The lion's share of bacteria in various environments cannot be cloned in the laboratory and thus cannot be sequenced using existing technologies. A major goal of single-cell genomics is to complement gene-centric metagenomic data with whole-genome assemblies of uncultivated organisms. Assembly of single-cell data is challenging because of highly non-uniform read coverage as well as elevated levels of sequencing errors and chimeric reads. We describe SPAdes, a new assembler for both single-cell and standard (multicell) assembly, and demonstrate that it improves on the recently released E+V−SC assembler (specialized for single-cell data) and on popular assemblers Velvet and SoapDeNovo (for multicell data). SPAdes generates single-cell assemblies, providing information about genomes of uncultivatable bacteria that vastly exceeds what may be obtained via traditional metagenomics studies. SPAdes is available online (http://bioinf.spbau.ru/spades). It is distributed as open source software.
The commented famous work by S.J. Gould and R.C. Lewontin is crucial not only to sociobiology critique but to polemics on evolutionary theory in general. Reflection provoked by Gould and Lewontin’s paper in the field of philosophy of biology enables to clarify the relation between the adaptationist program and biological reductionism.
The paper analyses the patterns of demographic dynamics of settlements and districts of various types in Russia within the framework of the core-periphery model. We test the hypotheses stating that population density is growing in regional centres and in their surroundings; variations in the dynamics of population growth (and its components) within regions are not less prominent than those between regions; differences between peripheral territories are less significant than those between re-gional centres, and these are the differences which define socio-economic inequality of the regions. The paper also looks into the dynamics of population growth in cities, district centres and rural settlements in relation to the proximity of an administrative unit to a regional centre.
Many environmental stimuli present a quasi-rhythmic structure at different timescales that the brain needs to decompose and integrate. Cortical oscillations have been proposed as instruments of sensory de-multiplexing, i.e., the parallel processing of different frequency streams in sensory signals. Yet their causal role in such a process has never been demonstrated. Here, we used a neural microcircuit model to address whether coupled theta–gamma oscillations, as observed in human auditory cortex, could underpin the multiscale sensory analysis of speech. We show that, in continuous speech, theta oscillations can flexibly track the syllabic rhythm and temporally organize the phoneme-level response of gamma neurons into a code that enables syllable identification. The tracking of slow speech fluctuations by theta oscillations, and its coupling to gamma-spiking activity both appeared as critical features for accurate speech encoding. These results demonstrate that cortical oscillations can be a key instrument of speech de-multiplexing, parsing, and encoding.
A statistical model describing a fine structure of the intra-chromosome maps obtained by a genome-wide chromosome conformation capture method (Hi-C) is proposed. It combines hierarchical chain folding with quenched heteropolymer structure of primary chromatin sequences. It is conjectured that the observed Hi-C maps are statistical averages over many different ways of hierarchical genome folding. It is shown that the existence of quenched primary structure coupled with hierarchical folding induces full range of features observed in experimental Hi-C maps: hierarchical elements, chess-board intermittency and large-scale compartmentalization
Brain-computer interface (BCI) paradigms are usually tested when environmental and biological artifacts are intentionally avoided. In this study, we deliberately introduced different perturbations in order to test the robustness of a steady state visual evoked potential (SSVEP) based BCI. Specifically we investigated to what extent a drop in performance is related to the degraded quality of EEG signals or rather due to increased cognitive load. In the online tasks, subjects focused on one of the four circles and gave feedback on the correctness of the classification under four conditions randomized across subjects: Control (no perturbation), Speaking (counting loudly and repeatedly from one to ten), Thinking (mentally counting repeatedly from one to ten), and Listening (listening to verbal counting from one to ten). Decision tree, Naïve Bayes and K-Nearest Neighbor classifiers were used to evaluate the classification performance using features generated by canonical correlation analysis. During the online condition, Speaking and Thinking decreased moderately the mean classification accuracy compared to Control condition whereas there was no significant difference between Listening and Control conditions across subjects. The performances were sensitive to the classification method and to the perturbation conditions. We have not observed significant artifacts in EEG during perturbations in the frequency range of interest except in theta band. Therefore we concluded that the drop in the performance is likely to have a cognitive origin. During the Listening condition relative alpha power in a broad area including central and temporal regions primarily over the left hemisphere correlated negatively with the performance thus most likely indicating active suppression of the distracting presentation of the playback. This is the first study that systematically evaluates the effects of natural artifacts (i.e. mental, verbal and audio perturbations) on SSVEP-based BCIs. The results can be used to improve individual classification performance taking into account effects of perturbations.
