45 results on '"Ryan, P.D."'
Search Results
2. Overexpression of BLM promotes DNA damage and increased sensitivity to platinum salts in triple-negative breast and serous ovarian cancers
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Birkbak, N.J., Li, Y., Pathania, S., Greene-Colozzi, A., Dreze, M., Bowman-Colin, C., Sztupinszki, Z., Krzystanek, M., Diossy, M., Tung, N., Ryan, P.D., Garber, J.E., Silver, D.P., Iglehart, J.D., Wang, Z.C., Szuts, D., Szallasi, Z., and Richardson, A.L.
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- 2018
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3. Phase I trial of olaparib in combination with cisplatin for the treatment of patients with advanced breast, ovarian and other solid tumors
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Balmaña, J., Tung, N.M., Isakoff, S.J., Graña, B., Ryan, P.D., Saura, C., Lowe, E.S., Frewer, P., Winer, E., Baselga, J., and Garber, J.E.
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- 2014
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4. Switching in Cerebellar Stellate Cell Excitability in Response to a Pair of Inhibitory/Excitatory Presynaptic Inputs: A Dynamical System Perspective
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Derek Bowie, Anmar Khadra, Ryan P.D. Alexander, and Saeed Farjami
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Cerebellum ,Cognitive Neuroscience ,Models, Neurological ,Action Potentials ,Stimulation ,Inhibitory postsynaptic potential ,01 natural sciences ,010305 fluids & plasmas ,03 medical and health sciences ,0302 clinical medicine ,Arts and Humanities (miscellaneous) ,0103 physical sciences ,Inhibitory synapses ,medicine ,Humans ,Neurons ,Quantitative Biology::Neurons and Cognition ,Chemistry ,Perspective (graphical) ,medicine.anatomical_structure ,Synapses ,Hepatic stellate cell ,Excitatory postsynaptic potential ,Neuroscience ,030217 neurology & neurosurgery - Abstract
Cerebellar stellate cells form inhibitory synapses with Purkinje cells, the sole output of the cerebellum. Upon stimulation by a pair of varying inhibitory and fixed excitatory presynaptic inputs, these cells do not respond to excitation (i.e., do not generate an action potential) when the magnitude of the inhibition is within a given range, but they do respond outside this range. We previously used a revised Hodgkin–Huxley type of model to study the nonmonotonic first-spike latency of these cells and their temporal increase in excitability in whole cell configuration (termed run-up). Here, we recompute these latency profiles using the same model by adapting an efficient computational technique, the two-point boundary value problem, that is combined with the continuation method. We then extend the study to investigate how switching in responsiveness, upon stimulation with presynaptic inputs, manifests itself in the context of run-up. A three-dimensional reduced model is initially derived from the original six-dimensional model and then analyzed to demonstrate that both models exhibit type 1 excitability possessing a saddle-node on an invariant cycle (SNIC) bifurcation when varying the amplitude of [Formula: see text]. Using slow-fast analysis, we show that the original model possesses three equilibria lying at the intersection of the critical manifold of the fast subsystem and the nullcline of the slow variable [Formula: see text] (the inactivation of the A-type K[Formula: see text] channel), the middle equilibrium is of saddle type with two-dimensional stable manifold (computed from the reduced model) acting as a boundary between the responsive and non-responsive regimes, and the (ghost of) SNIC is formed when the [Formula: see text]-nullcline is (nearly) tangential to the critical manifold. We also show that the slow dynamics associated with (the ghost of) the SNIC and the lower stable branch of the critical manifold are responsible for generating the nonmonotonic first-spike latency. These results thus provide important insight into the complex dynamics of stellate cells.
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- 2020
5. Paradoxical hyperexcitability from NaV1.2 sodium channel loss in neocortical pyramidal cells
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Stephen Sanders, Caroline M. Keeshen, Kevin J. Bender, Henry Kyoung, Atehsa Sahagun, Ryan P.D. Alexander, Perry W.E. Spratt, and Roy Ben-Shalom
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Knockout ,Intellectual and Developmental Disabilities (IDD) ,Medical Physiology ,Action Potentials ,autism ,Dendrite ,Neocortex ,autism spectrum disorder ,NaV1.2 ,Neurodegenerative ,Inbred C57BL ,General Biochemistry, Genetics and Molecular Biology ,dendrite ,03 medical and health sciences ,Mice ,0302 clinical medicine ,medicine ,Premovement neuronal activity ,Animals ,2.1 Biological and endogenous factors ,Aetiology ,030304 developmental biology ,0303 health sciences ,prefrontal cortex ,pyramidal cell ,NAV1.2 Voltage-Gated Sodium Channel ,Epilepsy ,Chemistry ,Sodium channel ,Pyramidal Cells ,Neurosciences ,Dendrites ,Potassium channel ,Brain Disorders ,medicine.anatomical_structure ,dynamic clamp ,NAV1 ,Neurological ,Excitatory postsynaptic potential ,Biochemistry and Cell Biology ,Pyramidal cell ,SCN2A ,Neuroscience ,030217 neurology & neurosurgery ,Gene Deletion - Abstract
Loss-of-function variants in the gene SCN2A, which encodes the sodium channel NaV1.2, are strongly associated with autism spectrum disorder and intellectual disability. An estimated 20%-30% of children with these variants also suffer from epilepsy, with altered neuronal activity originating in neocortex, a region where NaV1.2 channels are expressed predominantly in excitatory pyramidal cells. This is paradoxical, as sodium channel loss in excitatory cells would be expected to dampen neocortical activity rather than promote seizure. Here, we examined pyramidal neurons lacking NaV1.2 channels and found that they were intrinsically hyperexcitable, firing high-frequency bursts of action potentials (APs) despite decrements in AP size and speed. Compartmental modeling and dynamic-clamp recordings revealed that NaV1.2 loss prevented potassium channels from properly repolarizing neurons between APs, increasing overall excitability by allowing neurons to reach threshold for subsequent APs more rapidly. This cell-intrinsic mechanism may, therefore, account for why SCN2A loss-of-function can paradoxically promote seizure.
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- 2021
6. Paradoxical hyperexcitability from NaV1.2 sodium channel loss in neocortical pyramidal cells
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Spratt, Perry W.E., primary, Alexander, Ryan P.D., additional, Ben-Shalom, Roy, additional, Sahagun, Atehsa, additional, Kyoung, Henry, additional, Keeshen, Caroline M., additional, Sanders, Stephan J., additional, and Bender, Kevin J., additional
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- 2021
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7. The Newer Granite problem revisited: a transtensional origin for the Early Devonian Trans-Suture Suite
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Brown, P.E., Ryan, P.D., Soper, N.J., and Woodcock, N.H.
