Aptamers in Virology: Recent Advances and Challenges

Aptamers generated from randomized libraries of nucleic acids have found utility in a wide variety of fields and in the clinic. Aptamers can be used to target both intracellular and extracellular components, including small molecules, proteins, cells, and viruses. With recent technological developments in stringent selection and rapid isolation strategies, it is likely that aptamers will continue to make an impact as useful tools and reagents. Although many recently developed aptamers are intended for use as therapeutic and diagnostic agents, use of aptamers for basic research, including target validation, remains an active area with high potential to impact our understanding of molecular mechanisms and for drug discovery. In this brief review, we will discuss recent aptamer discoveries, their potential role in structural virology, as well as challenges and future prospects

A 3-D numerical model of the influence of meanders on groundwater discharge to a gaining stream in an unconfined sandy aquifer

Groundwater discharge to streams depends on stream morphology and groundwater flow direction, but are not always well understood. Here a 3-D groundwater flow model is employed to investigate the impact of meandering stream geometries on groundwater discharge to streams in an unconfined and homogenous sandy aquifer at the reach scale (10–200 m). The effect of meander geometry was examined by considering three scenarios with varying stream sinuosity. The interaction with regional groundwater flow was examined for each scenario by considering three groundwater flow directions. The sensitivity of stream morphology and flow direction to other parameters was quantified by varying the stream width, the meander amplitude, the magnitude of the hydraulic gradient, the hydraulic conductivity, and the aquifer thickness. Implications for a real stream were then investigated by simulating groundwater flow to a stream at a field site located in Grindsted, Denmark. The simulation of multiple scenarios was made possible by the employment of a computationally efficient coordinate transform numerical method. Comparison of the scenarios showed that the geometry of meanders greatly affect the spatial distribution of groundwater flow to streams. The shallow part of the aquifer discharges to the outward pointing meanders, while deeper groundwater flows beneath the stream and enters from the opposite side. The balance between these two types of flow depends on the aquifer thickness and meander geometry. Regional groundwater flow can combine with the effect of stream meanders and can either enhance or smooth the effect of a meander bend, depending on the regional flow direction. Results from the Grindsted site model showed that real meander geometries had similar effects to those observed for the simpler sinuous streams, and showed that despite large temporal variations in stream discharge, the spatial pattern of flow is almost constant in time for a gaining stream

Monitoring and Modeling Farmland Productivity Along the Venice Coastland, Italy

AbstractThe southern portion of the Venice coastland is a very precarious environment and salt contamination of land and groundwater is a severe problem that is seriously impacting the farmland productivity. Geophysical surveys, lab testing and continuous monitoring of hydrological parameters together with crop yield distribution were performed and acquired from 2010 to 2012 in a 21ha basin cultivated with maize crop and representative of the area. The dataset is here used to set-up a numerical model of soil moisture dynamics coupled with plant transpiration, photosynthesis and growth. The hydraulic model is linked to the atmosphere by the calculation of the stomatal conductance which is optimized for maximum carbon gain. The model is applied to the field site to understand the impact of land elevation, soil heterogeneities, and seawater contamination on land productivity

Sulfide-binding hemoglobins: Effects of mutations on active-site flexibility

The dynamics of Hemoglobin I (HbI) from the clam Lucina pectinata, from wild-type sperm whale (SW) myoglobin, and from the L29F/H64Q/V68F triple mutant of SW, both unligated and bound to hydrogen sulfide (H2S), have been studied in molecular dynamics simulations. Features that account for differences in H2S affinity among the three have been examined. Our results verify the existence of an unusual heme rocking motion in unligated HbI that can promote the entrance of large ligands such as H2S. The FQF-mutant partially reproduces the amplitude and relative orientation of the motion of HbI's heme group. Therefore, besides introducing favorable electrostatic interactions with H2S, the three mutations in the distal pocket change the dynamic properties of the heme group. The active-site residues Gln-64(E7), Phe-43(CD1), and His-93(F8) are also shown to be more flexible in unligated HbI than in FQF-mutant and SW. Further contributions to H2S affinity come from differences in hydrogen bonding between the heme propionate groups and nearby amino acid residues.Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicada

Sulfide-binding hemoglobins: Effects of mutations on active-site flexibility

The dynamics of Hemoglobin I (HbI) from the clam Lucina pectinata, from wild-type sperm whale (SW) myoglobin, and from the L29F/H64Q/V68F triple mutant of SW, both unligated and bound to hydrogen sulfide (H2S), have been studied in molecular dynamics simulations. Features that account for differences in H2S affinity among the three have been examined. Our results verify the existence of an unusual heme rocking motion in unligated HbI that can promote the entrance of large ligands such as H2S. The FQF-mutant partially reproduces the amplitude and relative orientation of the motion of HbI's heme group. Therefore, besides introducing favorable electrostatic interactions with H2S, the three mutations in the distal pocket change the dynamic properties of the heme group. The active-site residues Gln-64(E7), Phe-43(CD1), and His-93(F8) are also shown to be more flexible in unligated HbI than in FQF-mutant and SW. Further contributions to H2S affinity come from differences in hydrogen bonding between the heme propionate groups and nearby amino acid residues.Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicada

Cryo-EM analysis of Ebola virus nucleocapsid-like assembly

This protocol describes the reconstitution of the filamentous Ebola virus nucleocapsid-like assembl