676 results on '"Ian Parker"'
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2. Psychoanalysis Under Occupation: Practicing Resistance in Palestine
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Ian Parker
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Cultural Studies ,Health (social science) ,Sociology and Political Science ,Social Psychology ,Applied Psychology - Published
- 2022
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3. Psicoanálisis y revolución: una psicología crítica para movimientos de liberación
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Ian Parker
- Abstract
Este manifiesto es para movimientos de liberación por un mundo mejor. Trata sobre la interrelación entre la realidad opresiva de la vida actual y nuestras vidas ‘internas’, nuestra psicología. El psicoanálisis capta esa íntima interconexión entre esta realidad y lo que se siente en lo profundo de cada uno/a de nosotros/as. Debemos comprender la naturaleza de esa interconexión para construir una alternativa práctica al capitalismo, el sexismo y el racismo. Nuestra tarea es reconstruir el psicoanálisis como una forma auténtica de ‘psicología crítica’. Analizamos el papel del inconsciente, la repetición, la pulsión y la transferencia en el análisis clínico y político para abordar cuestiones de transformación subjetiva.
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- 2021
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4. The Durability and Invisibility of Practice Fields: Insights from Math Teachers Doing Math
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Ke Wu, David Erickson, Ian Parker Renga, and Frederick A. Peck
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Invisibility ,Situated learning ,media_common.quotation_subject ,Developmental and Educational Psychology ,Mathematics education ,Experimental and Cognitive Psychology ,Conversation ,Discipline ,General Psychology ,Education ,media_common - Abstract
In this paper, we revisit a long-running conversation about situated learning and the design of environments for disciplinary engagement. Throughout the 1970s and 1980s, scholars advanced an anthro...
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- 2021
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5. Intracellular Injection of Brain Extracts from Alzheimer’s Disease Patients Triggers Unregulated Ca2+ Release from Intracellular Stores That Hinders Cellular Bioenergetics
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Anna Pensalfini, Abdul Rahim Umar, Charles Glabe, Ian Parker, Ghanim Ullah, and Angelo Demuro
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General Medicine ,upregulated calcium signaling ,endoplasmic reticulum ,amyloid beta (Aβ) ,Alzheimer’s ,inositol 1,4,5-trisphospahte receptors ,cellular bioenergetics - Abstract
Strong evidence indicates that amyloid beta (Aβ) inflicts its toxicity in Alzheimer’s disease (AD) by promoting uncontrolled elevation of cytosolic Ca2+ in neurons. We have previously shown that synthetic Aβ42 oligomers stimulate abnormal intracellular Ca2+ release from the endoplasmic reticulum stores, suggesting that a similar mechanism of Ca2+ toxicity may be common to the endogenous Aβs oligomers. Here, we use human postmortem brain extracts from AD-affected patients and test their ability to trigger Ca2+ fluxes when injected intracellularly into Xenopus oocytes. Immunological characterization of the samples revealed the elevated content of soluble Aβ oligomers only in samples from AD patients. Intracellular injection of brain extracts from control patients failed to trigger detectable changes in intracellular Ca2+. Conversely, brain extracts from AD patients triggered Ca2+ events consisting of local and global Ca2+ fluorescent transients. Pre-incubation with either the conformation-specific OC antiserum or caffeine completely suppressed the brain extract’s ability to trigger cytosolic Ca2+ events. Computational modeling suggests that these Ca2+ fluxes may impair cells bioenergetic by affecting ATP and ROS production. These results support the hypothesis that Aβ oligomers contained in neurons of AD-affected brains may represent the toxic agents responsible for neuronal malfunctioning and death associated with the disruption of Ca2+ homeostasis.
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- 2022
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6. Ricardo Miledi. 15 September 1927—18 December 2017
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Clarke R. Slater, Angela Vincent, Stuart G. Cull-Candy, and Ian Parker
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medicine.medical_specialty ,Family medicine ,medicine ,General Medicine ,Medical doctor - Abstract
For nearly five decades, Ricardo Miledi was among the foremost researchers in elucidating how nerves transmit signals across synapses. Born in Chihuahua, Mexico, he qualified as a medical doctor, obtained a PhD with Arturo Rosenblueth and then, while in Canberra with John Eccles FRS, was invited by Bernard Katz FRS to join the Biophysics department at University College London, where he stayed from 1958 to 1984. Both independently and with Katz, he demonstrated that influx of calcium into the presynaptic nerve terminal is the essential trigger for the release of the neurotransmitter that carries signals across to the postsynaptic cell. He found that cutting the nerve to a frog's muscle increased the number and distribution of its muscle acetylcholine (ACh) receptors, which he purified and established as membrane proteins. Together with Katz, he introduced the technique of membrane noise analysis to determine the properties of the individual ion channels opened by ACh, providing the first functional characterization of a single receptor with integral ion channel. With Eric Barnard (FRS 1981), he pioneered a new approach facilitating the study of neurotransmitter receptors and ion channels by ‘transplanting’ them from brain and other tissues into largeXenopusoocyte cells by injection of messenger RNA. After moving to the University of California, Irvine, in 1984, he helped to establish the Mexican Institute for Neurobiology at Querétaro. Working in Irvine and Mexico he extended this oocyte expression technique to incorporate transplanted brain membranes, particularly from patients with epilepsy or other neurological disorders. He received many honours for his work, including the Royal Medal (1998), but was happiest working in his lab applying his extraordinary technical skills and imagination to study synaptic transmission and inspiring a generation of neuroscientists.