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United Kingdom -- Natural history ,Granite -- Natural history ,Earth sciences - Abstract
The origin of the Newer Granites is long-standing problem. In the Caledonian orthotectonic zone the intrusions span the period of late orogenic convergence and uplift, but attempts to relate them as a group to late lapetan subduction have been unsuccessful. A range of rock types is represented, mainly with I-type affinities, and granodiorite is the most voluminous. In contrast, granitic intrusions south of the Moniaive shear zone in Scotland and also in the north of England have significant S-type characteristics, span the trace of the Iapetus suture and have ages in the range 400-390 Ma, significantly younger than intrusions to the north. We refer to these younger granitic intrusions, along with others of similar character along-strike to the southwest, as the Trans-Suture Suite. We explore the link between the Trans-Suture Suite and recently recognized orogen-wide sinistral transtension in the Early Devonian period. Importantly, the Trans-Suture Suite intrusions are accompanied by an intense suite of lamprophyre dykes, the origin of which is to be sought in extension, decompression and heating of enriched Avalonian sub-continental lithosphere. In some instances the granite intrusions carry clots of lamprophyric origin and the Criffel body is particularly important in being continuously zoned from an I-type with lamprophyric enclaves to an S-type interior. We propose that generation of these lamprophyres during transtension advected heat into the base of the crust to produce the S-type component of the Trans-Suture Suite. Modelling presented shows that generation of voluminous S-type magmas requires the coincidence of several factors: hydrated sub-continental lithospheric mantle preserved during 'soft' collision under the Trans-Suture Suite zone; thermal relaxation to remove any subduction refrigeration; crust composed of juvenile volcanogenic material; and Devonian transtension. Our models suggest that if hydration pre-dated transtension then only small granitic bodies could be produced, unless the zone of lamprophyre generation extends beyond the rift zone. The emplacement of the Trans-Suture Suite intrusions overlapped the Acadian deformation period that succeeded the transtensional episode during which the granite magmas were generated. Keywords: granite, transtension, trans-suture suite, lamprophyre, Acadian.
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- 2008
8. Intrinsic plasticity of cerebellar stellate cells is mediated by NMDA receptor regulation of voltage-gated Na
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Derek Bowie and Ryan P.D. Alexander
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0301 basic medicine ,Cerebellum ,Patch-Clamp Techniques ,Action potential ,Voltage-gated ion channel ,Physiology ,Chemistry ,Sodium ,Action Potentials ,Gating ,Receptors, N-Methyl-D-Aspartate ,03 medical and health sciences ,Electrophysiology ,030104 developmental biology ,0302 clinical medicine ,medicine.anatomical_structure ,nervous system ,Neurotransmitter receptor ,Cerebellar cortex ,medicine ,Animals ,Neuroscience ,030217 neurology & neurosurgery ,Ion channel - Abstract
Key points We show that NMDA receptors (NMDARs) elicit a long-term increase in the firing rates of inhibitory stellate cells of the cerebellum NMDARs induce intrinsic plasticity through a Ca2+ - and CaMKII-dependent pathway that drives shifts in the activation and inactivation properties of voltage-gated Na+ (Nav ) channels An identical Ca2+ - and CaMKII-dependent signalling pathway is triggered during whole-cell recording which lowers the action potential threshold by causing a hyperpolarizing shift in the gating properties of Nav channels. Our findings open the more general possibility that NMDAR-mediated intrinsic plasticity found in other cerebellar neurons may involve similar shifts in Nav channel gating. Abstract Memory storage in the mammalian brain is mediated not only by long-lasting changes in the efficacy of neurotransmitter receptors but also by long-term modifications to the activity of voltage-gated ion channels. Activity-dependent plasticity of voltage-gated ion channels, or intrinsic plasticity, is found throughout the brain in virtually all neuronal types, including principal cells and interneurons. Although intrinsic plasticity has been identified in neurons of the cerebellum, it has yet to be studied in inhibitory cerebellar stellate cells of the molecular layer which regulate activity outflow from the cerebellar cortex by feedforward inhibition onto Purkinje cells. The study of intrinsic plasticity in stellate cells has been particularly challenging as membrane patch breakthrough in electrophysiology experiments unintentionally triggers changes in spontaneous firing rates. Using cell-attached patch recordings to avoid disruption, we show that activation of extrasynaptic N-methyl-d-aspartate receptors (NMDARs) elicits a long-term increase in the firing properties of stellate cells by stimulating a rise in cytosolic Ca2+ and activation of Ca²⁺/calmodulin-dependent protein kinase II (CaMKII). An identical signalling pathway is triggered during whole-cell recording which lowers the action potential threshold by causing a hyperpolarizing shift in the gating properties of voltage-gated sodium (Nav ) channels. Together, our findings identify an unappreciated role of Nav channel-dependent intrinsic plasticity in cerebellar stellate cells which, in concert with non-canonical NMDAR signalling, provides the cerebellum with an unconventional mechanism to fine-tune motor behaviour.
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- 2020
9. Intrinsic plasticity of cerebellar stellate cells is mediated by NMDA receptor regulation of voltage‐gated Na + channels
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Alexander, Ryan P.D., primary and Bowie, Derek, additional
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- 2020
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10. Cerebellar Stellate Cell Excitability Is Coordinated by Shifts in the Gating Behavior of Voltage-Gated Na+ and A-Type K+ Channels
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Derek Bowie, John Mitry, Anmar Khadra, Vasu Sareen, and Ryan P.D. Alexander
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computational modeling ,Male ,Cerebellum ,cerebellum ,Models, Neurological ,Action Potentials ,Neuronal Excitability ,Gating ,Voltage-Gated Sodium Channels ,Inhibitory postsynaptic potential ,Membrane Potentials ,03 medical and health sciences ,0302 clinical medicine ,action potential ,medicine ,Animals ,Ion channel ,030304 developmental biology ,Membrane potential ,Neurons ,0303 health sciences ,Voltage-gated ion channel ,Chemistry ,General Neuroscience ,Sodium channel ,General Medicine ,New Research ,A-type potassium channel ,Mice, Inbred C57BL ,medicine.anatomical_structure ,nervous system ,6.1 ,Potassium Channels, Voltage-Gated ,stellate cell ,Biophysics ,Hepatic stellate cell ,Female ,Ion Channel Gating ,030217 neurology & neurosurgery ,sodium channel - Abstract
Neuronal excitability in the vertebrate brain is governed by the coordinated activity of both ligand- and voltage-gated ion channels. In the cerebellum, spontaneous action potential (AP) firing of inhibitory stellate cells (SCs) is variable, typically operating within the 5- to 30-Hz frequency range. AP frequency is shaped by the activity of somatodendritic A-type K+channels and the inhibitory effect of GABAergic transmission. An added complication, however, is that whole-cell recording from SCs induces a time-dependent and sustained increase in membrane excitability making it difficult to define the full range of firing rates. Here, we show that whole-cell recording in cerebellar SCs of both male and female mice augments firing rates by reducing the membrane potential at which APs are initiated. AP threshold is lowered due to a hyperpolarizing shift in the gating behavior of voltage-gated Na+channels. Whole-cell recording also elicits a hyperpolarizing shift in the gating behavior of A-type K+channels which contributes to increased firing rates. Hodgkin–Huxley modeling and pharmacological experiments reveal that gating shifts in A-type K+channel activity do not impact AP threshold, but rather promote channel inactivation which removes restraint on the upper limit of firing rates. Taken together, our work reveals an unappreciated impact of voltage-gated Na+channels that work in coordination with A-type K+channels to regulate the firing frequency of cerebellar SCs.