Objectives. Arterial blood pressure and serum blood glucose concentration, and the level of anxiety, as determined by the Spielberger test, as physical and psychological markers of stress under “modernization”, were studied in groups of native Siberians: the Khanty and the Mansi.
Results. The fraction of respondents with a high level of anxiety is 64% of the total sample. The average values of systolic and diastolic blood pressure are higher among natives living in large than in small “national” settlements (p<0.05). The arterial blood pressure of town dwellers is even higher. The same patterns are seen in the blood serum glucose concentrations in female samples. The average arterial blood pressure (in males and females) and the blood serum glucose concentration (in females) increases as people diverge from “traditional” lifestyles.
Conclusions. The results demonstrate that “modernization” and urbanization have a serious stressing influence on the aborigines of North Siberia.
Background: Recent evidence suggests that stroke is increasing as a cause of morbidity and mortality in younger adults, where it carries particular significance for working individuals. Accurate and up-to-date estimates of stroke burden are important for planning stroke prevention and management in younger adults. Objectives: This study aims to estimate prevalence, mortality and disability-adjusted life years (DALYs) and their trends for total, ischemic stroke (IS) and hemorrhagic stroke (HS) in the world for 1990-2013 in adults aged 20-64 years. Methodology: Stroke prevalence, mortality and DALYs were estimated using the Global Burden of Disease (GBD) 2013 methods. All available data on rates of stroke incidence, excess mortality, prevalence and death were collected. Statistical models were used along with country-level covariates to estimate country-specific stroke burden. Stroke-specific disability weights were used to compute years lived with disability and DALYs. Means and 95% uncertainty intervals (UIs) were calculated for prevalence, mortality and DALYs. The median of the percent change and 95% UI were determined for the period from 1990 to 2013. Results: In 2013, in younger adults aged 20-64 years, the global prevalence of HS was 3,725,085 cases (95% UI 3,548,098-3,871,018) and IS was 7,258,216 cases (95% UI 6,996,272-7,569,403). Globally, between 1990 and 2013, there were significant increases in absolute numbers and prevalence rates of both HS and IS for younger adults. There were 1,483,707 (95% UI 1,340,579-1,658,929) stroke deaths globally among younger adults but the number of deaths from HS (1,047,735 (95% UI 945,087-1,184,192)) was significantly higher than the number of deaths from IS (435,972 (95% UI 354,018-504,656)). There was a 20.1% (95% UI -23.6 to -10.3) decline in the number of total stroke deaths among younger adults in developed countries but a 36.7% (95% UI 26.3-48.5) increase in developing countries. Death rates for all strokes among younger adults declined significantly in developing countries from 47 (95% UI 42.6-51.7) in 1990 to 39 (95% UI 35.0-43.8) in 2013. Death rates for all strokes among younger adults also declined significantly in developed countries from 33.3 (95% UI 29.8-37.0) in 1990 to 23.5 (95% UI 21.1-26.9) in 2013. A significant decrease in HS death rates for younger adults was seen only in developed countries between 1990 and 2013 (19.8 (95% UI 16.9-22.6) and 13.7 (95% UI 12.1-15.9)) per 100,000). No significant change was detected in IS death rates among younger adults. The total DALYs from all strokes in those aged 20-64 years was 51,429,440 (95% UI 46,561,382-57,320,085). Globally, there was a 24.4% (95% UI 16.6-33.8) increase in total DALY numbers for this age group, with a 20% (95% UI 11.7-31.1) and 37.3% (95% UI 23.4-52.2) increase in HS and IS numbers, respectively. Conclusions: Between 1990 and 2013, there were significant increases in prevalent cases, total deaths and DALYs due to HS and IS in younger adults aged 20-64 years. Death and DALY rates declined in both developed and developing countries but a significant increase in absolute numbers of stroke deaths among younger adults was detected in developing countries. Most of the burden of stroke was in developing countries. In 2013, the greatest burden of stroke among younger adults was due to HS. While the trends in declining death and DALY rates in developing countries are encouraging, these regions still fall far behind those of developed regions of the world. A more aggressive approach toward primary prevention and increased access to adequate healthcare services for stroke is required to substantially narrow these disparities.
