Ionic Perturbations Research Articles

A Robust Parallel Computing Data Extraction Framework for Nanopore Experiments.

The success of a nanopore experiment relies not only on the quality of the experimental design but also on the performance of the analysis program utilized to decipher the ionic perturbations necessary for understanding the fundamental molecular intricacies. An event extraction framework is developed that leverages parallel computing, efficient memory management, and vectorization, yielding significant performance enhancement. The newly developed abf-ultra-simple function extracts key parameters from the header critical for the operation of open-seek-read-close data loading architecture running on multiple cores. This underpins the swift analysis of large files where an ≈×18 improvement is found for a 100min-long file (≈4.5GB) compared to the more traditional single (cell) array data loading method. The application is benchmarked against five other analysis platforms showcasing significant performance enhancement (>2×-1120×). The integrated provisions for batch analysis enable concurrently analyzing multiple files (vital for high-bandwidth experiments). Furthermore, the application is equipped with multi-level data fitting based on abrupt changes in the event waveform. The application condenses the extracted events to a single binary file improving data portability (e.g., 16GB file with 28182 events reduces to 47.9MB-343× size reduction) and enables a multitude of post-analysis extractions to be done efficiently.

Simultaneous Increases in Intracellular Sodium and Tonicity Boost Antimicrobial Activity of Macrophages.

Inflamed and infected tissues can display increased local sodium (Na+) levels, which can have various effects on immune cells. In macrophages, high salt (HS) leads to a Na+/Ca2+-exchanger 1 (NCX1)-dependent increase in intracellular Na+ levels. This results in augmented osmoprotective signaling and enhanced proinflammatory activation, such as enhanced expression of type 2 nitric oxide synthase and antimicrobial function. In this study, the role of elevated intracellular Na+ levels in macrophages was investigated. Therefore, the Na+/K+-ATPase (NKA) was pharmacologically inhibited with two cardiac glycosides (CGs), ouabain (OUA) and digoxin (DIG), to raise intracellular Na+ without increasing extracellular Na+ levels. Exposure to HS conditions and treatment with both inhibitors resulted in intracellular Na+ accumulation and subsequent phosphorylation of p38/MAPK. The CGs had different effects on intracellular Ca2+ and K+ compared to HS stimulation. Moreover, the osmoprotective transcription factor nuclear factor of activated T cells 5 (NFAT5) was not upregulated on RNA and protein levels upon OUA and DIG treatment. Accordingly, OUA and DIG did not boost nitric oxide (NO) production and showed heterogeneous effects toward eliminating intracellular bacteria. While HS environments cause hypertonic stress and ionic perturbations, cardiac glycosides only induce the latter. Cotreatment of macrophages with OUA and non-ionic osmolyte mannitol (MAN) partially mimicked the HS-boosted antimicrobial macrophage activity. These findings suggest that intracellular Na+ accumulation and hypertonic stress are required but not sufficient to mimic boosted macrophage function induced by increased extracellular sodium availability.

Coupling and heterogeneity modulate pacemaking capability in healthy and diseased two-dimensional sinoatrial node tissue models.

Both experimental and modeling studies have attempted to determine mechanisms by which a small anatomical region, such as the sinoatrial node (SAN), can robustly drive electrical activity in the human heart. However, despite many advances from prior research, important questions remain unanswered. This study aimed to investigate, through mathematical modeling, the roles of intercellular coupling and cellular heterogeneity in synchronization and pacemaking within the healthy and diseased SAN. In a multicellular computational model of a monolayer of either human or rabbit SAN cells, simulations revealed that heterogenous cells synchronize their discharge frequency into a unique beating rhythm across a wide range of heterogeneity and intercellular coupling values. However, an unanticipated behavior appeared under pathological conditions where perturbation of ionic currents led to reduced excitability. Under these conditions, an intermediate range of intercellular coupling (900-4000 MΩ) was beneficial to SAN automaticity, enabling a very small portion of tissue (3.4%) to drive propagation, with propagation failure occurring at both lower and higher resistances. This protective effect of intercellular coupling and heterogeneity, seen in both human and rabbit tissues, highlights the remarkable resilience of the SAN. Overall, the model presented in this work allowed insight into how spontaneous beating of the SAN tissue may be preserved in the face of perturbations that can cause individual cells to lose automaticity. The simulations suggest that certain degrees of gap junctional coupling protect the SAN from ionic perturbations that can be caused by drugs or mutations.

