ORCID Profile
0000-0003-4431-5015
Current Organisations
University of British Columbia
,
UniversitätsKlinikum Heidelberg
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Sensory Processes, Perception and Performance | Psychology
Publisher: Elsevier BV
Date: 03-2016
DOI: 10.1016/J.CLINPH.2015.12.009
Abstract: Validate independent component analysis (ICA) for removal of EMG contamination from EEG, and demonstrate a heuristic, based on the gradient of EEG spectra (slope of graph of log EEG power vs log frequency, 7-70 Hz) from paralysed awake humans, to automatically identify and remove components that are predominantly EMG. We studied the gradient of EMG-free EEG spectra to quantitatively inform the choice of threshold. Then, pre-existing EEG from 3 disparate experimental groups was examined before and after applying the heuristic to validate that the heuristic preserved neurogenic activity (Berger effect, auditory odd ball, visual and auditory steady state responses). (1) ICA-based EMG removal diminished EMG contamination up to approximately 50 Hz, (2) residual EMG contamination using automatic selection was similar to manual selection, and (3) task-induced cortical activity remained, was enhanced, or was revealed using the ICA-based methodology. This study further validates ICA as a powerful technique for separating and removing myogenic signals from EEG. Automatic processing based on spectral gradients to exclude EMG-containing components is a conceptually simple and valid technique. This study strengthens ICA as a technique to remove EMG contamination from EEG whilst preserving neurogenic activity to 50 Hz.
Publisher: Elsevier BV
Date: 08-2015
DOI: 10.1038/MT.2015.93
Publisher: Springer Science and Business Media LLC
Date: 20-06-2011
DOI: 10.1038/NRN3061
Abstract: Although typically assumed to degrade performance, random fluctuations, or noise, can sometimes improve information processing in non-linear systems. One such form of 'stochastic facilitation', stochastic resonance, has been observed to enhance processing both in theoretical models of neural systems and in experimental neuroscience. However, the two approaches have yet to be fully reconciled. Understanding the erse roles of noise in neural computation will require the design of experiments based on new theory and models, into which biologically appropriate experimental detail feeds back at various levels of abstraction.
Publisher: Informa UK Limited
Date: 11-03-2015
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-01-2011
DOI: 10.1161/CIRCRESAHA.110.225201
Abstract: The G βγ -sequestering peptide β-adrenergic receptor kinase (βARK)ct derived from the G-protein–coupled receptor kinase (GRK)2 carboxyl terminus has emerged as a promising target for gene-based heart failure therapy. Enhanced downstream cAMP signaling has been proposed as the underlying mechanism for increased β-adrenergic receptor (βAR) responsiveness. However, molecular targets mediating improved cardiac contractile performance by βARKct and its impact on G βγ -mediated signaling have yet to be fully elucidated. We sought to identify G βγ -regulated targets and signaling mechanisms conveying βARKct-mediated enhanced βAR responsiveness in normal (NC) and failing (FC) adult rat ventricular cardiomyocytes. Assessing viral-based βARKct gene delivery with electrophysiological techniques, analysis of contractile performance, subcellular Ca 2+ handling, and site-specific protein phosphorylation, we demonstrate that βARKct enhances the cardiac L-type Ca 2+ channel (LCC) current ( I Ca ) both in NCs and FCs on βAR stimulation. Mechanistically, βARKct augments I Ca by preventing enhanced inhibitory interaction between the α1-LCC subunit (Cav1.2α) and liberated G βγ subunits downstream of activated βARs. Despite improved βAR contractile responsiveness, βARKct neither increased nor restored cAMP-dependent protein kinase (PKA) and calmodulin-dependent kinase II signaling including unchanged protein kinase (PK)Cε, extracellular signal-regulated kinase (ERK)1/2, Akt, ERK5, and p38 activation both in NCs and FCs. Accordingly, although βARKct significantly increases I Ca and Ca 2+ transients, being susceptible to suppression by recombinant G βγ protein and use-dependent LCC blocker, βARKct-expressing cardiomyocytes exhibit equal basal and βAR-stimulated sarcoplasmic reticulum Ca 2+ load, spontaneous diastolic Ca 2+ leakage, and survival rates and were less susceptible to field-stimulated Ca 2+ waves compared with controls. Our study identifies a G βγ -dependent signaling pathway attenuating cardiomyocyte I Ca on βAR as molecular target for the G βγ -sequestering peptide βARKct. Targeted interruption of this inhibitory signaling pathway by βARKct confers improved βAR contractile responsiveness through increased I Ca without enhancing regular or restoring abnormal cAMP-signaling. βARKct-mediated improvement of I Ca rendered cardiomyocytes neither susceptible to βAR-induced damage nor arrhythmogenic sarcoplasmic reticulum Ca 2+ leakage.
