Sensory and cognitive deficits are common in schizophrenia. They are associated with abnormal brain rhythms, including disturbances in γ frequency (30–80 Hz) oscillations (GFO) in cortex-related networks. However, the underlying anatomofunctional mechanisms remain elusive. Clinical and experimental evidence suggests that these deficits result from a hyporegulation of glutamate N-methyl-D-aspartate receptors. Here we modeled these deficits in rats with ketamine, a non-competitive N-methyl-D-aspartate receptor antagonist and a translational psychotomimetic substance at subanesthetic doses. We tested the hypothesis that ketamine-induced sensory deficits involve an impairment of the ability of the thalamocortical (TC) system to discriminate the relevant information from the baseline activity. Furthermore, we wanted to assess whether ketamine disrupts synaptic plasticity in TC systems. We conducted multisite network recordings in the rat somatosensory TC system, natural stimulation of the vibrissae and high-frequency electrical stimulation (HFS) of the thalamus. A single systemic injection of ketamine increased the amount of baseline GFO, reduced the amplitude of the sensory-evoked TC response and decreased the power of the sensory-evoked GFO. Furthermore, cortical application of ketamine elicited local and distant increases in baseline GFO. The ketamine effects were transient. Unexpectedly, HFS of the TC pathway had opposite actions. In conclusion, ketamine and thalamic HFS have opposite effects on the ability of the somatosensory TC system to discriminate the sensory-evoked response from the baseline GFO during information processing. Investigating the link between the state and function of the TC system may conceptually be a key strategy to design innovative therapies against neuropsychiatric disorders.
Motivation: Target-specific hybridization depends on oligo-probe characteristics that improve hybridization specificity and minimize genome-wide cross-hybridization. Interplay between specific hybridization and genome-wide cross-hybridization has been insufficiently studied, despite its crucial role in efficient probe design and in data analysis. Results: In this study, we defined hybridization specificity as a ratio between oligo target-specific hybridization and oligo genome-wide cross-hybridization. A microarray database, derived from the Genomic Comparison Hybridization (GCH) experiment and performed using the Affymetrix platform, contains two different types of probes. The first type of oligo-probes does not have a specific target on the genome and their hybridization signals are derived from genome-wide cross-hybridization alone. The second type includes oligonucleotides that have a specific target on the genomic DNA and their signals are derived from specific and cross-hybridization components combined to- gether in a total signal. A comparative analysis of hybridization specificity of oligo-probes, as well as their nucleotide sequences and thermodynamic features was performed on the database. The comparison has revealed that hybridization specificity was negatively affected by low stability of the fully-paired oligo-target duplex, stable probe self-folding, G-rich content, including GGG motifs, low sequence complexity and nucleotide composition symmetry. Conclusion: Filtering out the probes with defined ‘negative’ characteristics significantly increases specific hybridization and dramatically decreasing genome-wide cross-hybridization. Selected oligo-probes have two times higher hybridization specificity on average, compared to the probes that were filtered from the analysis by applying suggested cutoff thresholds to the described parameters. A new approach for efficient oligo-probe design is described in our study.
High and moderate intensity endurance exercise alters gene expression in human white blood cells (WBCs), but the understanding of how this effect occurs is limited. To increase our knowledge of the nature of this process, we investigated the effects of passing the anaerobic threshold (AnT) on the gene expression profile in WBCs of athletes. Nineteen highly trained skiers participated in a treadmill test with an incremental step protocol until exhaustion (ramp test to exhaustion, RTE). The average total time to exhaustion was 14:40 min and time after AnT was 4:50 min. Two weeks later, seven of these skiers participated in a moderate treadmill test (MT) at 80% peak O(2) uptake for 30 min, which was slightly below their AnTs. Blood samples were obtained before and immediately after both tests. RTE was associated with substantially greater leukocytosis and acidosis than MT. Gene expression in WBCs was measured using whole genome microarray expression analysis before and immediately after each test. A total of 310 upregulated genes were found after RTE, and 69 genes after MT of which 64 were identical to RTE. Both tests influenced a variety of known gene pathways related to inflammation, stress response, signal transduction and apoptosis. A large group of differentially expressed previously unknown small nucleolar RNA and small Cajal body RNA was found. In conclusion, a 15-min test to exhaustion was associated with substantially greater changes of gene expression than a 30-min test just below the AnT.
