Chakraborty S

References (13)

Title : Alkaloids as drug leads in Alzheimer's treatment: Mechanistic and therapeutic insights - Rezaul_2024_Brain.Res__148886
Author(s) : Rezaul Islam M , Akash S , Murshedul Islam M , Sarkar N , Kumer A , Chakraborty S , Dhama K , Ahmed Al-Shaeri M , Anwar Y , Wilairatana P , Rauf A , Halawani IF , Alzahrani FM , Khan H
Ref : Brain Research , :148886 , 2024
Abstract : Alzheimer's disease (AD) has few effective treatment options and continues to be a major global health concern. AD is a neurodegenerative disease that typically affects elderly people. Alkaloids have potential sources for novel drug discovery due to their diverse chemical structures and pharmacological activities. Alkaloids, natural products with heterocyclic nitrogen-containing structures, are considered potential treatments for AD. This review explores the neuroprotective properties of alkaloids in AD, focusing on their ability to regulate pathways such as amyloid-beta aggregation, oxidative stress, synaptic dysfunction, tau hyperphosphorylation, and neuroinflammation. The FDA has approved alkaloids such as acetylcholinesterase inhibitors like galantamine and rivastigmine. This article explores AD's origins, current market medications, and clinical applications of plant alkaloids in AD therapy. This review explores the development of alkaloid-based drugs for AD, focusing on pharmacokinetics, blood-brain barrier penetration, and potential adverse effects. Future research should focus on the clinical evaluation of promising alkaloids, developing recently discovered alkaloids, and the ongoing search for novel alkaloids for medical treatment. A pharmaceutical option containing an alkaloid may potentially slow down the progression of AD while enhancing its symptoms. This review highlights the potential of alkaloids as valuable drug leads in treating AD, providing a comprehensive understanding of their mechanisms of action and therapeutic implications.
ESTHER : Rezaul_2024_Brain.Res__148886
PubMedSearch : Rezaul_2024_Brain.Res__148886
PubMedID: 38582413

Title : Focal acetylcholinergic modulation of the human midcingulo-insular network during attention: Meta-analytic neuroimaging and behavioral evidence - Chakraborty_2023_J.Neurochem_17thISCM__
Author(s) : Chakraborty S , Lee SK , Arnold SM , Haast RAM , Khan AR , Schmitz TW
Ref : Journal of Neurochemistry , : , 2023
Abstract : The basal forebrain cholinergic neurons provide acetylcholine to the cortex via large projections. Recent molecular imaging work in humans indicates that the cortical cholinergic innervation is not uniformly distributed, but rather may disproportionately innervate cortical areas relevant to supervisory attention. In this study, we therefore reexamined the spatial relationship between acetylcholinergic modulation and attention in the human cortex using meta-analytic strategies targeting both pharmacological and non-pharmacological neuroimaging studies. We found that pharmaco-modulation of acetylcholine evoked both increased activity in the anterior cingulate and decreased activity in the opercular and insular cortex. In large independent meta-analyses of non-pharmacological neuroimaging research, we demonstrate that during attentional engagement these cortical areas exhibit (1) task-related co-activation with the basal forebrain, (2) task-related co-activation with one another, and (3) spatial overlap with dense cholinergic innervations originating from the basal forebrain, as estimated by multimodal positron emission tomography and magnetic resonance imaging. Finally, we provide meta-analytic evidence that pharmaco-modulation of acetylcholine also induces a speeding of responses to targets with no apparent tradeoff in accuracy. In sum, we demonstrate in humans that acetylcholinergic modulation of midcingulo-insular hubs of the ventral attention/salience network via basal forebrain afferents may coordinate selection of task relevant information, thereby facilitating cognition and behavior.
ESTHER : Chakraborty_2023_J.Neurochem_17thISCM__
PubMedSearch : Chakraborty_2023_J.Neurochem_17thISCM__
PubMedID: 37864501