Publisher: Public Library of Science (PLoS)
Date: 08-12-2014
Publisher: Elsevier BV
Date: 02-2007
DOI: 10.1016/J.CECA.2006.06.001
Abstract: S100A1, a Ca2+-sensor protein of the EF-hand type, exerts positive inotropic effects in the heart via enhanced cardiac ryanodine receptor (RyR2) activity. Here we report that S100A1 protein (0.1microM) interacts with the RyR2 in resting permeabilized cardiomyocytes at free Ca2+-levels comparable to diastolic Ca2+-concentrations ( approximately 150nM). Alterations of RyR2 function due to S100A1 binding was assessed via analysis of Ca2+-spark characteristics. Ca2+-spark frequency, litude and duration were all reduced upon perfusion with 0.1microM S100A1 protein by 38%, 14% and 18%, respectively. Most likely, these effects were conveyed through the S100A1 C-terminus (S100A1-ct amino acids 75-94) as the corresponding S100A1-ct peptide (0.1microM) inhibited S100A1 protein binding to the RyR2 and similarly attenuated frequency, litude and duration of Ca2+-sparks by 52%, 8% and 26%, respectively. Accordingly, the sarcoplasmic reticulum (SR) Ca2+-content was slightly increased but the stoichiometry of other accessory RyR2 modulators (sorcin/FKBP12.6) remained unaltered by S100A1. Hence, we propose S100A1 as a novel inhibitory modulator of RyR2 function at diastolic Ca2+-concentrations in rabbit ventricular cardiomyocytes.
Publisher: Springer Science and Business Media LLC
Date: 11-2006
DOI: 10.3758/BF03193730
Abstract: In experiments examining inhibition of return (IOR), it is common practice to present a second cue at fixation during the cue-target interval. The purpose of this fixation cue is to reorient attention away from the cued location to ensure that the facilitative effects of spatial attention do not obscure IOR. However, despite their frequent use, relatively little is known about the relationship between fixation cues and IOR. In the present experiments, we examined the role of fixation cues by manipulating their presence in tasks that either did or did not require target identification. When the participants were required to either detect (Experiment 1A) or localize (Experiment 2A) a target, the magnitude of IOR was unaffected by the presence of a fixation cue. In contrast, when the participants were required to identify a target (Experiments 1B, 2B, and 3), IOR was observed only when a fixation cue was presented. This result was obtained regardless of the type of response that was required (two-alternative forced choice or go/no go). The effectiveness of the fixation cue in revealing IOR in these tasks is consistent with its putative role in reorienting attention away from the cued location.
Publisher: IEEE
Date: 07-2013
Publisher: MIT Press - Journals
Date: 2015
DOI: 10.1162/NECO_A_00688
Abstract: In this letter, we provide a stochastic analysis of, and supporting simulation data for, a stochastic model of the generation of gamma bursts in local field potential (LFP) recordings by interacting populations of excitatory and inhibitory neurons. Our interest is in behavior near a fixed point of the stochastic dynamics of the model. We apply a recent limit theorem of stochastic dynamics to probe into details of this local behavior, obtaining several new results. We show that the stochastic model can be written in terms of a rotation multiplied by a two-dimensional standard Ornstein-Uhlenbeck (OU) process. Viewing the rewritten process in terms of phase and litude processes, we are able to proceed further in analysis. We demonstrate that gamma bursts arise in the model as excursions of the modulus of the OU process. The associated pair of stochastic phase and litude processes satisfies their own pair of stochastic differential equations, which indicates that large phase slips occur between gamma bursts. This behavior is mirrored in LFP data simulated from the original model. These results suggest that the rewritten model is a valid representation of the behavior near the fixed point for a wide class of models of oscillatory neural processes.
