Pub Date : 2021-06-01Epub Date: 2021-06-16DOI: 10.1089/bioe.2021.0013
Joshua M Jones, Joseph W Larkin
Bacteria are electrically powered organisms; cells maintain an electrical potential across their plasma membrane as a source of free energy to drive essential processes. In recent years, however, bacterial membrane potential has been increasingly recognized as dynamic. Those dynamics have been implicated in diverse physiological functions and behaviors, including cell division and cell-to-cell signaling. In eukaryotic cells, such dynamics play major roles in coupling bioelectrical stimuli to changes in internal cell states. Neuroscientists and physiologists have established detailed molecular pathways that transduce eukaryotic membrane potential dynamics to physiological and gene expression responses. We are only just beginning to explore these intracellular responses to bioelectrical activity in bacteria. In this review, we summarize progress in this area, including evidence of gene expression responses to stimuli from electrodes and mechanically induced membrane potential spikes. We argue that the combination of provocative results, missing molecular detail, and emerging tools makes the investigation of bioelectrically induced long-term intracellular responses an important and rewarding effort in the future of microbiology.
{"title":"Toward Bacterial Bioelectric Signal Transduction.","authors":"Joshua M Jones, Joseph W Larkin","doi":"10.1089/bioe.2021.0013","DOIUrl":"https://doi.org/10.1089/bioe.2021.0013","url":null,"abstract":"<p><p>Bacteria are electrically powered organisms; cells maintain an electrical potential across their plasma membrane as a source of free energy to drive essential processes. In recent years, however, bacterial membrane potential has been increasingly recognized as dynamic. Those dynamics have been implicated in diverse physiological functions and behaviors, including cell division and cell-to-cell signaling. In eukaryotic cells, such dynamics play major roles in coupling bioelectrical stimuli to changes in internal cell states. Neuroscientists and physiologists have established detailed molecular pathways that transduce eukaryotic membrane potential dynamics to physiological and gene expression responses. We are only just beginning to explore these intracellular responses to bioelectrical activity in bacteria. In this review, we summarize progress in this area, including evidence of gene expression responses to stimuli from electrodes and mechanically induced membrane potential spikes. We argue that the combination of provocative results, missing molecular detail, and emerging tools makes the investigation of bioelectrically induced long-term intracellular responses an important and rewarding effort in the future of microbiology.</p>","PeriodicalId":29923,"journal":{"name":"Bioelectricity","volume":"3 2","pages":"116-119"},"PeriodicalIF":2.3,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8380937/pdf/bioe.2021.0013.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39380227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-06-01Epub Date: 2021-06-16DOI: 10.1089/bioe.2021.0008
Giuseppe Maria Paternò, Gaia Bondelli, Guglielmo Lanzani
The observation of neuron-like behavior in bacteria, such as the occurrence of electric spiking and extended bioelectric signaling, points to the role of membrane dynamics in prokaryotes. Electrophysiology of bacteria, however, has been overlooked for long time, due to the difficulties in monitoring bacterial bioelectric phenomena with those probing techniques that are commonly used for eukaryotes. Optical technologies can allow a paradigm shift in the field of electrophysiology of bacteria, as they would permit to elicit and monitor signaling rapidly, remotely, and with high spatiotemporal precision. In this perspective, we discuss about the potentiality of light interrogation methods in microbiology, encouraging the development of all-optical electrophysiology of bacteria.
