scholarly journals Unveiling the Gating Mechanism of CRAC Channel: A Computational Study

2021 ◽  
Vol 8 ◽  
Author(s):  
Carlo Guardiani ◽  
Delia Sun ◽  
Alberto Giacomello
Keyword(s):  
Ion Channels ◽  
Computational Study ◽  
Sampling Technique ◽  
Empty Space ◽  
Enhanced Sampling ◽  
Hydrophobic Region ◽  
Gating Mechanism ◽  
Crac Channel ◽  
First Time

CRAC channel is ubiquitous and its importance in the regulation of the immune system is testified by the severe immunodeficiencies caused by its mutations. In this work we took advantage of the availability of open and closed structures of this channel to run for the first time simulations of the whole gating process reaching the relevant time-scale with an enhanced sampling technique, Targeted Molecular Dynamics. Our simulations highlighted a complex allosteric propagation of the conformational change from peripheral helices, where the activator STIM1 binds, to the central pore helices. In agreement with mutagenesis data, our simulations revealed the key role of residue H206 whose displacement creates an empty space behind the hydrophobic region of the pore, thus releasing a steric brake and allowing the opening of the channel. Conversely, the process of pore closing culminates with the formation of a bubble that occludes the pore even in the absence of steric block. This mechanism, known as “hydrophobic gating”, has been observed in an increasing number of biological ion channels and also in artificial nanopores. Our study therefore shows promise not only to better understand the molecular origin of diseases caused by disrupted calcium signaling, but also to clarify the mode of action of hydrophobically gated ion channels, possibly even suggesting strategies for the biomimetic design of synthetic nanopores.

scholarly journals Computational study of critical moisture and depth of burn in peat fires

2015 ◽  
Vol 24 (6) ◽  
pp. 798 ◽  
Author(s):  
Xinyan Huang ◽  
Guillermo Rein
Keyword(s):  
Computational Study ◽  
Reaction Rates ◽  
Organic Layers ◽  
Field Samples ◽  
Critical Ignition ◽  
Critical Moisture ◽  
Peat Fires ◽  
First Time ◽  
Smouldering Combustion

Smouldering combustion is the slow, low-temperature, flameless burning of porous fuels and the most important phenomenon of wildfires in peatlands. Smouldering fires propagate both horizontally and vertically through organic layers of the ground and can reach deep into the soil. In this work, we develop a one-dimensional computational model of reactive porous media in the open-source code Gpyro. We investigate the vertical in-depth spread of smouldering fires into peat columns 20 cm deep with heterogeneous profiles of moisture content (MC), inert content (IC) and density. The model solves the species, momentum and energy conservation equations with five-step heterogeneous chemistry, to predict the transient profiles of temperature, species concentration, reaction rates and depth of burn from ignition to spread and to extinction. Modelling results reveal that smouldering combustion can spread over peat layers with very high MC (>250%) if the layer is thin and located below a thick, drier layer. It is shown that the critical moisture for extinction can be much higher than the previously reported critical MC for ignition (e.g. extinction MC up to 256% for low-IC peat, with critical ignition MC of 117%). The predicted critical MC values and depths of burn are compared with experimental measurements for field samples in the literature, showing good agreement. This study provides the physical understanding of the role of moisture in the ignition and extinction of smouldering peat fires, and explains for the first time the phenomenon of smouldering in very wet peat layers.

Modulatory effects of acid-sensing ion channels on action potential generation in hippocampal neurons

2004 ◽  
Vol 287 (3) ◽  
pp. C682-C690 ◽  
Author(s):  
Marija Vukicevic ◽  
Stephan Kellenberger
Keyword(s):  
Ion Channels ◽  
Hippocampal Neurons ◽  
Extracellular Ph ◽  
Ph Changes ◽  
Acid Sensing Ion Channels ◽  
Close Proximity ◽  
First Time ◽  
Rapid Drop ◽  
Cultured Hippocampal Neurons

