Genetic Variation/Evolution and Differential Host Responses Resulting from In-Patient Adaptation of Mycobacterium avium.

Members of the Mycobacterium avium complex (MAC) are characterized as nontuberculosis mycobacteria and are pathogenic mainly in immunocompromised individuals. MAC strains show a wide genetic variability, and there is growing evidence suggesting that genetic differences may contribute to a varied immune response that may impact the infection outcome. The current study aimed to characterize the genomic changes within M.avium isolates collected from single patients over time and test the host immune responses to these clinical isolates. Pulsed-field gel electrophoresis and whole-genome sequencing were performed on 40 MAC isolates isolated from 15 patients at the Department of Medical Microbiology at St. Olavs Hospital in Trondheim, Norway. Isolates from patients (patients 4, 9, and 13) for whom more than two isolates were available were selected for further analysis. These isolates exhibited extensive sequence variation in the form of single-nucleotide polymorphisms (SNPs), suggesting that M. avium accumulates mutations at higher rates during persistent infections than other mycobacteria. Infection of murine macrophages and mice with sequential isolates from patients showed a tendency toward increased persistence and the downregulation of inflammatory cytokines by host-adapted M. avium strains. The study revealed the rapid genetic evolution of M. avium in chronically infected patients, accompanied by changes in the virulence properties of the sequential mycobacterial isolates.

An integrated modeling approach for estimating the water quality benefits of conservation practices at the river basin scale.

The USDA initiated the Conservation Effects Assessment Project (CEAP) to quantify the environmental benefits of conservation practices at regional and national scales. For this assessment, a sampling and modeling approach is used. This paper provides a technical overview of the modeling approach used in CEAP cropland assessment to estimate the off-site water quality benefits of conservation practices using the Ohio River Basin (ORB) as an example. The modeling approach uses a farm-scale model, Agricultural Policy Environmental Extender (APEX), and a watershed scale model (the Soil and Water Assessment Tool [SWAT]) and databases in the Hydrologic Unit Modeling for the United States system. Databases of land use, soils, land use management, topography, weather, point sources, and atmospheric depositions were developed to derive model inputs. APEX simulates the cultivated cropland, Conserve Reserve Program land, and the practices implemented on them, whereas SWAT simulates the noncultivated land (e.g., pasture, range, urban, and forest) and point sources. Simulation results from APEX are input into SWAT. SWAT routes all sources, including APEX's, to the basin outlet through each eight-digit watershed. Each basin is calibrated for stream flow, sediment, and nutrient loads at multiple gaging sites and turned in for simulating the effects of conservation practice scenarios on water quality. Results indicate that sediment, nitrogen, and phosphorus loads delivered to the Mississippi River from ORB could be reduced by 16, 15, and 23%, respectively, due to current conservation practices. Modeling tools are useful to provide science-based information for assessing existing conservation programs, developing future programs, and developing insights on load reductions necessary for hypoxia in the Gulf of Mexico.

Effects of agricultural conservation practices on N loads in the Mississippi-atchafalaya river basin.

A modeling framework consisting of a farm-scale model, Agricultural Policy Environmental Extender (APEX); a watershed-scale model, Soil and Water Assessment Tool (SWAT); and databases was used in the Conservation Effects Assessment Project to quantify the environmental benefits of conservation practices on cropland. APEX is used to simulate conservation practices on cultivated cropland and Conservation Reserve Program land to assess the edge-of-field water-quality benefits. Flow and pollutant loadings from APEX are input to SWAT. SWAT simulates the remaining noncultivated land and routes flow and loads generated from noncultivated land, point sources, and cropland to the basin outlet. SWAT is used for assessing the effects of practices on local and in-stream water-quality benefits. Each river basin is calibrated and validated for streamflow and loads at multiple gauging stations. The objectives of the current study are to estimate the effects of currently existing and additional conservation practices on total N (TN) loads in the Mississippi-Atchafalaya River Basin (MARB) and draw insights on TN load reductions necessary for reducing the hypoxic zone in the Gulf of Mexico. The effects of conservation practice scenarios on local and in-stream (riverine) water quality are evaluated. Model results indicate that conservation practices currently on cropland have reduced the TN losses to local waters between 20 and 59% in the six river basins within MARB and the TN load discharged to the Gulf by 17%. Further water-quality improvement can be obtained in the MARB with additional conservation treatment.

