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The flapping kinematics have revealed a new paradigm of locomotion which is highly maneuverable and efficient compared to traditional propulsion systems. This work numerically investigates a three-dimensional wing undergoing pitching oscillations using Large eddy simulation (LES). The wake structure is presented using the Q -function, and the influence of pitching frequency on the structure of the wake is discussed. The vortices appear to travel as interconnected vortex rings in the bifurcated wake and are completely different from the two-dimensional investigations. The increase in pitching frequency ( St D) generates the interlinking structures between the two limbs of the bifurcated wake. The interlinking between the two limbs increases with St D and will get disrupted at sufficiently high St D . The increase in St D increased the force generated by the pitching wing, and the periodic dynamics between the force coefficients slowly transformed to quasi-periodic dynamics. The transition to quasi-periodic dynamics has not reduced the force generation of the pitching wing. The disruption of interlinking structures between the two limbs enhanced the lift generated by the pitching wing. The present investigation shows that the wake vortex structure strongly depends on St D . The generation of a jet in the wake is visible in the mean velocity profile indicating the thrust developed by the wing. The formation of multiple peak profiles indicated the formation of multiple jets, which resulted in enhanced thrust production. The Reynolds stress field generated from the velocity fluctuations appears to be influenced by both the pitching oscillations and vortex interactions. This study can guide the selection of better kinematic parameters to enhance the propulsive performance. [ABSTRACT FROM AUTHOR]

This study focuses on improving the performance of Savonius hydrokinetic turbines (SHTs) by analyzing the influence of blade aerodynamics and varying overlap ratios ( e D = 0 to 0.15). The study compares the performance of conventional and a new type of Savonius turbine blade, referred to as S R 5050. The study uses the incompressible SST k − ω model to evaluate the performance of a rotor under an upstream velocity of 0. 46 m s , with the numerical flow-driven approach where no artificial rotor motion has been provided. The results show that the new blade shape of the S R 5050 rotor outperforms conventional rotors in all e D ratios. The blade shape of the S R 5050 rotor effectively captures the energy of fluid passing between the blades, increasing both the coefficient of power C p and the coefficient of torque C m . The S R 5050 rotor with an e D ratio of 0.15 displays the highest value of C p at 0.38. It shows a maximum performance improvement of 39.19% over conventional rotors. For conventional rotors, the highest values of C m were observed at rotor position around ≈ 15 ° and ≈ 195 ° , while for S R 5050 rotors with all e D ratios, the highest values of C m were observed at rotor position of ≈ 20 ° and ≈ 200 °. [Display omitted] • Influence of aerodynamic blade shape (SR5050) on the SHT. • Influence of different overlap ratios on the SHT. • Increasing the overlap ratio results in higher mean value of the TSR, C m and C p. • The S R 5050 shows better starting characteristics. • The S R 5050 exhibited a 39.19% increase in C p = 0. 38 compared to the conventional rotor. [ABSTRACT FROM AUTHOR]

The three-dimensional flow around a custom wing performing pitching oscillation is analyzed numerically using large-eddy simulation with the wall adapting local eddy-viscosity subgrid-scale model. The wake characteristics behind the pitching wing with three different aspect ratios, AR = 2 / 3 , 1 , 4 / 3 , is investigated in an upstream flow with Reynolds number, Re = 2640. The Q − function is employed to identify the swirling structures in the flow field, and four primary vortices, namely, primary leading edge vortex (PLEV), secondary leading edge vortex, wing tip vortices, and trailing edge vortex, are identified. The evolution of vortices over the wing surface is presented in detail, and the arrangement of vortex rings in the wake is compared for three different aspect ratios. The PLEV develops into an arch vortex using the self-induction phenomenon, and the interlinking between the subsequent vortex rings depends on the arch vortex leaving the trailing edge. The force coefficient computed over the wing shows a positive thrust for AR = 4 / 3. The mean velocity field contours indicate a spanwise loading on the wing, which is unaccountable in two-dimensional studies. The Reynolds stresses generated due to large-scale periodic velocity fluctuations in the wake are presented. The vorticity field in the midplane of the wing appears to be diffusive at higher aspect ratios. The comparison of vorticity from the three-dimensional and two-dimensional models suggests that a two-dimensional model will over predict the vorticity distribution and force coefficients in the wake. [ABSTRACT FROM AUTHOR]

The application of a flapping wing mechanism offers a vast range of development possibilities for unmanned aerial vehicles (UAVs) and autonomous underwater vehicles (AUVs). The influence of wake transitions on flapping wing mechanism's capabilities is not fully understood particularly at low Reynolds numbers. The numerical investigation of a symmetric airfoil performing sinusoidal heaving oscillations is performed to explore the wake transitions. The influence of heaving parameters on wake transitions when exposed to a constant velocity flow is investigated. The existence of reverse von Karman vortex street, deflected wake and chaotic wake is observed. The wake deflection is found to switch its direction before transforming into a chaotic wake. The coherent structures and its evolution with the flow are presented using proper orthogonal decomposition (POD). The underlying structures and their interactions for different wake situations are identified. Correlations for the nondimensional maximum velocity in the wake in terms of frequency and amplitude is proposed. The wake dynamics is found to depend significantly on the leading edge vortices. The time-varying velocity fluctuations in the flow field are presented and discussed in detail. The velocity fluctuation contours are used to identify the regions of momentum transfer. The transient nature of the flow field is studied using the phase plot. A transition route from the periodic to chaotic regime though a quasi-periodic regime is established using time series analysis. The wake transitions are observed to be more sensitive towards heaving frequency than the heaving amplitude. [ABSTRACT FROM AUTHOR]

The wake dynamics behind a sinusoidally pitching custom designed symmetrical airfoil is analyzed computationally. The effect of pitching frequency and pitching amplitude is investigated independently at a constant Reynolds number. The wake patterns are found to exhibit a transition from von Karman to reverse von Karman vortex street and from symmetric reverse von Karman vortex street to asymmetric deflected wake as established. For laminar flow under investigation, the contours of time-varying velocity fluctuations are presented. The mean profiles of velocity and the fluctuations at different locations in the wake show that the thrust wakes are generated at the expense of energy of the surrounding fluid. The temporal behavior of the flow field is analyzed using the phase plot. The time series plots of force coefficients show a periodic loading on the airfoil. Proper orthogonal decomposition (POD) analysis of drag, neutral and thrust wakes displayed the evolution of coherent structures in the flow field. The evolution of these structures portray the transitions in the wake of the airfoil. The merging of coherent structures in an asymmetric deflected wake turns out to be an efficient way of identifying the location of deflection. • The vortex pairing mechanism is identified for the deflected wake. • The time average of fluctuating quantities are evaluated to quantify flow field. • The chaotic behavior of the flow field is identified using the u − v phase plot. • Time series analysis shows the effect of frequency is more prominent on force coefficients. • The coherent structures are identified using Proper orthogonal decomposition. [ABSTRACT FROM AUTHOR]

The incompressible turbulent flow field of the slot impinging jet has been studied numerically at a Reynolds number of 7900 and d = 6w using large-eddy simulation with the wall adapting local eddy-viscosity subgrid-scale model for the angles of impingement 70° and 90°. The validity of the computation is confirmed by reasonable comparisons of the wall shear stress, pressure variation over the impingement plate, jet-centerline velocity, and second-order turbulent properties with past experimental and numerical results. The turbulent stress, turbulent length scales, and turbulent structure sizes are observed to be increased in the oblique impingement. The appearance of the oblate spheroid-shaped, three-dimensional isotropic, and prolate spheroid-shaped turbulence has been marked in the wall-jet region using the anisotropy invariant map. The power spectra of the fluctuating field maintain the −5/3 slope in the inertial subrange, which as expected becomes steeper in the dissipation range, as stated by Kolmogorov. Both positively skewed and negatively skewed fluctuations are seen in the flow field, and their probability density functions suggest that the fluctuation range increases in the case of oblique impingement. The involvement of various shearing and swirling structures has been investigated employing the proper orthogonal decomposition, the Q- function, and the λ2- function, where the isosurface of vorticity components is used to represent the direction of rotations. [ABSTRACT FROM AUTHOR]

