Development and Validation of an Artificial Mechanical Skin Model for the Study of Interactions between Skin and Microneedles

Microneedles are small needle‐like structures that are almost invisible to the naked eye. They have an immense potential to serve as a valuable tool in many medical applications, such as painless vaccination. Microneedles work by breaking through the stratum corneum, the outermost barrier layer of the skin, and providing a direct path for drug delivery into the skin. A lot of research has been presented over the past two decades on the applications of microneedles, yet the fundamental mechanism of how they interact, pressure, and penetrate the skin in its native state is worth examining further. As such, a major difficulty with understanding the mechanism of microneedle–skin interaction is the lack of an artificial mechanical human skin model to use as a standardized substrate. In this research news, the development of an artificial mechanical skin model based on a thorough mechanical study of fresh human and porcine skin samples is presented. The artificial mechanical skin model can be used to study the mechanical interactions between microneedles and skin, but not diffusion of molecules across skin. This model can assist in improving the performance of microneedles by enhancing the reproducibility of microneedle depth insertions for optimal drug delivery and biosensing.

     

Body Odors of Parasitized Caterpillars Give Away the Presence of Parasitoid Larvae to Their Primary Hyperparasitoid Enemies

Foraging success of parasitoids depends on the utilization of reliable information on the presence of their often, inconspicuous hosts. These parasitic wasps use herbivore-induced plant volatiles (HIPVs) that provide reliable cues on host presence. However, host searching of hyperparasitoids, a group of parasitoids that parasitize the larvae and pupae of other parasitoids, is more constrained. Their hosts do not feed on plants, and often are even concealed inside the body of the herbivore host. Hyperparasitoids recently have been found to use HIPVs of plants damaged by herbivore hosts in which the parasitoid larvae develop. However, hyperparasitoids that search for these parasitoid larvae may be confronted with healthy and parasitized caterpillars on the same plant, further complicating their host location. In this study, we addressed whether the primary hyperparasitoid Baryscapus galactopus uses caterpillar body odors to discriminate between unparasitized herbivores and herbivores carrying larvae of parasitoid hosts. We show that the hyperparasitoids made faster first contact and spent a longer mounting time with parasitized caterpillars. Moreover, although the three parasitoid hosts conferred different fitness values for the development of B. galactopus, the hyperparasitoids showed similar behavioral responses to caterpillar hosts carrying different primary parasitoid hosts. In addition, a two-chamber olfactometer assay revealed that volatiles emitted by parasitized caterpillars were more attractive to the hyperparasitoids than those emitted by unparasitized caterpillars. Analysis of volatiles revealed that body odors of parasitized caterpillars differ from unparasitized caterpillars, allowing the hyperparasitoids to detect their parasitoid host.     

Pulsed laser reshaping and fragmentation of upconversion nanoparticles — from hexagonal prisms to 1D nanorods through “Medusa”-like structures

One dimensional (1D) nanostructures attract considerable attention, enabling a broad application owing to their unique properties. However, the precise mechanism of 1D morphology attainment remains a matter of debate. In this study, ultrafast picosecond (ps) laser-induced treatment on upconversion nanoparticles (UCNPs) is offered as a tool for 1D-nanostructures formation. Fragmentation, reshaping through recrystallization process and bioadaptation of initially hydrophobic (β-Na_1.5Y_1.5F₆: Yb³⁺, Tm³⁺/β-Na_1.5Y_1.5F₆) core/shell nanoparticles by means of one-step laser treatment in water are demonstrated. “True” 1D nanostructures through “Medusa”-like structures can be obtained, maintaining anti-Stokes luminescence functionalities. A matter of the one-dimensional UCNPs based on direction of energy migration processes is debated. The proposed laser treatment approach is suitable for fast UCNP surface modification and nano-to-nano transformation, that open unique opportunities to expand UCNP applications in industry and biomedicine.

     

Effect of Betaine and Arginine on Interaction of αB-Crystallin with Glycogen Phosphorylase b

Protein–protein interactions (PPIs) play an important role in many biological processes in a living cell. Among them chaperone–client interactions are the most important. In this work PPIs of αB-crystallin and glycogen phosphorylase b (Phb) in the presence of betaine (Bet) and arginine (Arg) at 48 °C and ionic strength of 0.15 M were studied using methods of dynamic light scattering, differential scanning calorimetry, and analytical ultracentrifugation. It was shown that Bet enhanced, while Arg reduced both the stability of αB-crystallin and its adsorption capacity (AC₀) to the target protein at the stage of aggregate growth. Thus, the anti-aggregation activity of αB-crystallin increased in the presence of Bet and decreased under the influence of Arg, which resulted in inhibition or acceleration of Phb aggregation, respectively. Our data show that chemical chaperones can influence the tertiary and quaternary structure of both the target protein and the protein chaperone. The presence of the substrate protein also affects the quaternary structure of αB-crystallin, causing its disassembly. This is inextricably linked to the anti-aggregation activity of αB-crystallin, which in turn affects its PPI with the target protein. Thus, our studies contribute to understanding the mechanism of interaction between chaperones and proteins.     

Methods and Applications of In Silico Aptamer Design and Modeling

Aptamers are nucleic acid analogues of antibodies with high affinity to different targets, such as cells, viruses, proteins, inorganic materials, and coenzymes. Empirical approaches allow the design of in vitro aptamers that bind particularly to a target molecule with high affinity and selectivity. Theoretical methods allow significant expansion of the possibilities of aptamer design. In this study, we review theoretical and joint theoretical-experimental studies dedicated to aptamer design and modeling. We consider aptamers with different targets, such as proteins, antibiotics, organophosphates, nucleobases, amino acids, and drugs. During nucleic acid modeling and in silico design, a full set of in silico methods can be applied, such as docking, molecular dynamics (MD), and statistical analysis. The typical modeling workflow starts with structure prediction. Then, docking of target and aptamer is performed. Next, MD simulations are performed, which allows for an evaluation of the stability of aptamer/ligand complexes and determination of the binding energies with higher accuracy. Then, aptamer/ligand interactions are analyzed, and mutations of studied aptamers made. Subsequently, the whole procedure of molecular modeling can be reiterated. Thus, the interactions between aptamers and their ligands are complex and difficult to understand using only experimental approaches. Docking and MD are irreplaceable when aptamers are studied in silico.     

Heuristic networks for space exploration

This paper reports new results from the development of Linguistic Geometry. This formal theory is intended to discover the inner properties of human expert heuristics, which have been successful in a certain class of complex control systems, and apply them to different systems. Linguistic Geometry relies on the formalization of search heuristics of high-skilled human experts, which allow for the decomposition of a complex system into a hierarchy of subsystems, and thus solve intractable problems by reducing the search. Currently, we investigate heuristics extracted in the form of hierarchical networks of paths. Employing Linguistic Geometry tools, the dynamic hierarchy of networks is represented as a hierarchy of formal attribute languages. This paper includes a formal survey of a Linguistic Geometry, and a new example of a solution of optimization problems for space robotic vehicles. This example includes the actual generation of the hierarchy of languages, with some details of trajectory generation, and it demonstrates the dramatic reduction of search in comparison with conventional search algorithms.