Human blood contains a big variety of natural antibodies, circulating throughout life at constant concentration. Previously, we have found natural antibodies capable of binding to trisaccharide Galα1-4Galβ1-4Glc (Pk) practically in all humans. Intriguingly, the same trisaccharide is a key fragment of glycosphingolipid globotriaosylceramide (Gb3Cer) – normal component of erythrocyte and endothelial cell membrane, i.e. the antibodies and their cognate antigen coexist without any immunological reaction.
To explain the inertness of human anti-Pk antibodies towards own cells.
Materials and methods
We used a combination of immunochemical and molecular dynamics (MD) experiments. Antibodies were isolated using affinity media with Pk trisaccharide, their epitope specificity was characterized using ELISA (enzyme-linked immunosorbent assay) with a set of synthetic glycans related to Pk synthetic glycans and FACS (Fluorescence-Activated Cell Sorting) analysis of cells with inserted natural Gb3Cer and its synthetic analogue. Conformations and clustering of glycolipids immersed into a lipid bilayer were studied using MD simulations.
Isolated specific antibodies were completely unable to bind natural Gb3Cer both inserted into cells and in artificial membrane, whereas strong interaction took place with synthetic analogue differing by the presence of a spacer between trisaccharide and lipid part. MD simulations revealed: i) although membrane-bound glycans do not form stable long-living aggregates, their transient packing is more compact in natural Gb3 as compared with the synthetic analog, ii) similar conformation of Pk glycan in composition of the glycolipids, iii) no effect on the mentioned above results when cholesterol was inserted into membrane, and iv) better accessibility of the synthetic version for interaction with proteins.
Both immunochemical and molecular dynamics data argue that the reason of the “tolerance” of natural anti-Pk antibodies towards cell-bound Gb3Cer is the spatial inaccessibility of Pk glycotope for interaction. We can conclude that the antibodies are not related to the blood group P system.
This article hypothesizes that in societies where spouses are considered to have relatively equal status, they are more likely to be intimate with one another than in societies where there is spousal status inequality. The authors ask: What are the core attributes of intimacy between husband and wife cross-culturally? And what sociocultural norms and practices are associated with intimate/nonintimate spousal relationships? Five variables are used as indicators of intimacy: husband– wife sleeping proximity, privacy in sleeping for husbands and wives, husband– wife eating arrangement, husband–wife spending leisure time together, and husband attending birth of his child. These variables are correlated with 60 variables for female status in “traditional” societies constructed and coded by Whyte. From this research, the authors develop a female kin power model based on five main sociocultural variables: war, skewed sex ratio, polygyny, parental warmth, and socialization for aggression. Results indicate that intimacy in spousal relationships is significantly predicted by female status.
Previous studies distinguish between right hemisphere-dominant processing of prosodic/tonal information and left-hemispheric modulation of grammatical information as well as lexical tones. Swedish word accents offer a prime testing ground to better understand this division. Although similar to lexical tones, word accents are determined by words' morphosyntactic structure, which enables listeners to use the tone at the beginning of a word to predict its grammatical ending. We recorded electrophysiological and hemodynamic brain responses to words where stem tones matched or mismatched inflectional suffixes. Tones produced brain potential effects after 136ms, correlating with subject variability in average BOLD in left primary auditory cortex, superior temporal gyrus, and inferior frontal gyrus. Invalidly cued suffixes activated the left inferior parietal lobe, arguably reflecting increased processing cost of their meaning. Thus, interaction of word accent tones with grammatical morphology yielded a rapid neural response correlating in subject variability with activations in predominantly left-hemispheric brain areas.
We studied the cytotoxicity of acadesine (5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside) for tumor and normal cells of various species and tissue origin. In tumor cells, acadesine triggered non-apoptotic death; the potency of the compound to normal cells was substantially lower. Acadesine was toxic for tumor cells with multidrug resistant phenotypes caused by the transmembrane transporter P-glycoprotein or lack of proapoptotic p53. Activity of adenosine receptors was required for acadesine-induced cell death, whereas functioning of AMP-dependent protein kinase was not required. A more pronounced cytotoxicity for tumor cells, as well as the non-canonical death mechanism(s), makes acadesine a promising candidate for antitumor therapy.
