A phenomenon termed negative priming is defined as an increase in reaction time and/or decrease in performance during instances in which current target stimuli are employed as distractor stimuli in the previous trial. A recent qualitative review on negative priming reported neural regions of interest underlined by activity within the right middle frontal gyrus and left middle temporal gyrus; however, these areas of interest have not been tested and supported by using coordinate-based, quantitative meta-analysis. We compiled functional magnetic resonance imaging studies that examined neural correlates of priming tasks using perceptual, conceptual and lexical primes. Effect-size signed differential mapping was used to perform a neuroimaging meta-analysis on the negative priming effect. Results from fourteen studies (245 participants; 85 foci) show concordance across studies in the right middle frontal gyrus and the left superior temporal gyrus, as suggested by the previous review; however, results also yielded concordance within the anterior cingulate cortex. Our data support the extant hypothesis and offer new insights into the neural mechanisms of the negative priming effect.
Humans are unique in developing large lexicons as their communication tool; to achieve this, they are able to learn new words rapidly. However, neural bases of this rapid learning, which may be an expression of a more general cognitive mechanism likely rooted in plasticity at cellular and synaptic levels, are not yet understood. In this update, the author highlights a selection of recent studies that attempted to trace word learning in the human brain noninvasively. A number of brain areas, most notably in hippocampus and neocortex, appear to take part in word acquisition. Critically, the currently available data not only demonstrate the hippocampal role in rapid encoding followed by slow-rate consolidation of cortical word memory traces but also suggest immediate neocortical involvement in the word memory trace formation. Echoing early behavioral studies in ultra-rapid word learning, the reviewed neuroimaging experiments can be taken to suggest that our brain may effectively form new cortical circuits online, as it gets exposed to novel linguistic patterns in the sensory input.
We investigated neural distinctions between inflectional and derivational morphology and their interaction with lexical frequency using the mismatch negativity (MMN), an established neurophysiological index of experience-dependent linguistic memory traces and automatic syntactic processing. We presented our electroencephalography (EEG) study participants with derived and inflected words of variable lexical frequencies against their monomorphemic base forms in a passive oddball paradigm, along with acoustically matched pseudowords. Sensor space and distributed source modelling results showed that at 100-150 msec after the suffix onset, derived words elicited larger responses than inflected words. Furthermore, real derived words showed advantage over pseudo-derivations and frequent derivations elicited larger activation than less frequent ones. This pattern of results is fully in line with previous research that explained lexical MMN enhancement by an activation of strongly connected word-specific long-term memory circuits, and thus suggests stronger lexicalisation for frequently used complex words. At the same time, a strikingly different pattern was found for inflectional forms: higher response amplitude for pseudo-inflections than for real inflected words, with no clear frequency effects. This is fully in line with previous MMN results on combinatorial processing of (morpho)syntactic stimuli: higher response to ungrammatical morpheme strings than grammatical ones, which does not depend on the string's surface frequency. This pattern suggests that, for inflectional forms, combinatorial processing route dominates over whole-form storage and access. In sum, our results suggest that derivations are more likely to form unitary representations than inflections which are likely to be processed combinatorially, and imply at least partially distinct brain mechanisms for the processing and representation of these two types of morphology. These dynamic mechanisms, underpinned by perisylvian networks, are activated rapidly, at 100-150 msec after the information arrives at the input, and in a largely automatic fashion, possibly providing neural basis for the first-pass morphological processing of spoken words.
Rapid and automatic processing of grammatical complexity is argued to take place during speech comprehension, engaging a left-lateralized fronto-temporal language network. Here we address how neural activity in these regions is modulated by the grammatical properties of spoken words. We used combined magneto- and electroencephalography to delineate the spatiotemporal patterns of activity that support the recognition of morphologically complex words in English with inflectional (-s) and derivational (-er) affixes (e.g., bakes, baker). The mismatch negativity, an index of linguistic memory traces elicited in a passive listening paradigm, was used to examine the neural dynamics elicited by morphologically complex words. Results revealed an initial peak 130-180 ms after the deviation point with a major source in left superior temporal cortex. The localization of this early activation showed a sensitivity to two grammatical properties of the stimuli: (1) the presence of morphological complexity, with affixed words showing increased left-laterality compared to non-affixed words; and (2) the grammatical category, with affixed verbs showing greater left-lateralization in inferior frontal gyrus compared to affixed nouns (bakes vs. beaks). This automatic brain response was additionally sensitive to semantic coherence (the meaning of the stem vs. the meaning of the whole form) in left middle temporal cortex. These results demonstrate that the spatiotemporal pattern of neural activity in spoken word processing is modulated by the presence of morphological structure, predominantly engaging the left-hemisphere's fronto-temporal language network, and does not require focused attention on the linguistic input.