N-terminal disordered domain of Saccharomyces cerevisiae Hop1 protein is dispensable for DNA binding, bridging, and synapsis of double-stranded DNA molecules but is necessary for spore formation.

The cytological architecture of the synaptonemal complex (SC), a meiosis-specific proteinaceous structure, is evolutionarily conserved among eukaryotes. However, little is known about the biochemical properties of SC components or the mechanisms underlying their roles in meiotic chromosome synapsis and recombination. Functional analysis of Saccharomyces cerevisiae Hop1, a key structural component of SC, has begun to reveal important insights into its function in interhomolog recombination. Previously, we showed that Hop1 is a structure-specific DNA-binding protein, exhibits higher binding affinity for the Holliday junction, and induces structural distortion at the core of the junction. Furthermore, Hop1 promotes DNA condensation and intra- and intermolecular synapsis between duplex DNA molecules. Here, we show that Hop1 possesses a modular domain organization, consisting of an intrinsically disordered N-terminal domain and a protease-resistant C-terminal domain (Hop1CTD). Furthermore, we found that Hop1CTD exhibits strong homotypic as well as heterotypic protein-protein interactions, and its biochemical activities were similar to those of the full-length Hop1 protein. However, Hop1CTD failed to complement the meiotic recombination defects of the Δhop1 strain, indicating that both N- and C-terminal domains of Hop1 are essential for meiosis and spore formation. Altogether, our findings reveal novel insights into the structure-function relationships of Hop1 and help to further our understanding of its role in meiotic chromosome synapsis and recombination.

Multiple in vitro bioassay approach in sediment toxicity evaluation: Masan Bay, Korea.

Extracts of 21 sediment samples from Masan Bay, Korea, used in an earlier chemical measurement, were screened for their ability to induce estrogen, - and dioxin - like gene expression using the E-Assay (+), DR-CALUX assay, respectively, and to inhibit acetylcholinesterase (AChE) activity using an in vitro AChE assay. Biological impact in the industry-rich inner bay is higher than outer bay. DDTs (0.65), coplanar PCBs (0.77), HCHs (0.64), PAHs (0.61) and APs (0.53) with good correlation to E-assay (+) are seen as environmental estrogens. The highest induction of DR-CALUX response was seen again at station M12 and 15 which received sewage effluents. PCDD/DFs gave the highest correlation (0.75). Interestingly, the M12 station at the sewage treatment outlet showed the highest activity. Among the targeted chemicals APs (0.66), PCBs (0.64), PAHs (0.61) and DDT (0.49) correlated well with the AChE bioassay. Spearman rank correlation on analytical and biochemical results affirmed the 'hot spots' and point sources (e.g., sewage treatment and industrial outfall) and suspected toxicants. Significant correlations between organo chlorine pesticides, PCBs, dioxins and alkylphenols and their biological effects were observed.

A comparative analysis of biomass and clean fuel exposure on pulmonary function during cooking among rural women in Tamilnadu, India.

It is of interest to document data on the comparative analysis of biomass and clean fuel exposure on pulmonary function during cooking among rural women. The study consisted of 100 biomass and 100 LPG fuel using women with no smoking habits and other related illness Parameters such as FVC, FEV1, FEV1/FVC, PEFR, FEF25-75%were obtained using the computerized spirometry to assess the pulmonary function in these subjects. The collected data were analyzed using the Student t-test method and Pearson correlation. The exposure index for biomass fuel users is 69.78±27.25 showing high exposure duration during cooking. The parameters for pulmonary functions significantly declined in FVC (42.34±13.6), FEV1 (45.55±15.98), PEFR (34.11±14.78) and FEF25-75% (45.56±23.00) for biomass fuel user. However, this is not true for FEV1/FVC ratio (107.56±16.9). The increase in PFT suggests the restrictive and obstructive patterns of pulmonary diseases. There was a negative correlation between increased duration of cooking and the value of FEV1/FVC (r = -0.2961), FEF25-75% (r = -0.3519) and PEFR (r = -0.2868). Thus, the deformation of pulmonary function due to extended exposure of biomass fuel for cooking women in rural Tamilnadu is shown using parameter features such as high exposure index, overcrowded area and improper ventilated houses.

