Social Media sites have become increasingly popular platforms for developing and maintaining interpersonal relationships. Although the usage of computer-mediated communication is normal in dayto-day life, the understanding behind how and why these relationships grow is scarce. This literature review considers relational elements such as self-disclosure and reciprocity, and how they are impacted by online elements such as an asynchronous context, controllability, and the disinhibition effect. Contrary to interpersonal relationships that develop in a physical context, the law of reciprocity is fulfilled and replaced by affirmation and recognition from relational partners, while self-disclosure continues to be a vital element within relationships. Developing an online relationship isn’t difficult, but the factors involved are varied and worth exploring in further study.
{"title":"“Hello? Are You Still There?” The Impact of Social Media on Self-Disclosure and Reciprocity in Interpersonal Relationships: A Literature Review","authors":"Costello, D. Clara","doi":"10.15385/jch.2018.2.2.3","DOIUrl":"https://doi.org/10.15385/jch.2018.2.2.3","url":null,"abstract":"Social Media sites have become increasingly popular platforms for developing and maintaining interpersonal relationships. Although the usage of computer-mediated communication is normal in dayto-day life, the understanding behind how and why these relationships grow is scarce. This literature review considers relational elements such as self-disclosure and reciprocity, and how they are impacted by online elements such as an asynchronous context, controllability, and the disinhibition effect. Contrary to interpersonal relationships that develop in a physical context, the law of reciprocity is fulfilled and replaced by affirmation and recognition from relational partners, while self-disclosure continues to be a vital element within relationships. Developing an online relationship isn’t difficult, but the factors involved are varied and worth exploring in further study.","PeriodicalId":9750,"journal":{"name":"Channels","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78273963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The Russo-Finnish War of 1939-1940, also known as the Winter War, forms a curious portion of World War II history that bears further study. Occurring during the “Phony War”—the period of calm following Hitler’s invasion of Poland—the Winter War offers a glimpse into the attitudes of the major powers as the growing necessity of the coming war becomes increasingly clear during 1939 and 1940. Specifically, the Winter War provides insight into Soviet imperialism and its concerns over German aggression, and forms a crucial portion of the German decision to invade Russia in the summer of 1941. Without consideration of the Winter War and the conclusions drawn from it by the major world powers, it is difficult to form a satisfactory explanation of each power’s behavior in the Second World War. Therefore, though it was a relatively brief conflict, the Winter War is crucial to a proper understanding of the events of World War II as a whole.
{"title":"The Winter War: Its Causes and Effects","authors":"E. Beck","doi":"10.15385/JCH.2018.2.2.4","DOIUrl":"https://doi.org/10.15385/JCH.2018.2.2.4","url":null,"abstract":"The Russo-Finnish War of 1939-1940, also known as the Winter War, forms a curious portion of World War II history that bears further study. Occurring during the “Phony War”—the period of calm following Hitler’s invasion of Poland—the Winter War offers a glimpse into the attitudes of the major powers as the growing necessity of the coming war becomes increasingly clear during 1939 and 1940. Specifically, the Winter War provides insight into Soviet imperialism and its concerns over German aggression, and forms a crucial portion of the German decision to invade Russia in the summer of 1941. Without consideration of the Winter War and the conclusions drawn from it by the major world powers, it is difficult to form a satisfactory explanation of each power’s behavior in the Second World War. Therefore, though it was a relatively brief conflict, the Winter War is crucial to a proper understanding of the events of World War II as a whole.","PeriodicalId":9750,"journal":{"name":"Channels","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84427263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Second language development is an important topic of discussion in an increasingly multilingual world. This study aims to examine and detail research on the effects of code-mixing (CM) on second language development, answering how CM facilitates or constrains second language acquisition. Peer-reviewed articles on the topic published between 2013 and 2018 were examined and synthesized. Language learners/ multilinguals answered questionnaires about their views on CM and second language acquisition, and a language teacher was interviewed regarding use of L1 in the language classroom and CM as a pedagogical tool. This study found that CM can be a beneficial tool for language learning and instruction at the beginning stages of a learner’s acquisition, but use of L1 becomes less necessary and less beneficial as a language learner moves closer to fluency. However, CM is not necessarily a sign of low language competence and is used by multilinguals for a number of reasons.
