Information processing in artificial neural networks is largely dependent on the nature of neuron... more Information processing in artificial neural networks is largely dependent on the nature of neuron models. While commonly used models are designed for linear integration of synaptic inputs, accumulating experimental evidence suggests that biological neurons are capable of nonlinear computations for many converging synaptic inputs via homo- and heterosynaptic mechanisms. This nonlinear neuronal computation may play an important role in complex information processing at the neural circuit level. Here we characterize the dynamics and coding properties of neuron models on synaptic transmissions delivered from two hidden states. The neuronal information processing is influenced by the cooperative and competitive interactions among synapses and the coherence of the hidden states. Furthermore, we demonstrate that neuronal information processing under two-input synaptic transmission can be mapped to linearly nonseparable XOR as well as basic AND/OR operations. In particular, the mixtures of ...
The purpose of this study was to explore different patterns of functional networks between amnest... more The purpose of this study was to explore different patterns of functional networks between amnestic mild cognitive impairment (aMCI) and non-aMCI (naMCI) using electroencephalography (EEG) graph theoretical analysis. The data of 197 drug-naïve individuals who complained cognitive impairment were reviewed. Resting-state EEG data was acquired. Graph analyses were performed and compared between aMCI and naMCI, as well as between early and late aMCI. Correlation analyses were conducted between the graph measures and neuropsychological test results. Machine learning algorithms were applied to determine whether the EEG graph measures could be used to distinguish aMCI from naMCI. Compared to naMCI, aMCI showed higher modularity in the beta band and lower radius in the gamma band. Modularity was negatively correlated with scores on the semantic fluency test, and the radius in the gamma band was positively correlated with visual memory, phonemic, and semantic fluency tests. The naïve Bayes a...
Significance Clustering of phosphatidylinositol 4,5-bisphosphate (PIP 2 ) with proteins into what... more Significance Clustering of phosphatidylinositol 4,5-bisphosphate (PIP 2 ) with proteins into what are known as “PIP 2 rafts” is a critical component of intracellular signaling, yet little is known about PIP 2 clusters at the atomic level. Using molecular dynamics simulations and network theory, this paper shows that Ca 2+ generates large clusters by linking PIP 2 dimers already formed by doubly charged P4/P5 phosphates, while monovalent cations form smaller and less-stable clusters by adding PIP 2 monomers preferentially via weaker interactions with P4/P5 (for Na + ) or with glycerol P1 (for K + ). Synergy arises between K + and Ca 2+ because each ion forms linkages with different phosphates, thereby giving clusters more ways to grow. This explains why Ca 2+ is pumped into cells by ion channels to form PIP 2 rafts.
Journal of Agricultural and Food Chemistry, Mar 28, 2022
Several studies have documented the broad-spectrum bioactivities of a lotus seed (Plumula nelumbi... more Several studies have documented the broad-spectrum bioactivities of a lotus seed (Plumula nelumbinis [PN]) green embryo extract. However, the specific bioactive components and associated molecular mechanisms remain largely unknown. This study aimed to identify the ion channel-activating mechanisms of PN extracts. Using fluorometric imaging and patch-clamp recordings, PN extracts were screened for calcium channel activation in dorsal root ganglion (DRG) neurons. The TRPV1 channels in DRG neurons were strongly activated by the PN extract (mean amplitude of 131 ± 45 pA at 200 μg/mL) and its purified glycosyloxyflavone narcissoside (401 ± 271 pA at 100 μM). Serial treatment with a 200 μg/mL PN extract in TRPV1-overexpressing HEK293T cells induced robust desensitization to 10 ± 10% of the initial current amplitude. Thus, we propose that the PN extract and narcissoside function as TRPV1 agonists. This new finding may advance our knowledge regarding the traditional and scientific functions of PN in human health and disease.
The purpose of this study was to identify the mechanisms underlying effects of coffee on cognitio... more The purpose of this study was to identify the mechanisms underlying effects of coffee on cognition in the context of brain networks. Here we investigated functional connectivity before and after drinking coffee using graph theoretical analysis of electroencephalography (EEG). Twenty-one healthy adults voluntarily participated in this study. The neuropsychological tests were consecutively performed at the start of the EEG recording and 30 min after coffee consumption. Graph analyses were performed and compared before and after coffee consumption. Correlation analyses were conducted to assess the relationship between changes in graph measures and those in cognitive function tests. FC was reorganized toward more efficient network properties after coffee consumption. Performance in Digit Span tests and Trail Making Test Part B improved after coffee consumption, and the improved performance in executive function was correlated with changes in graph measures, reflecting a shift toward eff...
