Modulation of Phospholipase A2 Membrane Activity by Anti-inflammatory Drugs.

The phospholipase A2 (PLA2) superfamily consists of lipolytic enzymes that hydrolyze specific cell membrane phospholipids and have long been considered a central hub of biosynthetic pathways, where their lipid metabolites exert a variety of physiological roles. A misregulated PLA2 activity is associated with mainly inflammatory-derived pathologies and thus has shown relevant therapeutic potential. Many natural and synthetic anti-inflammatory drugs (AIDs) have been proposed as direct modulators of PLA2 activity. However, despite the specific chemical properties that these drugs share in common, little is known about the indirect modulation able to finely tune membrane structural changes at the precise lipid-binding site. Here, we use a novel experimental strategy based on differential scanning calorimetry to systematically study the structural properties of lipid membrane systems during PLA2 cleavage and under the influence of several AIDs. For a better understanding of the AIDs-membrane interaction, we present a comprehensive and comparative set of molecular dynamics (MD) simulations. Our thermodynamic results clearly demonstrate that PLA2 cleavage is hindered by those AIDs that significantly reduce the lipid membrane cooperativity, while the rest of the AIDs oppositely tend to catalyze PLA2 activity to different extents. On the other hand, our MD simulations support experimental results by providing atomistic details on the binding, insertion, and dynamics of each AID on a pure lipid system; the drug efficacy to impact membrane cooperativity is related to the lipid order perturbation. This work suggests a membrane-based mechanism of action for diverse AIDs against PLA2 activity and provides relevant clues that must be considered in its modulation.

Xenon and Krypton Dissolved in Water Form Nanoblobs: No Evidence for Nanobubbles.

We demonstrate, experimentally and by molecular dynamics simulations, that krypton and xenon form nanostructured water-gas domains. High pressure was applied to force the inert gases to dissolve in water following Henry's law, then the liquid was depressurized, centrifuged, and inspected by dynamic light scattering. The observed objects have similar sizes and electrical properties to nanobubbles, but we found that they have fairly neutral buoyancy even at high gravitational fields. We posit that the formed nano objects are not bubbles but blobs, unique structures conceived as clathrate-hydrate precursors, thus resolving the so-called Laplace pressure bubble catastrophe.

On the evolution of the exclusion zone produced by hydrophilic surfaces: A contracted description.

After exciting scientific debates about its nature, the development of the exclusion zone, a region near hydrophilic surfaces from which charged colloidal particles are strongly expelled, has been finally traced back to the diffusiophoresis produced by unbalanced ion gradients. This was done by numerically solving the coupled Poisson equation for electrostatics, the two stationary Stokes equations for low Reynolds numbers in incompressible fluids, and the Nernst-Planck equation for mass transport. Recently, it has also been claimed that the leading mechanism behind the diffusiophoretic phenomenon is electrophoresis [Esplandiu et al., Soft Matter 16, 3717 (2020)]. In this paper, we analyze the evolution of the exclusion zone based on a one-component interaction model at the Langevin equation level, which leads to simple analytical expressions instead of the complex numerical scheme of previous works, yet being consistent with it. We manage to reproduce the evolution of the exclusion zone width and the mean-square displacements of colloidal particles we measure near Nafion, a perfluorinated polymer membrane material, along with all characteristic time regimes, in a unified way. Our findings are also strongly supported by complementary experiments using two parallel planar conductors kept at a fixed voltage, mimicking the hydrophilic surfaces, and some computer simulations.

Cholesterol sequestration by xenon nano bubbles leads to lipid raft destabilization.

Combined coarse-grained (CG) and atomistic molecular dynamics (MD) simulations were performed to study the interactions of xenon with model lipid rafts consisting of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-dilauroyl-sn-glycero-3-phosphocholine (DLPC) and cholesterol (Chol). At a concentration of 2 Xe/lipid we observed an unexpected result: spontaneous nucleation of Xe nano bubbles which rapidly plunged into the bilayer. In this process Chol, essential for raft stabilization, was pulled out from the raft into the hydrophobic zone. When concentration was further increased (3 Xe/lipid), the bubbles increase in size and disrupted both the membrane and raft. We computed the radial distribution functions, pair-wise potentials, second virial coefficients and Schlitter entropy to scrutinize the nature of the interactions. Our findings, concurring with a recent report on the origin of general anaesthesia (M. A. Pavel, E. N. Petersen, H. Wang, R. A. Lerner and S. B. Hansen, Proc. Natl. Acad. Sci. U. S. A., 2020, 117(24), 13757-13766), suggest that the well-known anaesthetic effect of Xe could be mediated by sequestration of Chol, which, in turn, compromises the stability of rafts where specialized proteins needed to produce the nervous signal are anchored.

