Potential of mean force of the hepatitis C virus core protein–monoclonal 19D9D6 antibody interaction

Antigen–antibody interactions are critical for understanding antigen–antibody associations in immunology. To shed further light on this question, we studied a dissociation of the 19D9D6-HCV core protein antibody complex structure. However, forced separations in single molecule experiments are difficult, and therefore molecular simulation techniques were applied in our study. The stretching, that is, the distance between the center of mass of the HCV core protein and the 19D9D6 antibody, has been studied using the potential of mean force calculations based on molecular dynamics and the explicit water model. Our simulations indicate that the 7 residues Gly70, Gly72, Gly134, Gly158, Glu219, Gln221 and Tyr314, the interaction region (antibody), and the 14 interprotein molecular hydrogen bonds might play important roles in the antigen–antibody interaction, and this finding may be useful for protein engineering of this antigen–antibody structure. In addition, the 3 residues Gly134, Gly158 and Tyr314 might be more important in the development of bioactive antibody analogs.     

Synthesis and characterization of different complexes derived from Schiff base and evaluation as a potential anticancer,antimicrobial, and insecticide agent

The condensation of (1H-benzimidazole-2-yl) methanamine, with 2-hydroxy naphthaldehyde lead to Schiff base ligand (H2L) (1). This was later reacted with metal salts (ZnCl₂, CrCl₃·6H₂O, and MnCl₂·4H₂O) to afford the corresponding metal complexes. Biological activity findings indicate that the metal complexes have promising activity against Escherichia coli and Bacillus subtilis and modest activity against Aspergillus niger. The in vitro anticancer activities of Zn (II), Cr (III), and Mn (II) complexes were investigated and the best results were observed with Mn (II) complex as the most potent cytotoxic agent toward human cell lines colorectal adenocarcinoma HCT 116, hepatocellular carcinoma HepG₂ and breast adenocarcinoma MCF-7 with 0.7, 1.1 and 6.7 μg of inhibitory concentration IC₅₀ values respectively. Consequently, the Mn (II) complex and ligand were docked inside the energetic site of ERK2 and exhibited favorable energy for binding. The investigation of biological tests towards mosquito larvae indicates that Cr (III) and Mn (II) complexes manifest strong toxicity against Aedes aegypti larvae with 3.458 and 4.764 ppm values of lethal concentration LC₅₀, respectively.     

Dynamic macroecology on ecological time-scales

Aim The discipline of macroecology is increasingly being regarded as an effective vehicle for the evaluation of recent population‐ to ecosystem‐level responses to widespread human and environmental influences. However, due to the prevalent use of time‐averaged and cumulative data in macroecological analyses, the majority of the patterns that emerge from research in this field can be regarded as static. Here we review the application of dynamic macroecological analyses to changes in relationships between macroecological variables on seasonal to decadal scales. We illustrate the strength of this perspective for documenting changing patterns and testing hypotheses related to these dynamics on ecological time‐scales. Location Studies were compiled and reviewed from terrestrial and aquatic ecosystems. Methods We review examples of temporal changes in macroecological patterns driven by recent anthropogenic influences and environmental change. Results The dynamic nature of macroecological patterns on ecological time‐scales has been revealed in recent years across a wide range of ecosystems, largely through the development, maintenance and analysis of biotic and environmental monitoring time series. The resultant analyses complement examinations of dynamics over evolutionary time and have similarly revealed that static portrayals can conceal important temporal dynamics that underlie the patterns of interest. As a consequence, static depictions, resting as they do on comparative analyses in which the validity of space‐for‐time substitutions is assumed, may be of limited use for testing hypotheses related to the mechanisms underlying the patterns revealed and, by extension, the development of reliable predictions of future states. Main conclusions Recent dynamic macroecological analyses have demonstrated the utility of combined spatial and temporal replication, and have contributed to hypothesis testing related to the mechanistic processes underlying changes in macroecological patterns on ecological time‐scales. We suggest four specific avenues of future research to further the development and application of temporal approaches on similar time‐scales within the field of macroecology.     

