Hyperspectral Imaging, Flow cytometry and Microscopic Morphology of Silver Nanoparticle within Cells

EPA Science Inventory

The ability to detect and track silver nanoparticles (AgNP) that enter cells is important to understand the potential biological and toxicological actions of AgNP. The uptake and fate in cells of four different types of AgNP was studied in a retinal pigment epithelial cell line ...

Parallel Evolution of Larval Feeding Behavior, Morphology, and Habitat in the Snail-Kiling fly Genus Tetanocera

NASA Astrophysics Data System (ADS)

Chapman, E. G.; Foote, B. A.; Malukiewicz, J.; Hoeh, W. R.

2005-05-01

Sciomyzid larvae (Diptera: Acalyptratae) display a wide range of feeding behaviors, typically preying on a wide variety of gastropods. The genus Tetanocera is particularly interesting because its species occupy five larval feeding groups with each species' larvae living in one of two habitat types (aquatic or terrestrial). We constructed a molecular phylogeny for Tetanocera, estimated evolutionary transitions in larval feeding behaviors and habitats that occurred during Tetanocera phylogenesis, and investigated potential correlations among larval habitat and morphological characteristics. Approximately 3800 base pairs (both mitochondrial and nuclear) of sequence data were used to build the phylogeny. Larval feeding groups and habitat type were mapped onto the phylogeny and pair-wise comparisons were used to evaluate potential associations between habitat and morphology. Feeding and habitat groups within Tetanocera were usually not monophyletic and it was estimated that Tetanocera lineages made at least three independent aquatic to terrestrial transitions. These parallel habitat shifts were typically accompanied by parallel character state changes in four morphological characteristics (larval color and three posterior spiracular disc characters). These larval habitat-morphology associations were statistically significant and consistent with the action of natural selection in facilitating the morphological changes that occurred during aquatic to terrestrial habitat transitions in Tetanocera.

Evaluation of Antifungal Activity and Mechanism of Action of Citral against Candida albicans.

PubMed

Leite, Maria Clerya Alvino; Bezerra, André Parente de Brito; de Sousa, Janiere Pereira; Guerra, Felipe Queiroga Sarmento; Lima, Edeltrudes de Oliveira

2014-01-01

Candida albicans is a yeast that commensally inhabits the human body and can cause opportunistic or pathogenic infections. Objective. To investigate the antifungal activity of citral against C. albicans. Methodology. The minimum inhibitory concentration (MIC) and the minimum fungicidal concentration (MFC) were determined by the broth microdilution techniques. We also investigated possible citral action on cell walls (0.8 M sorbitol), cell membranes (citral to ergosterol binding), the time-kill curve, and biological activity on the yeast's morphology. Results. The MIC and MFC of citral were, respectively, 64 µg/mL and 256 µg/mL. Involvement with the cell wall and ergosterol binding were excluded as possible mechanisms of action. In the morphological interference assay, it was observed that the product inhibited pseudohyphae and chlamydoconidia formation. The MIC and the MFC of citral required only 4 hours of exposure to effectively kill 99.9% of the inoculum. Conclusion. Citral showed in vitro antifungal potential against strains of C. albicans. Citral's mechanism of action does not involve the cell wall or ergosterol, and further study is needed to completely describe its effects before being used in the future as a component of new antifungals.

Action of vanillin (Vanilla planifolia) on the morphology of tibialis anterior and soleus muscles after nerve injury

PubMed Central

Peretti, Ana Luiza; Antunes, Juliana Sobral; Lovison, Keli; Kunz, Regina Inês; Castor, Lidyane Regina Gomes; Brancalhão, Rose Meire Costa; Bertolini, Gladson Ricardo Flor; Ribeiro, Lucinéia de Fátima Chasko

2017-01-01

ABSTRACT Objective To evaluate the action of vanillin (Vanilla planifolia) on the morphology of tibialis anterior and soleus muscles after peripheral nerve injury. Methods Wistar rats were divided into four groups, with seven animals each: Control Group, Vanillin Group, Injury Group, and Injury + Vanillin Group. The Injury Group and the Injury + Vanillin Group animals were submitted to nerve injury by compression of the sciatic nerve; the Vanillin Group and Injury + Vanillin Group, were treated daily with oral doses of vanillin (150mg/kg) from the 3rd to the 21st day after induction of nerve injury. At the end of the experiment, the tibialis anterior and soleus muscles were dissected and processed for light microscopy and submitted to morphological analysis. Results The nerve compression promoted morphological changes, typical of denervation, and the treatment with vanillin was responsible for different responses in the studied muscles. For the tibialis anterior, there was an increase in the number of satellite cells, central nuclei and fiber atrophy, as well as fascicular disorganization. In the soleus, only increased vascularization was observed, with no exacerbation of the morphological alterations in the fibers. Conclusion The treatment with vanillin promoted increase in intramuscular vascularization for the muscles studied, with pro-inflammatory potential for tibialis anterior, but not for soleus muscle. PMID:28767917

Tibolone protects T98G cells from glucose deprivation.

PubMed

Ávila Rodriguez, Marco; Garcia-Segura, Luis Miguel; Cabezas, Ricardo; Torrente, Daniel; Capani, Francisco; Gonzalez, Janneth; Barreto, George E

2014-10-01

The steroidal drug Tibolone is used for the treatment of climacteric symptoms and osteoporosis in post-menopausal women. Although Tibolone has been shown to exert neuroprotective actions after middle cerebral artery occlusion, its specific actions on glial cells have received very little attention. In the present study we have assessed whether Tibolone exerts protective actions in a human astrocyte cell model, the T98G cells, subjected to glucose deprivation. Our findings indicate that Tibolone decreases the effects of glucose deprivation on cell death, nuclear fragmentation, superoxide ion production, mitochondrial membrane potential, cytoplasmic calcium concentration and morphological parameters. These findings suggest that glial cells may participate in the neuroprotective actions of Tibolone in the brain. Copyright © 2014 Elsevier Ltd. All rights reserved.

Loss of Gravitropism in Farnesene-Treated Arabidopsis Is Due to Microtubule Malformations Related to Hormonal and ROS Unbalance

PubMed Central

Araniti, Fabrizio; Graña, Elisa; Krasuska, Urszula; Bogatek, Renata; Reigosa, Manuel J.; Abenavoli, Maria Rosa; Sánchez-Moreiras, Adela M.

2016-01-01

Mode of action of farnesene, a volatile sesquiterpene commonly found in the essential oils of several plants, was deeply studied on the model species Arabidopsis thaliana. The effects of farnesene on the Arabidopsis root morphology were evaluated by different microscopic techniques. As well, microtubules immunolabeling, phytohormone measurements and ROS staining helped us to elucidate the single or multi-modes of action of this sesquiterpene on plant metabolism. Farnesene-treated roots showed a strong growth inhibition and marked modifications on morphology, important tissue alterations, cellular damages and anisotropic growth. Left-handed growth of farnesene-treated roots, reverted by taxol (a known microtubule stabilizer), was related to microtubule condensation and disorganization. As well, the inhibition of primary root growth, lateral root number, lateral root length, and both root hairs length and density could be explained by the strong increment in ethylene production and auxin content detected in farnesene-treated seedlings. Microtubule alteration and hormonal unbalance appear as important components in the mode of action of farnesene and confirm the strong phytotoxic potential of this sesquiterpene. PMID:27490179

Loss of Gravitropism in Farnesene-Treated Arabidopsis Is Due to Microtubule Malformations Related to Hormonal and ROS Unbalance.

PubMed

Araniti, Fabrizio; Graña, Elisa; Krasuska, Urszula; Bogatek, Renata; Reigosa, Manuel J; Abenavoli, Maria Rosa; Sánchez-Moreiras, Adela M

2016-01-01

Mode of action of farnesene, a volatile sesquiterpene commonly found in the essential oils of several plants, was deeply studied on the model species Arabidopsis thaliana. The effects of farnesene on the Arabidopsis root morphology were evaluated by different microscopic techniques. As well, microtubules immunolabeling, phytohormone measurements and ROS staining helped us to elucidate the single or multi-modes of action of this sesquiterpene on plant metabolism. Farnesene-treated roots showed a strong growth inhibition and marked modifications on morphology, important tissue alterations, cellular damages and anisotropic growth. Left-handed growth of farnesene-treated roots, reverted by taxol (a known microtubule stabilizer), was related to microtubule condensation and disorganization. As well, the inhibition of primary root growth, lateral root number, lateral root length, and both root hairs length and density could be explained by the strong increment in ethylene production and auxin content detected in farnesene-treated seedlings. Microtubule alteration and hormonal unbalance appear as important components in the mode of action of farnesene and confirm the strong phytotoxic potential of this sesquiterpene.

Mammary gland morphology and gene expression signature of prepubertal male and female rats following exposure to exogenous estradiol

USDA-ARS?s Scientific Manuscript database

In order to properly screen environmental chemicals for potential toxic effects such as increased cancer risk and risk of infertility resulting from actions similar to those of female sex steroids such as estrogens, it is essential to understand the effects of treatment with the most important femal...

Electrophysiological evidence of doubly innervated branched muscle fibers in the human brachioradialis muscle.

PubMed

Lateva, Zoia C; McGill, Kevin C

2007-12-01

Motor-unit action potentials (MUAPs) with unstable satellite (late-latency) components are found in EMG signals from the brachioradialis muscles of normal subjects. We analyzed the morphology and blocking behavior of these MUAPs to determine their anatomical origin. EMG signals were recorded from the brachioradialis muscles of 5 normal subjects during moderate-level isometric contractions. MUAP waveforms, discharge patterns, and blocking were determined using computer-aided EMG decomposition. Twelve MUAPs with unstable satellite potentials were detected, always two together in the same signal. Each MUAP also had a second unstable component associated with its main spike. The blocking behavior of the unstable components depended on how close together the two MUAPs were when they discharged. The latencies and blocking behavior indicate that the unstable components came from branched muscle fibers innervated by two different motoneurons. The satellite potentials were due to action potentials that traveled to the branching point along one branch and back along the other. The blockings were due to action-potential collisions when both motoneurons discharged close together in time. Animal studies suggest that branched muscle fibers may be a normal characteristic of series-fibered muscles. This study adds to our understanding of these muscles in humans.

Relationship between increasing concentrations of two carcinogens and statistical image descriptors of foci morphology in the cell transformation assay.

PubMed

Callegaro, Giulia; Corvi, Raffaella; Salovaara, Susan; Urani, Chiara; Stefanini, Federico M

2017-06-01

Cell Transformation Assays (CTAs) have long been proposed for the identification of chemical carcinogenicity potential. The endpoint of these in vitro assays is represented by the phenotypic alterations in cultured cells, which are characterized by the change from the non-transformed to the transformed phenotype. Despite the wide fields of application and the numerous advantages of CTAs, their use in regulatory toxicology has been limited in part due to concerns about the subjective nature of visual scoring, i.e. the step in which transformed colonies or foci are evaluated through morphological features. An objective evaluation of morphological features has been previously obtained through automated digital processing of foci images to extract the value of three statistical image descriptors. In this study a further potential of the CTA using BALB/c 3T3 cells is addressed by analysing the effect of increasing concentrations of two known carcinogens, benzo[a]pyrene and NiCl 2 , with different modes of action on foci morphology. The main result of our quantitative evaluation shows that the concentration of the considered carcinogens has an effect on foci morphology that is statistically significant for the mean of two among the three selected descriptors. Statistical significance also corresponds to visual relevance. The statistical analysis of variations in foci morphology due to concentration allowed to quantify morphological changes that can be visually appreciated but not precisely determined. Therefore, it has the potential of providing new quantitative parameters in CTAs, and of exploiting all the information encoded in foci. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Stress tolerance and biocontrol performance of the yeast antagonist, Candida diversa, change with morphology transition.

PubMed

Li, Guangkun; Chi, Mengshan; Chen, Huizhen; Sui, Yuan; Li, Yan; Liu, Yongsheng; Zhang, Xiaojing; Sun, Zhiqiang; Liu, Guoqing; Wang, Qi; Liu, Jia

2016-02-01

As an eco-friendly management method, biological control of postharvest diseases, utilizing antagonistic yeasts, is a research topic receiving considerable attention. Detailed knowledge on the biology of yeast antagonists is crucial when considering their potential application and development as biocontrol products. Changes in the growth form, such as single-cell to pseudohyphae, have been associated with the mode of action in postharvest biocontrol yeasts. In this study, the antagonistic yeast, Candida diversa, reversibly shifted from a single-cell morphology on yeast peptone dextrose (YPD) medium with 2 % agar to a pseudohyphal morphology on YPD with 0.3 % agar. The tolerance of the pseudohyphal form to heat and oxidative stresses, as well as the biocontrol efficacy against Botrytis cinerea on apple and kiwifruit stored at 25 and 4 °C, was significantly higher as compared to the single-cell form. This study provides new information on the ability of C. diversa to change its morphology and the impact of the morphology shift on stress tolerance and biocontrol performance.

Voltage-gated currents in identified rat olfactory receptor neurons.

PubMed

Trombley, P Q; Westbrook, G L

1991-02-01

Whole-cell recording techniques were used to characterize voltage-gated membrane currents in neonatal rat olfactory receptor neurons (ORNs) in cell culture. Mature ORNs were identified in culture by their characteristic bipolar morphology, by retrograde labeling techniques, and by olfactory marker protein (OMP) immunoreactivity. ORNs did not have spontaneous activity, but fired action potentials to depolarizing current pulses. Action potentials were blocked by tetrodotoxin (TTX), which contrasts with the TTX-resistant action potentials in salamander olfactory receptor cells (e.g., Firestein and Werblin, 1987). Prolonged, suprathreshold current pulses evoked only a single action potential; however, repetitive firing up to 35 Hz could be elicited by a series of brief depolarizing pulses. Under voltage clamp, the TTX-sensitive sodium current had activation and inactivation properties similar to other excitable cells. In TTX and 20 mM barium, sustained inward current were evoked by voltage steps positive to -30 mV. This current was blocked by Cd (100 microM) and by nifedipine (IC50 = 368 nM) consistent with L-type calcium channels in other neurons. No T-type calcium current was observed. Voltage steps positive to -20 mV also evoked an outward current that did not inactivate during 100-msec depolarizations. Tail current analysis of this current was consistent with a selective potassium conductance. The outward current was blocked by external tetraethylammonium but was unaffected by Cd or 4-aminopyridine (4-AP) or by removal of external calcium. A transient outward current was not observed. The 3 voltage-dependent conductances in cultured rat ORNs appear to be sufficient for 2 essential functions: action potential generation and transmitter release. As a single odorant-activated channel can trigger an action potential (e.g., Lynch and Barry, 1989), the repetitive firing seen with brief depolarizing pulses suggests that ORNs do not integrate sensory input, but rather act as high-fidelity relays such that each opening of an odorant-activated channel reaches the olfactory bulb glomeruli as an action potential.

Dendritic Properties Control Energy Efficiency of Action Potentials in Cortical Pyramidal Cells

PubMed Central

Yi, Guosheng; Wang, Jiang; Wei, Xile; Deng, Bin

2017-01-01

Neural computation is performed by transforming input signals into sequences of action potentials (APs), which is metabolically expensive and limited by the energy available to the brain. The metabolic efficiency of single AP has important consequences for the computational power of the cell, which is determined by its biophysical properties and morphologies. Here we adopt biophysically-based two-compartment models to investigate how dendrites affect energy efficiency of APs in cortical pyramidal neurons. We measure the Na+ entry during the spike and examine how it is efficiently used for generating AP depolarization. We show that increasing the proportion of dendritic area or coupling conductance between two chambers decreases Na+ entry efficiency of somatic AP. Activating inward Ca2+ current in dendrites results in dendritic spike, which increases AP efficiency. Activating Ca2+-activated outward K+ current in dendrites, however, decreases Na+ entry efficiency. We demonstrate that the active and passive dendrites take effects by altering the overlap between Na+ influx and internal current flowing from soma to dendrite. We explain a fundamental link between dendritic properties and AP efficiency, which is essential to interpret how neural computation consumes metabolic energy and how biophysics and morphologies contribute to such consumption. PMID:28919852

Dendritic Properties Control Energy Efficiency of Action Potentials in Cortical Pyramidal Cells.

PubMed

Yi, Guosheng; Wang, Jiang; Wei, Xile; Deng, Bin

2017-01-01

Neural computation is performed by transforming input signals into sequences of action potentials (APs), which is metabolically expensive and limited by the energy available to the brain. The metabolic efficiency of single AP has important consequences for the computational power of the cell, which is determined by its biophysical properties and morphologies. Here we adopt biophysically-based two-compartment models to investigate how dendrites affect energy efficiency of APs in cortical pyramidal neurons. We measure the Na + entry during the spike and examine how it is efficiently used for generating AP depolarization. We show that increasing the proportion of dendritic area or coupling conductance between two chambers decreases Na + entry efficiency of somatic AP. Activating inward Ca 2+ current in dendrites results in dendritic spike, which increases AP efficiency. Activating Ca 2+ -activated outward K + current in dendrites, however, decreases Na + entry efficiency. We demonstrate that the active and passive dendrites take effects by altering the overlap between Na + influx and internal current flowing from soma to dendrite. We explain a fundamental link between dendritic properties and AP efficiency, which is essential to interpret how neural computation consumes metabolic energy and how biophysics and morphologies contribute to such consumption.

Effect of anti-GM2 antibodies on rat sciatic nerve: electrophysiological and morphological study.

PubMed

Ortiz, Nicolau; Sabaté, M Mar; Garcia, Neus; Santafe, Manel M; Lanuza, M Angel; Tomàs, Marta; Tomàs, Josep

2009-03-31

We found that a monoclonal human IgM anti-GM2 was fixed in rat sciatic axons and Schwann cells and was able to activate human complement. The passive transfer of IgM and complement in sciatic nerves can induce an acute alteration in nerve conduction. When the transfer of IgM plus complement was repeated for 10 days, the compound action motor potential amplitude was very low and the morphological study showed axons and myelin damage. Without human complement, IgM can only slightly disorganize the myelin by separating some layers, probably by interfering with the functional role of gangliosides in the myelin package.

An Excel‐based implementation of the spectral method of action potential alternans analysis

PubMed Central

Pearman, Charles M.

2014-01-01

Abstract Action potential (AP) alternans has been well established as a mechanism of arrhythmogenesis and sudden cardiac death. Proper interpretation of AP alternans requires a robust method of alternans quantification. Traditional methods of alternans analysis neglect higher order periodicities that may have greater pro‐arrhythmic potential than classical 2:1 alternans. The spectral method of alternans analysis, already widely used in the related study of microvolt T‐wave alternans, has also been used to study AP alternans. Software to meet the specific needs of AP alternans analysis is not currently available in the public domain. An AP analysis tool is implemented here, written in Visual Basic for Applications and using Microsoft Excel as a shell. This performs a sophisticated analysis of alternans behavior allowing reliable distinction of alternans from random fluctuations, quantification of alternans magnitude, and identification of which phases of the AP are most affected. In addition, the spectral method has been adapted to allow detection and quantification of higher order regular oscillations. Analysis of action potential morphology is also performed. A simple user interface enables easy import, analysis, and export of collated results. PMID:25501439

Feeding soy protein isolate and treatment with estradiol have different effects on mammary gland morphology and gene expression in weanling male and female rats

USDA-ARS?s Scientific Manuscript database

Isoflavones are phytochemical components of soy diets that bind weakly to estrogen receptors (ERs). To study potential estrogen-like actions of soy in the mammary gland during early development, we fed weanling male and female Sprague-Dawley rats a semi-purified diet with casein as the sole protein ...

Spine Calcium Transients Induced by Synaptically-Evoked Action Potentials Can Predict Synapse Location and Establish Synaptic Democracy

PubMed Central

Meredith, Rhiannon M.; van Ooyen, Arjen

2012-01-01

CA1 pyramidal neurons receive hundreds of synaptic inputs at different distances from the soma. Distance-dependent synaptic scaling enables distal and proximal synapses to influence the somatic membrane equally, a phenomenon called “synaptic democracy”. How this is established is unclear. The backpropagating action potential (BAP) is hypothesised to provide distance-dependent information to synapses, allowing synaptic strengths to scale accordingly. Experimental measurements show that a BAP evoked by current injection at the soma causes calcium currents in the apical shaft whose amplitudes decay with distance from the soma. However, in vivo action potentials are not induced by somatic current injection but by synaptic inputs along the dendrites, which creates a different excitable state of the dendrites. Due to technical limitations, it is not possible to study experimentally whether distance information can also be provided by synaptically-evoked BAPs. Therefore we adapted a realistic morphological and electrophysiological model to measure BAP-induced voltage and calcium signals in spines after Schaffer collateral synapse stimulation. We show that peak calcium concentration is highly correlated with soma-synapse distance under a number of physiologically-realistic suprathreshold stimulation regimes and for a range of dendritic morphologies. Peak calcium levels also predicted the attenuation of the EPSP across the dendritic tree. Furthermore, we show that peak calcium can be used to set up a synaptic democracy in a homeostatic manner, whereby synapses regulate their synaptic strength on the basis of the difference between peak calcium and a uniform target value. We conclude that information derived from synaptically-generated BAPs can indicate synapse location and can subsequently be utilised to implement a synaptic democracy. PMID:22719238

Fitting membrane resistance along with action potential shape in cardiac myocytes improves convergence: application of a multi-objective parallel genetic algorithm.

PubMed

Kaur, Jaspreet; Nygren, Anders; Vigmond, Edward J

2014-01-01

Fitting parameter sets of non-linear equations in cardiac single cell ionic models to reproduce experimental behavior is a time consuming process. The standard procedure is to adjust maximum channel conductances in ionic models to reproduce action potentials (APs) recorded in isolated cells. However, vastly different sets of parameters can produce similar APs. Furthermore, even with an excellent AP match in case of single cell, tissue behaviour may be very different. We hypothesize that this uncertainty can be reduced by additionally fitting membrane resistance (Rm). To investigate the importance of Rm, we developed a genetic algorithm approach which incorporated Rm data calculated at a few points in the cycle, in addition to AP morphology. Performance was compared to a genetic algorithm using only AP morphology data. The optimal parameter sets and goodness of fit as computed by the different methods were compared. First, we fit an ionic model to itself, starting from a random parameter set. Next, we fit the AP of one ionic model to that of another. Finally, we fit an ionic model to experimentally recorded rabbit action potentials. Adding the extra objective (Rm, at a few voltages) to the AP fit, lead to much better convergence. Typically, a smaller MSE (mean square error, defined as the average of the squared error between the target AP and AP that is to be fitted) was achieved in one fifth of the number of generations compared to using only AP data. Importantly, the variability in fit parameters was also greatly reduced, with many parameters showing an order of magnitude decrease in variability. Adding Rm to the objective function improves the robustness of fitting, better preserving tissue level behavior, and should be incorporated.

Differential roles of two delayed rectifier potassium currents in regulation of ventricular action potential duration and arrhythmia susceptibility.

PubMed

Devenyi, Ryan A; Ortega, Francis A; Groenendaal, Willemijn; Krogh-Madsen, Trine; Christini, David J; Sobie, Eric A

2017-04-01

Arrhythmias result from disruptions to cardiac electrical activity, although the factors that control cellular action potentials are incompletely understood. We combined mathematical modelling with experiments in heart cells from guinea pigs to determine how cellular electrical activity is regulated. A mismatch between modelling predictions and the experimental results allowed us to construct an improved, more predictive mathematical model. The balance between two particular potassium currents dictates how heart cells respond to perturbations and their susceptibility to arrhythmias. Imbalances of ionic currents can destabilize the cardiac action potential and potentially trigger lethal cardiac arrhythmias. In the present study, we combined mathematical modelling with information-rich dynamic clamp experiments to determine the regulation of action potential morphology in guinea pig ventricular myocytes. Parameter sensitivity analysis was used to predict how changes in ionic currents alter action potential duration, and these were tested experimentally using dynamic clamp, a technique that allows for multiple perturbations to be tested in each cell. Surprisingly, we found that a leading mathematical model, developed with traditional approaches, systematically underestimated experimental responses to dynamic clamp perturbations. We then re-parameterized the model using a genetic algorithm, which allowed us to estimate ionic current levels in each of the cells studied. This unbiased model adjustment consistently predicted an increase in the rapid delayed rectifier K + current and a drastic decrease in the slow delayed rectifier K + current, and this prediction was validated experimentally. Subsequent simulations with the adjusted model generated the clinically relevant prediction that the slow delayed rectifier is better able to stabilize the action potential and suppress pro-arrhythmic events than the rapid delayed rectifier. In summary, iterative coupling of simulations and experiments enabled novel insight into how the balance between cardiac K + currents influences ventricular arrhythmia susceptibility. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

[The compensatory and adaptive e reactions of the respiratory system as the diagnostic criteria for histological studies in forensic medicine].

PubMed

Os'minkin, V A; Os'minkin, S V

2015-01-01

The objective of the present study was to characterize the structural changes in the respiratory system equivalent to its compensatory and adaptive reactions in response to the action of various factors under the normal and extreme conditions for the assessment of the possibility of their further use for the purpose of diagnostics. The action of various factors on the tissues obtained from the human respiratory system for forensic medical examination was shown to cause combined histomorphological alterations that refelect a wide spectrum of protective, compensatory, and adaptive reactions. The range of potential morphological and functional changes in the respiratory system depends on the characteristics of endogenous and exogenous factors influencing the organism of the affected subjects. It is concluded that the use of the proposed approach to morphological diagnostics may be useful for the development of criteria for the evaluation of various variants of tanatogenesis with their objective confirmation by mathematical models.

Myelin Loss and Axonal Ion Channel Adaptations Associated with Gray Matter Neuronal Hyperexcitability

PubMed Central

Hamada, Mustafa S.

2015-01-01

Myelination and voltage-gated ion channel clustering at the nodes of Ranvier are essential for the rapid saltatory conduction of action potentials. Whether myelination influences the structural organization of the axon initial segment (AIS) and action potential initiation is poorly understood. Using the cuprizone mouse model, we combined electrophysiological recordings with immunofluorescence of the voltage-gated Nav1.6 and Kv7.3 subunits and anchoring proteins to analyze the functional and structural properties of single demyelinated neocortical L5 axons. Whole-cell recordings demonstrated that neurons with demyelinated axons were intrinsically more excitable, characterized by increased spontaneous suprathreshold depolarizations as well as antidromically propagating action potentials ectopically generated in distal parts of the axon. Immunofluorescence examination of demyelinated axons showed that βIV-spectrin, Nav1.6, and the Kv7.3 channels in nodes of Ranvier either dissolved or extended into the paranodal domains. In contrast, while the AIS in demyelinated axons started more closely to the soma, ankyrin G, βIV-spectrin, and the ion channel expression were maintained. Structure–function analysis and computational modeling, constrained by the AIS location and realistic dendritic and axonal morphologies, confirmed that a more proximal onset of the AIS slightly reduced the efficacy of action potential generation, suggesting a compensatory role. These results suggest that oligodendroglial myelination is not only important for maximizing conduction velocity, but also for limiting hyperexcitability of pyramidal neurons. PMID:25948275

Assessment of the effects of multiple extreme floods on flow and transport processes under competing flood protection and environmental management strategies.

PubMed

Tu, Tongbi; Carr, Kara J; Ercan, Ali; Trinh, Toan; Kavvas, M Levent; Nosacka, John

2017-12-31

Extreme floods are regarded as one of the most catastrophic natural hazards and can result in significant morphological changes induced by pronounced sediment erosion and deposition processes over the landscape. However, the effects of extreme floods of different return intervals on the floodplain and river channel morphological evolution with the associated sediment transport processes are not well explored. Furthermore, different basin management action plans, such as engineering structure modifications, may also greatly affect the flood inundation, sediment transport, solute transport and morphological processes within extreme flood events. In this study, a coupled two-dimensional hydrodynamic, sediment transport and morphological model is applied to evaluate the impact of different river and basin management strategies on the flood inundation, sediment transport dynamics and morphological changes within extreme flood events of different magnitudes. The 10-year, 50-year, 100-year and 200-year floods are evaluated for the Lower Cache Creek system in California under existing condition and a potential future modification scenario. Modeling results showed that select locations of flood inundation within the study area tend to experience larger inundation depth and more sediment is likely to be trapped in the study area under potential modification scenario. The proposed two dimensional flow and sediment transport modeling approach implemented with a variety of inflow conditions can provide guidance to decision-makers when considering implementation of potential modification plans, especially as they relate to competing management strategies of large water bodies, such as the modeling area in this study. Copyright © 2017 Elsevier B.V. All rights reserved.

Bathymetry, morphology, and lakebed geologic characteristics of potential Kokanee salmon spawning habitat in Lake Pend Oreille, Bayview and Lakeview quadrangles, Idaho

USGS Publications Warehouse

Barton, Gary J.; Dux, Andrew M.

2013-01-01

Kokanee salmon (Oncorhynchus nerka) are a keystone species in Lake Pend Oreille in northern Idaho, historically supporting a high-yield recreational fishery and serving as the primary prey for the threatened native bull trout (Salvelinus confluentus) and the Gerrard-strain rainbow trout (Oncorhynchus mykiss). After 1965, the kokanee population rapidly declined and has remained at a low level of abundance. Lake Pend Oreille is one of the deepest lakes in the United States, the largest lake in Idaho, and home to the U.S. Navy Acoustic Research Detachment Base. The U.S. Geological Survey and Idaho Department of Fish and Game are mapping the bathymetry, morphology, and the lakebed geologic units and embeddedness of potential kokanee salmon spawning habitat in Lake Pend Oreille. Relations between lake morphology, lakebed geologic units, and substrate embeddedness are characterized for the shore zone, rise zone, and open water in bays and the main stem of the lake. This detailed knowledge of physical habitat along the shoreline of Lake Pend Oreille is necessary to better evaluate and develop kokanee recovery actions.