Title : Psychotropic Medication Prescribing to Patients with Dementia Admitted to Acute Hospitals in Ireland - Timmons_2023_Drugs.Aging__1
Author(s) : Timmons S , Bracken-Scally M , Chakraborty S , Gallagher P , Hamilton V , Begley E , x , Shea E
Ref : Drugs & Aging , :1 , 2023
Abstract : BACKGROUND: Psychotropic medications are commonly prescribed to people with dementia (PwD) for non-cognitive symptoms of dementia (NCSD), but have significant risks. A national audit was performed in acute hospitals in the Republic of Ireland (ROI) to establish baseline practice prior to the launch and implementation of a National Clinical Guideline on the appropriate prescribing of psychotropic medications for NCSD. The objective of this study was to analyse psychotropic prescribing patterns and compare these with international data and with existing (limited) data from a previous audit round. METHODS: The pooled anonymous dataset from the second round of the Irish National Audit of Dementia Care (INAD-2) was analysed. The audit had collected retrospective data from 30 random healthcare records from each of 30 acute hospitals in 2019. Inclusion criteria were a clinical diagnosis of dementia of any type, hospital stay of 72 hours or more, and discharge or death within the audit period. Most hospitals (87%) self-audited their healthcare records, but a random sample of six healthcare records (20%) from each hospital were re-audited by a highly trained healthcare auditor. The audit tool was based on a tool used in the England and Wales National Audit of Dementia audit rounds (Royal College of Psychiatrists), adapted to the Irish healthcare setting and national priorities. RESULTS: In total, 893 cases were included, as one hospital could not retrieve 30 cases even within a more prolonged audit period. The sample comprised 55% females and 45% males; the median age was 84 years (interquartile range 79-88 years) and the majority (89.6%) were >75 years of age. Only 52% of healthcare records specified the type of dementia; within these, the most common diagnosis was Alzheimer's disease (45%). Most PwD (83%) were receiving psychotropic medication on admission; 40% were prescribed new or increased psychotropic medication during admission, mainly for medical indications, including end-of-life care and delirium. Anticonvulsants or cognitive enhancers were rarely prescribed for NCSD in hospital. However, new/increased antipsychotic medication was prescribed for NCSD in 11.8-17.6% of the total cohort, while 4.5-7.7% were prescribed a benzodiazepine for anxiety or NCSD. Overall, there was poor documentation of risk/benefit, or of discussion with the patient/family, and apparently inadequate review for efficacy and tolerability. Concurrently, acetylcholinesterase inhibitors appeared to be underused for cognitive impairment in the community. CONCLUSION: This audit provides baseline data on psychotropic medication prescription for NCSD in Irish hospitals prior to a specific Irish guideline on this topic. Reflecting this, most PwD were receiving psychotropic medications on admission, and many were prescribed new/increased psychotropic medication in hospital, often without evidence of appropriate decision making and prescribing processes.
ESTHER : Timmons_2023_Drugs.Aging__1
PubMedSearch : Timmons_2023_Drugs.Aging__1
PubMedID: 36995582

Title : Dual assessment of transcriptional and metabolomic responses in the American dog tick following exposure to different pesticides and repellents - Pathak_2022_Ticks.Tick.Borne.Dis_13_102033
Author(s) : Pathak A , Chakraborty S , Oyen K , Rosendale AJ , Benoit JB
Ref : Ticks Tick Borne Dis , 13 :102033 , 2022
Abstract : The American dog tick, Dermacentor variabilis, is a major pest to humans and animals, serving as a vector to Rickettsia rickettsii, a bacterium responsible for Rocky Mountain spotted fever, and Francisella tularensis, which is responsible for tularemia. Although several tactics for management have been deployed, very little is known about the molecular response following pesticidal treatments in ticks. In this study, we used a combined approach utilizing transcriptomics and metabolomics to understand the response of the American dog tick to five common pesticides (amitraz, chlorpyrifos, fipronil, permethrin, and propoxur), and analyzed previous experimental data utilizing DEET repellent. Exposure to different chemicals led to significant differential expression of a varying number of transcripts, where 42 were downregulated and only one was upregulated across all treatments. A metabolomic analysis identified significant changes in acetate and aspartate levels following exposure to chlorpyrifos and propoxur, which was attributed to reduced cholinesterase activity. Integrating the metabolomics study with RNA-seq analysis, we found the physiological manifestations of the combined metabolic and transcriptional differences, revealing several novel biomolecular pathways. In particular, we discovered the downregulation of amino sugar metabolism and methylhistidine metabolism after permethrin exposure, as well as an upregulation of glutamate metabolism in amitraz treated samples. Understanding these altered biochemical pathways following pesticide and repellent exposure can help us formulate more effective chemical treatments to reduce the burden of ticks.
ESTHER : Pathak_2022_Ticks.Tick.Borne.Dis_13_102033
PubMedSearch : Pathak_2022_Ticks.Tick.Borne.Dis_13_102033
PubMedID: 36099731