Impacts of deep open drains on water quality and biodiversity of receiving waterways in the Wheatbelt of Western Australia

Extensive networks of deep drains are being built in Western Australia to reduce the effects of dryland salinity on agricultural lands. Most of these drains discharge into natural river and wetland systems, with little consideration given to the environmental impacts. This study examined the downstream ecological impacts of one of the oldest deep drain networks in Western Australia, located in the Wakeman subcatchment near Narembeen. Twelve sites were sampled bi-monthly from October 2004 to September 2006. On each occasion, water quality parameters were measured and the macro-invertebrate fauna was sampled. Significant differences in water quality and macro-invertebrates were observed between the untreated sites and those affected by the drain discharge. Surface water at untreated sites was always fresh (<3 ppt), alkaline (pH 7.6–8.9) and turbid (49–600 NTU), whereas treatment sites were always saline (28–147 ppt), acidic (pH 1.9–3.8) and mostly clear (0–100 NTU). No recovery of water quality was observed with distance from discharge point (20 km). Invertebrates reflected differences in water quality, with drain discharge resulting in a sharp decline in species richness, and significant changes in macro-invertebrate community composition. Sites affected by drain discharge were dominated by fly larvae such as Orthocladiinae and Ceratopogonidae. Microcrustaceans were far more abundant at sites unaffected by drainage. The ecological values of Wheatbelt streams are likely to be further compromised by discharge of poor water quality from deep drainage. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users. Handling editor: K. Martens     

Extending the diffuse layer model of surface acidity constant behaviour: IV. Diffuse layer charge/potential relationships

Abstract

Most current electrostatic surface complexation models describing ionic binding at the particle/water interface rely on the use of Poisson–Boltzmann (PB) theory for relating diffuse layer charge densities to diffuse layer electrostatic potentials. PB theory is known to contain a number of implicit assumptions whose significance in environmental applications is largely unknown. This study seeks to better quantify the impact of these assumptions by: (1) comparing potentials obtained from planar analytical solutions to the PB with those obtained from Hypernetted Chain (HNC) theory (Attard, 2006), (2) assessing the accuracy of the Ohshima et al. (1982) spherical approximate analytical solution to the PB equation by comparison with published numerical values (Loeb et al., 1961), and (3) comparing interfacial potential estimates obtained from the spherical approximate analytical solution to the PB equation at and adjacent to the particle surface with potential estimates obtained from the Entropic Balanced Surface Potential (EB) model (Loux, 1985; Loux and Anderson, 2001) and published potential estimates obtained from the Hypernetted Chain/Mean Spherical Approximation procedure (HNC/MSA; Gonzalez-Tovar and Lozada-Cassou, 1989). EB potential estimates were obtained assuming a surface volume thickness equal to the Bjerrum length (0.357 nm in a room temperature monovalent electrolyte solution). Findings from the study included: (1) the planar, surficial HNC estimates compared favourably with planar surficial PB relationships at charge densities equal to or less than 0.05 C m^?2, (2) the Ohshima et al. (1982) approximate spherical analytical solution to the PB equation replicated the numerical charge density estimates required to obtain 72 datapoints over an e<img>/kT range of one to four with a maximum error of 3.37% and a coefficient of variation of 0.92%, (3) for a 0.1 μm radius particle in a room temperature 0.01 M (1 : 1) ionic strength solution, potential estimates over a surface charge density range of 0 to 0.3C m^?2 occurred in the following order: ψ_HNC/MSA,R >ψ_PB,R >_{ψHNC/MSA,R+0.2125nm} >ψ_PB,R+0.2nm ~ ψ_EB >ψ_{HNC/MSA,R+0.425nm} ~ _ψPB,R+0.4nm and (4) with 45 datapoints including both 1 μm and 10 nm radius particles over an ionic strength range of 1.0 to 0.001 M, the PB potential estimates 0.2 nm from the particle surface (ψ_PBR+02nm) closely tracked the corresponding EB estimates (ψ_EB) with a 5.3% coefficient of variation. If one assumes that interfacial potential values adjacent to the particle surface are most relevant for describing environmental phenomena and that a 10% coefficient of variation in potential estimates is acceptable, then presumably any of the non-surficial charge/potential relationships would be useful below an absolute charge density of 0.125 C m ^?2 (with monovalent electrolyte solutions).     