Individual Contributions of Cardiac Ion Channels on Atrial Repolarization and Reentrant Waves: A Multiscale In-Silico Study.

The excitation, contraction, and relaxation of an atrial cardiomyocyte are maintained by the activation and inactivation of numerous cardiac ion channels. Their collaborative efforts cause time-dependent changes of membrane potential, generating an action potential (AP), which is a surrogate marker of atrial arrhythmias. Recently, computational models of atrial electrophysiology emerged as a modality to investigate arrhythmia mechanisms and to predict the outcome of antiarrhythmic therapies. However, the individual contribution of atrial ion channels on atrial action potential and reentrant arrhythmia is not yet fully understood. Thus, in this multiscale in-silico study, perturbations of individual atrial ionic currents (INa, Ito, ICaL, IKur, IKr, IKs, IK1, INCX and INaK) in two in-silico models of human atrial cardiomyocyte (i.e., Courtemanche-1998 and Grandi-2011) were performed at both cellular and tissue levels. The results show that the inhibition of ICaL and INCX resulted in AP shortening, while the inhibition of IKur, IKr, IKs, IK1 and INaK prolonged AP duration (APD). Particularly, in-silico perturbations (inhibition and upregulation) of IKr and IKs only minorly affected atrial repolarization in the Grandi model. In contrast, in the Courtemanche model, the inhibition of IKr and IKs significantly prolonged APD and vice versa. Additionally, a 50% reduction of Ito density abbreviated APD in the Courtemanche model, while the same perturbation prolonged APD in the Grandi model. Similarly, a strong model dependence was also observed at tissue scale, with an observable IK1-mediated reentry stabilizing effect in the Courtemanche model but not in the Grandi atrial model. Moreover, the Grandi model was highly sensitive to a change on intracellular Ca2+ concentration, promoting a repolarization failure in ICaL upregulation above 150% and facilitating reentrant spiral waves stabilization by ICaL inhibition. Finally, by incorporating the previously published atrial fibrillation (AF)-associated ionic remodeling in the Courtemanche atrial model, in-silico modeling revealed the antiarrhythmic effect of IKr inhibition in both acute and chronic settings. Overall, our multiscale computational study highlights the strong model-dependent effects of ionic perturbations which could affect the model’s accuracy, interpretability, and prediction. This observation also suggests the need for a careful selection of in-silico models of atrial electrophysiology to achieve specific research aims.

Cardiomyocytes Cellular Phenotypes After Myocardial Infarction.

Despite the increasing success of interventional coronary reperfusion strategies, mortality related to acute myocardial infarction (MI) is still substantial. MI is defined as sudden death of myocardial tissue caused by an ischemic episode. Ischaemia leads to adverse remodelling in the affected myocardium, inducing metabolic and ionic perturbations at a single cell level, ultimately leading to cell death. The adult mammalian heart has limited regenerative capacity to replace lost cells. Identifying and enhancing physiological cardioprotective processes may be a promising therapy for patients with MI. Studies report an increasing amount of evidence stating the intricacy of the pathophysiology of the infarcted heart. Besides apoptosis, other cellular phenotypes have emerged as key players in the ischemic myocardium, in particular senescence, inflammation, and dedifferentiation. Furthermore, some cardiomyocytes in the infarct border zone uncouple from the surviving myocardium and dedifferentiate, while other cells become senescent in response to injury and start to produce a pro-inflammatory secretome. Enhancing electric coupling between cardiomyocytes in the border zone, eliminating senescent cells with senolytic compounds, and upregulating cardioprotective cellular processes like autophagy, may increase the number of functional cardiomyocytes and therefore enhance cardiac contractility. This review describes the different cellular phenotypes and pathways implicated in injury, remodelling, and regeneration of the myocardium after MI. Moreover, we discuss implications of the complex pathophysiological attributes of the infarcted heart in designing new therapeutic strategies.