Title : Combined Structure and Ligand-Based Design of Selective Acetylcholinesterase Inhibitors - Perez-Sanchez_2021_J.Chem.Inf.Model_61_467
Author(s) : Perez-Sanchez H , den Haan H , Perez-Garrido A , Pena-Garcia J , Chakraborty S , Erdogan Orhan I , Senol Deniz FS , Villalgordo JM
Ref : J Chem Inf Model , 61 :467 , 2021
Abstract : Acetylcholinesterase is a prime target for therapeutic intervention in Alzheimer's disease. Acetylcholinesterase inhibitors (AChEIs) are used to improve cognitive abilities, playing therefore an important role in disease management. Drug repurposing screening has been performed on a corporate chemical library containing 11 353 compounds using a target fishing approach comprising three-dimensional (3D) shape similarity and pharmacophore modeling against an approved drug database, Drugbank. This initial screening identified 108 hits. Among them, eight molecules showed structural similarity to the known AChEI drug, pyridostigmine. Further structure-based screening using a pharmacophore-guided rescoring method identifies one more potential hit. Experimental evaluations of the identified hits sieve out a highly selective AChEI scaffold. Further lead optimization using a substructure search approach identifies 24 new potential hits. Three of the 24 compounds (compounds 10b, 10h, and 10i) based on a 6-(2-(pyrrolidin-1-yl)pyrimidin-4-yl)-thiazolo[3,2-a]pyrimidine scaffold showed highly promising AChE inhibition ability with IC(50) values of 13.10 +/- 0.53, 16.02 +/- 0.46, and 6.22 +/- 0.54 microM, respectively. Moreover, these compounds are highly selective toward AChE. Compound 10i shows AChE inhibitory activity similar to a known Food and Drug Administration (FDA)-approved drug, galantamine, but with even better selectivity. Interaction analysis reveals that hydrophobic and hydrogen-bonding interactions are the primary driving forces responsible for the observed high affinity of the compound with AChE.
ESTHER : Perez-Sanchez_2021_J.Chem.Inf.Model_61_467
PubMedSearch : Perez-Sanchez_2021_J.Chem.Inf.Model_61_467
PubMedID: 33320652

Title : Human prostasomes an extracellular vesicle - Biomarkers for male infertility and prostrate cancer: The journey from identification to current knowledge - Vickram_2020_Int.J.Biol.Macromol_146_946
Author(s) : Vickram AS , Samad HA , Latheef SK , Chakraborty S , Dhama K , Sridharan TB , Sundaram T , Gulothungan G
Ref : Int J Biol Macromol , 146 :946 , 2020
Abstract : Extracellular vesicles (EVs) are gaining attention among the cell biologists and researchers over the last two decades. Prostasomes are considered to be (Evs) secreted by prostate epithelial cells into the semen during emission or ejaculation. Prostasomes contain various proteins required for immune regulation namely, amino and dipeptidyl peptidase; endopeptidase (neutral); decay accelerating factor; angiotensin-converting enzyme. Sperm cells need a few prerequisites in order to fertilize the egg. The role of prostasomes in enhancing the male fertility was reviewed extensively throughout the manuscript. Also, prostasomes have an immunosuppressive, immunomodulatory, antibacterial role in the female reproductive tract, and in some cases they can be used as immunocontraceptive agent to regulate the fertility status. This review will give insights to many active researchers in the field of prostasomal research and male infertility/fertility research. This review will open many unanswered mechanisms of prostasomes with respect to structure-function analysis, fatty acids patterns in diagnosis as well as prognosis of male infertility/fertility. More scientific reports are in need to support the mechanism of prostasomes and its role in immunomodulation. The development of prostasomes as a biomarker for the prostate cancer is still miserable with a lot of controversial results by various researchers.
ESTHER : Vickram_2020_Int.J.Biol.Macromol_146_946
PubMedSearch : Vickram_2020_Int.J.Biol.Macromol_146_946
PubMedID: 31730983