[Functional organization and structure of the serotonergic neuronal network of terrestrial snail].

PubMed

Nikitin, E S; Balaban, P M

2011-01-01

The extension of knowledge how the brain works requires permanent improvement of methods of recording of neuronal activity and increase in the number of neurons recorded simultaneously to better understand the collective work of neuronal networks and assemblies. Conventional methods allow simultaneous intracellular recording up to 2-5 neurons and their membrane potentials, currents or monosynaptic connections or observation of spiking of neuronal groups with subsequent discrimination of individual spikes with loss of details of the dynamics of membrane potential. We recorded activity of a compact group of serotonergic neurons (up to 56 simultaneously) in the ganglion of a terrestrial mollusk using the method of optical recording of membrane potential that allowed to record individual action potentials in details with action potential parameters and to reveal morphology of the neurons rcorded. We demonstrated clear clustering in the group in relation with the dynamics of action potentials and phasic or tonic components in the neuronal responses to external electrophysiological and tactile stimuli. Also, we showed that identified neuron Pd2 could induce activation of a significant number of neurons in the group whereas neuron Pd4 did not induce any activation. However, its activation is delayed with regard to activation of the reacting group of neurons. Our data strongly support the concept of possible delegation of the integrative function by the network to a single neuron.

An Excel-based implementation of the spectral method of action potential alternans analysis.

PubMed

Pearman, Charles M

2014-12-01

Action potential (AP) alternans has been well established as a mechanism of arrhythmogenesis and sudden cardiac death. Proper interpretation of AP alternans requires a robust method of alternans quantification. Traditional methods of alternans analysis neglect higher order periodicities that may have greater pro-arrhythmic potential than classical 2:1 alternans. The spectral method of alternans analysis, already widely used in the related study of microvolt T-wave alternans, has also been used to study AP alternans. Software to meet the specific needs of AP alternans analysis is not currently available in the public domain. An AP analysis tool is implemented here, written in Visual Basic for Applications and using Microsoft Excel as a shell. This performs a sophisticated analysis of alternans behavior allowing reliable distinction of alternans from random fluctuations, quantification of alternans magnitude, and identification of which phases of the AP are most affected. In addition, the spectral method has been adapted to allow detection and quantification of higher order regular oscillations. Analysis of action potential morphology is also performed. A simple user interface enables easy import, analysis, and export of collated results. © 2014 The Author. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Antimicrobial and Antiproliferative Potential of Anadenanthera colubrina (Vell.) Brenan

PubMed Central

Lima, Rennaly de Freitas; Alves, Érika Ponchet; Rosalen, Pedro Luiz; Ruiz, Ana Lúcia Tasca Gois; Teixeira Duarte, Marta Cristina; Góes, Vivian Fernandes Furletti; de Medeiros, Ana Cláudia Dantas; Pereira, Jozinete Vieira; Godoy, Gustavo Pina; Melo de Brito Costa, Edja Maria

2014-01-01

The aim of the present study was to perform an in vitro analysis of the antimicrobial and antiproliferative potential of an extract from Anadenanthera colubrina (Vell.) Brenan (angico) and chemically characterize the crude extract. Antimicrobial action was evaluated based on the minimum inhibitory concentration (MIC), minimum bactericidal/fungicidal concentration, and the inhibition of formation to oral biofilm. Cell morphology was determined through scanning electron microscopy (SEM). Six strains of tumor cells were used for the determination of antiproliferative potential. The extract demonstrated strong antifungal activity against Candida albicans ATCC 18804 (MIC = 0.031 mg/mL), with similar activity found regarding the ethyl acetate fraction. The extract and active fraction also demonstrated the capacity to inhibit the formation of Candida albicans to oral biofilm after 48 hours, with median values equal to or greater than the control group, but the difference did not achieve statistical significance (P > 0.05). SEM revealed alterations in the cell morphology of the yeast. Regarding antiproliferative activity, the extract demonstrated cytostatic potential in all strains tested. The present findings suggest strong antifungal potential for Anadenanthera colubrina (Vell.) Brenan as well as a tendency toward diminishing the growth of human tumor cells. PMID:25093029

Electrical Identification and Selective Microstimulation of Neuronal Compartments Based on Features of Extracellular Action Potentials

NASA Astrophysics Data System (ADS)

Radivojevic, Milos; Jäckel, David; Altermatt, Michael; Müller, Jan; Viswam, Vijay; Hierlemann, Andreas; Bakkum, Douglas J.

2016-08-01

A detailed, high-spatiotemporal-resolution characterization of neuronal responses to local electrical fields and the capability of precise extracellular microstimulation of selected neurons are pivotal for studying and manipulating neuronal activity and circuits in networks and for developing neural prosthetics. Here, we studied cultured neocortical neurons by using high-density microelectrode arrays and optical imaging, complemented by the patch-clamp technique, and with the aim to correlate morphological and electrical features of neuronal compartments with their responsiveness to extracellular stimulation. We developed strategies to electrically identify any neuron in the network, while subcellular spatial resolution recording of extracellular action potential (AP) traces enabled their assignment to the axon initial segment (AIS), axonal arbor and proximal somatodendritic compartments. Stimulation at the AIS required low voltages and provided immediate, selective and reliable neuronal activation, whereas stimulation at the soma required high voltages and produced delayed and unreliable responses. Subthreshold stimulation at the soma depolarized the somatic membrane potential without eliciting APs.

An evaluation of the utility and limitations of counting motor unit action potentials in the surface electromyogram

NASA Astrophysics Data System (ADS)

Zhou, Ping; Zev Rymer, William

2004-12-01

The number of motor unit action potentials (MUAPs) appearing in the surface electromyogram (EMG) signal is directly related to motor unit recruitment and firing rates and therefore offers potentially valuable information about the level of activation of the motoneuron pool. In this paper, based on morphological features of the surface MUAPs, we try to estimate the number of MUAPs present in the surface EMG by counting the negative peaks in the signal. Several signal processing procedures are applied to the surface EMG to facilitate this peak counting process. The MUAP number estimation performance by this approach is first illustrated using the surface EMG simulations. Then, by evaluating the peak counting results from the EMG records detected by a very selective surface electrode, at different contraction levels of the first dorsal interosseous (FDI) muscles, the utility and limitations of such direct peak counts for MUAP number estimation in surface EMG are further explored.

Microelectrode array measurement of potassium ion channel remodeling on the field action potential duration in rapid atrial pacing rabbits model.

PubMed

Sun, Juan; Yan, Huang; Wugeti, Najina; Guo, Yujun; Zhang, Ling; Ma, Mei; Guo, Xingui; Jiao, Changan; Xu, Wenli; Li, Tianqi

2015-01-01

Atrial fibrillation (AF) arises from abnormalities in atrial structure and electrical activity. Microelectrode arrays (MEA) is a real-time, nondestructive measurement of the resting and action potential signal, from myocardial cells, to the peripheral circuit of electrophysiological activity. This study examined the field action potential duration (fAPD) of the right atrial appendage (RAA) by MEA in rapid atrial pacing (RAP) in the right atrium of rabbits. In addition, this study also investigated the effect of potassium ion channel blockers on fAPD. 40 New Zealand white rabbits of either sex were randomly divided into 3 groups: 1) the control, 2) potassium ion channel blocker (TEA, 4-Ap and BaCl2), and 3) amiodarone groups. The hearts were quickly removed and right atrial appendage sectioned (slice thickness 500 μm). Each slice was perfused with Tyrode's solution and continuously stimulated for 30 minutes. Sections from the control group were superfused with Tyrode's solution for 10 minutes, while the blocker groups and amiodarone were both treated with their respective compounds for 10 minutes each. The fAPD of RAA and action field action potential morphology were measured using MEA. In non-pace (control) groups, fAPD was 188.33 ± 18.29 ms after Tyrode's solution superfusion, and 173.91 ± 6.83 ms after RAP. In pace/potassium ion channel groups, TEA and BaCl2 superfusion prolonged atrial field action potential (fAPD) (control vs blocker: 176.67 ± 8.66 ms vs 196.11 ± 10.76 ms, 182.22 ± 12.87 ms vs 191.11 ± 13.09 ms with TEA and BaCl2 superfusion, respectively, P < 0.05). 4-AP superfusion significantly prolonged FAPD. In pace/amiodarone groups, 4-Ap superfusion extended fAPD. MEA was a sensitive and stable reporter for the measurement of the tissue action potential in animal heart slices. After superfusing potassium ion channel blockers, fAPD was prolonged. These results suggest that Ito, IKur and IK1 remodel and mediate RAP-induced atrial electrical remodeling. Amiodarone alter potassium ion channel activity (Ito, IKur, IK1 and IKs), shortening fAPD.

Sorting Out Effects of Active Stream Restoration: Channel Morphology, Channel Change Processes and Potential Controls

NASA Astrophysics Data System (ADS)

McDowell, P. F.

2017-12-01

In many active restoration projects, instream structures or modifications are designed to produce specific change in channel form, such as reduced W:D or increased pool depth, yet there is little monitoring to evaluate effectiveness. Active restoration often takes place within a context of other land management changes that can have an effect on channel form. Thus, the effects of active restoration are difficult to separate from the effects of other management actions. We measured morphologic response to restoration designs on sections of the Middle Fork John Day River, a gravel-cobble bed river under a cattle grazing regime in the Blue Mountain of Oregon. Since 2000, restoration actions have included elimination of cattle grazing in the riparian zone (passive restoration), riparian planting of woody vegetation, instream log structures for fish habitat and pool maintenance, and elimination of a major flow diversion. We listed the hypothetical effects of each of these management changes, showing overlap among effects of active and passive restoration. Repeat cross-section and longitudinal profile surveys over eight years, and repeat aerial imagery, documented changes in channel width, depth and bed morphology, and processes of change (bank erosion or aggradation, point bar erosion or aggradation, bed incision or aggradation), in two restored reaches and two adjacent control (unrestored) reaches. Morphologic changes were modest. Bankfull cross-section area, width, and W:D all decreased slightly in both restored reaches. Control reaches were unchanged or increased slightly. Processes of change were markedly different among the four reaches, with different reaches dominated by different processes. One restored reach was dominated by slight bed aggradation, increased pool depth and deep pools/km, while the other restored reach was dominated by bank erosion, bar aggradation and slight bed incision, along with increased deep pools/km. The longitudinal profile showed significant re-arrangement of bed morphology. The spatial context of processes and controls allows some separation of the effectiveness of different management actions. Active restoration directly increased pool depth, but passive restoration apparently had more impact on aggradation/degradation and width.

Isolation and culture of adult mouse vestibular nucleus neurons

PubMed

Him, Aydın; Altuntaş, Serap; Öztürk, Gürkan; Erdoğan, Ender; Cengiz, Nureddin

2017-12-19

Background/aim: Isolated cell cultures are widely used to study neuronal properties due to their advantages. Although embryonic animals are preferred for culturing, their morphological or electrophysiological properties may not reflect adult neurons, which may be important in neurodegenerative diseases. This paper aims to develop a method for preparing isolated cell cultures of medial vestibular nucleus (MVN) from adult mice and describe its morphological and electrophysiological properties.Materials and methods: Vestibular nucleus neurons were mechanically and enzymatically isolated and cultured using a defined medium with known growth factors. Cell survival was measured with propidium iodide, and electrophysiological properties were investigated with current-clamp recording.Results: Vestibular neurons grew neurites in cultures, gaining adult-like morphological properties, and stayed viable for 3 days in culture. Adding bovine calf serum, nerve growth factor, or insulin-like growth factor into the culture medium enhanced neuronal viability. Current-clamp recording of the cultured neurons revealed tonic and phasic-type neurons with similar input resistance, resting membrane potential, action potential amplitude, and duration. Conclusion: Vestibular neurons from adult mice can be cultured, and regenerate axons in a medium containing appropriate growth factors. Culturing adult vestibular neurons provides a new method to study age-related pathologies of the vestibular system.

Role of the Axon Initial Segment in the Control of Spontaneous Frequency of Nigral Dopaminergic Neurons In Vivo.

PubMed

Meza, Rodrigo C; López-Jury, Luciana; Canavier, Carmen C; Henny, Pablo

2018-01-17

The spontaneous tonic discharge activity of nigral dopamine neurons plays a fundamental role in dopaminergic signaling. To investigate the role of neuronal morphology and architecture with respect to spontaneous activity in this population, we visualized the 3D structure of the axon initial segment (AIS) along with the entire somatodendritic domain of adult male mouse dopaminergic neurons, previously recorded in vivo We observed a positive correlation of the firing rate with both proximity and size of the AIS. Computational modeling showed that the size of the AIS, but not its position within the somatodendritic domain, is the major causal determinant of the tonic firing rate in the intact model, by virtue of the higher intrinsic frequency of the isolated AIS. Further mechanistic analysis of the relationship between neuronal morphology and firing rate showed that dopaminergic neurons function as a coupled oscillator whose frequency of discharge results from a compromise between AIS and somatodendritic oscillators. Thus, morphology plays a critical role in setting the basal tonic firing rate, which in turn could control striatal dopaminergic signaling that mediates motivation and movement. SIGNIFICANCE STATEMENT The frequency at which nigral dopamine neurons discharge action potentials sets baseline dopamine levels in the brain, which enables activity in motor, cognitive, and motivational systems. Here, we demonstrate that the size of the axon initial segment, a subcellular compartment responsible for initiating action potentials, is a key determinant of the firing rate in these neurons. The axon initial segment and all the molecular components that underlie its critical function may provide a novel target for the regulation of dopamine levels in the brain. Copyright © 2018 the authors 0270-6474/18/380733-12$15.00/0.

Investigating the dental toolkit of primates based on food mechanical properties: Feeding action does matter.

PubMed

Thiery, Ghislain; Guy, Franck; Lazzari, Vincent

2017-06-01

Although conveying an indisputable morphological and behavioral signal, traditional dietary categories such as frugivorous or folivorous tend to group a wide range of food mechanical properties together. Because food/tooth interactions are mostly mechanical, it seems relevant to investigate the dental morphology of primates based on mechanical categories. However, existing mechanical categories classify food by its properties but cannot be used as factors to classify primate dietary habits. This comes from the fact that one primate species might be adapted to a wide range of food mechanical properties. To tackle this issue, what follows is an original framework based on action-related categories. The proposal here is to classify extant primates based on the range of food mechanical properties they can process through one given action. The resulting categories can be used as factors to investigate the dental tools available to primates. Furthermore, cracking, grinding, and shearing categories assigned depending on the hardness and the toughness of food are shown to be supported by morphological data (3D relative enamel thickness) and topographic data (relief index, occlusal complexity, and Dirichlet normal energy). Inferring food mechanical properties from dental morphology is especially relevant for the study of extinct primates, which are mainly documented by dental remains. Hence, we use action-related categories to investigate the molar morphology of an extinct colobine monkey Mesopithecus pentelicus from the Miocene of Pikermi, Greece. Action-related categories show contrasting results compared with classical categories and give us new insights into the dietary adaptations of this extinct primate. Finally, we provide some possible directions for future research aiming to test action-related categories. In particular, we suggest acquiring more data on mechanically challenging fallback foods and advocate the use of other food mechanical properties such as abrasiveness. The development of new action-related dental metrics is also crucial for primate dental studies. © 2017 Wiley Periodicals, Inc.

Structure of the stigma and style of Callaeum psilophyllum (Malpighiaceae) and its relation with potential pollinators.

PubMed

Aliscioni, Sandra Silvina; Gotelli, Marina; Torretta, Juan Pablo

2018-03-29

The family Malpighiaceae, particularly in the Neotropic, shows a similar floral morphology. Although floral attraction and rewards to pollinators are alike, stigmas and styles show more diversity. The stigmas were described covered with a thin and impermeable cuticle that needs to be ruptured by the mechanical action of the pollinators. However, this characteristic was only mentioned for a few species and the anatomy and ultrastructure of the stigmas were not explored. In this work, we analyze the morphology, anatomy, and ultrastructure of the stigma and style of Callaeum psilophyllum. Moreover, we identify the potential pollinators in order to evaluate how the disposition of the stigmas is related with their size and its role in the exposure of the receptive stigmatic surface. Our observations indicate that Centris flavifrons, C. fuscata, C. tarsata, and C. trigonoides are probably efficient pollinators of C. psilophyllum. The three stigmas are covered by a cuticle that remained intact in bagged flowers. The flowers exposed to visitors show the cuticle broken, more secretion in the intercellular spaces between sub-stigmatic cells and abundant electron-dense components inside vacuoles in stigmatic papillae. This indicates that the stigmas prepares in similar ways to receive pollen grains, but the pollinator action is required to break the cuticle, and once pollen tubes start growing, stigmatic and sub-stigmatic cells release more secretion by a granulocrine process.

Sodium Channel β2 Subunits Prevent Action Potential Propagation Failures at Axonal Branch Points.

PubMed

Cho, In Ha; Panzera, Lauren C; Chin, Morven; Hoppa, Michael B

2017-09-27

Neurotransmitter release depends on voltage-gated Na + channels (Na v s) to propagate an action potential (AP) successfully from the axon hillock to a synaptic terminal. Unmyelinated sections of axon are very diverse structures encompassing branch points and numerous presynaptic terminals with undefined molecular partners of Na + channels. Using optical recordings of Ca 2+ and membrane voltage, we demonstrate here that Na + channel β2 subunits (Na v β2s) are required to prevent AP propagation failures across the axonal arborization of cultured rat hippocampal neurons (mixed male and female). When Na v β2 expression was reduced, we identified two specific phenotypes: (1) membrane excitability and AP-evoked Ca 2+ entry were impaired at synapses and (2) AP propagation was severely compromised with >40% of axonal branches no longer responding to AP-stimulation. We went on to show that a great deal of electrical signaling heterogeneity exists in AP waveforms across the axonal arborization independent of axon morphology. Therefore, Na v β2 is a critical regulator of axonal excitability and synaptic function in unmyelinated axons. SIGNIFICANCE STATEMENT Voltage-gated Ca 2+ channels are fulcrums of neurotransmission that convert electrical inputs into chemical outputs in the form of vesicle fusion at synaptic terminals. However, the role of the electrical signal, the presynaptic action potential (AP), in modulating synaptic transmission is less clear. What is the fidelity of a propagating AP waveform in the axon and what molecules shape it throughout the axonal arborization? Our work identifies several new features of AP propagation in unmyelinated axons: (1) branches of a single axonal arborization have variable AP waveforms independent of morphology, (2) Na + channel β2 subunits modulate AP-evoked Ca 2+ -influx, and (3) β2 subunits maintain successful AP propagation across the axonal arbor. These findings are relevant to understanding the flow of excitation in the brain. Copyright © 2017 the authors 0270-6474/17/379519-15$15.00/0.

Beyond the morphology of the glucose curve following an oral glucose tolerance test in obese youth.

PubMed

Nolfe, Giuseppe; Spreghini, Maria Rita; Sforza, Rita Wietrzycowska; Morino, Giuseppe; Manco, Melania

2012-01-01

To describe the morphology of glucose curve during the oral glucose tolerance test (OGTT) and any association with glucose tolerance, insulin action and secretion in obese youth. Cross-sectional. OGTT data of 553 patients were analysed. Subjects were divided in groups based on the morphology (i.e. monophasic, biphasic, triphasic and upward monotonous) of glucose curve. Insulin action was estimated by the homeostasis model assessment of insulin resistance, the insulin sensitivity, the muscle insulin sensitivity and the hepatic insulin resistance indexes (HIRI), and the oral glucose insulin sensitivity (OGIS). Insulin secretion was estimated by the insulinogenic index (IGI). Disposition index, including the insulin secretion-sensitivity index-2, and areas under glucose (AUC(G)) and insulin (AUC(I)) curves were computed. In patients with normal glucose tolerance (n=522), prevalent morphology of the glucose curve was monophasic (n=285, 54%). Monophasic morphology was associated with the highest concentration of 1 h plasma glucose (P<0.0001) and AUC(G) (P<0.0001); biphasic morphology with better insulin sensitivity as estimated by OGIS (P<0.03) and lower AUC(I) (P<0.0001); triphasic morphology with the highest values of HIRI (P<0.02) and IGI (P<0.007). By combining morphologies of glucose and insulin curves or time of the glucose peak, a deeper characterisation of different phenotypes of glucose metabolism emerged. Morphologies of the glucose curve seem reflecting different metabolic phenotypes of insulin action and secretion, particularly when combined with morphologies of insulin curve or time of glucose peak. Such findings may deserve validation in cohort study, in which glucose metabolism would be estimated by using gold standard techniques.

A Fossilized Energy Distribution of Lightning.

PubMed

Pasek, Matthew A; Hurst, Marc

2016-07-28

When lightning strikes soil, it may generate a cylindrical tube of glass known as a fulgurite. The morphology of a fulgurite is ultimately a consequence of the energy of the lightning strike that formed it, and hence fulgurites may be useful in elucidating the energy distribution frequency of cloud-to-ground lightning. Fulgurites from sand mines in Polk County, Florida, USA were collected and analyzed to determine morphologic properties. Here we show that the energy per unit length of lightning strikes within quartz sand has a geometric mean of ~1.0 MJ/m, and that the distribution is lognormal with respect to energy per length and frequency. Energy per length is determined from fulgurites as a function of diameter, and frequency is determined both by cumulative number and by cumulative length. This distribution parallels those determined for a number of lightning parameters measured in actual atmospheric discharge events, such as charge transferred, voltage, and action integral. This methodology suggests a potential useful pathway for elucidating lightning energy and damage potential of strikes.

A Fossilized Energy Distribution of Lightning

PubMed Central

Pasek, Matthew A.; Hurst, Marc

2016-01-01

When lightning strikes soil, it may generate a cylindrical tube of glass known as a fulgurite. The morphology of a fulgurite is ultimately a consequence of the energy of the lightning strike that formed it, and hence fulgurites may be useful in elucidating the energy distribution frequency of cloud-to-ground lightning. Fulgurites from sand mines in Polk County, Florida, USA were collected and analyzed to determine morphologic properties. Here we show that the energy per unit length of lightning strikes within quartz sand has a geometric mean of ~1.0 MJ/m, and that the distribution is lognormal with respect to energy per length and frequency. Energy per length is determined from fulgurites as a function of diameter, and frequency is determined both by cumulative number and by cumulative length. This distribution parallels those determined for a number of lightning parameters measured in actual atmospheric discharge events, such as charge transferred, voltage, and action integral. This methodology suggests a potential useful pathway for elucidating lightning energy and damage potential of strikes. PMID:27466230

Natural hybridization and genetic and morphological variation between two epiphytic bromeliads

PubMed Central

Neri, Jordana; Wendt, Tânia

2018-01-01

Abstract Reproductive isolation is of fundamental importance for maintaining species boundaries in sympatry. Here, we examine the genetic and morphological differences between two closely related bromeliad species: Vriesea simplex and Vriesea scalaris. Furthermore, we examined the occurrence of natural hybridization and discuss the action of reproductive isolation barriers. Nuclear genomic admixture suggests hybridization in sympatric populations, although interspecific gene flow is low among species in all sympatric zones (Nem < 0.5). Thus, morphological and genetic divergence (10.99 %) between species can be maintained despite ongoing natural hybridization. Cross-evaluation of our genetic and morphological data suggests that species integrity is maintained by the simultaneous action of multiple barriers, such as divergent reproductive systems among species, differences in floral traits and low hybrid seed viability. PMID:29308124

Hepatoprotective Effect of Houttuynia cordata Thunb Extract against Carbon Tetrachloride-induced Hepatic Damage in Mice

PubMed Central

Kang, H.; Koppula, S.

2014-01-01

Houttuynia cordata Thunb (Saururaceae) is a traditional medicinal herb used to treat several disease symptoms. The present study was focused on the hepatoprotective effects of H. cordata ethyl acetate extract in experimental mice. Further the antioxidant potential of the extract was also evaluated to substantiate its hepatoprotective properties. Carbon tetrachloride-induced hepatic damage in mice was used to measure the serum biochemical parameters. Morphological changes in hepatocyte architecture were studied by haematoxylin and eosin staining. In vitro alkyl and hydroxyl free radical scavenging assays were performed to evaluate the antioxidant effect. Administration of H. cordata extract significantly reduced the elevated serum levels and regulated the altered levels of serum cholesterol in carbon tetrachloride-treated mice (P<0.05). The morphological changes in hepatocyte architecture were also reversed by H. cordata treatment. Further, the extract showed significant antioxidant actions by scavenging the alkyl and hydroxyl free radicals. The concentration of the extract necessary for 50% scavenging of alkyl and hydroxyl radicals was 15.5 and 410 μg/ml, respectively. H. cordata extract exhibited significant hepatoprotective property in carbon tetrachloride-induced hepatotoxicity in mice. The strong antioxidant activities possessed by the extract might be responsible for such actions. PMID:25284923

Hepatoprotective Effect of Houttuynia cordata Thunb Extract against Carbon Tetrachloride-induced Hepatic Damage in Mice.

PubMed

Kang, H; Koppula, S

2014-07-01

Houttuynia cordata Thunb (Saururaceae) is a traditional medicinal herb used to treat several disease symptoms. The present study was focused on the hepatoprotective effects of H. cordata ethyl acetate extract in experimental mice. Further the antioxidant potential of the extract was also evaluated to substantiate its hepatoprotective properties. Carbon tetrachloride-induced hepatic damage in mice was used to measure the serum biochemical parameters. Morphological changes in hepatocyte architecture were studied by haematoxylin and eosin staining. In vitro alkyl and hydroxyl free radical scavenging assays were performed to evaluate the antioxidant effect. Administration of H. cordata extract significantly reduced the elevated serum levels and regulated the altered levels of serum cholesterol in carbon tetrachloride-treated mice (P<0.05). The morphological changes in hepatocyte architecture were also reversed by H. cordata treatment. Further, the extract showed significant antioxidant actions by scavenging the alkyl and hydroxyl free radicals. The concentration of the extract necessary for 50% scavenging of alkyl and hydroxyl radicals was 15.5 and 410 μg/ml, respectively. H. cordata extract exhibited significant hepatoprotective property in carbon tetrachloride-induced hepatotoxicity in mice. The strong antioxidant activities possessed by the extract might be responsible for such actions.

Directed fusion of cardiac spheroids into larger heterocellular microtissues enables investigation of cardiac action potential propagation via cardiac fibroblasts

PubMed Central

Markes, Alexander R.; Okundaye, Amenawon O.; Qu, Zhilin; Mende, Ulrike; Choi, Bum-Rak

2018-01-01

Multicellular spheroids generated through cellular self-assembly provide cytoarchitectural complexities of native tissue including three-dimensionality, extensive cell-cell contacts, and appropriate cell-extracellular matrix interactions. They are increasingly suggested as building blocks for larger engineered tissues to achieve shapes, organization, heterogeneity, and other biomimetic complexities. Application of these tissue culture platforms is of particular importance in cardiac research as the myocardium is comprised of distinct but intermingled cell types. Here, we generated scaffold-free 3D cardiac microtissue spheroids comprised of cardiac myocytes (CMs) and/or cardiac fibroblasts (CFs) and used them as building blocks to form larger microtissues with different spatial distributions of CMs and CFs. Characterization of fusing homotypic and heterotypic spheroid pairs revealed an important influence of CFs on fusion kinetics, but most strikingly showed rapid fusion kinetics between heterotypic pairs consisting of one CF and one CM spheroid, indicating that CMs and CFs self-sort in vitro into the intermixed morphology found in the healthy myocardium. We then examined electrophysiological integration of fused homotypic and heterotypic microtissues by mapping action potential propagation. Heterocellular elongated microtissues which recapitulate the disproportionate CF spatial distribution seen in the infarcted myocardium showed that action potentials propagate through CF volumes albeit with significant delay. Complementary computational modeling revealed an important role of CF sodium currents and the spatial distribution of the CM-CF boundary in action potential conduction through CF volumes. Taken together, this study provides useful insights for the development of complex, heterocellular engineered 3D tissue constructs and their engraftment via tissue fusion and has implications for arrhythmogenesis in cardiac disease and repair. PMID:29715271

Fruits for Prevention and Treatment of Cardiovascular Diseases

PubMed Central

Zhao, Cai-Ning; Meng, Xiao; Li, Ya; Li, Sha; Liu, Qing; Tang, Guo-Yi; Li, Hua-Bin

2017-01-01

Cardiovascular diseases (CVDs) are leading global health problems. Accumulating epidemiological studies have indicated that consuming fruits was inversely related to the risk of CVDs. Moreover, substantial experimental studies have supported the protective role of fruits against CVDs, and several fruits (grape, blueberry, pomegranate, apple, hawthorn, and avocado) have been widely studied and have shown potent cardiovascular protective action. Fruits can prevent CVDs or facilitate the restoration of morphology and functions of heart and vessels after injury. The involved mechanisms included protecting vascular endothelial function, regulating lipids metabolism, modulating blood pressure, inhibiting platelets function, alleviating ischemia/reperfusion injury, suppressing thrombosis, reducing oxidative stress, and attenuating inflammation. The present review summarizes recent discoveries about the effects of fruits on CVDs and discusses potential mechanisms of actions based on evidence from epidemiological, experimental, and clinical studies. PMID:28608832

An infrared optical pacing system for screening cardiac electrophysiology in human cardiomyocytes.