PROSPECTIVE ANALYSIS OF IMPACT OF PHARMCOTHERAPY ADHERENCE ON TREATMENT EFFECTIVENESS IN POST OPERATIVE HEART PATIENTS

Myocardial infarction is the irreversible damage of myocardial tissue caused by prolonged ischemia and hypoxia. This most commonly occurs when a coronary artery becomese blocked following the rupture of an atherosclerotic plaque, which then leads to the formation of a blood clot (coronary thrombosis). This event can also trigger coronary vasospasm. Ischemia induces profound metabolic and ionic perturbations in the affected myocardium and causes rapid depression of systolic function. Prolonged myocardial ischemia activates a "wavefront" of cardiomyocyte death that extends from the subendocardium to the subepicardium. Mitochondrial alterations are prominently involved in apoptosis and necrosis of cardiomyocytes in the infarcted heart.
 This prospective, pilot, observational study performed confirmed the hypothesis that systematic identifications and interventions administered through continued physician follow-up and patients counselling will improve adherence to therapy and therefore improvement in treatment effectiveness by lowering especially Troponin level ,CPK and quality of life in MI patients.
 Study was shown that lack of proper knowledge about disease and patients counseling and chronic treatment, most of patients takes disease and its treatment lightly and shows lower adherence attitude. The study analysis shown that female are generally more aware than males for adherence. Study analysis concluded that there was significant reduction in their Troponin level and CPK values in different comparison groups after each level of follow up.
 Statistical analysis concluded that patients with adherence ˃ 95% showed significant reduction in Troponin level and CPK values and patients with age group ≤50 shows more adherence than older.
 Most heart patients recorded with hypertension and Coronary Artery Diseases only few ones with diabetic complications. During study patients shows good control over their blood pressure and only few adverse events but no complications occur during study period.

Simulation of less‐mobile porosity dynamics in contrasting sediment water interface porous media

AbstractConsidering heterogeneity in porous media pore size and connectivity is essential to predicting reactive solute transport across interfaces. However, exchange with less‐mobile porosity is rarely considered in surface water/groundwater recharge studies. Previous research indicates that a combination of pore‐fluid sampling and geoelectrical measurements can be used to quantify less‐mobile porosity exchange dynamics using the time‐varying relation between fluid and bulk electrical conductivity. For this study, we use macro‐scale (10 s of cm) advection–dispersion solute transport models linked with electrical conduction in COMSOL Multiphysics to explore less‐mobile porosity dynamics in two different types of observed sediment water interface porous media. Modeled sediment textures contrast from strongly layered streambed deposits to poorly sorted lakebed sands and cobbles. During simulated ionic tracer perturbations, a lag between fluid and bulk electrical conductivity, and the resultant hysteresis, is observed for all simulations indicating differential loading of pore spaces with tracer. Less‐mobile exchange parameters are determined graphically from these tracer time series data without the need for inverse numerical model simulation. In both sediment types, effective less‐mobile porosity exchange parameters are variable in response to changes in flow direction and fluid flux. These observed flow‐dependent effects directly impact local less‐mobile residence times and associated contact time for biogeochemical reaction. The simulations indicate that for the sediment textures explored here, less‐mobile porosity exchange is dominated by variable rates of advection through the domain, rather than diffusion of solute, for typical low‐to‐moderate rate (approximately 3–40 cm/day) hyporheic fluid fluxes. Overall, our model‐based results show that less‐mobile porosity may be expected in a range of natural hyporheic sediments and that changes in flowpath orientation and magnitude will impact less‐mobile exchange parameters. These temporal dynamics can be assessed with the geoelectrical experimental tracer method applied at laboratory and field scales.

A Computational Study of the Ionic Liquid-Induced Destabilization of the Miniprotein Trp-Cage.

Fundamental understanding of protein stability away from physiological conditions is important due to its evolutionary implications and relevance to industrial processing and storage of biological materials. The molecular mechanisms of stabilization/destabilization by environmental perturbations are incompletely understood. We use replica-exchange molecular dynamics simulations and thermodynamic analysis to investigate the effects of ionic liquid-induced perturbations on the folding/unfolding thermodynamics of the Trp-cage miniprotein. We find that ionic liquid-induced denaturation resembles cold unfolding, where the unfolded states are populated by compact, partially folded structures in which elements of the secondary structure are conserved, while the tertiary structure is disrupted. Our simulations show that the intrusion of ions and water into Trp-cage's hydrophobic core is facilitated by the disruption of its salt bridge and 310-helix by specific ion-residue interactions. Despite the swelling and widening of the hydrophobic core, however, Trp-cage's α-helix remains stable. We further show that ionic liquid disrupts protein-protein and protein-water hydrogen bonds while favoring the formation of ion-protein bonds, shifting the equilibrium of conformational states and promoting denaturation near room temperature.