{"title":"The Effects of Code-Mixing on Second Language Development","authors":"Aimee K Spice","doi":"10.15385/JCH.2018.3.1.1","DOIUrl":"https://doi.org/10.15385/JCH.2018.3.1.1","url":null,"abstract":"Second language development is an important topic of discussion in an increasingly multilingual world. This study aims to examine and detail research on the effects of code-mixing (CM) on second language development, answering how CM facilitates or constrains second language acquisition. Peer-reviewed articles on the topic published between 2013 and 2018 were examined and synthesized. Language learners/ multilinguals answered questionnaires about their views on CM and second language acquisition, and a language teacher was interviewed regarding use of L1 in the language classroom and CM as a pedagogical tool. This study found that CM can be a beneficial tool for language learning and instruction at the beginning stages of a learner’s acquisition, but use of L1 becomes less necessary and less beneficial as a language learner moves closer to fluency. However, CM is not necessarily a sign of low language competence and is used by multilinguals for a number of reasons.","PeriodicalId":9750,"journal":{"name":"Channels","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73959568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This paper presents a brief overview of the biblical theological theme of atonement. This paper attempts to demonstrate that atonement is a central theme by using biblical theological tools to show its connection to the canon. Specifically, this paper observes the work of Leviticus and Hebrews, looking at the Day of Atonement and its relationship to Christ's atonement presented in Hebrews. This is accomplished through looking at specific aspects related to the atonement such as sacrifice and priesthood that allow the intertextual connections to be seen and demonstrated. These connections aid one in seeing atonement as a key biblical theological theme.
{"title":"The Accomplishment of Biblical Theology on Atonement","authors":"Braydon Pape","doi":"10.15385/jch.2018.2.2.1","DOIUrl":"https://doi.org/10.15385/jch.2018.2.2.1","url":null,"abstract":"This paper presents a brief overview of the biblical theological theme of atonement. This paper attempts to demonstrate that atonement is a central theme by using biblical theological tools to show its connection to the canon. Specifically, this paper observes the work of Leviticus and Hebrews, looking at the Day of Atonement and its relationship to Christ's atonement presented in Hebrews. This is accomplished through looking at specific aspects related to the atonement such as sacrifice and priesthood that allow the intertextual connections to be seen and demonstrated. These connections aid one in seeing atonement as a key biblical theological theme.","PeriodicalId":9750,"journal":{"name":"Channels","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89034886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Before Vietnam: Understanding the Initial Stages of US Involvement in Southeast Asia, 1945-1949","authors":"Jacob T. Mach","doi":"10.15385/JCH.2018.3.1.4","DOIUrl":"https://doi.org/10.15385/JCH.2018.3.1.4","url":null,"abstract":"","PeriodicalId":9750,"journal":{"name":"Channels","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81719970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This paper explores qualified immunity jurisprudence in the context of Section 1983 lawsuits against police officers. Following an overview of the history behind this jurisprudence, this research looks into the current problems with the application of qualified immunity: lack of guidance for lower courts, a need for constitutional rights articulation, and a divergence from notice-based standard for particularity. This study suggests guiding the trajectory of case law toward solutions with foundations already present in precedent rather than overhauling the system of qualified immunity.
