Rapid information processing in the human brain is vital to survival in a highly dynamic environment. The key tool humans use to exchange information is spoken language, but the exact speed of the neuronal mechanisms underpinning speech comprehension is still unknown. Here we investigate the time course of neuro-lexical processing by analyzing neuromagnetic brain activity elicited in response to psycholinguistically and acoustically matched groups of words and pseudowords. We show an ultra-early dissociation in cortical activation elicited by these stimulus types, emerging ∼50 ms after acoustic information required for word identification first becomes available. This dissociation is the earliest brain signature of lexical processing of words so far reported, and may help explain the evolutionary advantage of human spoken language.
The interactions among fluid species such as H2O, CO2, and CH4 confined in nano- and meso-pores in shales and other rocks is of central concern to understanding the chemical behavior and transport properties of these species in the earthâ€™s subsurface and is of special concern to geological C-sequestration and enhanced production of oil and natural gas. The behavior of CO2, and CH4 are less well understood than that of H2O. This paper presents the results of a computational modeling study of the partitioning of CO2 and CH4 between bulk fluid and nano- and meso-pores bounded by the common clay mineral montmorillonite. The calculations were done at 323 K and a total fluid pressure of 124 bars using a novel approach (constant reservoir composition molecular dynamics, CRC-MD) that uses bias forces to maintain a constant composition in the fluid external to the pore. This purely MD approach overcomes the difficulties in making stochastic particle insertion-deletion moves in dense fluids encountered in grand canonical Monte Carlo and related hybrid approaches. The results show that both the basal siloxane surfaces and protonated broken edge surfaces of montmorillonite both prefer CO2 relative to CH4 suggesting that methods of enhanced oil and gas production using CO2 will readily displace CH4 from such pores. This preference for CO2 is due to its preferred interaction with the surfaces and extends to approximately 20 Ã… from them.
Neuronal nicotinic acetylcholine receptors (NNRs) of the α7 subtype have been shown to contribute to the release of dopamine in the nucleus accumbens. The site of action and the underlying mechanism, however, are unclear. Here we applied a circuit modeling approach, supported by electrochemical in vivo recordings, to clarify this issue. Modeling revealed two potential mechanisms for the drop in accumbal dopamine efflux evoked by the selective α7 partial agonist TC-7020. TC-7020 could desensitize α7 NNRs located predominantly on dopamine neurons or glutamatergic afferents to them or, alternatively, activate α7 NNRs located on the glutamatergic afferents to GABAergic interneurons in the ventral tegmental area. Only the model based on desensitization, however, was able to explain the neutralizing effect of coapplied PNU-120596, a positive allosteric modulator. According to our results, the most likely sites of action are the preterminal α7 NNRs controlling glutamate release from cortical afferents to the nucleus accumbens. These findings offer a rationale for the further investigation of α7 NNR agonists as therapy for diseases associated with enhanced mesolimbic dopaminergic tone, such as schizophrenia and addiction
The Universe of RNA Structures DataBase (URSDB) stores information obtained from all RNA-containing PDB entries (2935 entries in October 2015). The content of the database is updated regularly. The database consists of 51 tables containing indexed data on various elements of the RNA structures. The database provides a web interface allowing user to select a subset of structures with desired features and to obtain various statistical data for a selected subset of structures or for all structures. In particular, one can easily obtain statistics on geometric parameters of base pairs, on structural motifs (stems, loops, etc.) or on different types of pseudoknots. The user can also view and get information on an individual structure or its selected parts, e.g. RNA–protein hydrogen bonds. URSDB employs a new original definition of loops in RNA structures. That definition fits both pseudoknot-free and pseudoknotted secondary structures and coincides with the classical definition in case of pseudoknot-free structures. To our knowledge, URSDB is the first database supporting searches based on topological classification of pseudoknots and on extended loop classification.
