Pair-wise sequence alignment is the basic method of comparative analysis of proteins and nucleic acids. Studying the results of alignment one has to consider two questions^ (1) did the program find all the interesting similarities (“sensitivity”) and (2) are all the found similarities interesting (“selectivity‘’). Definitely, one has to specify, what alignments are considered as the interesting ones. Analogous questions can be addressed to each of the obtained alignments: (3) which part of the aligned positions are aligned correctly (“confidence”) and (4) does alignment contain all pairs of the corresponding positions of compared sequences (“accuracy”). Naturally, the answer on the questions depends on the definition of correct alignment. The presentation addresses above two pairs of questions that are extremely important in interpreting of the results of sequence comparison.
We establish the equivalence between the refined topological vertex of Iqbal-Kozcaz-Vafa and a certain representation theory of the quantum algebra of type W1+∞ introduced by Miki. Our construction involves trivalent intertwining operators Φ and Φ* associated with triples of the bosonic Fock modules. Resembling the topological vertex, a triple of vectors ∈ Z2 is attached to each intertwining operator, which satisfy the Calabi-Yau and smoothness conditions. It is shown that certain matrix elements of Φ and Φ* give the refined topological vertex Cλμν (t, q) of Iqbal-Kozcaz-Vafa. With another choice of basis, we recover the refined topological vertex Cλμν (q, t) of Awata-Kanno. The gluing factors appears correctly when we consider any compositions of Φ and Φ*. The spectral parameters attached to Fock spaces play the role of the Kahler parameters.
Despite a century of research into visual word recognition, basic questions remain unresolved about the functional architecture of the process that maps visual inputs from orthographic analysis onto lexical form and meaning and about the units of analysis in terms of which these processes are conducted. Here we use magnetoencephalography, supported by a masked priming behavioral study, to address these questions using contrasting sets of simple (walk), complex (swimmer), and pseudo-complex (corner) forms. Early analyses of orthographic structure, detectable in bilateral posterior temporal regions within a 150-230 msec time frame, are shown to segment the visual input into linguistic substrings (words and morphemes) that trigger lexical access in left middle temporal locations from 300 msec. These are primarily feedforward processes and are not initially constrained by lexical-level variables. Lexical constraints become significant from 390 msec, in both simple and complex words, with increased processing of pseudowords and pseudo-complex forms. These results, consistent with morpho-orthographic models based on masked priming data, map out the real-time functional architecture of visual word recognition, establishing basic feedforward processing relationships between orthographic form, morphological structure, and lexical meaning
Bacteria are known to exchange genetic information by horizontal gene transfer. Since the frequency of homologous recombination depends on the similarity between the recombining segments, several studies examined whether this could lead to the emergence of subspecies. Most of them simulated fixed-size Wright-Fisher populations, in which the genetic drift should be taken into account. Here, we use nonlinear Markov processes to describe a bacterial population evolving under mutation and recombination. We consider a population structure as a probability measure on the space of genomes. This approach implies the infinite population size limit, and thus, the genetic drift is not assumed. We prove that under these conditions, the emergence of subspecies is impossible.
A community of hamadryas baboons (Papio hamadryas) consists of a unique organization with four structural levels and marked hierarchical relationships between males and females. This makes it an ideal system for testing the hypothesis that relationship quality influences reconciliation between individuals. Post-conflict reconciliation was studied in hamadryas baboons. The behavior of 436 conflicting pairs was studied. Reconciliation was found to be characteristic of pairs of different composition, including: 1) pairs consisting of a male and a female from his harem; 2) pairs consisting of two females from the same harem; 3) pairs consisting of two related animals; 4) pairs consisting of two males; 5) pairs including a female and a young (almost adult) male. Significant differences in reconciliatory tendencies were seen in different pair categories, along with a high level of selectivity of the interactions between former antagonists, evidencing that the probability of reconciliation between hamadryas baboon individuals depends on the quality of the relationships between them. Keywords: hamadryas baboons, reconciliation, male-female bonds.
Arctic driftwood represents a unique proxy archive at the interface of marine and terrestrial environments. Combined wood anatomical and dendrochronological analyses have been used to detect the origin of driftwood and may allow past timber floating activities, as well as past sea ice and ocean current dynamics to be reconstructed. However, the success of driftwood provenancing studies depends on the length, number, and quality of circumpolar boreal reference chronologies. Here, we introduce a Eurasian-wide high-latitude network of 286 ring width chronologies from the International Tree Ring Data Bank (ITRDB) and 160 additional sites comprising the three main boreal conifers Pinus, Larix, and Picea. We assess the correlation structure within the network to identify growth patterns in the catchment areas of large Eurasian rivers, the main driftwood deliverers. The occurrence of common growth patterns between and differing patterns within catchments indicates the importance of biogeographic zones for ring width formation and emphasizes the degree of spatial precision when provenancing. Reference chronologies covering millennial timescales are so far restricted to a few larch sites in Central and Eastern Siberia (eastern Taimyr, Yamal Peninsula and north-eastern Yakutia), as well as several pine sites in Scandinavia, where large rivers are missing though. The general good spatial coverage of tree-ring sites across northern Eurasia indicates the need for updating and extending existing chronologies rather than developing new sites.