{"title":"The Right Balance: Qualified Immunity and Section 1983","authors":"Jana Minich","doi":"10.15385/JCH.2017.2.1.4","DOIUrl":"https://doi.org/10.15385/JCH.2017.2.1.4","url":null,"abstract":"This paper explores qualified immunity jurisprudence in the context of Section 1983 lawsuits against police officers. Following an overview of the history behind this jurisprudence, this research looks into the current problems with the application of qualified immunity: lack of guidance for lower courts, a need for constitutional rights articulation, and a divergence from notice-based standard for particularity. This study suggests guiding the trajectory of case law toward solutions with foundations already present in precedent rather than overhauling the system of qualified immunity.","PeriodicalId":9750,"journal":{"name":"Channels","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2017-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72444020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-05-04DOI: 10.1080/19336950.2016.1256517
Jeffery A. Boychuk, G. Teskey
Hyperpolarisation-activated, cyclic nucleotide-gated (HCN) channel mutations are linked to disorders characterized by the occurrence of recurrent seizures (epilepsies) and HCN channel dysfunction has also been observed following evoked seizures in otherwise typical brains. Whether HCN channels contribute to the behavioral co-morbidities associated with epilepsy has received limited attention, despite extensive work to show that they serve as key regulators of neuronal excitability. A recent article, co-authored by us, provides evidence that experimental seizures disrupt HCN channel function and that this type of disruption leads to long-term impairments in skilled motor behavior. Given that interictal motor impairments are observed following experimental seizures and clinical epilepsy, this new study suggests an intriguing possibility that HCN channels represent a novel therapeutic target to treat co-morbidities of this disorder. HCN channels provide a diverse set of contributions to brain excitability. At the level of individual neurons, the current mediated by HCN channels, referred to by many names including Ih, affects integration of synaptic input as well as patterns of action potential firing. It has previously been shown that HCN channels serve as a mechanism to restrict spatial firing fields within entorhinal cortex. HCN channels also restrict hippocampal-dependent spatial memory. In our recent work, we sought to examine the role of HCN channels for networks located in motor cortex. The study manipulated HCN channels using 3 separate approaches. Repeated experimental seizures were used as they reduce Ih in layer 5 pyramidal cells that make up the cortical spinal tract. The pharmacological blocker ZD7288 was locally applied within motor cortex and global HCN1 knockout (HCN1) mice were used as a genetic strategy. In order to examine network function of motor cortex, in vivo studies were performed using standard intracortical microstimulation (ICMS) to systematically measure evoked forelimb movement responses across sites within neocortex. With short-train ICMS parameters, stimulation at individual sites within motor cortex predominantly results in responses on the contralateral side of the body that are characterized by simple flexion or extension across a single joint. With repeated seizures there was a substantial increase in the number of stimulation sites that exhibited complex forelimb movement responses rather than the simple flexion or extension movements. These new complex forelimb responses occurred as combinations of simple movement responses and were present contralateral to stimulation and often bilaterally. This result was also seen after direct application of ZD7228 and in HCN1 mice. Additionally, no further change in ICMS responses occurred when the effects of ZD7228 were tested in HCN1 mice. Since experimental seizures had previously been shown to impair skilled motor behavior, additional experiments tested whether genetic o
{"title":"Loss of HCN channel mediated Ih current following seizures accounts for movement dysfunction","authors":"Jeffery A. Boychuk, G. Teskey","doi":"10.1080/19336950.2016.1256517","DOIUrl":"https://doi.org/10.1080/19336950.2016.1256517","url":null,"abstract":"Hyperpolarisation-activated, cyclic nucleotide-gated (HCN) channel mutations are linked to disorders characterized by the occurrence of recurrent seizures (epilepsies) and HCN channel dysfunction has also been observed following evoked seizures in otherwise typical brains. Whether HCN channels contribute to the behavioral co-morbidities associated with epilepsy has received limited attention, despite extensive work to show that they serve as key regulators of neuronal excitability. A recent article, co-authored by us, provides evidence that experimental seizures disrupt HCN channel function and that this type of disruption leads to long-term impairments in skilled motor behavior. Given that interictal motor impairments are observed following experimental seizures and clinical epilepsy, this new study suggests an intriguing