Abstract:
:Na(+)/Ca(2+) exchanger (NCX) proteins extrude Ca(2+) from the cell to maintain cellular homeostasis. Since NCX proteins contribute to numerous physiological and pathophysiological events, their pharmacological targeting has been desired for a long time. This intervention remains challenging owing to our poor understanding of the underlying structure-dynamic mechanisms. Recent structural studies have shed light on the structure-function relationships underlying the ion-transport and allosteric regulation of NCX. The crystal structure of an archaeal NCX (NCX_Mj) along with molecular dynamics simulations and ion flux analyses, have assigned the ion binding sites for 3Na(+) and 1Ca(2+), which are being transported in separate steps. In contrast with NCX_Mj, eukaryotic NCXs contain the regulatory Ca(2+)-binding domains, CBD1 and CBD2, which affect the membrane embedded ion-transport domains over a distance of ~80 Å. The Ca(2+)-dependent regulation is ortholog, isoform, and splice-variant dependent to meet physiological requirements, exhibiting either a positive, negative, or no response to regulatory Ca(2+). The crystal structures of the two-domain (CBD12) tandem have revealed a common mechanism involving a Ca(2+)-driven tethering of CBDs in diverse NCX variants. However, dissociation kinetics of occluded Ca(2+) (entrapped at the two-domain interface) depends on the alternative-splicing segment (at CBD2), thereby representing splicing-dependent dynamic coupling of CBDs. The HDX-MS, SAXS, NMR, FRET, equilibrium (45)Ca(2+) binding and stopped-flow techniques provided insights into the dynamic mechanisms of CBDs. Ca(2+) binding to CBD1 results in a population shift, where more constraint conformational states become highly populated without global conformational changes in the alignment of CBDs. This mechanism is common among NCXs. Recent HDX-MS studies have demonstrated that the apo CBD1 and CBD2 are stabilized by interacting with each other, while Ca(2+) binding to CBD1 rigidifies local backbone segments of CBD2, but not of CBD1. The extent and strength of Ca(2+)-dependent rigidification at CBD2 is splice-variant dependent, showing clear correlations with phenotypes of matching NCX variants. Therefore, diverse NCX variants share a common mechanism for the initial decoding of the regulatory signal upon Ca(2+) binding at the interface of CBDs, whereas the allosteric message is shaped by CBD2, the dynamic features of which are dictated by the splicing segment.
journal_name
Front Physioljournal_title
Frontiers in physiologyauthors
Giladi M,Tal I,Khananshvili Ddoi
10.3389/fphys.2016.00030subject
Has Abstractpub_date
2016-02-09 00:00:00pages
30issn
1664-042Xjournal_volume
7pub_type
杂志文章,评审abstract::Aphidius gifuensis is one of the most important aphid natural enemies and has been successfully used to control Myzys persicae and other aphid species. High temperature in summer is one of the key barriers for the application of A. gifuensis in the field and greenhouse. In this work, we investigated the biological per...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2017.00976
更新日期:2017-11-28 00:00:00
abstract:Purpose:This study aimed to evaluate effects of remote ischemic preconditioning (RIPC) on myocardial injury in patients undergoing off-pump coronary artery bypass graft surgery (OPCABG). Methods:Sixty-five patients scheduled for the OPCABG were randomly assigned to control (n = 32) or RIPC group (n = 33). All patients...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2019.00495
更新日期:2019-04-29 00:00:00
abstract::Background: Hypoxia represents both an outcome of cardiopulmonary diseases and a trigger for severe pulmonary complications as pulmonary hypertension. Because nitric oxide (NO) is a critical mediator in the development of pulmonary hypertension, the modulators of its downstream function may become target of pharmacolo...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2018.00289
更新日期:2018-03-27 00:00:00
abstract::Spinal cord injury (SCI) causes chronic peripheral sensitization of nociceptors and persistent generation of spontaneous action potentials (SA) in peripheral branches and the somata of hyperexcitable nociceptors within dorsal root ganglia (DRG). Here it is proposed that SCI triggers in numerous nociceptors a persisten...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2012.00309
更新日期:2012-08-02 00:00:00
abstract::Chronic kidney disease (CKD) is a significant worldwide healthcare problem. Regardless of the initial injury, renal fibrosis is the common final pathway leading to end stage renal disease. Although the underlying mechanisms are not fully defined, evidence indicates that besides inflammation, oxidative stress plays a c...