The characteristics of heat transfer from a hot wall surface for the oblique impingement of a free turbulent slot jet have been investigated numerically. Different turbulent models — the k - ϵ , k - ω , SST k - ω , cubic k - ϵ and quadratic k - ϵ models — are used for the prediction of heat transfer and their results were compared with experimental results reported in the literature. The comparison shows that the k - ϵ , quadratic k - ϵ and SST k - ω models give more unsatisfactory results for the investigated configuration, while the cubic k - ϵ model is capable of predicting the local Nusselt number in wall-jet region only. The k - ω model exhibits the best agreement with the experimental results in both stagnation and wall-jet regions. Further, the k - ω model is applied to analyze the obliquely impinging jet heat transfer problem. The parametric effects of the jet inclination (ϕ = 5 0 ∘ , 7 0 ∘ and 9 0 ∘ ), jet-to-surface distance ( d L = 4 , 6 and 8), Reynolds number (Re = 1 2 0 0 0 , 15 000 and 20 000), and turbulent intensity (I = 5 % , 7. 5 % and 1 0 %) have been presented. The heat transfer on the upward direction is seen to decrease, while that on the downward direction it rises for the increasing angle. It is to be noted that as the value of ϕ decreases, the point of maximum Nusselt number ( Nu max ) displaces toward the upward direction from the geometric center point as well as its value reduces. The shifting of the Nu max is found to be independent of Re and d L within the range considered for the study. [ABSTRACT FROM AUTHOR]

In this paper, a dimensionless numerical study of the flow-field and heat transfer characteristics of an incompressible turbulent slot jet impinging obliquely over a moving surface of finite thickness is presented. Simulations were performed using k − ϵ eddy viscosity turbulence model. The temperature field was solved simultaneously in the solid and the fluid domain. For a fixed impingement distance and a fixed Reynolds number, the impingement angle (ϕ) and plate velocity ( U p ) were varied in the range of 30–75∘ and 0–0.3, respectively. In the results, the length of the potential core depends on the jet inclination, which increases with increase in jet angle. The jet angle and plate velocity have more influence on the uphill side compared to the downhill side. The location of stagnation displaces toward the uphill side as the inclination angle decreases, and the drifting of stagnation point is noted with the variation in plate velocity. The average skin-friction coefficient increases with increase in ϕ and U p , and the influence of U p on the skin-friction coefficient is reduced as ϕ increases. The maximum Nusselt number (N u max ) increases with increase in ϕ , and the drifting of N u max is observed with increase in plate velocity. It is found that the average Nusselt number increases quickly with increase in plate velocity for lower angles of impingement. The distribution of local heat flux follows the same trend as the local Nusselt number. [ABSTRACT FROM AUTHOR]

Soil pollution in Guwahati city, Assam, India has become a major concern since the last few decades. To study the impact of automobile and industrial emission, distribution patterns of 16 different polycyclic aromatic hydrocarbons (PAHs) and eight heavy metals were investigated in the soil samples collected from 15 different sites. Higher concentration of total PAHs and heavy metals was found in the industrial areas compared to the high traffic areas. Differences in the pollutants observed between the polluted and nonpolluted sites, endorse that anthropogenic activities are the major cause of soil contamination. [ABSTRACT FROM AUTHOR]

Abstract: Large-eddy simulation (LES) of the incompressible turbulent flow in a two-sided lid-driven cubical cavity with lids moving in anti-parallel direction has been carried out at a Reynolds number of 12,000. The transient behaviour of the corner eddies have been discussed on the statistically symmetric plane. Time averaged solutions have been obtained by performing a long-lasting simulations using multiprocessing. The presence of four more eddies except the well known two corner eddies have been found in the transverse plane of the main core flow direction. The extent of the main average recirculating flow in the central core region in the x–z and y–z plane has been reported. The specific features of turbulent flow inside the cavity such as inhomogeneity of turbulence, small-scales localisation, second order turbulent statistics, cross-correlation of vorticity component and coherent structure of flow have been investigated. [Copyright &y& Elsevier]

Abstract: Large-eddy simulation (LES) using the dynamic Smagorinsky model (DSM) of incompressible turbulent flow in a lid-driven cubical cavity with lids moving in anti-parallel direction has been carried out at a Reynolds number of 12000. The time history and power spectra of variables such as velocity components, turbulent production, turbulent kinetic energy have been reported for the maximum turbulent production zone. The distribution about the size of turbulent structure passing through the maximum turbulent production zone has been discussed. The shearing and the swirling structures are identified on statistically symmetric plane. The turbulent production and dissipation have been investigated at each impingement area in the averaged flow field. [Copyright &y& Elsevier]

A dimensionless numerical investigation of turbulent flow and heat transfer characteristics due to the impingement of a free inclined slot jet onto the moving hot surface has been performed using the k − ω turbulence model. The parameters considered for the investigation are: the Reynolds number, impingement angle and plate velocity. The influence of parameters on the properties such as the pressure and velocity profiles, skin-friction coefficients, Nusselt number, interface temperature, and the location of stagnation has been presented. The displacement of stagnation point depends primarily on ϕ , whereas the effect of plate velocity is less significant. These relocations are found in between X = − 2 to 0. The effect of plate velocity on average skin-friction coefficient is continuously decreasing with increase in jet angle. A continuous increase in average Nu has been found with increase in Re for all values of ϕ and U p considered in the present study. It is revealed that the change in plate velocity has more influence on the average Nu for lower angles of impingement. Further reduction in the impingement angle shows an adverse effect on the average Nu. Correlations have been developed for Nusselt number at different zones based on the parameters considered for the study. [ABSTRACT FROM AUTHOR]

Large eddy simulation (LES) with dynamic Smagorinsky model (DSM) has been implemented to elicit the turbulence characteristic of the flow inside a cubic lid-driven cavity at Reynolds number of 10000. The coherent organized structures tear, pair and disintegrate leading to the evolution of turbulence. They are reflected in the RMS (root mean square) plots of the turbulent fluctuations in different planes. The flow has a near zero helicity value; unlike the other two velocity component, the probability density function of span wise velocity component shows the flow symmetry on the both side of the mid plane in span wise direction; kurtosis being largely leptokurtic except near wall locations indicates their peakedness. The quadrant analysis shows presence of more coherent structures near the down stream wall and the joint probability distribution function shows that turbulence is anisotropic. Power spectra is observed to follow the − 5 ∕ 3 law. Both Taylor microscale λ and Kolmogorov length scale η show greater near-wall dissipation • Large eddy simulation of cubic lid-driven cavity flow has been performed at Re =10000. • Q- criterion shows the coherent organized structures tear, pair and disintegrate leading to the evolution of turbulence. • The Fourier spectra of auto correlation shows a slope of − 5 ∕ 3 in the sub inertial range. • The probability density function of span wise velocity component on the symmetrical mid plane shows the flow maintains symmetry even at high Reynolds number and has very low skewness value. Kurtosis is mostly leptokurti except near wall location. • Joint probability density function shows the turbulent fluctuations distribution is anisotropic. [ABSTRACT FROM AUTHOR]

Fipronil is a highly effective, broad-spectrum insecticide used to control pests, globally. The increased usage has led to contamination of soil, water, fruits, and vegetables. The wide and frequent usage of fipronil across the globe calls for attention regarding risk assessment of undesirable effects on non-target microorganisms. In this context, the present study was carried to understand the impact of fipronil on non-pathogenic Escherichia coli. The non-pathogenic E. coli are important commensal of the intestinal tract of humans and animals and are also indicator organisms in the environment. Our study indicates that exposure of E. coli to fipronil (100 μM concentration) leads to significant reactive oxygen species production, loss of membrane potential and viability. Further, we have witnessed the bioaccumulation and biotransformation of fipronil by E. coli at non-lethal concentrations. The bio-transformed products (fipronil sulfone and fipronil sulfide) are also the major metabolites (along with amide) reported in the feces of the mammals when exposed to fipronil. Thus, there is a possibility that the gut E. coli might play a role in the degradation and thereby removal of fipronil. In addition, the bioaccumulation of fipronil in bacteria is of concern and need to be further explored because it can lead to biomagnification in the higher trophic level and can disturb the ecological balance. In our knowledge, this is the first report on the determination of fipronil and its metabolites in bacteria through GC-MS/MS. Image 1067 • Fipronil at 100 μM concentration is toxic to E. coli. • E. coli K12 biotransforms fipronil into fipronil sulfone and fipronil sulfide. • Fipronil bioaccumulates in bacteria. [ABSTRACT FROM AUTHOR]

