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This paper presents a systematic discussion of the design of all key subsystems of the ACCULINNA-2 facility: components of the primary beam line and beam diagnostics equipment, production target, and primary beam absorbers; equipment for the transport, purification, and diagnostics of the secondary beam; a RF-filter for additional beam purification; the cryogenic physical target; the forward spectrometer; and the automated control system. The characteristics of secondary beams are presented, such as angular and spatial distribution in the final focus; the quality of identification of ions by the E-ToF method; and the yields of the certain isotopes obtained during experiments in 2018-2020 with primary beams B (33.5 AMeV), N (49.3 AMeV), and 32S (52.7 AMeV) while tuning to secondary He, Li, Li, Be, S, and P beams with different energies. A comparison of secondary beam transport with the calculated one has been performed. The possibility is substantiated to carry out experiments with light exotic ions at high accuracy of detection and measuring parameters of the incident ion on condensed targets of hydrogen and helium isotopes. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the peculiarities and localization of the current source of α- and θ-rhythms accompanying competition and cooperation with another player, as well as solo figure building in a computer game. The sample included 42 volunteers (24 females) aged from 18 to 47 years. The analysis of differences in the current source density registered with a 127-channel EEG in different game conditions was performed in the eLoreta software. The θ-rhythm spectral density was greater during competition than during cooperation and most prominent in the anterior cingulate cortex and medial prefrontal cortex. According to the literature on functional correlates of the θ-rhythm, it can be suggested that the greater increase in the frontal-midline θ-rhythm detected during competition may be related to focused attention and cognitive control processes. The source density of α-rhythm in the parietal and visual cortex areas during interactive game modes (cooperation and competition) was lower compared to the solo mode. During cooperation the α-rhythm spectral density was lower compared to the competition mode. The greatest decrease of α-rhythm spectral density in the cooperation mode was consistent with the concept of relation between α-rhythm decrease and the processes of understanding the other person's intentions. [ABSTRACT FROM AUTHOR]

The grounds for identifying the Eboraciceras subordinarium Zone in the Upper Callovian of Siberia are critically discussed. The key sections of this zone and the ammonite assemblage that characterizes it are examined in detail. It is concluded that it is impossible to recognize the Eboraciceras subordinarium Zone and its further use in stratigraphic schemes is not suggested. North Siberian taxa, previously identified as Late Callovian Eboraciceras, are mostly assigned to Rondiceras and indicate a Middle Callovian age of the host rocks. Beds with Cadoquenstedtoceras begichevi have been proposed as an approximate equivalent of the European Q. lamberti Zone in the Upper Callovian of Siberia. [ABSTRACT FROM AUTHOR]

We report here a study of 45 students (all men) of different ethnicities (mainly Tajik and Kyrgyz) aged 17–28 years, who moved to the North (Yakutsk, Republic of Sakha (Yakutia)). The study addressed the balance of connectivity of resting state networks in study condition 1, when participants entered new and unfamiliar living conditions, and in study condition 2, when subjects had lived in these conditions for one year. The 128-channel EEG was recorded at rest. Connectivity between nodes of the resting state networks and the rest of the brain was calculated. Connectivity contrasts the attention networks vs default mode network in conditions 1 and 2 were performed. Condition 1 was characterized by a predominance of attention networks over the default mode network of the brain, which may be associated with an increase in attention focused on the perception of new stimuli and tasks in the new conditions. In condition 2, after living in these environmental conditions for one year, the balance of the resting state networks shifted towards a predominance of the brain's default mode network over the attention networks. [ABSTRACT FROM AUTHOR]

