100,605 research outputs found

    Modal gating of human Ca(v)2.1 (P/Q-type) calcium channels: II. The b mode and reversible uncoupling of inactivation

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    he single channel gating properties of human Ca(V)2.1 (P/Q-type) calcium channels were investigated with cell-attached patch-clamp recordings on HEK293 cells stably expressing these calcium channels. Human Ca(V)2.1 channels showed a complex modal gating, which is described in this and the preceding paper (Luvisetto, S., T. Fellin, M. Spagnolo, B. Hivert, RE Brust, M.M. Harpold, K.A. Stauderman, M.E. Williams, and D. Pietrobon. 2004. J Gev. Physiol. 124:445-461). Here, we report the characterization of the so-called b gating mode. A Ca(V)2.1 channel in the b gating mode shows a bell-shaped voltage dependence of the open probability and a characteristic low open probability at high positive voltages, that decreases with increasing voltage, as a consequence of both shorter mean open time and longer mean closed time. Reversible transitions of single human Ca(V)2.1 channels between the b gating mode and the mode of gating in which the channel shows the usual voltage dependence of the open probability (nb gating mode) were much more frequent (time scale of seconds) than those between the slow and fast gating modes (time scale of minutes; Luvisetto et al., 2004), and Occurred independently of whether the channel was in the fast or slow mode. We show that the b gating mode produces reversible uncoupling of inactivation in human Ca(V)2.1 channels. In fact, a Ca(V)2.1 channel in the b gating mode does not inactivate during long pulses at high positive voltages, where the same channel in both fast-nb and slow-jib gating modes inactivates relatively rapidly Moreover, a Ca(V)2.1 channel in the b gating mode shows a larger availability to open than in the rib gating modes. Regulation of the complex modal gating of human Ca(V)2.1 channels could be a potent and verb satile mechanism for the modulation of synaptic strength and plasticity as well as of neuronal excitability and other postsynaptic Ca2+-dependent processes

    Modal gating of human Ca(v)2.1 (P/Q-type) calcium channels: I. The slow and the fast gating modes and their modulation by beta subunits

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    The single channel gating properties of human Ca(V)2.1 (P/Q-type) calcium channels and their modulation by the auxiliary beta(1b), beta(2c), beta(3a), and beta(4a), subunits were investigated with cell-attached patch-clamp recordings on HEK293 cells stably expressing human Ca(V)2.1 channels. These calcium channels showed a complex modal grating. which is described in this and the following paper (Fellin, T., S. Luvisetto, M. Spagnolo, and D. Pietrobon. 2004. J Gen. Physiol. 124:463-474). Here, we report the characterization of two modes of gating of human Ca(V)2.1 channels, the slow mode and the fast mode. A channel in the two gating modes differs in mean closed times and latency to first opening (both longer in the slow mode), in voltage dependence of the open probability (larger depolarizations are necessary to open the channel in the slow mode), in kinetics of inactivation (slowed in the slow mode), and voltage dependence of steady-state inactivation (occurring at less negative voltages in the slow mode). Ca(V)2.1 channels containing any of the four beta subtypes can gate in either the slow or the fast mode, with only minor differences in the rate constants of the transitions between closed and open states within each mode. In both modes; Ca(V)2.1 channels display different rates of inactivation and different steady-state inactivation depending oil the P subtype. The type of beta subunit also modulates the relative occurrence of the slow and the fast gating mode of Ca(V)2.1 channels, beta(3a), promotes the fast mode, whereas beta(4a) Promotes the slow mode. The prevailing mode of gating, of Ca(V)2.1 channels lacking a beta subunit is a gating mode in which the channel shows shorter mean open times, longer mean closed times, longer first latency, a much larger fraction of mills, and activates at more positive voltages than in either the fast or slow mode

    A TERMINATING INTUITIONISTIC CALCULUS

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    A terminating sequent calculus for intuitionistic propositional logic is obtained by modifying the R superset of rule of the labelled sequent calculus G3I. This is done by adding a variant of the principle of a fortiori in the left-hand side of the premiss of the rule. In the resulting calculus, called G3I(t,) derivability of any given sequent is directly decidable by root-first proof search, without any extra device such as loop-checking. In the negative case, the failed proof search gives a finite countermodel to the sequent on a reflexive, transitive, and Noetherian Kripke frame. As a byproduct, a direct proof of faithfulness of the embedding of intuitionistic logic into Grzegorcyk logic is obtained

