125 research outputs found
Regulation of voltage-gated Ca2+ channels by lipids
No full textGreat skepticism has surrounded the question of whether modulation of voltage-gated Ca(2+) channels (VGCCs) by the polyunsaturated free fatty acid arachidonic acid (AA) has any physiological basis. Here we synthesize findings from studies of both native and recombinant channels where micromolar concentrations of AA consistently inhibit both native and recombinant activity by stabilizing VGCCs in one or more closed states. Structural requirements for these inhibitory actions include a chain length of at least 18 carbons and multiple double bonds located near the fatty acid's carboxy terminus. Acting at a second site, AA increases the rate of VGCC activation kinetics, and in Ca(V)2.2 channels, increases current amplitude. We present evidence that phosphatidylinositol 4,5-bisphosphate (PIP(2)), a palmitoylated accessory subunit (beta(2a)) of VGCCs and AA appear to have overlapping sites of action giving rise to complex channel behavior. Their actions converge in a physiologically relevant manner during muscarinic modulation of VGCCs. We speculate that M(1) muscarinic receptors may stimulate multiple lipases to break down the PIP(2) associated with VGCCs and leave PIP(2)'s freed fatty acid tails bound to the channels to confer modulation. This unexpectedly simple scheme gives rise to unanticipated predictions and redirects thinking about lipid regulation of VGCCs
The Ca2+ channel beta subunit determines whether stimulation of Gq-coupled receptors enhances or inhibits N current
No full textIn superior cervical ganglion (SCG) neurons, stimulation of M(1) receptors (M(1)Rs) produces a distinct pattern of modulation of N-type calcium (N-) channel activity, enhancing currents elicited with negative test potentials and inhibiting currents elicited with positive test potentials. Exogenously applied arachidonic acid (AA) reproduces this profile of modulation, suggesting AA functions as a downstream messenger of M(1)Rs. In addition, techniques that diminish AA's concentration during M(1)R stimulation minimize N-current modulation. However, other studies suggest depletion of phosphatidylinositol-4,5-bisphosphate during M(1)R stimulation suffices to elicit modulation. In this study, we used an expression system to examine the physiological mechanisms regulating modulation. We found the beta subunit (Ca(V)beta) acts as a molecular switch regulating whether modulation results in enhancement or inhibition. In human embryonic kidney 293 cells, stimulation of M(1)Rs or neurokinin-1 receptors (NK-1Rs) inhibited activity of N channels formed by Ca(V)2.2 and coexpressed with Ca(V)beta1b, Ca(V)beta3, or Ca(V)beta4 but enhanced activity of N channels containing Ca(V)beta2a. Exogenously applied AA produced the same pattern of modulation. Coexpression of Ca(V)beta2a, Ca(V)beta3, and Ca(V)beta4 recapitulated the modulatory response previously seen in SCG neurons, implying heterogeneous association of Ca(V)beta with Ca(V)2.2. Further experiments with mutated, chimeric Ca(V)beta subunits and free palmitic acid revealed that palmitoylation of Ca(V)beta2a is essential for loss of inhibition. The data presented here fit a model in which Ca(V)beta2a blocks inhibition, thus unmasking enhancement. Our discovery that the presence or absence of palmitoylated Ca(V)beta2a toggles M(1)R- or NK-1R-mediated modulation of N current between enhancement and inhibition identifies a novel role for palmitoylation. Moreover, these findings predict that at synapses, modulation of N-channel activity by M(1)Rs or NK-1Rs will fluctuate between enhancement and inhibition based on the presence of palmitoylated Ca(V)beta2a
Published chapter on “hen” in translations to Czech
No full textCitation (Chicago 18 author-date):
Elmerot, Irene, Tora Hedin, and Jonáš Thál. 2026. ‘A Person, a Man, or Something in between – a Short Study of the Gender-Neutral Personal Pronoun Hen and Its Translations’. In Korpus Třicetiletý, edited by Michal Škrabal, Barbora Štěpánková, and Hana Skoumalová. Studie z Korpusové Lingvistiky 30. Nakladatelství Lidové noviny. https://www.nln.cz/knihy/korpus-tricetilety/
The Written Tora and the Oral Tora – Can one exist without the other?