Sensing smells of foods, prey, or predators determines animal survival. Olfactory sensory neurons... more Sensing smells of foods, prey, or predators determines animal survival. Olfactory sensory neurons in the olfactory epithelium (OE) detect odorants, where cAMP and Ca2+ play a significant role in transducing odorant inputs to electrical activity. Here we show Anoctamin 9, a cation channel activated by cAMP/PKA pathway, is expressed in the OE and amplifies olfactory signals. Ano9- deficient mice had reduced olfactory behavioral sensitivity, electro-olfactogram signals, and neural activity in the olfactory bulb. In line with the difference in olfaction between birds and other vertebrates, chick ANO9 failed to respond to odorants, whereas chick CNGA2, a major transduction channel, showed greater responses to cAMP. Importantly, single-cell transcriptome data from Covid-19 patients revealed that Ano9 transcripts were markedly suppressed among genes in the olfactory signal pathway. The signal amplification by ANO9 is essential for mammalian olfactory transduction, whose downregulation may ...
The purpose of this study was to identify the mechanisms underlying effects of coffee on cognitio... more The purpose of this study was to identify the mechanisms underlying effects of coffee on cognition in the context of brain networks. Here we investigated functional connectivity before and after drinking coffee using graph-theoretic analysis of electroencephalography (EEG). Twenty-one healthy adults voluntarily participated in this study. The resting-state EEG data and results of neuropsychological tests were consecutively acquired before and 30 min after coffee consumption. Graph analyses were performed and compared before and after coffee consumption. Correlation analyses were conducted to assess the relationship between changes in graph measures and those in cognitive function tests. Functional connectivity (FC) was reorganized toward more efficient network properties after coffee consumption. Performance in Digit Span tests and Trail Making Test Part B improved after coffee consumption, and the improved performance in executive function was correlated with changes in graph measu...
Journal of Physics A: Mathematical and Theoretical
The integrate-and-fire (IF) model is the most widely used simple spiking neuron model in neuromor... more The integrate-and-fire (IF) model is the most widely used simple spiking neuron model in neuromorphic computing as well as in artificial neural network algorithms. Here, we characterize the dynamics and information processing of IF models using computer simulations and information-theoretic approaches. Neural dynamics is analysed by means of the time evolution of axonal spikes and the phase-plane portrait, and the coding efficiency of a neuron is estimated by the ratio of mutual information of input and output spikes for the binary hidden neural state. The exponential IF model exhibits higher similarity to the biophysical model in both neural dynamics and coding, compared to other IF type models. Electronic circuit simulations based on the simulation programme with integrated circuit emphasis reveal the nonlinear current–voltage characteristics of the IF neuron models and criticalities in the neural networks. Relevant information-theoretic measures indicate that the computational capabilities of neuromorphic devices largely depend on the neuron models. Such an approach combined with the analysis of neural dynamics provides a useful tool to investigate underlying dynamics of mathematical neuron models; it is applicable to the design and evaluation of neuromorphic models.
The environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) causes hepatic toxicity ... more The environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) causes hepatic toxicity associated with prominent lipid accumulation in humans. Here, the authors report that the lysosomal copper transporter SLC46A3 is induced by TCDD and underlies the hepatic lipid accumulation in mice, potentially via effects on mitochondrial function. SLC46A3 was localized to the lysosome where it modulated intracellular copper levels. Forced expression of hepatic SLC46A3 resulted in decreased mitochondrial membrane potential and abnormal mitochondria morphology consistent with lower copper levels. SLC46A3 expression increased hepatic lipid accumulation similar to the known effects of TCDD exposure in mice and humans. The TCDD-induced hepatic triglyceride accumulation was significantly decreased in Slc46a3−/− mice and was more pronounced when these mice were fed a high-fat diet, as compared to wild-type mice. These data are consistent with a model where lysosomal SLC46A3 induction by TCDD...
OBJECTIVES/GOALS: Mammals require iron for hemoglobin, respiration, immunity and as cofactor in e... more OBJECTIVES/GOALS: Mammals require iron for hemoglobin, respiration, immunity and as cofactor in enzymes. But free iron is toxic from the production of reactive oxygen species. Ferroportin is the sole exporter of cellular iron and it crucially determines cellular and systemic iron levels. Labile iron must be tightly regulated. This requires structural understanding. METHODS/STUDY POPULATION: We built structure of human ferroportin (FPN1) using the ab ignition prediction approaches of Rosetta/Robetta and by comparative modeling with distance restraints in MODELLER. Templates selected were from solute carrier protein families of distantly related orthologs and homologs including a proton coupled peptide transporter (PDB ID: 4IKV) and the bacterial iron transporter in outward-open and inward-open states, (PDB ID: 5AYM, 5AYO). Each model was validated by experimental mass spectrometry data. The energy minimized structural model was inserted into a lipid bilayer, placed in a rectangular s...