Synthesis and characterization of BiVO4 nanoparticles for environmental applications.

In the present study, a chemical precipitation method is adopted to synthesize bismuth vanadate nanoparticles. The calcination temperature dependent photocatalytic and antibacterial activities of BiVO4 nanoparticles are examined. The structural analysis evidences the monoclinic phase of BiVO4 nanoparticles, where the grain size increases with calcination temperature. Interestingly, BiVO4 nanoparticles calcined at 400 °C exhibit superior photocatalytic behaviour against methylene blue dye (K = 0.02169 min-1) under natural solar irradiation, which exhibits good stability for up to three cycles. The evolution of antibacterial activity studies using a well diffusion assay suggest that the BiVO4 nanoparticles calcined at 400 °C can act as an effective growth inhibitor of pathogenic Gram-negative (P. aeruginosa & A. baumannii) and Gram-positive bacteria (S. aureus).

Understanding the effects of pasture type and stocking rate on the hydrology of the Southern Great Plains.

Grassland is one of the major biomes in the United States (US) and the world. In the US, the majority of grasslands are concentrated in the Great Plains and has undergone through significant interventions or management changes over the last few decades. A key economy-driven intervention in the Southern Great Plains (SGP) include the introduction of new forage species and conversion of native grassland to introduced pasture to increase productivity and its nutritive value for improved cattle production. Since water is one of the fundamental resources needed to sustain grassland productivity, it is important to understand how such pasture conversion and prevailing cattle grazing practices affect water balance and biomass production in a given pasture system. In this study, the Nutrient Tracking Tool (NTT) with its core APEX (Agricultural Policy Environmental eXtender) model was used to assess the hydrological impacts of the pasture introduction, i.e., native pasture (little bluestem, Schizachyrium halapense) vs. introduced pasture (old world bluestem, Bothriochloa caucasica), and the stocking rate in the SGP. Monthly evapotranspiration (ET) and biomass estimates from NTT compared well with observed data at two USDA-ARS experimental pastures (native and introduced) near El Reno, Oklahoma, for the years 2015 and 2016. Simulated long-term average annual hydrologic fluxes (i.e., ET, runoff, and groundwater recharge) from the introduced pasture were slightly lower than the observed data but not significantly different than those from the native pasture under the current management conditions. NTT predicted higher water yield (runoff and recharge) and significantly lower ET for the introduced pasture than the native pasture. Results suggest that grazing has the potential to alter the hydrological balance in the SGP. For example, the increase in stocking rate within the carrying capacity of the farm decreases ET and increases runoff and groundwater recharge for both pastures. Comparison of estimated biomass production between native and introduced pastures indicated that introduced pastures are more efficient in using the available water and thus produce a higher forage biomass per unit of water in the SGP. This study highlighted the potential significance of considering hydrological and other biophysical impacts of new forage introduction and stocking rate changes for the sustainable management of grazing and pasture systems in the SGP.

Generalized lattice Boltzmann equation with forcing term for computation of wall-bounded turbulent flows.