Benzodiazepines can make victims more docile, they are frequently used in drug-facilitated crimes, such as robberies and sexual assaults. Therefore, it is essential to develop techniques for determining whether these chemicals are present in relation with illegal activity is crucial. Therefore, to determine the presence of five benzodiazepines (alprazolam, clonazepam, diazepam, lorazepam, and oxazepam) in water, alcoholic beverages, and non-alcoholic beverages, a simple and direct, miniaturized, and effective vortex assisted ultrasound based microextraction using solidification of floating organic droplets (VAUS-ME-SFO) in combination with LC-MS/MS was developed. 1-Undecanol and acetonitrile, respectively, served as the extractant and disperser solvents. Many other parameters affect the efficiency of the developed analytical procedure VAUS-ME-SFO/LC-MS/MS. These parameters were optimized using Plackett Burman Design and Central Composite Design to obtain reliable results. The optimum conditions for the extraction were: 10.0 mL of sample; 180 μL acetonitrile, as a dispersive solvent; 200 μL of 1-undecanol, as an extraction solvent; pH 7; 105 s of vortex agitation; 120 s of ultrasonication application and 3 min of centrifugation at 7000 rpm. The benzodiazepines were separated by a chromatographic separation technique carried out by a UPLC system consisting of a binary mobile phase. The solvent system comprises of 0.1% Formic acid in Milli-Q (Solvent A) and 0.1% Formic acid in ACN (Solvent B) with a gradient flow of 3.5 min total analysis time. Under the optimized conditions, the calibration curve was studied in the range of 0.124–7.810 ng mL−1. The regression correlation coefficient (R2) value of all targeted analytes ranges from 0.993 to 0.999. The LOD and LOQ of VAUS-ME-SFO methods using LC-MS/MS analysis range from 0.316 to 0.968 ng mL−1 and 1.055–3.277 ng mL−1 respectively. The repeatability within a day varied from 0.6 to 3.5%, and the reproducibility across days varied from 2.2 to 6.3%. The recoveries ranges for water, alcoholic and non-alcoholic beverages from 70.77 to 114.53%, 63.20–102.21% and 66.23–113.28% respectively. Further, the degradation kinetics was studied to establish the half-life of each targeted analyte in the matrix undertaken in the study. The water samples were classified based on their BDZs residues. This implies that the more health care and anthropogenic activity, the more the BDZs residue will be in water samples. [Display omitted] • Using a statistical tool for optimization, a simple and précised extraction and analysis approach for the simultaneous analysis of benzodiazepine residue in drainage water samples. • The Plackett Burman Design (PBD) and Central Composite Design (CCD) were used as statistical tools for optimization and obtaining more reliable analytical results. • A degradation kinetics study is performed to assess the half-live and rate constant of benzodiazepines in water, alcoholic and non-alcoholic beverages. [ABSTRACT FROM AUTHOR]

Landmark-based truss morphometric analysis and elemental composition in otoliths were used to identify the stock structure of Clarias batrachus inhabiting the river Ganga and its tributaries: Yamuna and Gomti rivers from India. Eleven morphometric landmarks were chosen to construct truss network on the fish body and inductively coupled plasma atomic emission spectrometry was used to analyze 12 trace elements in otoliths. The morphometric data showed that the discriminant functions DFI and DFII accounted for 49.5% and 30.1%, respectively of group variability. Twenty-four out of 30 morphometric measurements showed statistically significant (Univariate ANOVA, P < 0.001) differences among all four populations. Mean concentrations of Mg, Mn, Ba, Cu, Ni, Fe, K, Zn and Pb in the otoliths were significantly ( P < 0.001) different from each other while the mean concentrations of Na, Ca and Sr did not show significant variations ( P > 0.01). About 68.39% of individuals were correctly classified to their original groups in discriminating space using truss network analysis while otoliths chemistry data showed comparatively finer (94%) classification success. A plot of first two discriminant functions was used to visually depict the discrimination among the populations. Results showed different stocks of the fish in the river Ganga and its tributaries. [ABSTRACT FROM AUTHOR]

The essential oil of Pelargonium graveolens (rose-scented geranium), an important aromatic plant, comprising mainly mono- and sesqui-terpenes, has applications in food and cosmetic industries. This study reports the characterization of isoprenyl disphosphate synthases (IDSs) involved in P. graveolens terpene biosynthesis. The six identified PgIDSs belonged to different classes of IDSs, comprising homomeric geranyl diphosphate synthases (GPPSs; PgGPPS1 and PgGPPS2), the large subunit of heteromeric GPPS or geranylgeranyl diphosphate synthases (GGPPSs; PgGGPPS), the small subunit of heteromeric GPPS (PgGPPS.SSUI and PgGPPS.SSUII), and farnesyl diphosphate synthases (FPPS; PgFPPS).All IDSs exhibited maximal expression in glandular trichomes (GTs), the site of aroma formation, and their expression except PgGPPS.SSUII was induced upon treatment with MeJA. Functional characterization of recombinant proteins revealed that PgGPPS1, PgGGPPS and PgFPPS were active enzymes producing GPP, GGPP/GPP, and FPP respectively, whereas both PgGPPS.SSUs and PgGPPS2 were inactive. Co-expression of PgGGPPS (that exhibited bifunctional G(G)PPS activity) with PgGPPS.SSUs in bacterial expression system showed lack of interaction between the two proteins, however, PgGGPPS interacted with a phylogenetically distant Antirrhinum majus GPPS.SSU. Further, transient expression of AmGPPS.SSU in P. graveolens leaf led to a significant increase in monoterpene levels. These findings provide insight into the types of IDSs and their role in providing precursors for different terpenoid components of P. graveolens essential oil. • Six IDSs that are highly expressed in glandular trichomes of P. graveolens were functionally characterized. • Results revealed geranium has a homomeric GPPS, a bifunctional G(G)PPS, and a FPPS involved in terpenoid precursor formation. • Enzyme kinetics indicated that both homomeric and bifunctional G(G)PPS provide precursors for monoterpene biosynthesis. [ABSTRACT FROM AUTHOR]

Abstract: Dolomite is a natural mineral of great industrial importance and used worldwide, thus millions of workers are at risk of occupational exposure. Its toxicity is however, meagerly documented. In the present investigation, a dolomite powder obtained from its milling unit was analyzed by some standard methods namely, optical microscopy, transmission electron microscopy and dynamic light scattering. Results showed that dolomite powder contained particles of different shapes and size both microparticles (MPs) and nanoparticles (NPs), suggesting potential occupational exposure of these particles. An attempt was therefore, made to investigate dolomite toxicity in a particle size-dependent manner in human lung epithelial cells A549. The comparative toxicity evaluation of MPs and NPs was carried out by assessing their effects on cell viability, membrane damage, glutathione, reactive oxygen species (ROS), lipid peroxidation (LPO), micronucleus (MN) and proinflammatory cytokines, namely tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6). These markers of cytotoxicity, genotoxicity and inflammation were assayed in cells exposed to MPs and NPs in a dose-and time-dependent manner. Invariably, their toxic effects were dose-and time-dependent while NPs in general were significantly more toxic. Notably, NPs caused oxidative stress, genotoxicity and inflammatory responses, as seen by significant induction of ROS, LPO, MN, TNF-α, IL-1β and IL-6. Thus, the study tends to suggest that separate health safety standards would be required for micrometer and nanometer scale particles of dolomite. [Copyright &y& Elsevier]

Oxidative stress is reported as one of the most widely accepted mechanisms of maneb (MB)- and paraquat (PQ)-induced nigrostriatal dopaminergic neurodegeneration leading to the Parkinson's disease (PD) phenotype. The study investigated the effects of silymarin, an antioxidant of plant origin, and melatonin, an indoleamine produced in all species, in MB- and PQ-induced mouse model of PD. The mice were treated intraperitoneally daily with silymarin (40 mg/kg) or melatonin (30 mg/kg) along with respective controls for 9 wk. Subsets of these animals were also treated with MB (30 mg/kg) and PQ (10 mg/kg), twice a week, for 9 wk, 2 hr after silymarin/melatonin treatment. Locomotor activities along with striatal dopamine content, tyrosine hydroxylase (TH) immunoreactivity, number of degenerating neurons, lipid peroxidation and nitrite content were estimated. Additionally, mRNA expression of vesicular monoamine transporter, cytochrome P-450 2E1 (CYP2E1), and glutathione-S-transferase A4-4 (GSTA4-4), catalytic activities of CYP2E1 and GSTA4-4 and protein expressions of unphosphorylated and phosphorylated p53 (p53 and P-p53), Bax and caspase 9 were measured in control and MB- and PQ-treated mice with either silymarin or melatonin treatments. Silymarin/melatonin significantly offset MB- and PQ-mediated reductions in locomotor activities, dopamine content, TH immunoreactivity, VMAT 2 mRNA expression and the expression of p53 protein. Silymarin/melatonin attenuated the increases in lipid peroxidation, number of degenerating neurons, nitrite content, mRNA expressions of cytochrome P-450 2E1 (CYP2E1) and GSTA4-4, catalytic activities of CYP2E1 and GST and P-p53, Bax and caspase 9 protein expressions. The results demonstrate that silymarin and melatonin offer nigrostriatal dopaminergic neuroprotection against MB- and PQ-induced PD by the modulation of oxidative stress and apoptotic machinery. [ABSTRACT FROM AUTHOR]