The neurobiological basis and temporal dynamics of communicative language processing pose important yet unresolved questions. It has previously been suggested that comprehension of the communicative function of an utterance, i.e. the so-called speech act, is supported by an ensemble of neural networks, comprising lexico-semantic, action and mirror neuron as well as theory of mind circuits, all activated in concert. It has also been demonstrated that recognition of the speech act type occurs extremely rapidly. These findings however, were obtained in experiments with insufficient spatio-temporal resolution, thus possibly concealing important facets of the neural dynamics of the speech act comprehension process. Here, we used magnetoencephalography to investigate the comprehension of Naming and Request actions performed with utterances controlled for physical features, psycholinguistic properties and the probability of occurrence in variable contexts. The results show that different communicative actions are underpinned by a dynamic neural network, which differentiates between speech act types very early after the speech act onset. Within 50-90 ms, Requests engaged mirror-neuron action-comprehension systems in sensorimotor cortex, possibly for processing action knowledge and intentions. Still, within the first 200 ms of stimulus onset (100-150 ms), Naming activated brain areas involved in referential semantic retrieval. Subsequently (200-300 ms), theory of mind and mentalising circuits were activated in medial prefrontal and temporo-parietal areas, possibly indexing processing of intentions and assumptions of both communication partners. This cascade of stages of processing information about actions and intentions, referential semantics, and theory of mind may underlie dynamic and interactive speech act comprehension.
Cognitive dissonance theory suggests that our preferences are modulated by the mere act of choosing. A choice between two similarly valued alternatives creates psychological tension (cognitive dissonance) that is reduced by a post-decisional reevaluation of the alternatives. Our study demonstrates that choices associated with stronger cognitive dissonance trigger a larger negative fronto-central evoked response similar to error-related negativity (ERN), which has in turn been implicated in general performance monitoring. Furthermore, the amplitude of the evoked response is correlated with the reevaluation of the alternatives. We also found a link between individual neural dynamics (long-range temporal correlations-LRTC) of the fronto-central cortices during rest and follow-up neural and behavioral effects of cognitive dissonance. Individuals with stronger resting-state LRTC demonstrated a greater post-decisional reevaluation of the alternatives and larger evoked brain responses associated with stronger cognitive dissonance. Thus, our results suggest that cognitive dissonance is reflected in both resting-state and choice-related activity of the prefrontal cortex as part of the general performance-monitoring circuitry.
We study the fraction f of nucleotides involved in the formation of a cactuslike secondary structure of random heteropolymer RNA-like molecules. In the low-temperature limit, we study this fraction as a function of the number c of different nucleotide species. We show, that with changing c, the secondary structures of random RNAs undergo a morphological transition:f(c)→1 for c≤ccr as the chain length n goes to infinity, signaling the formation of a virtually perfect gapless secondary structure; while f(c)<1 for c>ccr, which means that a nonperfect structure with gaps is formed. The strict upper and lower bounds 2≤ccr≤4 are proven, and the numerical evidence for ccr is presented. The relevance of the transition from the evolutional point of view is discussed.
Neuraminidase 1 (NEU1) is a lysosomal sialidase catalyzing the removal of terminal sialic acids from sialyloconjugates. A plasma membrane-bound NEU1 modulating a plethora of receptors by desialylation, has been consistently documented from the last ten years. Despite a growing interest of the scientific community to NEU1, its membrane organization is not understood and current structural and biochemical data cannot account for such membrane localization. By combining molecular biology and biochemical analyses with structural biophysics and computational approaches, we identified here two regions in human NEU1 - segments 139–159 (TM1) and 316–333 (TM2) - as potential transmembrane (TM) domains. In membrane mimicking environments, the corresponding peptides form stable α-helices and TM2 is suited for self-association. This was confirmed with full-size NEU1 by co-immunoprecipitations from membrane preparations and split-ubiquitin yeast two hybrids. The TM2 region was shown to be critical for dimerization since introduction of point mutations within TM2 leads to disruption of NEU1 dimerization and decrease of sialidase activity in membrane. In conclusion, these results bring new insights in the molecular organization of membrane-bound NEU1 and demonstrate, for the first time, the presence of two potential TM domains that may anchor NEU1 in the membrane, control its dimerization and sialidase activity.
