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Objective: To examine the prevalence and correlates of tobacco use during pregnancy in a rural area of India.Methods: In the present cross-sectional study, 400 women who gave birth between June 20, 2011, and June 19, 2012, were enrolled in the district of Pakur in Jharkhand, using multistage cluster sampling. Information on tobacco use, awareness of associated adverse health effects, and exposure to secondhand smoke was collected by interview. Multiple logistic regression analysis was used to find correlates of tobacco use.Results: Overall, 59 (14.8%, 95% confidence interval [CI] 11.0%-18.7%) women reported tobacco use during pregnancy. Awareness of the adverse health effects of tobacco during pregnancy was poor for 213 (53.3%) women. Tobacco use during pregnancy was significantly associated with an age of 25 years or older (odds ratio [OR] 8.20, 95% CI 2.48-27.15; P = 0.001) and poor awareness of adverse health effects (OR 4.48, 95% CI 2.03-9.90; P < 0.001).Conclusion: There is an urgent need to prevent tobacco use among pregnant women in India and to offer tobacco cessation services during prenatal checkups to those who continue tobacco use during pregnancy. [ABSTRACT FROM AUTHOR]

Glucokinase Activators (GKA) are novel small molecules that target GK and reduce plasma blood glucose by binding GK allosterically. It is considered as a potential therapeutic target to treat T2D. So, in an effort to identify compounds to treat T2D efficiently, a structure‐based virtual screening was performed on compounds from Universal Natural Product Database (UNPD) using FRED. Among 229358 compounds from UNPD, four compounds were identified as potential small molecules. The hit compounds UNPD 1354, UNPD 85595, UNPD 6604, and UNPD 88147 are found to interact strongly with active site residues ARG 63, VAL62, VAL452, TYR215, VAL 455, MET210, MET235, and TYR214. In addition, ADME predictions show that the compounds satisfy drug‐likeness criteria. Finally, the molecular dynamics simulation was carried out for 50 ns using the GROMACS 2020 package, the results confirm the stability of the enzyme‐HIT throughout the simulation time. Thus, this study may provide valuable insights into identifying novel small molecules as GKAs. [ABSTRACT FROM AUTHOR]

Cyclin-dependent kinases (CDKs) are core components of the cell cycle machinery that govern the transition between phases during cell cycle progression. Abnormalities in CDKs activity and regulation are common features of cancer, making CDK family members attractive targets for the development of anticancer drugs. Their inhibitors have entered in clinical trials to treat cancer. Very recently, Heathcote et al. (J. Med. Chem. 2010, 53:8508-8522) have found a ligand BS194 that has a high affinity with CDK2 (IC50 = 3 n m) but shows low affinity with CDK1 (IC50 = 30 n m). To understand the selectivity, we used homology modeling, molecular docking, molecular dynamics, and free-energy calculation to analyze the interactions. A rational three-dimensional model of the CDK1/BS194 complex is built. We found that Leu83 is a key residue that recognizes BS194 more effectively with CDK2 with good binding free energies rather than CDK1. Energetic analysis reveals that van der Waals interaction and non-polar contributions to solvent are favorable in the formation of complexes and amine group of the ligand, which plays a crucial role for binding selectivity between CDK2 and CDK1. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The value of environmental regulation through command and control measures has been questioned because of inflexibility and high cost. Voluntary environmental initiatives have been proposed as an alternative approach to save costs, overcome problems of inadequate enforcement and monitoring and to take advantage of the environmental leadership of transnational corporations (TNCs). Amongst voluntary environmental initiatives certified environmental management system standards have so far had most impact in Singapore and the rest of Southeast Asia. This paper investigates the environmental policy statements of 52 ISO14001 certified organisations in Singapore and shows that the environmental commitments being made are no substitute for traditional environmental regulations. [ABSTRACT FROM AUTHOR]

Objective: The irrational use of antibiotics is a leading contributor to antibiotic resistance. Antibiotic stewardship (AS) interventions predominantly focus on prescribers. This study investigated the influence and participation of inpatients in infection‐related care, including antibiotic decision‐making, within and across two tertiary hospitals in South Africa (Cape Town) and India (Kerala). Methods: Through ethnographic enquiry of clinical practice in surgical pathways, including direct nonparticipant observation of clinical practices, healthcare worker (HCW), patient and carer interactions in surgical ward rounds and face‐to‐face interviews with participants (HCWs and patients), we sought to capture the implicit and explicit influence that patients and carers have in infection‐related care. Field notes and interview transcripts were thematically coded, aided by NVivo 12® Pro software. Results: Whilst observational data revealed the nuanced roles that patients/carers play in antibiotic decision‐making, HCWs did not recognize these roles. Patients and carers, though invested in patient care, are not routinely involved, nor are they aware of the opportunities for engagement in infection‐related decision‐making. Patients associated clinical improvement with antibiotic use and did not consider hospitalization to be associated with infection acquisition or transmission, highlighting a lack of understanding of the threat of infection and antibiotic resistance. Patients' economic and cultural positionalities may influence their infection‐related behaviours. In the study site in India, cultural norms mean that carers play widespread but unrecognized roles in inpatient care, participating in infection prevention activities. Conclusion: For patients to have a valuable role in AS and make informed decisions regarding their infection‐related care, a mutual understanding of their role in this process among HCWs and patients is crucial. The observed differences between the two study sites indicate the critical need for understanding and addressing the contextual drivers that impact effective patient‐centred healthcare delivery. Patient or Public Contribution: Ethnographic observations and interviews conducted in this study involved patients as participants. Patients were recruited for interviews after obtaining signed informed consent forms. Patients' identities were completely anonymized when presenting the study findings. [ABSTRACT FROM AUTHOR]