Information processing in artificial neural networks is largely dependent on the nature of neuron... more Information processing in artificial neural networks is largely dependent on the nature of neuron models. While commonly used models are designed for linear integration of synaptic inputs, accumulating experimental evidence suggests that biological neurons are capable of nonlinear computations for many converging synaptic inputs via homo- and heterosynaptic mechanisms. This nonlinear neuronal computation may play an important role in complex information processing at the neural circuit level. Here we characterize the dynamics and coding properties of neuron models on synaptic transmissions delivered from two hidden states. The neuronal information processing is influenced by the cooperative and competitive interactions among synapses and the coherence of the hidden states. Furthermore, we demonstrate that neuronal information processing under two-input synaptic transmission can be mapped to linearly nonseparable XOR as well as basic AND/OR operations. In particular, the mixtures of ...
The purpose of this study was to explore different patterns of functional networks between amnest... more The purpose of this study was to explore different patterns of functional networks between amnestic mild cognitive impairment (aMCI) and non-aMCI (naMCI) using electroencephalography (EEG) graph theoretical analysis. The data of 197 drug-naïve individuals who complained cognitive impairment were reviewed. Resting-state EEG data was acquired. Graph analyses were performed and compared between aMCI and naMCI, as well as between early and late aMCI. Correlation analyses were conducted between the graph measures and neuropsychological test results. Machine learning algorithms were applied to determine whether the EEG graph measures could be used to distinguish aMCI from naMCI. Compared to naMCI, aMCI showed higher modularity in the beta band and lower radius in the gamma band. Modularity was negatively correlated with scores on the semantic fluency test, and the radius in the gamma band was positively correlated with visual memory, phonemic, and semantic fluency tests. The naïve Bayes a...
Significance Clustering of phosphatidylinositol 4,5-bisphosphate (PIP 2 ) with proteins into what... more Significance Clustering of phosphatidylinositol 4,5-bisphosphate (PIP 2 ) with proteins into what are known as “PIP 2 rafts” is a critical component of intracellular signaling, yet little is known about PIP 2 clusters at the atomic level. Using molecular dynamics simulations and network theory, this paper shows that Ca 2+ generates large clusters by linking PIP 2 dimers already formed by doubly charged P4/P5 phosphates, while monovalent cations form smaller and less-stable clusters by adding PIP 2 monomers preferentially via weaker interactions with P4/P5 (for Na + ) or with glycerol P1 (for K + ). Synergy arises between K + and Ca 2+ because each ion forms linkages with different phosphates, thereby giving clusters more ways to grow. This explains why Ca 2+ is pumped into cells by ion channels to form PIP 2 rafts.
Journal of Agricultural and Food Chemistry, Mar 28, 2022
Several studies have documented the broad-spectrum bioactivities of a lotus seed (Plumula nelumbi... more Several studies have documented the broad-spectrum bioactivities of a lotus seed (Plumula nelumbinis [PN]) green embryo extract. However, the specific bioactive components and associated molecular mechanisms remain largely unknown. This study aimed to identify the ion channel-activating mechanisms of PN extracts. Using fluorometric imaging and patch-clamp recordings, PN extracts were screened for calcium channel activation in dorsal root ganglion (DRG) neurons. The TRPV1 channels in DRG neurons were strongly activated by the PN extract (mean amplitude of 131 ± 45 pA at 200 μg/mL) and its purified glycosyloxyflavone narcissoside (401 ± 271 pA at 100 μM). Serial treatment with a 200 μg/mL PN extract in TRPV1-overexpressing HEK293T cells induced robust desensitization to 10 ± 10% of the initial current amplitude. Thus, we propose that the PN extract and narcissoside function as TRPV1 agonists. This new finding may advance our knowledge regarding the traditional and scientific functions of PN in human health and disease.
The purpose of this study was to identify the mechanisms underlying effects of coffee on cognitio... more The purpose of this study was to identify the mechanisms underlying effects of coffee on cognition in the context of brain networks. Here we investigated functional connectivity before and after drinking coffee using graph theoretical analysis of electroencephalography (EEG). Twenty-one healthy adults voluntarily participated in this study. The neuropsychological tests were consecutively performed at the start of the EEG recording and 30 min after coffee consumption. Graph analyses were performed and compared before and after coffee consumption. Correlation analyses were conducted to assess the relationship between changes in graph measures and those in cognitive function tests. FC was reorganized toward more efficient network properties after coffee consumption. Performance in Digit Span tests and Trail Making Test Part B improved after coffee consumption, and the improved performance in executive function was correlated with changes in graph measures, reflecting a shift toward eff...
