotype structure of the human carboxylesterase 2 gene - Wu_2004_Pharmacogenet_14_595
Author(s) : Wu MH , Chen P , Wu X , Liu W , Strom S , Das S , Cook EH, Jr. , Rosner GL , Dolan ME
Ref : Pharmacogenetics , 14 :595 , 2004
Abstract : Carboxylesterases are members of the serine esterase super family important in the metabolism of a wide variety of substrates, including xenobiotics and prodrugs. There are two known carboxylesterases expressed in human liver, small intestine and other tissues, carboxylesterase 1 (CES1) and carboxylesterase 2 (CES2). The aim of this study was to identify polymorphisms in the CES2 gene and determine whether these polymorphisms affect expression levels of CES2 or rate of metabolism of irinotecan (7-ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyloxy-camptothecin). Microsome samples prepared from liver tissues of 78 normal individuals were used to determine the rate of hydrolysis of irinotecan and procaine (an anaesthetic hydrolysed by CES2 but not CES1). The rate of hydrolysis of irinotecan is highly variable among individuals, ranging from 2.7-138 pmol/mg protein/h (mean +/- SD 26.0 +/- 22.9). Fifteen single nucleotide polymorphisms (SNPs) were identified, one is in an exon, 9 are in introns, three are in the 3'-untranslated region (UTR), and two are in the 5'-flanking region. Eight of the 15 SNP loci have rare allele frequencies greater than 5%, of which three were greater than 20%. Genotyping of samples from the SNP Consortium demonstrated different distributions among African-Americans, Asian-Americans and European-Americans. We also analysed the haplotype structure and estimated linkage disequilibrium (LD). A SNP located in the 5'-UTR (5'-UTR-363) was found in LD with loci in intron 1 (Intron1 + 947, Intron1 + 1361, Intron1 + 1643). Haplotypes with homozygous rare alleles on these loci exhibit lower mRNA levels as determined by real time polymerase chain reaction (P < 0.01) and the incorporation of rare alleles in haplotypes correlate with reduced mRNA (P = 0.03). The 5'-UTR-363 SNP is located in one of the three promoters of CES2. However, we did not observe significant differences in CES2 activities (irinotecan and procaine hydrolysis) among individuals with different haplotypes.
ESTHER : Wu_2004_Pharmacogenet_14_595
PubMedSearch : Wu_2004_Pharmacogenet_14_595
PubMedID: 15475733
Gene_locus related to this paper: human-CES2

Title : Characterization of multiple promoters in the human carboxylesterase 2 gene - Wu_2003_Pharmacogenet_13_425
Author(s) : Wu MH , Chen P , Remo BF , Cook EH, Jr. , Das S , Dolan ME
Ref : Pharmacogenetics , 13 :425 , 2003
Abstract : Carboxylesterases are a broad class of enzymes important in the detoxification of many ester- or amide-bond containing xenobiotics. They also activate analgesics, anticancer prodrugs, and other biologically active compounds, such as cocaine and heroin. The objective of this work was to identify the CES2 gene structure, complex 5' untranslated regions and three potential promoters for the initiation of transcription in different human tissues. Using bioinformatics and progressive reverse transcriptase-polymerase chain reaction, we found that the 5' untranslated region is more than 1100 bases longer than previously reported. Rapid amplification of cDNA ends showed three distinctive transcription start sites at -74, -629 and -1187. DNA fragments upstream of each of the three transcription start sites were found to be transcriptionally active in HepG2 cells. The distal promoter is active in both orientations, suggesting its potential role in the transcription of another gene, CGI-128, located immediately upstream to the distal promoter in the opposite direction with respect to CES2. Hybridization analyses showed that CES2 is highly expressed in the heart, skeletal muscle, colon, spleen, kidney and liver, but considerably less expressed in fetal tissues (e.g. fetal heart, kidney, spleen, and liver) and cancer cells. It is also evident that the distal promoter is responsible for low level expression of the gene in many tissues, whereas the other two promoters are tissue specific. These findings shed some light on CES2 gene regulation, a gene important in the metabolism of many drugs.
ESTHER : Wu_2003_Pharmacogenet_13_425
PubMedSearch : Wu_2003_Pharmacogenet_13_425
PubMedID: 12835618
Gene_locus related to this paper: human-CES2

Title : The involvement of amyloid associated proteins in the formation of beta-protein filaments in Alzheimer's disease. - Potter_1994_Prog.Clin.Biol.Res_390_57
Author(s) : Potter H , Ma J , Das S , Kayyali U
Ref : Progress in Clinical & Biological Research , 390 :57 , 1994
Abstract :
ESTHER : Potter_1994_Prog.Clin.Biol.Res_390_57
PubMedSearch : Potter_1994_Prog.Clin.Biol.Res_390_57
PubMedID: 7724651