No full textOvaj članak analizira mogućnost razumijevanja teksta pisane Tore bez tradicije usmene Tore. Povijesni je to spor koji datira još iz vremena Drugog hrama u Jeruzalemu, spor između raznih židovskih i filozofskih struja, uglavnom farizeja i saduceja. Ova je rasprava nastavila uznemiravati židovski narod i tijekom srednjega vijeka s pojavom karaitskog pokreta. Ovaj rad započinje definiranjem pojmova pisane i usmene Tore, a potom izlaže nekoliko biblijskih zapovijedi iz kojih je razvidno da bez rješenja koja daje usmena tradicija jednostavno ne bi bilo moguće razumjeti značenje tih tekstova ili zapovijedi. Posljednji dio ovoga rada raščlanjuje ovo pitanje na temelju niza izvora rabinske literature, od talmudskih vremena do srednjega vijeka, literature koja je sada po prvi puta prevedena na hrvatski jezik. Tekstove je s hebrejskog i aramejskog preveo sam autor.This article is analyzing the possibility of understanding the text of the Written Tora without the tradition of the Oral Tora. A historical dispute that is dating already during the second Temple period in Jerusalem, between the different Jewish religious and philosophical streams, mainly the Pharisees and the Sadducees. This debate is continuing to bother the Jewish People during the middle ages with the arrival of the Karaitic movement. This work is starting with defining the concepts of the Written and the Oral Tora, then showing through few biblical commandments from which it is clear that without and determinative oral tradition it would be simply impossible to understand the meaning of those texts or commandments. The last part of this work is analyzing this issue through many sources of Rabbinical literature from the Talmud time through the middle ages, literature that for the first time is being translated to the Croatian language by the author from Hebrew and Aramaic
Endosperm in Cassia tora Linn
No full textDURING the course of a comparative study of several members of the Leguminosæ, I found an interesting type of endosperm formation in Cassia tora Linn. (family Cæsalpiniaceæ), a common roadside plant in India. The primary endosperm nucleus, by repeated division, gives rise to a number of free nuclei which are at first more or less uniformly distributed throughout the embryo-sac. Afterwards, one of the nuclei situated near the chalazal end becomes more prominent than the rest of the endosperm. Wall formation takes place only in the micropylar part of the endosperm. The chalazal part, which remains free nuclear, becomes a narrow tube with denser cytoplasm in its elongated lower end (Figs. 1 and 2). As the mass of endosperm tissue increases, the lower tubular process becomes irregularly coiled and twisted. The sac-like portion at its tip is often displaced so that it is sometimes found lying on one side of the cellular zone or superposed on it (Fig. 3). Microtome sections naturally fail to give any clear or complete picture of this interesting tubular process; but whole mounts of the endosperm showed it quite clearly
Contemporary art in school - post internet age
No full textTITLE: Contemporary art at school - post internet age AUTHOR: Nikola Tora Dvořáková DEPARTMENT: Department of art education SUPERVISOR: Ph.Dr. Leonora Kitzbergerová, PhD. ABSTRACT: The thesis - Contemporary art at school - post internet age is about current arts occasions, concretely Post internet art. I try to state and define this kind of art and place post internet art to context with art education afterwards. Specific art pieces and their similarities in related zones of art are reflected in didactic transformations. The research is focused on difficulties, which can come into the art education lessons. It is realized with different methods, on different kind of school. In concluision my original art piece is bringing more comprehensive knowledge about post internet art. KEYWORDS: Contemporary art, post internet art, interpreter vs. consumer, new medi
Fabaeformiscandona tora Smith and Kamiya 2007, n. sp.
