On the differential diagnostic prospects of determining the profile of the lateral organization of the personality during assessment of the systematic alcohol abuse

The article is devoted to the question of the possible improvement of the psychological examination of persons previously examined in alcoholic intoxication (hereinafter—PEAI). The authors propose an original view on the definition of the target of «alcohol screening», the principles and methods of assessing psychological markers of the systematic substance abuse. Purpose of the study: to determine the differential diagnostic significance of identifying the profile of the lateral organization (hereinafter—PLO) when assessing of the systematic of alcohol abuse in those previously examined in a state of alcoholic intoxication. The researchers made an attempt to highlight the features of PLO of such a «risk group» as those previously examined in a state of alcoholic intoxication (based on data obtained during the study according to the typology of E.D. Khomskaya (with a combination of three types of asymmetries: manual, auditory-verbal and visual) of lateral preferences of 19 PEAI patients of the branch of the Moscow Research and Practical Center for Narcology). As a result, the tendency of those previously examined in the state of intoxication to the lack of a «leading ear» and «leading eye», significant differences in the distribution of the attribute «leading hand» among those previously examined in a state of alcoholic intoxication and in the population were revealed. Conclusion. According to the results of this study, it is difficult to assume the presence of a significant differential diagnostic significance of PLO detection during «alcohol screening» among those previously examined in a state of alcoholic intoxication. At the same time, it should be noted that taking into account lateral preferences can contribute to the improvement of preventive work programs in the narcological service, providing greater individualization of psychological support measures. Directly in the rehabilitation work with PEAI, it is advisable to actively apply social and psychological training (because of a significant part of the contingent among the main factors of relapse with a high degree of probability has social stressors). The creation of short-term (3-5 meetings) programs of group exercises of a preventive orientation, which have different targets depending on the «vulnerability factors» of the owners of certain lateral profiles, also seems justified.

Enthalpic and Entropic Contributions to Interleaflet Coupling Drive Domain Registration and Anti-registration in Biological Membrane

Biological membrane is a complex self-assembly of lipids, sterols and proteins organized as a fluid bilayer of two closely stacked lipid leaflets. Differential molecular interactions among its diverse constituents give rise to heterogeneities in the membrane lateral organization. Under certain conditions, heterogeneities in the two leaflets can be spatially synchronised and exist as registered domains across the bilayer. Several contrasting theories behind mechanisms that induce registration of nanoscale domains have been suggested[1–3]. Following a recent study[4] showing the effect of position of lipid tail unsaturation on domain registration behavior, we decided to develop an analytical theory to elucidate the driving forces that create and maintain domain registry across leaflets. Towards this, we formulated a Hamiltonian for a stacked lattice system where site variables encapsulate the lipid molecular properties including the position of unsaturation and various other interactions that could drive phase separation and interleaflet coupling. We solve the Hamiltonian using Monte Carlo simulations and create a complete phase diagram that reports the presence or absence of registered domains as a function of various Hamiltonian parameters. We find that the interleaflet coupling should be described as a competing enthalpic contribution due to interaction of lipid tail termini, primarily due to saturated-saturated interactions, and an interleaflet entropic contribution from overlap of unsaturated tail termini. We find that higher position of unsaturation provides weaker interleaflet coupling. We also find points in our parameter space that allow thermodynamically stable nanodomains in our bilayer model, which we have verified by carrying out extended Monte Carlo simulations. These persistent non-coalescing registered nanodomains close to the lower end of the accepted nanodomain size range also point towards a possible “nanoscale” emulsion description of lateral heterogeneities in biological membrane leaflets.

High-Level Expression of Palmitoylated MPP1 Recombinant Protein in Mammalian Cells

Our recent studies have pointed to an important role of the MAGUK family member, MPP1, as a crucial molecule interacting with flotillins and involved in the lateral organization of the erythroid plasma membrane. The palmitoylation of MPP1 seems to be an important element in this process; however, studies on the direct effect of palmitoylation on protein–protein or protein–membrane interactions in vitro are still challenging due to the difficulties in obtaining functional post-translationally modified recombinant proteins and the lack of comprehensive protocols for the purification of palmitoylated proteins. In this work, we present an optimized approach for the high-yield overexpression and purification of palmitoylated recombinant MPP1 protein in mammalian HEK-293F cells. The presented approach facilitates further studies on the molecular mechanism of lateral membrane organization and the functional impact of the palmitoylation of MPP1, which could also be carried out for other palmitoylated proteins.