Publisher: Oxford University Press (OUP)
Date: 07-03-2023
DOI: 10.1093/NAR/GKAD121
Abstract: The existence of naturally occurring ribosome heterogeneity is now a well-acknowledged phenomenon. However, whether this heterogeneity leads to functionally erse ‘specialized ribosomes’ is still a controversial topic. Here, we explore the biological function of RPL3L (uL3L), a ribosomal protein (RP) paralogue of RPL3 (uL3) that is exclusively expressed in skeletal muscle and heart tissues, by generating a viable homozygous Rpl3l knockout mouse strain. We identify a rescue mechanism in which, upon RPL3L depletion, RPL3 becomes up-regulated, yielding RPL3-containing ribosomes instead of RPL3L-containing ribosomes that are typically found in cardiomyocytes. Using both ribosome profiling (Ribo-seq) and a novel orthogonal approach consisting of ribosome pulldown coupled to nanopore sequencing (Nano-TRAP), we find that RPL3L modulates neither translational efficiency nor ribosome affinity towards a specific subset of transcripts. In contrast, we show that depletion of RPL3L leads to increased ribosome–mitochondria interactions in cardiomyocytes, which is accompanied by a significant increase in ATP levels, potentially as a result of fine-tuning of mitochondrial activity. Our results demonstrate that the existence of tissue-specific RP paralogues does not necessarily lead to enhanced translation of specific transcripts or modulation of translational output. Instead, we reveal a complex cellular scenario in which RPL3L modulates the expression of RPL3, which in turn affects ribosomal subcellular localization and, ultimately, mitochondrial activity.
Publisher: Springer Science and Business Media LLC
Date: 07-09-2011
DOI: 10.1038/NRN3061-C2
Publisher: Cold Spring Harbor Laboratory
Date: 04-12-2021
DOI: 10.1101/2021.12.04.471171
Abstract: The existence of naturally occurring ribosome heterogeneity is now a well-acknowledged phenomenon. However, whether this heterogeneity leads to functionally erse ‘specialized ribosomes’ is still a controversial topic. Here, we explore the biological function of RPL3L (uL3L), a ribosomal protein (RP) paralog of RPL3 (uL3) that is exclusively expressed in muscle and heart tissues, by generating a viable homozygous Rpl3l knockout mouse strain. We identify a rescue mechanism in which, upon RPL3L depletion, RPL3 becomes upregulated, yielding RPL3-containing ribosomes instead of RPL3L-containing ribosomes that are typically found in cardiomyocytes. Using both ribosome profiling (Ribo-Seq) and a novel orthogonal approach consisting of ribosome pulldown coupled to nanopore sequencing (Nano-TRAP), we find that RPL3L neither modulates translational efficiency nor ribosome affinity towards a specific subset of transcripts. By contrast, we show that depletion of RPL3L leads to increased ribosome-mitochondria interactions in cardiomyocytes, which is accompanied by a significant increase in ATP levels, potentially as a result of mitochondrial activity fine-tuning. Our results demonstrate that the existence of tissue-specific RP paralogs does not necessarily lead to enhanced translation of specific transcripts or modulation of translational output. Instead, we reveal a complex cellular scenario in which RPL3L modulates the expression of RPL3, which in turn affects ribosomal subcellular localization and, ultimately, mitochondrial activity.
Publisher: Public Library of Science (PLoS)
Date: 17-04-2014
Publisher: Elsevier BV
Date: 2012
DOI: 10.1016/J.BRAINRES.2011.08.070
Abstract: Simulated networks of excitatory and inhibitory neurons have previously been shown to reproduce critical features of experimental data regarding neural coding in V1, such as a positive relationship between thalamic input spike rate and the power of gamma frequency oscillations. This effect, referred to as modulated gamma power, could represent a neural code in V1 for stimulus characteristics that affect thalamic spike rate such as contrast or intensity. The simulated network's assumptions included homogeneous random connectivity, equal synaptic delays after spike arrival, and constant synaptic efficacies. Plausible alternative assumptions include small world connectivity, a wide distribution of axonal propagation delays, and short term synaptic plasticity, and here we assess the in idual impact of each of these on the model's success in reproducing modulated gamma power. First, we developed several alternative algorithms for simulating directed networks with clustered connectivity and balanced excitation and inhibition. We found that modulated gamma power was absent in all small-world networks that had a relatively low abundance of reciprocal connectivity, which suggests that such motifs are present in V1 cortical networks at levels at least equal to those found in random networks. We also found in a different network type that the balance of excitation and inhibition could be destroyed when the network was in the small-world regime. Given all neurons had identical in-degrees, this result suggests that balance relies on motif distributions as well as mean connectivity. Second, altering the distribution of axonal delays had little effect, but increasing the mean delay led to a secondary gamma modulation at harmonics of the main peak, and since this is not observed experimentally, it suggests a mean delay in V1 networks less than 2 ms. Finally, we compared two types of excitatory synaptic plasticity, and found that modulated beta power emerged in addition to gamma power for one type, in the presence of short term depression in interneurons. This article is part of a Special Issue entitled "Neural Coding".
Publisher: Elsevier BV
Date: 06-2010
Location: Germany
Start Date: 05-2022
End Date: 04-2025
Amount: $285,504.00
Funder: Australian Research Council
View Funded Activity