Extracellular acidification has been shown to generate action potentials (APs) in several types of neurons. In this study, we investigated the role of acid-sensing ion channels (ASICs) in acid-induced AP generation in brain neurons. ASICs are neuronal Na+ channels that belong to the epithelial Na+ channel/degenerin family and are transiently activated by a rapid drop in extracellular pH. We compared the pharmacological and biophysical properties of acid-induced AP generation with those of ASIC currents in cultured hippocampal neurons. Our results show that acid-induced AP generation in these neurons is essentially due to ASIC activation. We demonstrate for the first time that the probability of inducing APs correlates with current entry through ASICs. We also show that ASIC activation in combination with other excitatory stimuli can either facilitate AP generation or inhibit AP bursts, depending on the conditions. ASIC-mediated generation and modulation of APs can be induced by extracellular pH changes from 7.4 to slightly <7. Such local extracellular pH values may be reached by pH fluctuations due to normal neuronal activity. Furthermore, in the plasma membrane, ASICs are localized in close proximity to voltage-gated Na+ and K+ channels, providing the conditions necessary for the transduction of local pH changes into electrical signals.

scholarly journals Role of the Fourth Transmembrane Segment in TRAAK Channel Mechanosensitivity

2018 ◽  
Author(s):  
Mingfeng Zhang ◽  
Fuqiang Yao ◽  
Chengfang Pan ◽  
Zhiqiang Yan
Keyword(s):  
Ion Channels ◽  
Transmembrane Domain ◽  
Mechanical Force ◽  
Dynamic Interactions ◽  
Functional Roles ◽  
Physiological Processes ◽  
Gating Mechanism ◽  
Voltage Gated Ion Channels ◽  
Voltage Sensing Domain

AbstractMechanosensitive ion channels such as Piezo, TRAAK, TRPs and OSCA are important transmembrane proteins that are involved in many physiological processes such as touch, hearing and blood pressure regulation. Unlike ligand-gated channels or voltage-gated ion channels, which have a canonical ligand-binding domain or voltage-sensing domain, the mechanosensitive domain and related gating mechanism remain elusive. TRAAK channels are mechanosensitive channels that convert a physical mechanical force into a flow of potassium ions. The structures of TRAAK channels have been solved, however, the functional roles of the structural domains associated with channel mechanosensitivity remains unclear. Here, we generated a series of chimeric mutations between TRAAK and a non-mechanosensitive silent TWIK-1 K2P channel. We found that the selectivity filter region functions as the major gate of outward rectification and found that lower part of fourth transmembrane domain (M4) is necessary for TRAAK channel mechanosensitivity. We further demonstrated that upper part of M4 can modulate the mechanosensitivity of TRAAK channel. Furthermore, we found that hydrophilic substitutions of W262 and F121 facing each other, and hydrophobic substitutions of Q258 and G124, which are above and below W262 and F121, respectively, greatly increase mechanosensitivity, which suggests that dynamic interactions in the upper part of M4 and PH1 domain are involved in TRAAK channel mechanosensitivity. Interestingly, these gain-of-function mutations are sensitive to cell-poking stimuli, indicating that cell-poking stimuli generate a low membrane mechanical force that opens TRAAK channels. Our results thus showed that fourth transmembrane domain of TRAAK is critical for the gating of TRAAK by mechanical force and suggested that multiple dynamic interactions in the upper part of M4 and PH1 domain are involved in this process.

scholarly journals Role of N-Terminal Hydrophobic Region in Modulating the Subcellular Localization and Enzyme Activity of the Bisphosphate Nucleotidase from Debaryomyces hansenii

2006 ◽  
Vol 5 (2) ◽  
pp. 262-271 ◽  
Author(s):  
Monika Aggarwal ◽  
Alok K. Mondal
Keyword(s):  
Salt Stress ◽  
Debaryomyces Hansenii ◽  
Hydrophobic Region ◽  
Major Mechanism ◽  
Halotolerant Yeast ◽  
Highly Sensitive ◽  
Membrane Bound ◽  
First Time ◽  
Rate Limiting