possibility that HCN channels represent a novel therapeutic target to treat co-morbidities of this disorder. HCN channels provide a diverse set of contributions to brain excitability. At the level of individual neurons, the current mediated by HCN channels, referred to by many names including Ih, affects integration of synaptic input as well as patterns of action potential firing. It has previously been shown that HCN channels serve as a mechanism to restrict spatial firing fields within entorhinal cortex. HCN channels also restrict hippocampal-dependent spatial memory. In our recent work, we sought to examine the role of HCN channels for networks located in motor cortex. The study manipulated HCN channels using 3 separate approaches. Repeated experimental seizures were used as they reduce Ih in layer 5 pyramidal cells that make up the cortical spinal tract. The pharmacological blocker ZD7288 was locally applied within motor cortex and global HCN1 knockout (HCN1) mice were used as a genetic strategy. In order to examine network function of motor cortex, in vivo studies were performed using standard intracortical microstimulation (ICMS) to systematically measure evoked forelimb movement responses across sites within neocortex. With short-train ICMS parameters, stimulation at individual sites within motor cortex predominantly results in responses on the contralateral side of the body that are characterized by simple flexion or extension across a single joint. With repeated seizures there was a substantial increase in the number of stimulation sites that exhibited complex forelimb movement responses rather than the simple flexion or extension movements. These new complex forelimb responses occurred as combinations of simple movement responses and were present contralateral to stimulation and often bilaterally. This result was also seen after direct application of ZD7228 and in HCN1 mice. Additionally, no further change in ICMS responses occurred when the effects of ZD7228 were tested in HCN1 mice. Since experimental seizures had previously been shown to impair skilled motor behavior, additional experiments tested whether genetic o","PeriodicalId":9750,"journal":{"name":"Channels","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2017-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89763434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-05-04DOI: 10.1080/19336950.2016.1259040
Emma N. Bardsley, H. Larsen, D. Paterson
Dysautonomia is a well-established contributor to the development and progression of hypertension and many other cardiovascular diseases. Sympathetic hyperactivity and vagal impairment are features of human hypertension, as well as in subjects with a familial predisposition for hypertension. This neural phenotype is also observed in the spontaneously hypertensive rat (SHR). Moreover, it is widely accepted that autonomic imbalance contributes to the pathogenesis of hypertension itself, where emerging research is beginning to shed light on the key cellular and molecular changes that occur in diseased neurons. The postganglionic sympathetic stellate neurons (PGSNs) of the SHR that predominantly innervate the heart, display increased intracellular calcium [Ca2C]i transients linked to impaired neuronal nitric oxide synthase (nNOS) activity. Together, with downstream reductions in nitric oxide (NO)-cyclic guanosine monophosphate (cGMP), this results in enhanced end-organ neurotransmission. Pharmacological and genetic techniques aimed at enhancing NO-cGMPprotein kinase G (PKG) signaling have been successful in rectifying the Ca2C phenotype in SHR PGSNs and decreasing sympathetic hyperactivity. Interestingly, sympathetic impairment is present in young prohypertensive SHRs (pro-SHR), suggesting that these intracellular changes form early hallmarks of hypertension; however, the precise nature of events that trigger sympathetic dysfunction remain unclear. Recently, we published data suggesting that sympathetic hyperactivity in the stellate neurons from the pro-SHR may be triggered by dysregulated Ca2C channel activity, resulting in greater Ca2C influx. N-type Ca channels (Cav2.2) were identified as the major contributor to Ca2C entry in PGSNs, that in turn facilitate sympathetic neurotransmission. Inhibition of the N-type Ca2C channel also reduces the propensity for fatal ventricular arrhythmias and ameliorates autonomic dysfunction in a heart failure mouse model. When taken together these findings support a significant physiological role of the N-type Ca2C channel in neural modulation associated with cardiovascular disease. In our study we reported that PGSNwhole-cell Ca2C currents of the pro-SHR are greater when compared to normotensive rats. Moreover, we demonstrated a novel link between impaired cyclic nucleotide signaling and increased N-type Ca2C channel activity in prohypertension. cAMP and cGMP are ubiquitous second messenger cyclic nucleotide signaling molecules that regulate fundamental intracellular processes through direct activation of their respective kinases: protein kinase A (PKA) and PKG. Importantly, cyclic nucleotide regulation of neuronal [Ca2C]i is necessary for normal PGSN function. Indeed, site-specific phospho-regulation of several voltage-gated Ca2C channel subtypes has been well documented, where a fine balance between PKA and PKG activity is maintained in order to regulate Ca2C-dependent neurotransmission. Additional regulatory me