Prophenoloxidase (ProPO) cascade is a principal defense system in crustaceans, which consists of a variety of pattern recognition proteins (lipopolysaccharide and β-glucan-binding protein [β-GBP], β-GBP, and β-glucan recognition protein), proteases (serine protease), and protease inhibitors (α2-macroglobulin and pacifastin) to regulate the protection mechanism in crustaceans. In the prophneoloxidase pathway, the protein-protein interactions (PPIs) and other immune-related analyses still have not been reported. Moreover, the structural features of ProPO cascade proteins have not yet been reported, hence we constructed the three-dimensional structural features for all ProPO pathway proteins. Their PPIs were studied through an in silico approach. Laminarin has been identified as a triggering activator and it showed energetic binding with homology modeled β-GBP and activated the β-GBP, followed by the protein-protein complex formation leading to phenoloxidase synthesis. These findings provided a novel view of the ProPO mechanism and enhanced our knowledge of the innate immune system in crustaceans via computation. In conclusion, we propose a combined experimental and computational approach to analyze the mechanism of ProPO cascade proteins. [ABSTRACT FROM AUTHOR]

The environmental performance of transnational corporations (TNCs) may need to be updated to include evidence of increased corporate environmental responsibility. This is a challenge to geographical perspectives that have been critical of the environmental performance of TNCs. The paper reports the findings of a survey of TNCs with branches in Singapore. Using the survey evidence, TNCs are classified according to their degree of participation in a range of voluntary environmental initiatives. According to the classification, there is a similar proportion of low and high performers but a dominance of medium level activity that can involve little organisational change. A significant association between organisational size and environmental activity is found. Respondents most frequently report that corporate environmental standards motivate environmental action in Singapore. Overall the survey evidence indicates that few TNCs are significantly changing their environmental behaviour. The absence of citizen, NGO and government pressure on TNCs is reducing the extent of voluntary environmental action in Singapore and expectations of widespread corporate greening overlook organisational differences in their opportunity to benefit from investment in environmental management. It is concluded that voluntary corporate environmentalism does not reduce the need for government regulation. [ABSTRACT FROM AUTHOR]

In invertebrates, the prophenoloxidase (proPO) pathway is involved in the phenol-like antioxidant production against invading pathogens. Overproduction of melanin and phenolic substances leads to the disruption of hemocytes (own host cells); therefore, there is a prerequisite to regulate the antioxidant production, which is performed by the proteases and proPO-associated cell adhesion protein peroxinectin (PX). PX is a macromolecular structure consisting of protein involved in the proPO pathway, which is a potential target in the regulatory mechanism in crustaceans. In the proPO cascade, pattern recognition proteins initiate the proPO cascade by the consequent reaction, and PX is involved in the key step in the regulatory mechanism of phenoloxidase enzyme synthesis. In the present study, Indian white shrimp Fenneropenaeus indicus PX ( Fein-PX) gene sequence was used. Upregulation of Fein-PX was determined using immunostimulants β-glucan (agonists) and examined its expression by quantitative RT-PCR. To find the downregulation or negative regulation of Fein-PX, inhibitors were screened, and its 3D model provides molecular insights into the rationale inhibitor design for developing an effective molecule against Fein-PX. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

A full-length cDNA of a β-glucan binding protein ( β-GBP) gene was identified from the mangrove crab Episesarma tetragonum. The open reading frame of the E. tetragonum β-GBP ( Epte β-GBP) is 1,167 bp long, encoding a polypeptide of 389 amino acids. The deduced amino acid sequence of Epte β-GBP gene has conserved a potential recognition motif for β-1,3 linkages of polysaccharides and putative RGD (Arg-Gly-Asp) cell adhesion sites. Phylogenetic analysis of the Epte β-GBP gene showed the similarity with β-GBPs of other crustaceans and arthropods. Quantitative RT-PCR results showed the upregulation of Epte β-GBP gene expression in E. tetragonum hemocytes following a 12-H challenge in response to β-glucan (β-G). Epte β-GBP was involved in the regulation and activation of the prophenoloxidase cascade. A three-dimensional structure of active Epte β-GBP was modeled by homology modeling and refined with molecular dynamics simulations. A structural aspect of the protein is discussed based on experimental and theoretical results obtained. [ABSTRACT FROM AUTHOR]