ABSTRACT 3′, 5′-Bisphosphate nucleotidase is a ubiquitous enzyme that converts 3′-phosphoadenosine-5′-phosphate to adenosine-5′-phosphate and inorganic phosphate. These enzymes are highly sensitive to sodium and lithium and, thus, perform a crucial rate-limiting metabolic step during salt stress in yeast. Recently, we have identified a bisphosphate nucleotidase gene (DHAL2) from the halotolerant yeast Debaryomyces hansenii. One of the unique features of Dhal2p is that it contains an N-terminal 54-amino-acid-residue hydrophobic extension. In this study, we have shown that Dhal2p exists as a cytosolic as well as a membrane-bound form and that salt stress markedly influences the accumulation of the latter form in the cell. We have demonstrated that the N-terminal hydrophobic region was necessary for the synthesis of the membrane-bound isoform. It appeared that an alternative translation initiation was the major mechanism for the synthesis of these two forms. Moreover, the two forms exhibit significant differences in their substrate specificity. Unlike the cytosolic form, the membrane-bound form showed very high activity against inositol-1,4-bisphosphate. Thus, the present study for the first time reports the existence of multiple forms of a bisphosphate nucleotidase in any organism.

Psychological Resilience Provides No Independent Protection From Suicidal Risk

Crisis ◽  
2016 ◽  
Vol 37 (2) ◽  
pp. 130-139 ◽  
Author(s):  
Danica W. Y. Liu ◽  
A. Kate Fairweather-Schmidt ◽  
Richard Burns ◽  
Rachel M. Roberts ◽  
Kaarin J. Anstey
Keyword(s):  
Risk Factors ◽  
Well Being ◽  
Current Status ◽  
Psychological Resilience ◽  
Cross Sectional ◽  
Life Project ◽  
Resilience Factors ◽  
First Time

Abstract. Background: Little is known about the role of resilience in the likelihood of suicidal ideation (SI) over time. Aims: We examined the association between resilience and SI in a young-adult cohort over 4 years. Our objectives were to determine whether resilience was associated with SI at follow-up or, conversely, whether SI was associated with lowered resilience at follow-up. Method: Participants were selected from the Personality and Total Health (PATH) Through Life Project from Canberra and Queanbeyan, Australia, aged 28–32 years at the first time point and 32–36 at the second. Multinomial, linear, and binary regression analyses explored the association between resilience and SI over two time points. Models were adjusted for suicidality risk factors. Results: While unadjusted analyses identified associations between resilience and SI, these effects were fully explained by the inclusion of other suicidality risk factors. Conclusion: Despite strong cross-sectional associations, resilience and SI appear to be unrelated in a longitudinal context, once risk/resilience factors are controlled for. As independent indicators of psychological well-being, suicidality and resilience are essential if current status is to be captured. However, the addition of other factors (e.g., support, mastery) makes this association tenuous. Consequently, resilience per se may not be protective of SI.

Role of Teachers in Building the Concept of Sustainable Development: Success or Failure

2020 ◽  
Vol 1 (1) ◽  
Author(s):  
Ayaz Muhammad Khan ◽  
Amber Jamshaid ◽  
Tayyibah Roohi ◽  
Amna Ramzan
Keyword(s):  
Sustainable Development ◽  
Primary School ◽  
Sampling Technique ◽  
School Teachers ◽  
Primary School Teachers ◽  
Primary Level ◽  
Significant Difference ◽  
Role Of Teachers ◽  
Major Factors

Sustainable Development (SD) is a rich, challenging and thought-provoking construct in social sciences. The main purpose of this paper was to identify and explore the role played by primary school teachers in building up the idea of sustainable development (SD) among students. This paper was intended to identify that how a teacher can successfully execute the concept of SD by influencing students’ minds at the primary level. Quantitative survey technique were utilized for data collection. All the primary school teachers of Lahore division comprised the population of the study. Through multistage sampling technique, 352 primary school teachers were selected as participants of the study. A self-developed SD questionnaire incorporating four major factors (teachers’ awareness, pedagogy, curricular and co-curricular activities) with Cronbach’s alpha value = .93 was used to measure the role of teachers in building the sustainability concept among students at primary level. The results indicated a significant mean score difference among SD scores of teachers, sector wise (private and public). Furthermore, the results also reconnoitered the significant difference (p=.04) between the mean scores of female and male teachers in building up the SD concept in students’ minds.