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- 2021
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7. Intracellular Injection of Brain Extracts from Alzheimer's Disease Patients Triggers Unregulated Ca
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Anna, Pensalfini, Abdul Rahim, Umar, Charles, Glabe, Ian, Parker, Ghanim, Ullah, and Angelo, Demuro
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Amyloid beta-Peptides ,Alzheimer Disease ,Humans ,Brain ,Calcium ,Energy Metabolism - Abstract
Strong evidence indicates that amyloid beta (Aβ) inflicts its toxicity in Alzheimer's disease (AD) by promoting uncontrolled elevation of cytosolic Ca
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- 2022
8. Aβ42 and Aβ40 oligomers form transient and persistent pores with different time evolutions and toxicities
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Syed Islamuddin Shah, Ian Parker, Ghanim Ullah, and Angelo Demuro
- Abstract
In Alzheimer’s disease (AD), formation of harmful self-gating pores formed by the insertion of amyloid beta oligomers (AβOs) into the plasma membrane have been shown to cause disruption of Ca2+ homeostasis, leading to neuronal malfunctioning and degeneration. Among different isoforms, the most studied Aβ40 and Aβ42 are also believed to be the most toxic ones. Using single channel imaging, we show that both isoforms can form functionally distinct populations of Ca2+ permeable pores, we named transient and persistent pores. The transient pores could be seen only for a few tens of milliseconds, while persistent pores can be observed for more than an hour. However, while the Ca2+-toxicity of pores formed by Aβ42Os tend to increase over time by displaying higher open probability and larger Ca2+ permeability, pores formed by Aβ40Os show opposite time dependent behavior. We conclude that although both isoforms can form Ca2+ permeable pores in the cell’s plasma membrane, pores due to Aβ42Os display worsening Ca2+ toxicity over time.
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- 2022
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9. Intracellular injection of brain extracts from Alzheimer’s disease patients trigger unregulated Ca2+ release from intracellular stores that hinders cellular bioenergetics
- Author
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Anna Pensalfini, Abdul Rahim Umar, Charles Glabe, Ian Parker, Ghanim Ullah, and Angelo Demuro
- Abstract
Strong evidence indicates that amyloid beta (Aβ) inflicts its toxicity in Alzheimer’s disease (AD) by promoting uncontrolled elevation of cytosolic Ca2+ in neurons. We have previously shown that synthetic Aβ42 oligomers stimulate abnormal intracellular Ca2+ release from the endoplasmic reticulum stores, suggesting that a similar mechanism of Ca2+ toxicity may be common to the endogenous Aβs oligomers. To investigate this possibility, we use human postmortem brain extracts from control and AD-affected patients and test their ability to trigger Ca2+ fluxes when injected intracellularly into Xenopus oocytes. Immunological characterization of samples from AD patients revealed elevated content of soluble Aβ oligomers, detected by the conformation-dependent OC-antibody, whereas no immunoreactivity was detected in the normal samples. Intracellular injection of brain extracts from control patients failed to trigger detectable changes in intracellular Ca2+. Conversely, brain extracts from AD patients triggered Ca2+ events consisting of local and global Ca2+ fluorescent transients rising within few seconds after injection and persisting for several seconds. Pre-incubation of brain extracts with the conformation specific OC antibody completely suppressed brain extract ability to trigger cytosolic Ca2+ events. Comparison of the elementary events triggered by brain extracts and synthetic Aβ42 oligomer showed comparable temporal evolution and amplitudes to events triggered by direct injection of IP3. Moreover, bath application of caffeine reversibly inhibited local and global Ca2+ signals in all the samples confirming the involvement of Ca2+ release from the ER. Analysis of the recorded Ca2+ fluorescence signals by computational modeling allowed quantification of the IP3 and Ca2+ generated by each sample. The model further shows that the abnormal increase of Ca2+ and IP3 may affect mitochondrial bioenergetics. These results, supports the hypothesis that endogenous amyloid oligomer contained in neurons of AD-affected brains may represent the toxic agents responsible for neurons malfunctioning and death, associated with the disruption of neuronal Ca2+ homeostasis.
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- 2022
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10. Lacanian Psychoanalysis and Marxism
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Ian Parker
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- 2022
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11. La psicología crítica como psicología histórica-cultural: Las dimensiones políticas y las limitaciones del conocimiento psicológico
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Ian Parker
- Abstract
Este capítulo explora la relación entre la teoría y la práctica de la psicología crítica, centrándose en la crítica del esencialismo, individualismo y el universalismo de la psicología social convencional y sentando las bases para un enfoque hacia la política y la justicia trabajando a favor y en contra de la disciplina. Argumento en este capítulo que la “psicología crítica” contemporánea es necesariamente social y ésta como forma de la psicología crítica histórica y cultural, siempre es necesariamente política. Esta naturaleza política de la psicología histórico-cultural, tiene que ser aclarada, no obstante, para ser contrastada con las maneras en las que la “política” algunas veces es entendida en “psicología comunitaria” . En este capítulo abordo preguntas de “alienación”, las maneras en las que la psicología crítica se configura a sí misma como respuesta de la psicología convencional como una garantía ideológica para el capitalismo. Describo las áreas emergentes de la búsqueda en la psicología crítica, tomando el ejemplo en particular de la psicología critica en Gran Bretaña, para ilustrar las oportunidades y los riesgos con respecto a nuestra preocupación frente a la justicia social que se relaciona íntimamente con las dificultades anti-capitalistas.