New technology for the repurposing of toxic industrial waste into non-toxic, multi-purpose products is elaborated. The use of novel compounds for flotation separates potash ores, and as a mixture component for the neutralisation and lithification of domestic and industrial wastes and bottom sediments, are presented
Voltage-gated Na+ channels are essential for the functioning of cardiovascular, muscular, and nervous systems. The α-subunit of eukaryotic Na+ channel consists of ~ 2000 amino acid residues and encloses 24 transmembrane (TM) helices, which form five membrane domains: four voltage-sensing (VSD) and one pore domain. The structural complexity significantly impedes recombinant production and structural studies of full-sized Na+channels. Modular organization of voltage-gated channels gives an idea for studying of the isolated second VSD of human skeletal muscle Nav1.4 channel (VSD-II). Several variants of VSD-II (~ 150 a.a., four TM helices) with different N- and C-termini were produced by cell-free expression. Screening of membrane mimetics revealed low stability of VSD-II samples in media containing phospholipids (bicelles, nanodiscs) associated with the aggregation of electrically neutral domain molecules. The almost complete resonance assignment of 13C,15N-labeled VSD-II was obtained in LPPG micelles. The secondary structure of VSD-II showed similarity with the structures of bacterial Na+ channels. The fragment of S4 TM helix between the first and second conserved Arg residues probably adopts 310-helical conformation. Water accessibility of S3 helix, observed by the Mn2 + titration, pointed to the formation of water-filled crevices in the micelle embedded VSD-II. 15N relaxation data revealed characteristic pattern of μs–ms time scale motions in the VSD-II regions sharing expected interhelical contacts. VSD-II demonstrated enhanced mobility at ps–ns time scale as compared to isolated VSDs of K+ channels. These results validate structural studies of isolated VSDs of Na+channels and show possible pitfalls in application of this ‘divide and conquer’ approach.
We investigated the effect of mobile phone use on the auditory sensory memory in children. Auditory event-related potentials (ERPs), P1, N2, mismatch negativity (MMN), and P3a, were recorded from 17 children, aged 11–12 years, in the recently developed multi-feature paradigm. This paradigm allows one to determine the neural change-detection profile consisting of several different types of acoustic changes. During the recording, an ordinary GSM (Global System for Mobile Communications) mobile phone emitting 902 MHz (pulsed at 217 Hz) electromagnetic field (EMF) was placed on the ear, over the left or right temporal area (SAR1g = 1.14 W/kg, SAR10g = 0.82 W/kg, peak value = 1.21 W/kg). The EMF was either on or off in a single-blind manner. We found that a short exposure (two 6 min blocks for each side) to mobile phone EMF has no statistically significant effects on the neural change-detection profile measured with the MMN. Furthermore, the multi-feature paradigm was shown to be well suited for studies of perception accuracy and sensory memory in children. However, it should be noted that the present study only had sufficient statistical power to detect a large effect size.
Using the linear theory of waves in a compressible atmosphere located in a gravitational field, we found a family of sound speed profiles for which the wavefield can be represented by a traveling wave with no reflection. The vertical flux of wave energy on these nonreflected profiles is retained, which proves that the energy transfer may occur over long distances.