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- 2019
11. Nanoscale Mobility of the Apo State and TARP Stoichiometry Dictate the Gating Behavior of Alternatively Spliced AMPA Receptors
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Mohammad Fahim Kadir, Camilo Navarrete, Christian Fuentes, R. Venskutonyte, M. Arsenault, Amanda M Perozzo, E.A. Santander, Y. Yan, John Michael Edwardson, Ryan P.D. Alexander, Derek Bowie, Jette S. Kastrup, Mark R. P. Aurousseau, Karla Frydenvang, Nelson P. Barrera, and George B. Dawe
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0301 basic medicine ,Patch-Clamp Techniques ,Allosteric regulation ,Gating ,AMPA receptor ,Crystallography, X-Ray ,Microscopy, Atomic Force ,03 medical and health sciences ,Mice ,Purkinje Cells ,0302 clinical medicine ,Allosteric Regulation ,Protein Domains ,Cerebellum ,Animals ,Humans ,Protein Isoforms ,Receptors, AMPA ,Receptor ,Protein Structure, Quaternary ,Ion channel ,Chemistry ,General Neuroscience ,Cryoelectron Microscopy ,Glutamate receptor ,Membrane Proteins ,Protein Structure, Tertiary ,Alternative Splicing ,030104 developmental biology ,HEK293 Cells ,Biophysics ,Ionotropic glutamate receptor ,Ion Channel Gating ,030217 neurology & neurosurgery ,Allosteric Site ,Ionotropic effect - Abstract
Summary Neurotransmitter-gated ion channels are allosteric proteins that switch on and off in response to agonist binding. Most studies have focused on the agonist-bound, activated channel while assigning a lesser role to the apo or resting state. Here, we show that nanoscale mobility of resting α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type ionotropic glutamate receptors (AMPA receptors) predetermines responsiveness to neurotransmitter, allosteric anions and TARP auxiliary subunits. Mobility at rest is regulated by alternative splicing of the flip/flop cassette of the ligand-binding domain, which controls motions in the distant AMPA receptor N-terminal domain (NTD). Flip variants promote moderate NTD movement, which establishes slower channel desensitization and robust regulation by anions and auxiliary subunits. In contrast, greater NTD mobility imparted by the flop cassette acts as a master switch to override allosteric regulation. In AMPA receptor heteromers, TARP stoichiometry further modifies these actions of the flip/flop cassette generating two functionally distinct classes of partially and fully TARPed receptors typical of cerebellar stellate and Purkinje cells.
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- 2018
12. Continental eclogites and the Wilson Cycle
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Ryan, P.D. and Dewey, J.F.
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Continental margins -- Research ,Oceanographic research -- Analysis ,Earth sciences - Abstract
The Wilson Cycle, the repeated opening and closing of oceans, commonly along roughly the same lines, is here attributed to the presence of eclogite-facies roots of partially collapsed orogens. We present a finite-element thermal model that suggests that such roots will weaken the orogenic lithosphere relative to that of the adjacent foreland for hundreds of millions of years and make it a preferred site for later rifting. Keywords: Wilson Cycle, continental margin, orogenic belts, eclogite.
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- 1997
13. Terrane geochemistry contrasts across the Iapetus Suture in Ireland
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Ryan, P.D., Stillman, C.J., Allen, M., and Pow, S.
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Ireland -- Natural history ,Geochemistry -- Analysis ,Shale -- Analysis ,Earth sciences - Abstract
In the Irish Caledonides, volcanism has been significant in terrane identification and in reconstructions of the Appalachian/Caledonian orogen. Crucial to these reconstructions is the recognition of ocean margins using obducted ocean floor relics (ophiolites) and supra-subduction zone volcanic assemblages. The voleanic rocks provide much evidence for the affinity of a terrane, however, by analogy with present day examples, the ocean floor sediments may provide the best way of tracing both ocean-floor magmatic activity, and continental source areas. This investigation shows that the Irish Lower Palaeozoic volcanogenic terranes can be discriminated in terms of their shale geochemistry, which also gives information on their provenance and environment of deposition. South Mayo shales are dominated by volcaniclastic material derived both from both an arc and from an ophiolitic source. The Northern and Central belts of the Central Teffane show very similar lithogeochemistries, apparently derived in part from intermediate to sihcic volcanic complexes. The Ordovician-Silurian inliers that straddle the Suture Zone, here termed the Southern Domain, show a chemistry close to that of the Leinster Terrane, which, coupled with a greater degree of sea-floor weathering, suggests a terrane with sediment of both volcanic and continental provenance being deposited in deeper water further from land. Across the suture the Leinster Terrane shows a mature chemistry which clearly suggests a continental provenance, together with a volcanogenic input from supra-subduction volcanism. This maturity is probably due to slower rates of sedimentation with longer residence times for volcanic detritus, plus the existence of a deeply weathered continental basement.
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- 1995
14. The Antrim-Galway Line: a resolution of the Highland Border fault enigma of the Caledonides of Britain and Ireland
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Ryan, P.D., Soper, N.J., Snyder, D.B., England, R.W., and Hutton, D.H.W.
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Scotland -- Natural history ,Ireland -- Natural history ,Earth sciences - Abstract
A geological study of the Highland Border fault of Caledonides of Britain and Ireland shows significant lineament from Antrim to Galway Bay, known as Antrim-Galway Line. It is probable that Antrim-Galway Line is a continuation of the Highland Border fault of Scotland. The study could help in solving problems related to correlation of Silurian Highland Border fault zone of Scotland with Ordovician Fair Head-Clew Bay Line of Ireland.