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- 2020
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12. Regulatory T cells suppress Th17 cell Ca 2+ signaling in the spinal cord during murine autoimmune neuroinflammation
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Chijioke Akunwafo, Tobias X. Dong, Angel Zavala, Ian Parker, Andriy V. Yeromin, Shivashankar Othy, Michael D. Cahalan, Joseph L. Dynes, Fangyi Chen, Cornelia Tune, and Amit Jairaman
- Subjects
Male ,0301 basic medicine ,regulatory T cell ,T-Lymphocytes ,Lymphocyte ,Cell ,Neurodegenerative ,Inbred C57BL ,Autoantigens ,T-Lymphocytes, Regulatory ,neuroinflammation ,Mice ,Immunology and Inflammation ,0302 clinical medicine ,2.1 Biological and endogenous factors ,Aetiology ,Myelin Sheath ,two-photon ,Th17 cell ,Multidisciplinary ,Experimental autoimmune encephalomyelitis ,Forkhead Transcription Factors ,hemic and immune systems ,Biological Sciences ,Regulatory ,Cell biology ,medicine.anatomical_structure ,Spinal Cord ,Female ,Multiple Sclerosis ,Regulatory T cell ,Green Fluorescent Proteins ,two-photon immunoimaging ,Motility ,chemical and pharmacologic phenomena ,Biology ,calcium signaling ,Autoimmune Disease ,03 medical and health sciences ,immunoimaging ,Immune system ,Commentaries ,medicine ,Animals ,Neuroinflammation ,Inflammatory and immune system ,Neurosciences ,T lymphocyte ,medicine.disease ,Brain Disorders ,Mice, Inbred C57BL ,Calcium, Dietary ,030104 developmental biology ,Th17 Cells ,Calcium ,030217 neurology & neurosurgery - Abstract
Significance Regulatory T (Treg) cells mediate immune homeostasis, aid in tissue repair, and resolve inflammation in numerous autoimmune diseases; however, little is known about the role of Treg cell motility dynamics in immunoregulation. We imaged the organization and motility patterns of endogenous Treg cells in the spinal cord together with pathogenic Th17 cells in a mouse model of neuroinflammation. Treg cells exhibit repetitive-scanning motility, which may be important in suppressing Th17 cell effector functions by inhibition of Ca2+ signaling and by limiting their access to APCs, thus limiting their reactivation in the spinal cord. These findings will help to understand how Treg cells prevent autoimmunity and dampen immune responses, and how autoimmune diseases can be effectively targeted using Treg-based cellular therapies., T lymphocyte motility and interaction dynamics with other immune cells are vital determinants of immune responses. Regulatory T (Treg) cells prevent autoimmune disorders by suppressing excessive lymphocyte activity, but how interstitial motility patterns of Treg cells limit neuroinflammation is not well understood. We used two-photon microscopy to elucidate the spatial organization, motility characteristics, and interactions of endogenous Treg and Th17 cells together with antigen-presenting cells (APCs) within the spinal cord leptomeninges in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. Th17 cells arrive before the onset of clinical symptoms, distribute uniformly during the peak, and decline in numbers during later stages of EAE. In contrast, Treg cells arrive after Th17 cells and persist during the chronic phase. Th17 cells meander widely, interact with APCs, and exhibit cytosolic Ca2+ transients and elevated basal Ca2+ levels before the arrival of Treg cells. In contrast, Treg cells adopt a confined, repetitive-scanning motility while contacting APCs. These locally confined but highly motile Treg cells limit Th17 cells from accessing APCs and suppress Th17 cell Ca2+ signaling by a mechanism that is upstream of store-operated Ca2+ entry. Finally, Treg cell depletion increases APC numbers in the spinal cord and exaggerates ongoing neuroinflammation. Our results point to fundamental differences in motility characteristics between Th17 and Treg cells in the inflamed spinal cord and reveal three potential cellular mechanisms by which Treg cells regulate Th17 cell effector functions: reduction of APC density, limiting access of Th17 cells to APCs, and suppression of Th17 Ca2+ signaling.
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- 2020
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13. Desire, liturgy, andthe joint construction of narrativein a teacher preparation program
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Ian Parker Renga
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050101 languages & linguistics ,History ,Literature and Literary Theory ,media_common.quotation_subject ,05 social sciences ,Lifelong learning ,050301 education ,Identity (social science) ,Social practice ,Teacher education ,Education ,Negotiation ,Pedagogy ,0501 psychology and cognitive sciences ,Joint (building) ,Narrative ,Liturgy ,Sociology ,0503 education ,Social Sciences (miscellaneous) ,media_common - Abstract
Treating narrative as a social practice has enabled examination of the identity work accomplished through interactive story construction within various communities, including teacher preparation programs. Largely unaddressed in this literature is the presence of desire – the sense of longing conveyed through expressed wants, wishes, and hopes – and how it works in and through narrative practice. Following James K. A. Smith (2009), I posit that some stories may be liturgical in their conscripting of tellers and listeners into narratives that shape their identities and direct their desires. To explore this empirically, I examined desire in the joint construction of a professional identity narrative – teacher as lifelong learner – within an urban teacher residency. My analysis suggests that program leaders’ expressed desires of and for the novice teachers established the leaders’ authority and worked to conscript novices into the narrative. However, novices were actively negotiating the narrative and the desirability of the professional identity.