Background: There is increasing recognition of stroke as an important contributor to childhood morbidity and mortality. Current estimates of global childhood stroke burden and its temporal trends are sparse. Accurate and up-to-date estimates of childhood stroke burden are important for planning research and the resulting evidence-based strategies for stroke prevention and management. Objectives: To estimate the prevalence, mortality and disability-adjusted life years (DALYs) for ischemic stroke (IS), hemorrhagic stroke (HS) and all stroke types combined globally from 1990 to 2013. Methodology: Stroke prevalence, mortality and DALYs were estimated using the Global Burden of Disease 2013 methods. All available data on stroke-related incidence, prevalence, excess mortality and deaths were collected. Statistical models and country-level covariates were employed to produce comprehensive and consistent estimates of prevalence and mortality. Stroke-specific disability weights were used to estimate years lived with disability and DALYs. Means and 95% uncertainty intervals (UIs) were calculated for prevalence, mortality and DALYs. The median of the percent change and 95% UI were determined for the period from 1990 to 2013. Results: In 2013, there were 97,792 (95% UI 90,564-106,016) prevalent cases of childhood IS and 67,621 (95% UI 62,899-72,214) prevalent cases of childhood HS, reflecting an increase of approximately 35% in the absolute numbers of prevalent childhood strokes since 1990. There were 33,069 (95% UI 28,627-38,998) deaths and 2,615,118 (95% UI 2,265,801-3,090,822) DALYs due to childhood stroke in 2013 globally, reflecting an approximately 200% decrease in the absolute numbers of death and DALYs in childhood stroke since 1990. Between 1990 and 2013, there were significant increases in the global prevalence rates of childhood IS, as well as significant decreases in the global death rate and DALYs rate of all strokes in those of age 0-19 years. While prevalence rates for childhood IS and HS decreased significantly in developed countries, a decline was seen only in HS, with no change in prevalence rates of IS, in developing countries. The childhood stroke DALY rates in 2013 were 13.3 (95% UI 10.6-17.1) for IS and 92.7 (95% UI 80.5-109.7) for HS per 100,000. While the prevalence of childhood IS compared to childhood HS was similar globally, the death rate and DALY rate of HS was 6- to 7-fold higher than that of IS. In 2013, the prevalence rate of both childhood IS and HS was significantly higher in developed countries than in developing countries. Conversely, both death and DALY rates for all stroke types were significantly lower in developed countries than in developing countries in 2013. Men showed a trend toward higher childhood stroke death rates (1.5 (1.3-1.8) per 100,000) than women (1.1 (0.9-1.5) per 100,000) and higher childhood stroke DALY rates (120.1 (100.8-143.4) per 100,000) than women (90.9 (74.6-122.4) per 100,000) globally in 2013. Conclusions: Globally, between 1990 and 2013, there was a significant increase in the absolute number of prevalent childhood strokes, while absolute numbers and rates of both deaths and DALYs declined significantly. The gap in childhood stroke burden between developed and developing countries is closing; however, in 2013, childhood stroke burden in terms of absolute numbers of prevalent strokes, deaths and DALYs remained much higher in developing countries. There is an urgent need to address these disparities with both global and country-level initiatives targeting prevention as well as improved access to acute and chronic stroke care.