Based on the data of experimental studies of wave disturbances in the Earth's atmosphere before and after the earthquakes in Uzbekistan (May 26, 2013) and Kyrgyzstan (January 8, 2007), earlier unknown changes in the parameters of internal gravity waves are revealed. These changes were manifested during the period of five days before the earthquake and in certain cases can be used for short-term prediction of the time when seismic events are to occur.
This study describes the analysis of changes in area and volume of the Mt.Elbrus glacier system, Central Caucasus from 1997 to 2017. It is based on helicopter-borne ice thickness measurements, comparison of high-resolution imagery and two digital elevation models (DEMs) with 10 m resolution. More than 250 km of ground-penetrating radar (GPR) profiles of ice thickness with reliable reflections were obtained. The total volume of Mt. Elbrus glaciers was 5.03 ± 0.85 km3 of ice in 2017. Our results show that 68% of the total ice volume is concentrated below 4,000 m a.s.l. where the average ice thickness was 44.6 ± 7.3 m, 18% of the volume lies within 4,000–4,500 m a.s.l. (thickness of 41.2 ± 7.3 m), and just 14% lies above 4,500 m a.s.l. (thickness of 29.7 ± 6.7 m). The glacier-covered area of Mt. Elbrus decreased from 125.76 ± 0.65 km2 in 1997 to 112.20 ± 0.58 km2 in 2017, a reduction of 10.8%. Over the same period the volume decreased by 22.8%. The mass balance of the Elbrus glaciers decreased by −0.55 ± 0.04 m w.e. a−1 from 1997 to 2017. Mass balance on west-oriented glaciers is less negative than on east-and south-oriented glaciers where mass balance is most negative. The mass balance of the east-oriented Djikiugankez glacier decreased at the fastest average rate (−0.97 ± 0.07 m w.e. a−1). This glacier contains 28% of the total Elbrus glacier system ice volume, most of which is concentrated below 4,000 m a.s.l. Only one small glacier on the western slope demonstrated mass gain. Our results match well with the long term direct mass balance measurements on the Garabashi glacier on Elbrus which lost 12.58 m w.e. and 12.92 ± 0.95 m w.e. between 1997 and 2017 estimated by glaciological and geodetic method, respectively. The rate of Elbrus glacier mass loss tripled in 1997-2017 compared with the 1957-1997 period.
It has been suggested that the preference for low WHRs evolved because low WHR provided a cue to female reproductive status and health, and therefore to her reproductive value. The present study aimed to test whether WHR might indeed be a reliable cue to female reproductive history (with lower WHRs indicating lower number of children). Previous studies showed such a relationship for modern and industrialized populations, but it has not been investigated in natural fertility, indigenous, more energy constrained populations facing greater trade-offs in energy allocation than do modern societies. Our sample comprised 925 women aged 13 to 95 years from seven non-industrial societies including tribes from Sub-Saharan Africa (Hadza, Datoga, and Isanzu), Western Siberia (Ob Ugric people: Khanty and Mansi), South America (Tsimane) and South Asia (Minahasans and Sangirese). We demonstrated a culturally stable, significant relationship between number of children and WHR among women, controlling for BMI and age. Based on these data, we suggest that WHR is a reliable cue to female reproductive history, and we discuss our results in the context of previous studies indicating usefulness of WHR as an indicator of health and fertility.
This paper focuses on the long-term situation with water resources, and water sector in particular, analyzed through a Foresight study. The authors attribute particular attention to implication for Russia, which is relatively better positioned regarding the availability of water resources. However, the country still faces challenges related to the protection of water resources, drinking water supply, water networks, consumption patterns, water discharge, treatment and re-use. The present study aims at identification and analysis of trends, factors and uncertainties in water supply, demand, use and re-use with a particular focus on sustainability of water systems; water use by households and industry; and new water services and products.