Studies of cerebral activity during the processing of self-referential information, in comparison with the processing of information related to other people, are based on use of mass univariate analysis with the assumption that activity in one region does not depend on activity in other regions. Recent times have seen an increase in interest in the use of neuroimaging in studies of spatially distributed information using multidimensional approaches such as multi-voxel pattern analysis (MVPA). We report here the use of MVPA to analyze fMRI data recorded during a task involving assessment of the self and other people of different degrees of closeness. Testing of the patterns identified by machine learning showed that these brain activity patterns predicted what the subject was assessing self or other in 75–88% of cases. Prognostically significant structures were widely distributed in different areas of the brain and, in addition to the cortical median structures making the greatest contribution, included areas of the visual, lateral prefrontal, and many other cortical areas. The most informative areas for the selection of the Self variant on classifying self/other were the ventral regions of the medial prefrontal and cingulate cortex, while for selection of Other the most informative were the parietal and occipital median areas. Principal components analysis revealed a combination of brain structures, including the anterior cingulate gyrus and the bilateral amygdalas, whose factor scores correlated positively with the psychometric reward sensitivity scale and negatively with the neuroticism scale. Activity in this combination of structures can be regarded as a protective factor against affective disorders. In general, the results obtained here demonstrate the productivity of using machine learning methods for analysis of data from experiments of this type. [ABSTRACT FROM AUTHOR]

The taxonomic composition of the ammonite family Cardioceratidae is studied in the Bathonian of northern Siberia in the range of distribution of the last representatives of the genus Arcticoceras and the first representatives of the genus Catacadoceras, aiming to solve the problem of the Middle-Upper Bathonian boundary. It is shown that all previous identifications of northern Siberian material as the Middle Bathonian species Arcticoceras cranocephaloide Callomon et Birkelund, 1985, were incorrect. The misidentified specimens were mainly the Late Bathonian ammonite species Catacadoceras barnstoni (Meek, 1859) or the form with a narrow umbilicus referred to herein as Cat. aff. barnstoni. An updated ammonite zonal scale of the Middle–Upper Bathonian of Siberia is proposed, which is recommended for use both in the regional stratigraphic schemes of the Jurassic deposits of Eastern (Middle) Siberia and in the Boreal (Siberian) zonal standard of the Bathonian Stage. The extreme importance of preserving an auxiliary biostratigraphic subdivision in this scale, the Cat. barnstoni Beds, is emphasized, because of the wide distribution and abundance of the index species in Siberian sections, as well as its significance for the correlation of the lower part of the Upper Bathonian of northern Canada, northern Siberia, Franz Josef Land, and East Greenland. In addition, two intervals, i.e., the interval with Cat. aff. barnstoni and interval with Cat. perrarum, are fixed as marker levels, which are useful for rapid age determination and correlation of the Upper Bathonian deposits in Arctic sections within the upper part of the Cat. barnstoni Beds. [ABSTRACT FROM AUTHOR]

Setup fitting the requirements for the detailed study of the five-body decay of the 7H nucleus obtained as a result of the proton transfer from the 8He projectiles to the deuterium target nuclei is being built at the radioactive beam line of ACCULINNA-2 separator in the G.N. Flerov Laboratory of Nuclear Reactions. Described here is the assembly of 100 BC-404 plastic scintillators, intended for neutron detection, the annular Si detector telescope for the 3He recoils, and the detector array providing the ΔE–E-TOF registration of 3H nuclei emitted at the 7H decay. Results obtained by the Monte Carlo simulations made for the energy values and flight passes of all these particles are given together with the luminosity expected for the discussed experiments. [ABSTRACT FROM AUTHOR]

Since the 1950s, the dominant paradigm in the cognitive sciences has been cognitivism, which arose as an alternative to behaviorism and regards cognitive processes predominantly as various kinds of "computations" similar to those performed by a computer; there is no fundamental difference from a universal Turing machine (TM). Despite significant progress made in the last quarter of the 20th century within the framework of this paradigm, many remain dissatisfied as it cannot adequately explain some features of cognitive processes. Connectionism, which emerged later, although recognizing the role of computational processes, regards them as based not on a TM, but on a neural network, as this provides a better model of brain functionality than TM-type computations. Neural networks, unlike classical computers, show resilience and flexibility in the face of problems arising in the real world, such as increasing input noise or blockade of part of the network. They are also well suited for tasks requiring parallel resolution of many conflicting constraints. Despite this, the analogy between the functioning of the human brain and artificial neural networks is still limited, because of radical differences in the design and associated capabilities of such systems. In parallel with the paradigms of cognitivism and connectionism, further ideas developed, whereby cognition is the result of strictly biological processes involved in the interaction of an organism with the external environment. These concepts, which have become increasingly popular in recent years, have taken shape in various strands of so-called enactivism. This review compares the theoretical postulates of cognitivism, connectionism, and enactivism, along with paradigms of predictive coding and the principle of free energy. [ABSTRACT FROM AUTHOR]

