Water Structure and Properties at Hydrophilic and Hydrophobic Surfaces

The properties of water on both molecular and macroscopic surfaces critically influence a wide range of physical behaviors, with applications spanning from membrane science to catalysis to protein engineering. Yet, our current understanding of water interfacing molecular and material surfaces is incomplete, in part because measurement of water structure and molecular-scale properties challenges even the most advanced experimental characterization techniques and computational approaches. This review highlights progress in the ongoing development of tools working to answer fundamental questions on the principles that govern the interactions between water and surfaces. One outstanding and critical question is what universal molecular signatures capture the hydrophobicity of different surfaces in an operationally meaningful way, since traditional macroscopic hydrophobicity measures like contact angles fail to capture even basic properties of molecular or extended surfaces with any heterogeneity at the nanometer length scale. Resolving this grand challenge will require close interactions between state-of-the-art experiments, simulations, and theory, spanning research groups and using agreed-upon model systems, to synthesize an integrated knowledge of solvation water structure, dynamics, and thermodynamics.

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Quantitative linear dichroism imaging of molecular processes in living cells made simple by open software tools

Communications Biology ◽

10.1038/s42003-021-01694-1 ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

Alexey Bondar ◽

Olga Rybakova ◽

Josef Melcr ◽

Jan Dohnálek ◽

Petro Khoroshyy ◽

...

Keyword(s):

Biological Systems ◽

Linear Dichroism ◽

Quantitative Information ◽

Living Cells ◽

Software Tools ◽

Model Systems ◽

Membrane Properties ◽

Polarization Microscopy ◽

Molecular Processes ◽

Wide Range

AbstractFluorescence-detected linear dichroism microscopy allows observing various molecular processes in living cells, as well as obtaining quantitative information on orientation of fluorescent molecules associated with cellular features. Such information can provide insights into protein structure, aid in development of genetically encoded probes, and allow determinations of lipid membrane properties. However, quantitating and interpreting linear dichroism in biological systems has been laborious and unreliable. Here we present a set of open source ImageJ-based software tools that allow fast and easy linear dichroism visualization and quantitation, as well as extraction of quantitative information on molecular orientations, even in living systems. The tools were tested on model synthetic lipid vesicles and applied to a variety of biological systems, including observations of conformational changes during G-protein signaling in living cells, using fluorescent proteins. Our results show that our tools and model systems are applicable to a wide range of molecules and polarization-resolved microscopy techniques, and represent a significant step towards making polarization microscopy a mainstream tool of biological imaging.

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Regulation of Cytochrome c Oxidase by Natural Compounds Resveratrol, (–)-Epicatechin, and Betaine

Cells ◽

10.3390/cells10061346 ◽

2021 ◽

Vol 10 (6) ◽

pp. 1346

Author(s):

Icksoo Lee

Keyword(s):

Cytochrome C ◽

Cytochrome C Oxidase ◽

Model Systems ◽

Health Improvement ◽

Published Data ◽

Mitochondrial Electron Transport Chain ◽

Naturally Occurring ◽

Transport Chain ◽

Wide Range ◽

Experimental Model Systems

Numerous naturally occurring molecules have been studied for their beneficial health effects. Many compounds have received considerable attention for their potential medical uses. Among them, several substances have been found to improve mitochondrial function. This review focuses on resveratrol, (–)-epicatechin, and betaine and summarizes the published data pertaining to their effects on cytochrome c oxidase (COX) which is the terminal enzyme of the mitochondrial electron transport chain and is considered to play an important role in the regulation of mitochondrial respiration. In a variety of experimental model systems, these compounds have been shown to improve mitochondrial biogenesis in addition to increased COX amount and/or its enzymatic activity. Given that they are inexpensive, safe in a wide range of concentrations, and effectively improve mitochondrial and COX function, these compounds could be attractive enough for possible therapeutic or health improvement strategies.