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- 1995
15. Bursting in cerebellar stellate cells induced by pharmacological agents: Non-sequential spike adding
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Anmar Khadra, Saeed Farjami, Derek Bowie, and Ryan P.D. Alexander
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Patch-Clamp Techniques ,Physiology ,Action Potentials ,Social Sciences ,Systems Science ,Biochemistry ,01 natural sciences ,010305 fluids & plasmas ,Synapse ,Mice ,Purkinje Cells ,0302 clinical medicine ,Animal Cells ,Cerebellum ,Active phase ,High doses ,Psychology ,4-Aminopyridine ,Biology (General) ,Bifurcation Theory ,Neurons ,Membrane potential ,Ecology ,Chemistry ,Eukaryota ,Olives ,Plants ,Calcium Channel Blockers ,3. Good health ,Electrophysiology ,Bifurcation analysis ,Computational Theory and Mathematics ,Modeling and Simulation ,Physical Sciences ,Cellular Types ,Research Article ,Cadmium ,Computer and Information Sciences ,QH301-705.5 ,Neurophysiology ,Bioenergetics ,Inhibitory postsynaptic potential ,Membrane Potential ,Models, Biological ,Fruits ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Bursting ,Interneurons ,Ionic Current ,0103 physical sciences ,Potassium Channel Blockers ,Genetics ,Animals ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics ,Behavior ,Dose-Response Relationship, Drug ,Organisms ,Biology and Life Sciences ,Cell Biology ,Mice, Inbred C57BL ,Cellular Neuroscience ,Hepatic stellate cell ,Biophysics ,Mathematics ,030217 neurology & neurosurgery ,Neuroscience - Abstract
Cerebellar stellate cells (CSCs) are spontaneously active, tonically firing (5-30 Hz), inhibitory interneurons that synapse onto Purkinje cells. We previously analyzed the excitability properties of CSCs, focusing on four key features: type I excitability, non-monotonic first-spike latency, switching in responsiveness and runup (i.e., temporal increase in excitability during whole-cell configuration). In this study, we extend this analysis by using whole-cell configuration to show that these neurons can also burst when treated with certain pharmacological agents separately or jointly. Indeed, treatment with 4-Aminopyridine (4-AP), a partial blocker of delayed rectifier and A-type K+ channels, at low doses induces a bursting profile in CSCs significantly different than that produced at high doses or when it is applied at low doses but with cadmium (Cd2+), a blocker of high voltage-activated (HVA) Ca2+ channels. By expanding a previously revised Hodgkin–Huxley type model, through the inclusion of Ca2+-activated K+ (K(Ca)) and HVA currents, we explain how these bursts are generated and what their underlying dynamics are. Specifically, we demonstrate that the expanded model preserves the four excitability features of CSCs, as well as captures their bursting patterns induced by 4-AP and Cd2+. Model investigation reveals that 4-AP is potentiating HVA, inducing square-wave bursting at low doses and pseudo-plateau bursting at high doses, whereas Cd2+ is potentiating K(Ca), inducing pseudo-plateau bursting when applied in combination with low doses of 4-AP. Using bifurcation analysis, we show that spike adding in square-wave bursts is non-sequential when gradually changing HVA and K(Ca) maximum conductances, delayed Hopf is responsible for generating the plateau segment within the active phase of pseudo-plateau bursts, and bursting can become “chaotic” when HVA and K(Ca) maximum conductances are made low and high, respectively. These results highlight the secondary effects of the drugs applied and suggest that CSCs have all the ingredients needed for bursting., Author summary Excitable cells, including neurons, fire action potentials (APs) in their membrane voltage that allow them to communicate with each other and to serve certain physiological purposes. They do so either tonically by firing APs periodically, or episodically by repeatedly firing clusters of APs (called bursts) separated by quiescent periods. Each one of those firing patterns can be neuron-specific and dependent on synaptic inputs and/or their physiological environment. Cerebellar stellate cells (CSCs) that synapse onto Purkinje cells, the sole output of the cerebellum responsible for motor control, are spontaneously active inhibitory interneurons that fire APs tonically. We previously studied the excitability properties of these neurons and showed that they possess several important key features, including type I excitability, runup, non-monotonic first spike latency and switching in responsiveness. In this study, we show that CSCs can also exhibit two modes of burst firing, called square-wave and pseudo-plateau, when treated with certain pharmacological agents. Using bifurcation theory, we demonstrate that spike adding in the square-wave burst is non-sequential, changing by several spikes when certain conductances are altered gradually. This study thus sheds lights onto the overall effects of the pharmacological agents and highlights the ability of CSCs to burst in certain biological conditions.
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- 2020
16. Geochemical evolution of an Ordovician island arc, South Mayo, Ireland
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Clift, P.D. and Ryan, P.D.
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Ireland -- Natural history ,Island arcs -- Natural history ,Volcanism -- Research ,Geology, Stratigraphic -- Research ,Petrofabric analysis -- Research ,Geochemistry -- Research ,Earth sciences - Abstract
Early Ordovician volcanic rocks exposed in the South Mayo region of western Ireland document the history of a volcanic arc complex, produced following the initiation of south-dipping subduction within the Iapetus Ocean in the Late Cambrian or Early Ordovician. Lavas of the Lough Nafooey Group (Tremadoc - Arenig) show an eruption history marked by an initial period of tholeiitic basaltic volcanism, followed by a shift to increasing silica compositions of calc-alkaline affinity. Subsequent volcanism of the Tourmakeady Group (Arenig) shows a mixture of rhyolitic and andesitic compositions, which are in turn succeeded by tuffs of the Rosroe and Mweelrea Formations of the Murrisk Group (Llanvirn). These are also rhyolitic and andesitic but are generally more siliceous. The overall increase in silica contents may reflect increasing fractional crystallization due to crustal thickening. Trace element studies of the basaltic members of the Lough Nafooey Group show a strong subduction zone influence. While absolute levels of immobile trace and rare earth elements decrease upsection, relative depletion of the most incompatible elements decreases over the same time period. These trends suggest decreasing degrees of partial melting of a progressively more depleted source mantle upsection. The basaltic Bohaun Volcanic Formation (Tremadoc - Arenig ?) shows greater depletion in its incompatible trace elements than the Lough Nafooey Group, so indicating a more depleted mantle source. Comparison with modern arc systems suggests that the Bohaun Volcanic Formation was probably generated shortly after the initiation of subduction and was erupted in a more trenchward position than the Lough Nafooey Group (i.e. in the forearc). This confirms a south-dipping polarity to the subduction zone, and suggests an age of initiation during the Late Cambrian or earliest Ordovician.
- Published
- 1994
17. Oroclinal bending in the Caledonides of western Ireland
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Smethurst, M.A., MacNiocaill, C., and Ryan, P.D.
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Ireland -- Natural history ,Geology, Structural -- Research ,Paleomagnetism -- Research ,Rock deformation -- Research ,Earth sciences - Abstract
New palaeomagnetic data from the Caledonides of western Ireland indicate that the Silurian rocks of South Mayo underwent oroclinal bending, following folding, in Siluro-Devonian time. Bending was accommodated on faults cutting the Silurian sequence, and was driven by strike slip motion across the Antrim - Galway Line, a recently recognized major curvilinear lineament. We propose that the Silurian rocks in the east of the region suffered up to 30 degrees clockwise rotation, increasing towards the west to approximately 70 degrees. This newly inferred differential rotation of the Silurian rocks, about a sub-vertical axis, implies that the underlying Dalradian rocks of the Connemara Massif to the south must also have undergone clockwise rotation in late Silurian/early Devonian time. This is consistent with published palaeomagnetic data from the Connemara Gabbro and accounts for the swing in strike of the Caledonian orogen in this part of western Ireland. From this we deduce that the swing in strike of the Caledonian rocks elsewhere on the west coast of Ireland might have a similar explanation.