PubMed

McPheeters, Matthew T; Wang, Yves T; Werdich, Andreas A; Jenkins, Michael W; Laurita, Kenneth R

2017-01-01

Human cardiac myocytes derived from pluripotent stem cells (hCM) have invigorated interest in genetic disease mechanisms and cardiac safety testing; however, the technology to fully assess electrophysiological function in an assay that is amenable to high throughput screening has lagged. We describe a fully contactless system using optical pacing with an infrared (IR) laser and multi-site high fidelity fluorescence imaging to assess multiple electrophysiological parameters from hCM monolayers in a standard 96-well plate. Simultaneous multi-site action potentials (FluoVolt) or Ca2+ transients (Fluo4-AM) were measured, from which high resolution maps of conduction velocity and action potential duration (APD) were obtained in a single well. Energy thresholds for optical pacing were determined for cell plating density, laser spot size, pulse width, and wavelength and found to be within ranges reported previously for reliable pacing. Action potentials measured using FluoVolt and a microelectrode exhibited the same morphology and rate of depolarization. Importantly, we show that this can be achieved accurately with minimal damage to hCM due to optical pacing or fluorescence excitation. Finally, using this assay we demonstrate that hCM exhibit reproducible changes in repolarization and impulse conduction velocity for Flecainide and Quinidine, two well described reference compounds. In conclusion, we demonstrate a high fidelity electrophysiological screening assay that incorporates optical pacing with IR light to control beating rate of hCM monolayers.

Green-fuel-mediated synthesis of self-assembled NiO nano-sticks for dual applications—photocatalytic activity on Rose Bengal dye and antimicrobial action on bacterial strains

NASA Astrophysics Data System (ADS)

Iyyappa Rajan, P.; Vijaya, J. Judith; Jesudoss, S. K.; Kaviyarasu, K.; Kennedy, L. John; Jothiramalingam, R.; Al-Lohedan, Hamad A.; Vaali-Mohammed, Mansoor-Ali

2017-08-01

With aim of promoting the employability of green fuels in the synthesis of nano-scaled materials with new kinds of morphologies for multiple applications, successful synthesis of self-assembled NiO nano-sticks was achieved through a 100% green-fuel-mediated hot-plate combustion reaction. The synthesized NiO nano-sticks show excellent photocatalytic activity on Rose Bengal dye and superior antibacterial potential towards both Gram-positive and Gram-negative bacteria.

Cytotoxic effect of artocarpin on T47D cells.

PubMed

Arung, Enos Tangke; Wicaksono, Britanto Dani; Handoko, Yohana Ayupriyanti; Kusuma, Irawan Wijaya; Shimizu, Kuniyoshi; Yulia, Dina; Sandra, Ferry

2010-10-01

In our screening projects for anticancer agents from natural resources, artocarpin [6-(3-methyl-1-butenyl)-5,2',4'-trihydroxy-3-isoprenyl-7-methoxyflavone] isolated from wood of jack fruit (Artocarpus heterophyllus) showed potent cytotoxic activity on human T47D breast cancer cells. The mode of action of artocarpin was evaluated by its effect on cell viability, nuclear morphology, cell cycle progression, expression of protein markers for apoptosis, and mitochondrial membrane potential (Delta psi m). These results showed that artocarpin caused a reduction of cell viability in a concentration-dependent manner and an alteration of cell and nuclear morphology. Moreover, the percentage of the sub-G1 phase formation was elevated dose-dependently. Artocarpin induced activation of caspase 8 and 10 as indicated by stronger signal intensity of cleaved-caspase 8 and weaker signal intensity of caspase 10 markers detected after artocarpin treatment. In addition, we also noticed the activation of caspase 3 by artocarpin. There were negligible changes in mitochondrial membrane potential (Delta psi m) due to artocarpin treatment. All together, these data indicated that artocarpin induced apoptosis in T47D cells possibly via an extrinsic pathway.

Morphological variation in salamanders and their potential response to climate change.

PubMed

Ficetola, Gentile Francesco; Colleoni, Emiliano; Renaud, Julien; Scali, Stefano; Padoa-Schioppa, Emilio; Thuiller, Wilfried

2016-06-01

Despite the recognition that some species might quickly adapt to new conditions under climate change, demonstrating and predicting such a fundamental response is challenging. Morphological variations in response to climate may be caused by evolutionary changes or phenotypic plasticity, or both, but teasing apart these processes is difficult. Here, we built on the number of thoracic vertebrae (NTV) in ectothermic vertebrates, a known genetically based feature, to establish a link with body size and evaluate how climate change might affect the future morphological response of this group of species. First, we show that in old-world salamanders, NTV variation is strongly related to changes in body size. Secondly, using 22 salamander species as a case study, we found support for relationships between the spatial variation in selected bioclimatic variables and NTV for most of species. For 44% of species, precipitation and aridity were the predominant drivers of geographical variation of the NTV. Temperature features were dominant for 31% of species, while for 19% temperature and precipitation played a comparable role. This two-step analysis demonstrates that ectothermic vertebrates may evolve in response to climate change by modifying the number of thoracic vertebrae. These findings allow to develop scenarios for potential morphological evolution under future climate change and to identify areas and species in which the most marked evolutionary responses are expected. Resistance to climate change estimated from species distribution models was positively related to present-day species morphological response, suggesting that the ability of morphological evolution may play a role for species' persistence under climate change. The possibility that present-day capacity for local adaptation might help the resistance response to climate change can be integrated into analyses of the impact of global changes and should also be considered when planning management actions favouring species persistence. © 2016 John Wiley & Sons Ltd.

High resolution multibeam and hydrodynamic datasets of tidal channels and inlets of the Venice Lagoon

NASA Astrophysics Data System (ADS)

Madricardo, Fantina; Foglini, Federica; Kruss, Aleksandra; Ferrarin, Christian; Pizzeghello, Nicola Marco; Murri, Chiara; Rossi, Monica; Bajo, Marco; Bellafiore, Debora; Campiani, Elisabetta; Fogarin, Stefano; Grande, Valentina; Janowski, Lukasz; Keppel, Erica; Leidi, Elisa; Lorenzetti, Giuliano; Maicu, Francesco; Maselli, Vittorio; Mercorella, Alessandra; Montereale Gavazzi, Giacomo; Minuzzo, Tiziano; Pellegrini, Claudio; Petrizzo, Antonio; Prampolini, Mariacristina; Remia, Alessandro; Rizzetto, Federica; Rovere, Marzia; Sarretta, Alessandro; Sigovini, Marco; Sinapi, Luigi; Umgiesser, Georg; Trincardi, Fabio

2017-09-01

Tidal channels are crucial for the functioning of wetlands, though their morphological properties, which are relevant for seafloor habitats and flow, have been understudied so far. Here, we release a dataset composed of Digital Terrain Models (DTMs) extracted from a total of 2,500 linear kilometres of high-resolution multibeam echosounder (MBES) data collected in 2013 covering the entire network of tidal channels and inlets of the Venice Lagoon, Italy. The dataset comprises also the backscatter (BS) data, which reflect the acoustic properties of the seafloor, and the tidal current fields simulated by means of a high-resolution three-dimensional unstructured hydrodynamic model. The DTMs and the current fields help define how morphological and benthic properties of tidal channels are affected by the action of currents. These data are of potential broad interest not only to geomorphologists, oceanographers and ecologists studying the morphology, hydrodynamics, sediment transport and benthic habitats of tidal environments, but also to coastal engineers and stakeholders for cost-effective monitoring and sustainable management of this peculiar shallow coastal system.

High resolution multibeam and hydrodynamic datasets of tidal channels and inlets of the Venice Lagoon

PubMed Central

Madricardo, Fantina; Foglini, Federica; Kruss, Aleksandra; Ferrarin, Christian; Pizzeghello, Nicola Marco; Murri, Chiara; Rossi, Monica; Bajo, Marco; Bellafiore, Debora; Campiani, Elisabetta; Fogarin, Stefano; Grande, Valentina; Janowski, Lukasz; Keppel, Erica; Leidi, Elisa; Lorenzetti, Giuliano; Maicu, Francesco; Maselli, Vittorio; Mercorella, Alessandra; Montereale Gavazzi, Giacomo; Minuzzo, Tiziano; Pellegrini, Claudio; Petrizzo, Antonio; Prampolini, Mariacristina; Remia, Alessandro; Rizzetto, Federica; Rovere, Marzia; Sarretta, Alessandro; Sigovini, Marco; Sinapi, Luigi; Umgiesser, Georg; Trincardi, Fabio

2017-01-01

Tidal channels are crucial for the functioning of wetlands, though their morphological properties, which are relevant for seafloor habitats and flow, have been understudied so far. Here, we release a dataset composed of Digital Terrain Models (DTMs) extracted from a total of 2,500 linear kilometres of high-resolution multibeam echosounder (MBES) data collected in 2013 covering the entire network of tidal channels and inlets of the Venice Lagoon, Italy. The dataset comprises also the backscatter (BS) data, which reflect the acoustic properties of the seafloor, and the tidal current fields simulated by means of a high-resolution three-dimensional unstructured hydrodynamic model. The DTMs and the current fields help define how morphological and benthic properties of tidal channels are affected by the action of currents. These data are of potential broad interest not only to geomorphologists, oceanographers and ecologists studying the morphology, hydrodynamics, sediment transport and benthic habitats of tidal environments, but also to coastal engineers and stakeholders for cost-effective monitoring and sustainable management of this peculiar shallow coastal system. PMID:28872636

High resolution multibeam and hydrodynamic datasets of tidal channels and inlets of the Venice Lagoon.

PubMed

Madricardo, Fantina; Foglini, Federica; Kruss, Aleksandra; Ferrarin, Christian; Pizzeghello, Nicola Marco; Murri, Chiara; Rossi, Monica; Bajo, Marco; Bellafiore, Debora; Campiani, Elisabetta; Fogarin, Stefano; Grande, Valentina; Janowski, Lukasz; Keppel, Erica; Leidi, Elisa; Lorenzetti, Giuliano; Maicu, Francesco; Maselli, Vittorio; Mercorella, Alessandra; Montereale Gavazzi, Giacomo; Minuzzo, Tiziano; Pellegrini, Claudio; Petrizzo, Antonio; Prampolini, Mariacristina; Remia, Alessandro; Rizzetto, Federica; Rovere, Marzia; Sarretta, Alessandro; Sigovini, Marco; Sinapi, Luigi; Umgiesser, Georg; Trincardi, Fabio

2017-09-05

Tidal channels are crucial for the functioning of wetlands, though their morphological properties, which are relevant for seafloor habitats and flow, have been understudied so far. Here, we release a dataset composed of Digital Terrain Models (DTMs) extracted from a total of 2,500 linear kilometres of high-resolution multibeam echosounder (MBES) data collected in 2013 covering the entire network of tidal channels and inlets of the Venice Lagoon, Italy. The dataset comprises also the backscatter (BS) data, which reflect the acoustic properties of the seafloor, and the tidal current fields simulated by means of a high-resolution three-dimensional unstructured hydrodynamic model. The DTMs and the current fields help define how morphological and benthic properties of tidal channels are affected by the action of currents. These data are of potential broad interest not only to geomorphologists, oceanographers and ecologists studying the morphology, hydrodynamics, sediment transport and benthic habitats of tidal environments, but also to coastal engineers and stakeholders for cost-effective monitoring and sustainable management of this peculiar shallow coastal system.

Contribution of the Axon Initial Segment to Action Potentials Recorded Extracellularly.

PubMed

Teleńczuk, Maria; Brette, Romain; Destexhe, Alain; Teleńczuk, Bartosz

2018-01-01

Action potentials (APs) are electric phenomena that are recorded both intracellularly and extracellularly. APs are usually initiated in the short segment of the axon called the axon initial segment (AIS). It was recently proposed that at the onset of an AP the soma and the AIS form a dipole. We study the extracellular signature [the extracellular AP (EAP)] generated by such a dipole. First, we demonstrate the formation of the dipole and its extracellular signature in detailed morphological models of a reconstructed pyramidal neuron. Then, we study the EAP waveform and its spatial dependence in models with axonal AP initiation and contrast it with the EAP obtained in models with somatic AP initiation. We show that in the models with axonal AP initiation the dipole forms between somatodendritic compartments and the AIS, and not between soma and dendrites as in the classical models. The soma-dendrites dipole is present only in models with somatic AP initiation. Our study has consequences for interpreting extracellular recordings of single-neuron activity and determining electrophysiological neuron types, but also for better understanding the origins of the high-frequency macroscopic extracellular potentials recorded in the brain.

Mathematical modelling of the antibiotic-induced morphological transition of Pseudomonas aeruginosa

PubMed Central

Keen, Emma; Smith, David J.

2018-01-01

Here we formulate a mechanistic mathematical model to describe the growth dynamics of P. aeruginosa in the presence of the β-lactam antibiotic meropenem. The model is mechanistic in the sense that carrying capacity is taken into account through the dynamics of nutrient availability rather than via logistic growth. In accordance with our experimental results we incorporate a sub-population of cells, differing in morphology from the normal bacillary shape of P. aeruginosa bacteria, which we assume have immunity from direct antibiotic action. By fitting this model to experimental data we obtain parameter values that give insight into the growth of a bacterial population that includes different cell morphologies. The analysis of two parameters sets, that produce different long term behaviour, allows us to manipulate the system theoretically in order to explore the advantages of a shape transition that may potentially be a mechanism that allows P. aeruginosa to withstand antibiotic effects. Our results suggest that inhibition of this shape transition may be detrimental to bacterial growth and thus suggest that the transition may be a defensive mechanism implemented by bacterial machinery. In addition to this we provide strong theoretical evidence for the potential therapeutic strategy of using antimicrobial peptides (AMPs) in combination with meropenem. This proposed combination therapy exploits the shape transition as AMPs induce cell lysis by forming pores in the cytoplasmic membrane, which becomes exposed in the spherical cells. PMID:29481562

Morphology of bone particles after harvesting with 4 different devices.

PubMed

Papadimitriou, Dimitrios E V; Schmidt, Erich C; Caton, Jack G; Romanos, Georgios E

2013-04-01

Autogenous bone is routinely used for regeneration of osseous defects around teeth and implants, and different instruments are available for bone harvesting. The purpose of this study was to describe the morphology of bone particles after harvesting with 4 different instruments. Bone particles were harvested from fresh cow ribs with 2 different types of back action chisels, a safescraper and a sonic device. The samples were examined morphologically using light microscopy and scanning electron microscopy. The bone particles after the back action chisel I had an appearance similar to "pencil shavings." With the back action chisel II, they were like thin paper with an "accordion bellows" appearance. After removal with the safescraper, they had an irregular shape (with an irregular surface) resembling "crushed stone." Finally, the appearance of the bone particles obtained with the sonic device was homogenous, condensed and continuous, and had a "seaweed" appearance. Harvesting of bone particles with 4 different devices produce distinctly difference sizes and shapes, which may influence the results of grafting procedures.

Female sexual maturation and reproduction after prepubertal exposure to estrogens and endocrine disrupting chemicals: a review of rodent and human data.

PubMed

Rasier, G; Toppari, J; Parent, A-S; Bourguignon, J-P

2006-07-25

Natural hormones and some synthetic chemicals spread into our surrounding environment share the capacity to interact with hormone action and metabolism. Exposure to such compounds can cause a variety of developmental and reproductive detrimental abnormalities in wildlife species and, potentially, in human. Many experimental and epidemiological data have reported that exposure of the developing fetus or neonate to environmentally relevant concentrations of some among these endocrine disrupters induces morphological, biochemical and/or physiological disorders in brain and reproductive organs, by interfering with the hormone actions. The impact of such exposures on the hypothalamic-pituitary-gonadal axis and subsequent sexual maturation is the subject of the present review. We will highlight epidemiological human studies and the effects of early exposure during gestational, perinatal or postnatal life in female rodents.

A COMPUTATIONAL MODEL OF MOTOR NEURON DEGENERATION

PubMed Central

Le Masson, Gwendal; Przedborski, Serge; Abbott, L.F.

2014-01-01

SUMMARY To explore the link between bioenergetics and motor neuron degeneration, we used a computational model in which detailed morphology and ion conductance are paired with intracellular ATP production and consumption. We found that reduced ATP availability increases the metabolic cost of a single action potential and disrupts K+/Na+ homeostasis, resulting in a chronic depolarization. The magnitude of the ATP shortage at which this ionic instability occurs depends on the morphology and intrinsic conductance characteristic of the neuron. If ATP shortage is confined to the distal part of the axon, the ensuing local ionic instability eventually spreads to the whole neuron and involves fasciculation-like spiking events. A shortage of ATP also causes a rise in intracellular calcium. Our modeling work supports the notion that mitochondrial dysfunction can account for salient features of the paralytic disorder amyotrophic lateral sclerosis, including motor neuron hyperexcitability, fasciculation, and differential vulnerability of motor neuron subpopulations. PMID:25088365

A computational model of motor neuron degeneration.

PubMed

Le Masson, Gwendal; Przedborski, Serge; Abbott, L F

2014-08-20

To explore the link between bioenergetics and motor neuron degeneration, we used a computational model in which detailed morphology and ion conductance are paired with intracellular ATP production and consumption. We found that reduced ATP availability increases the metabolic cost of a single action potential and disrupts K+/Na+ homeostasis, resulting in a chronic depolarization. The magnitude of the ATP shortage at which this ionic instability occurs depends on the morphology and intrinsic conductance characteristic of the neuron. If ATP shortage is confined to the distal part of the axon, the ensuing local ionic instability eventually spreads to the whole neuron and involves fasciculation-like spiking events. A shortage of ATP also causes a rise in intracellular calcium. Our modeling work supports the notion that mitochondrial dysfunction can account for salient features of the paralytic disorder amyotrophic lateral sclerosis, including motor neuron hyperexcitability, fasciculation, and differential vulnerability of motor neuron subpopulations. Copyright © 2014 Elsevier Inc. All rights reserved.

Antimicrobial Activity of Ferulic Acid Against Cronobacter sakazakii and Possible Mechanism of Action.

PubMed

Shi, Chao; Zhang, Xiaorong; Sun, Yi; Yang, Miaochun; Song, Kaikuo; Zheng, Zhiwei; Chen, Yifei; Liu, Xin; Jia, Zhenyu; Dong, Rui; Cui, Lu; Xia, Xiaodong

2016-04-01

Cronobacter sakazakii is an opportunistic pathogen transmitted by food that affects mainly newborns, infants, and immune-compromised adults. In this study, the antibacterial activity of ferulic acid was tested against C. sakazakii strains. Minimum inhibitory concentration of ferulic acid against C. sakazakii strains was determined using the agar dilution method. Changes in intracellular pH, membrane potential and intracellular ATP concentration were measured to elucidate the possible antibacterial mechanism. Moreover, SYTO 9 nucleic acid staining was used to assess the effect of ferulic acid on bacterial membrane integrity. Cell morphology changes were observed under a field emission scanning electron microscope. The minimum inhibitory concentrations of ferulic acid against C. sakazakii strains ranged from 2.5 to 5.0 mg/mL. Addition of ferulic acid exerted an immediate and sustained inhibition of C. sakazakii proliferation. Ferulic acid affected the membrane integrity of C. sakazakii, as evidenced by intracellular ATP concentration decrease. Moreover, reduction of intracellular pH and cell membrane hyperpolarization were detected in C. sakazakii after exposure to ferulic acid. Reduction of green fluorescence indicated the injury of cell membrane. Electronic microscopy confirmed that cell membrane of C. sakazakii was damaged by ferulic acid. Our results demonstrate that ferulic acid has moderate antimicrobial activity against C. sakazakii. It exerts its antimicrobial action partly through causing cell membrane dysfunction and changes in cellular morphology. Considering its antimicrobial properties, together with its well-known nutritional functions, ferulic acid has potential to be developed as a supplement in infant formula or other foods to control C. sakazakii.

Aspects of masticatory form and function in common tree shrews, Tupaia glis.

PubMed

Fish, D R

1983-04-01

Tree shrews have relatively primitive tribosphenic molars that are apparently similar to those of basal eutherians; thus, these animals have been used as a model to describe mastication in early mammals. In this study the gross morphology of the bony skull, joints, dentition, and muscles of mastication are related to potential jaw movements and cuspal relationships. Potential for complex mandibular movements is indicated by a mobile mandibular symphysis, shallow mandibular fossa that is large compared to its resident condyle, and relatively loose temporomandibular joint ligaments. Abrasive tooth wear is noticeable, and is most marked at the first molars and buccal aspects of the upper cheek teeth distal to P2. Muscle morphology is basically similar to that previously described for Tupaia minor and Ptilocercus lowii. However, in T. glis, an intraorbital part of deep temporalis has the potential for inducing lingual translation of its dentary, and the large medial pterygoid has extended its origin anteriorly to the floor of the orbit, which would enhance protrusion. The importance of the tongue and hyoid muscles during mastication is suggested by broadly expanded anterior bellies of digastrics, which may assist mylohyoids in tensing the floor of the mouth during forceful tongue actions, and by preliminary electromyography, which suggests that masticatory muscles alone cannot fully account for jaw movements in this species.

A dataset of images and morphological profiles of 30 000 small-molecule treatments using the Cell Painting assay

PubMed Central

Bray, Mark-Anthony; Gustafsdottir, Sigrun M; Rohban, Mohammad H; Singh, Shantanu; Ljosa, Vebjorn; Sokolnicki, Katherine L; Bittker, Joshua A; Bodycombe, Nicole E; Dančík, Vlado; Hasaka, Thomas P; Hon, Cindy S; Kemp, Melissa M; Li, Kejie; Walpita, Deepika; Wawer, Mathias J; Golub, Todd R; Schreiber, Stuart L; Clemons, Paul A; Shamji, Alykhan F

2017-01-01

Abstract Background Large-scale image sets acquired by automated microscopy of perturbed samples enable a detailed comparison of cell states induced by each perturbation, such as a small molecule from a diverse library. Highly multiplexed measurements of cellular morphology can be extracted from each image and subsequently mined for a number of applications. Findings This microscopy dataset includes 919 265 five-channel fields of view, representing 30 616 tested compounds, available at “The Cell Image Library” (CIL) repository. It also includes data files containing morphological features derived from each cell in each image, both at the single-cell level and population-averaged (i.e., per-well) level; the image analysis workflows that generated the morphological features are also provided. Quality-control metrics are provided as metadata, indicating fields of view that are out-of-focus or containing highly fluorescent material or debris. Lastly, chemical annotations are supplied for the compound treatments applied. Conclusions Because computational algorithms and methods for handling single-cell morphological measurements are not yet routine, the dataset serves as a useful resource for the wider scientific community applying morphological (image-based) profiling. The dataset can be mined for many purposes, including small-molecule library enrichment and chemical mechanism-of-action studies, such as target identification. Integration with genetically perturbed datasets could enable identification of small-molecule mimetics of particular disease- or gene-related phenotypes that could be useful as probes or potential starting points for development of future therapeutics. PMID:28327978

The morphology and adhesion mechanism of Octopus vulgaris suckers.

PubMed

Tramacere, Francesca; Beccai, Lucia; Kuba, Michael; Gozzi, Alessandro; Bifone, Angelo; Mazzolai, Barbara

2013-01-01

The octopus sucker represents a fascinating natural system performing adhesion on different terrains and substrates. Octopuses use suckers to anchor the body to the substrate or to grasp, investigate and manipulate objects, just to mention a few of their functions. Our study focuses on the morphology and adhesion mechanism of suckers in Octopus vulgaris. We use three different techniques (MRI, ultrasonography, and histology) and a 3D reconstruction approach to contribute knowledge on both morphology and functionality of the sucker structure in O. vulgaris. The results of our investigation are two-fold. First, we observe some morphological differences with respect to the octopus species previously studied (i.e., Octopus joubini, Octopus maya, Octopus bimaculoides/bimaculatus and Eledone cirrosa). In particular, in O. vulgaris the acetabular chamber, that is a hollow spherical cavity in other octopuses, shows an ellipsoidal cavity which roof has an important protuberance with surface roughness. Second, based on our findings, we propose a hypothesis on the sucker adhesion mechanism in O. vulgaris. We hypothesize that the process of continuous adhesion is achieved by sealing the orifice between acetabulum and infundibulum portions via the acetabular protuberance. We suggest this to take place while the infundibular part achieves a completely flat shape; and, by sustaining adhesion through preservation of sucker configuration. In vivo ultrasonographic recordings support our proposed adhesion model by showing the sucker in action. Such an underlying physical mechanism offers innovative potential cues for developing bioinspired artificial adhesion systems. Furthermore, we think that it could possibly represent a useful approach in order to investigate any potential difference in the ecology and in the performance of adhesion by different species.

The Morphology and Adhesion Mechanism of Octopus vulgaris Suckers

PubMed Central

Tramacere, Francesca; Beccai, Lucia; Kuba, Michael; Gozzi, Alessandro; Bifone, Angelo; Mazzolai, Barbara

2013-01-01

The octopus sucker represents a fascinating natural system performing adhesion on different terrains and substrates. Octopuses use suckers to anchor the body to the substrate or to grasp, investigate and manipulate objects, just to mention a few of their functions. Our study focuses on the morphology and adhesion mechanism of suckers in Octopus vulgaris. We use three different techniques (MRI, ultrasonography, and histology) and a 3D reconstruction approach to contribute knowledge on both morphology and functionality of the sucker structure in O. vulgaris. The results of our investigation are two-fold. First, we observe some morphological differences with respect to the octopus species previously studied (i.e., Octopus joubini, Octopus maya, Octopus bimaculoides/bimaculatus and Eledone cirrosa). In particular, in O. vulgaris the acetabular chamber, that is a hollow spherical cavity in other octopuses, shows an ellipsoidal cavity which roof has an important protuberance with surface roughness. Second, based on our findings, we propose a hypothesis on the sucker adhesion mechanism in O. vulgaris. We hypothesize that the process of continuous adhesion is achieved by sealing the orifice between acetabulum and infundibulum portions via the acetabular protuberance. We suggest this to take place while the infundibular part achieves a completely flat shape; and, by sustaining adhesion through preservation of sucker configuration. In vivo ultrasonographic recordings support our proposed adhesion model by showing the sucker in action. Such an underlying physical mechanism offers innovative potential cues for developing bioinspired artificial adhesion systems. Furthermore, we think that it could possibly represent a useful approach in order to investigate any potential difference in the ecology and in the performance of adhesion by different species. PMID:23750233

Effect of low-level monochromatic radiations on some morphological and physiological parameters of plants.

PubMed

Siposan, Dan Georgel

2011-01-01

Studying the behavior of living organisms under the action of some physical or chemical factors (corpuscular or electromagnetic radiation, magnetic or electric field, sound waves, salinity, stimulants etc.) is enjoying major interest nowadays.(1,2)) The main goal is to understand the mechanisms of action of these factors on biological tissues, and use this knowledge for applications in biology and medicine. A special place in modern medicine is occupied by the therapeutic applications of laser radiation. In the current study we are attempting to determine whether the therapeutic lasers used in medicine have the potential to produce changes of some morphological and physiological parameters of plants. If these changes actually occur, the next task is to determine whether they are due to laser action on water used for watering by changing its properties, or by the direct action of laser radiation on the plants cells. Matcrials and Mcthods: We used as samples two groups of wheat seeds, planted in cotton. In the first group we only irradiated irrigation water, while in the second group only plants. We used as sources of radiation lasers and LEDs, with wavelengths between 455 nm and 850 nm. Power density was P = 50 mW/cm(2) for all samples, the exposure time ranged between 1s and 80s, and energy density (or fluence) between 0 and 4J/cm(2). We measured modifications of some morphological and physiological parameters (the biomass quantity, germination rate of seeds, number and height of the seedlings etc.) as a function of fluence. When only irrigation water was irradiated, we have found for all wavelength used a strong inhibitory effect on germination (between 30% and 50% for samples grown in the ground and between 13% and 40% for those grown in cotton). Regarding the other parameters determined, a stimulating effect, but less pronounced than if the plant was only irradiated, was noticed. When only plant was irradiated, the effects are altered depending on the wavelength and fluence. Although apparently different, plant and animal cells have some similar characteristics, the differences between them not being essential, involving mainly the quantitative aspect. In these circumstances the study of the monochromatic radiation effects on plants is useful to characterize the action of those radiations on the animal and human tissues. Studies on plants exhibit a series of advantages: they are cheap, easily reproduced and suitable for producing good statistics etc. It can also be verified as to which extent the laws of classic photobiology show modifications when low level lasers are utilized.

Loss of Local Astrocyte Support Disrupts Action Potential Propagation and Glutamate Release Synchrony from Unmyelinated Hippocampal Axon Terminals In Vitro.