Active ionospheric experiments using high-power, high-frequency transmitters, heaters, to study plasma processes in the ionosphere and magnetosphere continue to provide new insights into understanding plasma and geophysical proceses. This review describes the heating facilities, past and present, and discusses scientific results from these facilities and associated space missions. Phenomena that have been observed with these facilities are reviewed along with theoretical explanations that have been proposed or are commonly accepted. Gaps or uncertainties in understanding of heating-initiated phenomena are discussed together with proposed science questions to be addressed in the future. Suggestions for improvements and additions to existing facilities are presented including important satellite missions which are necessary to answer the outstanding questions in this field.
A controversial issue in neuro- and psycholinguistics is whether regular past-tense forms of verbs are stored lexically or generated productively by the application of abstract combinatorial schemas, for example affixation rules. The success or failure of models in accounting for this particular issue can be used to draw more general conclusions about cognition and the degree to which abstract, symbolic representations and rules are psychologically and neurobiologically real. This debate can potentially be resolved using a neurophysiological paradigm, in which alternative predictions of the brain response patterns for lexical and syntactic processing are put to the test. We used magnetoencephalography (MEG) to record neural responses to spoken monomorphemic words ('hide'), pseudowords ('smide'), regular past-tense forms ('cried') and ungrammatical (overregularised) past-tense forms ('flied') in a passive listening oddball paradigm, in which lexically and syntactically modulated stimuli are known to elicit distinct patterns of the mismatch negativity (MMN) brain response. We observed an enhanced ('lexical') MMN to monomorphemic words relative to pseudowords, but a reversed ('syntactic') MMN to ungrammatically inflected past tenses relative to grammatical forms. This dissociation between responses to monomorphemic and bimorphemic stimuli indicates that regular past tenses are processed more similarly to syntactic sequences than to lexically stored monomorphemic words, suggesting that regular past tenses are generated productively by the application of a combinatorial scheme to their separately represented stems and affixes. We suggest discrete combinatorial neuronal assemblies, which bind classes of sequentially occurring lexical elements into morphologically complex units, as the neurobiological basis of regular past tense inflection.
tDecision-makers show an increased risk appetite when they gamble with previously wonmoney, the house money effect, and when they have a chance to make up for a prior loss,the break even effect. To explore the origins of these effects, we use functional magneticresonance imaging to record the brain activities of subjects while they make sequential riskychoices. The behavioral data from our experiment confirm the path dependence of choices,despite the short trial duration and the many task repetitions required for neuroimaging.The brain data yield evidence that the increased risk appetite after gains and losses is relatedto an increased activity of affective brain processes and a decreased activity of deliberativebrain processes.
One of the key advances in genome assembly that has led to a significant improvement in contig lengths has been improved algorithms for utilization of paired reads (mate-pairs). While in most assemblers, mate-pair information is used in a post-processing step, the recently proposed Paired de Bruijn Graph (PDBG) approach incorporates the mate-pair information directly in the assembly graph structure. However, the PDBG approach faces difficulties when the variation in the insert sizes is high. To address this problem, we first transform mate-pairs into edge-pair histograms that allow one to better estimate the distance between edges in the assembly graph that represent regions linked by multiple mate-pairs. Further, we combine the ideas of mate-pair transformation and PDBGs to construct new data structures for genome assembly: pathsets and pathset graphs.