Title : The walnut (Juglans regia) genome sequence reveals diversity in genes coding for the biosynthesis of non-structural polyphenols - Martinez-Garcia_2016_Plant.J_87_507
Author(s) : Martinez-Garcia PJ , Crepeau MW , Puiu D , Gonzalez-Ibeas D , Whalen J , Stevens KA , Paul R , Butterfield TS , Britton MT , Reagan RL , Chakraborty S , Walawage SL , Vasquez-Gross HA , Cardeno C , Famula RA , Pratt K , Kuruganti S , Aradhya MK , Leslie CA , Dandekar AM , Salzberg SL , Wegrzyn JL , Langley CH , Neale DB
Ref : Plant J , 87 :507 , 2016
Abstract : The Persian walnut (Juglans regia L.), a diploid species native to the mountainous regions of Central Asia, is the major walnut species cultivated for nut production and is one of the most widespread tree nut species in the world. The high nutritional value of J. regia nuts is associated with a rich array of polyphenolic compounds, whose complete biosynthetic pathways are still unknown. A J. regia genome sequence was obtained from the cultivar 'Chandler' to discover target genes and additional unknown genes. The 667-Mbp genome was assembled using two different methods (SOAPdenovo2 and MaSuRCA), with an N50 scaffold size of 464 955 bp (based on a genome size of 606 Mbp), 221 640 contigs and a GC content of 37%. Annotation with MAKER-P and other genomic resources yielded 32 498 gene models. Previous studies in walnut relying on tissue-specific methods have only identified a single polyphenol oxidase (PPO) gene (JrPPO1). Enabled by the J. regia genome sequence, a second homolog of PPO (JrPPO2) was discovered. In addition, about 130 genes in the large gallate 1-beta-glucosyltransferase (GGT) superfamily were detected. Specifically, two genes, JrGGT1 and JrGGT2, were significantly homologous to the GGT from Quercus robur (QrGGT), which is involved in the synthesis of 1-O-galloyl-beta-d-glucose, a precursor for the synthesis of hydrolysable tannins. The reference genome for J. regia provides meaningful insight into the complex pathways required for the synthesis of polyphenols. The walnut genome sequence provides important tools and methods to accelerate breeding and to facilitate the genetic dissection of complex traits.
ESTHER : Martinez-Garcia_2016_Plant.J_87_507
PubMedSearch : Martinez-Garcia_2016_Plant.J_87_507
PubMedID: 27145194
Gene_locus related to this paper: jugre-a0a2i4fez2 , jugre-a0a2i4h0n2 , jugre-a0a2i4gzr6 , jugre-a0a2i4hni2 , jugre-a0a2i4gla1 , jugre-a0a2i4e0e6 , jugre-a0a2i4es54 , jugre-a0a2i4e9m5 , jugre-a0a2i4hql8 , jugre-a0a2i4gf09 , jugre-a0a2i4fj48 , jugre-a0a2i4flz2

