The Experts below are selected from a list of 318 Experts worldwide ranked by ideXlab platform
Martin P. Nawrot - One of the best experts on this subject based on the ideXlab platform.
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Cellular Adaptation Facilitates Sparse and Reliable Coding in Sensory Pathways
PLoS computational biology, 2013Co-Authors: Farzad Farkhooi, Anja Froese, Eilif Muller, Randolf Menzel, Martin P. NawrotAbstract:Most neurons in peripheral sensory pathways initially respond vigorously when a preferred stimulus is presented, but adapt as stimulation continues. It is unclear how this phenomenon affects stimulus coding in the later stages of sensory processing. Here, we show that a temporally sparse and reliable stimulus representation develops naturally in sequential stages of a sensory network with adapting neurons. As a modeling framework we employ a mean-field approach together with an adaptive population density treatment, accompanied by numerical simulations of spiking neural networks. We find that Cellular Adaptation plays a critical role in the dynamic reduction of the trial-by-trial variability of cortical spike responses by transiently suppressing self-generated fast fluctuations in the cortical balanced network. This provides an explanation for a widespread cortical phenomenon by a simple mechanism. We further show that in the insect olfactory system Cellular Adaptation is sufficient to explain the emergence of the temporally sparse and reliable stimulus representation in the mushroom body. Our results reveal a generic, biophysically plausible mechanism that can explain the emergence of a temporally sparse and reliable stimulus representation within a sequential processing architecture.
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Cellular Adaptation Accounts for the Sparse and Reliable Sensory Stimulus Representation
arXiv: Neurons and Cognition, 2012Co-Authors: Farzad Farkhooi, Anja Froese, Eilif Muller, Randolf Menzel, Martin P. NawrotAbstract:Most neurons in peripheral sensory pathways initially respond vigorously when a preferred stimulus is presented, but adapt as stimulation continues. It is unclear how this phenomenon affects stimulus representation in the later stages of cortical sensory processing. Here, we show that a temporally sparse and reliable stimulus representation develops naturally in a network with adapting neurons. We find that Cellular Adaptation plays a critical role in the transient reduction of the trial-by-trial variability of cortical spiking, providing an explanation for a wide-spread and hitherto unexplained phenomenon by a simple mechanism. In insect olfaction, Cellular Adaptation is sufficient to explain the emergence of the temporally sparse and reliable stimulus representation in the mushroom body, independent of inhibitory mechanisms. Our results reveal a computational principle that relates neuronal firing rate Adaptation to temporal sparse coding and variability suppression in nervous systems with a sequential processing architecture.
Lars-eric Thornell - One of the best experts on this subject based on the ideXlab platform.
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Cellular Adaptation of the trapezius muscle in strength-trained athletes.
Histochemistry and Cell Biology, 1999Co-Authors: Fawzi Kadi, Anders Eriksson, Staffan Holmner, Gillian Butler-browne, Lars-eric ThornellAbstract:The aim of this study was to elucidate the Cellular events that occur in the trapezius muscle following several years of strength training. In muscle biopsies from ten elite power lifters (PL) and six control subjects (C), several parameters were studied: cross-sectional area of muscle fibres, myosin heavy chain composition (MHC) and capillary supply [capillaries around fibres (CAF) and CAF/fibre area]. A method was also developed for counting the number of myonuclei and satellite cell nuclei. The proportion of fibres expressing MHC IIA, the cross-sectional area of each fibre type and the number of myonuclei, satellite cells and fibres expressing markers for early myogenesis were significantly higher in PL than in C (P
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Cellular Adaptation of the trapezius muscle in strength trained athletes
Histochemistry and Cell Biology, 1999Co-Authors: Fawzi Kadi, Anders Eriksson, Staffan Holmner, Gillian Butlerbrowne, Lars-eric ThornellAbstract:The aim of this study was to elucidate the Cellular events that occur in the trapezius muscle following several years of strength training. In muscle biopsies from ten elite power lifters (PL) and six control subjects (C), several parameters were studied: cross-sectional area of muscle fibres, myosin heavy chain composition (MHC) and capillary supply [capillaries around fibres (CAF) and CAF/fibre area]. A method was also developed for counting the number of myonuclei and satellite cell nuclei. The proportion of fibres expressing MHC IIA, the cross-sectional area of each fibre type and the number of myonuclei, satellite cells and fibres expressing markers for early myogenesis were significantly higher in PL than in C (P<0.05). A significant correlation between the myonuclear number and the cross-sectional area was observed. Since myonuclei in mature muscle fibres are not able to divide, we suggest that the incorporation of satellite cell nuclei into muscle fibres resulted in the maintenance of a constant nuclear to cytoplasmic ratio. The presence of small diameter fibres expressing markers for early myogenesis indicates the formation of new muscle fibres.