journal_title:Frontiers in physiology
pub_type: 杂志文章,评审
doi:10.3389/fphys.2018.00105
更新日期:2018-02-16 00:00:00
abstract::Although cardiac recovery is an important criterion for ranking horses in endurance competitions, heart rate variability (HRV) has hardly ever been studied in the context of this equestrian discipline. In the present study, we sought to determine whether HRV is affected by parameters such as age, exercise duration and...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2016.00155
更新日期:2016-05-02 00:00:00
abstract:INTRODUCTION:Exercise reduces arterial and central venous blood pressures during recovery, which contributes to its valuable anti-hypertensive effects and to facilitating hypervolemia. Repeated sprint exercise potently improves metabolic function, but its cardiovascular effects (esp. hematological) are less well-charac...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2016.00199
更新日期:2016-05-31 00:00:00
abstract::The fluid transport and mixing induced by beating cilia, present in the bronchial airways, are studied using a coupled lattice Boltzmann-Immersed Boundary solver. This solver allows the simulation of both single and multi-component fluid flows around moving solid boundaries. The cilia are modeled by a set of Lagrangia...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2018.00161
更新日期:2018-03-06 00:00:00
abstract::In this study, we analyzed the role of mammalian STE20-like protein kinase 2 (Mst2), a serine-threonine protein kinase, in Lipopolysaccharides (LPS)-mediated inflammation and apoptosis in the H9C2 cardiomyocytes. Mst2 mRNA and protein levels were significantly upregulated in the LPS-treated H9C2 cardiomyocytes. LPS tr...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2020.00897
更新日期:2020-08-06 00:00:00
abstract::A colony of social insects is not only an aggregation of individuals but also a functional unit. To achieve adaptive social behavior in fluctuating environmental conditions, in addition to coordination of physiological status in each individual, the whole colony is coordinated by interactions among colony members. The...
journal_title:Frontiers in physiology
pub_type: 杂志文章,评审
doi:10.3389/fphys.2014.00127
更新日期:2014-04-09 00:00:00
abstract::Objective: Neuromuscular injury prevention programs (IPP) can reduce injury rate by about 40% in youth sport. Multimodal IPP include, for instance, balance, strength, power, and agility exercises. Our systematic review and meta-analysis aimed to evaluate the effects of multimodal IPP on neuromuscular performance in yo...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2017.00791
更新日期:2017-10-12 00:00:00
abstract::Preterm premature rupture of membranes is a leading cause of preterm births. Cytokine induced matrix metalloproteinase1 and interleukin 8 production from amnion mesenchymal cells may contribute to fetal membrane weakening and rupture. Progestins inhibit inflammation induced fetal membrane weakening but their effect on...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2020.00900
更新日期:2020-07-24 00:00:00
abstract::Lepidopteran species detect CO2 via a specialized organ located on the peripheral segment of the labial palps, the labial palp pit organ (LPO). Based on tracing of LPO sensory neurons targeting one distinct antennal-lobe glomerulus, Kent and her colleagues described the projections originating from the LPO in the sphi...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2020.00202
更新日期:2020-03-17 00:00:00
abstract::Secondary shifts develop in post-translational phosphorylation of sarcomeric proteins in multiple animal models of inherited cardiomyopathy. These signaling alterations together with the primary mutation are predicted to contribute to the overall cardiac phenotype. As a result, identification and integration of post-t...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2016.00407
更新日期:2016-09-14 00:00:00
abstract::The development of cardiovascular disease during renal impairment involves striking multi-tiered, multi-dimensional complex alterations encompassing the entire oxygen transport system. Complex interactions between target organ systems involving alterations of the heart, vascular, musculoskeletal and respiratory system...
journal_title:Frontiers in physiology
pub_type: 杂志文章,评审
doi:10.3389/fphys.2020.572355
更新日期:2020-09-15 00:00:00
abstract::Purpose: To provide insights into the energy requirements as well as the physiological adaptations of an experienced 50-year-old ultra-marathon male athlete during the world's most challenging mountain ultra-marathon (MUM). Methods: The international race supporting the study was the Tor des Geants®, characterized by ...
journal_title:Frontiers in physiology
pub_type:
doi:10.3389/fphys.2017.01003
更新日期:2017-12-05 00:00:00
abstract::Human induced pluripotent stem cell derived cardiomyocytes (iPSC-CMs) have applications in disease modeling, cell therapy, drug screening and personalized medicine. Computational models can be used to interpret experimental findings in iPSC-CMs, provide mechanistic insights, and translate these findings to adult cardi...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2017.00986
更新日期:2017-12-12 00:00:00
abstract::Purpose: This study aimed to examine the exercise-mediated musculoskeletal recovery following hindlimb suspension (HS) in order to identify whether bone modeling and muscle hypertrophy would eventuate in a synchronized manner during recovery stage. Methods: To identify whether 2-week HS would be sufficient to induce a...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2018.01085
更新日期:2018-08-13 00:00:00
abstract::This review details the manner in which the central nervous system regulates metabolic homeostasis in normal weight and obese rodents and humans. It includes a review of the homeostatic contributions of neurons located in the hypothalamus, the midbrain and limbic structures, the pons and the medullary area postrema, n...