- Published
- 1994
18. Deep structure of southern Ireland: anew geological synthesis using BIRPS deep reflection profiling
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Ford, M., Klemperer, S.L., and Ryan, P.D.
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Ireland -- Natural history ,Geology, Stratigraphic -- Research ,Seismic reflection method -- Usage ,Earth sciences - Abstract
An analysis describing the geological historical structure of southern Ireland is presented. The analysis combines BIRPS deep seismic reflection data with other geological and geophysical data to examine the tectonic character of Ireland's crust. It is shown that the reflector called the 'Variscan Front' only draws a map line across the British Isles but has no consistent tectonic character.
- Published
- 1992
19. The Iapetus suture zone in England, Scotland and eastern Ireland: a reconciliation of geological and deep seismic data
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Soper, N.J., England, R.W., Snyder, D.B., and Ryan, P.D.
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North Sea -- Natural history ,Paleogeography -- Paleozoic ,Plate tectonics -- Research ,Gondwana (Geology) -- Research ,Laurasia (Geology) -- Research ,Earth sciences - Abstract
Iapetus suture zone crustal structure is examined via deep seismic profiles of the Irish and North seas. Interpretation of such data is often problematic in that the suture reflectors chosen project to the basement well top, south ofthe Solway Line. A revised method is proposed, involving the identification of the leading end of imbricated Avalonian crust as a common reflectivity boundary. This makes invoking northward suture backthrusting unnecessary.
- Published
- 1992
20. Modeling excitability in cerebellar stellate cells: Temporal changes in threshold, latency and frequency of firing
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John Mitry, Derek Bowie, Anmar Khadra, Ryan P.D. Alexander, and Saeed Farjami
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Physics ,0303 health sciences ,Numerical Analysis ,Applied Mathematics ,Saddle-node bifurcation ,Inhibitory postsynaptic potential ,03 medical and health sciences ,0302 clinical medicine ,Modeling and Simulation ,Cerebellar cortex ,Limit cycle ,Hepatic stellate cell ,Excitatory postsynaptic potential ,Latency (engineering) ,Neuroscience ,030217 neurology & neurosurgery ,Bifurcation ,030304 developmental biology - Abstract
Cerebellar stellate cells are inhibitory molecular interneurons that regulate the firing properties of Purkinje cells, the sole output of cerebellar cortex. Recent evidence suggests that these cells exhibit temporal increase in excitability during whole-cell patch-clamp configuration in a phenomenon termed runup. They also exhibit a non-monotonic first-spike latency profile as a function of the holding potential in response to a fixed step-current. In this study, we use modeling approaches to unravel the dynamics of runup and categorize the firing behavior of cerebellar stellate cells as either type I or type II oscillators. We then extend this analysis to investigate how the non-monotonic latency profile manifests itself during runup. We employ a previously developed, but revised, Hodgkin–Huxley type model to show that stellate cells are indeed type I oscillators possessing a saddle node on an invariant cycle (SNIC) bifurcation. The SNIC in the model acts as a “threshold” for tonic firing and produces a slow region in the phase space called the ghost of the SNIC. The model reveals that (i) the SNIC gets left-shifted during runup with respect to I app = I test in the current-step protocol, and (ii) both the distance from the stable limit cycle along with the slow region produce the non-monotonic latency profile as a function of holding potential. Using the model, we elucidate how latency can be made arbitrarily large for a specific range of holding potentials close to the SNIC during pre-runup (post-runup). We also demonstrate that the model can produce transient single spikes in response to step-currents entirely below ISNIC, and that a pair of dynamic inhibitory and excitatory post-synaptic inputs can robustly evoke action potentials, provided that the magnitude of the inhibition is either low or high but not intermediate. Our results show that the topology of the SNIC is the key to explaining such behaviors.
- Published
- 2020
21. Nanoscale Mobility of the Apo State and TARP Stoichiometry Dictate the Gating Behavior of Alternatively Spliced AMPA Receptors
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Dawe, G. Brent, primary, Kadir, Md. Fahim, additional, Venskutonytė, Raminta, additional, Perozzo, Amanda M., additional, Yan, Yuhao, additional, Alexander, Ryan P.D., additional, Navarrete, Camilo, additional, Santander, Eduardo A., additional, Arsenault, Marika, additional, Fuentes, Christian, additional, Aurousseau, Mark R.P., additional, Frydenvang, Karla, additional, Barrera, Nelson P., additional, Kastrup, Jette S., additional, Edwardson, J. Michael, additional, and Bowie, Derek, additional
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- 2019
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22. Cerebellar Stellate Cell Excitability Is Coordinated by Shifts in the Gating Behavior of Voltage-Gated Na+ and A-Type K+ Channels
- Author
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Alexander, Ryan P.D., primary, Mitry, John, additional, Sareen, Vasu, additional, Khadra, Anmar, additional, and Bowie, Derek, additional
- Published
- 2019
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23. Intrinsic plasticity of cerebellar stellate cells is mediated by NMDA receptor regulation of voltage‐gated Na+ channels.