Kinetic-Simulation Study of Propagation of Langmuir-Like Ionic Waves in Dusty Plasma

The propagation of ionic perturbations in a dusty plasma is considered through a three-species kinetic simulation approach, in which the temporal evolution of all three elements, i.e., electrons, ions, and dust particles are followed based on the Vlasov equation coupled with the Poisson equation. Two cases are focused upon: first, a fully electron-depleted dusty plasma, i.e., a plasma consisting of ions and dust particles. The second case includes dusty plasmas with large electron-to-ion temperature ratios. The main features of the ionic waves in these two settings, including the dispersion relation and the Landau damping rate, are studied. It is shown that the dispersion relation of the ionic waves perfectly matches the dispersion relation of Langmuir waves and hence is called Langmuir-like ionic waves and can be considered as Langmuir-like ionic waves. These waves can be theoretically predicted by the dispersion relation of the dust-ion-acoustic waves. The transition of ionic waves from dust-ion-acoustic to Langmuir-like waves is shown to be sharp/smooth in first/second case. The Landau damping rates based on simulation results are presented and compared with theoretical predictions wherever possible.

Limitations in intense exercise performance of athletes - effect of speed endurance training on ion handling and fatigue development.

Mechanisms underlying fatigue development and limitations for performance during intense exercise have been intensively studied during the past couple of decades. Fatigue development may involve several interacting factors and depends on type of exercise undertaken and training level of the individual. Intense exercise (½-6min) causes major ionic perturbations (Ca2+ , Cl- , H+ , K+ , lactate- and Na+ ) that may reduce sarcolemmal excitability, Ca2+ release and force production of skeletal muscle. Maintenance of ion homeostasis is thus essential to sustain force production and power output during intense exercise. Regular speed endurance training (SET), i.e. exercise performed at intensities above that corresponding to maximum oxygen consumption (V̇O2, max ), enhances intense exercise performance. However, most of the studies that have provided mechanistic insight into the beneficial effects of SET have been conducted in untrained and recreationally active individuals, making extrapolation towards athletes' performance difficult. Nevertheless, recent studies indicate that only a few weeks of SET enhances intense exercise performance in highly trained individuals. In these studies, the enhanced performance was not associated with changes in V̇O2, max and muscle oxidative capacity, but rather with adaptations in muscle ion handling, including lowered interstitial concentrations of K+ during and in recovery from intense exercise, improved lactate- -H+ transport and H+ regulation, and enhanced Ca2+ release function. The purpose of this Topical Review is to provide an overview of the effect of SET and to discuss potential mechanisms underlying enhancements in performance induced by SET in already well-trained individuals with special emphasis on ion handling in skeletal muscle.

Pathophysiology of Myocardial Infarction.

Myocardial infarction is defined as sudden ischemic death of myocardial tissue. In the clinical context, myocardial infarction is usually due to thrombotic occlusion of a coronary vessel caused by rupture of a vulnerable plaque. Ischemia induces profound metabolic and ionic perturbations in the affected myocardium and causes rapid depression of systolic function. Prolonged myocardial ischemia activates a "wavefront" of cardiomyocyte death that extends from the subendocardium to the subepicardium. Mitochondrial alterations are prominently involved in apoptosis and necrosis of cardiomyocytes in the infarcted heart. The adult mammalian heart has negligible regenerative capacity, thus the infarcted myocardium heals through formation of a scar. Infarct healing is dependent on an inflammatory cascade, triggered by alarmins released by dying cells. Clearance of dead cells and matrix debris by infiltrating phagocytes activates anti-inflammatory pathways leading to suppression of cytokine and chemokine signaling. Activation of the renin-angiotensin-aldosterone system and release of transforming growth factor-β induce conversion of fibroblasts into myofibroblasts, promoting deposition of extracellular matrix proteins. Infarct healing is intertwined with geometric remodeling of the chamber, characterized by dilation, hypertrophy of viable segments, and progressive dysfunction. This review manuscript describes the molecular signals and cellular effectors implicated in injury, repair, and remodeling of the infarcted heart, the mechanistic basis of the most common complications associated with myocardial infarction, and the pathophysiologic effects of established treatment strategies. Moreover, we discuss the implications of pathophysiological insights in design and implementation of new promising therapeutic approaches for patients with myocardial infarction.