Retroviruses HTLV-1 and HIV-1 are the primary causative agents of fatal adult T-cell leukemia and acquired immune deficiency syndrome (AIDS) disease. Both retroviruses are similar in characteristics mechanism, and it encodes for protease that mainly involved in the viral replication process. On the basis of the therapeutic success of HIV-1 PR inhibitors, the protease of HTLV-1 is mainly considered as a potential target for chemotherapy. At the same time, structural similarities in both enzymes that originate HIV PR inhibitors can also be an HTLV-1 PR inhibitor. But the expectations failed because of rejection of HIV PR inhibitors from the HTLV-1 PR binding pocket. In this present study, the reason for the HIV PR inhibitor rejection from the HTLV-1 binding site was identified through sequence analysis and molecular dynamics simulation method. Functional analysis of M37A mutation in HTLV PR clearly shows that the MET37 specificity and screening of potential inhibitors targeting MET37 is performed by using approved 90% similar HIV PR inhibitor compounds. From this approach, we report few compounds with a tendency to accept/donate electron specifically to an important site residue MET37 in HTLV-1 PR binding pocket. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

In invertebrates, crustaceans' immune system consists of pattern recognition receptors (PRRs) instead of immunoglobulin's, which involves in the microbial recognition and initiates the protein-ligand interaction between hosts and pathogens. In the present study, PRRs namely β-1,3 glucan binding protein (β-GBP) from mangrove crab Episesarma tetragonum and its interactions with the pathogens such as bacterial and fungal outer membrane proteins (OMP) were investigated through microbial aggregation and computational interaction studies. Molecular recognition and microbial aggregation results of Episesarma tetragonum β-GBP showed the specific binding affinity toward the fungal β-1,3 glucan molecule when compared to other bacterial ligands. Because of this microbial recognition, prophenoloxidase activity was enhanced and triggers the innate immunity inside the host animal. Our findings disclose the role of β-GBP in molecular recognition, host-pathogen interaction through microbial aggregation, and docking analysis. In vitro results were concurred with the in silico docking, and molecular dynamics simulation analysis. This study would be helpful to understand the molecular mechanism of β-GBP and update the current knowledge on the PRRs of crustaceans. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The LuxS-based signalling pathway has an important role in physiological and pathogenic functions that are capable of causing different infections. In the present study, cinnamaldehyde (CN) and their derivatives were evaluated for their inhibitory efficiency against LuxS by molecular modelling, docking, dynamics and free-energy calculations. Sequence and structure-similarity analysis of LuxS protein, five different amino acids were found to be highly conserved, of which GLY128 was identified as the key residue involved in the effective binding of the ligands. Quantum-polarized ligand docking protocol showed that 2nitro and 4nitro CN has a higher binding efficiency than CN, which very well corroborates with the in vitro studies. COMSTAT analysis for the microscopic images of the S. pyogenes biofilm showed that the ligands have antibiofilm potential. In addition, the results of quantitative polymerase chain reaction (qPCR) analysis revealed that the transcripts treated with the compounds showed decrease in luxS expression, which directly reflects with the reduction in expression of speB. No substantial effect was observed on the virulence regulator ( srv) transcript. These results confirm that speB is controlled by the regulation of luxS. The decreased rate of S. pyogenes survival in the presence of these ligands envisaged the fact that the compounds could readily enhance opsonophagocytosis with the reduction of virulence factor secretion. Thus, the overall data supports the use of CN derivatives against quorum sensing-mediated infections caused by S. pyogene s. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Wiskott‐Aldrich syndrome (WAS) also called the eczema‐thrombocytopenia‐immunodeficiency syndrome is a primary immunodeficiency disease with X‐linked recessive inheritance caused by mutations in the WAS protein (WASp) gene and characterized by thrombocytopenia with reduced platelet volume, eczema, immunodeficiency, and increased risk of malignant tumours. The mutations will lead to separate WAS severity which can be typical severe 'classical' WAS or less severe 'non‐classical' WAS. This article will review and analyse clinical and immune characteristics of five unrelated Chinese families harbouring classical and non‐classical WAS. The expression of WASp was detected in the peripheral blood monocytes (PBMC) by flow cytometry, and five mutations were found by WAS gene sequencing, one of which had not been reported in the literature, namely frameshift mutation c.1240_1247delCCACTCCC (p. P414Sfs*41). [ABSTRACT FROM AUTHOR]