ExSTED microscopy reveals contrasting functions of dopamine and somatostatin CSF-c neurons along the central canal

The spatial location of cerebrospinal fluid contacting (CSF-c) neurons enables important regulatory homeostatic functions regarding pH and motion control. Their intricate organization, facing the central canal and extending across the spinal cord, in relation to specific subtypes is poorly understood. This calls for imaging methods with a high spatial resolution (5-10 nm) to resolve the synaptic and ciliary compartments of each individual cell to elucidate their signalling pathways and enough throughput to dissect the cellular organization. Here, light-sheet and expansion microscopy resolved the persistent ventral and lateral organization of dopamine and somatostatin CSF-c neuronal types.The number of somatostatin-containing dense core vesicles, resolved by STED microscopy, was shown to be markedly reduced upon each exposure to alkaline or acidic pH inhibiting any movement as part of a homeostatic response. Their cilia symmetry was unravelled by ExSTED as sensory in contrast with the motile one found in the dopaminergic ph insensitive neurons. This novel experimental workflow elucidates the functional role of CSF-c neuron subtypes in situ paving the way for further spatial and functional cell type classification.

Cholesterol Oxidation Modulates the Formation of Liquid-Ordered Domains in Model Membranes

7-ketocholesterol (KChol) is one of the most cytotoxic oxysterols found in the plasma membrane, and increased levels of KChol are associated with numerous pathologies. It is thought to induce apoptosis via inactivation of the phosphatidylinositol 3-kinase/Akt signaling pathway - a pathway that depends on lipid-rafts as signaling platforms. By means of coarse-grained molecular dynamics simulations, we demonstrate that KChol disrupts the liquid-liquid phase separation seen in an equimolar mixture of (dipalmitoylphosphatidylcholine) DPPC, (dioleoylphosphatidylcholine) DOPC, and Cholesterol (Chol). This disruption occurs via two mechanisms: i) KChol adopts a wider range of orientations with the membrane, which disrupts the packing of neighboring lipids and ii) KChol has no preference for DPPC over DOPC, which is the main driving force for lateral demixing in DPPC/DOPC/Chol membranes. This provides a molecular description of the means by which KChol induces apoptosis, and illustrates that a single chemical substitution to cholesterol can have a profound impact on the lateral organization of lipid membranes.

Overexpression of a Pak Choi Gene, BcAS2, Causes Leaf Curvature in Arabidopsis thaliana

The LBD (Lateral Organ Boundaries Domain) family are a new group of plant-specific genes, which encode a class of transcription factors containing conserved Lateral Organization Boundary (LOB) domains, and play an important role in regulating the adaxial–abaxial polarity of plant leaves. In Arabidopsis thaliana, ASYMMETRIC LEAVES 2 (AS2) has a typical LOB domain and is involved in determining the adaxial cell fate. In this study, we isolated the BcAS2 gene from the pak choi cultivar “NHCC001”, and analyzed its expression pattern. The results showed that the BcAS2 encoded a protein made up of 202 amino acid residues which were located in the nucleus and cytomembrane. The Yeast two-hybrid system (Y2H) assay indicated that BcAS2 interacts with BcAS1-1 and BcAS1-2 (the homologous genes of AS1 gene in pak choi). In the transgenic Arabidopsis thaliana that overexpressed BcAS2 gene, it presented an abnormal phenotype with a curly shape. Taken together, our findings not only validate the function of BcAS2 in leaf development in Arabidopsis thaliana, but also contribute in unravelling the molecular regulatory mechanism of BcAS2, which fulfills a special role by forming complexes with BcAS1-1/2 in the establishment of the adaxial–abaxial polarity of the lateral organs in pak choi.

Impact of the number of rhamnose moieties of rhamnolipids on the structure, lateral organization and morphology of model biomembranes

Various studies have described remarkable biological activities and surface-active properties of rhamnolipids, leading to their proposed use in a wide range of industrial applications.

NEUROSYCHOLOGICAL COMPONENT IN THE COMPREHENSIVE ASSESSMENT OF STUDENTS‘ HEALTH

It was revealed that the gradations of the health of the examined students, which were assessed by objective indicators, differ depending on the lateral organization of the visual system. It was found that young men with left-sided signs in the visual system were characterized by the best objective health indicators.

Critical Phenomena in Plasma Membrane Organization and Function

Lateral organization in the plane of the plasma membrane is an important driver of biological processes. The past dozen years have seen increasing experimental support for the notion that lipid organization plays an important role in modulating this heterogeneity. Various biophysical mechanisms rooted in the concept of liquid–liquid phase separation have been proposed to explain diverse experimental observations of heterogeneity in model and cell membranes with distinct but overlapping applicability. In this review, we focus on the evidence for and the consequences of the hypothesis that the plasma membrane is poised near an equilibrium miscibility critical point. Critical phenomena explain certain features of the heterogeneity observed in cells and model systems but also go beyond heterogeneity to predict other interesting phenomena, including responses to perturbations in membrane composition. Expected final online publication date for the Annual Review of Physical Chemistry, Volume 72 is April 20, 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.