{"title":"Bringing Microbiology to Light: Toward All-Optical Electrophysiology in Bacteria.","authors":"Giuseppe Maria Paternò, Gaia Bondelli, Guglielmo Lanzani","doi":"10.1089/bioe.2021.0008","DOIUrl":"https://doi.org/10.1089/bioe.2021.0008","url":null,"abstract":"<p><p>The observation of neuron-like behavior in bacteria, such as the occurrence of electric spiking and extended bioelectric signaling, points to the role of membrane dynamics in prokaryotes. Electrophysiology of bacteria, however, has been overlooked for long time, due to the difficulties in monitoring bacterial bioelectric phenomena with those probing techniques that are commonly used for eukaryotes. Optical technologies can allow a paradigm shift in the field of electrophysiology of bacteria, as they would permit to elicit and monitor signaling rapidly, remotely, and with high spatiotemporal precision. In this perspective, we discuss about the potentiality of light interrogation methods in microbiology, encouraging the development of all-optical electrophysiology of bacteria.</p>","PeriodicalId":29923,"journal":{"name":"Bioelectricity","volume":"3 2","pages":"136-142"},"PeriodicalIF":2.3,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8380939/pdf/bioe.2021.0008.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39380163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-06-01Epub Date: 2021-06-16DOI: 10.1089/bioe.2021.0012
Sarah J Quillin, Peter Tran, Arthur Prindle
It is now established that the gut microbiome influences human neurology and behavior, and vice versa. Distinct mechanisms underlying this bidirectional communication pathway, termed the gut-brain axis, are becoming increasingly uncovered. This review summarizes recent interkingdom signaling research focused on gamma-aminobutyric acid (GABA), a human neurotransmitter and ubiquitous signaling molecule found in bacteria, fungi, plants, invertebrates, and mammals. We detail how GABAergic signaling has been shown to be a crucial component of the gut-brain axis. We further describe how GABA is also being found to mediate interkingdom signaling between algae and invertebrates, plants and invertebrates, and plants and bacteria. Based on these emerging results, we argue that obtaining a complete understanding of GABA-mediated communication in the gut-brain axis will involve deciphering the role of GABA signaling and metabolism within bacterial communities themselves.
{"title":"Potential Roles for Gamma-Aminobutyric Acid Signaling in Bacterial Communities.","authors":"Sarah J Quillin, Peter Tran, Arthur Prindle","doi":"10.1089/bioe.2021.0012","DOIUrl":"https://doi.org/10.1089/bioe.2021.0012","url":null,"abstract":"<p><p>It is now established that the gut microbiome influences human neurology and behavior, and vice versa. Distinct mechanisms underlying this bidirectional communication pathway, termed the gut-brain axis, are becoming increasingly uncovered. This review summarizes recent interkingdom signaling research focused on gamma-aminobutyric acid (GABA), a human neurotransmitter and ubiquitous signaling molecule found in bacteria, fungi, plants, invertebrates, and mammals. We detail how GABAergic signaling has been shown to be a crucial component of the gut-brain axis. We further describe how GABA is also being found to mediate interkingdom signaling between algae and invertebrates, plants and invertebrates, and plants and bacteria. Based on these emerging results, we argue that obtaining a complete understanding of GABA-mediated communication in the gut-brain axis will involve deciphering the role of GABA signaling and metabolism within bacterial communities themselves.</p>","PeriodicalId":29923,"journal":{"name":"Bioelectricity","volume":"3 2","pages":"120-125"},"PeriodicalIF":2.3,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8380936/pdf/bioe.2021.0012.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39380228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-06-01Epub Date: 2021-06-16DOI: 10.1089/bioe.2021.0017
Joel M Kralj
It began, as with many good things, at a happy hour. Adam Cohen, a young assistant professor asked whether rhodopsins could be used to optically sense voltage. In the heady days of 2009, channel rhodopsin had just been unveiled as a voltage actuator in neurons. Adam had the insight to question whether rhodopsins could be run in reverse; could optical changes in a protein relay the cellular voltage state using light? This was one of the earliest lessons I learned under his mentorship, and the first piece of advice in this retrospective-turning a scientific question or statement on its head can be the basis for many fantastic research projects.