Polycyclic aromatic hydrocarbons (PAHs) are common ubiquitous pollutants existing in nature with high recalcitrance and toxicity. In this study a bacterium capable of aerobic degradation of high molecular weight PAHs (with special reference to pyrene) was isolated by selective enrichment culture technique from oil refinery effluent sludge. The isolate was characterized as Achromobacter xylooxidans by 16S rRNA gene sequence analysis technique. For the first time it is hereby reported a bacterium capable of effectively degrading pyrene (up to 80%), as evident by reverse phase high performance liquid chromatographic analysis (RP-HPLC). After incubation of Achromobacter xylooxidans in minimal salt medium (MSM) containing pyrene, at concentration of 200 mg/L, as sole source of carbon and energy, there was decrease in pyrene concentration concomitant with increase in bacterial cell protein concentration. RP-HPLC analysis revealed that pyrene was degraded into three metabolites viz. I, II and III. The RP-HPLC eluent fraction were collected from 2.5 to 32.0 min by repeated injection of degraded sample, concentrated and analyzed on gas chromatography mass spectroscopy (GC-MS) for metabolite identification. The fraction shows 1-hydroxypyrene, 1-hydroxy-6-methoxypyrene and 1,6dimethoxypyrene as metabolic product of pyrene degradation, on the basis of their m/ z values. On contrary to the reported PAH degradation with reference to pyrene by different isolates till date; the efficient degradation, as evident by RP-HPLC, by this isolate holds a promising potential for planning of bioremediation strategies of contaminated sites. [ABSTRACT FROM AUTHOR]

Otoliths are commonly used to discriminate between fish stocks, through both elemental composition and otolith shape. Typical studies also have a large number of elemental compositions and shape measures relative to the number of otolith samples, with these measures exhibiting strong mean–variance relationships. These properties make otolith composition and shape data highly suitable for use within a multivariate generalised linear model (MGLM) framework, yet MGLMs have never been applied to otolith data. Here we apply both a traditional distance based permutational multivariate analysis of variance (PERMANOVA) and MGLMs to a case study of striped snakehead (Channa striata) in India. We also introduce the Tweedie and gamma distributions as suitable error structures for the MGLMs, drawing similarities to the properties of Biomass data. We demonstrate that otolith elemental data and combined otolith elemental and shape data violate the assumption of homogeneity of variance of PERMANOVA and may give misleading results, while the assumptions of the MGLM with Tweedie and gamma distributions are shown to be satisfied and are appropriate for both otolith shape and elemental composition data. Consistent differences between three groups of C. striata were identified using otolith shape, otolith chemistry and a combined otolith shape and chemistry dataset. This suggests that future research should be conducted into whether there are demographic differences between these groups which may influence management considerations. The MGLM method is widely applicable and could be applied to any multivariate otolith shape or elemental composition dataset. [ABSTRACT FROM AUTHOR]

Cadmium (Cd) exposure to the animals including humans is reported as nephrotoxic compounds i.e. , disturbing redox status (increase oxidative stress), mitochondrial dysfunction, renal cell death and altered transporters in the renal system. Hsp27 (a small heat shock protein) has been shown as one of the modulators in the renal dysfunction and increased against the Cd induced toxicity. However, no studies are reported on the genetic modulation of stress protein against the Cd-induced nephrotoxicity. The current study aimed to examine the protective role of hsp27 overexpression against the Cd-induced nephrotoxicity using Drosophila melanogaster as an animal model. D. melanogaster renal system includes nephrocytes and Malpighian tubules (MTs) that show the functional similarity with mammalian kidney nephron. Overexpression of the hsp27 was found to reduce the Cd induced oxidative stress, rescue cell death in MTs of Cd exposed D. melanogaster larvae. The rescued GSH level, NADPH level and glucose 6 phosphate dehydrogenase (G6PD) activity were also observed in the MTs of the Cd exposed organism. Function (efflux activity and fluid secretion rate) of the MTs was restored in Cd exposed hsp27 overexpressed larvae. Further, results were confirmed by restored brush border microvilli density and reduced uric acid level. Tissue specific knockdown of hsp27 developed Cd like phenotypes in MTs and the phenotypes enhanced in Cd exposed condition. The present study clearly shows the role of hsp27 overexpression in restoration of the MTs function and protection against the Cd induced renal toxicity. [Display omitted] • This study first time report nephroprotective role of hsp27 in Cd induce renal toxicity in MTs of the D. melanogaster larvae. • This study first time report nephroprotective role of hsp27 in Cd induce renal toxicity in MTs of the D. melanogaster larvae. • hsp27 overexpression restores MMP, ATP level and microvilli brush border density in MTs of Cd exposed D. melanogaster larvae. • hsp27 knockdown negatively alter MTs functions in D. melanogaster larvae and more severely affect after the Cd exposure. [ABSTRACT FROM AUTHOR]

The increased incidence of diabetes to the magnitude of a global epidemic is attributed to non-traditional risk factors, including exposure to environmental chemicals. However, the contribution of xenobiotic exposure during the development of an organism to the etiology of diabetes is not fully addressed. Developing stages are more susceptible to chemical insult, but knowledge on the consequence of the same to the onset of diabetes is residual. In this context, by using Drosophila melanogaster having conserved Insulin/Insulin growth factor-like signaling (IIS) as well as glucose homeostasis as a model, we evaluated the potential of developmental exposure to dichlorvos (DDVP, an organophosphorus pesticide) or atrazine (herbicide) to cause diabetes in exposed organisms. Flies exposed to DDVP during their development display insulin deficiency or type 1 diabetes (T1D) while those exposed to atrazine show insulin resistance or type 2 diabetes (T2D), suggesting that exposure to these xenobiotics during organismal development can result in diabetes and that different mechanisms underlie pesticide mediated diabetes. We show that oxidative stress-mediated c-Jun N-terminal kinase (JNK) signaling activation underlies insulin resistance in flies exposed to atrazine during their development while DDVP-mediated T1D involves activation of caspase-mediated cell death pathway. Mitigation of oxidative stress through over-expression of SOD2 in atrazine (20μg/ml) exposed flies, revealed significantly decreased oxidative stress levels and reduced phosphorylation of JNK. Moreover, glucose and Akt phosphorylation levels in SOD2 over-expression flies exposed to atrazine were comparable to those in controls, suggesting restoration in insulin sensitivity. Therefore, exposure to xenobiotics during development is a common risk factor for the development of type 1 or type 2 diabetes. Accordingly, the present study cautions against the use of such diabetogenic pesticides. Also, mitigation of oxidative stress or anti-oxidant supplementation could be a potential therapy for xenobiotic mediated type 2 diabetes. Image 1 • Dichlorvos exposure during development leads to type 1 diabetes in Drosophila. • Activation of cell death pathway underlies DDVP mediated Type 1 diabetes. • Atrazine exposure during development causes type 2 diabetes in Drosophila. • Elevated oxidative stress along with insulin resistance in Atrazine exposed flies. • Oxidative stress alleviation in Atrazine exposed flies restores glucose homeostasis. [ABSTRACT FROM AUTHOR]