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Alexander, Ryan P.D. and Bowie, Derek
- Subjects
- *
VOLTAGE-gated ion channels , *METHYL aspartate receptors , *PURKINJE cells , *ENTORHINAL cortex , *CEREBELLAR cortex , *NEUROTRANSMITTER receptors , *HYPERPOLARIZATION (Cytology) , *PROTEIN kinases - Abstract
Key points: We show that NMDA receptors (NMDARs) elicit a long‐term increase in the firing rates of inhibitory stellate cells of the cerebellumNMDARs induce intrinsic plasticity through a Ca2+‐ and CaMKII‐dependent pathway that drives shifts in the activation and inactivation properties of voltage‐gated Na+ (Nav) channelsAn identical Ca2+‐ and CaMKII‐dependent signalling pathway is triggered during whole‐cell recording which lowers the action potential threshold by causing a hyperpolarizing shift in the gating properties of Nav channels.Our findings open the more general possibility that NMDAR‐mediated intrinsic plasticity found in other cerebellar neurons may involve similar shifts in Nav channel gating. Memory storage in the mammalian brain is mediated not only by long‐lasting changes in the efficacy of neurotransmitter receptors but also by long‐term modifications to the activity of voltage‐gated ion channels. Activity‐dependent plasticity of voltage‐gated ion channels, or intrinsic plasticity, is found throughout the brain in virtually all neuronal types, including principal cells and interneurons. Although intrinsic plasticity has been identified in neurons of the cerebellum, it has yet to be studied in inhibitory cerebellar stellate cells of the molecular layer which regulate activity outflow from the cerebellar cortex by feedforward inhibition onto Purkinje cells. The study of intrinsic plasticity in stellate cells has been particularly challenging as membrane patch breakthrough in electrophysiology experiments unintentionally triggers changes in spontaneous firing rates. Using cell‐attached patch recordings to avoid disruption, we show that activation of extrasynaptic N‐methyl‐d‐aspartate receptors (NMDARs) elicits a long‐term increase in the firing properties of stellate cells by stimulating a rise in cytosolic Ca2+ and activation of Ca²⁺/calmodulin‐dependent protein kinase II (CaMKII). An identical signalling pathway is triggered during whole‐cell recording which lowers the action potential threshold by causing a hyperpolarizing shift in the gating properties of voltage‐gated sodium (Nav) channels. Together, our findings identify an unappreciated role of Nav channel‐dependent intrinsic plasticity in cerebellar stellate cells which, in concert with non‐canonical NMDAR signalling, provides the cerebellum with an unconventional mechanism to fine‐tune motor behaviour. Key points: We show that NMDA receptors (NMDARs) elicit a long‐term increase in the firing rates of inhibitory stellate cells of the cerebellumNMDARs induce intrinsic plasticity through a Ca2+‐ and CaMKII‐dependent pathway that drives shifts in the activation and inactivation properties of voltage‐gated Na+ (Nav) channelsAn identical Ca2+‐ and CaMKII‐dependent signalling pathway is triggered during whole‐cell recording which lowers the action potential threshold by causing a hyperpolarizing shift in the gating properties of Nav channels.Our findings open the more general possibility that NMDAR‐mediated intrinsic plasticity found in other cerebellar neurons may involve similar shifts in Nav channel gating. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
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24. STIM1 Controls Neuronal Ca2+ Signaling, mGluR1-Dependent Synaptic Transmission, and Cerebellar Motor Behavior
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Thomas Misgeld, Ryan P.D. Alexander, Yoshihiro Baba, Charlotta Rühlmann, Arthur Konnerth, Anna Ansel, Helmuth Adelsberger, Tomohiro Kurosaki, Jana Hartmann, Rosa Maria Karl, Monika S. Brill, and Kenji Sakimura
- Subjects
inorganic chemicals ,Cerebellum ,Neuroscience(all) ,General Neuroscience ,Glutamate receptor ,Biology ,Neurotransmission ,Cell biology ,Metabotropic receptor ,medicine.anatomical_structure ,Metabotropic glutamate receptor ,medicine ,Excitatory postsynaptic potential ,Metabotropic glutamate receptor 1 ,Neuroscience ,Calcium signaling - Abstract
In central mammalian neurons, activation of metabotropic glutamate receptor type1 (mGluR1) evokes a complex synaptic response consisting of IP3 receptor-dependent Ca(2+) release from internal Ca(2+) stores and a slow depolarizing potential involving TRPC3 channels. It is largely unclear how mGluR1 is linked to its downstream effectors. Here, we explored the role of stromal interaction molecule 1 (STIM1) in regulating neuronal Ca(2+) signaling and mGluR1-dependent synaptic transmission. By analyzing mouse cerebellar Purkinje neurons, we demonstrate that STIM1 is an essential regulator of the Ca(2+) level in neuronal endoplasmic reticulum Ca(2+) stores. Both mGluR1-dependent synaptic potentials and IP3 receptor-dependent Ca(2+) signals are strongly attenuated in the absence of STIM1. Furthermore, the Purkinje neuron-specific deletion of Stim1 causes impairments in cerebellar motor behavior. Together, our results demonstrate that in the mammalian nervous system STIM1 is a key regulator of intracellular Ca(2+) signaling, metabotropic glutamate receptor-dependent synaptic transmission, and motor coordination.
- Published
- 2014
25. Correlations between limbic white matter and cognitive function in temporal lobe epilepsy, preliminary findings
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Luis Concha, Donald W. Gross, Ryan P.D. Alexander, Thomas Snyder, and Christian Beaulieu
- Subjects
Aging ,Diffusion tensor imaging (DTI) ,mesial temporal sclerosis ,Cognitive Neuroscience ,behavioral disciplines and activities ,Temporal lobe ,lcsh:RC321-571 ,Limbic system ,Temporal Lobe Epilepsy ,Fractional anisotropy ,medicine ,Cingulum (brain) ,processing speed ,Neuropsychological assessment ,lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry ,Original Research ,medicine.diagnostic_test ,temporal-lobe epilepsy ,Fornix ,Neuropsychology ,diffusion tensor imaging ,neuropsychological assessment ,medicine.anatomical_structure ,nervous system ,Psychology ,Neuroscience ,psychological phenomena and processes ,Diffusion MRI - Abstract
The limbic system is presumed to have a central role in cognitive performance, in particular memory. The purpose of this study was to investigate the relationship between limbic white matter microstructure and neuropsychological function in temporal lobe epilepsy (TLE) patients using diffusion tensor imaging (DTI). Twenty-one adult TLE patients, including seven non-lesional (nlTLE) and fourteen with unilateral mesial temporal sclerosis (uTLE), were studied with both DTI and hippocampal T2 relaxometry. Correlations were performed between fractional anisotropy (FA) of the bilateral fornix and cingulum, hippocampal T2, neuropsychological tests. Positive correlations were observed in the whole group for the left fornix and Processing Speed Index. In contrast, memory tests did not show significant correlations with DTI findings. Subgroup analysis demonstrated an association between the left fornix and Processing Speed in nlTLE but not uTLE. No correlations were observed between hippocampal T2 and test scores in either the TLE group as a whole or after subgroup analysis. Our findings suggest that integrity of the left fornix specifically is an important anatomical correlate of cognitive function in TLE patients, in particular patients with nlTLE.
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- 2014
26. Isolated febrile seizures are not associated with structural abnormalities of the limbic system
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Gong, Gaolang, Alexander, Ryan P.D., Shi, Feng, Beaulieu, Christian, and Gross, Donald W.
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- 2012
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27. Isolated febrile seizures are not associated with structural abnormalities of the limbic system
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Gaolang Gong, Donald W. Gross, Christian Beaulieu, Feng Shi, and Ryan P.D. Alexander
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Adult ,Male ,Pathology ,medicine.medical_specialty ,Adolescent ,Hippocampus ,behavioral disciplines and activities ,Functional Laterality ,Seizures, Febrile ,Temporal lobe ,Epilepsy ,Young Adult ,Limbic system ,Fractional anisotropy ,medicine ,Image Processing, Computer-Assisted ,Limbic System ,Cingulum (brain) ,Humans ,Fornix ,medicine.disease ,Magnetic Resonance Imaging ,nervous system diseases ,medicine.anatomical_structure ,nervous system ,Neurology ,Epilepsy, Temporal Lobe ,Female ,Neurology (clinical) ,Psychology ,Neuroscience ,psychological phenomena and processes ,Diffusion MRI - Abstract
Summary The nature of the relationship between childhood febrile seizures (CFSs) and temporal lobe epilepsy (TLE) remains unknown. The purpose of this study was to perform a comprehensive analysis of measures of structural changes of the hippocampus and limbic white matter to determine whether structural abnormalities previously demonstrated in TLE were present in adults with isolated CFS. Twenty-three adults with past CFS but no history of nonfebrile seizures and 21 controls underwent research MRI for measurement of volume, T2 and mean diffusivity of the hippocampus and fractional anisotropy of the fornix and cingulum. No significant group differences were found in any of the measured parameters. These findings suggest that structural abnormalities of the hippocampus and limbic white matter that have been demonstrated in TLE are not associated with isolated CFS.