Robert J Gillies - One of the best experts on this subject based on the ideXlab platform.
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abstract 3538 enhanced dependence on lipid metabolism is a Cellular Adaptation to acidic microenvironment
Cancer Research, 2017Co-Authors: Smitha Pillai, Jonathan W Wojtkowiak, Mehdi Damaghi, Robert A Gatenby, Robert J GilliesAbstract:Malignant tumors exhibit altered metabolism and consume higher levels of glucose compared to surrounding normal tissue, resulting in highly acidic microenvironment. Adaptation to acidic conditions is a pre-requisite for tumor cells to survive and thrive and to out-compete the stroma into which they invade. Acid Adaptation is associated with chronic activation of autophagy as well as redistribution of the lysosomal proteins to the plasma membrane. These processes are major survival mechanisms adopted by tumor cells under acidic conditions. We have also observed that under acidic conditions, there is a rapid, reversible and robust increase in the accumulation of cytoplasmic lipid droplets (adiposomes) in a panel of breast cancer cells. Adiposomes are dynamic organelles that store neutral lipids surrounded by a shell of proteins and a phospholipid monolayer. Breast cancer cells when grown in acidic media accumulated adiposomes as revealed by nile red and perilipin-2 staining followed by confocal microscopy. The acid-induced lipogenic phenotype persists even when the cells are grown in de-lipidated serum, indicating that the source of lipids is de-novo and endogenous. When cells were treated with inhibitors of fatty acid synthesis such as TOFA, an inhibitor of Acetyl CoA Carboxylase or FAS inhibitor C75, adiposome formation at low pH was attenuated. Inhibition of either lipid anabolic or catabolic pathways was specifically cytotoxic in acid-adapted cells, but not in control cells where the FAS inhibitor, C75, is selectively toxic under acidic conditions. Additionally, when treated with etomoxir, an inhibitor of carnitine palmitoyltransferase 1, the rate limiting step in βeta-oxidation, acid adapted cells showed increased sensitivity. To investigate the role of de novo fatty acid synthesis further, we employed high resolution NMR spectroscopy to measure 13C enriched lactate isotopomers following metabolism of D-[1,2-13C] glucose. These analyses showed that glucose flux through the pentose phosphate pathway (PPP) was significantly (>2.5 fold) higher in low pH exposed cells, compared to controls, representing a major shift in glucose metabolism from Embden Meyerhof to PPP, which results in increased production of NADPH, necessary for de novo lipid synthesis. Additional metabolic profiling using the Seahorse XF revealed that cells at low pH had higher rates of oxygen consumption (OCR) and that this was reversible. Further, we investigated the role of various acid sensing G-protein coupled receptors such as OGR1, TDAG8 and GPR4 in transducing the acid signal that results in the accumulation of lipid droplets. CRISPR/Cas9 mediated depletion of these receptors indicates that they might play a major role in inducing adiposome accumulation under acidic conditions. Taken together, increased dependence on lipid metabolism by cancer cells under acidic conditions reveals novel therapeutic vulnerabilities. Citation Format: Smitha Pillai, Jonathan W. Wojtkowiak, Mehdi Damaghi, Robert Gatenby, Robert Gillies. Enhanced dependence on lipid metabolism is a Cellular Adaptation to acidic microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3538. doi:10.1158/1538-7445.AM2017-3538
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chronic autophagy is a Cellular Adaptation to tumor acidic ph microenvironments