Release of colloids from primary minimum contact under unfavorable conditions by perturbations in ionic strength and flow rate.

Colloid release from surfaces in response to ionic strength and flow perturbations has been mechanistically simulated. However, these models do not address the mechanism by which colloid attachment occurs, at least in the presence of bulk colloid-collector repulsion (unfavorable conditions), which is a prevalent environmental condition. We test whether a mechanistic model that predicts colloid attachment under unfavorable conditions also predicts colloid release in response to reduced ionic strength (IS) and increased fluid velocity (conditions thought prevalent for mobilization of environmental colloids). The model trades in mean-field colloid-collector interaction for discrete representation of surface heterogeneity, which accounts for a combination of attractive and repulsive interactions simultaneously, and results in an attached colloid population (in primary minimum contact with the surface) having a distribution of strengths of attraction. The model moderates equilibrium separation distance by inclusion of steric interactions. By using the same model parameters to quantitatively predict attachment under unfavorable conditions, simulated release of colloids (for all three sizes) from primary minimum attachment in response to perturbations qualitatively matched experimental results, demonstrating that both attachment and detachment were mechanistically simulated.

Comprehensive Analyses of Ventricular Myocyte Models Identify Targets Exhibiting Favorable Rate Dependence

Reverse rate dependence is a problematic property of antiarrhythmic drugs that prolong the cardiac action potential (AP). The prolongation caused by reverse rate dependent agents is greater at slow heart rates, resulting in both reduced arrhythmia suppression at fast rates and increased arrhythmia risk at slow rates. The opposite property, forward rate dependence, would theoretically overcome these parallel problems, yet forward rate dependent (FRD) antiarrhythmics remain elusive. Moreover, there is evidence that reverse rate dependence is an intrinsic property of perturbations to the AP. We have addressed the possibility of forward rate dependence by performing a comprehensive analysis of 13 ventricular myocyte models. By simulating populations of myocytes with varying properties and analyzing population results statistically, we simultaneously predicted the rate-dependent effects of changes in multiple model parameters. An average of 40 parameters were tested in each model, and effects on AP duration were assessed at slow (0.2 Hz) and fast (2 Hz) rates. The analysis identified a variety of FRD ionic current perturbations and generated specific predictions regarding their mechanisms. For instance, an increase in L-type calcium current is FRD when this is accompanied by indirect, rate-dependent changes in slow delayed rectifier potassium current. A comparison of predictions across models identified inward rectifier potassium current and the sodium-potassium pump as the two targets most likely to produce FRD AP prolongation. Finally, a statistical analysis of results from the 13 models demonstrated that models displaying minimal rate-dependent changes in AP shape have little capacity for FRD perturbations, whereas models with large shape changes have considerable FRD potential. This can explain differences between species and between ventricular cell types. Overall, this study provides new insights, both specific and general, into the determinants of AP duration rate dependence, and illustrates a strategy for the design of potentially beneficial antiarrhythmic drugs.

Influence of Ionic Strength and Flow Rate on Silt Particle Deposition and Release in Saturated Porous Medium: Experiment and Modeling

In this paper, the influence of ionic strength on the dynamic transport of silt microparticles through saturated sand texture is studied in the presence of repulsive interactions. The deposition and release phenomenon is investigated through experimental column trials. Different ionic strengths are applied by adjustment of suspension salinity. Two trial configurations are performed: Monotonic experiments highlight particle deposition mechanisms, and non-monotonic tests focus on release phenomena under ionic strength and flow rate perturbations. Through this experimental study, the ionic strength influence on the deposition and release phenomenon is shown. The presence of both mechanical and physico-chemical mechanisms is proved experimentally. This study proves that ionic strength variation is a primal parameter which predicts the attachment and detachment of particles at constant flow. These experiments are simulated and reproduced through a numerical model based on original deposit and release kinetics which are proposed in this study. This model is the coupling of two multiphasic problems describing conservative salt and microparticle transport. The proposed kinetics formulations are founded on performed experimental test constitutions in this study. They take into account the flow rate and the suspension ionic strength. The suggested model reproduces well the experimental description of the suspended particles transport under the influence of ionic strength and flow velocity variations. It permits to predict the deposition and release phenomenon.