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- 2012
28. STIM1 Controls Neuronal Ca2+ Signaling, mGluR1-Dependent Synaptic Transmission, and Cerebellar Motor Behavior
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Hartmann, Jana, primary, Karl, Rosa M., additional, Alexander, Ryan P.D., additional, Adelsberger, Helmuth, additional, Brill, Monika S., additional, Rühlmann, Charlotta, additional, Ansel, Anna, additional, Sakimura, Kenji, additional, Baba, Yoshihiro, additional, Kurosaki, Tomohiro, additional, Misgeld, Thomas, additional, and Konnerth, Arthur, additional
- Published
- 2014
- Full Text
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29. Arc-continent collision: The making of an orogen
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Brown, Dennis, Ryan, P.D., Afonso, Juan Carlos, Boutelier, D., Burg, J.P., Byrne, T., Calvert, A., Cook, F., Debari, S., Dewey, J.F., Gerya, Taras V., Harris, R., Herrington, R., Konstantinovskaya, E., Reston, Timothy, Zagorevski, A., Brown, Dennis, Ryan, P.D., Afonso, Juan Carlos, Boutelier, D., Burg, J.P., Byrne, T., Calvert, A., Cook, F., Debari, S., Dewey, J.F., Gerya, Taras V., Harris, R., Herrington, R., Konstantinovskaya, E., Reston, Timothy, and Zagorevski, A.
- Published
- 2011
30. HTTP://folk.uio.no/ohammer/past
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Hammer, Ø., Harper, D.A.T., Ryan, P.D., Hammer, Ø., Harper, D.A.T., and Ryan, P.D.
- Published
- 2001
31. Paleontological Statistics Software: Package for Education and Data Analysis.
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Hammer, Ø., Harper, D.A.T., Ryan, P.D., Hammer, Ø., Harper, D.A.T., and Ryan, P.D.
- Published
- 2001
32. Seriation: A new approach.
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Ryan, P.D., Ryan, M., Harper, D.A.T., Ryan, P.D., Ryan, M., and Harper, D.A.T.
- Published
- 1999
33. Producing subjectivities, taking risks: New directions for teaching women?s poetry in South Africa
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Ryan, P.D., primary
- Published
- 2002
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34. Rifted Continent-Ocean boundaries
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Ryan, P.D., primary
- Published
- 1997
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35. Coordinate Systems and Map Projections
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Ryan, P.D., primary
- Published
- 1993
- Full Text
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36. The deep geology and geophysics of Ireland and its continental margin
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BROCK, A., primary, RYAN, P.D., additional, and SHANNON, P. M., additional
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- 1991
- Full Text
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37. Age of the Grampian orogeny in Scotland and Ireland.
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Soper, N.J. and Ryan, P.D.
- Subjects
- *
OROGENY , *PROTEROZOIC stratigraphic geology , *GEOLOGICAL time scales - Abstract
Details a study which resolved the conflict between stratigraphical and geochronological evidence for the age of the Grampian orogeny in Scotland and Ireland. Biostratigraphical and geochronological evidences; Principal evidence for an end-Proterozoic Grampian orogeny; Summary.
- Published
- 1999
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38. Deep structure of southern Ireland: a new geological synthesis using BIRPS deep reflection profiling
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Ford, M., Klemperer, S.L., and Ryan, P.D.
- Abstract
The BIRPS deep seismic reflection data of WIRE (West of IREland) 1/1B from Galway Bay to the Celtic Sea are integrated with geological and other geophysical data to produce a synthesis of the fundamental tectonic character of the crust in and around southern Ireland. The Iapetus Suture forms a zone of north-dipping reflectors which projects up between the Shannon estuary and the Dingle peninsula and is overlain by ɛ late Caledonian reflector with a shallow, south dip. Across the Iapetus Suture zone the crust thickens southward and the lower crust becomes less reflective. It is proposed that the Lower Palaeozoic volcano-sedimentary rocks which form the Leinster massif extend southwestward beneath the Variscan province and at least 30 km offshore to the WIRE lines. We argue that the weak south-dipping reflectors in the upper and middle crust south of the Iapetus Suture represent an early-Caledonian fault system linked to a mid-crustal detachment which formed during the south-dipping subduction event recorded onshore by the Ordovician volcano-sedimentary successions. These faults were selectively reactivated causing the predominant ENE trend of younger regional tectonic features in and around southern Ireland. The three onshore Upper Palaeozoic basins close east of the WIRE lines.We point out that the 'Variscan Front' is only a map line across the British Isles with no consistent tectonic character. Thus the south-dipping reflector below the north margin of the North Celtic Sea Basin on SWAT 4, generally referred to as the 'Variscan Front', is correlated by us with the northern boundary of the Rosslare complex, thus making it the northern tectonic boundary of the Caledonian basement block known as the Rosslare-Monian Terrane. Furthermore the north-dipping South Irish Sea Lineament on WINCH 4 can be correlated with the Menai Straits Lineament and could thus be the southern boundary of this terrane. The south-dipping reflector on SWAT 2, also previously called the 'Variscan Front' is correlated with the Johnston-Benton fault system in southwest Wales.
- Published
- 1992
39. Discussion towards a statistical system for palaeontologist, Journal, Vol. 147, 1990, pp. 935-948
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Eager, R.M.C., Harper, D.A.T., and Ryan, P.D.
- Published
- 1991
40. A geological and tectonic cross-section of the Caledonides of western Ireland
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Ryan, P.D. and dewey, J.F.
- Abstract
Geological and geophysical criteria allow division of the Caledonides of western Ireland into four principal zones. Zone 1, in the north, contains Grenvillian basement with late Proterozoic supra-crustals. Zone 2 contains the Westport Complex, the Deer Park Complex and the South Mayo Trough. Connemara and the Delany Dome Formation occupy Zone 3. Zone 4 contains the South Connemara Group and mid- to late-Ordovician and Silurian sediments and volcanic rocks. The various tectonic models proposed for these zones are discussed and a 'minimum' tectonic model is presented, which involves early Ordovician collision of the northern part of Zone 2 with the Laurentian margin (Zone 1) followed by subduction flip (northern part of Zone 4). The site of early collision between Zones 1 and 2 subsequently underwent orogenic collapse and strike-slip dismemberment leading to the sinistral transpressive emplacement of Zone 3. Assemblages in Zone 4 were accreted to the now south-facing arc. Northwards stress transfer consequent on suturing deformed the thinned crust and overlying Silurian sequences in Zones 2 and 3.
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- 1991
41. A deep seismic reflection transect across the Irish Caledonides
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Klemperer, S.L., Ryan, P.D., and Snyder, D.B.