PubMed

Sobieski, Courtney; Jiang, Xiaoping; Crawford, Devon C; Mennerick, Steven

2015-08-05

Neuron-astrocyte interactions are critical for proper CNS development and function. Astrocytes secrete factors that are pivotal for synaptic development and function, neuronal metabolism, and neuronal survival. Our understanding of this relationship, however, remains incomplete due to technical hurdles that have prevented the removal of astrocytes from neuronal circuits without changing other important conditions. Here we overcame this obstacle by growing solitary rat hippocampal neurons on microcultures that were comprised of either an astrocyte bed (+astrocyte) or a collagen bed (-astrocyte) within the same culture dish. -Astrocyte autaptic evoked EPSCs, but not IPSCs, displayed an altered temporal profile, which included increased synaptic delay, increased time to peak, and severe glutamate release asynchrony, distinct from previously described quantal asynchrony. Although we observed minimal alteration of the somatically recorded action potential waveform, action potential propagation was altered. We observed a longer latency between somatic initiation and arrival at distal locations, which likely explains asynchronous EPSC peaks, and we observed broadening of the axonal spike, which likely underlies changes to evoked EPSC onset. No apparent changes in axon structure were observed, suggesting altered axonal excitability. In conclusion, we propose that local astrocyte support has an unappreciated role in maintaining glutamate release synchrony by disturbing axonal signal propagation. Certain glial cell types (oligodendrocytes, Schwann cells) facilitate the propagation of neuronal electrical signals, but a role for astrocytes has not been identified despite many other functions of astrocytes in supporting and modulating neuronal signaling. Under identical global conditions, we cultured neurons with or without local astrocyte support. Without local astrocytes, glutamate transmission was desynchronized by an alteration of the waveform and arrival time of axonal action potentials to synaptic terminals. GABA transmission was not disrupted. The disruption did not involve detectable morphological changes to axons of glutamate neurons. Our work identifies a developmental role for astrocytes in the temporal precision of excitatory signals. Copyright © 2015 the authors 0270-6474/15/3511105-13$15.00/0.

Loss of Local Astrocyte Support Disrupts Action Potential Propagation and Glutamate Release Synchrony from Unmyelinated Hippocampal Axon Terminals In Vitro

PubMed Central

Sobieski, Courtney; Jiang, Xiaoping; Crawford, Devon C.

2015-01-01

Neuron–astrocyte interactions are critical for proper CNS development and function. Astrocytes secrete factors that are pivotal for synaptic development and function, neuronal metabolism, and neuronal survival. Our understanding of this relationship, however, remains incomplete due to technical hurdles that have prevented the removal of astrocytes from neuronal circuits without changing other important conditions. Here we overcame this obstacle by growing solitary rat hippocampal neurons on microcultures that were comprised of either an astrocyte bed (+astrocyte) or a collagen bed (−astrocyte) within the same culture dish. −Astrocyte autaptic evoked EPSCs, but not IPSCs, displayed an altered temporal profile, which included increased synaptic delay, increased time to peak, and severe glutamate release asynchrony, distinct from previously described quantal asynchrony. Although we observed minimal alteration of the somatically recorded action potential waveform, action potential propagation was altered. We observed a longer latency between somatic initiation and arrival at distal locations, which likely explains asynchronous EPSC peaks, and we observed broadening of the axonal spike, which likely underlies changes to evoked EPSC onset. No apparent changes in axon structure were observed, suggesting altered axonal excitability. In conclusion, we propose that local astrocyte support has an unappreciated role in maintaining glutamate release synchrony by disturbing axonal signal propagation. SIGNIFICANCE STATEMENT Certain glial cell types (oligodendrocytes, Schwann cells) facilitate the propagation of neuronal electrical signals, but a role for astrocytes has not been identified despite many other functions of astrocytes in supporting and modulating neuronal signaling. Under identical global conditions, we cultured neurons with or without local astrocyte support. Without local astrocytes, glutamate transmission was desynchronized by an alteration of the waveform and arrival time of axonal action potentials to synaptic terminals. GABA transmission was not disrupted. The disruption did not involve detectable morphological changes to axons of glutamate neurons. Our work identifies a developmental role for astrocytes in the temporal precision of excitatory signals. PMID:26245971

Lengthening our perspective: morphological, cellular, and molecular responses to eccentric exercise.

PubMed

Hyldahl, Robert D; Hubal, Monica J

2014-02-01

The response of skeletal muscle to unaccustomed eccentric exercise has been studied widely, yet it is incompletely understood. This review is intended to provide an up-to-date overview of our understanding of how skeletal muscle responds to eccentric actions, with particular emphasis on the underlying molecular and cellular mechanisms of damage and recovery. This review begins by addressing the question of whether eccentric actions result in physical damage to muscle fibers and/or connective tissue. We next review the symptomatic manifestations of eccentric exercise (i.e., indirect damage markers, such as delayed onset muscle soreness), with emphasis on their relatively poorly understood molecular underpinnings. We then highlight factors that potentially modify the muscle damage response following eccentric exercise. Finally, we explore the utility of using eccentric training to improve muscle function in populations of healthy and aging individuals, as well as those living with neuromuscular disorders. Copyright © 2013 Wiley Periodicals, Inc.

NS5806 partially restores action potential duration but fails to ameliorate calcium transient dysfunction in a computational model of canine heart failure.

PubMed

Maleckar, Mary M; Lines, Glenn T; Koivumäki, Jussi T; Cordeiro, Jonathan M; Calloe, Kirstine

2014-11-01

The study investigates how increased Ito, as mediated by the activator NS5806, affects excitation-contraction coupling in chronic heart failure (HF). We hypothesized that restoring spike-and-dome morphology of the action potential (AP) to a healthy phenotype would be insufficient to restore the intracellular Ca(2) (+) transient (CaT), due to HF-induced remodelling of Ca(2+) handling. An existing mathematical model of the canine ventricular myocyte was modified to incorporate recent experimental data from healthy and failing myocytes, resulting in models of both healthy and HF epicardial, midmyocardial, and endocardial cell variants. Affects of NS5806 were also included in HF models through its direct interaction with Kv4.3 and Kv1.4. Single-cell simulations performed in all models (control, HF, and HF + drug) and variants (epi, mid, and endo) assessed AP morphology and underlying ionic processes with a focus on calcium transients (CaT), how these were altered in HF across the ventricular wall, and the subsequent effects of varying compound concentration in HF. Heart failure model variants recapitulated a characteristic increase in AP duration (APD) in the disease. The qualitative effects of application of half-maximal effective concentration (EC50) of NS5806 on APs and CaT are heterogeneous and non-linear. Deepening in the AP notch with drug is a direct effect of the activation of Ito; both Ito and consequent alteration of IK1 kinetics cause decrease in AP plateau potential. Decreased APD50 and APD90 are both due to altered IK1. Analysis revealed that drug effects depend on transmurality. Ca(2+) transient morphology changes-increased amplitude and shorter time to peak-are due to direct increase in ICa,L and indirect larger SR Ca(2+) release subsequent to Ito activation. Downstream effects of a compound acting exclusively on sarcolemmal ion channels are difficult to predict. Remediation of APD to pre-failing state does not ameliorate dysfunction in CaT; however, restoration of notch depth appears to impart modest benefit and a likelihood of therapeutic value in modulating early repolarization. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

Physiological and morphological characterization of organotypic cocultures of the chick forebrain area MNH and its main input area DMA/DMP.

PubMed

Endepols, H; Jungnickel, J; Braun, K

2001-01-01

Cocultures of the learning-relevant forebrain region mediorostral neostriatum and hyperstriatum ventrale (MNH) and its main glutamatergic input area nucleus dorsomedialis anterior thalami/posterior thalami were morphologically and physiologically characterized. Synaptic contacts of thalamic fibers were light- and electron-microscopically detected on MNH neurons by applying the fluorescence tracer DiI-C18(3) into the thalamus part of the coculture. Most thalamic synapses on MNH neurons were symmetric and located on dendritic shafts, but no correlation between Gray-type ultrastructure and dendritic localization was found. Using intracellular current clamp recordings, we found that the electrophysiological properties, such as input resistance, time constant, action potential threshold, amplitude, and duration of MNH neurons, remain stable for over 30 days in vitro. Pharmacological blockade experiments revealed glutamate as the main neurotransmitter of thalamic synapses on MNH neurons, which were also found on inhibitory neurons. High frequency stimulation of thalamic inputs evoked synaptic potentiation in 22% of MNH neurons. The results indicate that DMA/DMP-MNH cocultures, which can be maintained under stable conditions for at least 4 weeks, provide an attractive in vitro model for investigating synaptic plasticity in the avian brain.

Physiological and Morphological Characterization of Organotypic Cocultures of the Chick Forebrain Area MNH and its Main Input Area DMA/DMP

PubMed Central

Endepols, Heike; Jungnickel, Julia; Braun, Katharina

2001-01-01

Cocultures of the learning-relevant forebrain region mediorostrai neostriatum and hyperstriatum ventrale (MNH) and its main glutamatergic input area nucleus dorsomedialis anterior thalami/posterior thalami were morphologically and physiologically characterized. Synaptic contacts of thalamic fibers were lightand electron-microscopically detected on MNH neurons by applying the fluorescence tracer DiI-C18(3) into the thalamus part of the coculture. Most thalamic synapses on MNH neurons were symmetric and located on dendritic shafts, but no correlation between Gray-type ultrastructure and dendritic localization was found. Using intraceilular current clamp recordings, we found that the electrophysiological properties, such as input resistance, time constant, action potential threshold, amplitude, and duration of MNH neurons, remain stable for over 30 days in vitro. Pharmacological blockade experiments revealed glutamate as the main neurotransmitter of thalamic synapses on MNH neurons, which were also found on inhibitory neurons. High frequency stimulation of thalamic inputs evoked synaptic potentiation in 22% of MNH neurons. The results indicate that DMA/DMP-MNH cocultures, which can be maintained under stable conditions for at least 4 weeks, provide an attractive in vitro model for investigating synaptic plasticity in the avian brain. PMID:12018771

Novel Activity of a Synthetic Decapeptide Against Toxoplasma gondii Tachyzoites.

PubMed

Giovati, Laura; Santinoli, Claudia; Mangia, Carlo; Vismarra, Alice; Belletti, Silvana; D'Adda, Tiziana; Fumarola, Claudia; Ciociola, Tecla; Bacci, Cristina; Magliani, Walter; Polonelli, Luciano; Conti, Stefania; Kramer, Laura H

2018-01-01

The killer peptide KP is a synthetic decapeptide derived from the sequence of the variable region of a recombinant yeast killer toxin-like microbicidal single-chain antibody. KP proved to exert significant activities against diverse microbial and viral pathogens through different mechanisms of action, but little is known of its effect on apicomplexan protozoa. The aim of the present study was to evaluate the in vitro activity of KP against Toxoplasma gondii , a globally widespread protozoan parasite of great medical interest. The effect of KP treatment and its potential mechanism of action on T. gondii were evaluated by various methods, including light microscopy, quantitative PCR, flow cytometry, confocal microscopy, and transmission electron microscopy. In the presence of KP, the number of T. gondii tachyzoites able to invade Vero cells and the parasite intracellular proliferation were significantly reduced. Morphological observation and analysis of apoptotic markers suggested that KP is able to trigger an apoptosis-like cell death in T. gondii . Overall, our results indicate that KP could be a promising candidate for the development of new anti- Toxoplasma drugs with a novel mechanism of action.

Antifungal activity of the ethanolic extracts of Punica granatum L. and evaluation of the morphological and structural modifications of its compounds upon the cells of Candida spp

PubMed Central

Anibal, Paula Cristina; Peixoto, Iza Teixeira Alves; Foglio, Mary Ann; Höfling, José Francisco

2013-01-01

Ethanolic crude extracts prepared from the arils and seeds, pericarp, peels and from the whole fruit of Punica granatum, known as pomegranate, had their antifungal activity tested against Candida spp. The ethanolic crude extracts were analyzed by Mass Spectrometry and yielded many compounds such as punicalagin and galladydilacton. The extracts from the pericarp and peel showed activity against Candida spp., with MICs of 125 μg/mL. The effect of pericarp and peel extracts upon the morphological and structure of C. albicans and C. krusei were examined by scanning and transmission electron microscopy, with the visualization of an irregular membrane and hyphae, formation of vacuoles and thickening of the cell wall. The data obtained revealed potential antimicrobial activity against yeasts cells of the Candida genus, and the bioactive compounds could be responsible for changes in cell morphology and structure. The data obtained open new perspectives for future research in continuation to this study, where information such as determination of the site of action of the compounds could contribute to an alternative therapy against these organisms. PMID:24516425

Evaluation of the morphological effects of TDT 067 (terbinafine in Transfersome) and conventional terbinafine on dermatophyte hyphae in vitro and in vivo.

PubMed

Ghannoum, M; Isham, N; Henry, W; Kroon, H-A; Yurdakul, S

2012-05-01

TDT 067 is a novel, carrier-based dosage form of terbinafine in Transfersome (1.5%) formulated for topical delivery of terbinafine to the nail, nail bed, and surrounding tissue. We examined the effects of TDT 067 and conventional terbinafine on the morphology of dermatophytes. Trichophyton rubrum hyphae were exposed to TDT 067 or terbinafine (15 mg/ml) and examined under white light, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). Subungual debris from patients treated with TDT 067 in a clinical trial was also examined. Exposure of T. rubrum hyphae to TDT 067 led to rapid and extensive ultrastructural changes. Hyphal distortion was evident as early as 4 h after exposure to TDT 067. After 24 h, there was complete disruption of hyphal structure with few intact hyphae remaining. Exposure to terbinafine resulted in morphological alterations similar to those seen with TDT 067; however, the effects of TDT 067 were more extensive, whereas a portion of hyphae remained intact after 24 h of exposure to terbinafine. Lipid droplets were observed under TEM following 30 min of exposure to TDT 067, which after 24 h had filled the intracellular space. These effects were confirmed in vivo in subungual debris from patients with onychomycosis who received topical treatment with TDT 067. The Transfersome in TDT 067 may potentiate the action of terbinafine by delivering terbinafine more effectively to its site of action inside the fungus. Our in vivo data confirm that TDT 067 can enter fungus in the nail bed of patients with onychomycosis and exert its antifungal effects.

Evaluation of the Morphological Effects of TDT 067 (Terbinafine in Transfersome) and Conventional Terbinafine on Dermatophyte Hyphae In Vitro and In Vivo

PubMed Central

Isham, N.; Henry, W.; Kroon, H.-A.; Yurdakul, S.

2012-01-01

TDT 067 is a novel, carrier-based dosage form of terbinafine in Transfersome (1.5%) formulated for topical delivery of terbinafine to the nail, nail bed, and surrounding tissue. We examined the effects of TDT 067 and conventional terbinafine on the morphology of dermatophytes. Trichophyton rubrum hyphae were exposed to TDT 067 or terbinafine (15 mg/ml) and examined under white light, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). Subungual debris from patients treated with TDT 067 in a clinical trial was also examined. Exposure of T. rubrum hyphae to TDT 067 led to rapid and extensive ultrastructural changes. Hyphal distortion was evident as early as 4 h after exposure to TDT 067. After 24 h, there was complete disruption of hyphal structure with few intact hyphae remaining. Exposure to terbinafine resulted in morphological alterations similar to those seen with TDT 067; however, the effects of TDT 067 were more extensive, whereas a portion of hyphae remained intact after 24 h of exposure to terbinafine. Lipid droplets were observed under TEM following 30 min of exposure to TDT 067, which after 24 h had filled the intracellular space. These effects were confirmed in vivo in subungual debris from patients with onychomycosis who received topical treatment with TDT 067. The Transfersome in TDT 067 may potentiate the action of terbinafine by delivering terbinafine more effectively to its site of action inside the fungus. Our in vivo data confirm that TDT 067 can enter fungus in the nail bed of patients with onychomycosis and exert its antifungal effects. PMID:22354309

Effect of 1.8 GHz radiofrequency electromagnetic radiation on novel object associative recognition memory in mice

PubMed Central

Wang, Kai; Lu, Jun-Mei; Xing, Zhen-He; Zhao, Qian-Ru; Hu, Lin-Qi; Xue, Lei; Zhang, Jie; Mei, Yan-Ai

2017-01-01

Mounting evidence suggests that exposure to radiofrequency electromagnetic radiation (RF-EMR) can influence learning and memory in rodents. In this study, we examined the effects of single exposure to 1.8 GHz RF-EMR for 30 min on subsequent recognition memory in mice, using the novel object recognition task (NORT). RF-EMR exposure at an intensity of >2.2 W/kg specific absorption rate (SAR) power density induced a significant density-dependent increase in NORT index with no corresponding changes in spontaneous locomotor activity. RF-EMR exposure increased dendritic-spine density and length in hippocampal and prefrontal cortical neurons, as shown by Golgi staining. Whole-cell recordings in acute hippocampal and medial prefrontal cortical slices showed that RF-EMR exposure significantly altered the resting membrane potential and action potential frequency, and reduced the action potential half-width, threshold, and onset delay in pyramidal neurons. These results demonstrate that exposure to 1.8 GHz RF-EMR for 30 min can significantly increase recognition memory in mice, and can change dendritic-spine morphology and neuronal excitability in the hippocampus and prefrontal cortex. The SAR in this study (3.3 W/kg) was outside the range encountered in normal daily life, and its relevance as a potential therapeutic approach for disorders associated with recognition memory deficits remains to be clarified. PMID:28303965

Developmental axon stretch stimulates neuron growth while maintaining normal electrical activity, intracellular calcium flux, and somatic morphology

PubMed Central

Loverde, Joseph R.; Pfister, Bryan J.

2015-01-01

Elongation of nerve fibers intuitively occurs throughout mammalian development, and is synchronized with expansion of the growing body. While most tissue systems enlarge through mitosis and differentiation, elongation of nerve fibers is remarkably unique. The emerging paradigm suggests that axons undergo stretch as contiguous tissues enlarge between the proximal and distal segments of spanning nerve fibers. While stretch is distinct from growth, tension is a known stimulus which regulates the growth of axons. Here, we hypothesized that the axon stretch-growth process may be a natural form of injury, whereby regenerative processes fortify elongating axons in order to prevent disconnection. Harnessing the live imaging capability of our axon stretch-growth bioreactors, we assessed neurons both during and following stretch for biomarkers associated with injury. Utilizing whole-cell patch clamp recording, we found no evidence of changes in spontaneous action potential activity or degradation of elicited action potentials during real-time axon stretch at strains of up to 18% applied over 5 min. Unlike traumatic axonal injury, functional calcium imaging of the soma revealed no shifts in free intracellular calcium during axon stretch. Finally, the cross-sectional areas of nuclei and cytoplasms were normal, with no evidence of chromatolysis following week-long stretch-growth limited to the lower of 25% strain or 3 mm total daily stretch. The neuronal growth cascade coupled to stretch was concluded to be independent of the changes in membrane potential, action potential generation, or calcium flux associated with traumatic injury. While axon stretch-growth is likely to share overlap with regenerative processes, we conclude that developmental stretch is a distinct stimulus from traumatic axon injury. PMID:26379492

Evidence for bisphenol A-induced female infertility - Review (2007–2016)

PubMed Central

Ziv-Gal, Ayelet; Flaws, Jodi A.

2016-01-01

We summarized the scientific literature published from 2007 to 2016 on the potential effects of bisphenol A (BPA) on female fertility. We focused on overall fertility outcomes (e.g., ability to become pregnant, number of offspring), organs that are important for female reproduction (i.e., oviduct, uterus, ovary, hypothalamus, and pituitary), and reproductive related processes (i.e., estrous cyclicity, implantation, and hormonal secretion). The reviewed literature indicates that BPA may be associated with infertility in women. Potential explanations for this association can be generated from experimental studies. Specifically, BPA may alter overall female reproductive capacity by affecting the morphology and function of the oviduct, uterus, ovary, and hypothalamus-pituitary-ovarian axis in animal models. Additionally, BPA may disrupt estrous cyclicity and implantation. Nevertheless, further studies are needed to better understand the exact mechanisms of action and to detect potential reproductive toxicity at earlier stages. PMID:27417731

Deciphering the mode of action of a mutant Allium sativum Leaf Agglutinin (mASAL), a potent antifungal protein on Rhizoctonia solani.

PubMed

Ghosh, Prithwi; Roy, Amit; Hess, Daniel; Ghosh, Anupama; Das, Sampa

2015-10-26

Mutant Allium sativum leaf agglutinin (mASAL) is a potent, biosafe, antifungal protein that exhibits fungicidal activity against different phytopathogenic fungi, including Rhizoctonia solani. The effect of mASAL on the morphology of R.solani was monitored primarily by scanning electron and light microscopic techniques. Besides different fluorescent probes were used for monitoring various intracellular changes associated with mASAL treatment like change in mitochondrial membrane potential (MMP), intracellular accumulation of reactive oxygen species (ROS) and induction of programmed cell death (PCD). In addition ligand blot followed by LC-MS/MS analyses were performed to detect the putative interactors of mASAL. Knowledge on the mode of function for any new protein is a prerequisite for its biotechnological application. Detailed morphological analysis of mASAL treated R. solani hyphae using different microscopic techniques revealed a detrimental effect of mASAL on both the cell wall and the plasma membrane. Moreover, exposure to mASAL caused the loss of mitochondrial membrane potential (MMP) and the subsequent intracellular accumulation of reactive oxygen species (ROS) in the target organism. In conjunction with this observation, evidence of the induction of programmed cell death (PCD) was also noted in the mASAL treated R. solani hyphae. Furthermore, we investigated its interacting partners from R. solani. Using ligand blots followed by liquid chromatography tandem mass spectrometry (LC-MS/MS) analyses, we identified different binding partners including Actin, HSP70, ATPase and 14-3-3 protein. Taken together, the present study provides insight into the probable mode of action of the antifungal protein, mASAL on R. solani which could be exploited in future biotechnological applications.

Spike propagation through the dorsal root ganglia in an unmyelinated sensory neuron: a modeling study

PubMed Central

Sundt, Danielle; Gamper, Nikita

2015-01-01

Unmyelinated C-fibers are a major type of sensory neurons conveying pain information. Action potential conduction is regulated by the bifurcation (T-junction) of sensory neuron axons within the dorsal root ganglia (DRG). Understanding how C-fiber signaling is influenced by the morphology of the T-junction and the local expression of ion channels is important for understanding pain signaling. In this study we used biophysical computer modeling to investigate the influence of axon morphology within the DRG and various membrane conductances on the reliability of spike propagation. As expected, calculated input impedance and the amplitude of propagating action potentials were both lowest at the T-junction. Propagation reliability for single spikes was highly sensitive to the diameter of the stem axon and the density of voltage-gated Na+ channels. A model containing only fast voltage-gated Na+ and delayed-rectifier K+ channels conducted trains of spikes up to frequencies of 110 Hz. The addition of slowly activating KCNQ channels (i.e., KV7 or M-channels) to the model reduced the following frequency to 30 Hz. Hyperpolarization produced by addition of a much slower conductance, such as a Ca2+-dependent K+ current, was needed to reduce the following frequency to 6 Hz. Attenuation of driving force due to ion accumulation or hyperpolarization produced by a Na+-K+ pump had no effect on following frequency but could influence the reliability of spike propagation mutually with the voltage shift generated by a Ca2+-dependent K+ current. These simulations suggest how specific ion channels within the DRG may contribute toward therapeutic treatments for chronic pain. PMID:26334005

Enhanced GABAergic Inputs Contribute to Functional Alterations of Cholinergic Interneurons in the R6/2 Mouse Model of Huntington's Disease.

PubMed

Holley, Sandra M; Joshi, Prasad R; Parievsky, Anna; Galvan, Laurie; Chen, Jane Y; Fisher, Yvette E; Huynh, My N; Cepeda, Carlos; Levine, Michael S

2015-01-01

In Huntington's disease (HD), a hereditary neurodegenerative disorder, striatal medium-sized spiny neurons undergo degenerative changes. In contrast, large cholinergic interneurons (LCIs) are relatively spared. However, their ability to release acetylcholine (ACh) is impaired. The present experiments examined morphological and electrophysiological properties of LCIs in the R6/2 mouse model of HD. R6/2 mice show a severe, rapidly progressing phenotype. Immunocytochemical analysis of choline acetyltransferase-positive striatal neurons showed that, although the total number of cells was not changed, somatic areas were significantly smaller in symptomatic R6/2 mice compared to wildtype (WT) littermates, For electrophysiology, brain slices were obtained from presymptomatic (3-4 weeks) and symptomatic (>8 weeks) R6/2 mice and their WT littermates. Striatal LCIs were identified by somatic size and spontaneous action potential firing in the cell-attached mode. Passive and active membrane properties of LCIs were similar in presymptomatic R6/2 and WT mice. In contrast, LCIs from symptomatic R6/2 animals displayed smaller membrane capacitance and higher input resistance, consistent with reduced somatic size. In addition, more LCIs from symptomatic mice displayed irregular firing patterns and bursts of action potentials. They also displayed a higher frequency of spontaneous GABAergic inhibitory postsynaptic currents (IPSCs) and larger amplitude of electrically evoked IPSCs. Selective optogenetic stimulation of somatostatin- but not parvalbumin-containing interneurons also evoked larger amplitude IPSCs in LCIs from R6/2 mice. In contrast, glutamatergic spontaneous or evoked postsynaptic currents were not affected. Morphological and electrophysiological alterations, in conjunction with the presence of mutant huntingtin in LCIs, could explain impaired ACh release in HD mouse models.

Regulation of cAMP and GSK3 signaling pathways contributes to the neuronal conversion of glioma

PubMed Central

Kim, Yongbo; Che, Lihua; Kim, Jeong Beom; Chang, Gyeong Eon; Cheong, Eunji; Kang, Seok-Gu; Ha, Yoon

2017-01-01

Glioma is the most malignant type of primary central nervous system tumors, and has an extremely poor prognosis. One potential therapeutic approach is to induce the terminal differentiation of glioma through the forced expression of pro-neural factors. Our goal is to show the proof of concept of the neuronal conversion of C6 glioma through the combined action of small molecules. We investigated the various changes in gene expression, cell-specific marker expression, signaling pathways, physiological characteristics, and morphology in glioma after combination treatment with two small molecules (CHIR99021, a glycogen synthase kinase 3 [GSK3] inhibitor and forskolin, a cyclic adenosine monophosphate [cAMP] activator). Here, we show that the combined action of CHIR99021 and forskolin converted malignant glioma into fully differentiated neurons with no malignant characteristics; inhibited the proliferation of malignant glioma; and significantly down-regulated gene ontology and gene expression profiles related to cell division, gliogenesis, and angiogenesis in small molecule–induced neurons. In vivo, the combined action of CHIR99021 and forskolin markedly delayed neurological deficits and significantly reduced the tumor volume. We suggest that reprogramming technology may be a potential treatment strategy replacing the therapeutic paradigm of traditional treatment of malignant glioma, and a combination molecule comprising a GSK3 inhibitor and a cAMP inducer could be the next generation of anticancer drugs. PMID:29161257

The natural product citral can cause significant damage to the hyphal cell walls of Magnaporthe grisea.

PubMed

Li, Rong-Yu; Wu, Xiao-Mao; Yin, Xian-Hui; Liang, Jing-Nan; Li, Ming

2014-07-15

In order to find a natural alternative to the synthetic fungicides currently used against the devastating rice blast fungus, Magnaporthe grisea, this study explored the antifungal potential of citral and its mechanism of action. It was found that citral not only inhibited hyphal growth of M. grisea, but also caused a series of marked hyphal morphological and structural alterations. Specifically, citral was tested for antifungal activity against M. grisea in vitro and was found to significantly inhibit colony development and mycelial growth with IC50 and IC90 values of 40.71 and 203.75 μg/mL, respectively. Furthermore, citral reduced spore germination and germ tube length in a concentration-dependent manner. Following exposure to citral, the hyphal cell surface became wrinkled with folds and cell breakage that were observed under scanning electron microscopy (SEM). There was damage to hyphal cell walls and membrane structures, loss of villous-like material outside of the cell wall, thinning of the cell wall, and discontinuities formed in the cell membrane following treatment based on transmission electron microscopy (TEM). This increase in chitinase activity both supports the morphological changes seen in the hyphae, and also suggests a mechanism of action. In conclusion, citral has strong antifungal properties, and treatment with this compound is capable of causing significant damage to the hyphal cell walls of M. grisea.

Analysis by UPLC-MS-QTOF and antifungal activity of guava (Psidium guajava L.).

PubMed

Bezerra, Camila Fonseca; Rocha, Janaína Esmeraldo; Nascimento Silva, Maria Karollyna do; de Freitas, Thiago Sampaio; de Sousa, Amanda Karine; Dos Santos, Antônia Thassya Lucas; da Cruz, Rafael Pereira; Ferreira, Maciel Horácio; da Silva, Josefa Carolaine Pereira; Machado, Antonio Judson Targino; Carneiro, Joara Nályda Pereira; Sales, Débora Lima; Coutinho, Henrique Douglas Melo; Ribeiro, Paulo Riceli Vasconcelos; de Brito, Edy Sousa; Morais-Braga, Maria Flaviana Bezerra

2018-05-08

Psidium guajava L. is a plant widely used for food and in folk medicine all over the world. Studies have shown that guava leaves have antifungal properties. In this study, Flavonoid and Tannic fractions were tested to investigate their chemical composition and antifungal potential in vitro.21 compounds in the two fractions, presenting a higher content of phenolic compounds. The antifungal assays were performed against Candida albicans, Candida tropicalis and Candida krusei by microdilution to determine the IC 50 and the cell viability curve. Minimal Fungicidal Concentration(MFC) and the inhibitory effects of the association of the fractions with Fluconazole, as well as the assays used to verify any morphological changes were performed in microculture chambers based on the concentrations from the microdilution. The IC 50 of the isolated fractions and the fractions associated with each other were calculated, varying from 69.29 to 3444.62 μg/mL and the fractions associated with fluconazole varied from 925.56 to 1.57 μg/mL, it was clear that the association of the natural product with the antifungal presented a synergism. The fractions affected pleomorphism capacity and have a potential antifungal activity as they caused fungal inhibition in isolated use, potentiated the action of Fluconazole, reducing its concentration and impeding morphological transition, one of the virulence factors of the genus. Copyright © 2018 Elsevier Ltd. All rights reserved.