PERANAN INSPEKTORAT KABUPATENSUMENEP DALAM MENCEGAH DAN MENDETEKSI FRAUD DI DINAS PENDIDIKAN SUMENEP

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Astri Furqani ◽  
Hafidhah .
Keyword(s):  
Local Government ◽  
Qualitative Study ◽  
Asset Management ◽  
Sampling Technique ◽  
Research Data ◽  
Qualitative Approach ◽  
Primary Data ◽  
The Government

In this era, a lot of activities that can not be separated from the practice of cheating or fraud , no exception In the government . Inspektorat Sumenep is the leading institution of internal Local Government in preventing and detecting fraud in the Local Government appropiate Perbup Sumenep No. 29 of 2008 . Dinas Pendidikan Sumenep need attention on the issue . This is due to Dinas Pendidikan Sumenep an agency with the largest number of assets and managing large budgets . These conditions led to the formulation of the problem is How Inspektorat Sumenep role in preventing and detecting fraud in Dinas Pendidikan Sumenep. This study used a qualitative approach in which the focus of this study is Inspektorat role in preventing and detecting fraud at Dinas Pendidikan Sumenep . Primary data obtained by direct interviews with the parties directly related to the determination of the source of research data in a qualitative study using nonprobability sampling . The sampling technique used was purposive sampling . The conclusion of this study, role of the Inspektorat Sumenep in the prevention of fraud in Dinas Pendidikan Sumenep still not maximal . This is due to Inspektorat Sumenep not supervise from the planning / budgeting and not optimal in overseeing and assisting the implementation of the SPIP as an instrument of fraud prevention in Dinas Pendidikan Sumenep . The role of Inspektorat Sumenep in the detection of fraud in Dinas Pendidikan Sumenep done by conducting an audit of financial and asset management in each financial year.Keywords: fraud, government, inspektorat.

Effectiveness Of Toilet Training Education On Mother's Behavior And Toddler Age Toilet Training Ability (18-36 Months)

2020 ◽  
Vol 5 (2) ◽  
pp. 49-55
Author(s):  
Hafiko Andresni ◽  
Zahtamal Zahtamal ◽  
Winda Septiani ◽  
Mitra Mitra ◽  
Lita Lita
Keyword(s):  
Sampling Technique ◽  
T Test ◽  
The Body ◽  
Toilet Training ◽  
Wilcoxon Test ◽  
Control Group ◽  
Maternal Knowledge ◽  
Control Group Design ◽  
Significant Difference

ABSTRACT Toilet training is an effort to train children to be able to control and urinate (BAK) and defecate (BAB). Toilet training is one of the main tasks of children at toddler age. Toilet training is one of the main tasks of children in toddler age which is very important to be done to create independence in children in controlling BAK and BAB and children know the parts of the body and their functions. Data in 2012 shows that ± 60% of parents do not teach toilet training to children from an early age. The aim of the study was to find out the effectiveness of toilet training education on maternal behavior and toilet skills in toddler age training (18-36 months). The study was conducted in July-August 2018. This type of quantitative research used the design of the Quasy pretest and posttest experiment with non-equivalent control group design. Samples were 36 mothers and 36 children with purposive sampling technique. Data analysis used Paired t test, Wilcoxon test, Man-Whitney test an Independent t test. The results showed that toilet training education through lecture methods, modules and maze games was more effective than toilet training education through lecture and leaflet methods on children's knowledge and abilities. Conversely, for the role of mothers in supervision there is no significant difference in effectiveness. Health education is recommended in health promotion programs to increase maternal knowledge, the role of mothers and the ability of toilet training children independently. Keywords: Toilet training, Lecture method, Module, Maze game, Leaflet, Knowledge, Role of mother, Children's ability.