Title : The Type II Secreted Lipase\/Esterase LesA is a Key Virulence Factor Required for Xylella fastidiosa Pathogenesis in Grapevines - Nascimento_2016_Sci.Rep_6_18598
Author(s) : Nascimento R , Gouran H , Chakraborty S , Gillespie HW , Almeida-Souza HO , Tu A , Rao BJ , Feldstein PA , Bruening G , Goulart LR , Dandekar AM
Ref : Sci Rep , 6 :18598 , 2016
Abstract : Pierce's disease (PD) of grapevines is caused by Xylella fastidiosa (Xf), a xylem-limited gamma-proteobacterium that is responsible for several economically important crop diseases. The occlusion of xylem elements and interference with water transport by Xf and its associated biofilm have been posited as the main cause of PD symptom development; however, Xf virulence mechanisms have not been described. Analysis of the Xf secretome revealed a putative lipase/esterase (LesA) that was abundantly secreted in bacterial culture supernatant and was characterized as a protein ortholog of the cell wall-degrading enzyme LipA of Xanthomonas strains. LesA was secreted by Xf and associated with a biofilm filamentous network. Additional proteomic analysis revealed its abundant presence in outer membrane vesicles (OMVs). Accumulation of LesA in leaf regions associated positively with PD symptoms and inversely with bacterial titer. The lipase/esterase also elicited a hypersensitive response in grapevine. Xf lesA mutants were significantly deficient for virulence when mechanically inoculated into grapevines. We propose that Xf pathogenesis is caused by LesA secretion mediated by OMV cargos and that its release and accumulation in leaf margins leads to early stages of observed PD symptoms.
ESTHER : Nascimento_2016_Sci.Rep_6_18598
PubMedSearch : Nascimento_2016_Sci.Rep_6_18598
PubMedID: 26753904
Gene_locus related to this paper: xylfa-XF0357

Title : In silico QSAR analysis of quercetin reveals its potential as therapeutic drug for Alzheimer's disease - Islam_2013_J.Young.Pharm_5_173
Author(s) : Islam MR , Zaman A , Jahan I , Chakravorty R , Chakraborty S
Ref : J Young Pharm , 5 :173 , 2013
Abstract : Acetylcholine-esterase (AchE) inhibitors are one of the most potent drug molecules against Alzheimer's disease (AD). But, patients treated with current AchE inhibitors often experience severe side effects. Quercetin is a plant flavonoid compound which can act as AchE inhibitor and it may be a better alternative to current AchE inhibitors in terms of effectiveness with no or fewer side effects. AIMS: The aim of the study was to compare quercetin with conventional AchE inhibitors to search for a better drug candidate. METHODS AND MATERIALS: Physico-chemical properties of conventional drugs and quercetin were predicted using bioinformatics tools. Molecular docking of these compounds on the active site of AchE was performed using AutoDock and comparative analysis was performed. Later, modification on the basic structure of quercetin with different functional groups was done to perform QSAR analysis. RESULT AND DISCUSSION: Quercetin showed a similar drug likeness score to the conventional drugs. The binding strength for quercetin in the active site of the enzyme was -8.8 kcal/mol, which was considerably higher than binding scores for some of the drugs such as donepezil (binding score -7.9 kcal/mol). Fifteen hydrogen bonds were predicted between quercetin and the enzyme whereas conventional drugs had fewer or even no hydrogen bonds. It implies that quercetin can act as a better inhibitor than conventional drugs. To find out even better inhibitor, similar structures of quercetin were searched through SIMCOMP database and a methylation in the 4-OH position of the molecule showed better binding affinity than parent quercetin. Quantitative structure activity relationship study indicated that O-4 methylation was specifically responsible for better affinity. CONCLUSION: This in silico study has conclusively predicted the superiority of the natural compound quercetin over the conventional drugs as AchE inhibitor and it sets the need for further in-vitro study of this compound in future.
ESTHER : Islam_2013_J.Young.Pharm_5_173
PubMedSearch : Islam_2013_J.Young.Pharm_5_173
PubMedID: 24563598

