Interaction of organophosphate pesticide chlorpyrifos with alpha-2-macroglobulin: Biophysical and molecular docking approach.

Organophosphate class of pesticides causes neurotoxicity and carcinogenicity in humans. Once inside the human body, these pesticides often interact with plasma proteins, such as alpha-2-macroglobulin (α2M) which is the key anti-proteinase. Our work focuses on the structural and functional alteration of α2M by chlorpyrifos (CPF), a member of organophosphates. We explored the binding interaction between alpha-2-macroglobulin and CPF by using UV absorption and fluorescence spectroscopy (steady state and synchronous), circular dichroism and molecular docking approach. The functional activity of α2M was analyzed by anti-proteinase trypsin inhibitory assay which showed dose-dependent decrease in alpha-2-macroglobulin antiproteolytic potential. UV absorption studies and fluorescence quenching experiments suggested the formation of a complex between α2M and CPF. The CD spectra suggested a reduction in the beta helical (ß helix) content of α2M. Analysis of thermodynamic parameters suggested the process is spontaneous and endothermic with the ΔG and ΔH values being -5.501 kJ/mol, 11.49 kJ/mol, respectively. CPF binds with Ile-1390, Pro-1391, Leu-1392, Lys-1393, Val-1396, Lys-1397, Arg-1407, Thr-1408, Glu-1409, Val-1410, Asp-282, Glu-281 of α2M as suggested by molecular docking.

Obstructive sleep apnea risk for driving license applicants in India - A community based study.

OBJECTIVES: To determine the risk of obstructive sleep apnea (OSA) for male permanent driving license (DL) applicants of Lucknow, India. MATERIAL AND METHODS: In this cross-sectional community based, study body mass index, waist-hip ratio, blood pressure of each subject were determined as an anthropometric parameter along with the history of habit of smoking, tobacco chewing, alcohol consumption. STOP-Bang (Snoring, Tired or sleepy, Observed apnea, high blood Pressure, Body mass index, Age, Neck, Gender) Questionnaire - a scoring risk assessment tool - was applied for assessment of OSA risk (high OSA risk defined by score ≥ 3) for 542 male DL recipients at 2 Regional Transport Office (RTO) centers in Lucknow, India. The statistical software SPSS 17.0 was applied to the testing. RESULTS: In total 23% (N = 125) of participants were found with the risk of OSA. High blood pressure (≥ 140/90 mm Hg) was found for the maximum number of participants (40.5%) followed by neck circumference > 40 cm (17.1%), age (> 50 years old) (15.3%), snoring (12.3%) and tired/sleepy (10.5%). Mean values of age, anthropometric measurements and blood pressure were observed significantly higher (p < 0.001) for participants with the OSA risk. In this population the risk of OSA risk (STOP-Bang score ≥ 3) was observed for 6.7% of young (< 35 years old), 34% of middle (35-45 years old) and 73% of elder age adults (> 45 years old). CONCLUSIONS: In view of findings of this study a high number of male driving license applicants were observed with the risk of OSA. Therefore efforts should be made to develop a national screening guideline/protocol for the OSA risk assessment for driving license applicants in India. This may reduce the possibility of road traffic accidents due to the OSA-associated fatigue and drowsiness behind the wheels. Int J Occup Med Environ Health 2018;31(1):25-36.

MAPK mediated cell cycle regulation is associated with Cdc25 turnover in S. pombe after exposure to genotoxic stress.

Genotoxic stress caused by carcinogens like cigarette smoke activate both the MAPK pathway and the S phase checkpoint in Schizosacchaomyces pombe. But the cross talk between these two pathways has not been investigated in great detail in fission yeast. This study deals with the molecular mechanism of co-ordination between the two regulatory pathways. We show that both the pathways have a common effector molecule, namely Cdc25, the cell cycle regulatory phosphatase. We demonstrate that the MAPK Sty1 interacts with Cdc25 and prevents mitotic entry in S.pombe cells exposed to CSE. To our knowledge, this is the first demonstration of interaction between Sty1 and Cdc25 in S. pombe. The functional significance of this interaction lies in effecting Cdc25 turnover after CSE exposure in S.pombe. We show that Cdc25 turnover after CSE treatment is dependent on the presence of Rad3 activity and Sty1-Cdc25 interaction. Our study suggests that the cigarette smoke extract (CSE) induced stress is counteracted by the simultaneous activation of a mitotic checkpoint in addition to the previously described S phase checkpoint. We also show that Sty1 activity is not essential for activation of the S phase checkpoint.