An effectiveness of training program on COVID-19 among healthcare students: A cross section study

2020 ◽  
Vol 11 (SPL1) ◽  
pp. 1250-1254
Author(s):  
Kurvatteppa Halemani ◽  
Merlin Cheema ◽  
Shabana Khatun ◽  
Yadidya ◽  
Bhumika Singh ◽  
...  
Keyword(s):  
Nursing Students ◽  
Training Program ◽  
Cross Section ◽  
Sampling Technique ◽  
Teaching Session ◽  
Post Intervention ◽  
Post Test ◽  
College Of Nursing ◽  
Novel Coronavirus ◽  
First Time

The pandemic COVID-19 is a highly infected disease caused by a novel coronavirus or SARS-Cov-2. The virus was reported for the first time  December 2019 in, China's Wuhan province. Later the virus has broken down into the world and claimed millions of lives. In India, the disease was reported for the first time in Kerala on 30th January 2020. a cross-section one group pre-test & post-test research design was used among the 40 final year BSc nursing students, College of Nursing SGPGIMS, Lucknow India. Samples were selected based on purposive sampling technique and sample criteria. An instrument, the first tool included demographic characteristics Similarly, second instrument used for knowledge assessment. After pre-test assessment, a teaching session was held at the seminar room, college of nursing SGPGIMS Lucknow, India. Subsequently post assessment was held after intervention.  A total of 40 participants responded to the study. Demographic variables like 30(75%) participants had less than 22 years of age, 22(55%) were girls, 14(35%) families income found INR 10000-15000, and the majority of participants obtained COVID-19 related knowledge from news paper16(40%). A gender was found significant with pretest knowledge, and other variables weren't found significant (P=0.05). Knowledge mean & standard deviation in pre & post-intervention, 11.90±2.16 vs15.82±1.39. The mean difference was found in a pre-test & post-test-1 &post-test-2, 3.9, 5.02, & 1.1, respectively. The effectiveness of the training program was checked by paired t-test -10.20 & -13.93, P=0.00.  The study revealed that the teaching session was efficient in the COVID-19 program among BSc nursing students.

Synergetic Theory of Document in Evolution of Document Science

2018 ◽  
pp. 1060-1068
Author(s):  
Galina A. Dvoenosova ◽  
Keyword(s):  
Social Role ◽  
Scientific Study ◽  
Self Organization ◽  
Universal Theory ◽  
Social Self ◽  
Social Goal ◽  
The Social ◽  
Synergetic Theory ◽  
First Time

The article assesses synergetic theory of document as a new development in document science. In information society the social role of document grows, as information involves all members of society in the process of documentation. The transformation of document under the influence of modern information technologies increases its interest to representatives of different sciences. Interdisciplinary nature of document as an object of research leads to an ambiguous interpretation of its nature and social role. The article expresses and contends the author's views on this issue. In her opinion, social role of document is incidental to its being a main social tool regulating the life of civilized society. Thus, the study aims to create a scientific theory of document, explaining its nature and social role as a tool of social (goal-oriented) action and social self-organization. Substantiation of this idea is based on application of synergetics (i.e., universal theory of self-organization) to scientific study of document. In the synergetic paradigm, social and historical development is seen as the change of phases of chaos and order, and document is considered a main tool that regulates social relations. Unlike other theories of document, synergetic theory studies document not as a carrier and means of information transfer, but as a unique social phenomenon and universal social tool. For the first time, the study of document steps out of traditional frameworks of office, archive, and library. The document is placed on the scales with society as a global social system with its functional subsystems of politics, economy, culture, and personality. For the first time, the methods of social sciences and modern sociological theories are applied to scientific study of document. This methodology provided a basis for theoretical vindication of nature and social role of document as a tool of social (goal-oriented) action and social self-organization. The study frames a synergetic theory of document with methodological foundations and basic concepts, synergetic model of document, laws of development and effectiveness of document in the social continuum. At the present stage of development of science, it can be considered the highest form of theoretical knowledge of document and its scientific explanatory theory.

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