RIM-Binding Protein 2 organizes Ca2+channel topography and regulates release probability and vesicle replenishment at a fast central synapse

RIM-Binding Protein 2 (RIM-BP2) is a multi-domain protein of the presynaptic active zone (AZ). By binding to Rab-interacting protein (RIM), bassoon and voltage-gated Ca²⁺channels (CaV), it is considered to be a central organizer of the topography of CaVand release sites of synaptic vesicles (SVs) at the AZ. Here, we investigated the role of RIM-BP2 at the endbulb of Held synapse of auditory nerve fibers with bushy cells of the cochlear nucleus, a fast relay of the auditory pathway with high release probability. Disruption of RIM-BP2 lowered release probability altering short-term plasticity and reduced evoked excitatory postsynaptic currents (EPSCs). Analysis of SV pool dynamics during high frequency train stimulation indicated a reduction of SVs with high release probability but an overall normal size of the readily releasable SV pool (RRP). The Ca2+-dependent fast component of SV replenishment after RRP depletion was slowed. Ultrastructural analysis by super-resolution light and electron microscopy revealed an impaired topography of presynaptic CaVand a reduction of docked and membrane-proximal SVs at the AZ. We conclude that RIM-BP2 organizes the topography of CaV, and promotes SV tethering and docking. This way RIM-BP2 is critical for establishing a high initial release probability as required to reliably signal sound onset information that we found to be degraded in bushy cells of RIM-BP2-deficient mice in vivo

Photoemission study of TiO2/VO2 interfaces

We have measured photoemission spectra of two kinds of TiO$_2$-capped VO$_2$ thin films, namely, that with rutile-type TiO$_2$ (r-TiO$_2$/VO$_2$) and that with amorphous TiO$_2$ (a-TiO$_2$/VO$_2$) capping layers. Below the Metal-insulator transition temperature of the VO$_2$ thin films, $\sim 300$ K, metallic states were not observed for the interfaces with TiO$_2$, in contrast with the interfaces between the band insulator SrTiO$_3$ and the Mott insulator LaTiO$_3$ in spite of the fact that both TiO$_2$ and SrTiO$_3$ are band insulators with $d^0$ electronic configurations and both VO$_2$ and LaTiO$_3$ are Mott insulators with $d^1$ electronic configurations. We discuss possible origins of this difference and suggest the importance of the polarity discontinuity of the interfaces. Stronger incoherent part was observed in r-TiO$_2$/VO$_2$ than in a-TiO$_2$/VO$_2$, suggesting Ti-V atomic diffusion due to the higher deposition temperature for r-TiO$_2$/VO$_2$.Comment: 5 pages, 6 figure

Association of masticatory muscle activity with sleep arousal and other concomitant movements during sleep

OBJECTIVE: This study aims to verify the associations among sleep bruxism (SB), sleep arousal (SA) and concurrent body movements. MATERIAL AND METHODS: Subjects underwent a standard overnight polysomnography test and audio-video recordings. Sleep quality was evaluated according to the Rechtschaffen and Kales criteria, while SA was determined as per the American Sleep Disorders Association criteria. Analyses were performed by an external institution after masking of the subjects' information. SB was assessed based on the presence/absence of rhythmic masticatory muscle activity (RMMA) episodes, which were identified by using electromyography of the masseter muscle. The observed simultaneous movements included lower leg movement (LLM), swallowing, face scratching, head movement, body movement, eye blinking, coughing, licking, sighing, body scratching, lip sucking, somniloquy and yawning. The LLM was determined visually, as well as through an increase in the tibialis electromyogram signal. Other movements were visually assessed using audio-video recordings. The incidences of all the simultaneous movements were compared between RMMA with intercurrent SA (SAwRMMA; RMMA episode derived from a masseter electromyogram showing more than 10% of maximum voluntary contraction) and SA without RMMA (SAw/oRMMA). RESULTS: Fourteen subjects were included in this study (females/males: 4/10, mean age: 31.5 ± 5.7 years). Among these, LLM, swallowing, body movement, licking, body scratching and lip sucking were frequently observed in SAwRMMA episodes than in SAw/oRMMA episodes, significantly. However, the non-specific simultaneous movements were higher observed in SAw/oRMMA episodes than that in SAwRMMA. CONCLUSION: Our results suggest that SB is concurrently activated with LLM in relation to arousal