{"title":"Finding the Spark.","authors":"Joel M Kralj","doi":"10.1089/bioe.2021.0017","DOIUrl":"https://doi.org/10.1089/bioe.2021.0017","url":null,"abstract":"<p><p>It began, as with many good things, at a happy hour. Adam Cohen, a young assistant professor asked whether rhodopsins could be used to optically sense voltage. In the heady days of 2009, channel rhodopsin had just been unveiled as a voltage actuator in neurons. Adam had the insight to question whether rhodopsins could be run in reverse; could optical changes in a protein relay the cellular voltage state using light? This was one of the earliest lessons I learned under his mentorship, and the first piece of advice in this retrospective-turning a scientific question or statement on its head can be the basis for many fantastic research projects.</p>","PeriodicalId":29923,"journal":{"name":"Bioelectricity","volume":"3 2","pages":"143-146"},"PeriodicalIF":2.3,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8370483/pdf/bioe.2021.0017.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39380164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-06-01Epub Date: 2021-06-16DOI: 10.1089/bioe.2021.0011
Tailise Carolina de Souza-Guerreiro, Munehiro Asally
During aging, mitochondrial membrane potential, a key indicator for bioenergetics of cells, depolarizes in a wide range of species-from yeasts, plants to animals. In humans, the decline of mitochondrial activities can impact the high-energy-consuming organs, such as the brain and heart, and increase the risks of age-linked diseases. Intriguingly, a mild depolarization of mitochondria has lifespan-extending effects, suggesting an important role played by bioelectricity during aging. However, the underpinning biophysical mechanism is not very well understood due in part to the difficulties associated with a multiscale process. Budding yeast Saccharomyces cerevisiae could provide a model system to bridge this knowledge gap and provide insights into aging. In this perspective, we overview recent studies on the yeast mitochondrial membrane electrophysiology and aging and call for more electrochemical and biophysical studies on aging.
{"title":"Seeking Insights into Aging Through Yeast Mitochondrial Electrophysiology.","authors":"Tailise Carolina de Souza-Guerreiro, Munehiro Asally","doi":"10.1089/bioe.2021.0011","DOIUrl":"https://doi.org/10.1089/bioe.2021.0011","url":null,"abstract":"<p><p>During aging, mitochondrial membrane potential, a key indicator for bioenergetics of cells, depolarizes in a wide range of species-from yeasts, plants to animals. In humans, the decline of mitochondrial activities can impact the high-energy-consuming organs, such as the brain and heart, and increase the risks of age-linked diseases. Intriguingly, a mild depolarization of mitochondria has lifespan-extending effects, suggesting an important role played by bioelectricity during aging. However, the underpinning biophysical mechanism is not very well understood due in part to the difficulties associated with a multiscale process. Budding yeast <i>Saccharomyces cerevisiae</i> could provide a model system to bridge this knowledge gap and provide insights into aging. In this perspective, we overview recent studies on the yeast mitochondrial membrane electrophysiology and aging and call for more electrochemical and biophysical studies on aging.</p>","PeriodicalId":29923,"journal":{"name":"Bioelectricity","volume":"3 2","pages":"111-115"},"PeriodicalIF":2.3,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8380933/pdf/bioe.2021.0011.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39380226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-06-01Epub Date: 2021-06-16DOI: 10.1089/bioe.2021.0010
James Q Boedicker, Manasi Gangan, Kyle Naughton, Fengjie Zhao, Jeffrey A Gralnick, Mohamed Y El-Naggar
Many species of bacteria are naturally capable of types of electron transport not observed in eukaryotic cells. Some species live in environments containing heavy metals not typically encountered by cells of multicellular organisms, such as arsenic, cadmium, and mercury, leading to the evolution of enzymes to deal with these environmental toxins. Bacteria also inhabit a variety of extreme environments, and are capable of respiration even in the absence of oxygen as a terminal electron acceptor. Over the years, several of these exotic redox and electron transport pathways have been discovered and characterized in molecular-level detail, and more recently synthetic biology has begun to utilize these pathways to engineer cells capable of detecting and processing a variety of metals and semimetals. One such application is the biologically controlled synthesis of nanoparticles. This review will introduce the basic concepts of bacterial metal reduction, summarize recent work in engineering bacteria for nanoparticle production, and highlight the most cutting-edge work in the characterization and application of bacterial electron transport pathways.