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- 2020
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14. Communism
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Ian Parker
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- 2022
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15. Author response: TREM2 regulates purinergic receptor-mediated calcium signaling and motility in human iPSC-derived microglia
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Amanda McQuade, Amit Jairaman, Alberto Granzotto, You Jung Kang, Jean Paul Chadarevian, Sunil Gandhi, Ian Parker, Ian Smith, Hansang Cho, Stefano L Sensi, Shivashankar Othy, Mathew Blurton-Jones, and Michael D Cahalan
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- 2022
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16. Situated Learning Within Practice, Culture, and Community: Jean Lave’s Political Project
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Ian Parker Renga
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- 2022
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17. Public Montessori as a Reform Model: Questions and Considerations for School Districts (Poster 16)
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Ian Parker
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- 2022
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18. Termination of Ca2+ puffs during IP3-evoked global Ca2+ signals
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Ian Parker and Jeffrey T. Lock
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Biochemistry & Molecular Biology ,Physiology ,Medical Physiology ,Calcium imaging ,IP3 receptor ,Gating ,IP3 signaling ,chemistry.chemical_compound ,stomatognathic system ,Molecular Biology ,5-Trisphosphate Receptors ,IP(3) signaling ,Calcium signaling ,5-Trisphosphate ,Ca(2+) puffs ,Inositol trisphosphate ,Cell Biology ,Inositol trisphosphate receptor ,Ca2+ puffs ,Inositol 1 ,respiratory tract diseases ,body regions ,Kinetics ,chemistry ,Biophysics ,Liberation ,Calcium ,sense organs ,IP(3) receptor ,Biochemistry and Cell Biology - Abstract
We previously described that cell-wide cytosolic Ca2+ transients evoked by inositol trisphosphate (IP3) are generated by two modes of Ca2+ liberation from the ER; ‘punctate’ release via an initial flurry of transient Ca2+ puffs from local clusters of IP3 receptors, succeeded by a spatially and temporally ‘diffuse’ Ca2+ liberation. Those findings were derived using statistical fluctuation analysis to monitor puff activity which is otherwise masked as global Ca2+ levels rise. Here, we devised imaging approaches to resolve individual puffs during global Ca2+ elevations to better investigate the mechanisms terminating the puff flurry. We find that puffs contribute about 40% (∼90 attomoles) of the total Ca2+ liberation, largely while the global Ca2+ signal rises halfway to its peak. The major factor terminating punctate Ca2+ release is an abrupt decline in puff frequency. Although the amplitudes of large puffs fall during the flurry, the amplitudes of more numerous small puffs remain steady, so overall puff amplitudes decline only modestly (∼30%). The Ca2+ flux through individual IP3 receptor/channels does not measurably decline during the flurry, or when puff activity is depressed by pharmacological lowering of Ca2+ levels in the ER lumen, indicating that the termination of punctate release is not a simple consequence of reduced driving force for Ca2+ liberation. We propose instead that the gating of IP3 receptors at puff sites is modulated such that their openings become suppressed as the bulk [Ca2+] in the ER lumen falls during global Ca2+ signals.
- Published
- 2021
19. KRAP is required for diffuse and punctate IP3-mediated Ca2+ liberation and determines the number of functional IP3R channels within clusters
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Irene Vorontsova, Jeffrey T. Lock, and Ian Parker
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Proto-Oncogene Proteins p21(ras) ,HEK293 Cells ,Physiology ,Humans ,Inositol 1,4,5-Trisphosphate Receptors ,Calcium ,Calcium Signaling ,Cell Biology ,RNA, Small Interfering ,Molecular Biology ,Article - Abstract
KRas-induced actin-interacting protein (KRAP) has been identified as crucial for the appropriate localization and functioning of the inositol trisphosphate receptors (IP(3)Rs) that mediate Ca(2+) release from the endoplasmic reticulum. Here, we used siRNA knockdown of KRAP expression in HeLa and HEK293 cells to examine the roles of KRAP in the generation of IP(3)-mediated local Ca(2+) puffs and global, cell-wide Ca(2+) signals. High resolution Ca(2+) imaging revealed that the mean amplitude of puffs was strongly reduced by KRAP knockdown, whereas the Ca(2+) flux during openings of individual IP(3)R channels was little affected. In both control and KRAP knockdown cells the numbers of functional channels in the clusters underlying puff sites were stochastically distributed following a Poisson relationship, but the mean number of functional channels per site was reduced by about two thirds by KRAP knockdown. We conclude that KRAP is required for activity of IP(3)R channels at puff sites and stochastically ‘licenses’ the function of individual channels on a one-to-one basis, rather than determining the functioning of the puff site as a whole. In addition to puff activity (‘punctate’ Ca(2+) release), global, cell-wide Ca(2+) signals evoked by higher levels of IP(3) are further composed from a discrete ‘diffuse’ mode of Ca(2+) release. By applying fluctuation analysis to isolate the punctate component during global Ca(2+) signals, we find that KRAP knockdown suppresses to similar extents punctate and diffuse Ca(2+) release in wild-type cells and in HEK293 cells exclusively expressing type 1 and type 3 IP3Rs. Thus, KRAP appears essential for the functioning of the IP(3)Rs involved in diffuse Ca(2+) release as well as the clustered IP(3)Rs that generate local Ca(2+) puffs.
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- 2022
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20. Transpersonal psychology
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Elliot Cohen and Ian Parker
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- 2021
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21. Resistance
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Elliot Cohen and Ian Parker
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- 2021
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22. The Dao of psychologisation
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Elliot Cohen and Ian Parker
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- 2021
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23. The commodification of ‘the East’
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Ian Parker and Elliot Cohen
- Subjects
Commodification ,Political science ,Political economy - Published
- 2021
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24. The Buddha as a psychologist, the Dharma as a psychotherapy
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Ian Parker and Elliot Cohen
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Dharma ,Psychotherapist ,Gautama Buddha ,Psychology - Published
- 2021
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25. Counterculture and the return to the East
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Ian Parker and Elliot Cohen
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Counterculture ,media_common.quotation_subject ,Art history ,Art ,media_common - Published
- 2021
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26. Termination of Ca
- Author
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Jeffrey T, Lock and Ian, Parker
- Subjects
Kinetics ,Inositol 1,4,5-Trisphosphate Receptors ,Calcium ,Calcium Signaling ,Inositol 1,4,5-Trisphosphate ,Article - Abstract
We previously described that cell-wide cytosolic Ca(2+) transients evoked by inositol trisphosphate (IP(3)) are generated by two modes of Ca(2+) liberation from the ER; ‘punctate’ release via an initial flurry of transient Ca(2+) puffs from local clusters of IP(3) receptors, succeeded by a spatially and temporally ‘diffuse’ Ca(2+) liberation. Those findings were derived using statistical fluctuation analysis to monitor puff activity which is otherwise masked as global Ca(2+) levels rise. Here, we devised imaging approaches to resolve individual puffs during global Ca(2+) elevations to better investigate the mechanisms terminating the puff flurry. We find that puffs contribute about 40% (~90 attomoles) of the total Ca(2+) liberation, largely while the global Ca(2+) signal rises halfway to its peak. The major factor terminating punctate Ca(2+) release is an abrupt decline in puff frequency. Although the amplitudes of large puffs fall during the flurry, the amplitudes of more numerous small puffs remain steady, so overall puff amplitudes decline only modestly (~30%). The Ca(2+) flux through individual IP(3) receptor/channels does not measurably decline during the flurry, or when puff activity is depressed by pharmacological lowering of Ca(2+) levels in the ER lumen, indicating that the termination of punctate release is not a simple consequence of reduced driving force for Ca(2+) liberation. We propose instead that the gating of IP(3) receptors at puff sites is modulated such that their openings become suppressed as the bulk [Ca(2+)] in the ER lumen falls during global Ca(2+) signals.