Investigating the antifungal activity and mechanism(s) of geraniol against Candida albicans strains.

PubMed

Leite, Maria Clerya Alvino; de Brito Bezerra, André Parente; de Sousa, Janiere Pereira; de Oliveira Lima, Edeltrudes

2015-04-01

Candida albicans can be a yeast that is a commensal on the human body but can cause opportunistic or pathogenic infections. Candida infections may create serious health problems and as a result has initiated a search for new drugs with an antifungal action. Geraniol is an acyclic monoterpene alcohol with known pharmacological properties, including antimicrobial activity. The aim of this work was to evaluate the antifungal activity and mechanism(s) of geraniol against C. albicans strains. The minimum inhibitory concentration (MIC) was determined through broth microdilution techniques. We investigated possible geraniol activity on the fungal cell wall (sorbitol protect effect), cell membrane (geraniol to ergosterol binding), the time-kill curve, and its biological activity on the yeast's morphology. Amphotericin B was used as control, and all tests were performed in duplicate. The MIC of geraniol was 16 μg/ml (for 90% of isolates) but its probable mechanism of action did not involve the cell wall and ergosterol binding. In the morphological interference assay, we observed that the product inhibited pseudohyphae and chlamydoconidia formation. Time-dependent kill curve assay demonstrated that the fungicidal activity for MIC × 2 started at 2 h for the ATCC 76485 strain, and at 4 h for the LM-70 strain. Geraniol showed in vitro antifungal potential against strains of C. albicans but did not involve action on the cell wall or ergosterol. This study contributes to the development of new antifungal drugs, especially against Candida spp. © The Author 2014. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Induction of apoptosis of liver cancer cells by nanosecond pulsed electric fields (nsPEFs).

PubMed

He, Ling; Xiao, Deyou; Feng, Jianguo; Yao, Chenguo; Tang, Liling

2017-02-01

The application of nanosecond pulsed electric fields (nsPEFs) is a novel method to induce the death of cancer cells. NsPEFs could directly function on the cell membrane and activate the apoptosis pathways, then induce apoptosis in various cell lines. However, the nsPEFs-inducing-apoptosis action sites and the exact pathways are not clear now. In this study, nsPEFs were applied to the human liver cancer cells HepG2 with different parameters. By apoptosis assay, morphological observation, detecting the mitochondrial membrane potential (ΔΨ m ), intracellular calcium ion concentration ([Ca 2+ ]i) and the expressions of key apoptosis factors, we demonstrated that nsPEFs could induce the morphology of cell apoptosis, the change in ΔΨ m , [Ca 2+ ]i and the upregulation of some key apoptosis factors, which revealed the responses of liver cancer cells and indicated that cells may undergo apoptosis through the mitochondria-dependent pathway after nsPEFs were applied.

Cytoprotective effect of Valeriana officinalis extract on an in vitro experimental model of Parkinson disease.

PubMed

de Oliveria, Diêgo Madureira; Barreto, George; De Andrade, Deyse Valverde G; Saraceno, Ezequiel; Aon-Bertolino, Laura; Capani, Francisco; Dos Santos El Bachá, Ramon; Giraldez, Lisandro Diego

2009-02-01

Parkinson's disease (PD) is one of the most important neurodegenerative worldwide disorders. The potential cytoprotective effects of aqueous extract of Valeriana officinalis on rotenone-induced apoptosis in human neuroblastoma SH-SY5Y cells were demonstrated. The cytotoxicity, cell viability and analysis of cellular morphology were performed by MTT-tetrazole (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and phase contrast microscopy, respectively. Significant changes in the cellular morphology, and condensation of the cell body could be observed when cells were treated with 300 nM rotenone for 48 h. Three different concentrations of Valeriana officinalis extract were used (0.049, 0.098 and 0.195 mg/mL). These extracts brought about an increase of 7.0 +/- 1.3%, 14.5 +/- 1.3% and 14.5 +/- 3.2% in cell viability. Our results indicated that neuroprotector action of the Valeriana officinalis extract provides support for later studies as they help understanding this drug for the development of cytoprotective various therapies in PD.

Image processing for safety assessment in civil engineering.

PubMed

Ferrer, Belen; Pomares, Juan C; Irles, Ramon; Espinosa, Julian; Mas, David

2013-06-20

Behavior analysis of construction safety systems is of fundamental importance to avoid accidental injuries. Traditionally, measurements of dynamic actions in civil engineering have been done through accelerometers, but high-speed cameras and image processing techniques can play an important role in this area. Here, we propose using morphological image filtering and Hough transform on high-speed video sequence as tools for dynamic measurements on that field. The presented method is applied to obtain the trajectory and acceleration of a cylindrical ballast falling from a building and trapped by a thread net. Results show that safety recommendations given in construction codes can be potentially dangerous for workers.

A supercritical density of fast Na+ channels ensures rapid propagation of action potentials in GABAergic interneuron axons

PubMed Central

Hu, Hua; Jonas, Peter

2014-01-01

Fast-spiking, parvalbumin-expressing GABAergic interneurons/basket cells (BCs) play a key role in feedforward and feedback inhibition, gamma oscillations, and complex information processing. For these functions, fast propagation of action potentials (APs) from the soma to the presynaptic terminals is important. However, the functional properties of interneuron axons remain elusive. Here, we examined interneuron axons by confocally targeted subcellular patch-clamp recording in rat hippocampal slices. APs were initiated in the proximal axon ~20 μm from the soma, and propagated to the distal axon with high reliability and speed. Subcellular mapping revealed a stepwise increase of Na+ conductance density from the soma to the proximal axon, followed by a further gradual increase in the distal axon. Active cable modeling and experiments with partial channel block indicated that low axonal Na+ conductance density was sufficient for reliability, but high Na+ density was necessary for both speed of propagation and fast-spiking AP phenotype. Our results suggest that a supercritical density of Na+ channels compensates for the morphological properties of interneuron axons (small segmental diameter, extensive branching, and high bouton density), ensuring fast AP propagation and high-frequency repetitive firing. PMID:24657965

Statins: Do they have potential in the treatment of polycystic ovary syndrome?

PubMed Central

Kodaman, Pinar H.; Duleba, Antoni J.

2010-01-01

Many women of reproductive age are affected by polycystic ovary syndrome (PCOS), a heterogeneous endocrinopathy characterized by androgen excess, chronic oligo-anovulation and/or polycystic ovarian morphology. In addition, PCOS is often associated with insulin resistance, systemic inflammation and oxidative stress which, on one hand, lead to endothelial dysfunction and dyslipidemia with subsequent cardiovascular sequelae and, on the other hand, to hyperplasia of the ovarian theca compartment with resultant hyperandrogenism and anovulation. While traditionally statins have been used to treat dyslipidemia by blocking HMG-CoA reductase, the rate limiting step in cholesterol biosynthesis; in fact, they possess pleiotropic actions, resulting in antioxidant, anti-inflammatory and anti-proliferative effects. Statins offer a novel therapeutic approach to PCOS in that they address the dyslipidemia associated with the syndrome, as well as hyperandrogenism/hyperandrogenemia. These actions may be due to an inhibition of the effects of systemic inflammation and insulin resistance/hyperinsulinemia. Evidence to date, both in vitro and in vivo, suggests that statins have potential in the treatment of PCOS; however, further clinical trials are needed before they can be considered a standard of care in the medical management of this common endocrinopathy. PMID:18181091

The Milky Way Halo in Action Space

NASA Astrophysics Data System (ADS)

Myeong, G. C.; Evans, N. W.; Belokurov, V.; Sanders, J. L.; Koposov, S. E.

2018-04-01

We analyze the structure of the local stellar halo of the Milky Way using ∼60000 stars with full phase space coordinates extracted from the SDSS–Gaia catalog. We display stars in action space as a function of metallicity in a realistic axisymmetric potential for the Milky Way Galaxy. The metal-rich population is more distended toward high radial action J R as compared to azimuthal or vertical action, J ϕ or J z . It has a mild prograde rotation (< {v}φ > ≈ 25 {km} {{{s}}}-1), is radially anisotropic and highly flattened, with axis ratio q ≈ 0.6–0.7. The metal-poor population is more evenly distributed in all three actions. It has larger prograde rotation (< {v}φ > ≈ 50 {km} {{{s}}}-1), a mild radial anisotropy, and a roundish morphology (q ≈ 0.9). We identify two further components of the halo in action space. There is a high-energy, retrograde component that is only present in the metal-rich stars. This is suggestive of an origin in a retrograde encounter, possibly the one that created the stripped dwarf galaxy nucleus, ωCentauri. Also visible as a distinct entity in action space is a resonant component, which is flattened and prograde. It extends over a range of metallicities down to [Fe/H] ≈ ‑3. It has a net outward radial velocity < {v}R> ≈ 12 {km} {{{s}}}-1 within the solar circle at | z| < 3.5 {kpc}. The existence of resonant stars at such extremely low metallicities has not been seen before.

Action of Micrurus dumerilii carinicauda coral snake venom on the mammalian neuromuscular junction.

PubMed

Serafim, Francine G; Reali, Marielga; Cruz-Höfling, Maria Alice; Fontana, Marcos D

2002-02-01

The venoms of coral snakes (mainly Micrurus species) have pre- and/or postsynaptic actions, but only a few of these have been studied in detail. We have investigated the effects of Micrurus dumerilii carinicauda coral snake venom on neurotransmission in rat isolated phrenic nerve-diaphragm muscle and chick biventer cervicis preparations stimulated directly or indirectly. M. d. carinicauda venom (5 or 10 microg/ml) produced neuromuscular blockade in rat (85-90% in 291.8+/-7.3 min and 108.3+/-13.8, respectively; n=5) and avian (95.0+/-2.0 min; 5 microg/ml, n=5) preparations. Neostigmine (5.8 microM) and 3,4-diaminopyridine (230 microM) partially reversed the venom-induced neuromuscular blockade in rat nerve-muscle preparations. In neither preparation did the venom depress the twitch response elicited by direct muscle stimulation. The contractures induced by acetylcholine in chick preparations were inhibited by the venom (95-100%; n=4; p<0.05). In rat preparations, the venom produced a progressive decrease in the amplitude of miniature end-plate potentials (m.e.p.ps control frequency=69.3+/-5.0/min and control amplitude=0.4+/-0.2 mV) until these were abolished. Neostigmine (5.8 microM) and 3,4-diaminopyridine (230 microM) partially antagonized this blockade of m.e.p.ps. The resting membrane potential was not altered with the venom (10 microg/ml). M. d. carinicauda venom produced dose-dependent morphological changes in indirectly stimulated mammal preparations. Twenty-five per cent of muscle fibers were affected by a venom concentration of 5 microg/ml, whilst 60.7% were damaged by 10 microg of venom/ml. In biventer cervicis preparations, the morphological changes were slower in onset and were generally characterized by undulating fibers and, to a lesser extent, by zones of disintegrating myofibrils. A venom concentration of 5 microg/ml damaged 52.2% of the fibers. These findings indicate that M. d. carinicauda venom has neurotoxic and myotoxic effects and that the neuromuscular blockade involves mainly a postsynaptic action.

Channel degradation and restoration of an Alpine river and related morphological changes

NASA Astrophysics Data System (ADS)

Campana, Daniela; Marchese, Enrico; Theule, Joshua I.; Comiti, Francesco

2014-09-01

River degradation and thus necessity for restoration are major issues worldwide. However, adequate methodologies to assess morphological variations linked to these actions and the morphological success of restoration interventions are still to be determined. The Ahr River (South Tyrol, Italian Alps) was characterized until the mid-twentieth century by an anabranching and meandering pattern, but starting from the 1960s it underwent intense channel degradation in terms of narrowing, incision, and floodplain disconnection. In the period 2003-2011, several reaches of the Ahr River were restored by widening and raising the channel bed. The planimetric changes that occurred historically in the Ahr River were determined by the interpretation of 10 maps and aerial photos covering the period 1820-2011. The estimation of the incision that occurred during the degradation phase was assessed by the difference in elevation between gravel surfaces, whereas the changes introduced by restoration interventions in two reaches were evaluated through the comparison of topographic cross sections surveyed in year 2000 and a high-resolution bathymetric LiDAR survey flown in late 2012. The MQI (Morphological Quality Index) was applied to different reaches in order to test how assessment methodologies respond to degradation and restoration actions. The combined analysis of planform and vertical changes indicates that gravel mining has been the largest pressure for the river, but a change in sediment/flow regimes probably led to the channel adjustments that occurred during the early twentieth century. The restoration measures have locally increased channel width, elevation, and morphometrical diversity compared to the unrestored reaches, as well as the morphological quality assessed by MQI. However, the extent of the modifications brought about by restoration works differs between the two restored reaches, pointing out the need for a quantitative analysis of the historical evolution of each river reach before designing and implementing restoration actions and to the necessity to monitor the subsequent morphological adjustments.

Leptin regulation of hippocampal synaptic function in health and disease

PubMed Central

Irving, Andrew J.; Harvey, Jenni

2014-01-01

The endocrine hormone leptin plays a key role in regulating food intake and body weight via its actions in the hypothalamus. However, leptin receptors are highly expressed in many extra-hypothalamic brain regions and evidence is growing that leptin influences many central processes including cognition. Indeed, recent studies indicate that leptin is a potential cognitive enhancer as it markedly facilitates the cellular events underlying hippocampal-dependent learning and memory, including effects on glutamate receptor trafficking, neuronal morphology and activity-dependent synaptic plasticity. However, the ability of leptin to regulate hippocampal synaptic function markedly declines with age and aberrant leptin function has been linked to neurodegenerative disorders such as Alzheimer's disease (AD). Here, we review the evidence supporting a cognitive enhancing role for the hormone leptin and discuss the therapeutic potential of using leptin-based agents to treat AD. PMID:24298156

Morphology and ventilatory function of gills in the carpet shark family Parascylliidae (Elasmobranchii, Orectolobiformes).

PubMed

Goto, Tomoaki; Shiba, Yojiro; Shibagaki, Kazuhiro; Nakaya, Kazuhiro

2013-06-01

We examined gill morphology and ventilatory function in the carpet shark family Parascylliidae using 14 preserved specimens of Parascyllium ferrugineum, P. variolatum, P. collare and Cirrhoscyllium japonicum, and two live specimens of P. ferrugineum and P. variolatum. Morphological examinations revealed eight morphological characteristics related to the fifth gill, based on comparisons with other elasmobranchs, viz. large fifth gill slit without gill filaments, anatomical modifications in the fourth ceratobranchial cartilage and coraco-branchialis muscle, and the hypaxialis muscle associated with the fifth gill arch. Ventilation examinations using dyed seawater and prey items showed different water flows through the gill slits for respiration and prey-capture actions. For respiration, water sucked into the mouth was expelled equally through the first to fourth gill slits via a "double-pump" action, there being no involvement of the fifth gill slit. In prey-capture, however, water sucked into the mouth was discharged only via the widely opened fifth gill slit. This form of water flow is similar to that in other benthic suction-feeding sharks (e.g., Chiloscyllium plagiosum), except for the active water discharge by wide expansion and contraction of the fifth parabranchial cavity. The latter is dependent upon the morphological modifications of the fourth and fifth gill arches, derived phylogenetically as a mechanistic suction specialization in Parascylliidae.

Trimetazidine prevents palmitate-induced mitochondrial fission and dysfunction in cultured cardiomyocytes.

PubMed

Kuzmicic, Jovan; Parra, Valentina; Verdejo, Hugo E; López-Crisosto, Camila; Chiong, Mario; García, Lorena; Jensen, Michael D; Bernlohr, David A; Castro, Pablo F; Lavandero, Sergio

2014-10-01

Metabolic and cardiovascular disease patients have increased plasma levels of lipids and, specifically, of palmitate, which can be toxic for several tissues. Trimetazidine (TMZ), a partial inhibitor of lipid oxidation, has been proposed as a metabolic modulator for several cardiovascular pathologies. However, its mechanism of action is controversial. Given the fact that TMZ is able to alter mitochondrial metabolism, we evaluated the protective role of TMZ on mitochondrial morphology and function in an in vitro model of lipotoxicity induced by palmitate. We treated cultured rat cardiomyocytes with BSA-conjugated palmitate (25 nM free), TMZ (0.1-100 μM), or a combination of both. We evaluated mitochondrial morphology and lipid accumulation by confocal fluorescence microscopy, parameters of mitochondrial metabolism (mitochondrial membrane potential, oxygen consumption rate [OCR], and ATP levels), and ceramide production by mass spectrometry and indirect immunofluorescence. Palmitate promoted mitochondrial fission evidenced by a decrease in mitochondrial volume (50%) and an increase in the number of mitochondria per cell (80%), whereas TMZ increased mitochondrial volume (39%), and decreased mitochondrial number (56%), suggesting mitochondrial fusion. Palmitate also decreased mitochondrial metabolism (ATP levels and OCR), while TMZ potentiated all the metabolic parameters assessed. Moreover, pretreatment with TMZ protected the cardiomyocytes from palmitate-induced mitochondrial fission and dysfunction. TMZ also increased lipid accumulation in cardiomyocytes, and prevented palmitate-induced ceramide production. Our data show that TMZ protects cardiomyocytes by changing intracellular lipid management. Thus, the beneficial effects of TMZ on patients with different cardiovascular pathologies can be related to modulation of the mitochondrial morphology and function. Copyright © 2014 Elsevier Inc. All rights reserved.

Does Morphological Adjustment During Tsunami Inundation Increase Levels of Hazard?

NASA Astrophysics Data System (ADS)

Tehranirad, B.; Kirby, J. T., Jr.; Shi, F.; Grilli, S. T.

2016-12-01

Previous inundation mapping results for the US East Coast have shown that barrier islands would be among the most impacted areas during a possible tsunami. Many of these barriers are home to large population centers such as Atlantic City, NJ and Ocean City, MD. A tsunami can significantly change coastal morphology. Post-tsunami surveys have shown that large amounts of sediment can be moved in bays and estuaries by tsunami action, especially over coastal dunes. During tsunami inundation, large amounts of sediment have been eroded from sandy coasts and deposited further onshore. In some cases, sand dunes have been completely eroded by a tsunami, with the eroded sediment being deposited either onshore behind the dunes, or offshore during the rundown process. Given the potential for tsunamis to change coastal morphology, it is necessary to consider whether barrier island morphology change during inundation, if accounted for, would increase the assessment of tsunami hazard identified in the development of inundation and evacuation maps. In this presentation, we will show the results of our recent study on the morphological response of barrier islands during possible tsunamis that threaten the US East Coast. For this purpose, we have coupled the Boussinesq model FUNWAVE-TVD with a depth-averaged advection-diffusion sediment transport model and a morphology module to capture bed evolution under tsunami conditions. The model is verified in comparison to laboratory observations and to observed erosion/deposition patterns in Crescent City, CA harbor during the 2011 Tohoku-oki tsunami. We then use the model to study the effect of morphology change on predicted inundation limits for two barrier islands: the undeveloped Assateague Island, and the developed Ocean City, MD, using the tsunami sources utilized in previous hazard analysis. Our results suggest that significant bathymetric changes could be expected on a barrier island during tsunami inundation, leading to large increases in inundation areas for some of the events, particularly for smaller events where inundation without progressive dune breaching is minor.

Cellular responses to endogenous electrochemical gradients in morphological development

NASA Technical Reports Server (NTRS)

Desrosiers, M. F.

1996-01-01

Endogenous electric fields give vectorial direction to morphological development in Zea mays (sweet corn) in response to gravity. Endogenous electrical fields are important because of their ability to influence: (1) intercellular organization and development through their effects on the membrane potential, (2) direct effects such as electrophoresis of membrane components, and (3) both intracellular and extracellular transport of charged compounds. Their primary influence is in providing a vectorial dimension to the progression of one physiological state to another. Gravity perception and transduction in the mesocotyl of vascular plants is a complex interplay of electrical and chemical gradients which ultimately provide the driving force for the resulting growth curvature called gravitropism. Among the earliest events in gravitropism are changes in impedance, voltage, and conductance between the vascular stele and the growth tissues, the cortex, in the mesocotyl of corn shoots. In response to gravistimulation: (1) a potential develops which is vectorial and of sufficient magnitude to be a driving force for transport between the vascular stele and cortex, (2) the ionic conductance changes within seconds showing altered transport between the tissues, and (3) the impedance shows a transient biphasic response which indicates that the mobility of charges is altered following gravistimulation and is possibly the triggering event for the cascade of actions which leads to growth curvature.

Ototoxicity of salicylate, nonsteroidal antiinflammatory drugs, and quinine.

PubMed

Jung, T T; Rhee, C K; Lee, C S; Park, Y S; Choi, D C

1993-10-01

Salicylates and most NSAIDS in high doses cause mild to moderate temporary hearing loss, either flat or greater in the high frequencies. Hearing loss is accompanied by tinnitus and suprathreshold changes. Salicylates may or may not exacerbate hearing loss and cochlear damage induced by noise. The mechanism of salicylate ototoxicity seems to be multifactorial. Morphologic studies suggest that no permanent cochlear damage occurs with salicylate ototoxicity. Electrophysiologic, morphologic, and in vitro data conclusively demonstrate that salicylate affects outer hair cells. In addition, salicylates appear to decrease cochlear blood flow. Salicylates and NSAIDs inhibit PG-forming cyclooxygenase, and recent studies suggest that abnormal levels of arachidonic acid metabolites consisting of decreased PGs and increased LTs may mediate salicylate ototoxicity. As with salicylate, quinine ototoxicity appears to be multifactorial in origin. The mechanism includes vasoconstriction and decreases in cochlear blood flow, as measured by laser Doppler flowmetry, motion photographic studies, and histologic studies. Reversible alterations of outer hair cells also appear to play an important role, as demonstrated by histology, electron microscopy, isolated hair cell studies, and cochlear potential evaluations. Unlike with salicylate, however, the role of prostaglandins in quinine ototoxicity has not been clearly demonstrated. Also, one of quinine's principal actions, antagonism of calcium-dependent potassium channels, has yet to be investigated for its potential role in ototoxicity.

Toxicity of the mycotoxin fumonisin B1 on the insect Sf9 cell line.

PubMed

Zhang, He; Zhang, Liyang; Diao, Xue; Li, Na; Liu, Chenglan

2017-04-01

Fumonisins are a type of mycotoxin produced by Fusarium spp., mainly F. proliferatum and F. vertieilliodes, and represent a potential hazard to the health of animals and human beings. The toxicity and mechanism of action of fumonisins is ambiguous, and it is unclear whether fumonisins are toxic to insect cells. This study examines the toxicity of fumonisin B 1 (FB 1 ) and its mechanism of action in the Spodoptera frugiperda Sf9 cell line. We found that FB 1 inhibited Sf9 cellular proliferation and arrested cell growth at the G 2 /M phase. Morphological observation showed that FB 1 induced swelling, vacuole formation, and loss of adhesion in Sf9 cells. Flow cytometry analysis showed that FB 1 caused depolarization of the cell membrane potential and hyperpolarization of the mitochondrial membrane potential. To uncover potential genes associated with the molecular mechanisms of FB 1 , 41 differentially expressed genes were identified by transcriptome analyses after FB 1 treatment. These genes are putatively involved in detoxification metabolism, insect hormone regulation, cell apoptosis, and other related processes. Finally, six differentially expressed genes were chosen and validated by quantitative real-time PCR (QRT-PCR). Our test could provide a reference for other kinds of insect cells studies on FB 1 stress. At the same time, our studies try to provide a possible for FB 1 as a precursor compounds of biological insecticide. Copyright © 2017 Elsevier Ltd. All rights reserved.

Numerical Modeling of Medium Term Morphological Changes at Manavgat River Mouth Due to Combined Action of Waves and River Discharges

NASA Astrophysics Data System (ADS)

Demirci, E.; Baykal, C.; Guler, I.

2016-12-01

In this study, hydrodynamic conditions due to river discharge, wave action and sea level fluctuations within a seven month period and the morphological response of the Manavgat river mouth are modeled with XBeach, a two-dimensional depth-averaged (2DH) numerical model developed to compute the natural coastal response during time-varying storm and hurricane conditions (Roelvink et al., 2010). The study area shows an active behavior on its nearshore morphology, thus, two jetties were constructed at the river mouth between years 1996-2000. Recently, Demirci et al. (2016) has studied the impacts of an excess river discharge and concurrent wave action and tidal fluctuations on the Manavgat river mouth morphology for the duration of 12 days (December 4th and 15th, 1998) while the construction of jetties were carried on. It is concluded that XBeach has presumed the final morphology fairly well with the calibrated set of input parameters. Here, the river mouth modeled at a further past date before the construction of jetties with the similar set of input parameters (between August 1st, 1995-March 8th, 1996) to reveal the drastic morphologic change near the mouth due to high river discharge and severe storms happened in a longer period of time. Wave climate effect is determined with the wave hindcasting model, W61, developed by Middle East Technical University-OERC with the NCEP-CFSR wind data as well as the sea level data. River discharge, wave and sea level data are introduced as input parameters in the XBeach numerical model and the final output morphological change is compared with the final bed level measurements. References:Demirci, E., Baykal, C., Guler, I., Ergin, A., & Sogut, E. (postponed). Numerical Modelling on Hydrodynamic Flow Conditions and Morphological Changes Using XBeach Near Manavgat River Mouth. Accepted as Oral presentation at the 35thInt. Conf. on Coastal Eng., Istanbul, Turkey. Guler, I., Ergin, A., Yalçıner, A. C., (2003). Monitoring Sediment Transport Processes at Manavgat River Mouth, Antalya Turkey. COPEDEC VI, 2003, Colombo, Sri Lanka Roelvink, D., Reniers, A., van Dongeren, A., van Thiel de Vries, J., Lescinski, J. and McCall, R., (2010). XBeach Model Description and Manual. Unesco-IHE Institute for Water Education, Deltares and Delft Univ. of Technology. Report June, 21, 2010 version 6.

The mechanism of antifungal action of essential oil from dill (Anethum graveolens L.) on Aspergillus flavus.

PubMed

Tian, Jun; Ban, Xiaoquan; Zeng, Hong; He, Jingsheng; Chen, Yuxin; Wang, Youwei

2012-01-01

The essential oil extracted from the seeds of dill (Anethum graveolens L.) was demonstrated in this study as a potential source of an eco-friendly antifungal agent. To elucidate the mechanism of the antifungal action further, the effect of the essential oil on the plasma membrane and mitochondria of Aspergillus flavus was investigated. The lesion in the plasma membrane was detected through flow cytometry and further verified through the inhibition of ergosterol synthesis. The essential oil caused morphological changes in the cells of A. flavus and a reduction in the ergosterol quantity. Moreover, mitochondrial membrane potential (MMP), acidification of external medium, and mitochondrial ATPase and dehydrogenase activities were detected. The reactive oxygen species (ROS) accumulation was also examined through fluorometric assay. Exposure to dill oil resulted in an elevation of MMP, and in the suppression of the glucose-induced decrease in external pH at 4 µl/ml. Decreased ATPase and dehydrogenase activities in A. flavus cells were also observed in a dose-dependent manner. The above dysfunctions of the mitochondria caused ROS accumulation in A. flavus. A reduction in cell viability was prevented through the addition of L-cysteine, which indicates that ROS is an important mediator of the antifungal action of dill oil. In summary, the antifungal activity of dill oil results from its ability to disrupt the permeability barrier of the plasma membrane and from the mitochondrial dysfunction-induced ROS accumulation in A. flavus.

Morphological alterations in salivary glands of Rhipicephalus sanguineus ticks (Acari: Ixodidae) exposed to neem seed oil with known azadirachtin concentration.

PubMed

Remedio, R N; Nunes, P H; Anholeto, L A; Oliveira, P R; Sá, I C G; Camargo-Mathias, M I

2016-04-01

Neem (Azadirachta indica) has attracted the attention of researchers worldwide due to its repellent properties and recognized effects on the morphology and physiology of arthropods, including ticks. Therefore, this study aimed to demonstrate the effects of neem seed oil enriched with azadirachtin on salivary glands of Rhipicephalus sanguineus ticks, targets of great veterinary interest because of their ability to transmit pathogens to dogs. For this, R. sanguineus semi-engorged females were subjected to treatment with neem seed oil, with known azadirachtin concentrations (200, 400 and 600ppm). After dissection, salivary glands were collected and evaluated through morphological techniques in light microscopy, confocal scanning laser microscopy and transmission electron microscopy, so that the possible relation between neem action and further impairment in these ectoparasites feed performance could be established. Neem oil demonstrated a clear dose-dependent effect in the analyzed samples. The agranular (type I) and granular acini (types II and III) showed, particularly in individuals treated with the highest concentrations of the product, cells with irregular shape, intense cytoplasmic disorganization and vacuolation, dilation of rough endoplasmic reticulum lumen, besides alterations in mitochondrial intermembrane space. These morphological damages may indicate modifications in salivary glands physiology, demonstrating the harmful effects of compounds present in neem oil on ticks. These results reinforce the potential of neem as an alternative method for controlling R. sanguineus ticks, instead of synthetic acaricides. Copyright © 2016 Elsevier Ltd. All rights reserved.