    Mental Health of Looked-After Children: Embodiment and Use of Space

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    Much psychological language uses metaphors of space and place to conceptualize human experience. In everyday conversation, people talk about needing “space to think” or “putting some distance” between our self and someone we find difficult. In psychotherapy, much emphasis is placed on the psychic geography of the “therapeutic space,” for instance, talk about maintaining boundaries, providing containment. Psychologists and psychotherapists use topographical models to envision psychological processes – like “levels of consciousness” (the conscious and the unconscious) – and use the language of movement and distance to make sense of our relationalities. And yet, psychologists and other mental health professionals have been surprisingly resistant to theorizing the importance of space and place in children’s daily lives and its implications for their mental health and well-being. This is particularly notable in research focused on children who are looked after away from home, where work on mental health has focused very strongly on the impact of being looked after on inner experiences of mental health and well-being, individualizing and pathologizing young people’s lives, but neglecting the importance of the impact of the many experiences of physical and material displacement that young people in care have. This chapter explores how the mental health of looked-after children is conceptualized and the implications of considering the importance of space and embodiment in looked-after children’s mental health and well-being. The importance of notions of “home” and “belonging” for young people in care is considered, and the implications of these for an understanding of their well-being, as well as their experiences of distress, are explored

    Optimizing Measures of Information Encoding in Astrocytic Calcium Signals

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    While most models of brain information encoding focus on neurons, recent studies have shown that calcium dynamics of astrocytes, the major class of non-neural cells in the brain, can add information about key cognitive variables that is not found in the activity of nearby neurons. This raises the question of what could be the contribution of astrocytes in information processing, and calls for analysis tools to characterize this contribution. Here we construct simulations with realistic dependencies of astrocytic activity on external variables and we use these simulations to understand how to optimally set parameters of information theoretic analysis of astrocytic activities. Applications of our techniques to simulated and real astrocytic data show how to set parameters of information analyses that provide conservative, yet reliable, estimates of astrocytic calcium dynamics contribution to circuit-level brain information processing

    Letter, [Author unclear] to Paulina T. Merritt

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    Handwritten letter to Paulina Merritt from an unknown author, October 1, 1876.

    Impianti elettrici

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    L’insegnamento di Impianti elettrici della Facolta` di Ingegneria dell’Universita` di Padova ha subı ` to negli ultimi dieci anni inusuali cambiamenti, passando da ‘‘dimidiamenti’’ (Impianti elettrici I e Impianti elettrici II) al definitivo (speriamo) ritorno ad un unico insegnamento di impianti elettrici. Si aggiunga che nell’a.a. 2010/2011 tale insegnamento viene tenuto per la prima volta agli studenti del terzo anno di Ingegneria dell’Energia, corso di laurea triennale che proviene dalla fusione di Ingegneria Energetica ed Ingegneria Elettrica. Una tale storica coincidenza meritava la pubblicazione di un nuovo testo. Gli argomenti che vengono classicamente trattati nell’insegnamento di impianti elettrici spaziano dal livello di bassa tensione a quello di media tensione, con alcuni riferimenti ai livelli di alta e altissima tensione (che sono maggiormente trattati nelle lauree magistrali). Questa vastita` di programma ha sempre costretto i docenti ad avere piu ` testi di riferimento con continui ‘‘voli’’ da uno all’altro. Tale ‘‘attivita` aerea’’ non risultava particolarmente gradita agli studenti. Si e` quindi sentita l’esigenza di avere un unico testo organico che contenesse tutti gli argomenti senza far ricorso a frazioni di altre pubblicazioni. Il presente testo tuttavia non va confuso con un mero ‘‘libro di testo’’ (dicitura presa in prestito dalle scuole inferiori e superiori), ma si articola su tre livelli che meritano oltre che menzione anche opportuna esegesi. Il primo e` quello per lo studente universitario piu ` preoccupato per il superamento dell’esame che per l’effettivo apprendimento (per quanto possa sembrare incredibile, questa tipologia di studente non e` puramente virtuale). Il secondo e` quello dello studente o del dottorando o dello studioso che voglia approfondire le questioni: sparse nel testo vi sono delle ‘‘porte’’ che immettono in ‘‘vaste stanze’’ (ad esempio la trattazione dell’I 2 t nel Cap. 8), in cui si intravede la profondita` degli argomenti. Infine il terzo livello (quasi tutto contenuto negli Approfondimenti) cerca di mostrare gli sviluppi di ricerca di alcuni degli argomenti trattati o la vastita` delle Norme Tecniche che disciplinano ‘‘l’arte’’ dell’impianto elettrico. Va assolutamente notato che quest’ultimo livello, per il primo aspetto, si basa su attivita` di ricerca sviluppata dagli autori e dal gruppo di ricerca a cui essi afferiscono e non e` quindi una mera collezione della letteratura tecnica da altri prodotta. Tutto il libro e` comunque corredato di un gran numero di riferimenti bibliografici che vanno anch’essi annoverati nel terzo livello come spunto di approfondimento. In alcune parti gli autori hanno fatto uno sforzo notevole per rendere comprensibili ai piu ` argomenti complessi (vedi la spiegazione dell’effetto di prossimita` ) con la speranza di non averli banalizzati. Il rischio e` sempre in agguato, ma vale la pena di correrlo se la possibile ricompensa e` la profusione di un sapere che, per quanto complicato, merita di essere (prima totalmente compreso e poi) reso fruibile a chi ne mostra interesse. Il taglio ‘‘professionalizzante’’ che il legislatore ha voluto imprimere alle lauree triennali di primo livello ha inoltre indotto a considerare nel testo taluni riferimenti alla normativa tecnica, e segnatamente alle Norme del Comitato Elettrotecnico Italiano (Norme CEI), pur nella consapevolezza che la rapidita` con cui evolvono i contenuti normativi, nei tempi in cui viviamo, rischia di renderle presto obsolete. Una certa attenzione alle Norme e` d’altro canto indispensabile sotto il profilo pedagogico, dato che apre all’allievo ingegnere quell’orizzonte nuovo e disciplinato con cui dovra` fare i conti nella sua vita professionale. Gli autori auspicano che il testo, grazie al delicato e faticoso equilibrio che si e` in esso raggiunto tra teoria e prassi, possa incontrare il favore anche di altri corsi di studio e di altri istituti universitari