{"title":"Impaired cAMP-cGMP cross-talk during cardiac sympathetic dysautonomia","authors":"Emma N. Bardsley, H. Larsen, D. Paterson","doi":"10.1080/19336950.2016.1259040","DOIUrl":"https://doi.org/10.1080/19336950.2016.1259040","url":null,"abstract":"Dysautonomia is a well-established contributor to the development and progression of hypertension and many other cardiovascular diseases. Sympathetic hyperactivity and vagal impairment are features of human hypertension, as well as in subjects with a familial predisposition for hypertension. This neural phenotype is also observed in the spontaneously hypertensive rat (SHR). Moreover, it is widely accepted that autonomic imbalance contributes to the pathogenesis of hypertension itself, where emerging research is beginning to shed light on the key cellular and molecular changes that occur in diseased neurons. The postganglionic sympathetic stellate neurons (PGSNs) of the SHR that predominantly innervate the heart, display increased intracellular calcium [Ca2C]i transients linked to impaired neuronal nitric oxide synthase (nNOS) activity. Together, with downstream reductions in nitric oxide (NO)-cyclic guanosine monophosphate (cGMP), this results in enhanced end-organ neurotransmission. Pharmacological and genetic techniques aimed at enhancing NO-cGMPprotein kinase G (PKG) signaling have been successful in rectifying the Ca2C phenotype in SHR PGSNs and decreasing sympathetic hyperactivity. Interestingly, sympathetic impairment is present in young prohypertensive SHRs (pro-SHR), suggesting that these intracellular changes form early hallmarks of hypertension; however, the precise nature of events that trigger sympathetic dysfunction remain unclear. Recently, we published data suggesting that sympathetic hyperactivity in the stellate neurons from the pro-SHR may be triggered by dysregulated Ca2C channel activity, resulting in greater Ca2C influx. N-type Ca channels (Cav2.2) were identified as the major contributor to Ca2C entry in PGSNs, that in turn facilitate sympathetic neurotransmission. Inhibition of the N-type Ca2C channel also reduces the propensity for fatal ventricular arrhythmias and ameliorates autonomic dysfunction in a heart failure mouse model. When taken together these findings support a significant physiological role of the N-type Ca2C channel in neural modulation associated with cardiovascular disease. In our study we reported that PGSNwhole-cell Ca2C currents of the pro-SHR are greater when compared to normotensive rats. Moreover, we demonstrated a novel link between impaired cyclic nucleotide signaling and increased N-type Ca2C channel activity in prohypertension. cAMP and cGMP are ubiquitous second messenger cyclic nucleotide signaling molecules that regulate fundamental intracellular processes through direct activation of their respective kinases: protein kinase A (PKA) and PKG. Importantly, cyclic nucleotide regulation of neuronal [Ca2C]i is necessary for normal PGSN function. Indeed, site-specific phospho-regulation of several voltage-gated Ca2C channel subtypes has been well documented, where a fine balance between PKA and PKG activity is maintained in order to regulate Ca2C-dependent neurotransmission. Additional regulatory me","PeriodicalId":9750,"journal":{"name":"Channels","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2017-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86042803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-04-14DOI: 10.1080/19336950.2016.1249077
N. Bavi, O. Bavi, M. Vossoughi, R. Naghdabadi, A. Hill, B. Martinac, Y. Jamali
ABSTRACT Gating of mechanosensitive (MS) channels is driven by a hierarchical cascade of movements and deformations of transmembrane helices in response to bilayer tension. Determining the intrinsic mechanical properties of the individual transmembrane helices is therefore central to understanding the intricacies of the gating mechanism of MS channels. We used a constant-force steered molecular dynamics (SMD) approach to perform unidirectional pulling tests on all the helices of MscL in M. tuberculosis and E. coli homologs. Using this method, we could overcome the issues encountered with the commonly used constant-velocity SMD simulations, such as low mechanical stability of the helix during stretching and high dependency of the elastic properties on the pulling rate. We estimated Young's moduli of the α-helices of MscL to vary between 0.2 and 12.5 GPa with TM2 helix being the stiffest. We also studied the effect of water on the properties of the pore-lining TM1 helix. In the absence of water, this helix exhibited a much stiffer response. By monitoring the number of hydrogen bonds, it appears that water acts like a ‘lubricant’ (softener) during TM1 helix elongation. These data shed light on another physical aspect underlying hydrophobic gating of MS channels, in particular MscL.