In this paper, we present a framework based on the generalized lattice Boltzmann equation (GLBE) using multiple relaxation times with forcing term for eddy capturing simulation of wall-bounded turbulent flows. Due to its flexibility in using disparate relaxation times, the GLBE is well suited to maintaining numerical stability on coarser grids and in obtaining improved solution fidelity of near-wall turbulent fluctuations. The subgrid scale (SGS) turbulence effects are represented by the standard Smagorinsky eddy viscosity model, which is modified by using the van Driest wall-damping function to account for reduction of turbulent length scales near walls. In order to be able to simulate a wider class of problems, we introduce forcing terms, which can represent the effects of general nonuniform forms of forces, in the natural moment space of the GLBE. Expressions for the strain rate tensor used in the SGS model are derived in terms of the nonequilibrium moments of the GLBE to include such forcing terms, which comprise a generalization of those presented in a recent work [Yu, Comput. Fluids 35, 957 (2006)]. Variable resolutions are introduced into this extended GLBE framework through a conservative multiblock approach. The approach, whose optimized implementation is also discussed, is assessed for two canonical flow problems bounded by walls, viz., fully developed turbulent channel flow at a shear or friction Reynolds number (Re) of 183.6 based on the channel half-width and three-dimensional (3D) shear-driven flows in a cubical cavity at a Re of 12 000 based on the side length of the cavity. Comparisons of detailed computed near-wall turbulent flow structure, given in terms of various turbulence statistics, with available data, including those from direct numerical simulations (DNS) and experiments showed good agreement. The GLBE approach also exhibited markedly better stability characteristics and avoided spurious near-wall turbulent fluctuations on coarser grids when compared with the single-relaxation-time (SRT)-based approach. Moreover, its implementation showed excellent parallel scalability on a large parallel cluster with over a thousand processors.

Computation of turbulent flow and secondary motions in a square duct using a forced generalized lattice Boltzmann equation.

Turbulent flow in a straight square duct driven by a pressure gradient exhibits remarkable flow structures such as the presence of mean streamwise vorticity or secondary flows. These secondary circulations take the form of two counter-rotating vortices near each corner of the duct. Even though their magnitudes are small compared with primary streamwise motions, they have a significant influence on flow and scalar transport and are challenging to accurately predict using computational approaches. In this paper, we employ a recently developed formulation of the generalized lattice Boltzmann equation (GLBE) with forcing term to perform large eddy simulation of fully developed turbulent flow in a square duct at a shear Reynolds number based on duct width equal to 300. Subgrid scale effects are represented by the Smagorinsky eddy viscosity model, which is modified by the van Driest damping function in the near-wall regions, in this GLBE approach, which is based on multiple relaxation times. It was found that the GLBE is able to correctly reproduce the existence of mean secondary motions and the computed detailed structure of first- and second-order statistics of main and secondary motions are in good agreement with prior direct numerical simulations based on the solution of the Navier-Stokes equations and experimental data.

Correction: Study on the inflammatory response of PMMA/polystyrene/silica nanocomposite membranes for drug delivery and dental applications.

[This corrects the article DOI: 10.1371/journal.pone.0209948.].

Study on the inflammatory response of PMMA/polystyrene/silica nanocomposite membranes for drug delivery and dental applications.

BACKGROUND: The application of polymeric materials in medical industry has grown drastically in the last two decades due to their various advantages compared to existing materials. The present research work emphases on the sol-gel technique to formulate the polymethyl methyl acrylate/polystyrene/silica composite membrane. METHODS: The characteristic of the composite was investigated through modern state art of instrumentation. RESULTS: The functional groups attached to the polymer was absorbed by FTIR. The FTIR spectrum confirm that the blend was mixed thoroughly and the formation of unite intimately between the polymers. The membranes were observed by SEM for its surface homogeneity which depends upon the composition of the two blending polymers. The captured SEM images showed the formation of microcracks on the surface, which was evidently controlled by varying the constituent polymer ratios. The prepared blend membranes with 2:1 ratio of PMMA/PS/Si displayed higher water uptake compared to other blended membranes. The composite membranes had good hydroxyl apatite growth in SBF solution. Furthermore, the in vitro cytotoxicity studies carried out by MTT method, using RAW macrophage cells showed that all the samples exhibited excellent cell viability. CONCLUSION: The inflammatory response of composite with equal concentration of PMMA-PS were performed and observed no inflammation in comparison with control and other tested concentrations.

HOXA1-stimulated oncogenicity is mediated by selective upregulation of components of the p44/42 MAP kinase pathway in human mammary carcinoma cells.