- Abstract
New reflection profiles recorded to 18 s (c. 60 km) along a 600 km north-south transect West of IREland (WIRE lines) provide a cross-section of the Irish Caledonides from Lewisian basement in the north to the Variscan fold-and-thrust belt in the south, and constrain the offshore extrapolations of major Caledonide structures.We interpret the profiles as showing the Great Glen fault and associated, NE-trending strike-slip faults as near-vertical structures which cut the whole crust and the uppermost mantle. Beneath the surface trace of the Fair Head-Clew Bay line we image a north-dipping zone which soles into horizontal layers just above the reflection Moho. The north-dipping zone separates south-dipping reflections above and to the north from north-dipping reflections below and to the south. From the Fair Head-Clew Bay line as far south as the Iapetus suture the lower crust contains north-dipping packages of reflectors possibly related to Acadian accretionary underplating. The Iapetus suture zone can be identified as a zone, more than 50 km wide, dipping north at 30° from 5 km depth offshore Dingle peninsula to sole into the Moho at c. 30 km depth west of the Shannon Estuary. In the upper crust the shallow part of the Iapetus suture zone appears to be transported to the north by late Caledonian retrocharriage or by Variscan thrusting. The Iapetus suture does not penetrate through the present-day reflection Moho, but there are scattered reflectors in the mantle not continuous with crustal reflectors, perhaps relics of a subducted slab.We recognize 'lower-crustal' reflectivity and the reflection Moho along almost all the WIRE profiles. Regionally the travel-time to the reflection Moho varies from 9 s (c. 28 km?) offshore Donegal (northwest of Ireland) to 12 s (c. 35 km?) offshore Kerry and Cork (southwest of Ireland). Apparent Moho offsets (rapid lateral changes in the travel-time to the reflection Moho) north of Donegal and north of Mayo are probably due to the Great Glen fault and associated faults. The 'lower-crustal' reflectivity varies considerably in thickness and prevalent dip direction along the WIRE profiles. In Donegal Bay this reflectivity is observed at depths less than 5 km (c. 1.5 s) whereas west of Kerry prominent reflectivity is only observed beneath 6 s (c. 17 km). Though the age of crustal reflectors cannot in general be determined, beneath central Ireland from Donegal to Dingle the lower-crustal reflectors mimic in dip direction the structural vergence of the exposed Dalradian and early Palaeozoic rocks, so that the lower-crustal reflectivity patterns, and probably much of the crust, must be Caledonian in age.
- Published
- 1991
42. Towards a statistical system for palaeontologists
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Harper, D.A.T. and Ryan, P.D.
- Abstract
Since the pioneer studies of Trueman and others in the 1920s, some palaeontologists have used a considerable variety of statistical techniques to describe and analyse individuals and associations of fossil taxa. The increasing sophistication of the algorithms used partly reflects advancing technology from long-hand calculations to computer-based analyses. A progression from univariate graphical and statistical techniques through bivariate analysis to the more sophisticated multivariate analyses can be illustrated by reference to a series of classic case histories on a wide variety of fossil organisms. Nevertheless, despite the necessity for the accurate description of fossils and fossil assemblages and a framework within which to test hypotheses, statistical analysis in palaeontology is far from routine. Access to powerful microcomputers is now widespread amongst palaeontologists but there is a shortage of specialist software packages designed to meet their needs. The PALSTAT package is one of a number of attempts, using the many advantages of the microcomputer, to provide a centralized system of routine graphical and statistical techniques within an investigative framework. The strategy is illustrated with two case histories.
- Published
- 1990
43. The stratigraphy and petrochemistry of the Lough Nafooey Group (Tremadocian), western Ireland
- Author
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Ryan, P.D., Floyd, P.A., and Archer, J.B.
- Abstract
The Lough Nafooey Group is divided into 4 formations. The lowermost Bencorragh Formation consists of spilitic pillowed tholeiites, passing up into the blocky andesite flows, breccias, cherts and basic pillow lavas of the Finny Formation. This is overlain by the Knock Kilbride Formation comprised of spilitized calc-alkali basic to intermediate lavas, often pillowed, that are interbedded with breccias and graptolitic shales. Proximal turbidites containing rhyolite, granite and spilite clasts represent the highest Derry Bay Formation. New palaeontological evidence shows the Knock Kilbride Formation to be of upper Tremadoc (Lancefield 3) age. Petrological and structural studies show that the Lough Nafooey Group was folded and subjected to burial metamorphism prior to the onset of upper Llandovery sedimentation. Assemblages typical of the zeolite, pumpellyite and greenschist facies are recorded. Geochemical studies indicate a similar tectonic setting for the two main phases of eruption of basic lava (Bencorragh and Knock Kilbride formations) and it is suggested that these represent the early development of a Tremadocian island arc possibly related to the Grampian orogeny.
- Published
- 1980
44. The Tuskar Group of southeastern Ireland: its geochemistry and depositional provenance
- Author
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Max, M.D., primary and Ryan, P.D., additional
- Published
- 1986
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45. STIM1 Controls Neuronal Ca2+ Signaling, mGluR1-Dependent Synaptic Transmission, and Cerebellar Motor Behavior.
- Author
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Hartmann, Jana, Karl, Rosa?M., Alexander, Ryan?P.D., Adelsberger, Helmuth, Brill, Monika?S., Rühlmann, Charlotta, Ansel, Anna, Sakimura, Kenji, Baba, Yoshihiro, Kurosaki, Tomohiro, Misgeld, Thomas, and Konnerth, Arthur
- Subjects
- *
CELLULAR signal transduction , *REGULATION of neural transmission , *GLUTAMATE receptors , *MOTOR neurons , *LABORATORY mice , *PHYSIOLOGICAL effects of calcium , *DEPOLARIZATION (Cytology) - Abstract
Summary: In central mammalian neurons, activation of metabotropic glutamate receptor type1 (mGluR1) evokes a complex synaptic response consisting of IP3 receptor-dependent Ca2+ release from internal Ca2+ stores and a slow depolarizing potential involving TRPC3 channels. It is largely unclear how mGluR1 is linked to its downstream effectors. Here, we explored the role of stromal interaction molecule 1 (STIM1) in regulating neuronal Ca2+ signaling and mGluR1-dependent synaptic transmission. By analyzing mouse cerebellar Purkinje neurons, we demonstrate that STIM1 is an essential regulator of the Ca2+ level in neuronal endoplasmic reticulum Ca2+ stores. Both mGluR1-dependent synaptic potentials and IP3 receptor-dependent Ca2+ signals are strongly attenuated in the absence of STIM1. Furthermore, the Purkinje neuron-specific deletion of Stim1 causes impairments in cerebellar motor behavior. Together, our results demonstrate that in the mammalian nervous system STIM1 is a key regulator of intracellular Ca2+ signaling, metabotropic glutamate receptor-dependent synaptic transmission, and motor coordination. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
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