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Is contact angle a cause or an effect? – A cautionary tale

E3S Web of Conferences ◽

10.1051/e3sconf/202014603004 ◽

2020 ◽

Vol 146 ◽

pp. 03004

Author(s):

Douglas Ruth

Keyword(s):

Contact Angle ◽

Solid Surface ◽

Contact Angles ◽

Two Dimensions ◽

Experimental Results ◽

Flow In Porous Media ◽

Two Dimensional ◽

Wide Range ◽

Fluid Drop ◽

Surrounding Fluid

The most influential parameter on the behavior of two-component flow in porous media is “wettability”. When wettability is being characterized, the most frequently used parameter is the “contact angle”. When a fluid-drop is placed on a solid surface, in the presence of a second, surrounding fluid, the fluid-fluid surface contacts the solid-surface at an angle that is typically measured through the fluid-drop. If this angle is less than 90°, the fluid in the drop is said to “wet” the surface. If this angle is greater than 90°, the surrounding fluid is said to “wet” the surface. This definition is universally accepted and appears to be scientifically justifiable, at least for a static situation where the solid surface is horizontal. Recently, this concept has been extended to characterize wettability in non-static situations using high-resolution, two-dimensional digital images of multi-component systems. Using simple thought experiments and published experimental results, many of them decades old, it will be demonstrated that contact angles are not primary parameters – their values depend on many other parameters. Using these arguments, it will be demonstrated that contact angles are not the cause of wettability behavior but the effect of wettability behavior and other parameters. The result of this is that the contact angle cannot be used as a primary indicator of wettability except in very restricted situations. Furthermore, it will be demonstrated that even for the simple case of a capillary interface in a vertical tube, attempting to use simply a two-dimensional image to determine the contact angle can result in a wide range of measured values. This observation is consistent with some published experimental results. It follows that contact angles measured in two-dimensions cannot be trusted to provide accurate values and these values should not be used to characterize the wettability of the system.

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Specific Control of Pseudomonas aeruginosa Surface-Associated Behaviors by Two c-di-GMP Diguanylate Cyclases

mBio ◽

10.1128/mbio.00183-10 ◽

2010 ◽

Vol 1 (4) ◽

Cited By ~ 106

Author(s):

Judith H. Merritt ◽

Dae-Gon Ha ◽

Kimberly N. Cowles ◽

Wenyun Lu ◽

Diana K. Morales ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Biofilm Formation ◽

Extracellular Polysaccharide ◽

Diguanylate Cyclase ◽

Flagellar Motility ◽

Critical Question ◽

Cyclic Diguanylate ◽

Critical Signal ◽

Content Type ◽

Wide Range

ABSTRACT The signaling nucleotide cyclic diguanylate (c-di-GMP) regulates the transition between motile and sessile growth in a wide range of bacteria. Understanding how microbes control c-di-GMP metabolism to activate specific pathways is complicated by the apparent multifold redundancy of enzymes that synthesize and degrade this dinucleotide, and several models have been proposed to explain how bacteria coordinate the actions of these many enzymes. Here we report the identification of a diguanylate cyclase (DGC), RoeA, of Pseudomonas aeruginosa that promotes the production of extracellular polysaccharide (EPS) and contributes to biofilm formation, that is, the transition from planktonic to surface-dwelling cells. Our studies reveal that RoeA and the previously described DGC SadC make distinct contributions to biofilm formation, controlling polysaccharide production and flagellar motility, respectively. Measurement of total cellular levels of c-di-GMP in ∆roeA and ∆sadC mutants in two different genetic backgrounds revealed no correlation between levels of c-di-GMP and the observed phenotypic output with regard to swarming motility and EPS production. Our data strongly argue against a model wherein changes in total levels of c-di-GMP can account for the specific surface-related phenotypes of P. aeruginosa. IMPORTANCE A critical question in the study of cyclic diguanylate (c-di-GMP) signaling is how the bacterial cell integrates contributions of multiple c-di-GMP-metabolizing enzymes to mediate its cognate functional outputs. One leading model suggests that the effects of c-di-GMP must, in part, be localized subcellularly. The data presented here show that the phenotypes controlled by two different diguanylate cyclase (DGC) enzymes have discrete outputs despite the same total level of c-di-GMP. These data support and extend the model in which localized c-di-GMP signaling likely contributes to coordination of the action of the multiple proteins involved in the synthesis, degradation, and/or binding of this critical signal.

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Microstructure representation of snow in coupled snowpack and microwave emission models

10.5194/tc-2016-181 ◽

2016 ◽

Cited By ~ 1

Author(s):

Melody Sandells ◽

Richard Essery ◽

Nick Rutter ◽

Leanne Wake ◽

Leena Leppänen ◽

...