Opposing actions of Arx and Pax4 in endocrine pancreas development

PubMed Central

Collombat, Patrick; Mansouri, Ahmed; Hecksher-Sørensen, Jacob; Serup, Palle; Krull, Jens; Gradwohl, Gerard; Gruss, Peter

2003-01-01

Genes encoding homeodomain-containing proteins potentially involved in endocrine pancreas development were isolated by combined in silico and nested-PCR approaches. One such transcription factor, Arx, exhibits Ngn3-dependent expression throughout endocrine pancreas development in α, β-precursor, and δ cells. We have used gene targeting in mouse embryonic stem cells to generate Arx loss-of-function mice. Arx-deficient animals are born at the expected Mendelian frequency, but develop early-onset hypoglycemia, dehydration, and weakness, and die 2 d after birth. Immunohistological analysis of pancreas from Arx mutants reveals an early-onset loss of mature endocrine α cells with a concomitant increase in β-and δ-cell numbers, whereas islet morphology remains intact. Our study indicates a requirement of Arx for α-cell fate acquisition and a repressive action on β-and δ-cell destiny, which is exactly the opposite of the action of Pax4 in endocrine commitment. Using multiplex reverse transcriptase PCR (RT-PCR), we demonstrate an accumulation of Pax4 and Arx transcripts in Arx and Pax4 mutant mice, respectively. We propose that the antagonistic functions of Arx and Pax4 for proper islet cell specification are related to the pancreatic levels of the respective transcripts. PMID:14561778

Opposing actions of Arx and Pax4 in endocrine pancreas development.

PubMed

Collombat, Patrick; Mansouri, Ahmed; Hecksher-Sorensen, Jacob; Serup, Palle; Krull, Jens; Gradwohl, Gerard; Gruss, Peter

2003-10-15

Genes encoding homeodomain-containing proteins potentially involved in endocrine pancreas development were isolated by combined in silico and nested-PCR approaches. One such transcription factor, Arx, exhibits Ngn3-dependent expression throughout endocrine pancreas development in alpha, beta-precursor, and delta cells. We have used gene targeting in mouse embryonic stem cells to generate Arx loss-of-function mice. Arx-deficient animals are born at the expected Mendelian frequency, but develop early-onset hypoglycemia, dehydration, and weakness, and die 2 d after birth. Immunohistological analysis of pancreas from Arx mutants reveals an early-onset loss of mature endocrine alpha cells with a concomitant increase in beta-and delta-cell numbers, whereas islet morphology remains intact. Our study indicates a requirement of Arx for alpha-cell fate acquisition and a repressive action on beta-and delta-cell destiny, which is exactly the opposite of the action of Pax4 in endocrine commitment. Using multiplex reverse transcriptase PCR (RT-PCR), we demonstrate an accumulation of Pax4 and Arx transcripts in Arx and Pax4 mutant mice, respectively. We propose that the antagonistic functions of Arx and Pax4 for proper islet cell specification are related to the pancreatic levels of the respective transcripts.

Retro-action model for the erosion of rocky coasts

NASA Astrophysics Data System (ADS)

Sapoval, B.; Baldassarri, A.

2009-12-01

Rocky coasts are estimated to represent 75% of the world’s shorelines [1]. We discuss various situations where the formation of rocky coast morphology could be attributed to the retro-action of the coast morphology on the erosive power of the see. In the case of rocky coasts, erosion can spontaneously create irregular seashores. But, in turn, the geometrical irregularity participates to the damping of sea-waves, decreasing the average wave amplitude and erosive power. There may then exist a mutual self-stabilization of the waves amplitude together with the irregular morphology of the coast. A simple model of such stabilization is discussed. It leads, through a complex dynamics of the earth-sea interface, to the spontaneous appearance of an irregular sea-shore. The final coast morphology is found to depend on the morphology/damping coupling of the coast and on the possible existence of built-in correlations within the coast lithologic properties. This is illustrated in the figure. In the limit case where the morphology/damping coupling is weak and when the earth lithology distribution exhibit only short range correlations, the process spontaneously build fractal morphologies with a dimension close to 4/3 [2]. It is shown that this dimension refers to the dimension of the so-called accessible perimeter in gradient percolation. However, even rugged but non-fractal sea-coasts morphology may emerge for strong damping or during the erosion process. When the distributions of the lithologies exhibit long range correlations, a variety of complex morphologies are obtained which mimics observed coastline complexity, well beyond simple fractality. On a somewhat different perspective, the design of breakwaters is suggested to be improved by using global irregular geometry with features sizes of the order of the wave-length of the sea oscillations. [1] R. A. Davis, Jr, D. M. Fitzgerald, Beaches and Coasts,(Blackwell, Oxford 2004). [2] B. Sapoval, A. Baldassarri, A. Gabrielli, Self-stabilized Fractality of Sea-coasts through Erosion, Phys. Rev. Lett. 93, 098501 (2004). Time evolution of the coastline morphology starting with a flat sea-shore. Left and right columns correspond respectively to weak and strong coupling. Top to bottom: suc- cessive morphologies with the final morphologies at the bottom.

Electrical properties associated with wide intercellular clefts in rabbit Purkinje fibres.

PubMed Central

Colatsky, T J; Tsien, R W

1979-01-01

1. Rabbit Purkinje fibres were studied using micro-electrode recordings of electrical activity or a two-micro-electrode voltage clamp. Previous morphological work had suggested that these preparations offer structural advantages for the analysis of ionic permeability mechanisms. 2. Viable preparations could be obtained consistently by exposure to a K glutamate Tyrode solution during excision and recovery. In NaCl Tyrode solution, the action potential showed a large overshoot and fully developed plateau, but no pacemaker depolarization at negative potentials. 3. The passive electrical properties were consistent with morphological evidence for the accessibility of cleft membranes within the cell bundle. Electrotonic responses to intracellular current steps showed the behaviour expected for a simple leaky capacitative cable. Capacitative current transients under voltage clamp were changed very little by an eightfold reduction in the external solution conductivity. 4. Slow current changes attributable to K depletion were small compared to those found in other cardiac preparations. The amount of depletion was close to that predicted by a cleft model which assumed free K diffusion in 1 micron clefts. 5. Step depolarizations over the plateau range of potentials evoked a slow inward current which was resistant to tetrodotoxin but blocked by D600. 6. Strong depolarizations to potentials near 0 mV elicited a transient outward current and a slowly activating late outward current. Both components resembled currents found in sheep or calf Purkinje fibres. 7. These experiments support previous interpretations of slow plateau currents in terms of genuine permeability changes. The rabbit Purkinje fibre may allow various ionic channels to be studied with relatively little interference from radial non-uniformities in membrane potential or ion concentration. Images Fig. 7 PMID:469754

Mechanistic kinetic modeling generates system-independent P-glycoprotein mediated transport elementary rate constants for inhibition and, in combination with 3D SIM microscopy, elucidates the importance of microvilli morphology on P-glycoprotein mediated efflux activity.

PubMed

Ellens, Harma; Meng, Zhou; Le Marchand, Sylvain J; Bentz, Joe

2018-06-01

In vitro transporter kinetics are typically analyzed by steady-state Michaelis-Menten approximations. However, no clear evidence exists that these approximations, applied to multiple transporters in biological membranes, yield system-independent mechanistic parameters needed for reliable in vivo hypothesis generation and testing. Areas covered: The classical mass action model has been developed for P-glycoprotein (P-gp) mediated transport across confluent polarized cell monolayers. Numerical integration of the mass action equations for transport using a stable global optimization program yields fitted elementary rate constants that are system-independent. The efflux active P-gp was defined by the rate at which P-gp delivers drugs to the apical chamber, since as much as 90% of drugs effluxed by P-gp partition back into nearby microvilli prior to reaching the apical chamber. The efflux active P-gp concentration was 10-fold smaller than the total expressed P-gp for Caco-2 cells, due to their microvilli membrane morphology. The mechanistic insights from this analysis are readily extrapolated to P-gp mediated transport in vivo. Expert opinion: In vitro system-independent elementary rate constants for transporters are essential for the generation and validation of robust mechanistic PBPK models. Our modeling approach and programs have broad application potential. They can be used for any drug transporter with minor adaptations.

Experimental and theoretical analysis of neuron-transistor hybrid electrical coupling: the relationships between the electro-anatomy of cultured Aplysia neurons and the recorded field potentials.

PubMed

Cohen, Ariel; Shappir, Joseph; Yitzchaik, Shlomo; Spira, Micha E

2006-12-15

Understanding the mechanisms that generate field potentials (FPs) by neurons grown on semiconductor chips is essential for implementing neuro-electronic devices. Earlier studies emphasized that FPs are generated by current flow between differentially expressed ion channels on the membranes facing the chip surface, and those facing the culture medium in electrically compact cells. Less is known, however, about the mechanisms that generate FPs by action potentials (APs) that propagate along typical non-isopotential neurons. Using Aplysia neurons cultured on floating gate-transistors, we found that the FPs generated by APs in cultured neurons are produced by current flow along neuronal compartments comprising the axon, cell body, and neurites, rather than by flow between the membrane facing the chip substrate and that facing the culture medium. We demonstrate that the FPs waveform generated by non-isopotential neurons largely depends on the morphology of the neuron.

[Morphologic changes in cultures of different tissues exposed to the toxins of C1. perfringens types B, C, E and F].

PubMed

Ermakova, M P; Zemlianitskaia, E P

1975-11-01

There were revealed morphological peculiarities of the action of C1. perfringens toxins, types B, C, D, E and F on the cultures of fibroblasts of chick embryo, amniotic cells and intestinal tissue. The toxin type B was characterized by a marked vocuolization of the cell cytoplasm; the action of the toxin of type C was expressed in the swelling of the nuclei and the lysis of the chromatine substance, the toxin of type E casued kariorhexis, and the toxin of type F--hyperchromatosis of the nuclei. All the cultures proved to be insensitive to the toxin of type D. Peculiarity of the morphological affection of the cells permitted to differentiate toxin of type B in the cultures of the fibroblasts of chick embryo, whereas the toxins of types C, E and F--in the cultures of the amniotic cells under control of the reaction of neutralization with the homologous antitoxic sera.

Biosynthesis of silver nanoparticles using Sida acuta extract for antimicrobial actions and corrosion inhibition potential.

PubMed

Idrees, Muhammad; Batool, Saima; Kalsoom, Tanzila; Raina, Sadaf; Sharif, Hafiz Muhammad Adeel; Yasmeen, Summera

2018-02-12

Nanotechnology exhibits a multidisciplinary area and gained interests for researchers. Nanoparticles produced via physical and chemical methods affects ecosystem drastically. Green synthesis is the charming technique that is inexpensive and safe for the environment. This study aimed to explore the antibacterial actions of as-synthesized silver nanoparticles (Ag-NPs) against Escherichia coli, Staphylococcus aureus and Streptococcus faecalis. Also, the anti-corrosion actions confirmed that the Ag-NPs proved as good inhibitors. In this way, Ag-NPs were prepared via biosynthesis technique by consuming the ground leaves and stem of 'Sida acuta' as a capping agent. The Ag-NPs were formed by irradiation of the aqueous solution of silver nitrate (AgNO 3 ) with extract of S. acuta stem and leaves. The as-synthesized reaction mixture of Ag-NPs was found to exhibit an absorbance band at 446-447 nm, by an UV/VIS spectrophotometer, which is a characteristic of Ag-NPs due to the surface plasmon resonance absorption band. The X-ray diffraction and transmission electron microscopy (TEM) were used for the confirmation of Ag-NPs' variety dimension, morphology and dispersion. The infrared spectra confirmed the bio-fabrication of the Ag-NPs displayed the existence of conceivable functional groups responsible for the bio-reduction and capping. The antimicrobial actions were measured and the zone of inhibition was compared with standard antibiotics.

Heterogeneity of adult masseter muscle satellite cells with cardiomyocyte differentiation potential.

PubMed

Huang, Wei; Liang, Jialiang; Feng, Yuliang; Jia, Zhanfeng; Jiang, Lin; Cai, Wenfeng; Paul, Christian; Gu, Jianguo G; Stambrook, Peter J; Millard, Ronald W; Zhu, Xiao-Lan; Zhu, Ping; Wang, Yigang

2018-05-26

Although resident cardiac stem cells have been reported, regeneration of functional cardiomyocytes (CMs) remains a challenge. The present study identifies an alternative progenitor source for CM regeneration without the need for genetic manipulation or invasive heart biopsy procedures. Unlike limb skeletal muscles, masseter muscles (MM) in the mouse head are developed from Nkx2-5 mesodermal progenitors. Adult masseter muscle satellite cells (MMSCs) display heterogeneity in developmental origin and cell phenotypes. The heterogeneous MMSCs that can be characterized by cell sorting based on stem cell antigen-1 (Sca1) show different lineage potential. While cardiogenic potential is preserved in Sca1 + MMSCs as shown by expression of cardiac progenitor genes (including Nkx2-5), skeletal myogenic capacity is maintained in Sca1 - MMSCs with Pax7 expression. Sca1 + MMSC-derived beating cells express cardiac genes and exhibit CM-like morphology. Electrophysiological properties of MMSC-derived CMs are demonstrated by calcium transients and action potentials. These findings show that MMSCs could serve as a novel cell source for cardiomyocyte replacement. Copyright © 2018. Published by Elsevier Inc.

Electrochemical analysis of the corrosion inhibition effect of trypsin complex on the pitting corrosion of 420 martensitic stainless steel in 2M H2SO4 solution.

PubMed

Loto, Roland Tolulope

2018-01-01

Inhibition effect of trypsin complex (TC) on the pitting corrosion of martensitic stainless steel (type 420) in 1M H2SO4 solution was studied with potentiodynamic polarization, open circuit potential measurement and optical microscopy. TC reduced the corrosion rate of the steel with maximum inhibition efficiency of 80.75%. Corrosion potential shifted anodically due to the electrochemical action of TC. The pitting potential increased from 1.088VAg/AgCl (3M) at 0% TC to 1.365VAg/AgCl(3M) at 4% TC. TC shifts the open circuit corrosion potential from -0.270s at 0% TC concentration to -0.255V at 5% TC. The compound completely adsorbed onto the steel according to Langmuir, Frumkin and Temkin isotherms. ATF-FTIR spectroscopy confirmed the inhibition mode to be through surface coverage. Thermodynamic calculations showed physisorption molecular interaction. Corrosion pits are present on the uninhibited 420 morphology in comparison to TC inhibited surface which slightly deteriorated.

Electrochemical analysis of the corrosion inhibition effect of trypsin complex on the pitting corrosion of 420 martensitic stainless steel in 2M H2SO4 solution

PubMed Central

Loto, Roland Tolulope

2018-01-01

Inhibition effect of trypsin complex (TC) on the pitting corrosion of martensitic stainless steel (type 420) in 1M H2SO4 solution was studied with potentiodynamic polarization, open circuit potential measurement and optical microscopy. TC reduced the corrosion rate of the steel with maximum inhibition efficiency of 80.75%. Corrosion potential shifted anodically due to the electrochemical action of TC. The pitting potential increased from 1.088VAg/AgCl (3M) at 0% TC to 1.365VAg/AgCl(3M) at 4% TC. TC shifts the open circuit corrosion potential from -0.270s at 0% TC concentration to -0.255V at 5% TC. The compound completely adsorbed onto the steel according to Langmuir, Frumkin and Temkin isotherms. ATF-FTIR spectroscopy confirmed the inhibition mode to be through surface coverage. Thermodynamic calculations showed physisorption molecular interaction. Corrosion pits are present on the uninhibited 420 morphology in comparison to TC inhibited surface which slightly deteriorated. PMID:29672541

Kinesin Mutations Cause Motor Neuron Disease Phenotypes by Disrupting Fast Axonal Transport in Drosophila

PubMed Central

Hurd, D. D.; Saxton, W. M.

1996-01-01

Previous work has shown that mutation of the gene that encodes the microtubule motor subunit kinesin heavy chain (Khc) in Drosophila inhibits neuronal sodium channel activity, action potentials and neurotransmitter secretion. These physiological defects cause progressive distal paralysis in larvae. To identify the cellular defects that cause these phenotypes, larval nerves were studied by light and electron microscopy. The axons of Khc mutants develop dramatic focal swellings along their lengths. The swellings are packed with fast axonal transport cargoes including vesicles, synaptic membrane proteins, mitochondria and prelysosomal organelles, but not with slow axonal transport cargoes such as cytoskeletal elements. Khc mutations also impair the development of larval motor axon terminals, causing dystrophic morphology and marked reductions in synaptic bouton numbers. These observations suggest that as the concentration of maternally provided wild-type KHC decreases, axonal organelles transported by kinesin periodically stall. This causes organelle jams that disrupt retrograde as well as anterograde fast axonal transport, leading to defective action potentials, dystrophic terminals, reduced transmitter secretion and progressive distal paralysis. These phenotypes parallel the pathologies of some vertebrate motor neuron diseases, including some forms of amyotrophic lateral sclerosis (ALS), and suggest that impaired fast axonal transport is a key element in those diseases. PMID:8913751

Electrical excitability: a spectrum of properties in the progeny of a single embryonic neuroblast.

PubMed Central

Goodman, C S; Pearson, K G; Spitzer, N C

1980-01-01

We have examined the range of some properties of the progeny of a single embryonic precursor cell in the grasshopper. The approximately 100 progeny of this single neuroblast share certain features such as their transmitter and some aspects of their morphology; at the same time, however, they demonstrate a broad spectrum of electrical properties, from spiking to non-spiking neurons. The first-born progeny are spiking neurons with peripheral axons. Many of the progeny, including all of the last-born, do not generate action potentials. The nonspiking progeny are local intraganglionic neurons and appear to compose a major proportion of the progeny of this neuroblast. All of the nonspiking neurons have calcium inward current channels and can make action potentials when outward current channels are blocked. We propose a model for grasshopper neurogenesis based on cell lineage such that (i) certain features (e.g., transmitter) are shared by the progeny of all cell divisions from a single neuroblast, and (ii) other features (e.g., electrical properties) are shared by the progeny of a given birth position (e.g., first versus last born) from all of the neuroblasts. According to this model, the first-born progeny from all neuroblasts are spiking neurons, whereas the last-born are nonspiking. Images PMID:6246499

Covariation of axon initial segment location and dendritic tree normalizes the somatic action potential

PubMed Central

Hamada, Mustafa S.; Goethals, Sarah; de Vries, Sharon I.; Brette, Romain

2016-01-01

In mammalian neurons, the axon initial segment (AIS) electrically connects the somatodendritic compartment with the axon and converts the incoming synaptic voltage changes into a temporally precise action potential (AP) output code. Although axons often emanate directly from the soma, they may also originate more distally from a dendrite, the implications of which are not well-understood. Here, we show that one-third of the thick-tufted layer 5 pyramidal neurons have an axon originating from a dendrite and are characterized by a reduced dendritic complexity and thinner main apical dendrite. Unexpectedly, the rising phase of somatic APs is electrically indistinguishable between neurons with a somatic or a dendritic axon origin. Cable analysis of the neurons indicated that the axonal axial current is inversely proportional to the AIS distance, denoting the path length between the soma and the start of the AIS, and to produce invariant somatic APs, it must scale with the local somatodendritic capacitance. In agreement, AIS distance inversely correlates with the apical dendrite diameter, and model simulations confirmed that the covariation suffices to normalize the somatic AP waveform. Therefore, in pyramidal neurons, the AIS location is finely tuned with the somatodendritic capacitive load, serving as a homeostatic regulation of the somatic AP in the face of diverse neuronal morphologies. PMID:27930291

N-acetylcysteine protects against motor, optomotor and morphological deficits induced by 6-OHDA in zebrafish larvae.

PubMed

Benvenutti, Radharani; Marcon, Matheus; Reis, Carlos G; Nery, Laura R; Miguel, Camila; Herrmann, Ana P; Vianna, Monica R M; Piato, Angelo

2018-01-01

Parkinson's disease (PD) is the second most common neurodegenerative disorder. In addition to its highly debilitating motor symptoms, non-motor symptoms may precede their motor counterparts by many years, which may characterize a prodromal phase of PD. A potential pharmacological strategy is to introduce neuroprotective agents at an earlier stage in order to prevent further neuronal death. N -acetylcysteine (NAC) has been used against paracetamol overdose hepatotoxicity by restoring hepatic concentrations of glutathione (GSH), and as a mucolytic in chronic obstructive pulmonary disease by reducing disulfide bonds in mucoproteins. It has been shown to be safe for humans at high doses. More recently, several studies have evidenced that NAC has a multifaceted mechanism of action, presenting indirect antioxidant effect by acting as a GSH precursor, besides its anti-inflammatory and neurotrophic effects. Moreover, NAC modulates glutamate release through activation of the cystine-glutamate antiporter in extra-synaptic astrocytes. Its therapeutic benefits have been demonstrated in clinical trials for several neuropsychiatric conditions but has not been tested in PD models yet. In this study, we evaluated the potential of NAC to prevent the damage induced by 6-hydroxydopamine (6-OHDA) on motor, optomotor and morphological parameters in a PD model in larval zebrafish. NAC was able to prevent the motor deficits (total distance, mean speed, maximum acceleration, absolute turn angle and immobility time), optomotor response impairment and morphological alterations (total length and head length) caused by exposure to 6-OHDA, which reinforce and broaden the relevance of its neuroprotective effects. NAC acts in different targets relevant to PD pathophysiology. Further studies and clinical trials are needed to assess this agent as a candidate for prevention and adjunctive treatment of PD.

Marine Food Protection in Testicular Damages Caused by Diabetes Mellitus.

PubMed

Caiaffo, Vitor; Ribeiro de Oliveira, Belisa Duarte; de Sa, Fabricio Bezerra; Neto, Joaqvim Evencio; da Silva Junior, Voldemiro Amaro

2017-01-01

Diabetes Mellitus (DM) is a chronic hyperglycemic condition with major health concern on a global scale. DM is a heterogeneous metabolic disorder stemming from defective insulin secretion and/or resistance to action of insulin. Diabetes is recognized cause of male sexual dysfunction and affects reproductive function in humans and animal models, including the endocrine control of spermatogenesis, erectile dysfunction and ejaculation disorder. Testicular disorder is characteristically marked by reductions of testicle weight, sperm count and motility, as well as changes in the morphology of the seminiferous epithelium. Altered testosterone level is another characteristic of diabetic animals. Studies have demonstrated that DM increases apoptosis in germ cells and lead to the interruption of spermatogenesis, mainly by exerting an influence on Bcl-2 protein and cysteinedependent aspartate-directed proteases. DM also increases oxidative stress in testicular cells and excessive production of radical oxygen species has been demonstrated. Several strategies can be used as means of prevention and/or treatment for diverse types of damage to testicles by DM such as regular physical exercise, stress reduction and food intake of substances with antioxidant potential. A hypoglycemic and antioxidant potential diet, in particular, the seafood, can be a valuable instrument of guard against damage caused by DM, both the systemic level as testicular level. The objective of this review is to summarize evidences that study the antioxidant, anti-inflammatory and anti-apoptosis role of seafood in testicles morphology damages induced by diabetes mellitus. The seafood plays an antioxidant, anti-inflammatory and anti-apoptosis role in testicles morphology damages induced by diabetes mellitus. This relation seems to be associated with Omega-3 and carotenoids (astaxanthin) levels. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

A comparison of manual neuronal reconstruction from biocytin histology or 2-photon imaging: morphometry and computer modeling

PubMed Central

Blackman, Arne V.; Grabuschnig, Stefan; Legenstein, Robert; Sjöström, P. Jesper

2014-01-01

Accurate 3D reconstruction of neurons is vital for applications linking anatomy and physiology. Reconstructions are typically created using Neurolucida after biocytin histology (BH). An alternative inexpensive and fast method is to use freeware such as Neuromantic to reconstruct from fluorescence imaging (FI) stacks acquired using 2-photon laser-scanning microscopy during physiological recording. We compare these two methods with respect to morphometry, cell classification, and multicompartmental modeling in the NEURON simulation environment. Quantitative morphological analysis of the same cells reconstructed using both methods reveals that whilst biocytin reconstructions facilitate tracing of more distal collaterals, both methods are comparable in representing the overall morphology: automated clustering of reconstructions from both methods successfully separates neocortical basket cells from pyramidal cells but not BH from FI reconstructions. BH reconstructions suffer more from tissue shrinkage and compression artifacts than FI reconstructions do. FI reconstructions, on the other hand, consistently have larger process diameters. Consequently, significant differences in NEURON modeling of excitatory post-synaptic potential (EPSP) forward propagation are seen between the two methods, with FI reconstructions exhibiting smaller depolarizations. Simulated action potential backpropagation (bAP), however, is indistinguishable between reconstructions obtained with the two methods. In our hands, BH reconstructions are necessary for NEURON modeling and detailed morphological tracing, and thus remain state of the art, although they are more labor intensive, more expensive, and suffer from a higher failure rate due to the occasional poor outcome of histological processing. However, for a subset of anatomical applications such as cell type identification, FI reconstructions are superior, because of indistinguishable classification performance with greater ease of use, essentially 100% success rate, and lower cost. PMID:25071470

Electrophysiological and structural determinants of electrotonic modulation of repolarization by the activation sequence

PubMed Central

Walton, Richard D.; Benson, Alan P.; Hardy, Matthew E. L.; White, Ed; Bernus, Olivier

2013-01-01

Spatial dispersion of repolarization is known to play an important role in arrhythmogenesis. Electrotonic modulation of repolarization by the activation sequence has been observed in some species and tissue preparations, but to varying extents. Our study sought to determine the mechanisms underlying species- and tissue-dependent electrotonic modulation of repolarization in ventricles. Epi-fluorescence optical imaging of whole rat hearts and pig left ventricular wedges were used to assess epicardial spatial activation and repolarization characteristics. Experiments were supported by computer simulations using realistic geometries. Tight coupling between activation times (AT) and action potential duration (APD) were observed in rat experiments but not in pig. Linear correlation analysis found slopes of −1.03 ± 0.59 and −0.26 ± 0.13 for rat and pig, respectively (p < 0.0001). In rat, maximal dispersion of APD was 11.0 ± 3.1 ms but dispersion of repolarization time (RT) was relatively homogeneous (8.2 ± 2.7, p < 0.0001). However, in pig no such difference was observed between the dispersion of APD and RT (17.8 ± 6.1 vs. 17.7 ± 6.5, respectively). Localized elevations of APD (12.9 ± 8.3%) were identified at ventricular insertion sites of rat hearts both in experiments and simulations. Tissue geometry and action potential (AP) morphology contributed significantly to determining influence of electrotonic modulation. Simulations of a rat AP in a pig geometry decreased the slope of AT and APD relationships by 70.6% whereas slopes were increased by 75.0% when implementing a pig AP in a rat geometry. A modified pig AP, shortened to match the rat APD, showed little coupling between AT and APD with greatly reduced slope compared to the rat AP. Electrotonic modulation of repolarization by the activation sequence is especially pronounced in small hearts with murine-like APs. Tissue architecture and AP morphology play an important role in electrotonic modulation of repolarization. PMID:24115934

Quantitative genetic analysis of agronomic and morphological traits in sorghum, Sorghum bicolor

PubMed Central

Mohammed, Riyazaddin; Are, Ashok K.; Bhavanasi, Ramaiah; Munghate, Rajendra S.; Kavi Kishor, Polavarapu B.; Sharma, Hari C.

2015-01-01

The productivity in sorghum is low, owing to various biotic and abiotic constraints. Combining insect resistance with desirable agronomic and morphological traits is important to increase sorghum productivity. Therefore, it is important to understand the variability for various agronomic traits, their heritabilities and nature of gene action to develop appropriate strategies for crop improvement. Therefore, a full diallel set of 10 parents and their 90 crosses including reciprocals were evaluated in replicated trials during the 2013–14 rainy and postrainy seasons. The crosses between the parents with early- and late-flowering flowered early, indicating dominance of earliness for anthesis in the test material used. Association between the shoot fly resistance, morphological, and agronomic traits suggested complex interactions between shoot fly resistance and morphological traits. Significance of the mean sum of squares for GCA (general combining ability) and SCA (specific combining ability) of all the studied traits suggested the importance of both additive and non-additive components in inheritance of these traits. The GCA/SCA, and the predictability ratios indicated predominance of additive gene effects for majority of the traits studied. High broad-sense and narrow-sense heritability estimates were observed for most of the morphological and agronomic traits. The significance of reciprocal combining ability effects for days to 50% flowering, plant height and 100 seed weight, suggested maternal effects for inheritance of these traits. Plant height and grain yield across seasons, days to 50% flowering, inflorescence exsertion, and panicle shape in the postrainy season showed greater specific combining ability variance, indicating the predominance of non-additive type of gene action/epistatic interactions in controlling the expression of these traits. Additive gene action in the rainy season, and dominance in the postrainy season for days to 50% flowering and plant height suggested G X E interactions for these traits. PMID:26579183

Electrically evoked compound action potentials recorded from the sheep spinal cord.

