115 research outputs found

    The study of personality preschool children in modern foreign research

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    The article deals with the problem of studying and describing the personality of the child in the preschool age. Provides the review of modern foreign studies on this issue. Grounded the importance of age characteristics for describing the structure of the child's personality.В статье рассматривается проблема изучения и описания личности ребенка в дошкольном возрасте. Представлен обзор современных зарубежных исследований, посвященных данному вопросу. Обосновывается важность возрастных характеристик для описания структуры личности ребенка

    Auxiliary subunit regulation of high-voltage activated calcium channels expressed in mammalian cells

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    The effects of auxiliary calcium channel subunits on the expression and functional properties of high-voltage activated (HVA) calcium channels have been studied extensively in the Xenopus oocyte expression system, but are less completely characterized in a mammalian cellular environment. Here, we provide the first systematic analysis of the effects of calcium channel beta and alpha(2)-delta subunits on expression levels and biophysical properties of three different types (Ca(v)1.2, Ca(v)2.1 and Ca(v)2.3) of HVA calcium channels expressed in tsA-201 cells. Our data show that Ca(v)1.2 and Ca(v)2.3 channels yield significant barium current in the absence of any auxiliary subunits. Although calcium channel beta subunits were in principle capable of increasing whole cell conductance, this effect was dependent on the type of calcium channel alpha(1) subunit, and beta(3) subunits altogether failed to enhance current amplitude irrespective of channel subtype. Moreover, the alpha(2)-delta subunit alone is capable of increasing current amplitude of each channel type examined, and at least for members of the Ca(v)2 channel family, appears to act synergistically with beta subunits. In general agreement with previous studies, channel activation and inactivation gating was regulated both by beta and by alpha(2)-delta subunits. However, whereas pronounced regulation of inactivation characteristics was seen with the majority of the auxiliary subunits, effects on voltage dependence of activation were only small (< 5 mV). Overall, through a systematic approach, we have elucidated a previously underestimated role of the alpha(2)-delta(1) subunit with regard to current enhancement and kinetics. Moreover, the effects of each auxiliary subunit on whole cell conductance and channel gating appear to be specifically tailored to subsets of calcium channel subtypes

    Sisäinen viestintä muutostilanteessa : Case: Suomenselän Osuuspankki

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    Tämän opinnäytetyön tarkoituksen oli selvittää, miten sisäinen viestintä on onnistunut fuusioitumisprosessin aikana Suomenselän Osuuspankissa. Tutkimus toteutettiin kvantitatiivisena kyselytutkimuksena tammikuussa 2016. Kyselyssä oli mukana myös toisen fuusioitumisprosessin osapuolen eli Pyhälaakson Osuuspankin henkilöstö ja hallinto. Opinnäytetyö koostuu toiminnallisesta, empiirisestä ja teoreettisesta osiosta. Työn teoreettinen viitekehys muodostuu muutoksesta, johdon ja esimiehen roolista muutoksessa, muutosvastarinnasta ja muutoksen aikaisesta sisäisestä viestinnästä. Työn empiirisessä osiossa esitellään työssä käytetyt tutkimusmenetelmät ja tutkimuksista saadut tulokset. Työn toiminnallisessa osuudessa Suomenselän Osuuspankkiin on laadittu dokumentti, johon on kirjattu Suomenselän Osuuspankin muutoksen aikaisen sisäisen viestinnän tärkeät asiat. Kyselyn tulokset osoittivat, että sisäinen viestintä on onnistunut molemmissa pankeissa henkilöstölle ja hallinnolle kokonaisuudessaan hyvin. Kuitenkin, kun kyselyiden tuloksia tarkastellaan eri taustamuuttujien avulla, voidaan niiden välillä havaita eroja. Tarkempi tulosten tarkkailu osoitti, että toimihenkilöille suunnatussa viestinnässä oli havaittavissa joitakin puutteita ja tulevaisuudessa sitä olisi hyvä tuoda enemmän henkilöstön tasolle. Suurin osa henkilöstön ja hallinnon jäsenistä kokee muutoksen positiivisena asiana ja heidän keskuudessa ei ollut havaittavissa suurempaa muutosvastarintaa. Toimeksiantaja saa tästä työstä hyödyllistä tietoa miten muutosprosessin viestinnässä onnistuttiin ja mihin tulee kiinnittää huomiota mahdollisissa tulevissa muutoksissa.The aim of this thesis was to look into the success of the internal communication implementation during a merger process in Suomenselän Osuuspankki. The study was carried out as a quantitative questionnaire in January 2016. The questionnaire was also sent to Pyhälaakson Osuuspankki which was the other party in the merger. This thesis consists of action-based, empirical and theoretical sections. The theoretical framework of the project consists of change, the role of management in the change situation, resistance to change and internal communication in change. In the empirical section of this thesis the methods and results of the study are presented. In the action-based section of this research the important points of the internal communication flow during the change in Suomenselän Osuuspankki were compiled into a document. The results of the study show that the internal communication implemented with personnel and administration has succeeded well in both of the banks. However, when the effect of background variables on the results were examined some differences can be observed. Closer investigation of the results shows some defects in the internal communication targeted at personnel. To develop further, in the future internal communication should be brought closer to the level of the personnel in the organisation. The majority of the personnel and administration find the organizational change to be a positive element and amongst them no considerable resistance to change can be discovered. This thesis gives the client useful information about the success of the internal communication flow and the factors worth consideration in the forthcoming changes in the organization