Chapter Seven - Mechanisms of Ictogenesis

Epilepsy is a paroxysmal condition characterized by repeated transient seizures separated by longer interictal periods. Ictogenesis describes the processes of transition from the interictal state to a seizure. The processes include a preictal state, with specific clinical signs and a distinct electrophysiology which may provide opportunities to anticipate, or even prevent, seizures. Biological mechanisms of ictogenesis remain poorly understood and may vary between conditions/syndromes. We review here ictogenic processes including the involvement of pyramidal cells, interneurons and astrocytes, GABAergic and glutamatergic signaling, and ionic perturbations. Our review suggests that specific excitatory influences at the transition to an ictal event include (1) GABA receptor activation with a neuronal Cl(-) load and (2) a transient increase in external K(+).

Lightning-associated VLF perturbations observed at low latitude: Occurrence and scattering characteristics

The occurrence of short-timescale (∼1–100 s) perturbations (early VLF events) on four Very Low Frequency (VLF) transmitter signals (call signs: NWC, NPM, VTX, NLK), recorded at Suva (18.1°S, 178.5°E, L = 1.16), shows the most frequent occurrence on the NWC signal and least on the VTX. Daytime early/fast events on the NWC transmission are (0.2–0.5 dB) with only negative amplitude perturbations with comparatively lower recovery times (10–30 s) as compared with most nighttime events with amplitude perturbations of 0.2–1.5 dB and recovery times of 20–80 s. The World-Wide Lightning Location Network detected causative lightnings for 74 of 453 early VLF events out of which 54 (73%) were produced due to narrow-angle scattering, and by 20 (27%) due to wide-angle scattering. The recovery (decay) of the scattered amplitude of early/fast events on the NWC signal shows both exponential and logarithmic forms, but the linear correlation coefficient is better with a logarithm fit. The first observations of early/slow events in daylight propagation are presented. Initial results on early/fast events with unusually long recoveries (≥5 min) and strong perturbations (≥1 dB) indicate that they are mainly observed on the transmissions from NPM and NLK in the nighttime only, with rare occurrence on other transmissions. Such unusually long recovery of early/fast events may be associated with large ionic conductivity perturbations associated with gigantic jets.

Role of Arbuscular Mycorrhizal (AM) Fungi on Growth, Cadmium Uptake, Osmolyte, and Phytochelatin Synthesis in Cajanus cajan (L.) Millsp. Under NaCl and Cd Stresses

Application of phosphatic (P) fertilizers and biosolids is known to enhance cadmium (Cd) contamination in saline soils. Increased concentration of dissolved chloride (Cl−) in soil solution significantly influences Cd bioavailability in P fertilizer- or biosolid-amended soils. Arbuscular mycorrhizal (AM) fungi have an ability to protect plants against salinity and heavy metals by mediating interactions between toxic ions and plant roots. The effects of Glomus mosseae (AM) and NaCl and Cd stresses on Cd uptake and osmolyte and phytochelatin (PCs) synthesis in Cajanus cajan (L.) Millsp. (pigeonpea) were studied under greenhouse conditions. Two genotypes [Sel 85 N (tolerant) and ICP 13997 (sensitive)] were subjected to NaCl (4 and 6 dS m−1) and Cd (CdCl2, 25 and 50 mg kg−1 dry soil) treatments. NaCl and Cd applied individually as well as in combination caused dramatic reductions in plant biomass and induced membrane peroxidation, ionic perturbations, and metabolite synthesis in both genotypes, although Sel 85 N was less affected than ICP 13997. Cadmium uptake was enhanced when NaCl was added along with Cd. The protection of growth in Sel 85 N was associated with restricted accumulation of Na+, Cl−, and Cd2+ and higher concentrations of stress metabolites (sugars, proteins, free amino acids, proline, glycine betaine). Cd led to a significant increase in biothiols (NP-SH) and glutathione (GSH), with a larger pool of NP-SH which strongly induced accumulation of phytochelatins, whereas no significant effects in their concentrations were detectable under NaCl stress. The interactive effects of NaCl and Cd on all parameters were larger than those of individual treatments. Fungal inoculations improved plant growth and reduced accumulation of toxic ions. Higher stress metabolite synthesis and PCs observed in AM plants of Sel 85 N indicated the role of an efficient AM symbiosis capable of attenuating NaCl and Cd stresses.