ABSTRACT Background To study the association between kidney injury biomarkers and urinary OH-PAH metabolites in kitchen workers, with microalbuminuria. Methods A cross-sectional pilot study was conducted among 120 male kitchen workers in a mega kitchen located at Coimbatore, India. Personal and sub-clinical details of study subjects were collected using a questionnaire. Albumin, creatinine, and albumin-creatinine ratio (ACR) were measured using urine dipstick test for the determination of microalbuminuria. Urinary hydroxylated PAHs metabolites (1-NAP, 9-HF, 3-HF, 2-HF, 9-PHN, and 1-OHP) were measured using GC–MS/MS and urinary kidney biomarkers (uNGAL, uCyst-C, uKIM-1, uOPN, and uTIMP-1) were measured using Multiplex Reader. Results Concentrations of urinary PAHs metabolites (1-NAP, 3-HF, 2-HF, 9-PHN, and 1-OHP) and kidney biomarkers (uKIM-1, uTIMP-1, uCyst-C and uNGAL) were significantly higher among kitchen workers with MAU compared to non-kitchen workers with MAU. Urinary kidney biomarkers viz., uKIM-1, uTIMP-1, uCyst-C, uNGAL, and uOPN showed higher median concentration among the kitchen workers with MAU compared to kitchen workers without MAU. Significant positive correlation was observed for 9-HF with uKIM-1 and uTIMP-1 and 1-OHP with uKIM-1. ACR was also well correlated with urinary kidney biomarkers. ROC analysis showed higher sensitivity and specificity for uKIM-1, uCyst-C, and uNGAL as biomarkers for early prediction of acute kidney injury among kitchen workers. Conclusions The PAHs exposure among kitchen workers can lead to kidney injury. This was evident from the association of OH-PAHs and kidney injury biomarkers in kitchen workers with microalbuminuria. Highlights • Prevalence of microalbuminuria was reported as a health problem among kitchen workers due to exposure of indoor air pollutants including PAHs at work place. • PAHs exposure (urinary PAHs metabolites) among kitchen workers can cause alterations in kidney injury profiles especially among workers with microalbuminuria. • Kidney biomarkers like uKIM-1, uCyst-C, and uNGAL along with routine kidney function tests including ACR may be included in the periodical occupational health assessment of kitchen workers, based on the study findings. [ABSTRACT FROM AUTHOR]

β-triketone herbicides have been efficiently employed as an alternate to atrazine. Triketones are 4-hydroxyphenylpyruvate dioxygenase (HPPD) enzyme inhibitors and exposure is reported to cause significant increase in plasma tyrosine levels. In this study, we have employed a non-target organism Caenorhabditis elegans to determine the impact of β-triketone exposures at recommended field doses (RfD). Our results indicate sulcotrione and mesotrione, negatively influence the survival, behavior, and reproduction of the organism at RfD. Additionally, we have traced the parallels regarding the impact of triketones on the tyrosine metabolism pathway, in C. elegans to those in mammalian models, wherein the expression of the tyrosine metabolism pathway genes are altered, directly influencing tyrosine catabolism leading to significant tyrosine accumulation in exposed organism. Further, we investigated the impact of sulcotrione and mesotrione exposure on fat deposition (triglyceride levels, Oil-Red-O staining and lipidomics) and the fatty acid metabolism pathway. In the exposed worms, the expression of enlongases and fatty acid desaturases were up-regulated along with an increase in the levels of triglycerides. Thus, the data indicates a positive association of β-triketone exposure to mis-regulation of the fatty acid metabolism pathway genes leading to fat accumulation in worms. Therefore, β-triketone might be a potential obesogen. [Display omitted] • β-triketone significantly impacts behavior, and reproduction in C. elegans. • β-triketone exposure causes tyrosine and triglyceride accumulation in C. elegans. • Up-regulation of desaturases and elongases leads to fat deposition in exposed worms. [ABSTRACT FROM AUTHOR]

Abstract: The presence of pesticides in food items and beverages is a big threat to humankind, and their quantitative estimation with high precision and accuracy is always a challenge for analytical chemists. Hence, a simple and rapid method is proposed for the simultaneous determination of 30 pesticides in beverages (alcoholic and non‐alcoholic drinks). The proposed method hyphenated with triple quadrupole liquid chromatography mass spectrometry has only 2 min chromatographic runtime for the analysis of all the pesticides. All the factors affecting the extraction yield have been optimized using an experimental design; and under optimized conditions, the developed method has been validated. The detection limits for all the pesticides were in the range of 0.001–0.348 μg/L with good linearity in the concentration range of 0.01–80.0 μg/L. The coefficient of determination was in the range of (R2) ≥ 0.977 to 0.999 for all the pesticides. The method was also checked for the precision of the relative standard deviation, which was below 4.75 (intra‐day) and 8.96% (inter‐day). The recovery of the method was 92–138%. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is the second most familiar, progressive and movement-related neurodegenerative disorder after Alzheimer disease. This study aimed to decipher the role of autophagy in cypermethrin-induced Parkinsonism, an animal model of PD. Indicators of autophagy [expression of beclin 1, autophagy-related protein 12 (Atg 12), unc-51 like autophagy activating kinase 1 (Ulk 1), p62 and lysosome-associated membrane protein 2 (LAMP 2) and conversion of microtubule-associated protein 1A/1B-light chain 3 (LC3) I to II], signalling cascade [phosphorylated (p) 5′ adenosine monophosphate-activated protein kinase (p-AMPK), sirtuin 1 (Sirt 1), phosphorylated-mammalian target of rapamycin (p-mTOR), tuberous sclerosis complex 2 (TSC 2), pUlk 1 and pUlk 1 levels] and lysosome morphology were assessed in control and cypermethrin-treated rat model of PD. Autophagy markers were also measured in cypermethrin-treated neuroblastoma cells in the presence of 3-methyl adenine, a phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) class III inhibitor; vinblastine, an autophagosome elongation inhibitor; bafilomycin A1, an autophagolysosome and lysosome fusion/abnormal acidification inhibitor or torin 1, a mechanistic target of rapamycin inhibitor. Cypermethrin reduced LAMP 2 and increased p-AMPK and Sirt 1 without causing any change in other signalling proteins. 3-Methyl adenine did not change LC3 conversion; vinblastine and bafilomycin A1 decreased LAMP 2 expression in controls. While cypermethrin increased LC3 conversion in the presence of 3-methyl adenine, LAMP 2 reduction was more pronounced in vinblastine and bafilomycin A1-treated cells. Torin 1 normalized the expression of LAMP 2 without any change in other autophagy markers. Results demonstrate that albeit cypermethrin activates autophagosome formation, it reduces LAMP 2 expression and lysosome quality leading to autophagy inhibition. [ABSTRACT FROM AUTHOR]

Turbulent characteristics of flow fields due to the interaction of two plane parallel jets separated by the jet width distance are studied. Numerical simulation is carried out by large eddy simulation with a dynamic Smagorinsky model for the sub-grid scale stresses. The energy spectra are observed to follow the -5/3 power law for the inertial sub-range. A proper orthogonal decomposition study indicates that the energy carrying large coherent structures is present close to the nozzle exit. It is shown that these coherent structures interact with each other and finally disintegrate into smaller vortices further downstream. The turbulent fluctuations in the longitudinal and lateral directions are shown to follow a similarity. The mean flow at the same time also maintains a close similarity. Prandtl's mixing length, the Taylor microscale, and the Kolmogorov length scales are shown along the lateral direction for different downstream locations. The autocorrelation in the longitudinal and transverse directions is seen to follow a similarity profile. By plotting the probability density function, the skewness and the flatness (kurtosis) are analyzed. The Reynolds stress anisotropy tensor is calculated, and the anisotropy invariant map known as Lumley's triangle is presented and analyzed. [ABSTRACT FROM AUTHOR]

A detailed study of a three-dimensional spatially developing planar turbulent jet has been carried out by large eddy simulation (LES). The jet Reynolds number is 4000 based on the inlet velocity and jet width. The dynamic Smagorinsky model (DSM) is used to resolve the subgrid scale stress tensor. The transition from laminar to turbulent flow has been numerically identified and discussed in details. The evolution of vortex roll ups, their transportation and final disintegration to smaller vortices have been visualized by the plot of isosurface of Q criterion. The coherent structures in a turbulent planar jet have been well demonstrated. The time series plots of λ 2 criterion shows the swirl and shear nature of the evolving vortices and their passage in the downstream. The time averaged velocity at far downstream ( x D = 10 and 15) shows a self-similarity behavior where the flow has established a fully turbulent nature. The energy spectra are shown to exhibit the −5/3 power law. The proper orthogonal decomposition (POD) shows that 90% of the fluctuating kinetic energy is contained within the first 100 modes. The probability density function on the centerline ( y D = 15 and z D = 2.5 ) for different x D locations are plotted and the corresponding skewness and kurtosis values are reported for u ̄ , v ̄ , w ̄ and p ̄ . [ABSTRACT FROM AUTHOR]