Today, recombinant proteins are quite widely used in biomedical and biotechnological applications. At the same time, the question about their full equivalence to the native analogues remains unanswered. To gain additional insight into this problem, intimate atomistic details of a relatively simple protein, small and structurally rigid recombinant cardiotoxin I (CTI) from cobra Naja oxiana venom, were characterized using nuclear magnetic resonance (NMR) spectroscopy and atomistic molecular dynamics (MD) simulations in water. Compared to the natural protein, it contains an additional Met residue at the N-terminus. In this work, the NMR-derived spatial structure of uniformly 13C- and 15N-labeled CTI and its dynamic behavior were investigated and subjected to comparative analysis with the corresponding data for the native toxin. The differences were found in dihedral angles of only a single residue, adjacent to the N-terminal methionine. Microsecond-long MD traces of the toxins reveal an increased flexibility in the residues spatially close to the N-Met. As the detected structural and dynamic changes of the two CTI models do not result in substantial differences in their cytotoxicities, we assume that the recombinant protein can be used for many purposes as a reasonable surrogate of the native one. In addition, we discuss general features of the spatial organization of cytotoxins, implied by the results of the current combined NMR and MD study.
Background: Prior studies of the human growth hormone receptor (GHR) revealed a distinct role of spatial rearrangements of its dimeric transmembrane domain in signal transduction across membrane. Detailed structural information obtained in the present study allowed elucidating the bases of such rearrangement and provided novel insights into receptor functioning.
Methods: We investigated the dimerization of recombinant TMD fragment GHR254-294 by means of high-resolution NMR in DPC micelles and molecular dynamics in explicit POPC membrane.
Results: We resolved two distinct dimeric structures of GHR TMD coexisting in membrane-mimicking micellar environment and providing left- and right-handed helix-helix association via different dimerization motifs. Based on the available mutagenesis data, the conformations correspond to the dormant and active receptor states and are distinguished by cis-trans isomerization of Phe-Pro266 bond in the transmembrane helix entry. Molecular dynamic relaxations of the structures in lipid bilayer revealed the role of the proline residue in functionally significant rearrangements of the adjacent juxtamembrane region supporting alternation between protein-protein and protein-lipid interactions of this region that can be triggered by ligand binding. Also, the importance of juxtamembrane S-S bonding for signal persistency, and somewhat unusual aspects of transmembrane region interaction with water molecules were demonstrated.
Conclusions: Two alternative dimeric structures of GHR TMD attributed to dormant and active receptor states interchange via allosteric rearrangements of transmembrane helices and extracellular juxtamembrane regions that support coordination between protein-protein and protein-lipid interactions.
General Significance: This study provides a holistic vision of GHR signal transduction across the membrane emphasizing the role of protein-lipid interactions.
The general structure and action of all eukaryotic and archaeal RNA polymerases machinery have an astonishing similarity despite the diversity of core promoter sequences in different species. The goal of our work is to find common characteristics of DNA region that define it as a promoter for the RNA polymerase II (Pol II).
The profiles of a large number of physical and structural characteristics, averaged over representative sets of the Pol II minimal core promoters of the evolutionary divergent species from animals, plants and unicellular fungi were analysed. In addition to the characteristics defined at the base-pair steps, we, for the first time, use profiles of the ultrasonic cleavage and DNase I cleavage indexes, informative for internal properties of each complementary strand.
DNA of the core promoters of metazoans and Schizosaccharomyces pombe has similar structural organization. Its mechanical and 3D structural characteristics have singular properties at the positions of TATA-box. The minor groove is broadened and conformational motion is decreased in that region. Special characteristics of conformational behavior are revealed in metazoans at the region, which connects the end of TATA-box and the transcription start site (TSS). The intensities of conformational motions in the complementary strands are periodically changed in opposite phases. They are noticeable, best of all, in mammals. Such conformational features are lacking in the core promoters of S. pombe. The profiles of Saccharomyces cerevisiae core promoters significantly differ: their singular region is shifted down thus pointing to the uniqueness of their structural organization. Obtained results may be useful in genetic engineering for artificial modulation of the promoter strength.