Research methodology in this paper involves a horizon scanning exercise for the identification of the key trends, factors and uncertainties along with the identification of weak signals of future emerging trends and wild cards in the form of future surprises, shocks and other unexpected events that may disrupt the preservation of water resources and the future of the water sector. Trends characterize broad parameters for shifts in attitudes, climate, policies and business focus over periods of several years that usually have global reach. These are usually experienced by everyone and often in similar contexts. Trends may represent threats, opportunities or a mixture of them, identified through underlying processes, possible events and other future developments.
A key systemic restriction of water use for the next decades both globally and in Russia relates to competition between agriculture, energy, manufacturing and household water use. Given that the amount of renewable water resources is almost fixed and even decreases because of pollution, circular economy solutions for water use will be required. Implications of the global trends identified in the study for Russia are dependent on the overall situation with water resources in the country. Russia has sufficient water supply: the overall intake of water for drinking and economic purposes in Russia amounts to 3 per cent of the total water resources, two-thirds of which are discarded back to water bodies. At the same time, there are substantial problems associated with the extremely uneven distribution of water resources across the country, as well as high “water intensity” of the Russian GDP. The Russian water sector is currently not very attractive for investors. Moreover, it has significantly less lobbying opportunities than other infrastructure sectors, and this complicates its institutional and financial positions. Meanwhile, there have been some positive changes with regard to activities with a short pay-off period.
The paper offers one of the first studies on the future of Russian water resources with a focus on the water supply and sanitation sector. A comprehensive approach to trends identification (not found in other studies on Russian water resources) allowed authors to identify social, technological, environmental, economic, policy and value-related global trends and uncertainties. Moreover, implications of these trends and uncertainties, as well as Russia-specific trends, were outlined.
Earth's global magnetic field generated by an internal dynamo mechanism has been continuously changing on different time scales since its formation. Paleodata indicate that relatively long periods of evolutionary changes can be replaced by quick magnetic inversions. Based on observations, Earth's magnetic field is currently weakening and the magnetic poles are shifting, possibly indicating the beginning of the inversion process. This paper invokes Gauss coefficients to approximate the behavior of Earth's magnetic field components over the past 100 years. Using the extrapolation method, it is estimated that the magnetic dipole component will vanish by the year 3600 and at that time the geomagnetic field will be determined by a smaller value of a quadrupole magnetic component. A numerical model is constructed which allows evaluating and comparing both galactic and solar cosmic ray fluxes in Earth's magnetosphere and on its surface during periods of dipole or quadrupole domination. The role of the atmosphere in absorbing particles of cosmic rays is taken into account. An estimate of the radiation danger to humans is obtained for the ground level and for the International Space Station altitude of km. It is shown that in the most unfavorable, minimum field interval of the inversion process, the galactic cosmic ray flux increases by no more than a factor of three, implying that the radiation danger does not exceed the maximum permissible dose. Thus, the danger of magnetic inversion periods generally should not have fatal consequences for humans and nature as a whole, despite dramatically changing the structure of Earth's magnetosphere.
We investigated the time-course of cortical activation during comprehension of literal and idiomatic sentences using MEG and anatomically guided distributed source analysis. Previous fMRI work had shown that the comprehension of sentences including action-related words elicits somatotopic semantic activation along the motor strip, reflecting meaning aspects of constituent words. Furthermore, idioms more strongly activated temporal pole and prefrontal cortex than literal sentences. Here we show that, compared to literal sentences, processing of idioms in a silent reading task modulates anterior fronto-temporal activity very early-on, already 150-250 ms after the sentences' critical disambiguating words ("kick the habit"). In parallel, the meaning of action words embedded in sentences is reflected by somatotopic activation of precentral motor systems. As neural reflections of constituent parts of idiomatic sentences are manifest at the same early latencies as brain indexes of idiomatic vs. literal meaning processing, we suggest that within ¼ of a second, compositional and abstract context-driven semantic processes in parallel contribute to the understanding of idiom meaning.
This opinion responds to the commentary by Papeo and Caramazza (2014).
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.