The atomic-scale diffusion of water in the presence of several lipid bilayers mimicking biomembranes is characterized via unconstrained molecular dynamics (MD) simulations. Although the overall water dynamics corresponds well to literature data – namely, the efficient braking near polar head groups of lipids - a number of interesting and biologically relevant details observed in this work have not been sufficiently discussed so far. For instance, the fact that waters “sense” the membrane unexpectedly early – before water density begins to decrease. In this “transitional zone” the velocity distributions of water and their H-bonding patterns deviate from those in the bulk solution. The boundaries of this zone are well preserved even despite the local (<1 nm size) perturbation of the lipid bilayer, thus indicating a decoupling of the surface and bulk dynamics of water. This is in excellent agreement with recent experimental data. Near the membrane surface, water movement becomes anisotropic – solvent molecules preferentially move outward the bilayer. Deep in the membrane interior, the velocities can even exceed those in the bulk solvent and undergo large-scale fluctuations. The analysis of MD trajectories of individual waters in the middle part of the acyl chain region of lipids reveals a number of interesting rare phenomena, such as the fast (c.a. 50 ps) breakthrough across the membrane or long-time (up to 750 ps) “roaming” between lipid leaflets. The analysis of these events was accomplished to delineate the mechanisms of spontaneous water permeation inside the hydrophobic membrane core. It was shown that such nontrivial dynamics of water in an “alien” environment is driven by the dynamic heterogeneities of the local bilayer structure and the formation of transient atomic-scale “defects” in it. The picture observed in lipid bilayers is drastically different from that in a primitive membrane mimic – a hydrated cyclohexane slab. The possible biological impact of such phenomena in equilibrated lipid bilayers is discussed.
The somatotopic layout of the primary somatosensory cortex is known for its fine spatial structure as delineated in single cell recordings and macroscopic EEG evoked responses. While a gross somatotopic layout has been revealed also for neuronal oscillations responding to sensorimotor stimulation of distant body parts (e.g. hand vs. foot), it is still unclear whether these oscillatory dynamics exhibit fine spatial layout comparable to those found in evoked responses. In twelve healthy subjects we applied electric stimuli to the first (D1) and fifth finger (D5) of the same hand while performing high-density electroencephalography. We used Common Spatial Pattern analysis to optimally extract components showing the strongest Event-Related Desynchronization (ERD) in neuronal alpha oscillations. In agreement with the previous studies, dipole locations of Somatosensory Evoked Potentials (SEPs) confirmed the existence of spatially distinct representations of each finger. In contrast, dipole locations of alpha-ERD patterns did not yield spatially different source locations, indicating that the stimulation of different fingers most likely resulted in oscillatory activity of overlapping neuronal populations. When both fingers were stimulated simultaneously the SEP dipole strength was found increased in comparison to a stimulation of either finger alone, in agreement with spatially distinct SEP to finger stimulation. The strength of ERD, on the other hand, was the same regardless of whether either one or both fingers were stimulated. Our findings might reflect anatomical constraints on the sequential temporal activation of fingers' skin where almost simultaneous activation of many fingers usually occurs in everyday activities, such as grasping or holding objects. Such simultaneity is unlikely to benefit from slow amplitude modulation of alpha oscillations, which would rather be beneficial for contrasting somatosensory processing of distinct body parts.
A series of novel fluorescent pyrimidine nucleosides containing 2,1,3-benzoxadiazole or naphtho[1,2,3-cd]indole-6 (2h)-one fragments was designed and synthesized. Introduction of fluorescent fragments into the position 5 of the uridine or cytidine heterocycle was carried out in two ways: by Sonogashira Coupling Reaction and CuI-catalyzed cycloaddition ("click" reaction). The obtained nucleoside derivatives became fluorescent due to the inserted fragments. The excitation wavelength (440-450 nm) was outside the absorption band of many biomolecules and significantly differed from the emission wavelength (560-600 nm). In addition, the intended nucleoside analogs were shown to kill cultured human tumor cells at submicromolar concentrations
The nonlinear stage of the modulational (Benjamin–Feir) instability of unidirectional deep-water surface gravity waves is simulated numerically by the fifth-order nonlinear envelope equations. The conditions of steep and breaking waves are concerned. The results are compared with the solution of the full potential Euler equations and with the lower-order envelope models (the 3-order nonlinear Schrödinger equation and the standard 4-order Dysthe equations). The generalized Dysthe model is shown to exhibit the tendency to re-stabilization of steep waves with respect to long perturbations.