    FIGURE 4. Cortinarius anaunianus a Spores. b Basidia. c Marginal cells. d in Cortinarius anaunianus (Agaricales, Cortinariaceae): a new species of the Humolentes clade from Italy

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    FIGURE 4. Cortinarius anaunianus a Spores. b Basidia. c Marginal cells. d Elements of the pileipellis. Coll. TR gmb 01246 (holotype). Scale bars: 10 μm. Drawings by T. Lezzi & R.J. Ferrari.Published as part of Fellin, Alessandro, Ercole, Enrico, Ferrari, Renato Jonny & Vizzini, Alfredo, 2021, Cortinarius anaunianus (Agaricales, Cortinariaceae): a new species of the Humolentes clade from Italy, pp. 225-240 in Phytotaxa 520 (3) on page 233, DOI: 10.11646/phytotaxa.520.3.1, http://zenodo.org/record/553033

    Elettrodotti blindati: una alternativa per la trasmissione

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    Il crescente consumo di energia elettrica può richiedere la costruzione di nuove linee ad alta e altissima tensione. Le linee aeree sono oggi la sola soluzione tecnica fattibile per i collegamenti su lunghe distanze, m a , come noto, esse appaiono sempre meno accettate a causa del loro impatto visivo e per il loro livello di campo elettromagnetic o ; l’impiego alternativo di linee in cavo comporta, per distanze maggiori di 20 km, notevoli difficoltà per la necessaria compensazione reattiva. Gli elettrodotti blindati trifase (EBLI) appaiono essere una risposta realistica (compatibilmente con il loro costo) per l’immediato futuro, soprattutto nelle situazioni più critiche di impatto a m b i e n t a l e : e s s i , i n f a t t i , uniscono i vantaggi di alte potenzialità di trasmissione con basse perdite e campo magnetico quasi nullo in prossimità della linea. Le possibilità offerte dalla tecnologia odierna degli EBLI meritano apprezzamento e inducono a considerare attentamente l’opportunità di realizzazioni anche su ampia s c a l a . Scopo della presente memoria è quello di illustrare sia le caratteristiche tecniche principali della nuova tecnologia sia i metodi di calcolo più idonei per determinarne le prestazioni, mentre gli autori si ripromettono di sviluppare in altre pubblicazioni aspetti tecnici particolari e una approfondita analisi dei costi

    Specific kinetic alterations of human Ca(V)2.1 calcium channels produced by mutation S218L causing familial hemiplegic migraine and delayed cerebral edema and coma after minor head trauma

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    Mutation S218L in the Ca(V)2.1 alpha(1) subunit of P/Q-type Ca2+ channels produces a severe clinical phenotype in which typical attacks of familial hemiplegic migraine (FHM) triggered by minor head trauma are followed, after a lucid interval, by deep (even fatal) coma and long lasting severe cerebral edema. We investigated the functional consequences of this mutation on human Ca(V)2.1 channels expressed in human embryonic kidney 293 cells and in neurons from Ca(V)2.1 alpha(1)(-/-) mice by combining single channel and whole cell patch clamp recordings. Mutation S218L produced a shift to lower voltages of the single channel activation curve and a consequent increase of both single channel and whole cell Ba2+ influx in both neurons and human embryonic kidney 293 cells. Compared with the other FHM-1 mutants, the S218L shows one of the largest gains of function, especially for small depolarizations, which are insufficient to open the wild-type channel. S218L channels open at voltages close to the resting potential of many neurons. Moreover, the S218L mutation has unique effects on the kinetics of inactivation of the channel because it introduces a large component of current that inactivates very slowly, and it increases the rate of recovery from inactivation. During long depolarizations at voltages that are attained during cortical spreading depression, the extent of inactivation of the S218L channel is considerably smaller than that of the wild-type channel. We discuss how the unique combination of a particularly slow inactivation during cortical spreading depression and a particularly low threshold of channel activation might lead to delayed severe cerebral edema and coma after minor head trauma
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