The question of the nature of the relationship between mental processes and activity in the brain is not the prerogative of philosophers. All professional scientists involved in studying the human brain must, one way or another, decide this question for themselves. The dominant approach in the modern scientific worldview is reductionism, which holds that mental states can in principle be reduced to activity in the brain. Here I review some of the data obtained in recent years that shed light on the nature of the relationship between the content of mental processes and cerebral activity. These data on the encoding of sensory and semantic linguistic information, as well as more complex information related to the content of abstract concepts, show that the cerebral activity accompanying the extraction of meaning is widely distributed and probabilistic in nature and does not correspond to the nature of mental content, which is generally certain and holistic. Thus, currently available empirical data indicate that reductionism cannot reasonably be seen as a viable option and the only variant possible within the framework of materialism is that of recognizing mentality as an emergent entity. [ABSTRACT FROM AUTHOR]

The information content of EEG recordings, which are widely used and important for assessing the functional activity of the brain, is significantly increased by the use of mathematical analysis, where an important place is occupied by the spatial synchronization characteristic, i.e., the functional connectivity of biopotentials (based on correlation and coherence analysis, phase synchronization, etc.). The success of neuroimaging methods in recent years has not only confirmed the significance of this indicator, but has also contributed to improvements in approaches to its statistical evaluation and visualization. Graph theory (GT) is a promising method for analyzing the neural network organization of the brain. Its advantages are that it provides a visual description of the entire structure of the network and its individual components, as well as defining the relationships between them. The purpose of this review is to present approaches to the application of graph theory and the potentials of this method based on the analysis of published data. We present general information on the areas of application of GT, address the most common and informative metrics, and provide recommendations for selecting software. Modifications of GT analysis of the EEG are described: without primary localization of the generation sources of EEG components and with their localization. Examples of the effective use of graph theory analysis of the electroencephalogram of the healthy and diseased brain are given. [ABSTRACT FROM AUTHOR]

The study involved 42 individuals (including 25 women) in the age range from 18 to 41. The aim of the study was to investigate the peculiarities of oscillatory dynamics accompanying the processes of interaction with a virtual character and to localize the effects detected. During the recording of the electroencephalogram (EEG), the subjects were asked to interact with a virtual character, choosing one of three options ("offer friendship," "attack," or "avoid contact"). Faces with five types of emotional expressions (angry, happy, frightened, sad, and neutral) were used as stimuli. Analysis of equivalent dipoles revealed that the choices of active interaction ("attack" and "offer friendship"), compared to avoidance of interaction, were accompanied by a greater decrease in α- and β-rhythms, which may be related to the processes of understanding the intentions of the virtual character. The choice of friendship, as compared to interaction avoidance, was accompanied by an increase in δ-rhythm, which may indicate the presence of a motivational component. The effects detected were found in clusters of equivalent dipoles, whose localization coincides with the structures of the mentalizing network and mirror neuron network, which are involved in the processes of evaluating people's intentions. [ABSTRACT FROM AUTHOR]