Weak toxin from Naja kaouthia (WTX) belongs to the group of nonconventional “three-finger” snake neurotoxins. It irreversibly inhibits nicotinic acetylcholine receptors and allosterically interacts with muscarinic acetylcholine receptors (mAChRs). Using site-directed mutagenesis, NMR spectroscopy, and computer modeling, we investigated the recombinant mutant WTX analogue (rWTX) which, compared with the native toxin, has an additional N-terminal methionine residue. In comparison with the wild-type toxin, rWTX demonstrated an altered pharmacological profile, decreased binding of orthosteric antagonist N-methylscopolamine to human M1- and M2-mAChRs, and increased antagonist binding to M3-mAChR. Positively charged arginine residues located in the flexible loop II were found to be crucial for rWTX interactions with all types of mAChR. Computer modeling suggested that the rWTX loop II protrudes to the M1-mAChR allosteric ligand-binding site blocking the entrance to the orthosteric site. In contrast, toxin interacts with M3-mAChR by loop II without penetration into the allosteric site. Data obtained provide new structural insight into the target-specific allosteric regulation of mAChRs by “three-finger” snake neurotoxins.
We studied structural peculiarities of 123 human genes which were previously identified as genes of early response to exercise stress. Compared to protein-coding genes in general, their structure revealed some peculiarities: they are shorter in both coding and non-coding regions and contain fewer introns. This result is in good agreement with the similar results reported for stress-responding genes in other species (yeasts, thale cress, and mice).
Toward the development of classical force fields for the accurate modeling of clay mineral-water systems, we have extended the use of metalâ€“Oâ€“H (Mâ€“Oâ€“H) angle bending terms to describe surface Siâ€“Oâ€“H bending for hydrated kaolinite edge structures. Kaolinite, comprising linked octahedral Al and tetrahedral Si sheets, provides a rigorous test by combining aluminol and silanol groups with water molecules in hydrated edge structures. Periodic density functional theory and classical force fields were used with molecular dynamics to evaluate the structure, dynamics, hydrogen bonding, and power spectra for deriving optimum bending force constants and optimal equilibrium angles. Cleavage energies derived from density functional theory molecular dynamics calculations indicate the relative stabilities of both AC1 and AC2 edge terminations of kaolinite where Siâ€“OH and Alâ€“(OH2) or Siâ€“OH, Alâ€“OH, and Alâ€“(OH2) groups exist, respectively. Although not examined in this study, the new Siâ€“Oâ€“H angle bending parameter should allow for improved modeling of hydroxylated surfaces of silica minerals such as quartz and cristobalite, as well as amorphous silica-based surfaces and potentially those of other silicate and aluminosilicate phases.
Microprocesses associated with plasma inhomogeneities are studied on the basis of data from the Investigation of Cusp Irregularities (ICI-3) sounding rocket. The ICI-3 rocket is devoted to investigating a reverse flow event in the cusp F region ionosphere. By numerical stability analysis, it is demonstrated that inhomogeneous-energy-density-driven (IEDD) instability can be a mechanism for the excitation of small-scale plasma inhomogeneities. The Local Intermittency Measure (LIM) method also applied the rocket data to analyze irregular structures of the electric field during rocket flight in the cusp. A qualitative agreement between high values of the growth rates of the IEDD instability and the regions with enhanced LIM is observed. This suggests that IEDD instability is connected to turbulent non-Gaussian processes. Published by AIP Publishing.
The principal possibility to measure the plasma density and its fluctuations in the ionosphere on ultra-small space vehicles using radiophysical methods is shown. These methods allow us to determine the characteristics of the medium by the properties of the received radiation. It is assumed that each small spacecraft has a satellite navigation receiver as well as a device for emitting and detecting a signal at two multiple frequencies in the radio band. In this approach, information on plasma density is contained in the received phase difference. Radio receivers and radio transmitters on satellites constantly exchange radio signals and then it is possible to determine the plasma density and its fluctuations from the phase shift. Numerical estimates are also made to determine the maximum distance between satellites where one can reliably receive a radio signal.