- Published
- 2021
27. TREM2 regulates purinergic receptor-mediated calcium signaling and motility in human iPSC-derived microglia
- Author
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Hansang Cho, Ian Parker, Sunil P. Gandhi, You Jung Kang, Amanda McQuade, Amit Jairaman, Shivashankar Othy, Ian H. Smith, Alberto Granzotto, Jean Paul Chadarevian, Mathew Blurton-Jones, and Michael D. Cahalan
- Subjects
Aging ,Purinergic ,Neurodegenerative ,Alzheimer's Disease ,immunology ,neuroscience ,Purinergic Agonists ,P2Y12 ,Immunologic ,Receptors ,TREM2 ,2.1 Biological and endogenous factors ,Aetiology ,Receptors, Immunologic ,store-operated Ca2+ entry ,Calcium signaling ,Membrane Glycoproteins ,Microglia ,Chemistry ,General Neuroscience ,Purinergic receptor ,Receptors, Purinergic ,General Medicine ,Alzheimer's disease ,Cell biology ,iPSC-derived microglia ,Adenosine Diphosphate ,medicine.anatomical_structure ,Immunology ,Induced Pluripotent Stem Cells ,Motility ,General Biochemistry, Genetics and Molecular Biology ,Alzheimer Disease ,Acquired Cognitive Impairment ,medicine ,Humans ,human ,Calcium Signaling ,Ca2+ signaling ,Inflammation ,General Immunology and Microbiology ,Neurosciences ,Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) ,P2Y receptor ,Chemotaxis ,Stem Cell Research ,Brain Disorders ,inflammation ,Store-operated Ca2+ entry ,Dementia ,Calcium ,Biochemistry and Cell Biology ,Neuroscience - Abstract
The membrane protein TREM2 (Triggering Receptor Expressed on Myeloid cells 2) regulates key microglial functions including phagocytosis and chemotaxis. Loss-of-function variants of TREM2 are associated with increased risk of Alzheimer’s disease (AD). Because abnormalities in Ca2+ signaling have been observed in several AD models, we investigated TREM2 regulation of Ca2+ signaling in human induced pluripotent stem cell-derived microglia (iPSC-microglia) with genetic deletion of TREM2. We found that iPSC-microglia lacking TREM2 (TREM2 KO) show exaggerated Ca2+ signals in response to purinergic agonists, such as ADP, that shape microglial injury responses. This ADP hypersensitivity, driven by increased expression of P2Y12 and P2Y13 receptors, results in greater release of Ca2+ from the endoplasmic reticulum (ER) stores, which triggers sustained Ca2+ influx through Orai channels and alters cell motility in TREM2 KO microglia. Using iPSC-microglia expressing the genetically encoded Ca2+ probe, Salsa6f, we found that cytosolic Ca2+ tunes motility to a greater extent in TREM2 KO microglia. Despite showing greater overall displacement, TREM2 KO microglia exhibit reduced directional chemotaxis along ADP gradients. Accordingly, the chemotactic defect in TREM2 KO microglia was rescued by reducing cytosolic Ca2+ using a P2Y12 receptor antagonist. Our results show that loss of TREM2 confers a defect in microglial Ca2+ response to purinergic signals, suggesting a window of Ca2+ signaling for optimal microglial motility.