Antibiotics that are used excessively and disposed of improperly are categorized as emerging pollutants. The determination of micropollutants in water with an accurate and precise method is always a big challenge. Hence, a simple, rapid, sensitive, economical and almost eco-friendly method is proposed for the quantitative determination of 19 antibiotics. The proposed method, ultrasound-assisted emulsification microextraction and solidified floating organic droplet coupled with liquid chromatography and triple quadrupole mass spectrometry, has only a 3 min chromatographic run time for the determination of the 19 antibiotics. We report for the first time the use of the developed method for the quantitative determination of the antibiotics in waste water samples with better results in terms of higher sensitivity, cost-effectiveness, better detection limits and a greener approach compared to the earlier reported methods. The limits of detection and quantification were in the range of 0.003-0.236 and 0.013-0.834 μg/L, respectively, with good linearity in the concentration range of 0.01-64.0 μg/L. The correlation coefficient was ≥0.987-0.99 for each analyte. The developed method has been successfully applied for the determination of antibiotics in water samples. [ABSTRACT FROM AUTHOR]

In the present study, effect of exposure of bisphenol A (BPA) and combined exposure of BPA + HSD has been investigated on the glucose homeostasis and associated renal complications in Drosophila. Exposure of 1.0 mM BPA alone induced type 2 diabetes like condition (T2D) in adult male D. melanogaster via oxidative stress. Elevated TGF-β signaling was evident by increased expression of baboon (babo) in BPA exposed organism that stimulated the modulation of extracellular matrix (ECM) component collagen IV resulting in the fibrosis of the Malpighian tubules (MTs). Combined exposure of BPA + HSD (high sucrose diet) resulted in the increased magnitude of T2D and MTs dysfunction parameters. Taken together, the study illustrates that BPA has diabetogenic potential in exposed Drosophila that caused adverse effects on their MTs and combined exposure with BPA and HSD could aggravate the renal tubular dysfunction. The study further suggests the use of Drosophila model to study the environmental chemicals induced diabetes mediated renal dysfunction. [Display omitted] • Bisphenol A (BPA) induces type 2 diabetes (T2D) like condition in Drosophila. • BPA induced oxidative stress results in fibrosis of Malpighian tubules (MTs). • Fibrosis in the MTs results in the structural deformities in them. • Structural deformities result in reduced function of MTs and shortened life span of Drosophila. • BPA + high sucrose diet (HSD) further increased the magnitude of T2D and MTs dysfunction parameters. [ABSTRACT FROM AUTHOR]

Adverse reports on the exposure of organisms to dichlorvos (DDVP; an organophosphate insecticide) necessitate studies of organismal resistance/tolerance by way of pharmacological or genetic means. In the context of genetic modulation, a mutation in methuselah ( mth; encodes a class II G-protein-coupled receptor (GPCR)) is reported to extend (~35%) the life span of Drosophila melanogaster and enhance their resistance to oxidative stress induced by paraquat exposure (short term, high level). A lack of studies on organismal tolerance of DDVP by genetic modulation prompted us to examine the protective efficacy of mth mutation in exposed Drosophila. Flies were exposed to 1.5 and 15.0 ng/ml DDVP for 12–48 h to examine oxidative stress endpoints and chemical resistance. After prolonged exposure of flies to DDVP, antioxidant enzyme activities, oxidative stress, glutathione content, and locomotor performance were assayed at various days (0, 10, 20, 30, 40, 50) of age. Flies with the mth mutation ( mth 1 ) showed improved chemical resistance and rescued redox impairment after acute DDVP exposure. Exposed mth 1 flies exhibited improved life span along with enhanced antioxidant enzyme activities and rescued oxidative perturbations and locomotor insufficiency up to middle age (~20 days) over similarly exposed w 1118 flies. However, at late (≥30 days) age, these benefits were undermined. Further, similarly exposed mth- knockdown flies showed effects similar to those observed in mth 1 flies. This study provides evidence of tolerance in organisms carrying a mth mutation against prolonged DDVP exposure and further warrants examination of similar class II GPCR signaling facets toward better organismal health. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is one of the most common neurodegenerative disorders with limited clinical interventions. A number of epidemiological as well as case-control studies have revealed an association between pesticide exposure, especially of paraquat (PQ) and occurrence of PD. Hsp70, a molecular chaperone by function, has been shown as one of the modulators of neurological disorders. However, paucity of information regarding the protective role of Hsp70 on PQ-induced PD like symptoms led us to hypothesize that modulation of hsp70 expression in the dopaminergic neurons would improve the health of these cells. We took advantage of Drosophila, which is a well-established model for neurological research and also possesses genetic tools for easy manipulation of gene expression with limited ethical concern. Over-expression of hsp70 was found to reduce PQ-induced oxidative stress along with JNK and caspase-3 mediated dopaminergic neuronal cell death in exposed organism. Further, anti-apoptotic effect of hsp70 was shown to confer better homeostasis in the dopaminergic neurons of PQ-exposed organism as evidenced by their improved locomotor performance and survival. The study has merit in the context of human concern since we observed protection of dopaminergic neurons in PQ-exposed organism by over-expressing a human homologue of hsp70, HSPA1L, in these cells. The effect was parallel to that observed with Drosophila hsp70. These findings reflect the potential therapeutic applicability of hsp70 against PQ-induced PD like symptoms in an organism. [ABSTRACT FROM AUTHOR]

[Display omitted] • Pesticides and phthalates analysis in breakfast cereal samples. • QuEChERS protocol coupled to GC–MS/MS. • Method validation with uncertainty determination. • Identification of compounds involved in flavored and unflavored cereals using multivariate approach. • Increased concentration of pesticides in flavored cereals. Pesticides and phthalates are toxic chemical compounds which could be present in our food items through their different usage. Some of these toxic analytes are present in traces and always a challenge to quantify for analytical chemist especially from complex food matrices. A simple, sensitive, fast and robust QuEChERS based method was developed, optimized and validated. The method showed good linearity in the range of 0.30–50.00 ng g−1 with (r2) ≥ 0.9855. The quantification limit was in the range of 0.0983–0.8934 ng g−1 with recovery and precision in the range of 71.1–112.5% and RSD < 7.9% for all the analytes. The combined and expanded uncertainty was also determined showing strong analytical significance of the method with negligible matrix interferences. The developed method was successfully used for the analysis of 12 packaged cereal samples (flavoured = 7 & unflavoured = 5). Partial least square discrimination analysis (PLS–DA) of Multivariate approach was used to find differences in profile of pesticides and phthalates between the flavoured and unflavoured cereal samples. We obtained three pesticides (S-BioAllethrin, Dieldrin, Chlorfenapyr) as most important discriminatory compounds for the two groups after comparing fold change (FC) and variable importance in projection (VIP) analysis. Univariate analysis of 8 pesticides obtained from FC analysis showed increased concentration in flavoured group than the unflavoured cereals. The proposed work will be of immense use for routine analysis of these toxic compounds to deal with food fraud and uncover associated risk to the consumer. [ABSTRACT FROM AUTHOR]

Abstract: A strong association between polymorphisms of the cytochrome P450 (CYP/Cyp) 2D6 gene and risk to Parkinson''s disease (PD) is well established. The present study investigated the neuroprotective potential of Cyp2d22, a mouse ortholog of human CYP2D6, in maneb- and paraquat-induced parkinsonism and the mechanisms involved therein along with the effects of resveratrol on various parameters associated with Cyp2d22-mediated neuroprotection. The animals were treated intraperitoneally with resveratrol (10mg/kg, daily) and paraquat (10mg/kg) alone or in combination with maneb (30mg/kg), twice a week, for 9weeks, along with their respective controls. The subsets of animals were also treated intraperitoneally with a Cyp2d22 inhibitor, ketoconazole (100mg/kg, daily). Maneb and paraquat reduced Cyp2d22 and vesicular monoamine transporter type 2 (VMAT-2) expressions, the number of tyrosine hydroxylase-positive cells, and dopamine content and increased paraquat accumulation in the nigrostriatal tissues, oxidative stress, microglial activation, neuroinflammation, and apoptosis. Cyp2d22 inhibitor significantly exacerbated all these neurodegenerative indexes. Resveratrol cotreatment, partially but significantly, ameliorated the neurodegenerative changes by altering Cyp2d22 expression and paraquat accumulation. The results obtained in the study demonstrate that Cyp2d22 offers neuroprotection in maneb- and paraquat-induced dopaminergic neurodegeneration and resveratrol enhances its neuroprotective credentials by influencing Cyp2d22 expression and paraquat accumulation. [Copyright &y& Elsevier]