In situ growth of Sphagnum riparium Ångstr. shoots were monitored during the 2015 and 2016 growing seasons in Karelia, Russia. It was established that shoot growth rates fluctuated with a period of around 30 days, that is, showed a circatrigintan rhythm. Such rhythms from mosses have not been previously reported. Correlation of growth rates with the percentage of the illuminated portion of the Moon was statistically significant (p< 0.01) in both years. Shoot growth rates were reliably higher around the new Moon compared to the full Moon. This phenomenon may be due either to causality or to a pure coincidence of processes with similar rhythms.
It has been shown that a single intratessticular injection of chemical mutagen dipin (experiment) or saline (control) into mise resulted in significant but reversible morphohistological damage of the spermatogenetic epithelium.
Changes in marine biodiversity through the Phanerozoic correlate much better with hyperbolic model (widely used in demography and macrosociology) than with exponential and logistic models (traditionally used in population biology and extensively applie to fossil biodiversity as well). The latter models imply that changes in diversity are guided by a *rst-order positive feedback (mo ancestors, more descendants) and/or a negative feedback arising from resource limitation. Hyperbolic model implies a second-order positive feedback. The hyperbolic pattern of the world population growth arises from a second-order positive feedback between the population size and the rate of technological growth. The hyperbolic character of biodiversity growth can be similarly accounted for by a feedback between the diversity and community structure complexity. The similarity between the curves of biodiversity and human population probably comes from the fact that both are derived from the interference of the hyperbolic trend with cyclical and stochastic dynamics.
Phase images of biological specimens were obtained by the method of Quadriwave Lateral Shearing Interferometry (QWLSI). The QWLSI technique produces, at high resolution, phase images of the cells having been exposed to a plasma treatment and enables the quantitative analysis of the changes in the surface area of the cells over time. Morphological changes in the HTori normal thyroid cells were demonstrated using this method. There was a comparison of the cell behaviour between control cells, cells treated by plasma of a nanosecond dielectric barrier discharge, including cells pre-treated by catalase, and cells treated with an equivalent amount of H2O2. The major changes in the cell membrane morphology were observed at only 5min after the plasma treatment. The primary role of reactive oxygen species (ROS) in this degradation is suggested. Deformation and condensation of the cell nucleus were observed 2–3 h after the treatment and are supposedly related to apoptosis induction. The coupling of the phase QWLSI with immunofluorescence imaging would give a deeper insight into the mechanisms of plasma induced cell death.
Background: The oxytocin (OT) system is known to be implicated in the regulation of complex social behavior, particularly empathy and parenting. The goal of this study was to estimate the gender and population differences in polymorphisms of two oxytocin receptor gene SNPs, rs53576 and rs2254298, in four populations. Results: These data were compared with each other and with 14 samples from the corresponding regions retrieved from the 1000 Genomes database. Low level of heterozygosity was observed for both SNPs in all populations in this study (rs53576: Catalonian, Hobs = 0.413; Hadza, Hobs = 0.556; sr2254698: Khanty-Mansi, Hobs = 0.250; Datoga, Hobs = 0.550). The amount of variance due to regional variability was almost equal for both SNPs (rs53576: FRT = 0.086, rs2554298: FRT = 0.072), whereas variance for the population level of variability was twice bigger for rs2554298 (rs53576: FST = 0.127, rs2554298: FST = 0.162). Pairwise coefficients of fixation demonstrate that the Hadza were well differentiated from other African populations except of Datoga, the Datoga were weakly differentiated from other African origin populations, the Ob Ugric people were extremely differentiated from all other populations. Catalans were extremely differentiated of Asian populations. Conclusions: It is hypothesized on the base of spatial distribution of the evolutionary novel A alleles of the both OXTR gene loci, that the spread of alleles of rs22542298 and rs53376 SNPs may be associated to some extant with manipulation of parental investment in humans.