Data in the literature suggest that the presence of the S allele of the serotonin transporter gene (5-HTTLPR) is associated with an increased risk of developing depression in individuals who have experienced the effects of stress in the recent past. However, there are many reports, including meta-analyses, which do not confirm this association. This inconsistency in results can be partly explained by the fact that the association between 5-HTTLPR polymorphisms, stressful life events, and symptoms of mental disorders may not be so direct and obvious. Here we report our analysis of the mechanisms of interaction of the 5-HTTLPR polymorphism with the level of stressful life events in terms of their influence on the onset of symptoms of mental disorders using intermediate variables regarded as indicators of resting state network connectivity and means of regulating the emotions. Cerebral responses to increased levels of stress were found not to differ in carriers of different alleles of the serotonin transporter gene, though these reactions could reduce the likelihood of depression in carriers of the LL genotype, and, conversely, provoke depression in carriers of the S allele. This difference is explained by the fact that carriers of the LL genotype tend to rethink stressful situations in a less negative light, which prevents the emergence of psychopathology, while stress reactions in carriers of the S allele are accompanied by the appearance of repetitive obsessive thoughts and futile attempts to suppress them, which can ultimately lead to depression. [ABSTRACT FROM AUTHOR]

The Dust Complex (DC) instrument was designed to be installed on the landing platform of the ExoMars project. The purpose of the experiment is to study the dynamics of dust particles in the near-surface atmosphere of Mars and to evaluate the main characteristics of the near-surface medium that determine their dynamics. The device makes it possible to register dust particles in the near-surface atmosphere of Mars, determine the main parameters and measure some characteristics of the plasma-dust medium related to the dynamics of dust particles near the Martian surface. The article provides a description of the device, its blocks and sensors, the main elements of the measurement program and characteristics of the measured parameters. [ABSTRACT FROM AUTHOR]

Polymorphism of the 5-HTTLPR serotonin transporter gene is one of the best studied markers of the serotoninergic system. Scientific interest in investigating 5-HTTLPR polymorphism arises because many studies have demonstrated an association between the short allele (S) and the development of a number of mental disorders. Several studies have shown that different 5-HTTLPR alleles are associated with different patterns of brain bioelectrical activity in the resting state and on performance of test tasks. However, despite a quite large number of studies of this marker, the results often contradict each other. Possible causes of disagreement between results may be that the complex structure of the SLC6A4 gene is ignored, heterogeneity in cohorts, and the use of different methods. The aim of the present work was to conduct a literature review and use this to carry out a complex analysis of psychological, behavioral, genetic, and neurophysiological data to summarize the effects associated with 5-HTTLPR polymorphism and at least partly to explain the variability in the results obtained by different authors. [ABSTRACT FROM AUTHOR]

The aim was to study the effect of adaptive (cognitive reappraisal) and non-adaptive (expressive suppression, suppression, and rumination) styles of emotion regulation on the balance of connectivity of resting state networks. Fifty-one healthy volunteers (29 women) aged from 18 to 51 years gave their permission to recordings their EEGs at rest and filled in the Emotional Regulation Questionnaire (Gross), White Bear Suppression Inventory and Ruminative Responses Scale. The connectivity measures of resting state networks were evaluated based on EEG data. Networks were identified using the "seed" method. The effects of different styles of emotional regulation on the balance of connectivity of networks were analyzed by regression method. Non-adaptive styles of emotional regulation (suppression and rumination) correlated with the dominance of the default mode network in the right temporal cortex, that could reflect the processes of emotional introspection. The adaptive strategy cognitive reappraisal of emotions correlated with the dominance of task-positive networks in the left dorsolateral prefrontal cortex, such result may be associated with more effective control of negative thoughts and a higher level of positive emotions. [ABSTRACT FROM AUTHOR]

The paper presents an acousto-optic lunar infrared spectrometer (LIS) intended for mineralogical analysis and assessment of the hydration of the lunar surface regolith near the lander. Its optical layout, characteristics, results of calibrations and laboratory measurements are given. The LIS is designed to measure the spectrum of solar radiation reflected by the lunar surface; it will function as part of the load complex of the Luna-25 lander. The instrument is mounted on the manipulator of the lander in such a way that its field of view is within the field of view of the television support stereo cameras of the robotic arm working zone (TV RPM). The instrument operates in the spectral range of 1.15–3.4 µm, including the OH/H2O absorption bands, with a spectral resolution of approximately 25 cm–1. The principle of operation of the device is based on acousto-optic spectral filtering of optical radiation. [ABSTRACT FROM AUTHOR]