Classical and Quantum Solutions and the Problem of Time in R2R^2 Cosmology

We have studied various classical solutions in $R^2$ cosmology. Especially we have obtained general classical solutions in pure $R^2$\ cosmology. Even in the quantum theory, we can solve the Wheeler-DeWitt equation in pure $R^2$\ cosmology exactly. Comparing these classical and quantum solutions in $R^2$\ cosmology, we have studied the problem of time in general relativity.Comment: 17 pages, latex, no figure, one reference is correcte

Charge dynamics in strongly correlated one-dimensional Cu-O chain systems revealed by inelastic X-ray scattering

We report on the Cu 1s resonant inelastic X-ray scattering (RIXS) of Cu-O one-dimensional (1D) strongly correlated insulator systems with contrasting atomic arrangements, namely edge-sharing CuGeO3 and corner-sharing Sr2CuO3. Owing to good statistics of the high-resolution RIXS data, so far unresolved fine structures are revealed. Detailed photon-energy and momentum dependence of the RIXS spectra in comparison with theoretical calculations has clarified the natures of the low-energy charge excitations and hybridization of the electronic states.Comment: 4 pages, 3 color figure

Sleep-wake sensitive mechanisms of adenosine release in the basal forebrain of rodents : an in vitro study

Adenosine acting in the basal forebrain is a key mediator of sleep homeostasis. Extracellular adenosine concentrations increase during wakefulness, especially during prolonged wakefulness and lead to increased sleep pressure and subsequent rebound sleep. The release of endogenous adenosine during the sleep-wake cycle has mainly been studied in vivo with microdialysis techniques. The biochemical changes that accompany sleep-wake status may be preserved in vitro. We have therefore used adenosine-sensitive biosensors in slices of the basal forebrain (BFB) to study both depolarization-evoked adenosine release and the steady state adenosine tone in rats, mice and hamsters. Adenosine release was evoked by high K+, AMPA, NMDA and mGlu receptor agonists, but not by other transmitters associated with wakefulness such as orexin, histamine or neurotensin. Evoked and basal adenosine release in the BFB in vitro exhibited three key features: the magnitude of each varied systematically with the diurnal time at which the animal was sacrificed; sleep deprivation prior to sacrifice greatly increased both evoked adenosine release and the basal tone; and the enhancement of evoked adenosine release and basal tone resulting from sleep deprivation was reversed by the inducible nitric oxide synthase (iNOS) inhibitor, 1400 W. These data indicate that characteristics of adenosine release recorded in the BFB in vitro reflect those that have been linked in vivo to the homeostatic control of sleep. Our results provide methodologically independent support for a key role for induction of iNOS as a trigger for enhanced adenosine release following sleep deprivation and suggest that this induction may constitute a biochemical memory of this state

Sisäinen viestintä muutostilanteessa : Case: Suomenselän Osuuspankki

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

Study of Transcriptional Effects in Cis at the IFIH1 Locus

Background: The Thr allele at the non-synonymous single-nucleotide polymorphism (nsSNP) Thr946Ala in the IFIH1 gene confers risk for Type 1 diabetes (T1D). The SNP is embedded in a 236 kb linkage disequilibrium (LD) block that includes four genes: IFIH1, GCA, FAP and KCNH7. The absence of common nsSNPs in the other genes makes the IFIH1 SNP the strongest functional candidate, but it could be merely a marker of association, due to LD with a variant regulating expression levels of IFIH1 or neighboring genes. Methodology/Principal Findings: We investigated the effect of the T1D-associated variation on mRNA transcript expression of these genes. Heterozygous mRNA from lymphoblastoid cell lines (LCLs), pancreas and thymus was examined by allelic expression imbalance, to detect effects in cis on mRNA expression. Using single-nucleotide primer extension, we found no difference between mRNA transcripts in 9 LCLs, 6 pancreas and 13 thymus samples, suggesting that GCA and FAP are not involved. On the other hand, KCNH7 was not expressed at a detectable level in all tissues examined. Moreover, the association of the Thr946Ala SNP with T1D is not due to modulation of IFIH1 expression in organs involved in the disease, pointing to the IFIH1 nsSNP as the causal variant. Conclusions/Significance: The mechanism of the association of the nsSNP with T1D remains to be determined, but does not involve mRNA modulation. It becomes necessary to study differential function of the IFIH1 protein alleles at Thr946Al