The paper looks into the dynamics of the population size of Russia, Ukraine and Belarus after the census of 1989. Regions and cities of these countries were the focus of the research (territorial units level NUTS-3). The analysis addresses the question to what degree the remoteness from the regional centre, i.e. the position in the core-periphery system, influences the dynamics of the population size of the territorial units of the given level. For the analytical purposes the distinction has been made between the regional centres including adjacent suburban areas and internal regional periphery comprising districts and cities. The main indicator employed was the distance between the periphery areas and regional centres. The results of the analysis show that in spite of the depopulation of all three countries and severe transformational crisis, there was a steady growth of the population size in the regional centres, while the periphery areas of the regions continued to lose the population. The mentioned differences are primarily determined by migration flows, since the fertility rates are below the replacement level in all the countries’ territories. Population tends to concentrate in the regional centres, which means urbanisation has not been completed yet. While similar patterns of population decline are observed in the periphery areas of Ukraine and Belarus, in Russia the depopulation rates are negatively influenced by the factor of remoteness of a periphery area from the regional centre. All three countries experienced rural population decline everywhere but suburban areas of the regional centres.
The hypothesis that population pressure causes increased warfare has been recently criticized on the empirical grounds. Both studies focusing on specific historical societies and analyses of cross-cultural data fail to find positive correlation between population density and incidence of warfare. In this paper we argue that such negative results do not falsify the population-warfare hypothesis. Population and warfare are dynamical variables, and if their interaction causes sustained oscillations, then we do not in general expect to find strong correlation between the two variables measured at the same time (that is, unlagged). We explore mathematically what the dynamical patterns of interaction between population and warfare (focusing on internal warfare) might be in both stateless and state societies. Next, we test the model predictions in several empirical case studies: early modern England, Han and Tang China, and the Roman Empire. Our empirical results support the population-warfare theory: we find that there is a tendency for population numbers and internal warfare intensity to oscillate with the same period but shifted in phase (with warfare peaks following population peaks). Furthermore, the rates of change of the two variables behave precisely as predicted by the theory: population rate of change is negatively affected by warfare intensity, while warfare rate of change is positively affected by population density.
In this paper, we consider a model of the influence of atmospheric infrasonic waves on VLF magnetospheric whistler wave excitation. This excitation occurs as a result of a succession of processes: a modulation of the plasma density by acoustic-gravity waves in the ionosphere, a reflection of the whistlers by ionosphere modulation, and a modification of whistler wave generation in the magnetospheric resonator. A variation of the magnetospheric resonator Q-factor has an influence on the operation of the plasma magnetospheric maser, where the active substances are radiation belt particles, and the working modes are electromagnetic whistler waves. The magnetospheric maser is an oscillating system which can be responsible for the excitation of self-oscillations. These self-oscillations are frequently characterized by alternating stages of accumulation and precipitation of energetic particles into the ionosphere during a pulse of whistler emissions. Numerical and analytical investigations of the response of self-oscillations to harmonic oscillations of the whistler reflection coefficient shows that even a small modulation rate can significantly change magnetospheric VLF emissions. Our results can explain the causes of the modulation of energetic electron fluxes and whistler wave intensity with a time scale from 10 to 150 s in the day-side magnetosphere. Such quasi-periodic VLF emissions are often observed in the sub-auroral and auroral magnetosphere and have a noticeable effect on the formation of space weather phenomena.
Liquid chromatography-tandem mass spectrometry was used to analyze plasma proteins of volunteers (control) and patients with glioblastoma multiform (GBM). A database search was pre-set with a variable post-translational modification (PTM): phosphorylation, acetylation or ubiquitination. There were no significant differences between the control and the GBM groups regarding the number of protein identifications, sequence coverage or number of PTMs. However, in GBM plasma, we unambiguously observed a decreased fraction in post-translationally modified peptides identified with high quality. The disease-specific PTM patterns were extracted and mapped to the set of FDA-approved plasma protein markers. Decreases of 46% and 24% in the number of acetylated and ubiquitinated peptides, respectively, were observed in the GBM samples. Significance of capturing disease-associated patterns of protein modifications was envisaged.