Seasonal variations in the physiological stress response to discrete bouts of aerial exposure in the little skate, Leucoraja erinacea

Aerial exposure and acute thermal stress have been shown to elicit profound physiological disruptions in obligate water-breathing teleosts. However, no study has investigated these responses in an elasmobranch. To address this, venous blood samples were collected and evaluated from little skates (Leucoraja erinacea) subjected to discrete aerial exposure durations (0, 15, and 50min) coupled with differing abrupt thermal changes (gradient between seawater and air; winter: ΔT=−3°C; summer: ΔT=+9°C) in two distinct laboratory studies. In general, blood acid–base properties (e.g. decline in pH; elevation in PCO2) and select metabolites (elevated whole-blood lactate) and electrolytes (elevated plasma K+) were significantly disrupted by aerial exposure, and were most disturbed after skates were exposed to air for 50min. However, the magnitude of the blood acid–base perturbations, metabolic contribution to the resulting blood acidosis, elevations to ionic and metabolic parameters, and delayed mortality were more extreme during the summer study, suggesting that acute thermal stress exacerbates the physiological impairments associated with aerial exposure in little skates. Conversely, a reduced thermal gradient (from seawater to air) may attenuate the magnitude of metabolic and ionic perturbations, resulting in a high physiological threshold for coping with extended aerial exposure.

Molecular and genetic characterization of osmosensing and signal transduction in the nematode Caenorhabditis elegans

Osmotic homeostasis is a fundamental requirement for life. In general, the effector mechanisms that mediate cellular and extracellular osmoregulation in animals are reasonably well defined. However, at the molecular level, little is known about how animals detect osmotic and ionic perturbations and transduce them into regulatory responses. The nematode Caenorhabditis elegans provides numerous powerful experimental advantages for defining the genes and integrated gene networks that underlie basic biological processes. These advantages include a fully sequenced and well-annotated genome, forward and reverse genetic and molecular tractability, and a relatively simple anatomy. C. elegans normally inhabits soil environments where it is exposed to repeated osmotic stress. In the laboratory, nematodes readily acclimate to and recover from extremes of hypertonicity. We review recent progress in defining the molecular mechanisms that underlie osmosensing and associated signal transduction in C. elegans. Some of these mechanisms are now known to be highly conserved. Therefore, studies of osmosensing in nematodes have provided, and will undoubtedly continue to provide, new insights into similar processes in more complex organisms including mammals.

Vocal Folds Detect Ionic Perturbations on the Luminal Surface: An In Vitro Investigation

The homeostasis of fluid bathing the luminal surface of the vocal folds is important for phonation and laryngeal defense. Dehydration of the respiratory tract during mouth breathing can perturb the concentration of sodium and chloride ions in surface fluid. Exposure to dry air also increases the osmolarity of airway surface fluid. We hypothesized that viable vocal fold epithelium would detect changes in the ionic and osmotic composition of fluid on the luminal surface. Therefore, we examined bioelectric responses of vocal folds exposed to physiologically real, luminal ionic and osmotic challenges in vitro. The study used randomized factorial design with experimental and sham control groups. Fifty native ovine vocal folds were exposed to five challenges (ionic, osmotic, combined ionic-osmotic, and sham) on the luminal surface. Bioelectric measures of potential difference (PD), short-circuit current (I(SC)), and tissue resistance were assessed at prechallenge baseline, during challenge, and after removal of challenge. Ionic and combined ionic-osmotic challenges reduced PD and I(SC) (P<0.01). These reductions depended on the nature of the ionic challenge, were observed within 10 minutes, lasted for the duration of exposure, and were reversible after removal of the challenge. Conversely, sham or osmotic challenge did not alter bioelectric parameters over time (P>0.05). Viable ovine vocal fold epithelia detect ionic perturbations to the luminal surface. This sensitivity to luminal ionic challenge may be necessary to maintain the homeostasis of surface fluid.