The regional differentiation of buyers' activity in the primary market of the Moscow agglomeration (MA) is analyzed based on address data of the buyers' initial registration. Acquisition of real estate by nonresident buyers (17% of transactions in Moscow and 23% in Moscow oblast) provides housing for about 100000 people per year, or 40% of the net migration inflow. The factor of the agglomeration effect gives leadership to buyers from St. Petersburg, and the factor of natural resource rent produces a high share of buyers from the Khanty–Mansi and Yamalo-Nenets autonomous okrugs (6.4% vs 1.6% of population), making their residents purchase real estate in Moscow under a low level of migration to the Moscow metropolitan area (MMA). Most nonresident buyers come from regions of the Russian provincial areas and earn the money to buy their housing in the labor market of the MMA. The distance factor makes the share of buyers from firstorder neighboring regions of the MMA 2.1 times higher than their share in the population in Moscow and 2.5 times higher than in Moscow oblast.
About the spatial-temporal approach in terrorism studies
We often change our decisions and judgments to conform with normative group behavior. However, the neural mechanisms of social conformity remain unclear. Here we show, using functional magnetic resonance imaging, that conformity is based on mechanisms that comply with principles of reinforcement learning. We found that individual judgments of facial attractiveness are adjusted in line with group opinion. Conflict with group opinion triggered a neuronal response in the rostral cingulate zone and the ventral striatum similar to the "prediction error" signal suggested by neuroscientific models of reinforcement learning. The amplitude of the conflict-related signal predicted subsequent conforming behavioral adjustments. Furthermore, the individual amplitude of the conflict-related signal in the ventral striatum correlated with differences in conforming behavior across subjects. These findings provide evidence that social group norms evoke conformity via learning mechanisms reflected in the activity of the rostral cingulate zone and ventral striatum.
Housing construction in the Moscow urban agglomeration is the main incentive mechanism for migration inflow via the lowering of such important barrier as housing prices. There is a positive feedback between the extensive development of the Moscow urban agglomeration and migration inflow to the metropolitan area, leading to hyperconcentration of population and economic activity. Theoretical analysis has shown that there is an equilibrium ratio between the new housing supply and the net migration into the Moscow metropolitan area. Empirical evidence shows that the ability of the Moscow urban agglomeration to accumulate migration in the 2000s at the respective rate of construction fell by half compared to the 1990s. Migration inflow is mostly contributed by extensive model of agglomeration development and urban sprawl due to the dominance of large-scale economy-class construction projects on unoccupied lands in a 30-km zone between the Moscow Automobile Ring Road (MKAD) and the Moscow Small Ring Road (MMK). The construction in this zone is a key regulator of the migration balance in the Moscow urban agglomeration and at the national level. Extensive development is subsidized by regional and federal budgetary investments, including transportation infrastructure, which contradicts state efforts to mitigate interregional inequality through fiscal redistribution.
The possible impact of El Niño–Southern Oscillation (ENSO) events on the main components of CO2 and H2O fluxes between the tropical rainforest and the atmosphere is investigated. The fluxes were continuously measured in an old-growth mountainous tropical rainforest in Central Sulawesi in Indonesia using the eddy covariance method for the period from January 2004 to June 2008. During this period, two episodes of El Niño and one episode of La Niña were observed. All these ENSO episodes had moderate intensity and were of the central Pacific type. The temporal variability analysis of the main meteorological parameters and components of CO2 and H2O exchange showed a high sensitivity of evapotranspiration (ET) and gross primary production (GPP) of the tropical rainforest to meteorological variations caused by both El Niño and La Niña episodes. Incoming solar radiation is the main governing factor that is responsible for ET and GPP variability. Ecosystem respiration (RE) dynamics depend mainly on the air temperature changes and are almost insensitive to ENSO. Changes in precipitation due to moderate ENSO events did not have any notable effect on ET and GPP, mainly because of sufficient soil moisture conditions even in periods of an anomalous reduction in precipitation in the region.
Mutations in transmembrane (TM) domains of receptor tyrosine kinases are shown to cause a number of inherited diseases and cancer development. Here, we use a combined molecular modeling approach to understand molecular mechanism of effect of G370R and A391E mutations on dimerization of TM domains of human fibroblast growth factor receptor 3 (FGFR3). According to results of Monte-Carlo conformational search in the implicit membrane and further molecular dynamics simulations, TM dimer of this receptor is able to form a number of various conformations, which differ significantly by the free energy of association in a full-atom model bilayer. The aforementioned mutations affect dimerization efficiency of TM segments and lead to repopulation of conformational ensemble for the dimer. Particularly, both mutations do not change the dimerization free energy of the predominant (putative “non-active”) symmetric conformation of TM dimer, while affect dimerization efficiency of its asymmetric (“intermediate”) and alternative symmetric (putative “active”) models. Results of our simulations provide novel atomistic prospective of the role of G370 and A391E mutations in dimerization of TM domains of FGFR3 and their consecutive contributions to the activation pathway of the receptor.