Quinolone resistance-determining region is known to be the druggability site of the target protein that undergoes frequent mutation and thus renders quinolone resistance. In the present study, ligands were tested for their inhibitory activity against DNA gyrase of Streptococcus pyogenes involved in DNA replication. In silico mutational analysis on modelled gyrase A revealed that GLU85 had the most possible interactions with all the ligands used for the study. The amino acid residue GLU85 had also been predicted with an essential role of maintaining the three-dimensional structure of the protein. When introduced with a mutation (GLU 85 LYS) on this particular residue, it had readily denatured the whole α-helix (from 80 to 90 amino acids). This was confirmed through the molecular dynamics simulation and revealed that this single mutation can cause many functional and structural changes. Furthermore, LYS85 mutation has altered the original secondary structure of the protein, which in turn led to the steric hindrance during the ligand-receptor interaction. The results based on the G-score revealed that ligands have reduced interaction with the mutant protein. The semisynthetic fluoroquinolone 6d, which is an exception, forms a strong interaction with the mutant protein and was experimentally verified using the antimicrobial test. Hence, the present study unravels the fact that mutation at the drug binding site is the major cause for different level of resistance by the S. pyogenes when exposed against the varying concentrations of the fluoroquinolones. Furthermore, a comparative assessment of quinolone derivative with the older generation fluoroquinolones will be of great impact for S. pyogenes-related infections. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Linkage of a cutting tool (a sickle) with a telephone cable of 100 pairs of copper wires is reported in a case of theft of a telephone cable. Telephone cables contain numerous insulated copper wires of small diameter inside an outer covering and are stolen for the relatively precious copper. The cutting pattern of the cable can only point to the type of the tool but because of the large number of copper wires, it is practically difficult to make a definite linkage with the tool used to cut the cable by comparing the tool marks. The present work reports the successful attempt of the authors in establishing a definite linkage of a stolen telephone cable with a sickle recovered from the suspects. Spot microchemical test was performed for detection of copper on the blade of the sickle, and then tool mark comparison was performed to link the tool marks on the metal strip inside the outer covering of the cable to the blade of the sickle. [ABSTRACT FROM AUTHOR]

Most bacteriophages rapidly infect and kill bacteria and, therefore, qualify as the next generation therapeutics for rapidly emerging drug-resistant bacteria such as Mycobacterium tuberculosis. We have previously characterized the mycobacteriophage D29-generated endolysin, Lysin A, for its activity against mycobacteria. Here, we present a detailed characterization of the lysozyme domain ( LD) of D29 Lysin A that hydrolyzes peptidoglycan of both gram-positive and gram-negative bacteria with high potency. By characterizing an exhaustive LD protein variant library, we have identified critical residues important for LD activity and stability. We further complement our in vitro experiments with detailed in silico investigations. We present LD as a potent candidate for developing phage-based broad-spectrum therapeutics. [ABSTRACT FROM AUTHOR]

The fundamental of molecular modeling is the interaction and binding to form a complex, because it explains the action of most drugs to a receptor active site. In the present study, different semiempirical ( RM1, AM1, PM3, MNDO) and ab intio ( HF, DFT) charge models were investigated for their performance in prediction of docking pose against CDK2 proteins with their respective inhibitor. Further, multiple docking approaches and Prime/ MM- GBSA calculations were applied to predict the binding mode with respective charge model against CDK2 inhibitors. A reliable docking result was obtained using RRD, which showed significance improvement on ligand binding poses and docking score accuracy to the IFD. The combined use of RRD and Prime/ MM- GBSA method could give a high correlation between the predicted binding free energy and experimental biological activity. The preliminary results point out that AM1 could be a precious charge model for design of new drugs with enhanced success rate. As a very similar result was also found for a different system of the protein-ligand binding, the suggested scoring function based on AM1 method seems to be applicable in drug design. The results from this study can provide insights into highest success rate for design of potent and selective CDK2 inhibitors. [ABSTRACT FROM AUTHOR]

The recognition of DNA by small molecules is of special importance in the design of new drugs. Many natural and synthetic compounds have the ability to interact with the minor groove of DNA. In the present study, identification of minor groove binding compounds was attained by the combined approach of pharmacophore modelling, virtual screening and molecular dynamics approach. Experimentally reported 32 minor groove binding compounds were used to develop the pharmacophore model. Based on the fitness score, best three pharmacophore hypotheses were selected and used as template for screening the compounds from drug bank database. This pharmacophore-based screening provides many compounds with the same pharmacological properties. All these compounds were subjected to four phases of docking protocols with combined Glide-quantum-polarized ligand docking approach. Molecular dynamics results indicated that selected compounds are more active and showed good interaction in the binding site of DNA. Based on the scoring parameters and energy values, the best compounds were selected, and antibacterial activity of these compounds was identified using in vitro antimicrobial techniques. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]