    Purkinje cell input to cerebellar nuclei in tottering: Ultrastructure and physiology

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    Homozygous tottering mice are spontaneous ataxic mutants, which carry a mutation in the gene encoding the ion pore of the P/Q-type voltage-gated calcium channels. P/Q-type calcium channels are prominently expressed in Purkinje cell terminals, but it is unknown to what extent these inhibitory terminals in tottering mice are affected at the morphological and electrophysiological level. Here, we investigated the distribution and ultrastructure of their Purkinje cell terminals in the cerebellar nuclei as well as the activities of their target neurons. The densities of Purkinje cell terminals and their synapses were not significantly affected in the mutants. However, the Purkinje cell terminals were enlarged and had an increased number of vacuoles, whorled bodies, and mitochondria. These differences started to occur between 3 and 5 weeks of age and persisted throughout adulthood. Stimulation of Purkinje cells in adult tottering mice resulted in inhibition at normal latencies, but the activities of their postsynaptic neurons in the cerebellar nuclei were abnormal in that the frequency and irregularity of their spiking patterns were enhanced. Thus, although the number of their terminals and their synaptic contacts appear quantitatively intact, Purkinje cells in tottering mice show several signs of axonal damage that may contribute to altered postsynaptic activities in the cerebellar nuclei

    Atomic Resolution Cryo-EM Structure Of A Nativelike CENP-A Nucleosome Aided By An Antibody Fragment

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    Genomic DNA in eukaryotes is organized into chromatin through association with core histones to form nucleosomes, each distinguished by their DNA sequences and histone variants. Here, we used a single-chain antibody fragment (scFv) derived from the anti-nucleosome antibody mAb PL2-6 to stabilize human CENP-A nucleosome containing a native α-satellite DNA and solved its structure by the cryo-electron microscopy (cryo-EM) to 2.6 Å resolution. In comparison, the corresponding cryo-EM structure of the free CENP-A nucleosome could only reach 3.4 Å resolution. We find that scFv binds to a conserved acidic patch on the histone H2A-H2B dimer without perturbing the nucleosome structure. Our results provide an atomic resolution cryo-EM structure of a nucleosome and insight into the structure and function of the CENP-A nucleosome. The scFv approach is applicable to the structural determination of other native-like nucleosomes with distinct DNA sequences

    The Ataxic Cacna1a-Mutant Mouse Rolling Nagoya: An Overview of Neuromorphological and Electrophysiological Findings

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    Homozygous rolling Nagoya natural mutant mice display a severe ataxic gait and frequently roll over to their side or back. The causative mutation resides in the Cacna1a gene, encoding the pore-forming α1 subunit of Cav2.1 type voltage-gated Ca2+ channels. These channels are crucially involved in neuronal Ca2+ signaling and in neurotransmitter release at many central synapses and, in the periphery, at the neuromuscular junction. We here review the behavioral, histological, biochemical, and neurophysiological studies on this mouse mutant and discuss its usefulness as a model of human neurological diseases associated with Cav2.1 dysfunction