Abstract: An association between excessive zinc (Zn) accumulation in brain and incidences of Parkinson''s disease (PD) has been shown in several epidemiological and experimental investigations. The involvement of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and glutathione (GSH) in the pathogenesis of PD has also been proposed in a few studies. Despite the implicated role of oxidative stress in PD, the entire mechanism of Zn-induced dopaminergic neurodegeneration has not yet been clearly understood. The present study aimed to investigate the involvement of NADPH oxidase and GSH in Zn-induced dopaminergic neurodegeneration and also to assess its similarity with paraquat (PQ)-induced rat model of PD. Male Wistar rats were treated either with Zn (20mg/kg; i.p.) or PQ (5mg/kg; i.p.) in the presence and absence of NADPH oxidase inhibitor, apocynin (10mg/kg; i.p.) and a GSH precursor, N-acetyl cysteine (NAC; 200mg/kg; i.p.) either alone or in combination along with the respective controls. Apocynin and/or NAC pre-treatment significantly alleviated Zn- and PQ-induced changes in neurobehavioral deficits, number of dopaminergic neurons and contents of the striatal dopamine and its metabolites. Apocynin and/or NAC also mitigated Zn- and PQ-induced alterations in oxidative stress, NADPH oxidase activation and cytochrome c release, caspases-9 and -3 activation and CD11b expression. The results obtained thus suggest that Zn induces oxidative stress via the activation of NADPH oxidase and depletion of GSH, which in turn activate the apoptotic machinery leading to dopaminergic neurodegeneration similar to PQ. [Copyright &y& Elsevier]

Abstract: The study aimed to investigate the effects of cypermethrin on biochemical, histopathological, and motor behavioral indices of the nigrostriatal dopaminergic system in adult rats treated with or without cypermethrin (1/10 adult dose) during postnatal days 5–19. Spontaneous locomotor activity (SLA) and rotarod tests were performed to assess motor behavior. Levels of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the striatum, and tyrosine hydroxylase (TH) immunoreactivity and 4′,6-diamidino-2-phenylindole (DAPI)/Fluoro-Jade B staining in the substantia nigra were measured to assess dopaminergic neurodegeneration. Postnatal treated animals did not exhibit significant changes in any measured parameters. The significant reduction in the time of stay on rotarod, spontaneous locomotor activity, dopamine, 3,4-dihydroxyphenylacetic acid, and tyrosine hydroxylase immunoreactivity while an increase in homovanillic acid level and Fluoro-Jade B-positive cells were observed in cypermethrin treated adult rats. These changes were more pronounced in the animals treated with cypermethrin during postnatal days followed by adulthood compared with adulthood alone. The results obtained thus demonstrate that exposure to cypermethrin during adulthood induces dopaminergic neurodegeneration in rats and postnatal exposure enhances the susceptibility of animals to dopaminergic neurodegeneration if rechallenged during adulthood. [Copyright &y& Elsevier]

The study was undertaken to investigate the effect of zinc (Zn) on glutathione S-transferase (GST) and superoxide dismutases (SOD) activities and on the expressions of cytosolic Cu, Zn-SOD (SOD1), mitochondrial Mn-SOD (SOD2), γ-glutamyl cysteine synthetase (γ-GCS) and heme oxygenase-1 (HO-1) in the nigrostriatal tissue of rats. Additionally, Zn-induced alterations in the neurobehavioral parameters, lipid peroxidation (LPO), striatal dopamine and its metabolites and tyrosine hydroxylase (TH) protein expression were measured to assess their correlations with the oxidative stress. Zn exposure reduced the locomotor activity, rotarod performance, striatal dopamine and its metabolites and TH protein expression. LPO, total SOD, SOD1 and SOD2 activities were increased while GST and catalase were reduced in a dose and time dependent manner. Expressions of SOD1 and HO-1 were increased while no change was observed in SOD2 and γ-GCS expressions. The results obtained suggest that Zn-induced augmentation of total SOD, SOD1, SOD2 and HO-1 was associated with increased oxidative stress and neurodegenerative indexes indicating the involvement of both cytosolic and mitochondrial machinery in Zn-induced oxidative stress leading to dopaminergic neurodegeneration. [ABSTRACT FROM AUTHOR]

The study aimed to identify the differentially expressed nigrostriatal proteins in cypermethrin-induced neurodegeneration and to investigate the role of microglial activation therein. Proteomic approaches were used to identify the differentially expressed proteins. Microglial activation, tyrosine hydroxylase immunoreactivity (TH-IR), dopamine content, and neurobehavioral changes were measured according to the standard procedures. The expressions of α-internexin intermediate filament (α-IIF), ATP synthase D chain (ATP-SD), heat shock protein (Hsp)-70, truncated connexin-47, Hsp-60, mitogen-activated protein kinase-activated kinase-5, nicotinamide adenine dinucleotide dehydrogenase 24k chain precursor, platelet-activating factor acetyl hydrolase 1b-α2 (PAF-AH 1b-α2), and synaptosomal-associated protein-25 (SNAP-25) were altered in the substantia nigra and nicotinamide adenine dinucleotide- specific isocitrate dehydrogenase, phosphatidylethanolamine-binding protein-1, prohibitin, protein disulfide isomerase-endoplasmic reticulum 60 protease, stathmin, and ubiquitin-conjugating enzyme in the striatum along with motor impairment, decreased dopamine and TH-IR, and increased microglial activation after cypermethrin exposure. Minocycline restored α-IIF, ATP-SD chain, truncated connexin-47, Hsp-60, PAF-AH 1b-α2, stathmin and SNAP-25 expressions, motor impairment, dopamine, TH-IR, and microglial activation. The results suggest that cypermethrin produces microglial activation-dependent and -independent changes in the expression patterns of the nigrostriatal proteins leading to dopaminergic neurodegeneration. [ABSTRACT FROM AUTHOR]

Abstract: In this in vitro study we investigated the toxic responses in hepatocytes treated with occupational dust to which workers are exposed in bone-based industrial units. The present study investigated the toxicity mechanism of bone-based occupational dust, from a particular industrial unit, on isolated rat hepatocytes. The hepatocytes were isolated by collagenase perfusion method and cell viability was determined by trypan blue exclusion and MTT [3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide] assay treated with occupational dust at 0.1–1.0mgmL−1, for 120min. The cell viability decreased significantly in a concentration-dependent manner. Dust induced significant membrane damage measured by lactate dehydrogenase (LDH) and glutathione (GSH) release in culture media for 30-, 60- and 120min treatment duration. The toxicity was found to be correlated with the induction of lipid peroxidation (LPO). In addition, nitric oxide (NO), and hydrogen peroxide (H2O2) generation by occupational dusts were also found to be time- and concentration-dependent. Over all the present study provides initial evidences for the toxic potential of occupational dust generated in bone-based industries and, therefore, the dust exposure to workers in unorganized industrial units should be controlled. [Copyright &y& Elsevier]

In this study, nerve conduction, organochlorine (OC) pesticide residues in blood and cholinesterase activity levels of pesticide sprayers employed in mango plantations at Lucknow, North India, were determined. Fifty-two sprayers from mango plantations who regularly spray mixture of pesticides like organophosphates (OP), OCs, and carbamates were considered as exposed group. Eighteen subjects with similar socio-economic status of exposed group, who do not handle pesticides, were selected as controls. Questionnaire-based interviews related to personal and occupational histories of the study subjects were carried out. Sprayers did not use any personal protective equipment during pesticide handling. The blood-pesticide analyses of sprayers show higher mean values of hexachlorohexane (HCH), γ-HCH, δ-HCH, total HCH, op-DDT compared with the controls. Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activites were significantly reduced among sprayers. Risk of motor nerve conduction deficits was observed in sprayers with low AChE activity. Negative correlation of motor and sensory nerve conduction deficits was observed with the duration of exposure and age among sprayers. The study demonstrated that the prolonged exposure to mixture of pesticides, ergonomic factors, decline in cholinesterase activity may lead to nerve conduction dysfunction. The findings suggest the need for controlled use of pesticides in the plantation and indicated the need for training and implementation of hygiene practices like proper usage of personal protective equipments. [ABSTRACT FROM AUTHOR]