Keyword(s):

Brightness Temperature ◽

Microstructure Evolution ◽

Microwave Emission ◽

Model Systems ◽

Research Centre ◽

Emission Model ◽

Mean Error ◽

Scale Factors ◽

Wide Range ◽

Emission Models

Abstract. This is the first study to encompass a wide range of coupled snow evolution and microwave emission models in a common modelling framework in order to generalise the link between snowpack microstructure predicted by the snow evolution models and microstructure required to reproduce observations of brightness temperature as simulated by snow emission models. Brightness temperatures at 18.7 and 36.5 GHz were simulated by 1323 ensemble members, formed from 63 Jules Investigation Model snowpack simulations, three microstructure evolution functions and seven microwave emission model configurations. Two years of meteorological data from the Sodankylä Arctic Research Centre, Finland were used to drive the model over the 2011–2012 and 2012–2013 winter periods. Comparisons between simulated snow grain diameters and field measurements with an IceCube instrument showed that the evolution functions from SNTHERM simulated snow grain diameters that were too large (mean error 0.12 to 0.16 mm), whereas MOSES and SNICAR microstructure evolution functions simulated grain diameters that were too small (mean error −0.16 to −0.24 mm for MOSES, and −0.14 to −0.18 mm for SNICAR). No model (HUT, MEMLS or DMRT-ML) provided a consistently good fit across all frequencies and polarizations. The smallest absolute values of mean bias in brightness temperature over a season for a particular frequency and polarization ranged from 0.9 to 7.2 K. Optimal scaling factors for the snow microstructure were presented to compare compatibility between snowpack model microstructure and emission model microstructure. Scale factors ranged between 0.3 for the SNTHERM-Empirical MEMLS model combination (2011–2012), and 5.0 or greater when considering non-sticky particles in DMRT-ML in conjunction with MOSES or SNICAR microstructure (2012–2013). Differences in scale factors between microstructure models were generally greater than the differences between microwave emission models, suggesting that more accurate simulations in coupled snowpack-microwave model systems will be achieved primarily through improvements in the snowpack microstructure representation, followed by improvements in the emission models. Other snowpack parameterisations in the snowpack model, mainly densification, led to a mean brightness temperature difference of 11 K when the JIM ensemble was applied to the MOSES microstructure and empirical MEMLS emission model for the 2011–2012 season. Consistency between snowpack microstructure and microwave emission models, and the choice of snowpack densification algorithms should be considered in the design of snow mass retrieval systems and microwave data assimilation systems.

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NESTED HIGH-RESOLUTION NOx AND PM SIMULATIONS OVER ZÜRICH

10.5194/egusphere-egu21-6202 ◽

2021 ◽

Author(s):

Ivo Suter ◽

Lukas Emmenegger ◽

Dominik Brunner

Keyword(s):

Air Pollution ◽

Air Quality ◽

Boundary Conditions ◽

Meteorological Conditions ◽

Model Systems ◽

Multi Scale ◽

Wide Range ◽

The Impact ◽

The City ◽

Concentration Levels

Reducing air pollution, which is the world's largest single environmental health risk, demands better-informed air quality policies. Consequently, multi-scale air quality models are being developed with the goal to resolve cities. One of the major challenges in such model systems is to accurately represent all large- and regional-scale processes that may critically determine the background concentration levels over a given city. This is particularly true for longer-lived species such as aerosols, for which background levels often dominate the concentration levels, even within the city. Furthermore, the heterogeneous local emissions, and complex dispersion in the city have to be considered carefully.In this study, the impact of processes across a wide range of scales on background concentrations over Switzerland and the city of Zurich was modelled by performing one year of nested European and Swiss national COSMO-ART simulations to obtain adequate boundary conditions for gas-phase chemical, aerosol and meteorological conditions for city-resolving simulations. The regional climate chemistry model COSMO-ART (Vogel et al. 2009) was used in a 1-way coupled mode. The outer, European, domain, which was driven by chemical boundary conditions from the global MOZART model, had a 6.6 km horizontal resolution and the inner, Swiss, domain one of 2.2 km. For the city scale, a catalogue of more than 1000 mesoscale flow patterns with 100 m resolution was created with the model GRAMM, based on a discrete set of atmospheric stabilities, wind speeds and directions, accounting for the influence of land-use and topography. Finally, the flow around buildings was solved with the CFD model GRAL forced at the boundaries by GRAMM. Subsequently, Lagrangian dispersion simulations for a set of air pollutants and emission sectors (traffic, industry, ...) based on extremely detailed building and emission data was performed in GRAL. The result of this nested procedure is a library of 3-dimensional air pollution maps representative of hourly situations in Zurich (Berchet et al. 2017). From these pre-computed situations, time-series and concentration maps can be obtained by selecting situations according to observed or modelled meteorological conditions.The results were compared to measurements from air quality monitoring network stations. Modelled concentrations of NOx and PM compared well to measurements across multiple locations, provided background conditions were considered carefully. The nested multi-scale modelling system COSMO-ART/GRAMM/GRAL can adequately reproduce local air quality and help understanding the relative contributions of local versus distant emissions, as well as fill the space between precise point measurements from monitoring sites. This information is useful for research, policy-making, and epidemiological studies particularly under the assumption that exceedingly high concentrations become more and more localised phenomenon in the future.