The methods and algorithms of XFEL data analysis for protein molecules are discussed. Experimental data on the structure and spatial distribution of the electron density in biomacromolecules and their complexes, algorithms, data analysis and integration of X-ray scattering, electron microscopy and molecular modeling techniques to study the structure and dynamics of biological macromolecules and their complexes are discussed as well.
Alcoholism as a cause of regression in learning and in pro-social behavior
Alexandrov Yu.I., Svarnik O.Ye., Znamenskaya I.I., Arutiunova K.R., Kolbeneva M.G., Krylov A.K., Bulava A.N.
Despite a long history of the notion of regression, its manifestations and mechanisms are still poorly researched, specific experimental studies are rare, points of view conflict. A study was conducted to discover dynamics of subjective experience and brain activity lying at the foundation of phenomena described as regression and observed in seemingly heterogeneous phenomena, such as stress, illness, violent emotions, alcoholic intoxication. The paper discusses the notion of regression from different angles, including the systemic evolutionary approach, and analyzes its potential brain and neuroenetic mechanisms. It has been experimentally proved that a high degree of alcoholic intoxication causes regression brought about by reverse de-differentiation: a relative increase of representation of lowly differentiated systems in actual experience.In experimental situations of learning in animals lowered activation of neurons of the first (drinking) skill was observed in the process of development of the second (eating) skill. In order to discover effects of alcohol on the general pattern of moral judgements the authors analyzed dynamics of the index of moral acceptance of the death of one for the sake of many. Complexity of behavior is simplified under alcohol and individual differences in pro-social behavior become less expressed. Findings demonstrate similarities in assessments of socially meaningful actions under alcohol, which, the authors believe, points to the effect of alcohol as “de-differentiator” causing regression. The effects may be linked to the general mechanism of reversible de-differentiation which determines repression of a number of systems (and, consequently, of activity of a number of neurons) in the most differentiated “complex” systems. This simplification may be linked to accelerated learning and also to the fact that organization of behavior becomes more uniform.
The paper considers the methods of acquisition and processing of optical data from small Unmanned Air Vehicles (UAVs) ― photogrammetric point clouds and derivative 3d-models — for the automatic extraction of explicit structure variables in sparse boreal forests of the central part of Kola Peninsula. We review main technological issues of UAV optical surveys, present flowcharts of point clouds classi-fication for the extraction of canopy height model (CHM), further CHM analysis, tree-level and area-based estimation of structural forest variables. Main tree-level variables are crown heights and extent; for forest stands CHM analysis leads to gridded data on tree canopy heights, amount of canopy peaks and tree density, share of tree cover. The definite limitations of optical photogrammetry connected with CHM extraction in dense forests can be partly overcome due to the complex use of point clouds from summer and winter (leaf-off) surveys and independent processing flow of CHM in forest stands with sparser and denser tree canopies.
Broadway is the most famous street of New York City. It follows the island of Manhattan along its whole length and through many of its vernacular regions. Field research of functional, social-economic, architectural and mental differentiation of the street from Bowling Green to 142 Street in Spanish Harlem shaped the methods of linear zoning and revealed 16 unique regions in the researched segment. These regions turned out to be functional, but their borders and composition are based on the vernacular regions of Manhattan. It appears that Broadway, as a major trade and social thruway, forms the surrounding urban landscape. But the role of vernacular regions, through which street passes, remains important and sometimes even crucial.
Verification of the PREFAB database containing golden standard protein alignments was performed. It has revealed a significant number of differences between the sequences from PREFAB and PDB databases. It was shown that, compared with the sequences given in the PDB, 575 alignments referred to a sequence with a gap; such alignments were excluded. Furthermore, compared with the PDB sequences, single substitutions or insertions were found for 440 amino acid sequences from PREFAB; these sequences were edited. SCOP domain analysis has shown that only 502 alignments in the resulting set contain sequences from the same family. Finally, eliminating duplicates, we have created a new golden standard alignment database PREFAB P based on PREFAB; the PREFAB P database contains 581 alignments.