The effect of green light on the motility of mouse sperm at two different temperatures.

Photo-modulation with visible light has been used to induce gains in the motility of the sperms of rabbits, boars, buffalo, bulls, fish, and humans. Although different hypotheses have been proposed to explain such an effect, the origin and mechanisms by which visible light affects sperm motility are still far from being completely understood. Several groups have observed changes in the intracellular Ca2+ concentration and significant differences in the production of ROS, which are attributed to specific photosensitizers. Also, it has been reported that blue light induces nitric oxide production in sperm cells, which plays a vital role in acrosome reaction and capacitation leading to an augmentation in the fertilisation probability. In the present work, we study the effects of green light (490-540 nm) on the sperm motility of mice. Firstly, we carried out experiments at 37 °C to confirm what previous researchers have observed before using red and blue light: that the overall sperm motility increases. Secondly, we studied the effects of green light at 10 °C and found that the motility drastically diminishes. In order to understand this opposing outcome, we carried out fluorescence measurements to evaluate reactive oxygen species production induced by green light at both temperatures. Our results suggest that the balance between the use and generation of ROS at 37 °C is favorable to the cells, while at 10 °C it is harmful.

Plant proteases for bioactive peptides release: A review.

Proteins are a potential source of health-promoting biomolecules with medical, nutraceutical, and food applications. Nowadays, bioactive peptides production, its isolation, characterization, and strategies for its delivery to target sites are a matter of intensive research. In vitro and in vivo studies regarding the bioactivity of peptides has generated strong evidence of their health benefits. Dairy proteins are considered the richest source of bioactive peptides, however proteins from animal and vegetable origin also have been shown to be important sources. Enzymatic hydrolysis has been the process most commonly used for bioactive peptide production. Most commercial enzymatic preparations frequently used are from animal (e.g., trypsin and pepsin) and microbial (e.g., Alcalase® and Neutrase®) sources. Although the use of plant proteases is still relatively limited to papain and bromelain from papaya and pineapple, respectively, the application of new plant proteases is increasing. This review presents the latest knowledge in the use and diversity of plant proteases for bioactive peptides release from food proteins including both available commercial plant proteases as well as new potential plant sources. Furthermore, the properties of peptides released by plant proteases and health benefits associated in the control of disorders such as hypertension, diabetes, obesity, and cancer are reviewed.

Calcium and protons affect the interaction of neurotransmitters and anesthetics with anionic lipid membranes.

We study how zwitterionic and anionic biomembrane models interact with neurotransmitters (NTs) and anesthetics (ATs) in the presence of Ca(2+) and different pH conditions. As NTs we used acetylcholine (ACh), γ-aminobutyric acid (GABA), and l-glutamic acid (LGlu). As ATs, tetracaine (TC), and pentobarbital (PB) were employed. By using differential scanning calorimetry (DSC), we analyzed the changes such molecules produce in the thermal properties of the membranes. We found that calcium and pH play important roles in the interactions of NTs and ATs with the anionic lipid membranes. Changes in pH promote deprotonation of the phosphate groups in anionic phospholipids inducing electrostatic interactions between them and NTs; but if Ca(2+) ions are in the system, these act as bridges. Such interactions impact the physical properties of the membranes in a similar manner that anesthetics do. Beyond the usual biochemical approach, we claim that these effects should be taken into account to understand the excitatory-inhibitory orchestrated balance in the nervous system.

Pentobarbital modifies the lipid raft-protein interaction: A first clue about the anesthesia mechanism on NMDA and GABAA receptors.