Rock glaciers and large ice‐debris complexes are common in many mountain ranges and are especially prominent in semi‐arid mountains such as the Andes or the Tien Shan. These features contain a significant amount of ice but their occurrence and evolution are not well known. Here, we present an inventory of the ice‐debris complexes for the Ak‐Shiirak, Tien Shan's second largest glacierised massif, and a holistic methodology to investigate two characteristic and large ice‐debris complexes in detail based on field investigations and remote sensing analysis using Sentinel‐1 SAR data, 1964 Corona and recent high resolution stereo images. Overall, we found 74 rock glaciers and ice‐debris complexes covering an area of 11.2 km2 (3.2% of the glacier coverage) with a mean elevation of about 3950 m asl. Most of the complexes are located south‐east of the main ridge of Ak‐Shiirak. Ground penetrating radar (GPR) measurements reveal high ice content with the occurrence of massif debris‐covered dead‐ice bodies in the parts within the Little Ice Age glacier extent. These parts showed significant surface lowering, in some places exceeding 20 m between 1964 and 2015. The periglacial parts are characterised by complex rock glaciers of different ages. These rock glaciers could be remnants of debris‐covered ice located in permafrost conditions. They show stable surface elevations with no or only very low surface movement. However, the characteristics of the fronts of most rock glacier parts indicate slight activity and elevation gains at the fronts slight advances. GPR data indicated less ice content and slanting layers which coincide with the ridges and furrows and could mainly be formed by glacier advances under permafrost conditions. Overall, the ice content is decreasing from the upper to the lower part of the ice‐debris complexes. Hence, these complexes, and especially the glacier‐affected parts, should be considered when assessing the hydrological impacts of climate change.
The bottom pressure distribution beneath large amplitude waves is studied within linear theory in time and space domain, weakly dispersive Serre–Green–Naghdi system and fully nonlinear potential equations. These approaches are used to compare pressure fields induced by solitary waves, but also by transient wave groups. It is shown that linear analysis in time domain is in good agreement with Serre– Green–Naghdi predictions for solitary waves with highest amplitude A = 0.7h, h being water depth. In the meantime, when comparing results to fully nonlinear potential equations, neither linear theory in time domain, nor in space domain, provide a good description of the pressure peak. The linear theory in time domain underestimates the peak by an amount similar to the overestimation by linear theory in space domain. For transient wave groups (up to A = 0.52h), linear analysis in time domain provides results very similar to those based on the Serre–Green–Naghdi system. In the meantime, linear theory in space domain provides a surprisingly good comparison with prediction of fully nonlinear theory. In all cases, it has to be emphasized that a discrepancy between linear theory in space domain and in time domain was always found, and presented an averaged value of 20%. Since linear theory is often used by coastal engineers to reconstruct water elevation from bottom mounted sensors, the so-called inverse problem, an important result of this work is that special caution should be given when doing so. The method might surprisingly work with strongly nonlinear waves, but is highly sensitive to the imbalance between nonlinearity and dispersion. In most cases, linear theory, in both time and space domain, will lead to important errors when solving this inverse problem.
he operative weather forecasts with lead-time 3-5 days from best forecasting hydrodynamic models as well as the archives of the models’ forecasts and of the meteorological measurements in 2800 cities of Russia, East Europe, and Central Asia are used. The output of our scheme includes the air temperature forecast for the standard observations moments with period 6 hours and extreme temperatures for lead times from 12 up 120 hours.
The results of the operative forecasting (about ~280 Russian and Belarus cities and separately 58 cities of Central Asia) are representing on the site of Hydrometeorological Center of Russia every day at 8.30 (a.m. and p.m.) of the Moscow time. Besides temperature we represent on the site amount of precipitation, wind (including gusts), and dew-point temperature with lead-time from 12 up 72 hours with period 6 hours.
The errors of the complex forecast of the temperature and of the dew-point temperature in the standard moments as well as extreme temperature with various lead-times for the period from July 2014 up to June 2017 are represented. The accuracy of these forecasts for the standard moments is much better that the forecasts’ accuracy of the original hydrodynamic models. The estimations for our forecasting extreme temperature are compared with the similar results of the forecasting scheme “weather element computation” (WEC) and with forecasts of meteorologists of regional meteorological centers.
We describe our scheme of the operative wind (and possible gusts) forecasts with lead-time up to 3 days and evaluate its success. It uses joint statistical processing of the results of several best operative forecasting hydrodynamic weather forecasting schemes. This approach allowed to reduce the error with respect to original schemes. The operative forecast and its evaluation for the period 2014 – 2016 y. realized for ~ 2800 cities of Russia, Belarus, and Central Asia. The update results are representing on the official site of Hydrometeorological Center of Russia every day at 8.30 (a.m. and p.m.) of the Moscow time.