journal_title:Frontiers in physiology
pub_type: 杂志文章,评审
doi:10.3389/fphys.2018.00574
更新日期:2018-05-17 00:00:00
abstract::Genome-scale metabolic models (GEMs) have become a popular tool for systems biology, and they have been used in many fields such as industrial biotechnology and systems medicine. Since more and more studies are being conducted using GEMs, they have recently received considerable attention. In this review, we introduce...
journal_title:Frontiers in physiology
pub_type: 杂志文章,评审
doi:10.3389/fphys.2015.00413
更新日期:2016-01-07 00:00:00
abstract::Cephalopod and vertebrate neural-systems are often highlighted as a traditional example of convergent evolution. Their large brains, relative to body size, and complexity of sensory-motor systems and behavioral repertoires offer opportunities for comparative analysis. Despite various attempts, questions on how cephalo...
journal_title:Frontiers in physiology
pub_type: 杂志文章,评审
doi:10.3389/fphys.2018.00952
更新日期:2018-07-20 00:00:00
abstract::Cytoplasmic Actin Gamma 1 (ACTG1) gene variant are autosomal dominant and can cause CNS anomalies (Baraitser Winter Malformation Syndrome; BWMS). ACTG1 anomalies in offspring include agenesis of the corpus callosum (ACC) and neuronal heterotopia which are ectopic nodules of nerve cells that failed to migrate appropria...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2019.00623
更新日期:2019-05-24 00:00:00
abstract::Despite vast improvement in perinatal care during the 30 years, the incidence rate of neonatal encephalopathy remains unchanged without any further Progress towards preventive strategies for the clinical impasse. Antenatal brain injury including fetal intracranial hemorrhage caused by ischemia/reperfusion is known as ...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2017.00340
更新日期:2017-05-24 00:00:00
abstract::Progressive aging induces several structural and functional alterations in the cardiovascular system, among whom particularly important are a reduced number of myocardial cells and increased interstitial collagen fibers, which result in impaired left ventricular diastolic function. Even in the absence of cardiovascula...
journal_title:Frontiers in physiology
pub_type: 杂志文章,评审
doi:10.3389/fphys.2014.00051
更新日期:2014-02-20 00:00:00
abstract::Purpose: To determine if acute slow breathing at 6 breaths/min would improve baroreflex sensitivity (BRS) and heart rate variability (HRV), and lower blood pressure (BP) in adults after stroke. Methods: Twelve individuals completed two randomized study visits where they performed a 15-min bout of breathing exercises a...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2020.573325
更新日期:2020-10-30 00:00:00
abstract::The purpose of this study was to examine the effects of a short-term ketogenic diet (KD) on body composition and cardiorespiratory fitness (CRF) in overweight/obese Chinese females. Twenty young females [age: 21.0 ± 3.7 years, weight: 65.5 ± 7.7 kg, body mass index (BMI): 24.9 ± 2.7 kg⋅m-2] consumed 4 weeks of a norma...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2020.00856
更新日期:2020-07-28 00:00:00
abstract::The detailed behavior of many molecular processes in the cell, such as protein folding, protein complex assembly, and gene regulation, transcription and translation, can often be accurately captured by stochastic chemical kinetic models. We investigate a novel computational problem involving these models - that of fin...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2010.00170
更新日期:2010-10-19 00:00:00
abstract::Regular physical exercise provides many health benefits, protecting against the development of chronic diseases, and improving quality of life. Some of the mechanisms by which exercise provides these effects are the promotion of an anti-inflammatory state, reinforcement of the neuromuscular function, and activation of...
journal_title:Frontiers in physiology
pub_type: 杂志文章,评审
doi:10.3389/fphys.2016.00051
更新日期:2016-02-18 00:00:00
abstract::During embryonic development, multipotent endodermal cells differentiate to form the pancreas. Islet cell clusters arising from the pancreatic bud form the acini tissue and exocrine ducts whilst pancreatic islets form around the edges of the clusters. The successive steps of islet differentiation are controlled by a c...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2013.00170
更新日期:2013-07-18 00:00:00
abstract::Ginseng, the root of Panax ginseng C.A. Meyer, is one of the oldest traditional medicines and is thought to be a tonic. It has been claimed that ginseng may improve vitality and health. Recent studies have advanced ginseng pharmacology and shown that ginseng has various pharmacological effects in the nervous system. G...
journal_title:Frontiers in physiology
pub_type: 杂志文章,评审
doi:10.3389/fphys.2014.00098
更新日期:2014-03-19 00:00:00