Molecular Mechanics Study of Flow and Surface Influence in Ligand–Protein Association

Ligand–protein association is the first and critical step for many biological and chemical processes. This study investigated the molecular association processes under different environments. In biology, cells have different compartments where ligand–protein binding may occur on a membrane. In experiments involving ligand–protein binding, such as the surface plasmon resonance and continuous flow biosynthesis, a substrate flow and surface are required in experimental settings. As compared with a simple binding condition, which includes only the ligand, protein, and solvent, the association rate and processes may be affected by additional ligand transporting forces and other intermolecular interactions between the ligand and environmental objects. We evaluated these environmental factors by using a ligand xk263 binding to HIV protease (HIVp) with atomistic details. Using Brownian dynamics simulations, we modeled xk263 and HIVp association time and probability when a system has xk263 diffusion flux and a non-polar self-assembled monolayer surface. We also examined different protein orientations and accessible surfaces for xk263. To allow xk263 to access to the dimer interface of immobilized HIVp, we simulated the system by placing the protein 20Å above the surface because immobilizing HIVp on a surface prevented xk263 from contacting with the interface. The non-specific interactions increased the binding probability while the association time remained unchanged. When the xk263 diffusion flux increased, the effective xk263 concentration around HIVp, xk263–HIVp association time and binding probability decreased non-linearly regardless of interacting with the self-assembled monolayer surface or not. The work sheds light on the effects of the solvent flow and surface environment on ligand–protein associations and provides a perspective on experimental design.

An experimental test to separate the effects of male age and mating history on female mate choice

Should females prefer older males as mates? Male survival to old age might indicate the presence of fitness-enhancing genes that increase offspring fitness. However, many correlational studies show that mating with older males can lower female fecundity and even reduce offspring fitness due to epigenetic or germline mutation effects. One problem in quantifying female choice based on male age is that age is usually confounded with mating history. This begs a question: Do females choose males based on their age or their mating history? The answer requires an experimental approach, but few such studies exist. Here, we test if experimentally induced variation in the mating history of old and young males (12-week difference in postmaturity age) affects female choice in the eastern mosquitofish (Gambusia holbrooki). To vary mating history, adult males were either allowed to freely mate with females for 3 weeks or they only had visual contact with females. Immediately thereafter, we ran four-choice mating trials, using association time, to test the effects of male age and mating history (2 × 2 design) on male attractiveness. Females did not show a clear preference for males based on either characteristic. This was not due to a lack of female choice: females spent significantly more time with larger males. In addition, female choice was significantly repeatable across four trials: twice as a virgin and twice as a nonvirgin. Finally, female mating status (virgin or nonvirgin) did not affect her choice of mate, although virgin females spent significantly more time associating with test males.

The Ripple Effect and Spatiotemporal Dynamics of Intra-Urban Housing Prices at the Submarket Level in Shanghai, China

The ripple effect of housing price movements between cities has been extensively investigated, but there are relatively few studies on this topic within a metropolitan context, especially at the submarket level. This paper describes the use of ripple effect theory to examine the diffusion process and convergence of intra-urban housing prices at the submarket level in Shanghai, an emerging global city in China. The analysis is based on directed acyclic graphs, local indicators of spatial association time-paths, and a recently developed convergence test. The empirical results of grouping analysis identify 25 submarkets in Shanghai, and the diffusion of housing prices between these submarkets is found to be caused by both geographical and economic proximities. There is also a complex recursive process of price spillovers from high- to low-priced submarkets, and vice versa, which contributes to the spiraling local housing prices. Housing prices diverge across all submarkets, and the whole market can be divided into three convergence clubs. Finally, these convergence clubs have a circular structure with a degree of continuity. This study broadens our knowledge of the price interrelationship among housing submarkets at the intra-urban level. These findings have profound implications for urban planners, policy makers, and local residents.

Kinetic, Thermodynamic and Isotherm Studies for the removal of Acid Red 88 from Aqueous Medium by Polyaniline-CuCl2 Composite

The metal salt doped polyaniline has been used as adsorbent for the removal of synthetic dye. The influence of experimental parameters like association time, adsorbent dosage, agitating speed, pH and electrical conductivity on adsorption of Acid Red 88 was systematically investigated. More than 95% of Acid Red 88 was removed after 55 minutes of adsorbent/adsorbate contact time for 0.3g/L of PANI-CuCl2. Calculations have been carried out to analyse the impact of weight of PANI-CuCl2 composite and concentration of Acid Red 88 on the percentage of decolourisation. Kinetics and isotherm analysis were also carried out to describe the adsorption process. Electrical conductivity, SEM and FTIR technique were used to characterize the adsorbent before and after adsorption. The thermodynamic parameters like changes in free energy, enthalpy and entropy were also evolved to predict the nature of adsorption. The adsorbent is stable, easy to prepare and suitable to remove Acid Red 88 from effluent.