    Orientation of the Calcium Channel β Relative to the α12.2 Subunit Is Critical for Its Regulation of Channel Activity

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    BACKGROUND: The Ca(v)beta subunits of high voltage-activated Ca(2+) channels control the trafficking and biophysical properties of the alpha(1) subunit. The Ca(v)beta-alpha(1) interaction site has been mapped by crystallographic studies. Nevertheless, how this interaction leads to channel regulation has not been determined. One hypothesis is that betas regulate channel gating by modulating movements of IS6. A key requirement for this direct-coupling model is that the linker connecting IS6 to the alpha-interaction domain (AID) be a rigid structure. METHODOLOGY/PRINCIPAL FINDINGS: The present study tests this hypothesis by altering the flexibility and orientation of this region in alpha(1)2.2, then testing for Ca(v)beta regulation using whole cell patch clamp electrophysiology. Flexibility was induced by replacement of the middle six amino acids of the IS6-AID linker with glycine (PG6). This mutation abolished beta2a and beta3 subunits ability to shift the voltage dependence of activation and inactivation, and the ability of beta2a to produce non-inactivating currents. Orientation of Ca(v)beta with respect to alpha(1)2.2 was altered by deletion of 1, 2, or 3 amino acids from the IS6-AID linker (Bdel1, Bdel2, Bdel3, respectively). Again, the ability of Ca(v)beta subunits to regulate these biophysical properties were totally abolished in the Bdel1 and Bdel3 mutants. Functional regulation by Ca(v)beta subunits was rescued in the Bdel2 mutant, indicating that this part of the linker forms beta-sheet. The orientation of beta with respect to alpha was confirmed by the bimolecular fluorescence complementation assay. CONCLUSIONS/SIGNIFICANCE: These results show that the orientation of the Ca(v)beta subunit relative to the alpha(1)2.2 subunit is critical, and suggests additional points of contact between these subunits are required for Ca(v)beta to regulate channel activity

    The alpha(2)delta auxiliary subunit reduces affinity of omega-conotoxins for recombinant N-type (Ca(v)2.2) calcium channels

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    The omega-conotoxins from fish-hunting cone snails are potent inhibitors of voltage-gated calcium channels. The omega-conotoxins MVIIA and CVID are selective N-type calcium channel inhibitors with potential in the treatment of chronic pain. The beta and alpha(2)delta-1 auxiliary subunits influence the expression and characteristics of the alpha(1B) subunit of N-type channels and are differentially regulated in disease states, including pain. In this study, we examined the influence of these auxiliary subunits on the ability of the omega-conotoxins GVIA, MVIIA, CVID and analogues to inhibit peripheral and central forms of the rat N-type channels. Although the beta3 subunit had little influence on the on- and off-rates of omega-conotoxins, coexpression of alpha(2)delta with alpha(1B) significantly reduced on- rates and equilibrium inhibition at both the central and peripheral isoforms of the N-type channels. The alpha(2)delta also enhanced the selectivity of MVIIA, but not CVID, for the central isoform. Similar but less pronounced trends were also observed for N-type channels expressed in human embryonic kidney cells. The influence of alpha(2)delta was not affected by oocyte deglycosylation. The extent of recovery from the omega-conotoxin block was least for GVIA, intermediate for MVIIA, and almost complete for CVID. Application of a hyperpolarizing holding potential ( - 120 mV) did not significantly enhance the extent of CVID recovery. Interestingly, [R10K] MVIIA and [O10K] GVIA had greater recovery from the block, whereas [K10R] CVID had reduced recovery from the block, indicating that position 10 had an important influence on the extent of omega-conotoxin reversibility. Recovery from CVID block was reduced in the presence of alpha(2)delta in human embryonic kidney cells and in oocytes expressing alpha(1B-b). These results may have implications for the antinociceptive properties of omega-conotoxins, given that the alpha(2)delta subunit is up-regulated in certain pain states

    Dual effect of glycine on isolated rat suprachiasmatic neurons

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