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Planarian Hox genes: novel patterns of expression during regeneration

Development ◽

10.1242/dev.124.1.141 ◽

1997 ◽

Vol 124 (1) ◽

pp. 141-148

Author(s):

J.R. Bayascas ◽

E. Castillo ◽

A.M. Munoz-Marmol ◽

E. Salo

Keyword(s):

Hox Genes ◽

Bilateral Symmetry ◽

Sister Group ◽

Model Systems ◽

Hox Cluster ◽

Positional Identity ◽

Wide Range ◽

Differential Timing ◽

Anteroposterior Polarity

Platyhelminthes are widely considered to be the sister group of coelomates (Philippe, H., Chenuil, A. and Adoutte, A. (1994)Development 1994 Supplement, 15–24) and the first organisms to show bilateral symmetry and cephalization. Within this phylum, the freshwater planarians (Turbellaria, Tricladida) have been used as model systems for studying bidirectional regeneration (Slack, J. M. W. (1980) J. Theor. Biol 82, 105–140). We have been attempting to identify potential pattern-control genes involved in the regeneration of planarian heads and tails after amputation. Since Hox cluster genes determine positional identity along the anteroposterior axis in a wide range of animals (Slack, J. M. W., Holland, P. W. H. and Graham, C. F. (1993) Nature 361,490-492), we performed an extensive search for Hox-related genes in the planarian Dugesia(G)tigrina. Sequence analyses of seven planarian Dthox genes (Dthox-A to Dthox-G) reveal high similarities with the homeodomain region of the Hox cluster genes, allowing us to assign planarian Dthox genes to anterior and medial Hox cluster paralogous groups. Whole-mount in situ hybridization studies in regenerating adults showed very early, synchronous and colocalized activation of Dthox-D, Dthox-A, Dthox-C, Dthox-E, Dthox-G and Dthox-F. After one hour of regeneration a clear expression was observed in all Dthox genes studied. In addition, all seemed to be expressed in the same regenerative tissue, although in the last stages of regeneration (9 to 15 days) a differential timing of deactivation was observed. The same Dthox genes were also expressed synchronously and were colocalized during intercalary regeneration, although their expression was delayed. Terminal regeneration showed identical Dthox gene expression in anterior and posterior blastemas, which may prevent these genes from directing the distinction between head and tail. Finally, continuous expression along the whole lateral blastema in sagittal regenerates reflected a ubiquitous Dthox response in all types of regeneration that was not related specifically with the anteroposterior polarity.

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Hybrid Dynamic Pharmacophore Models as Effective Tools to Identify Novel Chemotypes for Anti-TB Inhibitor Design: A Case Study With Mtb-DapB

Frontiers in Chemistry ◽

10.3389/fchem.2020.596412 ◽

2020 ◽

Vol 8 ◽

Author(s):

Chinmayee Choudhury ◽

Anshu Bhardwaj

Keyword(s):