The summary paper argues that the phenomenon of male alliance (friendship) emerges as a consequence of mutual preference demonstrated by male individuals - both human and animal, - and such preference can be empirically captured. Friendly relations between men are built on two different foundations: (1) the principle of biological and social similarity and (2) the principle of psychological complementarity of the alliance members. Friendship is predominantly formed between boys and men of the same ethnic (racial) origin, similar age, behavior, and common social background. By contrast, psychologically friends are selected based on the complementarity of their temperament and main personality traits, such as ergonicity, sthenicity, emotionality, neophobia/neophilia, extraversion/introversion, dependence/independence of behavior, and dominance/submissiveness. These principles trigger the following key effects: a person is more likely to develop an individual preference and find a friend in childhood, and the number of potential friends is very limited.
The aim of this study was to estimate dependence of saccadic latency during stimulation of the dominant and subdominant eye in various conditions of presentation of target and distracting stimuli.
Human-secreted Ly-6/uPAR-related protein-2 (SLURP-2) regulates the growth and differentiation of epithelial cells. Previously, the auto/paracrine activity of SLURP-2 was considered to be mediated via its interaction with the α3β2 subtype of the nicotinic acetylcholine receptors (nAChRs). Here, we describe the structure and pharmacology of a recombinant analogue of SLURP-2. Nuclear magnetic resonance spectroscopy revealed a ‘three-finger’ fold of SLURP-2 with a conserved β-structural core and three protruding loops. Affinity purification using cortical extracts revealed that SLURP-2 could interact with the α3, α4, α5, α7, β2, and β4 nAChR subunits, revealing its broader pharmacological profile. SLURP-2 inhibits acetylcholine-evoked currents at α4β2 and α3β2-nAChRs (IC50 ~0.17 and >3 μM, respectively) expressed in Xenopus oocytes. In contrast, at α7-nAChRs, SLURP-2 significantly enhances acetylcholine-evoked currents at concentrations <1 μM but induces inhibition at higher concentrations. SLURP-2 allosterically interacts with human M1 and M3 muscarinic acetylcholine receptors (mAChRs) that are overexpressed in CHO cells. SLURP-2 was found to promote the proliferation of human oral keratinocytes via interactions with α3β2-nAChRs, while it inhibited cell growth via α7-nAChRs. SLURP-2/mAChRs interactions are also probably involved in the control of keratinocyte growth. Computer modeling revealed possible SLURP-2 binding to the ‘classical’ orthosteric agonist/antagonist binding sites at α7 and α3β2-nAChRs.
The variant His at codon 48 of the alcohol dehydrogenase gene (ADH1B) results in more efficient ethanol metabolism than with the “typical” codon 48Arg. In this study we introduced selection properties of Arg48His genotypes of ADH1B and estimated fitness in four ethnic-geographical clusters in Asia. Population genetics models were employed that derive observed gene frequencies from fitness relationships among genotypes, to infer the selection pattern of polymorphisms in an indirect manner. The data were analyzed using the model of “complete stationary distribution” by Wright that takes into account random genetic drift, pressure of migrations, mutations, and selection as influential factors of gene frequency. We found that the different population groups showed some variation in the types of selection for Arg48His. Han Chinese from eastern and southeastern China and the Japanese and Korean populations showed stabilizing selection, while the groups from Central Asian and Indochina showed divergent selection. However, all the groups demonstrated a strong positive selection for Arg48His.
Although semantic processing has traditionally been associated with brain responses maximal at 350-400 ms, recent studies reported that words of different semantic types elicit topographically distinct brain responses substantially earlier, at 100-200 ms. These earlier responses have, however, been achieved using insufficiently precise source localisation techniques, therefore casting doubt on reported differences in brain generators. Here, we used high-density MEG-EEG recordings in combination with individual MRI images and state-of-the-art source reconstruction techniques to compare localised early activations elicited by words from different semantic categories in different cortical areas. Reliable neurophysiological word-category dissociations emerged bilaterally at ~ 150 ms, at which point action-related words most strongly activated frontocentral motor areas and visual object-words occipitotemporal cortex. These data now show that different cortical areas are activated rapidly by words with different meanings and that aspects of their category-specific semantics is reflected by dissociating neurophysiological sources in motor and visual brain systems.
A new statistical approach to alignment (finding the longest common subsequence) of two random RNA-type sequences is proposed. We have constructed a generalized ‘dynamic programming’ algorithm for finding the extreme value of the free energy of two noncoding RNAs. In our procedure, we take into account the binding free energy of two random heteropolymer chains which are capable of forming the cloverleaf-like spatial structures typical for RNA molecules. The algorithm is based on two observations: (i) the standard alignment problem can be considered as a zero-temperature limit of a more general statistical problem of binding of two associating heteropolymer chains; (ii) this last problem can be generalized naturally to consider sequences with hierarchical cloverleaf-like structures (i.e. of RNA type). The approach also permits us to perform a ‘secondary structure recovery’. Namely, we can predict the optimal secondary structures of interacting RNAs in a zero-temperature limit knowing only their primary sequences.