No full text<i>Fabaeformiscandona tora</i> Smith and Kamiya, 2007 <p> 2007 <i>Fabaeformiscandona tora</i> n. sp. —Smith & Kamiya: 227–228, Figs 1a–b, g–h, 2 a–b, 3, 4a–d, 5, 9.</p> <p> <b>Material examined.</b> Two males from a muddy seep at the edge of a track in Hino-cho, Shiga Prefecture, N35º 00’ 05.1”, E136º 19’ 35.5”, 16 April 2008. 29 males and 46 females from a small seep in a small forest clearing, Otsu, Shiga Prefecture, N34º 57’ 47.0”, E135º 52’ 01.9”, 10 May 2009. All material collected by the author.</p> <p> <b>Remarks.</b> This species has been reported from Lake Biwa in Shiga Prefecture and seeps in Kanazawa, Ishikawa Prefecture (Smith and Janz 2008; Smith and Kamiya 2007).</p>Published as part of <i>Smith, Robin J., 2011, Groundwater, spring and interstitial Ostracoda (Crustacea) from Shiga Prefecture, Japan, including descriptions of three new species and one new genus, pp. 15-37 in Zootaxa 3140</i> on page 27, DOI: <a href="http://zenodo.org/record/207945">10.5281/zenodo.207945</a>
Modulation of Voltage-Gated N-Type Calcium Channels by G Protein-Coupled Receptors Involves Lipids and Proteins: A Dissertation
No full textPain signaling involves transmission of nociceptive stimuli in the spinal cord where a critical balance between excitatory and inhibitory inputs determines the response to noxious stimuli. The neuropeptide, substance P (SP), mediates transmission of pain in part by binding to the tachykinin receptor (NK-1R) in the dorsal horn (DH) of the spinal cord. One of SP’s downstream effects is to modulate N-type Ca2+(N-) channels. While phospholipid breakdown is a part of the inflammatory process that accompanies tissue damage, the role of this metabolic pathway has not been completely described with respect to N-channel modulation during pain signaling. Despite the incomplete understanding of this modulation, pharmacological antagonists of both NK-1R and N-channels have been used to treat pain. In Chapter II, using whole-cell patch clamp recording techniques, the SP signaling cascade that mediates inhibition of recombinant N-channel activity was characterized. By adopting a pharmacological approach, I show that this pathway resembles the slow pathway that was earlier described for modulation of N-current by the M1 muscarinic receptor (M1R). M1R couples to Gq to stimulate phospholipid breakdown. Together with previous observations, the data presented in this chapter provide evidence for involvement of the extracellular receptor kinase (ERK1/2), phospholipase A2 and release of phospholipid metabolites in the modulation of N-current by SP. Overall, this chapter shows that phospholipid metabolism involved in modulation of N-currents is not specific to M1Rs but that other Gq-coupled receptors may also modulate N-currents via the same signal transduction pathway. In Chapter III, enhancement of N-current by SP was studied as part of a collaborative project to understand current enhancement that occurs when a palmitoylated accessory CaVβ2a subunit is co-expressed with the pore-forming subunit CaV2.2 and the accessory subunit α2δ-1. When CaVβ3 is present, SP inhibits N-current as described in Chapter II. However, when palmitoylated CaVβ2a is co-expressed with CaV2.2 (and α2δ-1), current enhancement is observed at negative test potentials, demonstrating that both M1Rs and NK-1Rs exhibit the same profile of N-current modulation. This change in modulation by muscarinic agonists is not observed in the presence of a depalmitoylated CaVβ2a. However a chimeric CaVβ2aβ1b subunit that contains the palmitoylated N-terminus from CaVβ2a confers enhancement. Normally expression of the β1b subunit resulted in current inhibition. These findings indicated that the palmitoylated CaVβ2a participates in enhancement of current. Our data support a model where inhibition dominates over enhancement; when inhibition is blocked, enhancement may be observed. Lastly, we show that N-current inhibition by SP is minimized when exogenous palmitic acid is applied to cells co-expressing CaVβ3 subunits with N-channels. These results indicate that the presence of palmitic acid can prevent N-current inhibition when SP is applied most likely by interacting with CaV2.2. We propose a model where palmitic acid occupies the inhibitory site and serves to antagonize inhibition by a lipid metabolite, which is most likely arachidonic acid. The CaVβ2a protein seems to have a role in positioning the palmitoyl groups near CaV2.2. This chapter provides a new role for protein palmitoylation where the palmitoyl groups of CaVβ2a are both necessary and sufficient to