PubMed

Parker, John L; Karantonis, Dean M; Single, Peter S; Obradovic, Milan; Laird, James; Gorman, Robert B; Ladd, Leigh A; Cousins, Michael J

2013-01-01

The study aims to characterize the electrical response of dorsal column axons to depolarizing stimuli to help understand the mechanisms of spinal cord stimulation (SCS) for the relief of chronic pain. We recorded electrically evoked compound action potentials (ECAPs) during SCS in 10 anesthetized sheep using stimulating and recording electrodes on the same epidural SCS leads. A novel stimulating and recording system allowed artifact contamination of the ECAP to be minimized. The ECAP in the sheep spinal cord demonstrates a triphasic morphology, with P1, N1, and P2 peaks. The amplitude of the ECAP varies along the length of the spinal cord, with minimum amplitudes recorded from electrodes positioned over each intervertebral disc, and maximum amplitudes recorded in the midvertebral positions. This anatomically correlated depression of ECAP also correlates with the areas of the spinal cord with the highest thresholds for stimulation; thus regions of weakest response invariably had least sensitivity to stimulation by as much as a factor of two. The choice of stimulating electrode location can therefore have a profound effect on the power consumption for an implanted stimulator for SCS. There may be optimal positions for stimulation in the sheep, and this observation may translate to humans. Almost no change in conduction velocity (∼100 ms) was observed with increasing currents from threshold to twice threshold, despite increased Aβ fiber recruitment. Amplitude of sheep Aβ fiber potentials during SCS exhibit dependence on electrode location, highlighting potential optimization of Aβ recruitment and power consumption in SCS devices. © 2013 International Neuromodulation Society.

Phytol shows anti-angiogenic activity and induces apoptosis in A549 cells by depolarizing the mitochondrial membrane potential.

PubMed

Sakthivel, Ravi; Malar, Dicson Sheeja; Devi, Kasi Pandima

2018-06-13

In the present study, the antiproliferative activity of phytol and its mechanism of action against human lung adenocarcinoma cell line A549 were studied in detail. Results showed that phytol exhibited potent antiproliferative activity against A549 cells in a dose and time-dependent manner with an IC 50 value of 70.81 ± 0.32 μM and 60.7 ± 0.47 μM at 24 and 48 h, respectively. Phytol showed no adverse toxic effect in normal human lung cells (L-132), but mild toxic effect was observed when treated with maximum dose (67 and 84 μM). No membrane-damaging effect was evidenced by PI staining and SEM analysis. The results of mitochondrial membrane potential analysis, cell cycle analysis, FT-IR and Western blotting analysis clearly demonstrated the molecular mechanism of phytol as induction of apoptosis in A549 cells, as evidenced by formation of shrinked cell morphology with membrane blebbing, depolarization of mitochondrial membrane potential, increased cell population in the sub-G0 phase, band variation in the DNA and lipid region, downregulation of Bcl-2, upregulation of Bax and the activation of caspase-9 and -3. In addition, phytol inhibited the CAM vascular growth as evidenced by CAM assay, which positively suggests that phytol has anti-angiogenic potential. Taken together, these findings clearly demonstrate the mode of action by which phytol induces cell death in A549 lung adenocarcinoma cells. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Relationships between morphology and physiology of pyramid-pyramid single axon connections in rat neocortex in vitro.

PubMed Central

Deuchars, J; West, D C; Thomson, A M

1994-01-01

1. Double intracellular recordings were made from 1163 pairs of pyramidal neurones in layer V-VI of the rat somatomotor cortex in vitro using sharp electrodes filled with biocytin. Monosynaptically connected pairs of cells were identified when an action potential in one could elicit a constant latency excitatory postsynaptic potential (EPSP) in the other and the cells were filled with biocytin. Labelled cells were subsequently identified histologically with avidin-horseradish peroxidase. 2. Thirty-four pairs of cells were found to be monosynaptically connected. Fifteen of these pairs were sufficiently stable for electrophysiological recordings and three of these were recovered sufficiently to permit full morphological reconstruction. 3. The EPSP recorded between the first pair of pyramids varied in amplitude between 0 and 3 mV (mean 1.33 +/- 1.06 mV) and fluctuated considerably (coefficient of variation, 0.796). This was largely due to a high incidence of apparent failures of transmission. On reconstruction two boutons from the presynaptic pyramid axon were in close apposition to the proximal portions of basal dendrites of the postsynaptic cell. 4. In the second pair of pyramids the EPSP had a mean amplitude of 1.06 mV, and displayed a 10-90% rise time of 2.8 ms and a width at half-amplitude of 23 ms. This EPSP did not alter significantly with changes in membrane potential at the soma. The presynaptic axon closely apposed the distal apical dendrite of the postsynaptic cell in eight places. 5. In the third pair of pyramids, the EPSPs, recorded at a relatively depolarized membrane potential, were long lasting and could elicit slow dendritic spikes with long and variable latencies. These slow spikes suggested that the postsynaptic recording site was dendritic and on reconstruction a possible location was identified on the apical dendrite. A total of five presynaptic boutons closely apposed three separate, proximal branches of the postsynaptic apical dendrite. 6. These results provide the first illustration of a morphological basis for variations in functional properties of pyramid-pyramid connections in the neocortex. Images Figure 1 Figure 3 Figure 5 PMID:7965856

Species specific effects of three morphologically different belowground seagrasses on sediment properties

NASA Astrophysics Data System (ADS)

Rattanachot, Ekkalak; Prathep, Anchana

2015-12-01

Roots and rhizomes of seagrass play an important role in coastline zone by anchoring the substrate firmly which prevent resuspension and also controlling sediment biogeochemistry. The aim of this study was to compare the physical and chemical differences of sediments for 3 seagrass species, which have different root morphology between summer (February 2013) and the monsoon month (September 2013). Seven seagrass communities were studied and are: the mono stand of Halophila ovalis, Thalassia hemprichii, and Cymodocea rotundata, the mixed patches of H. ovalis with T. hemprichii, H. ovalis with C. rotundata, and T. hemprichii with C. rotundata and the mixed patches of 3 seagrass species. The roots of seagrasses were the main driver of differences in sediment properties; the branched, long root species, C. rotundata, showed an increasing redox potential by means of oxygen releasing from their roots. The unbranched, long root with dense root hair species, T. hemprichii, tended to cause more poorly sorted sediments. The carbon storage was also estimated and results showed a trend of higher organic carbon density was in the multispecific patches, the mono specific patches and bare sand, respectively. Season also influenced the sediment properties; high wave action in the monsoon stirred up the sediments, this led to lower organic carbon density and high redox potential. Our results suggest that the roots of seagrass species both increase and decrease sediment properties.

Evidence from immunoneutralization and antisense studies that the inhibitory actions of glucocorticoids on growth hormone release in vitro require annexin 1 (lipocortin 1)

PubMed Central

Taylor, A D; Christian, H C; Morris, J F; Flower, R J; Buckingham, J C

2000-01-01

Our previous studies have identified a role for annexin 1 as a mediator of glucocorticoid action in the neuroendocrine system. The present study centred on growth hormone (GH) and exploited antisense and immunoneutralization strategies to examine in vitro the potential role of annexin 1 in effecting the regulatory actions of glucocorticoids on the secretion of this pituitary hormone. Rat anterior pituitary tissue responded in vitro to growth hormone releasing hormone, forskolin, 8-Bromo-cyclic adenosine 3′5′-monophosphate (8-Br-cyclic AMP) and an L-Ca2+ channel opener (BAY K8644) with concentration-dependent increases GH release which were readily inhibited by corticosterone and dexamethasone. The inhibitory actions of the steroids on GH release elicited by the above secretagogues were effectively reversed by an annexin 1 antisense oligodeoxynucleotide (ODN), but not by control (sense or scrambled) ODNs, as also were the glucocorticoid-induced increases in annexin 1. Similarly, a specific anti-annexin 1 monoclonal antibody quenched the corticosterone-induced suppression of secretagogue-evoked GH release while an isotype matched control antibody was without effect. Transmission electron micrographs showed that the integrity and ultrastructural morphology of the pituitary cells were well preserved at the end of the incubation and unaffected by exposure to the ODNs, antibodies, steroids or secretagogues. The results provide novel evidence for a role for annexin 1 as a mediator of the inhibitory actions of glucocorticoids on the secretion of GH by the anterior pituitary gland and suggest that its actions are effected at a point distal to the formation of cyclic AMP and Ca2+ entry. PMID:11090102

Evidence from immunoneutralization and antisense studies that the inhibitory actions of glucocorticoids on growth hormone release in vitro require annexin 1 (lipocortin 1).

PubMed

Taylor, A D; Christian, H C; Morris, J F; Flower, R J; Buckingham, J C

2000-12-01

1. Our previous studies have identified a role for annexin 1 as a mediator of glucocorticoid action in the neuroendocrine system. The present study centred on growth hormone (GH) and exploited antisense and immunoneutralization strategies to examine in vitro the potential role of annexin 1 in effecting the regulatory actions of glucocorticoids on the secretion of this pituitary hormone. 2. Rat anterior pituitary tissue responded in vitro to growth hormone releasing hormone, forskolin, 8-Bromo-cyclic adenosine 3'5'-monophosphate (8-Br-cyclic AMP) and an L-Ca(2+) channel opener (BAY K8644) with concentration-dependent increases GH release which were readily inhibited by corticosterone and dexamethasone. 3. The inhibitory actions of the steroids on GH release elicited by the above secretagogues were effectively reversed by an annexin 1 antisense oligodeoxynucleotide (ODN), but not by control (sense or scrambled) ODNs, as also were the glucocorticoid-induced increases in annexin 1. Similarly, a specific anti-annexin 1 monoclonal antibody quenched the corticosterone-induced suppression of secretagogue-evoked GH release while an isotype matched control antibody was without effect. 4. Transmission electron micrographs showed that the integrity and ultrastructural morphology of the pituitary cells were well preserved at the end of the incubation and unaffected by exposure to the ODNs, antibodies, steroids or secretagogues. 5. The results provide novel evidence for a role for annexin 1 as a mediator of the inhibitory actions of glucocorticoids on the secretion of GH by the anterior pituitary gland and suggest that its actions are effected at a point distal to the formation of cyclic AMP and Ca(2+) entry.

Action potentials reliably invade axonal arbors of rat neocortical neurons

PubMed Central

Cox, Charles L.; Denk, Winfried; Tank, David W.; Svoboda, Karel

2000-01-01

Neocortical pyramidal neurons have extensive axonal arborizations that make thousands of synapses. Action potentials can invade these arbors and cause calcium influx that is required for neurotransmitter release and excitation of postsynaptic targets. Thus, the regulation of action potential invasion in axonal branches might shape the spread of excitation in cortical neural networks. To measure the reliability and extent of action potential invasion into axonal arbors, we have used two-photon excitation laser scanning microscopy to directly image action-potential-mediated calcium influx in single varicosities of layer 2/3 pyramidal neurons in acute brain slices. Our data show that single action potentials or bursts of action potentials reliably invade axonal arbors over a range of developmental ages (postnatal 10–24 days) and temperatures (24°C-30°C). Hyperpolarizing current steps preceding action potential initiation, protocols that had previously been observed to produce failures of action potential propagation in cultured preparations, were ineffective in modulating the spread of action potentials in acute slices. Our data show that action potentials reliably invade the axonal arbors of neocortical pyramidal neurons. Failures in synaptic transmission must therefore originate downstream of action potential invasion. We also explored the function of modulators that inhibit presynaptic calcium influx. Consistent with previous studies, we find that adenosine reduces action-potential-mediated calcium influx in presynaptic terminals. This reduction was observed in all terminals tested, suggesting that some modulatory systems are expressed homogeneously in most terminals of the same neuron. PMID:10931955

Ethylhexylglycerin Impairs Membrane Integrity and Enhances the Lethal Effect of Phenoxyethanol

PubMed Central

Langsrud, Solveig; Steinhauer, Katrin; Lüthje, Sonja; Weber, Klaus; Goroncy-Bermes, Peter; Holck, Askild L.

2016-01-01

Preservatives are added to cosmetics to protect the consumers from infections and prevent product spoilage. The concentration of preservatives should be kept as low as possible and this can be achieved by adding potentiating agents. The aim of the study was to investigate the mechanisms behind potentiation of the bactericidal effect of a commonly used preservative, 2-phenoxyethanol (PE), by the potentiating agent ethylhexylglycerin (EHG). Sub-lethal concentrations of EHG (0.075%) and PE (0.675%) in combination led to rapid killing of E. coli (> 5 log reduction of cfu after 30 min), leakage of cellular constituents, disruption of the energy metabolism, morphological deformities of cells and condensation of DNA. Used alone, EHG disrupted the membrane integrity even at low concentrations. In conclusion, sub-lethal concentrations of EHG potentiate the effect of PE through damage of the cell membrane integrity. Thus, adding EHG to PE in a 1:9 ratio has a similar effect on membrane damage and bacterial viability as doubling the concentration of PE. This study provides insight about the mechanism of action of a strong potentiating agent, EHG, which is commonly used in cosmetics together with PE. PMID:27783695

Antimicrobial effect and mode of action of terpeneless cold-pressed Valencia orange essential oil on methicillin-resistant Staphylococcus aureus.

PubMed

Muthaiyan, A; Martin, E M; Natesan, S; Crandall, P G; Wilkinson, B J; Ricke, S C

2012-05-01

The objectives of this study were to evaluate the antistaphylococcal effect and elucidate the mechanism of action of orange essential oil against antibiotic-resistant Staphylococcus aureus strains. The inhibitory effect of commercial orange essential oil (EO) against six Staph. aureus strains was tested using disc diffusion and agar dilution methods. The mechanism of EO action on MRSA was analysed by transcriptional profiling. Morphological changes of EO-treated Staph. aureus were examined using transmission electron microscopy. Results showed that 0·1% of terpeneless cold-pressed Valencia orange oil (CPV) induced the cell wall stress stimulon consistent with the inhibition of cell wall synthesis. Transmission electron microscopic observation revealed cell lysis and suggested a cell wall lysis-related mechanism of CPV. CPV inhibits the growth of Staph. aureus, causes gene expression changes consistent with the inhibition of cell wall synthesis, and triggers cell lysis. Multiple antibiotics resistance is becoming a serious problem in the management of Staph. aureus infections. In this study, the altered expression of cell wall-associated genes and subsequent cell lysis in MRSA caused by CPV suggest that it may be a potential antimicrobial agent to control antibiotic-resistant Staph. aureus. © 2012 The Authors. Journal of Applied Microbiology © 2012 The Society for Applied Microbiology.

Effects of methotrexate on the viscoelastic properties of single cells probed by atomic force microscopy.

PubMed

Li, Mi; Liu, Lianqing; Xiao, Xiubin; Xi, Ning; Wang, Yuechao

2016-10-01

Methotrexate is a commonly used anti-cancer chemotherapy drug. Cellular mechanical properties are fundamental parameters that reflect the physiological state of a cell. However, so far the role of cellular mechanical properties in the actions of methotrexate is still unclear. In recent years, probing the behaviors of single cells with the use of atomic force microscopy (AFM) has contributed much to the field of cell biomechanics. In this work, with the use of AFM, the effects of methotrexate on the viscoelastic properties of four types of cells were quantitatively investigated. The inhibitory and cytotoxic effects of methotrexate on the proliferation of cells were observed by optical and fluorescence microscopy. AFM indenting was used to measure the changes of cellular viscoelastic properties (Young's modulus and relaxation time) by using both conical tip and spherical tip, quantitatively showing that the stimulation of methotrexate resulted in a significant decrease of both cellular Young's modulus and relaxation times. The morphological changes of cells induced by methotrexate were visualized by AFM imaging. The study improves our understanding of methotrexate action and offers a novel way to quantify drug actions at the single-cell level by measuring cellular viscoelastic properties, which may have potential impacts on developing label-free methods for drug evaluation.

Assessment of Mouse Germinal Vesicle Stage Oocyte Quality by Evaluating the Cumulus Layer, Zona Pellucida, and Perivitelline Space

PubMed Central

Liu, Ying-Lei; Chen, Ying; Zhou, Cheng-Jie; Wu, Sha-Na; Shen, Jiang-Peng; Liang, Cheng-Guang

2014-01-01

To improve the outcome of assisted reproductive technology (ART) for patients with ovulation problems, it is necessary to retrieve and select germinal vesicle (GV) stage oocytes with high developmental potential. Oocytes with high developmental potential are characterized by their ability to undergo proper maturation, fertilization, and embryo development. In this study, we analyzed morphological traits of GV stage mouse oocytes, including cumulus cell layer thickness, zona pellucida thickness, and perivitelline space width. Then, we assessed the corresponding developmental potential of each of these oocytes and found that it varies across the range measured for each morphological trait. Furthermore, by manipulating these morphological traits in vitro, we were able to determine the influence of morphological variation on oocyte developmental potential. Manually altering the thickness of the cumulus layer showed strong effects on the fertilization and embryo development potentials of oocytes, whereas manipulation of zona pellucida thickness effected the oocyte maturation potential. Our results provide a systematic detailed method for selecting GV stage oocytes based on a morphological assessment approach that would benefit for several downstream ART applications. PMID:25144310

Mitochondria-dependent apoptogenic activity of the aqueous root extract of Croton membranaceus against human BPH-1 cells.

PubMed

Afriyie, D K; Asare, G A; Bugyei, K; Lin, J; Peng, J; Hong, Z

2015-01-15

Croton membranaceus aqueous root extract (CMARE) is among the widely used phytotherapeutics in Ghana for the management of benign prostatic hyperplasia (BPH) and prostate cancer. However, the mechanism of action of CMARE remains to be elucidated. This study aimed to establish whether apoptosis is involved in the antiproliferative effect of CMARE on human BPH-1 cells. We determined the effect of treatment with 0, 1, 3, and 5 mg/mL CMARE for 24, 48, and 72 h on the viability and morphology of BPH-1 cells using the MMT assay and phase-contrast microscopy, respectively. We examined the apoptosis-inducing effects of CMARE after 48 h at the cellular level using Hoescht 33258 and JC-1 dye staining and flow cytometry analysis. We performed reverse transcription polymerase chain reaction and Western blotting to confirm the apoptotic effects of CMARE at the molecular level. CMARE induced a significant dose-dependent inhibition in the proliferation of BPH-1 cells (P < 0.05) and an alteration in their morphology and a reduction their density. Furthermore, CMARE induced dose-dependent staining of the nuclear chromatin, significant DNA fragmentation with G₀/G₁ sub-diploid cells (P < 0.01), and loss of the mitochondrial membrane potential in the treated cells compared to the controls after 48 h (P < 0.01). Additionally, while CMARE induced a significant upregulation of the mRNA and protein levels of Bax, those of Bcl2 did not change significantly. Therefore, induction of mitochondria-dependent apoptosis of BPH-1 cells may be a possible mechanism of action of CMARE.

Interspeaker Variability in Hard Palate Morphology and Vowel Production

ERIC Educational Resources Information Center

Lammert, Adam; Proctor, Michael; Narayanan, Shrikanth

2013-01-01

Purpose: Differences in vocal tract morphology have the potential to explain interspeaker variability in speech production. The potential acoustic impact of hard palate shape was examined in simulation, in addition to the interplay among morphology, articulation, and acoustics in real vowel production data. Method: High-front vowel production from…

Cytotoxicity of aflatoxin on red blood corpuscles

DOE Office of Scientific and Technical Information (OSTI.GOV)

Verma, R.J.; Raval, P.J.

The exact mechanism of aflatoxin action is not clearly understood. In the present investigation the authors report morphological aberrations and increased rate of hemolysis caused by aflatoxins in vitro.

The Antimicrobial Mechanism of Action of Epsilon-Poly-l-Lysine

PubMed Central

Hyldgaard, Morten; Mygind, Tina; Vad, Brian S.; Stenvang, Marcel; Otzen, Daniel E.

2014-01-01

Epsilon-poly-l-lysine (ε-PL) is a natural antimicrobial cationic peptide which is generally regarded as safe (GRAS) as a food preservative. Although its antimicrobial activity is well documented, its mechanism of action is only vaguely described. The aim of this study was to clarify ε-PL's mechanism of action using Escherichia coli and Listeria innocua as model organisms. We examined ε-PL's effect on cell morphology and membrane integrity and used an array of E. coli deletion mutants to study how specific outer membrane components affected the action of ε-PL. We furthermore studied its interaction with lipid bilayers using membrane models. In vitro cell studies indicated that divalent cations and the heptose I and II phosphate groups in the lipopolysaccharide layer of E. coli are critical for ε-PL's binding efficiency. ε-PL removed the lipopolysaccharide layer and affected cell morphology of E. coli, while L. innocua underwent minor morphological changes. Propidium iodide staining showed that ε-PL permeabilized the cytoplasmic membrane in both species, indicating the membrane as the site of attack. We compared the interaction with neutral or negatively charged membrane systems and showed that the interaction with ε-PL relied on negative charges on the membrane. Suspended membrane vesicles were disrupted by ε-PL, and a detergent-like disruption of E. coli membrane was confirmed by atomic force microscopy imaging of supported lipid bilayers. We hypothesize that ε-PL destabilizes membranes in a carpet-like mechanism by interacting with negatively charged phospholipid head groups, which displace divalent cations and enforce a negative curvature folding on membranes that leads to formation of vesicles/micelles. PMID:25304506

The antimicrobial mechanism of action of epsilon-poly-l-lysine.

PubMed

Hyldgaard, Morten; Mygind, Tina; Vad, Brian S; Stenvang, Marcel; Otzen, Daniel E; Meyer, Rikke L

2014-12-01

Epsilon-poly-l-lysine (ε-PL) is a natural antimicrobial cationic peptide which is generally regarded as safe (GRAS) as a food preservative. Although its antimicrobial activity is well documented, its mechanism of action is only vaguely described. The aim of this study was to clarify ε-PL's mechanism of action using Escherichia coli and Listeria innocua as model organisms. We examined ε-PL's effect on cell morphology and membrane integrity and used an array of E. coli deletion mutants to study how specific outer membrane components affected the action of ε-PL. We furthermore studied its interaction with lipid bilayers using membrane models. In vitro cell studies indicated that divalent cations and the heptose I and II phosphate groups in the lipopolysaccharide layer of E. coli are critical for ε-PL's binding efficiency. ε-PL removed the lipopolysaccharide layer and affected cell morphology of E. coli, while L. innocua underwent minor morphological changes. Propidium iodide staining showed that ε-PL permeabilized the cytoplasmic membrane in both species, indicating the membrane as the site of attack. We compared the interaction with neutral or negatively charged membrane systems and showed that the interaction with ε-PL relied on negative charges on the membrane. Suspended membrane vesicles were disrupted by ε-PL, and a detergent-like disruption of E. coli membrane was confirmed by atomic force microscopy imaging of supported lipid bilayers. We hypothesize that ε-PL destabilizes membranes in a carpet-like mechanism by interacting with negatively charged phospholipid head groups, which displace divalent cations and enforce a negative curvature folding on membranes that leads to formation of vesicles/micelles. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Purification, Characterization, and Mode of Action of Plantaricin GZ1-27, a Novel Bacteriocin against Bacillus cereus.

PubMed

Du, Hechao; Yang, Jie; Lu, Xiaohong; Lu, Zhaoxin; Bie, Xiaomei; Zhao, Haizhen; Zhang, Chong; Lu, Fengxia

2018-05-09

Bacillus cereus is an opportunistic pathogen that causes foodborne diseases. We isolated a novel bacteriocin, designated plantaricin GZ1-27, and elucidated its mode of action against B. cereus. Plantaricin GZ1-27 was purified using ammonium sulfate precipitation, gel-filtration chromatography, and RP-HPLC. MALDI-TOF/MS revealed that its molecular mass was 975 Da, and Q-TOF-MS/MS analysis predicted the amino acid sequence as VSGPAGPPGTH. Plantaricin GZ1-27 showed thermostability and pH stability. The antibacterial mechanism was investigated using flow cytometry, confocal laser-scanning microscopy, scanning and transmission electron microscopy, and RT-PCR, which revealed that GZ1-27 increased cell membrane permeability, triggered K + leakage and pore formation, damaged cell membrane integrity, altered cell morphology and intracellular organization, and reduced the expression of genes related to cytotoxin production, peptidoglycan synthesis, and cell division. These results suggest that plantaricin GZ1-27 effectively inhibits B. cereus at both the cellular and the molecular levels and is a potential natural food preservative targeting B. cereus.

Methamphetamine Regulation of Firing Activity of Dopamine Neurons

PubMed Central

Lin, Min; Sambo, Danielle

2016-01-01

Methamphetamine (METH) is a substrate for the dopamine transporter that increases extracellular dopamine levels by competing with dopamine uptake and increasing reverse transport of dopamine via the transporter. METH has also been shown to alter the excitability of dopamine neurons. The mechanism of METH regulation of the intrinsic firing behaviors of dopamine neurons is less understood. Here we identified an unexpected and unique property of METH on the regulation of firing activity of mouse dopamine neurons. METH produced a transient augmentation of spontaneous spike activity of midbrain dopamine neurons that was followed by a progressive reduction of spontaneous spike activity. Inspection of action potential morphology revealed that METH increased the half-width and produced larger coefficients of variation of the interspike interval, suggesting that METH exposure affected the activity of voltage-dependent potassium channels in these neurons. Since METH has been shown to affect Ca2+ homeostasis, the unexpected findings that METH broadened the action potential and decreased the amplitude of afterhyperpolarization led us to ask whether METH alters the activity of Ca2+-activated potassium (BK) channels. First, we identified BK channels in dopamine neurons by their voltage dependence and their response to a BK channel blocker or opener. While METH suppressed the amplitude of BK channel-mediated unitary currents, the BK channel opener NS1619 attenuated the effects of METH on action potential broadening, afterhyperpolarization repression, and spontaneous spike activity reduction. Live-cell total internal reflection fluorescence microscopy, electrophysiology, and biochemical analysis suggest METH exposure decreased the activity of BK channels by decreasing BK-α subunit levels at the plasma membrane. SIGNIFICANCE STATEMENT Methamphetamine (METH) competes with dopamine uptake, increases dopamine efflux via the dopamine transporter, and affects the excitability of dopamine neurons. Here, we identified an unexpected property of METH on dopamine neuron firing activity. METH transiently increased the spontaneous spike activity of dopamine neurons followed by a progressive reduction of the spontaneous spike activity. METH broadened the action potentials, increased coefficients of variation of the interspike interval, and decreased the amplitude of afterhyperpolarization, which are consistent with changes in the activity of Ca2+-activated potassium (BK) channels. We found that METH decreased the activity of BK channels by stimulating BK-α subunit trafficking. Thus, METH modulation of dopamine neurotransmission and resulting behavioral responses is, in part, due to METH regulation of BK channel activity. PMID:27707972

Characteristics of action potentials and their underlying outward currents in rat taste receptor cells.

PubMed

Chen, Y; Sun, X D; Herness, S

1996-02-01

1. Taste receptor cells produce action potentials as a result of transduction mechanisms that occur when these cells are stimulated with tastants. These action potentials are thought to be key signaling events in relaying information to the central nervous system. We explored the ionic basis of action potentials from dissociated posterior rat taste cells using the patch-clamp recording technique in both voltage-clamp and current-clamp modes. 2. Action potentials were evoked by intracellular injection of depolarizing current pulses from a holding potential of -80 mV. The threshold potential for firing of action potentials was approximately -35 mV; the input resistance of these cells averaged 6.9 G omega. With long depolarizing pulses, two or three action potentials could be elicited with successive attenuation of the spike height. Afterhyperpolarizations were observed often. 3. Both sodium and calcium currents contribute to depolarizing phases of the action potential. Action potentials were blocked completely in the presence of the sodium channel blocker tetrodotoxin. Calcium contributions could be visualized as prolonged calcium plateaus when repolarizing potassium currents were blocked and barium was used as a charge carrier. 4. Outward currents were composed of sustained delayed rectifier current, transient potassium current, and calcium-activated potassium current. Transient and sustained potassium currents activated close to -30 mV and increased monotonically with further depolarization. Up to half the outward current inactivated with decay constants on the order of seconds. Sustained and transient currents displayed steep voltage dependence in conductance and inactivation curves. Half inactivation occurred at -20 +/- 3.1 mV (mean +/- SE) with a decrease of 11.2 +/- 0.5 mV per e-fold. Half maximal conductance occurred at 3.6 +/- 1.8 mV and increased 12.2 +/- 0.6 mV per e-fold. Calcium-activated potassium current was evidenced by application of apamin and the use of calcium-free bathing solution. It was most obvious at more depolarized holding potentials that inactivated much of the transient and sustained outward currents. 5. Potassium currents contribute to both the repolarization and afterhyperpolarization phases of the action potential. These currents were blocked by bath application of tetraethylammonium, which also substantially broadened the action potential. Application of 4-aminopyridine was able to selectively block transient potassium currents without affecting sustained currents. This also broadened the action potential as well as eliminated the afterhyperpolarization. 6. A second type of action potential was observed that differed in duration. These slow action potentials had t1/2 durations of 9.6 ms compared with 1.4 ms for fast action potentials. Input resistances of the two groups were indistinguishable. Approximately one-fourth of the cells eliciting action potentials were of the slow type. 7. Cells eliciting fast action potentials had large outward currents capable of producing a quick repolarization, whereas cells with slow action potentials had small outward currents by comparison. The average values of fast cells were 2,563 pA and 1.4 ms compared with 373 pA and 9.6 ms for slow cells. Current and duration values were related exponentially. No significant difference was noted for inward currents. 8. These results suggest that many taste receptor cells conduct action potentials, which may be classified broadly into two groups on the basis of action potential duration and potassium current magnitude. These groups may be related to cell turnover. The physiological role of action potentials remains to be elucidated but may be important for communication within the taste bud as well as to the afferent nerve.

State and location dependence of action potential metabolic cost in cortical pyramidal neurons.