The run-up of random long-wave ensemble (swell, storm surge, and tsunami) on the constant-slope beach is studied in the framework of the nonlinear shallow-water theory in the approximation of non-breaking waves. If the incident wave approaches the shore from the deepest water, run-up characteristics can be found in two stages: in the first stage, linear equations are solved and the wave characteristics at the fixed (undisturbed) shoreline are found, and in the second stage the nonlinear dynamics of the moving shoreline is studied by means of the Riemann (nonlinear) transformation of linear solutions. In this paper, detailed results are obtained for quasi-harmonic (narrow-band) waves with random amplitude and phase. It is shown that the probabilistic characteristics of the run-up extremes can be found from the linear theory, while the same ones of the moving shoreline are from the nonlinear theory. The role of wave-breaking due to large-amplitude outliers is discussed, so that it becomes necessary to consider wave ensembles with non-Gaussian statistics within the framework of the analytical theory of nonbreaking waves. The basic formulas for calculating the probabilistic characteristics of the moving shoreline and its velocity through the incident wave characteristics are given. They can be used for estimates of the flooding zone characteristics in marine natural hazards.
Russian Federation inherited a wide and well-developed timber harvesting infrastructure from the Soviet Union. It also inherited relatively strong timber processing industry, especially a network of giant pulp-and-paper plants with access to abundant water supply and cheap electricity. However, a number of factors deteriorate Russia's timber processing competitiveness. First, military security reasons made Soviet Union locate its processing industry, including timber processing, deep within the continent. Therefore, major Russian pulp-and-paper plants, as well as sawmills, panels and plywood plants face higher transportation costs when exporting their production than their counterparts in the United States and Finland. Second, major timber processing plants had been technologically advanced in time of deployment (1970-1980-s), but their technology and machinery has become quite backward over the decades, while investment in the production has nearly stopped altogether in 1990-s and was scarce in 2000-s.
BACKGROUND AND PURPOSE Acid-sensing ion channels (ASICs) play an important role in synaptic plasticity and learning, as well as in nociception and mechanosensation. ASICs are involved in pain and in neurological and psychiatric diseases, but their therapeutic potential is limited by the lack of ligands activating them at physiological pH. EXPERIMENTAL APPROACH We extracted, purified and determined the structure of a bisbenzylisoquinoline alkaloid, lindoldhamine, (LIN) from laurel leaves. Its effect on ASIC3 channels were characterized, using two-electrode voltage-clamp electrophysiological recordings from Xenopus laevis oocytes. KEY RESULTS At pH 7.4 or higher, LIN activated a sustained, proton-independent, current through rat and human ASIC3 channels, but not rat ASIC1a or ASIC2a channels. LIN also potentiated proton-induced transient currents and promoted recovery from desensitization in human, but not rat, ASIC3 channels. CONCLUSIONS AND IMPLICATIONS We describe a novel ASIC subtype-specific agonist LIN, which induced proton-independent activation of human and rat ASIC3 channels at physiological pH. LIN also acts as a positive allosteric modulator of human, but not rat, ASIC3 channels. This unique, species-selective, ligand of ASIC3, opens new avenues in studies of ASIC structure and function, as well as providing new approaches to drug design.
Eukaryotic cells possess a sensible chemical compass allowing them to orient toward sources of soluble chemicals. The extracellular chemical signal triggers separation of the cell membrane into two domains populated by different phospholipid molecules and oriented along the signal anisotropy. We propose a theory of this polarization process, which is articulated into subsequent stages of germ nucleation, patch coarsening, and merging into a single domain. We find that the polarization time, t, depends on the anisotropy degree through the power law t / 2, and that in a cell of radius R there should exist a threshold value th / R1 for the smallest detectable anisotropy