Cancer Research, 2012Co-Authors: Jonathan W Wojtkowiak, Karla J Schramm, Jennifer M Rothberg, Virendra Kumar, Edward M Haller, Joshua B Proemsey, Mark C Lloyd, Bonnie F Sloane, Robert J GilliesAbstract:Tumor cell survival relies upon Adaptation to the acidic conditions of the tumor microenvironment. To investigate potential acidosis survival mechanisms, we examined the effect of low pH (6.7) on human breast carcinoma cells. Acute low pH exposure reduced proliferation rate, induced a G1 cell cycle arrest, and increased cytoplasmic vacuolization. Gene expression analysis revealed elevated levels of ATG5 and BNIP3 in acid-conditioned cells, suggesting cells exposed to low pH may utilize autophagy as a survival mechanism. In support of this hypothesis, we found that acute low pH stimulated autophagy as defined by an increase in LC3-positive punctate vesicles, double-membrane vacuoles, and decreased phosphorylation of AKT and ribosomal protein S6. Notably, cells exposed to low pH for approximately 3 months restored their proliferative capacity while maintaining the cytoplasmic vacuolated phenotype. Although autophagy is typically transient, elevated autophagy markers were maintained chronically in low pH conditioned cells as visualized by increased protein expression of LC3-II and double-membrane vacuoles. Furthermore, these cells exhibited elevated sensitivity to PI3K-class III inhibition by 3-methyladenine. In mouse tumors, LC3 expression was reduced by systemic treatment with sodium bicarbonate, which raises intratumoral pH. Taken together, these results argue that acidic conditions in the tumor microenvironment promote autophagy, and that chronic autophagy occurs as a survival Adaptation in this setting.
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drug resistance and Cellular Adaptation to tumor acidic ph microenvironment
Molecular Pharmaceutics, 2011Co-Authors: Jonathan W Wojtkowiak, Daniel Verduzco, Karla J Schramm, Robert J GilliesAbstract:Despite advances in developing novel therapeutic strategies, a major factor underlying cancer related death remains resistance to therapy. In addition to biochemical resistance, mediated by xenobiotic transporters or binding site mutations, resistance can be physiological, emerging as a consequence of the tumor’s physical microenvironment. This review focuses on extraCellular acidosis, an end result of high glycolytic flux and poor vascular perfusion. Low extraCellular pH, pHe, forms a physiological drug barrier described by an “ion trapping” phenomenon. We describe how the acid-outside plasmalemmal pH gradient negatively impacts drug efficacy of weak base chemotherapies but is better suited for weakly acidic therapeutics. We will also explore the physiologic changes tumor cells undergo in response to extraCellular acidosis which contribute to drug resistance including reduced apoptotic potential, genetic alterations, and elevated activity of a multidrug transporter, p-glycoprotein, pGP. Since low pHe is ...
Farzad Farkhooi - One of the best experts on this subject based on the ideXlab platform.
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Cellular Adaptation Facilitates Sparse and Reliable Coding in Sensory Pathways
PLoS computational biology, 2013Co-Authors: Farzad Farkhooi, Anja Froese, Eilif Muller, Randolf Menzel, Martin P. NawrotAbstract:Most neurons in peripheral sensory pathways initially respond vigorously when a preferred stimulus is presented, but adapt as stimulation continues. It is unclear how this phenomenon affects stimulus coding in the later stages of sensory processing. Here, we show that a temporally sparse and reliable stimulus representation develops naturally in sequential stages of a sensory network with adapting neurons. As a modeling framework we employ a mean-field approach together with an adaptive population density treatment, accompanied by numerical simulations of spiking neural networks. We find that Cellular Adaptation plays a critical role in the dynamic reduction of the trial-by-trial variability of cortical spike responses by transiently suppressing self-generated fast fluctuations in the cortical balanced network. This provides an explanation for a widespread cortical phenomenon by a simple mechanism. We further show that in the insect olfactory system Cellular Adaptation is sufficient to explain the emergence of the temporally sparse and reliable stimulus representation in the mushroom body. Our results reveal a generic, biophysically plausible mechanism that can explain the emergence of a temporally sparse and reliable stimulus representation within a sequential processing architecture.