{"title":"Engineering Biological Electron Transfer and Redox Pathways for Nanoparticle Synthesis.","authors":"James Q Boedicker, Manasi Gangan, Kyle Naughton, Fengjie Zhao, Jeffrey A Gralnick, Mohamed Y El-Naggar","doi":"10.1089/bioe.2021.0010","DOIUrl":"https://doi.org/10.1089/bioe.2021.0010","url":null,"abstract":"<p><p>Many species of bacteria are naturally capable of types of electron transport not observed in eukaryotic cells. Some species live in environments containing heavy metals not typically encountered by cells of multicellular organisms, such as arsenic, cadmium, and mercury, leading to the evolution of enzymes to deal with these environmental toxins. Bacteria also inhabit a variety of extreme environments, and are capable of respiration even in the absence of oxygen as a terminal electron acceptor. Over the years, several of these exotic redox and electron transport pathways have been discovered and characterized in molecular-level detail, and more recently synthetic biology has begun to utilize these pathways to engineer cells capable of detecting and processing a variety of metals and semimetals. One such application is the biologically controlled synthesis of nanoparticles. This review will introduce the basic concepts of bacterial metal reduction, summarize recent work in engineering bacteria for nanoparticle production, and highlight the most cutting-edge work in the characterization and application of bacterial electron transport pathways.</p>","PeriodicalId":29923,"journal":{"name":"Bioelectricity","volume":"3 2","pages":"126-135"},"PeriodicalIF":2.3,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8380940/pdf/bioe.2021.0010.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39380229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-06-01Epub Date: 2021-06-16DOI: 10.1089/bioe.2021.0018
Ann M Rajnicek
The Buzz for this Special Issue on the Bioelectricity of the Tumor Microenvironment includes reviews and primary articles to whet your appetite on topics related to tumor cells (of course!) but also encompasses topics on the nano-scale (ions, small molecules, membranes and nanoparticles), micro-scale (electroactive microorganisms), electrode-tissue interfaces (in spinal cord, brain and tumor microenvironments) and ion transporting tissues (organoids). Enjoy! Cells versus tissues: The potential for cancer There is growing interest in controlling tumors by changing the bioelectrical traits of cancer cells. This paper describes a bioelectric model underpinning cancer progression and treatment that reflects the dynamic interaction of the bioelectrical properties of cells and tissues.
{"title":"Recent, Bioelectricity-Related Articles Selected by Ann M. Rajnicek, Media Editor of <i>Bioelectricity</i>.","authors":"Ann M Rajnicek","doi":"10.1089/bioe.2021.0018","DOIUrl":"https://doi.org/10.1089/bioe.2021.0018","url":null,"abstract":"The Buzz for this Special Issue on the Bioelectricity of the Tumor Microenvironment includes reviews and primary articles to whet your appetite on topics related to tumor cells (of course!) but also encompasses topics on the nano-scale (ions, small molecules, membranes and nanoparticles), micro-scale (electroactive microorganisms), electrode-tissue interfaces (in spinal cord, brain and tumor microenvironments) and ion transporting tissues (organoids). Enjoy! Cells versus tissues: The potential for cancer There is growing interest in controlling tumors by changing the bioelectrical traits of cancer cells. This paper describes a bioelectric model underpinning cancer progression and treatment that reflects the dynamic interaction of the bioelectrical properties of cells and tissues.","PeriodicalId":29923,"journal":{"name":"Bioelectricity","volume":"3 2","pages":"147-153"},"PeriodicalIF":2.3,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8380929/pdf/bioe.2021.0018.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39380165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-03-01Epub Date: 2021-03-16DOI: 10.1089/bioe.2020.0026
Devon Davidian, Benjamin Ziman, Ariel L Escobar, Néstor J Oviedo
Background: The use of direct current electric stimulation (DCS) is an effective strategy to treat disease and enhance body functionality. Thus, treatment with DCS is an attractive biomedical alternative, but the molecular underpinnings remain mostly unknown. The lack of experimental models to dissect the effects of DCS from molecular to organismal levels is an important caveat. Here, we introduce the planarian flatworm Schmidtea mediterranea as a tractable organism for in vivo studies of DCS. We developed an experimental method that facilitates the application of direct current electrical stimulation to the whole planarian body (pDCS). Materials and Methods: Planarian immobilization was achieved by combining treatment with anesthesia, agar embedding, and low temperature via a dedicated thermoelectric cooling unit. Electric currents for pDCS were delivered using pulled glass microelectrodes. The electric potential was supplied through a constant voltage power supply. pDCS was administered up to six hours, and behavioral and molecular effects were measured by using video recordings, immunohistochemistry, and gene expression analysis. Results: The behavioral immobilization effects are reversible, and pDCS resulted in a redistribution of mitotic cells along the mediolateral axis of the planarian body. The pDCS effects were dependent on the polarity of the electric field, which led to either increase in reductions in mitotic densities associated with the time of pDCS. The changes in mitotic cells were consistent with apparent redistribution in gene expression of the stem cell marker smedwi-1. Conclusion: The immobilization technique presented in this work facilitates studies aimed at dissecting the effects of exogenous electric stimulation in the adult body. Treatment with DCS can be administered for varying times, and the consequences evaluated at different levels, including animal behavior, cellular and transcriptional changes. Indeed, treatment with pDCS can alter cellular and transcriptional parameters depending on the polarity of the electric field and duration of the exposure.