The aim of the present work was to study the relationships between the individual characteristics of emotional control and changes in brain bioelectrical activity during the implicit perception of emotional coloration of verbal information. The study, which included 43 volunteers (26 women) aged 18–34 years evaluated individual features of emotional control strategies using the Gross questionnaire and total brain bioelectrical activity (the EEG) was measured during presentation of negative, positive, and neutral sentences. Attention was distracted from the emotional content of the sentences by giving study participants a task consisting of finding syntax errors. The search for syntax errors had to be done as quickly as possible, the presence of the emotional component in the sentence not being emphasized. The study identified a positive correlation between cognitive reappraisal of emotions and spectral power in the θ range in the period between 100 msec and 300 msec during presentation of negative sentences not containing syntax errors. A positive correlation was also found between expressive suppression and spectral power in the β range in the period from 100 to 1300 msec during presentation of positive sentences containing syntax errors. [ABSTRACT FROM AUTHOR]

For many decades in psychology and the history of science the phenomenon of incubation has been known but not fully understood; this is the preparation of a solution to a problem during a period of relative rest. The aim of the present work was to use EEG data to seek patterns of resting state network connectivity during incubation associated with successful postincubation solution of tasks. Subjects carried out a remote associations tests in three stages: a fi rst attempt, incubation (listening to an audio recording irrelevant to solving the task), and a second attempt to solve the unsolved tasks. Subjects who after incubation solved at least one additional task showed a more marked association of the left sensorimotor cortex with the insula and a less marked association with the left dorsolateral frontal cortex during the period of incubation. These data are consistent with the view that at the stage of seeking a solution, the optimum situation is a combination of decreased activity in the executive control network, leading to defocusing of attention, and increased activity in the motivational salience network. [ABSTRACT FROM AUTHOR]

The aim of the research was to study the effect of depression, anxiety, and rumination scores on the balance of activity of the default mode network and attention networks revealed in the resting state EEG records. Forty-five healthy volunteers (24 men aged from 18 to 25 years) participated in the resting state EEG recording. The participants filled in the Beck Depression Inventory-II (BDI II), Ruminative Responses Scale, and Eysenck Personality Profiler. The connectivity measures of resting state networks were calculated in EEG data. The networks were detected by the "seed" method. The effects of depressive symptoms, anxiety, and rumination on the connectivity of the networks were analyzed by the regression method. The depressive symptom scores and the rumination scores were correlated with the dominance of the default mode network over attention networks in the right temporal cortex. The depression scores and the anxiety scores were correlated with the dominance of attention networks over the default mode network in the anterior cingulate cortex. It could be suggested that rumination processes are specific for depressive symptoms and are reflected in the dominance of the default mode network in brain structures associated with the processing of emotional introspection. Common to depressive and anxious symptoms is a state of alertness, which is reflected in the dominance of attention networks in brain structures associated with decision-making. [ABSTRACT FROM AUTHOR]

The study of Callovian ammonites Longaeviceras and closely related taxa from the east coast of Anabar Bay (section 109, northern Siberia) is presented. Genera and species previously unknown here, such as Rondiceras milaschevici, Pseudolongaeviceras densicostatum gen. et sp. nov., Platylongoceras holtedahli, and Pseudocadoceras laminatum, are identified. The presence of the Eboraciceras subordinarium Zone in the studied section is not confirmed. The division of genus Longaeviceras into Longoceras and Longaeviceras (including subgenus Soaniceras) is discussed. According to Cardioceras maltonense found in the upper part of the section studied, the age of the Oxfordian beds is defined more accurately. [ABSTRACT FROM AUTHOR]

The aim of the present work was to study brain activity using fMRI data during assessment of the self and other people. Subjects were presented with adjectives describing positive, neutral, or negative characteristics and were asked to assess the extent to which these characteristics applied to the subject him- or herself, or to a friend, a stranger, or an unpleasant person. The main effect of the Object of assessment factor was apparent in the right upper parietal lobe, which is part of the default network of the brain and overlaps with the temporoparietal junction area. Activation in this area was maximal on self-evaluation. The main effect of the Type of adjective factor was also seen in structures in the posterior center of the default network. As these areas are involved in constructing perspectives from the point of view of other people, it can be suggested that the "I" is perceived in continuous relation to the social environment and is assessed in terms of the presumed views of other people. [ABSTRACT FROM AUTHOR]