Binding Site ◽

Binding Sites ◽

Chemical Space ◽

Pharmacophore Model ◽

Model Systems ◽

Receptor Interaction ◽

Hybrid Molecules ◽

Wide Range ◽

Binding Pockets ◽

Pharmacophore Models

Antimicrobial resistance (AMR) is one of the most serious global public health threats as it compromises the successful treatment of deadly infectious diseases like tuberculosis. New therapeutics are constantly needed but it takes a long time and is expensive to explore new biochemical space. One way to address this issue is to repurpose the validated targets and identify novel chemotypes that can simultaneously bind to multiple binding pockets of these targets as a new lead generation strategy. This study reports such a strategy, dynamic hybrid pharmacophore model (DHPM), which represents the combined interaction features of different binding pockets contrary to the conventional approaches, where pharmacophore models are generated from single binding sites. We have considered Mtb-DapB, a validated mycobacterial drug target, as our model system to explore the effectiveness of DHPMs to screen novel unexplored compounds. Mtb-DapB has a cofactor binding site (CBS) and an adjacent substrate binding site (SBS). Four different model systems of Mtb-DapB were designed where, either NADPH/NADH occupies CBS in presence/absence of an inhibitor 2, 6-PDC in the adjacent SBS. Two more model systems were designed, where 2, 6-PDC was linked to NADPH and NADH to form hybrid molecules. The six model systems were subjected to 200 ns molecular dynamics simulations and trajectories were analyzed to identify stable ligand-receptor interaction features. Based on these interactions, conventional pharmacophore models (CPM) were generated from the individual binding sites while DHPMs were created from hybrid-molecules occupying both binding sites. A huge library of 1,563,764 publicly available molecules were screened by CPMs and DHPMs. The screened hits obtained from both types of models were compared based on their Hashed binary molecular fingerprints and 4-point pharmacophore fingerprints using Tanimoto, Cosine, Dice and Tversky similarity matrices. Molecules screened by DHPM exhibited significant structural diversity, better binding strength and drug like properties as compared to the compounds screened by CPMs indicating the efficiency of DHPM to explore new chemical space for anti-TB drug discovery. The idea of DHPM can be applied for a wide range of mycobacterial or other pathogen targets to venture into unexplored chemical space.

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Transcranial alternating current stimulation entrains single-neuron activity in the primate brain

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1815958116 ◽

2019 ◽

Vol 116 (12) ◽

pp. 5747-5755 ◽

Cited By ~ 63

Author(s):

Matthew R. Krause ◽

Pedro G. Vieira ◽

Bennett A. Csorba ◽

Praveen K. Pilly ◽

Christopher C. Pack

Keyword(s):

Human Brain ◽

Electric Fields ◽

Critical Role ◽

Spike Timing ◽

Model Systems ◽

Neuron Activity ◽

Transcranial Electrical Stimulation ◽

Noninvasive Technique ◽

Early Results ◽

Wide Range

Spike timing is thought to play a critical role in neural computation and communication. Methods for adjusting spike timing are therefore of great interest to researchers and clinicians alike. Transcranial electrical stimulation (tES) is a noninvasive technique that uses weak electric fields to manipulate brain activity. Early results have suggested that this technique can improve subjects’ behavioral performance on a wide range of tasks and ameliorate some clinical conditions. Nevertheless, considerable skepticism remains about its efficacy, especially because the electric fields reaching the brain during tES are small, whereas the likelihood of indirect effects is large. Our understanding of its effects in humans is largely based on extrapolations from simple model systems and indirect measures of neural activity. As a result, fundamental questions remain about whether and how tES can influence neuronal activity in the human brain. Here, we demonstrate that tES, as typically applied to humans, affects the firing patterns of individual neurons in alert nonhuman primates, which are the best available animal model for the human brain. Specifically, tES consistently influences the timing, but not the rate, of spiking activity within the targeted brain region. Such effects are frequency- and location-specific and can reach deep brain structures; control experiments show that they cannot be explained by sensory stimulation or other indirect influences. These data thus provide a strong mechanistic rationale for the use of tES in humans and will help guide the development of future tES applications.

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A spherical particle straddling a fluid/gas interface in an axisymmetric straining flow

Journal of Fluid Mechanics ◽

10.1017/s0022112090000726 ◽

1990 ◽

Vol 217 ◽

pp. 263-298 ◽

Cited By ~ 9

Author(s):

J. A. Stoos ◽

L. G. Leal

Keyword(s):

Contact Angle ◽

Spherical Particle ◽

Numerical Solutions ◽

Contact Angles ◽

Boundary Integral ◽

Equilibrium Contact Angle ◽

Equilibrium Configurations ◽

Wide Range ◽

The Stability ◽

Neutrally Buoyant

Numerical solutions, obtained via the boundary-integral technique, are used to consider the effect of a linear axisymmetric straining flow on the existence of steady-state configurations in which a neutrally buoyant spherical particle straddles a gas–liquid interface. The problem is directly applicable to predictions of the stability of particle capture in flotation processes, and is also of interest in the context of contact angle and surface tension measurements. A primary goal of the present study is a determination of the critical capillary number, Cac, beyond which an initially captured particle is pulled from the interface by the flow, and the dependence of Cac on the equilibrium contact angle θc. We also present equilibrium configurations for a wide range of contact angles and subcritical capillary numbers.

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