Recent studies have shown that anesthetic agents alter the physical properties of lipid rafts on model membranes. However, if this destabilization occurs in brain membranes, altering the lipid raft-protein interaction, remains unknown. We analyzed the effects produced by pentobarbital (PB) on brain plasma membranes and lipid rafts in vivo. We characterized for the first time the thermotropic behavior of plasma membranes, synaptosomes, and lipid rafts from rat brain. We found that the transition temperature from the ordered gel to disordered liquid phase of lipids is close to physiological temperature. We then studied the effect of PB on protein composition of lipid rafts. Our results show a reduction of the total protein associated to rafts, with a higher reduction of the NMDAR compared to the GABAA receptor. Both receptors are considered the main targets of PB. In general, our results suggest that lipid rafts could be plausible mediators in anesthetic action.

Propagation of a thermo-mechanical perturbation on a lipid membrane.

The propagation of sound waves on lipid monolayers supported on water has been previously studied during the melting transition. Since changes in volume, area, and compressibility in lipid membranes have biological relevance, the observed sound propagation is of paramount importance. However, it is unknown what would occur on a lipid bilayer, which is a more approximate model of a cell membrane. With the aim to answer this relevant question, we built an experimental setup to assemble long artificial lipid membranes. We found that if these membranes are heated in order to force local melting, a thermo-mechanical perturbation propagates a long distance. Our findings may support the existence of solitary waves, postulated to explain the propagation of isentropic signals together with the action potential in neurons.

Exploring the physics of sand drawings: The role of craters, furrows and piles.

Few years ago an article addressing the physics behind aaabstract paintings was published by Herczynski et al. (Phys. Today 64, 31 (2011) issue No. 6). The authors aimed to understand how artists like Jackson Pollock manipulated paints to create pieces of art where the theory of fluid dynamics had a clear and perceivable role. Scaling laws were found to explain the plasticity observed in the artists's traces that we admire in worldwide museums. Because sand drawings are not only wonderful artistic expressions but also intangible cultural heritages of humanity, we wonder if they could be analyzed in a similar fashion. Our goal is to explore the physics behind the formation of such drawings. In order to do so, we carry out experimental studies on the formation of sand cavities, furrows and piles, which individually or interconnected, give rise to artistic patterns. Moreover, in order to manipulate such three observables, some control parameters are needed. Altogether, they conform into simple exponential and power laws that collapse when a scaling is performed.

Coefficient of restitution mediated by a diamagnetic interaction.

We study how a magnetic bead bounces onto a horizontal diamagnetic conducting plane. The bead, falling down by gravity from a certain height, produces an Eddy current that creates a repelling force. For low velocities the bead is trapped by the surface, for intermediate ones it escapes. In such a case the induced current changes its sign, and so does the force. The balance between diamagnetic and viscoelastic interactions determines the bouncing dynamics. We find experimentally the restitution coefficient as a function of the impact speed of the bead and develop, taking into account simple energetic considerations, a model able to reproduce our findings.

Diastolic dysfunction in the critically ill patient.

Left ventricular diastolic dysfunction is a common finding in critically ill patients. It is characterized by a progressive deterioration of the relaxation and the compliance of the left ventricle. Two-dimensional and Doppler echocardiography is a cornerstone in its diagnosis. Acute pulmonary edema associated with hypertensive crisis is the most frequent presentation of diastolic dysfunction critically ill patients. Myocardial ischemia, sepsis and weaning failure from mechanical ventilation also may be associated with diastolic dysfunction. The treatment is based on the reduction of pulmonary congestion and left ventricular filling pressures. Some studies have found a prognostic role of diastolic dysfunction in some diseases such as sepsis. The present review aims to analyze thoroughly the echocardiographic diagnosis and the most frequent scenarios in critically ill patients in whom diastolic dysfunction plays a key role.

Free-energy landscapes of granular clusters grown by magnetic interaction.

We experimentally study the aggregation of small clusters made of non-Brownian dipolar beads in a vibro-fluidized system. The particles are paramagnetic spheres that add around a fixed magnetic seed inside a granular gas of glass beads. We observe that under appropriate physical conditions symmetric and asymmetric cluster configurations are created and, as the number of particles increases, the aggregation time obeys a power law. We use an ensemble statistics to evaluate the free-energies and entropies landscapes of the granular clusters. The correspondence between such landscapes shows that, even if the system is of macroscopic scale and not in strict equilibrium, our approach to understand the relationship between the cluster structures and the interactions that create them is reliable.

Penetration of projectiles into granular targets.