Contrasting female mate preferences for red coloration in a fish

Understanding how animals select their mates requires knowing the factors that shape mate preferences. Recent theoretical and empirical considerations suggest that female mating status can influence the degree to which a female engages in mate choice, with virgin females predicted to be less choosy than mated females. In this study, we investigated mate choice in both virgin and mated females in the pygmy halfbeak Dermogenys collettei. Halfbeaks are small, live-bearing, internally fertilizing freshwater fish that live in mixed-sex groups where females have ample opportunity to engage in mate choice. Using a dichotomous choice assay, we quantified and contrasted in virgin and mated females mate preferences for differences in male body size, beak size, and area of yellow and red coloration. We also examined how mating status influenced the amount of time a female associated with the first male encountered and the relative amount of time a female associated with each male. We demonstrate that mate preferences of female halfbeaks are driven primarily by the size of red coloration present on males. Females showed contrasting preferences based on mating status, with virgin females preferentially associating with drab males whereas mated females preferentially associate with males possessing large areas of red. Contrary to expectations, female mating status did not influence how females associate with the first males encountered or how females biased their association time among males. Although the precise drivers of these effects need further studying, our finding highlights a possible explanation for how variation in male ornamentation can be maintained.

Electronic nose with polymer-composite sensors for monitoring fungal deterioration of stored rapeseed

Investigations were performed to examine the possibility of using an electronic nose to monitor development of fungal microflora during the first eighteen days of rapeseed storage. The Cyranose 320 device manufactured by Sensigent was used to analyse volatile organic compounds. Each sample of infected material was divided into three parts and the degree of spoilage was measured in three ways: analysis of colony forming units, determination of ergosterol content, and measurement of volatile organic compounds with the e-nose. Principal component analysis was performed on the generated patterns of signals and six groups of different spoilage levels were isolated. An analysis of sensorgrams for a few sensors with a strong signal for each group of rapeseed spoilage was performed. The ratio of the association time to the steady state was calculated. This ratio was different for the low level and the highest level of ergosterol and colony forming units. The results have shown that the e-nose can be a useful tool for quick estimation of the degree of rapeseed spoilage.

Successful completion of EGFR/ALK testing in non-squamous non-small cell lung cancer (non-sq NSCLC) with the implementation of reflex testing (RT) by pathologists.

93 Background: EGFR mutation and ALK rearrangement testing is standard in the management of advanced non-sq NSCLC patients (pts). Previously at our centre, EGFR/ALK biomarker testing was requested by medical oncologists (MO). In June 2013 we implemented biomarker RT, defined as pathologists requesting EGFR/ALK at time of diagnosis of non sq-NSCLC irrespective of stage. The objective of this study was to test the hypothesis that if pathologists requested biomarker testing, appropriate tissue would be preserved and selected for testing, which would improve success rates of biomarker testing. Methods: Retrospective review of advanced non-sq NSCLC pts seen by MO at Sunnybrook Odette Cancer Centre from March 2010 to April 2014. Pt and EGFR/ALK test characteristics were compared before and after RT using Chi-square tests of association. Time outcomes were compared using Mann-Whitney U tests. Results: Of the 310 pts included, median age was 68, 44% female, 47% Caucasian, 93% adenocarcinoma, 22% EGFR+, 1% ALK+ and 84% either presented with or developed stage IV. Samples tested for EGFR and ALK were respectively: 53%, 51% core biopsies; 25%, 32% surgical resections; 20%, 16% cytology. The number of biomarker tests across all stages increased with RT (EGFR 70% vs 95%, p < 0.001 / ALK 44% vs 83%, p < 0.001). RT improved the rate of successfully completed tests (EGFR 86% vs 96%, p = 0.04 / ALK 83% vs 97%, p = 0.04). The remainder of tests were unsuccessful due to inconclusive results (EGFR 9% vs 4%, p = 0.25 / ALK 7% vs 2%, p = 0.25), insufficient tissue (EGFR 3% vs 0%, p = 0.33 / ALK 10% vs 0%, p = 0.03) or cancellation due to appropriate tissue not being sent from holding lab to testing lab (EGFR 2% vs 0, p = NS / ALK 0% vs 2%, p = NS). From core biopsies, there was trend to improved success of EGFR testing with RT (82% vs 97%, p = 0.06) and significant improvement of ALK testing (82% vs 100%, p = 0.04), with no impact on success from cytology samples. Rebiopsy rate for biomarker testing was low in both cohorts. Turnaround time for EGFR testing decreased [19 days (IQR 15-25) vs 17 days (IQR 12-21), p = 0.02]; ALK was unchanged. Conclusions: Implementation of RT improved successful completion of EGFR/ALK testing.