Title : Cell to organ: physiological, immunotoxic and oxidative stress responses of Lamellidens marginalis to inorganic arsenite - Chakraborty_2013_Ecotoxicol.Environ.Saf_94_153
Author(s) : Chakraborty S , Ray M , Ray S
Ref : Ecotoxicology & Environmental Safety , 94 :153 , 2013
Abstract : The emerging pollutants in diverse habitats have created a need for basic research towards profiling the structural and functional parameters ranging from cell to organs in a diversity of species, thus enabling realistic analyses of the risks imposed by the environmental stressors. In the present study, the circulating haemocytes and digestive gland of an edible bivalve mollusc from eastern India, Lamellidens marginalis, were investigated for morphological and functional attributes under the challenge of inorganic arsenite-an up-coming threat to the natural freshwater reserves of the Indo-Gangetic flood plains. The molluscs were exposed to three sublethal concentrations of sodium arsenite under controlled laboratory conditions for a maximum time span of thirty days. The toxic exposure caused significant alteration in the haemocytometric profile. It inhibited the activities of phosphatases, transaminases and acetylcholinesterase which are iconic for assessment of the physiological homoeostasis in the haemocytes and digestive tissue. At both cellular and tissue level, immune surveillance was compromised through inhibited generation of nitric oxide, phenoloxidase and superoxide anions. Moreover, exposure to sodium arsenite promoted xenometabolic and oxidative stress in both haemocytes and digestive gland by reducing the activity of glutathione S-transferase and catalase. It inflicted inflammatory damage and promoted neplasia in the digestive tissue as evident from the histopathological observations. The findings would be crucial to gauge the impending threats from inorganic arsenite exposure to the freshwater invertebrates. Further, it creates an avenue to speculate a new model for arsenic biomonitoring.
ESTHER : Chakraborty_2013_Ecotoxicol.Environ.Saf_94_153
PubMedSearch : Chakraborty_2013_Ecotoxicol.Environ.Saf_94_153
PubMedID: 23711797

Title : Comparative pathogenomics reveals horizontally acquired novel virulence genes in fungi infecting cereal hosts - Gardiner_2012_PLoS.Pathog_8_e1002952
Author(s) : Gardiner DM , McDonald MC , Covarelli L , Solomon PS , Rusu AG , Marshall M , Kazan K , Chakraborty S , McDonald BA , Manners JM
Ref : PLoS Pathog , 8 :e1002952 , 2012
Abstract : Comparative analyses of pathogen genomes provide new insights into how pathogens have evolved common and divergent virulence strategies to invade related plant species. Fusarium crown and root rots are important diseases of wheat and barley world-wide. In Australia, these diseases are primarily caused by the fungal pathogen Fusarium pseudograminearum. Comparative genomic analyses showed that the F. pseudograminearum genome encodes proteins that are present in other fungal pathogens of cereals but absent in non-cereal pathogens. In some cases, these cereal pathogen specific genes were also found in bacteria associated with plants. Phylogenetic analysis of selected F. pseudograminearum genes supported the hypothesis of horizontal gene transfer into diverse cereal pathogens. Two horizontally acquired genes with no previously known role in fungal pathogenesis were studied functionally via gene knockout methods and shown to significantly affect virulence of F. pseudograminearum on the cereal hosts wheat and barley. Our results indicate using comparative genomics to identify genes specific to pathogens of related hosts reveals novel virulence genes and illustrates the importance of horizontal gene transfer in the evolution of plant infecting fungal pathogens.
ESTHER : Gardiner_2012_PLoS.Pathog_8_e1002952
PubMedSearch : Gardiner_2012_PLoS.Pathog_8_e1002952
PubMedID: 23028337
Gene_locus related to this paper: gibze-a8w610 , gibze-i1rda9 , gibze-i1rdk7 , gibze-i1rec8 , gibze-i1rgs0 , gibze-i1rgy0 , gibze-i1rh52 , gibze-i1rig9 , gibze-i1rip5 , gibze-i1rpg6 , gibze-i1rsg2 , gibze-i1rv36 , gibze-i1rxm5 , gibze-i1rxp8 , gibze-i1rxv5 , gibze-i1s3j9 , gibze-i1s8i8 , gibze-i1s9x4 , gibze-q4huy1 , fuspc-k3u8z2 , fuspc-k3vzd3 , fuspc-k3w1u7 , gibza-a0a016pl96 , fuspc-k3ufi3 , gibze-i1rkc4 , fuspc-fdb26 , fuspc-w4935