Expression of homeobox A1 (HOXA1) results in oncogenic transformation of immortalized human mammary epithelial cells with aggressive tumor formation in vivo. However, the mechanisms by which HOXA1 mediates oncogenic transformation is not well defined. To identify molecules that could potentially be involved in HOXA1-mediated oncogenic transformation, microarray analysis was utilized to characterize and compare the gene expression pattern in response to forced expression or depletion of HOXA1 in human mammary carcinoma cells. Gene expression profiling identified that genes involved in the p44/42 mitogen-activated protein (MAP) kinase activation pathway (GRB2, MAP kinase kinase (MEK1) and SDFR1) or p44/42 MAP kinase-regulated genes (IER3, EPAS1, PCNA and catalase) are downstream expression targets of HOXA1. Forced expression of HOXA1 increased GRB2 and MEK1 mRNA and protein expression and increased p44/42 MAP kinase phosphorylation, activity and Elk-1-mediated transcription. Use of a MEK1 inhibitor demonstrated that increased p44/42 MAP kinase activity is required for the HOXA1-mediated increase in cell proliferation, survival, oncogenicity and oncogenic transformation. Thus, modulation of the p44/42 MAP kinase pathway is one mechanism by which HOXA1 mediates oncogenic transformation of the human mammary epithelial cell.

Assessment of heavy metals (Cd, Cr and Pb) in water, sediment and seaweed (Ulva lactuca) in the Pulicat Lake, South East India.

The concentrations of three heavy metals chromium (Cr), cadmium (Cd) and lead (Pb) were examined in water, sediment and green algae (Ulva lactuca); collected from six different stations at Pulicat Lake, which receives effluents from industries located in North Chennai Coastal region. Concentrations of Cd (64.21 microg g(-1)) and Cr (28.51 microg g(-1)) were found to be high in sediment, whereas in green algae concentration of Pb (8.32 microg g(-1)) was higher than water and sediment samples. The relative abundance of these heavy metals in U. lactuca and sediment were found to be in the order Cd>Cr>Pb, whereas in water the ratio was found to be Cr>Pb>Cd. The seasonal variations in Cd and Pb followed a similar pattern in both seaweeds and sediments, but not in water samples. Spearman correlation coefficient study showed no significant correlation in the concentration of metals in U. lactuca, water and sediment samples.

Neural adaptive control for vibration suppression in composite fin-tip of aircraft.

In this paper, we present a neural adaptive control scheme for active vibration suppression of a composite aircraft fin tip. The mathematical model of a composite aircraft fin tip is derived using the finite element approach. The finite element model is updated experimentally to reflect the natural frequencies and mode shapes very accurately. Piezo-electric actuators and sensors are placed at optimal locations such that the vibration suppression is a maximum. Model-reference direct adaptive neural network control scheme is proposed to force the vibration level within the minimum acceptable limit. In this scheme, Gaussian neural network with linear filters is used to approximate the inverse dynamics of the system and the parameters of the neural controller are estimated using Lyapunov based update law. In order to reduce the computational burden, which is critical for real-time applications, the number of hidden neurons is also estimated in the proposed scheme. The global asymptotic stability of the overall system is ensured using the principles of Lyapunov approach. Simulation studies are carried-out using sinusoidal force functions of varying frequency. Experimental results show that the proposed neural adaptive control scheme is capable of providing significant vibration suppression in the multiple bending modes of interest. The performance of the proposed scheme is better than the H(infinity) control scheme.

Paper pulp modification and deinking efficiency of cellulase-xylanase complex from Escherichia coli SD5.

Ligno-cellulosic enzymes like cellulase and xylanase have potential for modification of paper pulp characteristics. A low molecular weight cellulase - xylanase complex (14KDa) was co-produced using Escherichia coli SD5. Co-existence of these enzymes was found to be advantageous in paper pulp modification and in deinking applications. The cellulase and xylanase exhibited specific activities of 51.95 and 24.64U/mg protein of respectively. Defibrillations, crack formation and changes in functional groups was evident from the SEM and FT-IR analysis of paper pulp following the enzyme treatment. The enzyme facilitated a better reduction of Kappa number and Hexenuronic acid (Hex A) compared to earlier studies. A Δ brightness of approximately 10% were achieved in case of both cellulase and xylanase for different treatment time. The tear strength of recycled paper was also found to increase after the enzymatic treatment. This is the first report on the application of a un-engineered E. coli isolate co-producing cellulase-xylanase for paper industrial application.