In this work, values of the fractal dimension and the connectivity index characterizing the structure of Hall conductivities on the night side of the auroral ionosphere are derived in general form. Restrictions imposed on fractal structure of the ionospheric conductivity are analyzed in terms of the percolation of the ionospheric Hall currents. It is shown that the structure of ionospheric Hall conductivities can be described as asymptotically path connected fractal. This result is supported by analysis of typical structure observed in auroral electron precipitation which are also the main source of ionization on the night side of the ionosphere. It is demonstrated that crossing the precipitation region in the direction perpendicular to the multiple arcs system, one should observe the structure of the precipitation which looks like a generalized Cantor set.
⎯The study of the indices of developmental homeostasis in natural populations leads to the definition of the fundamentals of population developmental biology, which is associated with the assessment of the nature of phenotypic diversity and the mechanisms of population dynamics and microevolutionary changes. Characterization of environmental quality based on the assessment of population status by developmental homeostasis determines the fundamentals of the health of environment concept. The use of the ideas of developmental homeostasis and the health of environment in the studies of homeostatic mechanisms of biological systems of different levels (from the organism and population to the community and ecosystem) is promising. This gives new opportunities for understanding the mechanisms that provide sustainability and their ratio at different levels as well as for the characterization of ontogenetic stability significance. The notion of developmental homeostasis, or homeorhesis, is promising for the elaboration of the ecological and biological basics of sustainable development.
Professor Yuri E. Gorbatywas born 30 July 1932 in the city Grozny, in the Soviet Union. He has graduated from the Mendeleev Institute of Chemical Technology,Moscow, in 1955. He has got his Candidate of Sciences (Ph.D.) degree in 1963 for his work on “Non-equilibrium crystallization of the three-componentmelts”, and later in 1988 he was awarded a Doctor of Sciences degree for the work “The effect of temperature and pressure on the nearest ordering in liquid and supercritical water”. Between these two dates and then later in his scientific career Yuri E. Gorbaty has become one of the leading experts in the field of experimental studies of the structure and properties of fluids, especially aqueous fluids at high temperatures and pressures, by methods of IR and Raman spectroscopy and by X-ray diffraction.
Knowledge of supra-glacial debris cover and its changes remain incomplete in the Greater Caucasus, in spite of recent glacier studies. Here we present data of supra-glacial debris cover for 659 glaciers across the Greater Caucasus based on Landsat and SPOT images from the years 1986, 2000 and 2014. We combined semi-automated methods for mapping the clean ice with manual digitization of debris-covered glacier parts and calculated supra-glacial debris-covered area as the residual between these two maps. The accuracy of the results was assessed by using high-resolution Google Earth imagery and GPS data for selected glaciers. From 1986 to 2014, the total glacier area decreased from 691.5±29.0 to 590.0±25.8 km2 (15.8±4.1 %, or ∼0.52 % yr−1), while the clean-ice area reduced from 643.2±25.9 to 511.0±20.9 km2 (20.1±4.0 %, or ∼0.73 % yr−1). In contrast supra-glacial debris cover increased from 7.0±6.4 %, or 48.3±3.1 km2, in 1986 to 13.4±6.2 % (∼0.22 % yr−1), or 79.0±4.9 km2, in 2014. Debris-free glaciers exhibited higher area and length reductions than debris-covered glaciers. The distribution of the supra-glacial debris cover differs between the northern and southern and between the western, central and eastern Greater Caucasus. The observed increase in supra-glacial debris cover is significantly stronger on the northern slopes. Overall, we have observed up-glacier average migration of supra-glacial debris cover from about 3015 to 3130 m a.s.l. (metres above sea level) during the investigated period.