A list and short description of the middle Callovian cardioceratid genera from Northern Siberia are given. These are Rondiceras and Stenocadoceras with specified diagnosis and also Bryocadoceras and Streptocadoceras, which were described earlier as subgenera of Cadoceras Fischer. The middle Callovian of Northern Siberia (section 503 at Bolshoy Begichev Island) is divided into the lower Rondiceras milaschevici, Protolongaeviceras arcticoides Zone (as the equivalent of the Kosmoceras jason Zone) and the upper Rondiceras nikolaevi, Stenocadoceras stenoloboide Zone (as the equivalent of the Erymnoceras coronatum Zone). [ABSTRACT FROM AUTHOR]

Analysis of fMRI in the resting state (RS) is a suitable methodological approach to studying basal levels of functional brain activity in humans in health and disease. The inadequate development of this direction in Russia is partly due to the small number of Russian publications describing approaches to data processing. This study uses an algorithm for analysis of fMRI signals in the RS based on independent components analysis (ICA) run in the FSL environment and used for studies of typical functional resting state networks (RSN) in health. Averaging observation data by group, which is applicable for studies of healthy people, is often not appropriate for studies of different forms of cerebral pathology, which are characterized by significantly greater levels of variation in hemodynamics. Thus, studies of 17 healthy subjects included comparative evaluation of the topography and a number of quantitative measures of typical RSN identified by group and individual analysis of fMRI signals. These networks were comparable with RSN described in the literature as main and were also reproducible in group and individual analysis, which confirms the suitability, reliability, and effectiveness of using this algorithm. Individual analysis of RSN identified variability linked with a number of psychophysiological characteristics of healthy subjects (sex, motor asymmetry profile, EEG pattern), partly explaining the different levels of compliance with the patterns of the group networks. Results obtained from individual fMRI and EEG comparisons showed the potential of analysis of the topography of the sources of individual rhythms as EEG markers for RSN. The lowest levels of variability of fMRI characteristics of resting networks in health (such as maximum network activation intensity, mean frequency of the active zone of the spectrum, frequency of dominant peak) may have diagnostic value for studies of RSN in pathology. [ABSTRACT FROM AUTHOR]

Photodynamic therapy uses photosensitizers (PS) to kill cancer cells by generating reactive oxygen species – like singlet oxygen (SO) - upon illumination with visible light. PS membrane anchoring augments local SO concentration, which in turn increases photodynamic efficiency. The latter may suffer from SO's escape into the aqueous solution or premature quenching. Here we determined the time constants of SO escape and quenching by target molecules to be in the nanosecond range, the former being threefold longer. We confined PS and dipolar target molecules either to different membrane monolayers or to the same leaflet and assessed their abundance by fluorescence correlation spectroscopy or membrane surface potential measurements. The rate at which the contribution of the dipolar target molecules to membrane dipole potential vanished, served as a measure of the photo-oxidation rate. The solution of the reaction–diffusion equations did not indicate diffusional rate limitations. Nevertheless, reducing the PS-target distance increased photodynamic efficiency by preventing other SO susceptible moieties from protecting the target. Importantly, our analytical model revealed a fourfold difference between SO generation rates per molecule of the two used PSs. Such analysis of PS quantum yield in a membrane environment may help in designing better PSs. [ABSTRACT FROM AUTHOR]

This review focusses on the energetics of protein translocation via the Sec translocation machinery. First we complement structural data about SecYEG's conformational rearrangements by insight obtained from functional assays. These include measurements of SecYEG permeability that allow assessment of channel gating by ligand binding and membrane voltage. Second we will discuss the power stroke and Brownian ratcheting models of substrate translocation and the role that the two models assign to the putative driving forces: (i) ATP (SecA) and GTP (ribosome) hydrolysis, (ii) interaction with accessory proteins, (iii) membrane partitioning and folding, (iv) proton motive force (PMF), and (v) entropic contributions. Our analysis underlines how important energized membranes are for unravelling the translocation mechanism in future experiments. [ABSTRACT FROM AUTHOR]