block inhibition of another protein: CaV2.2. In Chapter IV, I probe the role of the relative orientation of CaVβ2a and the pore-forming subunit of the N-channel in N-current modulation. Evidence is presented that shows that not just the presence of a palmitoylated CaVβ2a is necessary, but the relative orientation of CaVβ2a to CaV2.2 is critical for blocking inhibition. Using N-channel mutants that cause a change in the orientation of CaVβ2a relative to CaV2.2, I show that the block of inhibition is disrupted; inhibition by the slow pathway is rescued. These findings further support my model that the palmitoyl groups of CaVβ2a normally reside in a specific location that overlaps with the slow pathway inhibitory site on CaV2.2. Lastly I present data showing that the enhancement of N-current, observed when palmitoylated CaVβ2a is present, occurs via the slow pathway. In Chapter V the effect of CaVβ’s orientation on N-channel modulation by the dopamine D2 receptor is tested. In this form of modulation, inhibition is rapid and voltage-dependent. The signaling pathway is membrane-delimited since Gβγ, released after receptor stimulation, directly interacts with the N-channel at a site that overlaps with a high affinity binding site for CaVβs. While N-currents are modulated by this pathway, the deletion mutants show aberrant membrane-delimited modulation. The findings in this chapter further underscore the importance of proper positioning of CaVβ to CaV2.2 for eliciting proper N-current modulation after GPCR stimulation. Overall, the data presented in this dissertation provides a mechanistic approach into examining modulation of N-current by different GPCRs via two different signaling pathways as well as the role CaVβ subunits serve in each modulatory pathway.Neuroscienc
Systems Thinking in an era of climate change: Does cognitive neuroscience hold the key to improving environmental decision making? A perspective on Climate-Smart Agriculture
No full textSystems Thinking (ST) can be defined as a mental construct that recognises patterns and connections in a particular complex system to make the “best decision” possible. In the field of sustainable agriculture and climate change, higher degrees of ST are assumed to be associated with more successful adaptation strategies under changing conditions, and “better” environmental decision making in a number of environmental and cultural settings. Future climate change scenarios highlight the negative effects on agricultural productivity worldwide, particularly in low-income countries (LICs) situated in the Global South. Alongside this, current measures of ST are limited by their reliance on recall, and are prone to possible measurement errors. Using Climate-Smart Agriculture (CSA), as an example case study, in this article we explore: (i) ST from a social science perspective; (ii) cognitive neuroscience tools that could be used to explore ST abilities in the context of LICs; (iii) an exploration of the possible correlates of systems thinking: observational learning, prospective thinking/memory and the theory of planned behaviour and (iv) a proposed theory of change highlighting the integration of social science frameworks and a cognitive neuroscience perspective. We find, recent advancements in the field of cognitive neuroscience such as Near-Infrared Spectroscopy (NIRS) provide exciting potential to explore previously hidden forms of cognition, especially in a low-income country/field setting; improving our understanding of environmental decision-making and the ability to more accurately test more complex hypotheses where access to laboratory studies is severely limited. We highlight that ST may correlate with other key aspects involved in environmental decision-making and posit motivating farmers via specific brain networks would: (a) enhance understanding of CSA practices (e.g., via the frontoparietal network extending from the dorsolateral prefrontal cortex (DLPFC) to the parietal cortex (PC) a control hub involved in ST and observational learning) such as tailoring training towards developing improved ST abilities among farmers and involving observational learning more explicitly and (b) motivate farmers to use such practices [e.g., via the network between the DLPFC and nucleus accumbens (NAc)] which mediates reward processing and motivation by focussing on a reward/emotion to engage farmers. Finally, our proposed interdisciplinary theory of change can be used as a starting point to encourage discussion and guide future research in this space
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