Energetic collisions of subatomic particles with fixed or moving targets have been very valuable to penetrate into the mysteries of nature. But the mysteries are quite intriguing when projectiles and targets are macroscopically immense. We know that countless debris wandering in space impacted (and still do) large asteroids, moons and planets; and that millions of craters on their surfaces are traces of such collisions. By classifying and studying the morphology of such craters, geologists and astrophysicists obtain important clues to understand the origin and evolution of the Solar System. This review surveys knowledge about crater phenomena in the planetary science context, avoiding detailed descriptions already found in excellent papers on the subject. Then, it examines the most important results reported in the literature related to impact and penetration phenomena in granular targets obtained by doing simple experiments. The main goal is to discern whether both schools, one that takes into account the right ingredients (planetary bodies and very high energies) but cannot physically reproduce the collisions, and the other that easily carries out the collisions but uses laboratory ingredients (small projectiles and low energies), can arrive at a synergistic intersection point.

Fluidized or not fluidized? Biophysical characterization of biohybrid lipid/protein/polymer liposomes and their interaction with tetracaine.

BACKGROUND: Nanomedicine and the pharmaceutical industry demand the investigation of new biomaterials to improve drug therapies. Combinations of lipids, proteins, and polymers represent innovative platforms for drug delivery. However, little is known about the interactions between such compounds and this knowledge is key to prepare successful drug delivery systems. METHODS: Biophysical properties of biohybrid vesicles (BhVs) composed of phospholipids, proteins, and amphiphilic block copolymers, assembled without using organic solvents, were investigated by differential scanning calorimetry and dynamic light scattering. We studied four biohybrid systems; two of them included the effect of incorporating tetracaine. Thermal changes of phospholipids and proteins when interacting with the amphiphilic block copolymers and tetracaine were analyzed. RESULTS: Lysozyme and the copolymers adsorb onto the lipid bilayer modifying the phase transition temperature, enthalpy change, and cooperativity. Dynamic light scattering investigations revealed relevant changes in the size and zeta potential of the BhVs. Interestingly, tetracaine, a membrane-active drug, can fluidize or rigidize BhVs. CONCLUSIONS: We conclude that positively charged regions of lysozyme are necessary to incorporate the block copolymer chains into the lipid membrane, turning the bilayer into a more rigid system. Electrostatic properties and the hydrophilic-lipophilic balance are determinant for the stability of biohybrid membranes. GENERAL SIGNIFICANCE: This investigation provides fundamental information associated with the performance of biohybrid drug delivery systems and can be of practical significance for designing more efficient drug nanocarriers.

Phase transitions of liposomes: when light meets heat.

Phase transitions of liposomes are normally studied by differential scanning calorimetry. A suspension of liposomes is subjected to an increase (decrease) of temperature and when heat is absorbed (released), the liposomes transit from a gel (liquid) to a liquid (gel) phase. This endothermic (exothermic) process takes place at a temperature called the melting temperatureTm, which is distinctive of the type of lipids forming the vesicles. The vesicles, though, also modify their size in the transition. Indeed, the thickness of the membranes decreases (increases) because carbon tails misalign (align). Concomitant with the modifications in the membrane thickness, the diameter (D) of the liposomes changes too. Therefore, when they are inspected by light, the scattered signal carries information from such dilatation (contraction) process. We performed careful experiments using dynamic light scattering as a function of temperature to detect the size changes of different liposomes. Gaussian fits of the derivatives of theDvsTcurves coincide within 1% with thermograms, which hints to the possibility of performing thermodynamic studies of lipid systems employing light.

Impact craters in granular media: grains against grains.

Impact experiments in granular media are usually performed with solid projectiles that do not fragment at all. Contrastingly, we study here the morphology produced by the impact of spherical granular projectiles whose structure is utterly lost after collision. Simple and complex craters are observed, depending on the packing fraction of the balls. Their diameters D and depths z are analyzed as a function of the drop height h. We find the same power law D ∝ h(1/4) obtained with solid spheres, but a discontinuity at a certain threshold height, related to the cohesive energy of the projectiles, shows up. Counterintuitively, instead of a monotonic increase with the collisional energy, z becomes constant above this threshold.

Infinite penetration of a projectile into a granular medium.

An object falling in a fluid reaches a terminal velocity when the drag force and its weight are balanced. Contrastingly, an object impacting into a granular medium rapidly dissipates all its energy and comes to rest always at a shallow depth. Here we study, experimentally and theoretically, the penetration dynamics of a projectile in a very long silo filled with expanded polystyrene particles. We discovered that, above a critical mass, the projectile reaches a terminal velocity and, therefore, an endless penetration.