Title : A measure of the promiscuity of proteins and characteristics of residues in the vicinity of the catalytic site that regulate promiscuity - Chakraborty_2012_PLoS.One_7_e32011
Author(s) : Chakraborty S , Rao BJ
Ref : PLoS ONE , 7 :e32011 , 2012
Abstract : Promiscuity, the basis for the evolution of new functions through 'tinkering' of residues in the vicinity of the catalytic site, is yet to be quantitatively defined. We present a computational method Promiscuity Indices Estimator (PROMISE)--based on signatures derived from the spatial and electrostatic properties of the catalytic residues, to estimate the promiscuity (PromIndex) of proteins with known active site residues and 3D structure. PromIndex reflects the number of different active site signatures that have congruent matches in close proximity of its native catalytic site, the quality of the matches and difference in the enzymatic activity. Promiscuity in proteins is observed to follow a lognormal distribution (micro=0.28, sigma=1.1 reduced chi-square=3.0E-5). The PROMISE predicted promiscuous functions in any protein can serve as the starting point for directed evolution experiments. PROMISE ranks carboxypeptidase A and ribonuclease A amongst the more promiscuous proteins. We have also investigated the properties of the residues in the vicinity of the catalytic site that regulates its promiscuity. Linear regression establishes a weak correlation (R(2)-0.1) between certain properties of the residues (charge, polar, etc) in the neighborhood of the catalytic residues and PromIndex. A stronger relationship states that most proteins with high promiscuity have high percentages of charged and polar residues within a radius of 3 A of the catalytic site, which is validated using one-tailed hypothesis tests (P-values-0.05). Since it is known that these characteristics are key factors in catalysis, their relationship with the promiscuity index cross validates the methodology of PROMISE.
ESTHER : Chakraborty_2012_PLoS.One_7_e32011
PubMedSearch : Chakraborty_2012_PLoS.One_7_e32011
PubMedID: 22359655

Title : Chronic exposures to cholinesterase-inhibiting pesticides adversely affect respiratory health of agricultural workers in India - Chakraborty_2009_J.Occup.Health_51_488
Author(s) : Chakraborty S , Mukherjee S , Roychoudhury S , Siddique S , Lahiri T , Ray MR
Ref : J Occup Health , 51 :488 , 2009
Abstract : OBJECTIVE: The impact of long term exposure to cholinesterase (ChE)-inhibiting organophosphate (OP) and carbamate (C) pesticides on the respiratory health of agricultural workers in India was investigated. METHODS: Three hundred and seventy-six nonsmoking agricultural workers (median age 41 yr) from eastern India who sprayed OP and C pesticides in the field and 348 age- and sex-matched control subjects with non-agricultural occupations from the same locality were enrolled. Prevalence of respiratory symptoms was obtained by questionnaire survey, and pulmonary function tests were carried out by spirometry. Chronic obstructive pulmonary disease (COPD) was diagnosed by the Global Obstructive Lung Disease (GOLD) criteria, and erythrocyte acetylcholinesterase (AChE) was measured by the Ellman method. RESULTS: Agricultural workers had greater prevalences of upper and lower respiratory symptoms, and appreciable reduction in spirometric measurements. Overall, lung function reduction was noted in 48.9% of agricultural workers compared with 22.7% of control, and a restrictive type of deficit was predominant. COPD was diagnosed in 10.9% of agricultural workers compared with 3.4% of controls (p<0.05 in chi(2) test), and the severity of the disease was greater in agricultural workers. Red blood cell (RBC) AChE was lowered by 34.2% in agricultural workers, and the fall in AChE level was positively associated with respiratory symptoms, lung function decrement and COPD after controlling for education and income as potential confounders. CONCLUSIONS: Long-term exposure to cholinesterase-inhibiting agricultural pesticides currently in use in India is associated with a reduction in lung function, COPD and a rise in respiratory symptoms.
ESTHER : Chakraborty_2009_J.Occup.Health_51_488
PubMedSearch : Chakraborty_2009_J.Occup.Health_51_488
PubMedID: 19851039