Sensing smells of foods, prey, or predators determines animal survival. Olfactory sensory neurons... more Sensing smells of foods, prey, or predators determines animal survival. Olfactory sensory neurons in the olfactory epithelium (OE) detect odorants, where cAMP and Ca2+ play a significant role in transducing odorant inputs to electrical activity. Here we show Anoctamin 9, a cation channel activated by cAMP/PKA pathway, is expressed in the OE and amplifies olfactory signals. Ano9- deficient mice had reduced olfactory behavioral sensitivity, electro-olfactogram signals, and neural activity in the olfactory bulb. In line with the difference in olfaction between birds and other vertebrates, chick ANO9 failed to respond to odorants, whereas chick CNGA2, a major transduction channel, showed greater responses to cAMP. Importantly, single-cell transcriptome data from Covid-19 patients revealed that Ano9 transcripts were markedly suppressed among genes in the olfactory signal pathway. The signal amplification by ANO9 is essential for mammalian olfactory transduction, whose downregulation may ...
The purpose of this study was to identify the mechanisms underlying effects of coffee on cognitio... more The purpose of this study was to identify the mechanisms underlying effects of coffee on cognition in the context of brain networks. Here we investigated functional connectivity before and after drinking coffee using graph-theoretic analysis of electroencephalography (EEG). Twenty-one healthy adults voluntarily participated in this study. The resting-state EEG data and results of neuropsychological tests were consecutively acquired before and 30 min after coffee consumption. Graph analyses were performed and compared before and after coffee consumption. Correlation analyses were conducted to assess the relationship between changes in graph measures and those in cognitive function tests. Functional connectivity (FC) was reorganized toward more efficient network properties after coffee consumption. Performance in Digit Span tests and Trail Making Test Part B improved after coffee consumption, and the improved performance in executive function was correlated with changes in graph measu...
Journal of Physics A: Mathematical and Theoretical
The integrate-and-fire (IF) model is the most widely used simple spiking neuron model in neuromor... more The integrate-and-fire (IF) model is the most widely used simple spiking neuron model in neuromorphic computing as well as in artificial neural network algorithms. Here, we characterize the dynamics and information processing of IF models using computer simulations and information-theoretic approaches. Neural dynamics is analysed by means of the time evolution of axonal spikes and the phase-plane portrait, and the coding efficiency of a neuron is estimated by the ratio of mutual information of input and output spikes for the binary hidden neural state. The exponential IF model exhibits higher similarity to the biophysical model in both neural dynamics and coding, compared to other IF type models. Electronic circuit simulations based on the simulation programme with integrated circuit emphasis reveal the nonlinear current–voltage characteristics of the IF neuron models and criticalities in the neural networks. Relevant information-theoretic measures indicate that the computational capabilities of neuromorphic devices largely depend on the neuron models. Such an approach combined with the analysis of neural dynamics provides a useful tool to investigate underlying dynamics of mathematical neuron models; it is applicable to the design and evaluation of neuromorphic models.
The environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) causes hepatic toxicity ... more The environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) causes hepatic toxicity associated with prominent lipid accumulation in humans. Here, the authors report that the lysosomal copper transporter SLC46A3 is induced by TCDD and underlies the hepatic lipid accumulation in mice, potentially via effects on mitochondrial function. SLC46A3 was localized to the lysosome where it modulated intracellular copper levels. Forced expression of hepatic SLC46A3 resulted in decreased mitochondrial membrane potential and abnormal mitochondria morphology consistent with lower copper levels. SLC46A3 expression increased hepatic lipid accumulation similar to the known effects of TCDD exposure in mice and humans. The TCDD-induced hepatic triglyceride accumulation was significantly decreased in Slc46a3−/− mice and was more pronounced when these mice were fed a high-fat diet, as compared to wild-type mice. These data are consistent with a model where lysosomal SLC46A3 induction by TCDD...
OBJECTIVES/GOALS: Mammals require iron for hemoglobin, respiration, immunity and as cofactor in e... more OBJECTIVES/GOALS: Mammals require iron for hemoglobin, respiration, immunity and as cofactor in enzymes. But free iron is toxic from the production of reactive oxygen species. Ferroportin is the sole exporter of cellular iron and it crucially determines cellular and systemic iron levels. Labile iron must be tightly regulated. This requires structural understanding. METHODS/STUDY POPULATION: We built structure of human ferroportin (FPN1) using the ab ignition prediction approaches of Rosetta/Robetta and by comparative modeling with distance restraints in MODELLER. Templates selected were from solute carrier protein families of distantly related orthologs and homologs including a proton coupled peptide transporter (PDB ID: 4IKV) and the bacterial iron transporter in outward-open and inward-open states, (PDB ID: 5AYM, 5AYO). Each model was validated by experimental mass spectrometry data. The energy minimized structural model was inserted into a lipid bilayer, placed in a rectangular s...
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Papers by Kyungreem Han