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Cellular Adaptation Accounts for the Sparse and Reliable Sensory Stimulus Representation
arXiv: Neurons and Cognition, 2012Co-Authors: Farzad Farkhooi, Anja Froese, Eilif Muller, Randolf Menzel, Martin P. NawrotAbstract:Most neurons in peripheral sensory pathways initially respond vigorously when a preferred stimulus is presented, but adapt as stimulation continues. It is unclear how this phenomenon affects stimulus representation in the later stages of cortical sensory processing. Here, we show that a temporally sparse and reliable stimulus representation develops naturally in a network with adapting neurons. We find that Cellular Adaptation plays a critical role in the transient reduction of the trial-by-trial variability of cortical spiking, providing an explanation for a wide-spread and hitherto unexplained phenomenon by a simple mechanism. In insect olfaction, Cellular Adaptation is sufficient to explain the emergence of the temporally sparse and reliable stimulus representation in the mushroom body, independent of inhibitory mechanisms. Our results reveal a computational principle that relates neuronal firing rate Adaptation to temporal sparse coding and variability suppression in nervous systems with a sequential processing architecture.
Fawzi Kadi - One of the best experts on this subject based on the ideXlab platform.
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Cellular Adaptation of the trapezius muscle in strength-trained athletes.
Histochemistry and Cell Biology, 1999Co-Authors: Fawzi Kadi, Anders Eriksson, Staffan Holmner, Gillian Butler-browne, Lars-eric ThornellAbstract:The aim of this study was to elucidate the Cellular events that occur in the trapezius muscle following several years of strength training. In muscle biopsies from ten elite power lifters (PL) and six control subjects (C), several parameters were studied: cross-sectional area of muscle fibres, myosin heavy chain composition (MHC) and capillary supply [capillaries around fibres (CAF) and CAF/fibre area]. A method was also developed for counting the number of myonuclei and satellite cell nuclei. The proportion of fibres expressing MHC IIA, the cross-sectional area of each fibre type and the number of myonuclei, satellite cells and fibres expressing markers for early myogenesis were significantly higher in PL than in C (P
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Cellular Adaptation of the trapezius muscle in strength trained athletes
Histochemistry and Cell Biology, 1999Co-Authors: Fawzi Kadi, Anders Eriksson, Staffan Holmner, Gillian Butlerbrowne, Lars-eric ThornellAbstract:The aim of this study was to elucidate the Cellular events that occur in the trapezius muscle following several years of strength training. In muscle biopsies from ten elite power lifters (PL) and six control subjects (C), several parameters were studied: cross-sectional area of muscle fibres, myosin heavy chain composition (MHC) and capillary supply [capillaries around fibres (CAF) and CAF/fibre area]. A method was also developed for counting the number of myonuclei and satellite cell nuclei. The proportion of fibres expressing MHC IIA, the cross-sectional area of each fibre type and the number of myonuclei, satellite cells and fibres expressing markers for early myogenesis were significantly higher in PL than in C (P<0.05). A significant correlation between the myonuclear number and the cross-sectional area was observed. Since myonuclei in mature muscle fibres are not able to divide, we suggest that the incorporation of satellite cell nuclei into muscle fibres resulted in the maintenance of a constant nuclear to cytoplasmic ratio. The presence of small diameter fibres expressing markers for early myogenesis indicates the formation of new muscle fibres.