Nanovesicles drive a tunable dynamical arrest of microparticles.

Vitrification in a dilute colloidal system needs an asymmetric particle composition (a mixture of nano and micro colloids) to materialize. The volume fraction of the large particles increases (up to ≈0.58) driven by depletion forces produced by the smaller colloids. Such entropic forces are short-ranged and attractive. We found a different type of dynamical arrest in an extremely dilute asymmetric mixture of nanovesicles and polystyrene microparticles, where energy, instead of entropy, is the main protagonist to drive the arrest. Furthermore, when the vesicles go through the gel-fluid phase transition, the mean square displacements of the microparticles suffer a sudden splitting indicating a viscous jump. If the vesicles are doped with negatively charged lipids, particles and vesicles repel each other and the rheology of the mixture becomes athermal and Newtonian. Our findings are important to understand caging phenomena in biological systems, where diverse electrostatic distributions are present.

[Bearing surfaces in primary hip arthroplasty. Is there any difference?] / Pares articulares en prótesis primaria de cadera. ¿Existe alguna diferencia?

INTRODUCTION: In primary hip replacement, different materials are used for bearing surfaces. In our medium metal or ceramic heads with highly crossed-linked polyethylene (PA) are the most used. These combinations have good results, but it is not clear which is clinically superior. The objective of this study is to determine whether there is any clinically significant difference based on a systematic review of the literature and national registries of arthroplasty. MATERIAL AND METHODS: We conduct a systematic review of the literature and national registries of arthroplasty and we were looking for studies comparing bearing surfaces: ceramic-highly cross-linked polyethylene (CP) and metal-highly cross-linked polyethylene (MP); describing the revision rate according to the surface type with a minimum 10-year follow-up. The outcome evaluated was: review rate for any cause depending on surface type. RESULTS: Two out of fifteen national registries were included. The Australian registry shows a difference in the 15-year revision rate: CP: 6.3 (IC 5.8, 6.7) vs MP: 5.1 (IC 4.6, 5.7). The New Zealand registry shows no differences in revision rate/100 components/year: CP 0.54 (0.48-0.61) vs MP 0.61 (0.57-0.66). We do not find clinical studies with inclusion criteria that answer the research question. CONCLUSION: The results of this review show a high survival rate with the use of highly cross-linked polyethylene, the results are similar when using ceramic or metal heads.

INTRODUCCIÓN: En un reemplazo total de cadera primario (RTC), diferentes materiales son los que se usan para las superficies de apoyo. En nuestro medio, las cabezas de metal o cerámica con polietileno altamente entrecruzado (PA) son los más utilizados. Estas combinaciones tienen buenos resultados, pero no es claro cuál es superior clínicamente. Basados en una revisión sistemática de la literatura y de los registros nacionales de artroplastía, el objetivo de este estudio es determinar si existe alguna diferencia significativa desde el punto de vista clínico. MATERIAL Y MÉTODOS: Realizamos una revisión sistemática de la literatura y de los registros nacionales de artroplastía. Buscamos estudios en los que se compararan los tipos de superficie de contacto: cerámica-polietileno altamente entrecruzado (CP) y metal-polietileno altamente entrecruzado (MP), además de los registros nacionales de artroplastía que describieran, con un seguimiento mínimo de 10 años, la tasa de revisión según el tipo de superficie. El desenlace evaluado fue: tasa de revisión por cualquier causa según el tipo de superficie. RESULTADOS: Dos de quince registros nacionales fueron incluidos: el registro australiano muestra una diferencia en la tasa de revisión a 15 años, comparando CP: 6.3 (IC 5.8, 6.7) contra MP: 5.1 (IC 4.6, 5.7). El registro de Nueva Zelanda no muestra diferencias en la tasa de revisión/100 componentes/año: CP de 0.54 (0.48-0.61) en comparación con MP de 0.61 (0.57-0.66). No encontramos estudios clínicos con los criterios de inclusión que respondan la pregunta de investigación. CONCLUSIÓN: Los resultados de esta revisión muestran una alta supervivencia cuando se usa polietileno altamente entrecruzado; asimismo, los resultados son similares cuando se utilizan cabezas de cerámica o metálicas.