- Published
- 2021
28. Piezo1 channels restrain regulatory T cells but are dispensable for effector CD4+ T cell responses
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Medha M. Pathak, Ian Parker, Francesco Marangoni, Stuart M. Cahalan, Joseph L. Dynes, Michael D. Cahalan, Jesse R. Holt, Amit Jairaman, Jamison L. Nourse, Milton L. Greenberg, Angel Zavala, Andriy V. Yeromin, and Shivashankar Othy
- Subjects
0301 basic medicine ,T-Lymphocytes ,Neurodegenerative ,Inbred C57BL ,Lymphocyte Activation ,T-Lymphocytes, Regulatory ,Ion Channels ,Mice ,0302 clinical medicine ,immune system diseases ,2.1 Biological and endogenous factors ,Aetiology ,Encephalomyelitis ,Research Articles ,Multidisciplinary ,Effector ,Experimental autoimmune encephalomyelitis ,SciAdv r-articles ,Cell Differentiation ,Regulatory ,Cell biology ,medicine.anatomical_structure ,Research Article ,Encephalomyelitis, Autoimmune, Experimental ,Multiple Sclerosis ,1.1 Normal biological development and functioning ,T cell ,Immunology ,Biology ,Autoimmune Disease ,Proinflammatory cytokine ,Experimental ,03 medical and health sciences ,Immune system ,Underpinning research ,medicine ,Animals ,Inflammatory and immune system ,PIEZO1 ,Neurosciences ,Cell Biology ,Th1 Cells ,medicine.disease ,Brain Disorders ,nervous system diseases ,Mice, Inbred C57BL ,030104 developmental biology ,Wound healing ,030217 neurology & neurosurgery ,Autoimmune ,Transforming growth factor - Abstract
Mechanosensitive Piezo1 channels restrict regulatory T cell expansion and limit disease remission in EAE., T lymphocytes encounter complex mechanical cues during an immune response. The mechanosensitive ion channel, Piezo1, drives inflammatory responses to bacterial infections, wound healing, and cancer; however, its role in helper T cell function remains unclear. In an animal model for multiple sclerosis, experimental autoimmune encephalomyelitis (EAE), we found that mice with genetic deletion of Piezo1 in T cells showed diminished disease severity. Unexpectedly, Piezo1 was not essential for lymph node homing, interstitial motility, Ca2+ signaling, T cell proliferation, or differentiation into proinflammatory T helper 1 (TH1) and TH17 subsets. However, Piezo1 deletion in T cells resulted in enhanced transforming growth factor–β (TGFβ) signaling and an expanded pool of regulatory T (Treg) cells. Moreover, mice with deletion of Piezo1 specifically in Treg cells showed significant attenuation of EAE. Our results indicate that Piezo1 selectively restrains Treg cells, without influencing activation events or effector T cell functions.
- Published
- 2021
29. Fritz Morgenthaler, On the Dialectics of Psychoanalytic Practice
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Ian Parker
- Subjects
Dialectic ,History ,Psychoanalysis ,Philosophy ,Psychoanalytic theory ,Applied Psychology - Published
- 2020
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30. Applications of FLIKA, a Python-based image processing and analysis platform, for studying local events of cellular calcium signaling
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Kyle L. Ellefsen, Ian Parker, Brett Settle, Jeffrey T. Lock, and Carley A. Karsten
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0301 basic medicine ,Computer science ,Image processing ,computer.software_genre ,Article ,03 medical and health sciences ,0302 clinical medicine ,Software ,Computer graphics (images) ,Image Processing, Computer-Assisted ,Humans ,Plug-in ,Calcium Signaling ,Molecular Biology ,Image resolution ,computer.programming_language ,Graphical user interface ,business.industry ,Suite ,Cell Biology ,Python (programming language) ,Visualization ,HEK293 Cells ,030104 developmental biology ,Microscopy, Fluorescence ,Programming Languages ,business ,computer ,030217 neurology & neurosurgery - Abstract
The patterning of cytosolic Ca2+ signals underlies their ubiquitous ability to specifically regulate numerous cellular processes. Advances in fluorescence microscopy have made it possible to image these signals with unprecedented temporal and spatial resolution. However, this is a double-edged sword, as the resulting enormous data sets necessitate development of software to automate image processing and analysis. Here, we describe Flika, an open source, graphical user interface program written in the Python environment that contains a suite of built-in image processing tools to enable intuitive visualization of image data and analysis. We illustrate the utility and power of Flika by three applications for studying cellular Ca2+ signaling: a script for measuring single-cell global Ca2+ signals; a plugin for the detection, localization and analysis of subcellular Ca2+ puffs; and a script that implements a novel approach for fluctuation analysis of transient, local Ca2+ fluorescence signals. This article is part of a Special Issue entitled: ECS Meeting edited by Claus Heizmann, Joachim Krebs and Jacques Haiech.
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- 2019
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31. Locke on biblical method and theological interpretation
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Kim Ian Parker
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Interpretation (philosophy) ,Philosophy ,Epistemology - Published
- 2021
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32. Miséria, dialética e libertação
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Ian Parker, David Pavón Cuéllar, and Paulo Antonio de Campos Beer
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Social sciences (General) ,H1-99 ,General Medicine ,Psicanálise. Miséria. Revolução - Abstract
Este artigo argumenta que Freud não aceitou a esfera da “psicologia” como algo dado, que poderia ser conhecido objetivamente. Tampouco ele a via como algo unitário que seria sempre o mesmo e em qualquer pessoa. Ao invés disso, ofereceu ideias valiosas sobre a natureza humana da miséria enquanto algo histórico, sobre o processo dialético através do qual podemos entender a miséria como algo condensado em sintomas, e sobre a relação entre compreensão e libertação. Nós argumentamos que a psicanálise precisa ser recriada por nós enquanto uma ferramenta de trabalho radical sobre a subjetividade para derrubar as condições existentes. Argumentamos em favor de uma compreensão dialética da psicanálise como uma ferramenta e um resultado; essa ferramenta é o resultado das elaborações teóricas de Freud e seus seguidores, que nos permitiram usá-la para um trabalho radical na clínica e em movimentos de libertação. Ela torna possível uma “subjetividade revolucionária”, um “sujeito revolucionário”.
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- 2021
33. Subjectivity, Psychology, Marxism and Critical Realism: Eleven Theses
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Ian Parker
- Subjects
Subjectivity ,Action (philosophy) ,Reading (process) ,media_common.quotation_subject ,Critical realism (philosophy of the social sciences) ,Cognition ,Psychology ,Social constructionism ,Relation (history of concept) ,Epistemology ,media_common - Abstract
This paper traces through the fraught relationship between psychology and Marxism through a reading of current critical debates in the discipline through Marx’s 1845 eleven ‘Theses on Feuerbach’. These theses enable us to grasp how Marxism tackles questions ranging from the relation between the individual and the social to social constructionism and discourse and then, crucially, to ‘critical realism’ in relation to psychology. Questions of behaviour, cognition and biology, as well as the radical status of psychoanalysis in relation to psychology are explored. These eleven theses radically rework human agency, providing an innovative basis for working inside psychology, but also, most importantly, for appreciating how necessary it is to work against psychology. Psychology as a discipline interprets the world, and we learn through Marx that is necessary to change it, in the process dispensing with psychology as such. We must remember that psychology is not a scientific discipline, and cannot become so. It is, as Fernando Gonzalez Rey reminds us, a discipline concerned with the nature of subjectivity. What is clear is that any realist approach to human action should be undertaken outside the discipline, not inside it. We approach the task of taking subjectivity seriously through Marx’s eleven theses.