{"title":"Nanomechanical properties of MscL α helices: A steered molecular dynamics study","authors":"N. Bavi, O. Bavi, M. Vossoughi, R. Naghdabadi, A. Hill, B. Martinac, Y. Jamali","doi":"10.1080/19336950.2016.1249077","DOIUrl":"https://doi.org/10.1080/19336950.2016.1249077","url":null,"abstract":"ABSTRACT Gating of mechanosensitive (MS) channels is driven by a hierarchical cascade of movements and deformations of transmembrane helices in response to bilayer tension. Determining the intrinsic mechanical properties of the individual transmembrane helices is therefore central to understanding the intricacies of the gating mechanism of MS channels. We used a constant-force steered molecular dynamics (SMD) approach to perform unidirectional pulling tests on all the helices of MscL in M. tuberculosis and E. coli homologs. Using this method, we could overcome the issues encountered with the commonly used constant-velocity SMD simulations, such as low mechanical stability of the helix during stretching and high dependency of the elastic properties on the pulling rate. We estimated Young's moduli of the α-helices of MscL to vary between 0.2 and 12.5 GPa with TM2 helix being the stiffest. We also studied the effect of water on the properties of the pore-lining TM1 helix. In the absence of water, this helix exhibited a much stiffer response. By monitoring the number of hydrogen bonds, it appears that water acts like a ‘lubricant’ (softener) during TM1 helix elongation. These data shed light on another physical aspect underlying hydrophobic gating of MS channels, in particular MscL.","PeriodicalId":9750,"journal":{"name":"Channels","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2017-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87270699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-03-04DOI: 10.1080/19336950.2016.1247133
Toshiaki Okada, Md. Rafiqul Islam, N. Tsiferova, Y. Okada, R. Sabirov
ABSTRACT The broadly expressed volume-sensitive outwardly rectifying anion channel (VSOR, also called VRAC) plays essential roles in cell survival and death. Recent findings have suggested that LRRC8A is a core component of VSOR in human cells. In the present study, VSOR currents were found to be largely reduced by siRNA against LRRC8A in mouse C127 cells as well. In contrast, LRRC8A knockdown never affected activities of 4 other types of anion channel activated by acid, Ca2+, patch excision or cAMP. While cisplatin-resistant KCP-4 cells poorly expressed endogenous VSOR activity, molecular expression levels of LRRC8A, LRRC8D and LRRC8E were indistinguishable between VSOR-deficient KCP-4 cells and the parental VSOR-rich KB cells. Furthermore, overexpression of LRRC8A alone or together with LRRC8D or LRRC8E in KCP-4 cells failed to restore VSOR activity. These results show that deficiency of VSOR currents in KCP-4 cells is not due to insufficient expression of the LRRC8A/D/E gene, suggesting an essential involvement of some other factor(s), and indicate that further study is required to better understand the complexities of the molecular determinants of VSOR, including the precise role of LRRC8 proteins.
{"title":"Specific and essential but not sufficient roles of LRRC8A in the activity of volume-sensitive outwardly rectifying anion channel (VSOR)","authors":"Toshiaki Okada, Md. Rafiqul Islam, N. Tsiferova, Y. Okada, R. Sabirov","doi":"10.1080/19336950.2016.1247133","DOIUrl":"https://doi.org/10.1080/19336950.2016.1247133","url":null,"abstract":"ABSTRACT The broadly expressed volume-sensitive outwardly rectifying anion channel (VSOR, also called VRAC) plays essential roles in cell survival and death. Recent findings have suggested that LRRC8A is a core component of VSOR in human cells. In the present study, VSOR currents were found to be largely reduced by siRNA against LRRC8A in mouse C127 cells as well. In contrast, LRRC8A knockdown never affected activities of 4 other types of anion channel activated by acid, Ca2+, patch excision or cAMP. While cisplatin-resistant KCP-4 cells poorly expressed endogenous VSOR activity, molecular expression levels of LRRC8A, LRRC8D and LRRC8E were indistinguishable between VSOR-deficient KCP-4 cells and the parental VSOR-rich KB cells. Furthermore, overexpression of LRRC8A alone or together with LRRC8D or LRRC8E in KCP-4 cells failed to restore VSOR activity. These results show that deficiency of VSOR currents in KCP-4 cells is not due to insufficient expression of the LRRC8A/D/E gene, suggesting an essential involvement of some other factor(s), and indicate that further study is required to better understand the complexities of the molecular determinants of VSOR, including the precise role of LRRC8 proteins.","PeriodicalId":9750,"journal":{"name":"Channels","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2017-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79682597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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