Unbinding free energy of acetylcholinesterase bound oxime drugs along the gorge pathway from metadynamics‐umbrella sampling investigation

Because of the pivotal role that the nerve enzyme, acetylcholinesterase plays in terminating nerve impulses at cholinergic synapses. Its active site, located deep inside a 20 Å gorge, is a vulnerable target of the lethal organophosphorus compounds. Potent reactivators of the intoxicated enzyme are nucleophiles, such as bispyridinium oxime that binds to the peripheral anionic site and the active site of the enzyme through suitable cation–π interactions. Atomic scale molecular dynamics and free energy calculations in explicit water are used to study unbinding pathways of two oxime drugs (Ortho‐7 and Obidoxime) from the gorge of the enzyme. The role of enzyme‐drug cation–π interactions are explored with the metadynamics simulation. The metadynamics discovered potential of mean force (PMF) of the unbinding events is refined by the umbrella sampling (US) corrections. The bidimensional free energy landscape of the metadynamics runs are further subjected to finite temperature string analysis to obtain the transition tube connecting the minima and bottlenecks of the unbinding pathway. The PMF is also obtained from US simulations using the biasing potential constructed from the transition tube and are found to be consistent with the metadynamics‐US corrected results. Although experimental structural data clearly shows analogous coordination of the two drugs inside the gorge in the bound state, the PMF of the drug trafficking along the gorge pathway point, within an equilibrium free energy context, to a multistep process that differs from one another. Routes, milestones and subtlety toward the unbinding pathway of the two oximes at finite temperature are identified. Proteins 2014; 82:1799–1818. © 2014 Wiley Periodicals, Inc.     

The impact of scallop drags on sea urchin populations and benthos in the Bay of Fundy,Canada

The fishery for the green sea urchin (Strongylocentrotus droebachiensis) began in New Brunswick in the late 1980s in response to increasing demand from Asian markets, primarily Japan. Fishing was initiated by members of the scallop industry and the harvesting practices were based on familiar fishing gear (scallop drags or dredges) and similar operations occurring simultaneously in Maine. Because of the potential impact of scallop gear on the shallow water populations in areas not traditionally fished, a study was initiated in 1993 to document (1) the proportion of sea urchins damaged during the harvesting operation, (2) the impact on and subsequent recovery time of the associated benthic flora and epifauna, and (3) the impacts on the bottom substrate. Two sites were chosen for the study based on a split-plot design with a control and experimental plot at each site. In each experimental plot, a towing lane was created parallel to shore. Divers used a fixed line transect method to survey the control and treatment plots prior to and after the harvesting operation done with commercial scallop Digby drags. Further diver-based surveys were done 3 and 6 months later. Results showed a significant decrease in sea urchin densities and an increase in the number of broken sea urchin tests after the harvesting operation at the Passamaquoddy Bay and Grand Manan sites (3–15%). On both sites, there were significant changes in the density of mobile predators such as lobsters, crabs, whelks and sculpins. Lobster density declined to zero after dragging, but the lack of body parts suggested they moved out of the area. Whelks were observed to move into each of the experimental areas, likely in response to probable increase in available food. The dragging operation increased the breakage rate of the kelp, Laminaria longicruris. From the study we concluded that there were short-term impacts from dragging, but the observable effects on the bottom from the single dragging event were gone in less than 3 months. The longer-term effects of dragging were unknown.