- Published
- 2021
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34. Viral Resistance
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Ian Parker
- Published
- 2021
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35. Las Ciencias sociales: al otro lado del discurso neoliberal
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Athanasios Marvakis, Luis Huerta Charles, Johanna Esquivel, Boia Efraime Júnior, Izabella Mendes Sant'Ana, Ian Parker, Sofia Triliv, Carlos Calvo Muñoz, David Pavón Cuéllar, Jorge Mario Flores Osorio, Omar Alejandro Bravo, Rolando Pinto Contreras, Ana Paula Gomes Moreira, Raquel Souza Lobo Guzzo, Adinete Sousa da Costa Mezzalira, Oscar Manuel Martínez Camarillo, Antonio Padilla Arroyo, Huerta Charles, Luis, Flores Osorio, Jorge Mario, and Bravo, Omar Alejandro
- Subjects
Armed conflict ,Conflicto armado ,Violencia ,Neoliberalism ,Ciencias sociales ,Pensamiento crítico ,Sociology ,Neoliberalismo ,Psicología social ,Social psychology ,Social sciences ,Critical thinking - Abstract
El libro asume de manera clara y directa que las ciencias sociales que recoge una tradición que ya, desde el informe de la Comisión Gulbenkian para la reestructuración de las ciencias sociales (Wallerstein, 1996), las caracterizan, a saber: su desprendimiento de la filosofía en el siglo XVII, su recorrido para posicionarse en el concierto del conocimiento académico, su centralidad en el conocimiento, la referencia que ellas hacen al mundo empírico, que puede ser indagado mediante el uso del método científico, sin que este se reduzca al experimento de laboratorio. Todo lo anterior se puede enmarcar para efectos reflexivos y de producción de un nuevo conocimiento que esté “al otro lado del neoliberalismo” [Álvaro Díaz Gómez]. CONTENIDO: Prólogo, Álvaro Díaz Gómez -- Al otro lado del discurso neoliberal: Actos de resistencia en el mundo, Luis Huerta-Charles -- Meditaciones teóricas y metodológicas para el estudio de los procesos histórico-culturales, Antonio Padilla Arroyo -- Fundamentos socio-antropológicos y epistemológicos de la pedagogía crítica latinoamericana, Rolando Pinto Contreras -- Pedagogía comunitaria: disoñando sinergias educativas con la comunidad, Carlos Calvo -- Writing Narratives with Mexican Bilingual Students: Participatory Action Research Explorations, Johanna Esquivel -- Escuela y comunidad: desafíos y cuestiones para la psicología, Raquel Souza Lobo Guzzo, Adinete Sousa da Costa Mezzalira, Ana Paula Gomes Moreira y Izabella Mendes Sant’Ana -- Reflexiones sobre el legado y papel histórico de la psicología social comunitaria en México, Oscar Manuel Martínez Camarillo -- Neoliberal Psy-Practices in Greece, Sofia Triliv y Athanasios Marvakis -- Academics and politics: intercectionnalyty and systemic violence, Ian Parker -- La rebeldía zapatista como arma y pauta para la crítica de la disciplina psicológica, David Pavón-Cuéllar -- Desafios actuales de la paz y la guerra en Mozambique. Notas de una lectura psicoanalítica, Boia Efaime Júnios -- Colonización del pensamento psicológico latinoamericano, Jorge Mario Flores Osorio -- Los múltiples atravesamientos de la intervención y la investigación con familiares de víctimas de desaparición forzada en el conflicto armado colombiano, Omar Alejandro Bravo. Incluye referencias bibliográficas
- Published
- 2020
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36. IP3 mediated global Ca2+ signals arise through two temporally and spatially distinct modes of Ca2+ release
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Ian Parker and Jeffrey T. Lock
- Subjects
Physics ,General Immunology and Microbiology ,QH301-705.5 ,General Neuroscience ,ip3 receptor ,Science ,Inositol trisphosphate ,General Medicine ,Inositol trisphosphate receptor ,calcium signaling ,General Biochemistry, Genetics and Molecular Biology ,chemistry.chemical_compound ,calcium imaging ,Calcium imaging ,Structural biology ,chemistry ,Biophysics ,Medicine ,Ca2 release ,Effector functions ,Biology (General) ,Calcium signaling - Abstract
The ‘building-block’ model of inositol trisphosphate (IP3)-mediated Ca2+ liberation posits that cell-wide cytosolic Ca2+ signals arise through coordinated activation of localized Ca2+ puffs generated by stationary clusters of IP3 receptors (IP3Rs). Here, we revise this hypothesis, applying fluctuation analysis to resolve Ca2+ signals otherwise obscured during large Ca2+ elevations. We find the rising phase of global Ca2+ signals is punctuated by a flurry of puffs, which terminate before the peak by a mechanism involving partial ER Ca2+ depletion. The continuing rise in Ca2+, and persistence of global signals even when puffs are absent, reveal a second mode of spatiotemporally diffuse Ca2+ signaling. Puffs make only small, transient contributions to global Ca2+ signals, which are sustained by diffuse release of Ca2+ through a functionally distinct process. These two modes of IP3-mediated Ca2+ liberation have important implications for downstream signaling, imparting spatial and kinetic specificity to Ca2+-dependent effector functions and Ca2+ transport.