{"title":"Direct Current Electric Stimulation Alters the Frequency and the Distribution of Mitotic Cells in Planarians.","authors":"Devon Davidian, Benjamin Ziman, Ariel L Escobar, Néstor J Oviedo","doi":"10.1089/bioe.2020.0026","DOIUrl":"https://doi.org/10.1089/bioe.2020.0026","url":null,"abstract":"<p><p><b><i>Background:</i></b> The use of direct current electric stimulation (DCS) is an effective strategy to treat disease and enhance body functionality. Thus, treatment with DCS is an attractive biomedical alternative, but the molecular underpinnings remain mostly unknown. The lack of experimental models to dissect the effects of DCS from molecular to organismal levels is an important caveat. Here, we introduce the planarian flatworm <i>Schmidtea mediterranea</i> as a tractable organism for <i>in vivo</i> studies of DCS. We developed an experimental method that facilitates the application of direct current electrical stimulation to the whole planarian body (pDCS). <b><i>Materials and Methods:</i></b> Planarian immobilization was achieved by combining treatment with anesthesia, agar embedding, and low temperature via a dedicated thermoelectric cooling unit. Electric currents for pDCS were delivered using pulled glass microelectrodes. The electric potential was supplied through a constant voltage power supply. pDCS was administered up to six hours, and behavioral and molecular effects were measured by using video recordings, immunohistochemistry, and gene expression analysis. <b><i>Results:</i></b> The behavioral immobilization effects are reversible, and pDCS resulted in a redistribution of mitotic cells along the mediolateral axis of the planarian body. The pDCS effects were dependent on the polarity of the electric field, which led to either increase in reductions in mitotic densities associated with the time of pDCS. The changes in mitotic cells were consistent with apparent redistribution in gene expression of the stem cell marker <i>smedwi-1</i>. <b><i>Conclusion:</i></b> The immobilization technique presented in this work facilitates studies aimed at dissecting the effects of exogenous electric stimulation in the adult body. Treatment with DCS can be administered for varying times, and the consequences evaluated at different levels, including animal behavior, cellular and transcriptional changes. Indeed, treatment with pDCS can alter cellular and transcriptional parameters depending on the polarity of the electric field and duration of the exposure.</p>","PeriodicalId":29923,"journal":{"name":"Bioelectricity","volume":"3 1","pages":"77-91"},"PeriodicalIF":2.3,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/bioe.2020.0026","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39379780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-03-01Epub Date: 2021-03-16DOI: 10.1089/bioe.2021.0004
Mustafa B A Djamgoz, Michael Levin
{"title":"Editorial.","authors":"Mustafa B A Djamgoz, Michael Levin","doi":"10.1089/bioe.2021.0004","DOIUrl":"https://doi.org/10.1089/bioe.2021.0004","url":null,"abstract":"","PeriodicalId":29923,"journal":{"name":"Bioelectricity","volume":"3 1","pages":"2"},"PeriodicalIF":2.3,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8380934/pdf/bioe.2021.0004.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39382118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}