Abstract: Experimental studies have shown that toxicant responsive genes, cytochrome P450s (CYPs) and glutathione S-transferases (GSTs) play a critical role in pesticide-induced toxicity. CYPs play pro-oxidant role and GSTs offer protection in maneb (MB) and paraquat (PQ)-induced brain and lung toxicities. The present study aimed to investigate the effect of repeated exposures of MB and/or PQ on lipid peroxidation (LPO), glutathione content (GSH) and toxicant responsive genes, i.e., CYP1A1, 1A2, 2E1, GSTA4-4, GSTA1-1 and GSTA3-3 in the liver and to correlate the same with polymorphonuclear leukocytes (PMNs). A significant augmentation in LPO and reduction in GSH content was observed in a time of exposure dependent manner in the liver and PMNs of MB and/or PQ treated animals. The expression and catalytic activity of CYP2E1 and GSTA4-4 were significantly increased following MB and/or PQ exposure both in the liver and PMNs. Although the expression of GSTA3-3 was increased, the expression of GSTA1-1 was unaltered after MB and/or PQ treatment in both the liver and PMNs. MB augmented the expression and catalytic activity of CYP1A1 in the liver, however, CYP1A2 was unaffected. PQ, on the other hand, significantly increased hepatic CYP1A2 expression and catalytic activity. MB and/or PQ did not produce any significant changes in CYP1A1 and CYP1A2 in PMNs. The results of the study thus demonstrate that MB and PQ differentially regulate hepatic CYP1A1 and CYP1A2 while LPO, GSH, CYP2E1, GSTA4-4 and GSTA3-3 are modulated in the similar fashions both in the liver and PMNs. [Copyright &y& Elsevier]

Long-term exposure to cypermethrin induces the nigrostriatal dopaminergic neurodegeneration in adult rats and its pre-exposure in the critical periods of brain development enhances the susceptibility during adulthood. Monoamine transporters, xenobiotic metabolizing enzymes and oxidative stress play critical roles in the nigrostriatal dopaminergic neurodegeneration. The study was undertaken to investigate the effects of cypermethrin on DAT, VMAT 2, CYP2E1, GST Ya, GST Yc and GSTA4-4 expressions, CYP2E1 and GST activities and lipid peroxidation in the nigrostriatal system of adult rats with/without post-natal exposure to cypermethrin. Cypermethrin reduced VMAT 2 and increased CYP2E1 expressions without causing significant change in DAT. Although GSTA4-4 mRNA expression and lipid peroxidation were increased, no significant changes were observed in GST Ya and GST Yc expressions and total GST activity. The results obtained demonstrate that long-term exposure to cypermethrin modulates VMAT 2, CYP2E1, GSTA4-4 expressions and lipid peroxidation, which could contribute to the nigrostriatal dopaminergic neurodegeneration. [ABSTRACT FROM AUTHOR]

The aim of this study was to examine the hematological and cholinesterase (ChE) activity levels of pesticide sprayers employed in mango plantations at Lucknow. Fifty-two sprayers from mango plantations who regularly spray mixtures of pesticides including organochlorines (OC), organophosphates (OP), and carbamates were included as exposed group. Twenty residents living close to mango plantations, but not involved in pesticide spraying were taken as controls. Pesticide residues for OC were analyzed in blood by gas chromatography with electron capture detector. There was a significant decrease in acetylcholinesterase and butyrylcholinesterase activities in pesticide sprayers (n = 52) relative to the control group (n = 20). A significant difference in the frequency distribution of hematological variations in red blood cell, white blood cell, monocytes, neutrophils, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, and platelet count was observed. Residues of OC pesticides including α-hexachlorocyclohexane (HCH) and total HCH were found to be significantly higher in the blood of sprayers compared to controls. Hematological variations were quantitatively more frequent among the sprayers with 5 years of pesticide exposure compared to the controls and to subjects with less than 5 years of exposure group. Hematological abnormalities in sprayers were correlated with pesticide exposure as evidenced by lower ChE activity as well as the presence of OC pesticides in blood. The poorly controlled use of pesticides in the plantation appeared to have produced sub-clinical intoxication in the sprayers and indicated the need for training and implementation of proper, safer hygiene practices. [ABSTRACT FROM AUTHOR]

Oxidative stress is implicated in Parkinson's disease (PD). Metallothioneins (MT), cytochrome P450 IIE1 (CYP2E1) and glutathione S-transferases alpha4-4 (GSTA4-4) are involved in oxidative stress-mediated damage. Altered dopamine transporter (DAT) and vesicular monoamine transporter-2 (VMAT-2) are also documented in PD. The present study was undertaken to investigate the effect of Zn and PQ co-exposure on neurodegeneration in rats. A significant reduction was observed in spontaneous locomotor activity (SLA), striatal dopamine (DA) levels, tyrosine hydroxylase (TH) immunoreactivity, glutathione reductase (GR) and catalase activity along with increased lipid peroxidation (LPO) and glutathione peroxidase (GPx) activity after Zn and/or PQ exposure. Zn and/or PQ exposure increased gene expression of DAT, CYP2E1, GSTA4-4, MT-I and MT-II, but reduced the expression of VMAT-2. Protein expression analysis of TH, VMAT-2 and DAT showed results similar to those obtained with gene expression study. Zn and PQ co-exposure caused a more pronounced effect than that of individual exposure. The results obtained in this study suggest that, similar to PQ, Zn induced neurodegeneration via alterations in oxidative stress and expression of the above-mentioned genes. However, the effect of Zn+PQ was only slightly higher than that of alone, indicating that probably Zn and PQ follow some different molecular events leading to neurodegeneration. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS), a progressive disorder that usually runs a fatal course within 2-5 years of onset, is characterized by loss of motor neurons in the cortex, brain stem, and spinal cord. In this study mercury (Hg) concentrations were determined in blood samples of 40 ALS patients, of whom 24 ALS patients were from the Ganga plain region and their metal levels were found to be significantly higher. In contrast, Hg levels in the 16 ALS patients from non-Ganga plain regions whose levels were similar to those of the control subjects. Mercury in stream water samples and freshly deposited stream sediment were determined in the locations of patients' native residences along the Ganga plain region and metal levels were found to be higher than the threshold guideline values for Hg in stream waters recommended by WHO. The geo-accumulation index in selected sites of freshly deposited stream sediment ranged from moderate to highly polluted. The high levels of Hg observed in ALS patients may potentially alter the redox status of neuronal cell components and induce cell-death pathways. [ABSTRACT FROM AUTHOR]

Abstract: Parkinson''s disease (PD) is a progressive neurodegenerative disorder, characterized by the selective loss of dopaminergic neurons of the nigrostriatal pathway. Epidemiological studies have shown an inverse relationship between coffee consumption and susceptibility to PD. Cytochrome P450 1A2 (CYP1A2) is involved in caffeine metabolism and its clearance. Caffeine, on the other hand, antagonizes adenosine A2A receptor and regulates dopamine signaling through dopamine transporter (DAT). The present study was undertaken to investigate the expression of CYP1A2, adenosine A2A receptor and DAT in mouse striatum and to assess their levels in 1-methyl 4-phenyl 1, 2, 3, 6-tetrahydropryridine (MPTP) treated mouse striatum with and without caffeine treatment. The animals were treated intraperitoneally daily with caffeine (20 mg/kg) for 8 weeks, followed by MPTP (20 mg/kg)+caffeine (20 mg/kg) for 4 weeks or vice versa, along with respective controls. Tyrosine hydroxylase immunoreactivity, levels of dopamine and 1-methyl 4-phenylpyridinium ion (MPP+), expressions of CYP1A2, adenosine A2A receptor and DAT and CYP1A2 catalytic activity were measured in control and treated mouse brain. Caffeine partially protected MPTP-induced neurodegenerative changes and modulated MPTP-mediated alterations in the expression and catalytic activity of CYP1A2, expression of adenosine A2A receptor and DAT. The results demonstrate that caffeine alters the striatal CYP1A2, adenosine A2A receptor and DAT expressions in mice exposed to MPTP. [Copyright &y& Elsevier]