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- 2020
37. ER-luminal [Ca2+] regulation of InsP3 receptor gating mediated by an ER-luminal peripheral Ca2+-binding protein
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Horia Vais, Ian Parker, Chris McKennan, Min Wang, Matthew Yan-lok Chan, Riley Payne, Don-On Daniel Mak, Carly Fiest, J. Kevin Foskett, Karthik Mallilankaraman, Jeffrey T. Lock, Steven H. Seeholzer, and Lynn A. Spruce
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QH301-705.5 ,Science ,calcium signaling ,General Biochemistry, Genetics and Molecular Biology ,chemistry.chemical_compound ,annexin ,Annexin ,Inositol ,Biology (General) ,Receptor ,Calcium signaling ,General Immunology and Microbiology ,inositol 1,4,5-trisphosphate receptor ,General Neuroscience ,Endoplasmic reticulum ,intracellular calcium-release channel ,General Medicine ,Cell biology ,endoplasmic reticulum lumen ,chemistry ,Cytoplasm ,Medicine ,Signal transduction ,single-channel gating regulation ,Annexin A1 - Abstract
Modulating cytoplasmic Ca2+ concentration ([Ca2+]i) by endoplasmic reticulum (ER)-localized inositol 1,4,5-trisphosphate receptor (InsP3R) Ca2+-release channels is a universal signaling pathway that regulates numerous cell-physiological processes. Whereas much is known regarding regulation of InsP3R activity by cytoplasmic ligands and processes, its regulation by ER-luminal Ca2+ concentration ([Ca2+]ER) is poorly understood and controversial. We discovered that the InsP3R is regulated by a peripheral membrane-associated ER-luminal protein that strongly inhibits the channel in the presence of high, physiological [Ca2+]ER. The widely-expressed Ca2+-binding protein annexin A1 (ANXA1) is present in the nuclear envelope lumen and, through interaction with a luminal region of the channel, can modify high-[Ca2+]ER inhibition of InsP3R activity. Genetic knockdown of ANXA1 expression enhanced global and local elementary InsP3-mediated Ca2+ signaling events. Thus, [Ca2+]ER is a major regulator of InsP3R channel activity and InsP3R-mediated [Ca2+]i signaling in cells by controlling an interaction of the channel with a peripheral membrane-associated Ca2+-binding protein, likely ANXA1.
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- 2020
38. Author response: IP3 mediated global Ca2+ signals arise through two temporally and spatially distinct modes of Ca2+ release
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Ian Parker and Jeffrey T. Lock
- Subjects
Chemistry ,Ca2 release ,Neuroscience - Published
- 2020
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39. Noise analysis of cytosolic calcium image data
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Angelo Demuro, Ian Parker, Divya Swaminathan, and George D. Dickinson
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0301 basic medicine ,Biochemistry & Molecular Biology ,Physiology ,Xenopus ,Medical Physiology ,Gating ,Noise analysis ,Article ,Fluorescence ,Image (mathematics) ,Cell Line ,Imaging ,03 medical and health sciences ,0302 clinical medicine ,Imaging, Three-Dimensional ,Cytosol ,Rare Diseases ,Ca2+ imaging ,Cell Line, Tumor ,Catalytic Domain ,Inositol 1,4,5-Trisphosphate Receptors ,Animals ,Humans ,Ca2+ noise ,Molecular Biology ,5-Trisphosphate Receptors ,Physics ,Total internal reflection fluorescence microscope ,Tumor ,Ca(2+) puffs ,Spectral density ,Cell Biology ,Ca2+ puffs ,Inositol 1 ,Ca(2+) imaging ,Electrophysiology ,Noise ,Kinetics ,030104 developmental biology ,Three-Dimensional ,Ca(2+) noise ,Calcium ,Calcium Channels ,Biochemistry and Cell Biology ,Biological system ,030217 neurology & neurosurgery ,Cytosolic calcium - Abstract
Cellular Ca(2+) signals are often constrained to cytosolic micro- or nano-domains where stochastic openings of Ca(2+) channels cause large fluctuations in local Ca(2+) concentration (Ca(2+) ‘noise’). With the advent of TIRF microscopy to image the fluorescence of Ca(2+)-sensitive probes from attoliter volumes it has become possible to directly monitor these signals, which closely track the gating of plasmalemmal and ER Ca(2+) permeable channels. Nevertheless, it is likely that many physiologically important Ca(2+) signals are too small to resolve as discrete events in fluorescence recordings. By analogy with noise analysis of electrophysiological data, we explore here the use of statistical approaches to detect and analyze such Ca(2+) noise in images obtained using Ca(2+)-sensitive indicator dyes. We describe two techniques - power spectrum analysis and spatio-temporal correlation - and demonstrate that both effectively identify discrete, spatially localized calcium release events (Ca(2+) puffs). Moreover, we show they are able to detect localized noise fluctuations in a case where discrete events cannot directly be resolved.
- Published
- 2020
40. Psychiatry
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Ian Parker
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- 2020
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41. Empirical
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Ian Parker
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- 2020
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42. Stress
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Ian Parker
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- 2020
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43. Cognition
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Ian Parker
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Race (biology) ,Cognition ,Psychology ,Developmental psychology - Published
- 2020
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44. Analysis
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Ian Parker
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- 2020
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45. Qualitative
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Ian Parker
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- 2020
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46. Experiments
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Ian Parker
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- 2020
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47. Personality
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Ian Parker
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- 2020
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48. Paradigms
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Ian Parker
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- 2020
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49. Quantitative
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Ian Parker
- Published
- 2020
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50. Science
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Ian Parker
- Published
- 2020
- Full Text
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