Epidermal growth factor receptor (EGFR) and Src tyrosine kinase cooperate in regulating EGFR-mediated cell signaling and promoting cell transformation and tumorigenesis in pathological conditions. Activation of Src is tightly regulated by the C-terminal Src kinase (Csk). The Csk-binding protein (Cbp) is a ubiquitously expressed transmembrane protein. Its functions include suppression of T-cell receptor activation through recruiting Csk and inhibiting Src family kinase (SFK). However, a potential role of Cbp in EGF-induced cell activities has not been investigated. Here, we report that EGF-stimulation-induced Cbp tyrosine phosphorylation followed by Cbp–Csk association, in a SFK-dependent manner. Expression of wild-type (wt) Cbp remarkably suppressed EGF-induced activation of Src, ERK1/2, and Akt-1 enzymes, and NIH3T3 cell transformation, as well as colony formation of a breast cancer cell line (MDA-MB-468) in soft agar. In contrast, expression of CbpY317F or knockdown endogenous Cbp in NIH3T3 cells by RNA interference significantly enhanced EGF-induced activation of these enzymes and cell transformation. In addition, overexpression of multiple receptor tyrosine kinases (RTKs)-induced Cbp tyrosine phosphorylation. These results demonstrate that Cbp functions as a negative regulator of cell transformation and tumor cell growth through downregulation of Src activation, suggesting that Cbp might be broadly involved in RTKs-activated signaling pathways and tumorigenesis.Oncogene (2006) 25, 5495–5506. doi:10.1038/sj.onc.1209554; published online 24 April 2006 [ABSTRACT FROM AUTHOR]

Receptor tyrosine kinases of the Axl family are activated by the vitamin K-dependent protein Gas6. Axl signalling plays important roles in cancer, spermatogenesis, immunity, and platelet function. The crystal structure at 3.3 Å resolution of a minimal human Gas6/Axl complex reveals an assembly of 2:2 stoichiometry, in which the two immunoglobulin-like domains of the Axl ectodomain are crosslinked by the first laminin G-like domain of Gas6, with no direct Axl/Axl or Gas6/Gas6 contacts. There are two distinct Gas6/Axl contacts of very different size, both featuring interactions between edge β-strands. Structure-based mutagenesis, protein binding assays and receptor activation experiments demonstrate that both the major and minor Gas6 binding sites are required for productive transmembrane signalling. Gas6-mediated Axl dimerisation is likely to occur in two steps, with a high-affinity 1:1 Gas6/Axl complex forming first. Only the minor Gas6 binding site is highly conserved in the other Axl family receptors, Sky/Tyro3 and Mer. Specificity at the major contact is suggested to result from the segregation of charged and apolar residues to opposite faces of the newly formed β-sheet. [ABSTRACT FROM AUTHOR]

Hybridization with cDNA arrays was used to obtain expression profiles of 214 protein-tyrosine kinase, protein-tyrosine phosphatase, dual specificity phosphatase, and other genes for kidney carcinomas (KC) and normal kidney tissues of 34 patients and for seven carcinoma cell lines. Computer analysis revealed three clusters of genes coexpressed in KC. The proliferating-cell gene cluster included MET, VIM, MYC, TOP2A, PCNA. The neoangiogenesis and blood-cell gene cluster included LCK, HCK, FGR, MMP9, CSFR1, VEGF, FLT1, and KDR. The cluster corresponding to normal, differentiated kidney cells included ERBB2 (HER2) for receptor protein-tyrosine kinase, several phosphatase genes (PTPRE, PTPRB, DUSP9), and EGF. The results suggested that MET, DUSP9, PCNA, TOP2A, and VIM may serve as diagnostic and prognostic markers in KC. Tubulin and topoisomerase II were assumed to be promising targets for cell proliferation inhibitors in KC. [ABSTRACT FROM AUTHOR]