Symmetrized operator split schemes for force and source modeling in cascaded lattice Boltzmann methods for flow and scalar transport.

Operator split forcing schemes exploiting a symmetrization principle, i.e., Strang splitting, for cascaded lattice Boltzmann (LB) methods in two- and three-dimensions for fluid flows with impressed local forces are presented. Analogous scheme for the passive scalar transport represented by a convection-diffusion equation with a source term in a novel cascaded LB formulation is also derived. They are based on symmetric applications of the split solutions of the changes on the scalar field or fluid momentum due to the sources or forces over half time steps before and after the collision step. The latter step is effectively represented in terms of the post-collision change of moments at zeroth and first orders, respectively, to represent the effect of the sources on the scalar transport and forces on the fluid flow. Such symmetrized operator split cascaded LB schemes are consistent with the second-order Strang splitting and naturally avoid any discrete effects due to forces or sources by appropriately projecting their effects for higher-order moments. All the force or source implementation steps are performed only in the moment space and they do not require formulations as extra terms and their additional transformations to the velocity space. These result in particularly simpler and efficient schemes to incorporate forces or sources in the cascaded LB methods unlike those considered previously. Numerical study for various benchmark problems in 2D and 3D for fluid flow problems with body forces and scalar transport with sources demonstrate the validity and accuracy, as well as the second-order convergence rate of the symmetrized operator split forcing or source schemes for the cascaded LB methods.

Galilean-invariant preconditioned central-moment lattice Boltzmann method without cubic velocity errors for efficient steady flow simulations.

Lattice Boltzmann (LB) models used for the computation of fluid flows represented by the Navier-Stokes (NS) equations on standard lattices can lead to non-Galilean-invariant (GI) viscous stress involving cubic velocity errors. This arises from the dependence of their third-order diagonal moments on the first-order moments for standard lattices, and strategies have recently been introduced to restore Galilean invariance without such errors using a modified collision operator involving corrections to either the relaxation times or the moment equilibria. Convergence acceleration in the simulation of steady flows can be achieved by solving the preconditioned NS equations, which contain a preconditioning parameter that can be used to tune the effective sound speed, and thereby alleviating the numerical stiffness. In the present paper, we present a GI formulation of the preconditioned cascaded central-moment LB method used to solve the preconditioned NS equations, which is free of cubic velocity errors on a standard lattice, for steady flows. A Chapman-Enskog analysis reveals the structure of the spurious non-GI defect terms and it is demonstrated that the anisotropy of the resulting viscous stress is dependent on the preconditioning parameter, in addition to the fluid velocity. It is shown that partial correction to eliminate the cubic velocity defects is achieved by scaling the cubic velocity terms in the off-diagonal third-order moment equilibria with the square of the preconditioning parameter. Furthermore, we develop additional corrections based on the extended moment equilibria involving gradient terms with coefficients dependent locally on the fluid velocity and the preconditioning parameter. Such parameter dependent corrections eliminate the remaining truncation errors arising from the degeneracy of the diagonal third-order moments and fully restore Galilean invariance without cubic defects for the preconditioned LB scheme on a standard lattice. Several conclusions are drawn from the analysis of the structure of the non-GI errors and the associated corrections, with particular emphasis on their dependence on the preconditioning parameter. The GI preconditioned central-moment LB method is validated for a number of complex flow benchmark problems and its effectiveness to achieve convergence acceleration and improvement in accuracy is demonstrated.

Correction: Physiochemical characterization and cytotoxicity evaluation of mercury-based formulation for the development of anticancer therapeuticals.

[This corrects the article DOI: 10.1371/journal.pone.0195800.].