PubMed

Hallermann, Stefan; de Kock, Christiaan P J; Stuart, Greg J; Kole, Maarten H P

2012-06-03

Action potential generation and conduction requires large quantities of energy to restore Na(+) and K(+) ion gradients. We investigated the subcellular location and voltage dependence of this metabolic cost in rat neocortical pyramidal neurons. Using Na(+)/K(+) charge overlap as a measure of action potential energy efficiency, we found that action potential initiation in the axon initial segment (AIS) and forward propagation into the axon were energetically inefficient, depending on the resting membrane potential. In contrast, action potential backpropagation into dendrites was efficient. Computer simulations predicted that, although the AIS and nodes of Ranvier had the highest metabolic cost per membrane area, action potential backpropagation into the dendrites and forward propagation into axon collaterals dominated energy consumption in cortical pyramidal neurons. Finally, we found that the high metabolic cost of action potential initiation and propagation down the axon is a trade-off between energy minimization and maximization of the conduction reliability of high-frequency action potentials.

The antifungal activity and membrane-disruptive action of dioscin extracted from Dioscorea nipponica.

PubMed

Cho, Jaeyong; Choi, Hyemin; Lee, Juneyoung; Kim, Mi-Sun; Sohn, Ho-Yong; Lee, Dong Gun

2013-03-01

Dioscin is a kind of steroidal saponin isolated from the root bark of wild yam Dioscorea nipponica. We investigated the antifungal effect of dioscin against different fungal strains and its antifungal mechanism(s) in Candida albicans cells. Using the propidium iodide assay and calcein-leakage measurement, we confirmed that dioscin caused fungal membrane damage. Furthermore, we evaluated the ability of dioscin to disrupt the plasma membrane potential, using 3,3'-dipropylthiadicarbocyanine iodide [DiSC(3)(5)] and bis-(1,3-dibarbituric acid)-trimethine oxanol [DiBAC(4)(3)]. Cells stained with the dyes had a significant increase in fluorescent intensity after exposure to dioscin, indicating that dioscin has an effect on the membrane potential. To visualize the effect of dioscin on the cell membrane, we synthesized rhodamine-labeled giant unilamellar vesicles (GUVs) mimicking the outer leaflet of the plasma membrane of C. albicans. As seen in the result, the membrane disruptive action of dioscin caused morphological change and rhodamine leakage of the GUVs. In three-dimensional contour-plot analysis using flow cytometry, we observed a decrease in cell size, which is in agreement with our result from the GUV assay. These results suggest that dioscin exerts a considerable antifungal activity by disrupting the structure in membrane after invading into the fungal membrane, resulting in fungal cell death. Copyright © 2012 Elsevier B.V. All rights reserved.

A novel numerical model to predict the morphological behavior of magnetic liquid marbles using coarse grained molecular dynamics concepts

NASA Astrophysics Data System (ADS)

Polwaththe-Gallage, Hasitha-Nayanajith; Sauret, Emilie; Nguyen, Nam-Trung; Saha, Suvash C.; Gu, YuanTong

2018-01-01

Liquid marbles are liquid droplets coated with superhydrophobic powders whose morphology is governed by the gravitational and surface tension forces. Small liquid marbles take spherical shapes, while larger liquid marbles exhibit puddle shapes due to the dominance of gravitational forces. Liquid marbles coated with hydrophobic magnetic powders respond to an external magnetic field. This unique feature of magnetic liquid marbles is very attractive for digital microfluidics and drug delivery systems. Several experimental studies have reported the behavior of the liquid marbles. However, the complete behavior of liquid marbles under various environmental conditions is yet to be understood. Modeling techniques can be used to predict the properties and the behavior of the liquid marbles effectively and efficiently. A robust liquid marble model will inspire new experiments and provide new insights. This paper presents a novel numerical modeling technique to predict the morphology of magnetic liquid marbles based on coarse grained molecular dynamics concepts. The proposed model is employed to predict the changes in height of a magnetic liquid marble against its width and compared with the experimental data. The model predictions agree well with the experimental findings. Subsequently, the relationship between the morphology of a liquid marble with the properties of the liquid is investigated. Furthermore, the developed model is capable of simulating the reversible process of opening and closing of the magnetic liquid marble under the action of a magnetic force. The scaling analysis shows that the model predictions are consistent with the scaling laws. Finally, the proposed model is used to assess the compressibility of the liquid marbles. The proposed modeling approach has the potential to be a powerful tool to predict the behavior of magnetic liquid marbles serving as bioreactors.

The fish gill: site of action and model for toxic effects of environmental pollutants.

PubMed Central

Evans, D H

1987-01-01

The gill epithelium is the site of gas exchange, ionic regulation, acid-base balance, and nitrogenous waste excretion by fishes. The last three processes are controlled by passive and active transport of various solutes across the epithelium. Various environmental pollutants (e.g., heavy metals, acid rain, and organic xenobiotics) have been found to affect the morphology of the gill epithelium. Associated with these morphological pathologies, one finds alterations in blood ionic levels, as well as gill Na,K-activated ATPase activity and ionic fluxes. Such physiological disturbances may underly the toxicities of these pollutants. In addition, the epithelial transport steps which are affected in the fish gill model resemble those described in the human gut and kidney, sites of action of a variety of environmental toxins. Images FIGURE 1. a FIGURE 1. b FIGURE 3. PMID:3297663

Voltage-gated sodium channel expression and action potential generation in differentiated NG108-15 cells.

PubMed

Liu, Jinxu; Tu, Huiyin; Zhang, Dongze; Zheng, Hong; Li, Yu-Long

2012-10-25

The generation of action potential is required for stimulus-evoked neurotransmitter release in most neurons. Although various voltage-gated ion channels are involved in action potential production, the initiation of the action potential is mainly mediated by voltage-gated Na+ channels. In the present study, differentiation-induced changes of mRNA and protein expression of Na+ channels, Na+ currents, and cell membrane excitability were investigated in NG108-15 cells. Whole-cell patch-clamp results showed that differentiation (9 days) didn't change cell membrane excitability, compared to undifferentiated state. But differentiation (21 days) induced the action potential generation in 45.5% of NG108-15 cells (25/55 cells). In 9-day-differentiated cells, Na+ currents were mildly increased, which was also found in 21-day differentiated cells without action potential. In 21-day differentiated cells with action potential, Na+ currents were significantly enhanced. Western blot data showed that the expression of Na+ channels was increased with differentiated-time dependent manner. Single-cell real-time PCR data demonstrated that the expression of Na+ channel mRNA was increased by 21 days of differentiation in NG108-15 cells. More importantly, the mRNA level of Na+ channels in cells with action potential was higher than that in cells without action potential. Differentiation induces expression of voltage-gated Na+ channels and action potential generation in NG108-15 cells. A high level of the Na+ channel density is required for differentiation-triggered action potential generation.

Morphological awareness and reading comprehension: Examining mediating factors.

PubMed

Levesque, Kyle C; Kieffer, Michael J; Deacon, S Hélène

2017-08-01

The relation between morphological awareness-defined as the awareness of and ability to manipulate the smallest units of meaning in language-and reading comprehension remains in need of specification. In this study, we evaluated four potential intervening variables through which morphological awareness may contribute indirectly to reading comprehension. We assessed word reading and vocabulary as well as children's ability to read and analyze the meaning of morphologically complex words (morphological decoding and morphological analysis, respectively). Controls of phonological awareness and nonverbal ability were included in the model. Participants were 221 English-speaking children in Grade 3. Multivariate path analyses revealed evidence of two indirect relations and one direct relation between morphological awareness and reading comprehension. In the first indirect path, morphological awareness contributed to morphological decoding, which then influenced word reading and finally reading comprehension. In a second indirect path, morphological awareness contributed to morphological analysis, which contributed to reading comprehension. Finally, in a direct path, morphological awareness contributed to reading comprehension beyond all other variables. These findings inform as to the potential mechanisms underlying the relation between morphological awareness and reading comprehension in children. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of premature stimulation on HERG K+ channels

PubMed Central

Lu, Yu; Mahaut-Smith, Martyn P; Varghese, Anthony; Huang, Christopher L-H; Kemp, Paul R; Vandenberg, Jamie I

2001-01-01

The unusual kinetics of human ether-à-go-go-related gene (HERG) K+ channels are consistent with a role in the suppression of arrhythmias initiated by premature beats. Action potential clamp protocols were used to investigate the effect of premature stimulation on HERG K+ channels, transfected in Chinese hamster ovary cells, at 37 °C. HERG K+ channel currents peaked during the terminal repolarization phase of normally paced action potential waveforms. However, the magnitude of the current and the time point at which conductance was maximal depended on the type of action potential waveform used (epicardial, endocardial, Purkinje fibre or atrial). HERG K+ channel currents recorded during premature action potentials consisted of an early transient outward current followed by a sustained outward current. The magnitude of the transient current component showed a biphasic dependence on the coupling interval between the normally paced and premature action potentials and was maximal at a coupling interval equivalent to 90% repolarization (APD90) for ventricular action potentials. The largest transient current response occurred at shorter coupling intervals for Purkinje fibre (APD90– 20 ms) and atrial (APD90– 30 ms) action potentials. The magnitude of the sustained current response following premature stimulation was similar to that recorded during the first action potential for ventricular action potential waveforms. However, for Purkinje and atrial action potentials the sustained current response was significantly larger during the premature action potential than during the normally paced action potential. A Markov model that included three closed states, one open and one inactivated state with transitions permitted between the pre-open closed state and the inactivated state, successfully reproduced our results for the effects of premature stimuli, both during square pulse and action potential clamp waveforms. These properties of HERG K+ channels may help to suppress arrhythmias initiated by early afterdepolarizations and premature beats in the ventricles, Purkinje fibres or atria. PMID:11744759

Short-chain carboxylic acids, a new class of teratogens: studies of potential biochemical mechanisms.

PubMed

Coakley, M E; Rawlings, S J; Brown, N A

1986-12-01

Certain short-chain carboxylic acids (SCCA) appear to share a common teratogenic potential, although the structural requirements for activity remain obscure. By using a whole rat embryo culture model system, several biochemical processes have been examined, either as potential initial sites of teratogenic action or as early steps in the pathway to malformation. Valproate, methoxyacetate, and butyrate were the prototype SCCA examined. Measurement of [14C]glucose utilization and lactate production confirmed that energy production by the early organogenesis embryo is predominantly from glycolysis. While the positive control agent, iodoacetate, caused a significant inhibition of lactate production, none of the SCCA affected this process or glucose utilization at teratogenic concentrations. Valproate did not influence embryonic acetyl CoA levels, in marked contrast to the reported response of adult liver, the other major target of valproate toxicity. Pinocytosis by the visceral yolk sac (VYS) was measured by the uptake of [125I]polyvinylpyrrolidone. This process ultimately supplies the embryo with amino-acids and is essential for normal development. SCCA induce morphological abnormalities of the VYS in embryo culture. Pinocytosis was slightly reduced by valporate, but not the other SCCA. However, comparison with the action of an antiserum, for which inhibition of pinocytosis is the initial teratogenic insult, suggests that this is not the mechanism for valproate. Incorporation of [3H]thymidine into embryo or yolk sac was not affected after 3 hr of SCCA exposure, but there was a marked effect of the positive control, hydroxyurea. This suggests that DNA synthesis is not directly influenced by SCCA.(ABSTRACT TRUNCATED AT 250 WORDS)

Short-chain carboxylic acids, a new class of teratogens: studies of potential biochemical mechanisms.

PubMed Central

Coakley, M E; Rawlings, S J; Brown, N A

1986-01-01

Certain short-chain carboxylic acids (SCCA) appear to share a common teratogenic potential, although the structural requirements for activity remain obscure. By using a whole rat embryo culture model system, several biochemical processes have been examined, either as potential initial sites of teratogenic action or as early steps in the pathway to malformation. Valproate, methoxyacetate, and butyrate were the prototype SCCA examined. Measurement of [14C]glucose utilization and lactate production confirmed that energy production by the early organogenesis embryo is predominantly from glycolysis. While the positive control agent, iodoacetate, caused a significant inhibition of lactate production, none of the SCCA affected this process or glucose utilization at teratogenic concentrations. Valproate did not influence embryonic acetyl CoA levels, in marked contrast to the reported response of adult liver, the other major target of valproate toxicity. Pinocytosis by the visceral yolk sac (VYS) was measured by the uptake of [125I]polyvinylpyrrolidone. This process ultimately supplies the embryo with amino-acids and is essential for normal development. SCCA induce morphological abnormalities of the VYS in embryo culture. Pinocytosis was slightly reduced by valporate, but not the other SCCA. However, comparison with the action of an antiserum, for which inhibition of pinocytosis is the initial teratogenic insult, suggests that this is not the mechanism for valproate. Incorporation of [3H]thymidine into embryo or yolk sac was not affected after 3 hr of SCCA exposure, but there was a marked effect of the positive control, hydroxyurea. This suggests that DNA synthesis is not directly influenced by SCCA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3830097

A novel approach to dual excitation ratiometric optical mapping of cardiac action potentials with di-4-ANEPPS using pulsed LED excitation.

PubMed

Bachtel, Andrew D; Gray, Richard A; Stohlman, Jayna M; Bourgeois, Elliot B; Pollard, Andrew E; Rogers, Jack M

2011-07-01

We developed a new method for ratiometric optical mapping of transmembrane potential (V(m)) in cardiac preparations stained with di-4-ANEPPS. V(m)-dependent shifts of excitation and emission spectra establish two excitation bands (<481 and >481 nm) that produce fluorescence changes of opposite polarity within a single emission band (575-620 nm). The ratio of these positive and negative fluorescence signals (excitation ratiometry) increases V(m) sensitivity and removes artifacts common to both signals. We pulsed blue (450 ± 10 nm) and cyan (505 ± 15 nm) light emitting diodes (LEDs) at 375 Hz in alternating phase synchronized to a camera (750 frames-per-second). Fluorescence was bandpass filtered (585 ± 20 nm). This produced signals with upright (blue) and inverted (cyan) action potentials (APs) interleaved in sequential frames. In four whole swine hearts with motion chemically arrested, fractional fluorescence for blue, cyan, and ratio signals was 1.2 ± 0.3%, 1.2 ± 0.3%, and 2.4 ± 0.6%, respectively. Signal-to-noise ratios were 4.3 ± 1.4, 4.0 ± 1.2, and 5.8 ± 1.9, respectively. After washing out the electromechanical uncoupling agent, we characterized motion artifact by cross-correlating blue, cyan, and ratio signals with a signal with normal AP morphology. Ratiometry improved cross-correlation coefficients from 0.50 ± 0.48 to 0.81 ± 0.25, but did not cancel all motion artifacts. These findings demonstrate the feasibility of pulsed LED excitation ratiometry in myocardium. © 2011 IEEE

A Novel Approach to Dual Excitation Ratiometric Optical Mapping of Cardiac Action Potentials with Di-4-ANEPPS using Pulsed LED Excitation

PubMed Central

Bachtel, Andrew D.; Gray, Richard A.; Stohlman, Jayna M.; Bourgeois, Elliot B.; Pollard, Andrew E.

2011-01-01

We developed a new method for ratiometric optical mapping of transmembrane potential (Vm) in cardiac preparations stained with di-4-ANEPPS. Vm-dependent shifts of excitation and emission spectra establish two excitation bands (<481 and >481 nm) that produce fluorescence changes of opposite polarity within a single emission band (575–620 nm). The ratio of these positive and negative fluorescence signals (excitation ratiometry) increases Vm sensitivity and removes artifacts common to both signals. We pulsed blue (450±10 nm) and cyan (505±15 nm) light emitting diodes (LEDs) at 375 Hz in alternating phase synchronized to a camera (750 frames-per-second). Fluorescence was bandpass filtered (585±20 nm). This produced signals with upright (blue) and inverted (cyan) action potentials (APs) interleaved in sequential frames. In 4 whole swine hearts with motion chemically arrested, fractional fluorescence for blue, cyan, and ratio signals was 1.2±0.3%, 1.2±0.3%, and 2.4±0.6%, respectively. Signal-to-noise ratios were 4.3±1.4, 4.0±1.2, and 5.8±1.9, respectively. After washing out the electromechanical uncoupling agent, we characterized motion artifact by cross-correlating blue, cyan, and ratio signals with a signal with normal AP morphology. Ratiometry improved cross-correlation coefficients from 0.50±0.48 to 0.81±0.25, but did not cancel all motion artifacts. These findings demonstrate the feasibility of pulsed LED excitation ratiometry in myocardium. PMID:21536528

Modeling study of mecamylamine block of muscle type acetylcholine receptors.

PubMed

Ostroumov, Konstantin; Shaikhutdinova, Asya; Skorinkin, Andrey

2008-04-01

The blocking action of mecamylamine on different types of nicotinic acetylcholine receptors (nAChRs) has been extensively studied and used as a tool to characterize the nAChRs from different synapses. However, mechanism of mecamylamine action was not fully explored for all types of nAChRs. In the present study, we provide brief description of the mecamylamine action on muscle nAChRs expressed at the frog neuromuscular junction. In this preparation mecamylamine block of nAChRs was accompanied by a use-dependent block relief induced by membrane depolarization combined with the activation of nAChRs by endogenous agonist acetylcholine (ACh). Further, three kinetic models of possible mecamylamine interaction with nAChRs were analyzed including simple open channel block, symmetrical trapping block and asymmetrical trapping block. This analysis suggested that mecamylamine action could be described on the basis of trapping mechanism, when the antagonist remained inside the channel even in the absence of bound agonist. Such receptors with trapped mecamylamine inside were predicted to have a closing rate constant about three times faster than resting one and a fast voltage-dependent unblocking rate constant. Specific experimental conditions and morphological organization of the neuromuscular synapses were considered to simulate time course of the mecamylamine block development. Thus, likewise for the neuronal nAChRs, the trapping mechanism determined the action of mecamylamine on synaptic neuromuscular currents evoked by the endogenous agonist acetylcholine (ACh), however specific morphological organization of the synaptic transmission delayed time development of the currents block.

The teratogenic risk.

PubMed

Tuchmann-Duplessis, H

1983-01-01

Reproduction can be impaired in animals and man by drugs and various environmental agents. Depending on the time of exposure--from fertilization through the fetal period and eventually during lactation--the consequences can range from embryotoxicity, gross malformations and a large variety of more subtle morphological, biochemical, and functional abnormalities. The high susceptibility of the embryo to exogenous agents is due to cellular multiplication and differentiation and to the lack of development of the enzyme systems necessary for the detoxification of chemicals. At present, developmental impairments represent the main cause of perinatal mortality and postnatal morbidity. After a review of prenatal physiology and teratogenic principles, the action of selected drugs and environmental agents is analyzed. The potential danger of environmental factors during intrauterine development is of particular concern because of its irreversible nature.

Oxidative stress due to aluminum exposure induces eryptosis which is prevented by erythropoietin.

PubMed

Vota, Daiana M; Crisp, Renée L; Nesse, Alcira B; Vittori, Daniela C

2012-05-01

The widespread use of aluminum (Al) provides easy exposure of humans to the metal and its accumulation remains a potential problem. In vivo and in vitro assays have associated Al overload with anemia. To better understand the mechanisms by which Al affects human erythrocytes, morphological and biochemical changes were analyzed after long-term treatment using an in vitro model. The appearance of erythrocytes with abnormal shapes suggested metal interaction with cell surface, supported by the fact that high amounts of Al attached to cell membrane. Long-term incubation of human erythrocytes with Al induced signs of premature erythrocyte death (eryptosis), such as phosphatidylserine externalization, increased intracellular calcium, and band 3 degradation. Signs of oxidative stress, such as significant increase in reactive oxygen species in parallel with decrease in the amount of reduced glutathione, were also observed. These oxidative effects were completely prevented by the antioxidant N-acetylcysteine. Interestingly, erythrocytes were also protected from the prooxidative action of Al by the presence of erythropoietin (EPO). In conclusion, results provide evidence that chronic Al exposure may lead to biochemical and morphological alterations similar to those shown in eryptosis induced by oxidant compounds in human erythrocytes. The antieryptotic effect of EPO may contribute to enhance the knowledge of its physiological role on erythroid cells. Irrespective of the antioxidant mechanism, this property of EPO, shown in this model of Al exposure, let us suggest potential benefits by EPO treatment of patients with anemia associated to altered redox environment. Copyright © 2011 Wiley Periodicals, Inc.

Vitamin K3 induces antiproliferative effect in cervical epithelial cells transformed by HPV 16 (SiHa cells) through the increase in reactive oxygen species production.

PubMed

de Carvalho Scharf Santana, Natália; Lima, Natália Alves; Desoti, Vânia Cristina; Bidóia, Danielle Lazarin; de Souza Bonfim Mendonça, Patrícia; Ratti, Bianca Altrão; Nakamura, Tânia Ueda; Nakamura, Celso Vataru; Consolaro, Marcia Edilaine Lopes; Ximenes, Valdecir Farias; de Oliveira Silva, Sueli

2016-10-01

Cervical cancer is characterized as an important public health problem. According to latest estimates, cancer of the cervix is the fourth most common cancer among women. Due to its high prevalence, the search for new and efficient drugs to treat this infection is continuous. The progression of HPV-associated cervical cancer involves the expression of two viral proteins, E6 and E7, which are rapidly degraded by the ubiquitin-proteasome system through the increase in reactive oxygen species generation. Vitamins are essential to human substances, participate in the regulation of metabolism, and facilitate the process of energy transfer. Some early studies have indicated that vitamin K3 exerts antitumor activity by inducing cell death by apoptosis through an increase in the generation of reactive oxygen species. Thus, we evaluated the antiproliferative effect and a likely mechanism of action of vitamin K3 against cervical epithelial cells transformed by HPV 16 (SiHa cells) assessing the production of total ROS, the mitochondrial membrane potential, the cell morphology, the cell volume, and the cell membrane integrity. Our results show that vitamin K3 induces an increase in ROS production in SiHa cells, triggering biochemical and morphological events, such as depolarization of mitochondrial membrane potential and decreasing cell volume. Our data showed that vitamin K3 generates an oxidative imbalance in SiHa cells, leading to mechanisms that induce cell death by apoptosis.

Electrophysiology of neurones of the inferior mesenteric ganglion of the cat.

PubMed Central

Julé, Y; Szurszewski, J H

1983-01-01

Intracellular recordings were obtained from cells in vitro in the inferior mesenteric ganglia of the cat. Neurones could be classified into three types: non-spontaneous, irregular discharging and regular discharging neurones. Non-spontaneous neurones had a stable resting membrane potential and responded with action potentials to indirect preganglionic nerve stimulation and to intracellular injection of depolarizing current. Irregular discharging neurones were characterized by a discharge of excitatory post-synaptic potentials (e.p.s.p.s.) which sometimes gave rise to action potentials. This activity was abolished by hexamethonium bromide, chlorisondamine and d-tubocurarine chloride. Tetrodotoxin and a low Ca2+ -high Mg2+ solution also blocked on-going activity in irregular discharging neurones. Regular discharging neurones were characterized by a rhythmic discharge of action potentials. Each action potential was preceded by a gradual depolarization of the intracellularly recorded membrane potential. Intracellular injection of hyperpolarizing current abolished the regular discharge of action potential. No synaptic potentials were observed during hyperpolarization of the membrane potential. Nicotinic, muscarinic and adrenergic receptor blocking drugs did not modify the discharge of action potentials in regular discharging neurones. A low Ca2+ -high Mg2+ solution also had no effect on the regular discharge of action potentials. Interpolation of an action potential between spontaneous action potentials in regular discharging neurones reset the rhythm of discharge. It is suggested that regular discharging neurones were endogenously active and that these neurones provided synaptic input to irregular discharging neurones. PMID:6140310

Electrophysiology of neurones of the inferior mesenteric ganglion of the cat.

PubMed

Julé, Y; Szurszewski, J H

1983-11-01

Intracellular recordings were obtained from cells in vitro in the inferior mesenteric ganglia of the cat. Neurones could be classified into three types: non-spontaneous, irregular discharging and regular discharging neurones. Non-spontaneous neurones had a stable resting membrane potential and responded with action potentials to indirect preganglionic nerve stimulation and to intracellular injection of depolarizing current. Irregular discharging neurones were characterized by a discharge of excitatory post-synaptic potentials (e.p.s.p.s.) which sometimes gave rise to action potentials. This activity was abolished by hexamethonium bromide, chlorisondamine and d-tubocurarine chloride. Tetrodotoxin and a low Ca2+ -high Mg2+ solution also blocked on-going activity in irregular discharging neurones. Regular discharging neurones were characterized by a rhythmic discharge of action potentials. Each action potential was preceded by a gradual depolarization of the intracellularly recorded membrane potential. Intracellular injection of hyperpolarizing current abolished the regular discharge of action potential. No synaptic potentials were observed during hyperpolarization of the membrane potential. Nicotinic, muscarinic and adrenergic receptor blocking drugs did not modify the discharge of action potentials in regular discharging neurones. A low Ca2+ -high Mg2+ solution also had no effect on the regular discharge of action potentials. Interpolation of an action potential between spontaneous action potentials in regular discharging neurones reset the rhythm of discharge. It is suggested that regular discharging neurones were endogenously active and that these neurones provided synaptic input to irregular discharging neurones.

Dynamics of action potential initiation in the GABAergic thalamic reticular nucleus in vivo.

PubMed

Muñoz, Fabián; Fuentealba, Pablo

2012-01-01

Understanding the neural mechanisms of action potential generation is critical to establish the way neural circuits generate and coordinate activity. Accordingly, we investigated the dynamics of action potential initiation in the GABAergic thalamic reticular nucleus (TRN) using in vivo intracellular recordings in cats in order to preserve anatomically-intact axo-dendritic distributions and naturally-occurring spatiotemporal patterns of synaptic activity in this structure that regulates the thalamic relay to neocortex. We found a wide operational range of voltage thresholds for action potentials, mostly due to intrinsic voltage-gated conductances and not synaptic activity driven by network oscillations. Varying levels of synchronous synaptic inputs produced fast rates of membrane potential depolarization preceding the action potential onset that were associated with lower thresholds and increased excitability, consistent with TRN neurons performing as coincidence detectors. On the other hand the presence of action potentials preceding any given spike was associated with more depolarized thresholds. The phase-plane trajectory of the action potential showed somato-dendritic propagation, but no obvious axon initial segment component, prominent in other neuronal classes and allegedly responsible for the high onset speed. Overall, our results suggest that TRN neurons could flexibly integrate synaptic inputs to discharge action potentials over wide voltage ranges, and perform as coincidence detectors and temporal integrators, supported by a dynamic action potential threshold.

Channel morphology and bed-sediment characteristics before and after riparian vegetation clearing in the Cottonwood Ranch, Platte River, Nebraska, water years 2001-2004

USGS Publications Warehouse

Kinzel, Paul J.; Nelson, Jonathan M.; Heckman, Ashley K.

2006-01-01

Riparian areas along a reach of Platte River passing through Nebraska Public Power District's Cottonwood Ranch Property were modified during 2002 to 2004 to enhance in-channel habitats for endangered and threatened avian species. A component of this alteration involved the removal of riparian vegetation from riverbanks and islands to provide roosting habitat for the endangered whooping crane and to provide nesting and foraging habitat for the endangered least tern and threatened piping plover. It was hypothesized that the removal of riparian vegetation could have the effect of stimulating channel widening in this reach by increasing the potential of these surfaces to erode under natural fluvial action. It also was hypothesized that as a direct or indirect consequence of the alterations, a local increase in sediment supply also might occur, potentially resulting in geomorphic change downstream and possibly initiating negative third-party effects. The cumulative effects of the management activities on the channel morphology and sediment transport in this reach were monitored during water years 2001-2004 by measuring transect elevation profiles and bed-sediment-size gradations upstream, within, and downstream from the managed area before and after the development activities. An analysis of variance (ANOVA) was performed to determine if the geomorphic variables measured before and after the development activities were significantly different. Although statistically significant differences were detected in some of the variables, increases in mean bed elevation did not occur in a greater percentage of the monitoring sections measured downstream compared to upstream from the management activities. This result suggests that the management activities did not have a substantial effect on the downstream river channel morphology and sediment transport. However, it is important to place these short-term and site-specific results in the context that river flows following the management activities were at historical low rates, and therefore the potential to affect and the opportunity to detect possible geomorphic change within and downstream from the managed reach were limited.

Heterogeneity of the Axon Initial Segment in Interneurons and Pyramidal Cells of Rodent Visual Cortex

PubMed Central

Höfflin, Felix; Jack, Alexander; Riedel, Christian; Mack-Bucher, Julia; Roos, Johannes; Corcelli, Corinna; Schultz, Christian; Wahle, Petra; Engelhardt, Maren

2017-01-01

The microdomain that orchestrates action potential initiation in neurons is the axon initial segment (AIS). It has long been considered to be a rather homogeneous domain at the very proximal axon hillock with relatively stable length, particularly in cortical pyramidal cells. However, studies in other brain regions paint a different picture. In hippocampal CA1, up to 50% of axons emerge from basal dendrites. Further, in about 30% of thick-tufted layer V pyramidal neurons in rat somatosensory cortex, axons have a dendritic origin. Consequently, the AIS is separated from the soma. Recent in vitro and in vivo studies have shown that cellular excitability is a function of AIS length/position and somatodendritic morphology, undermining a potentially significant impact of AIS heterogeneity for neuronal function. We therefore investigated neocortical axon morphology and AIS composition, hypothesizing that the initial observation of seemingly homogeneous AIS is inadequate and needs to take into account neuronal cell types. Here, we biolistically transfected cortical neurons in organotypic cultures to visualize the entire neuron and classify cell types in combination with immunolabeling against AIS markers. Using confocal microscopy and morphometric analysis, we investigated axon origin, AIS position, length, diameter as well as distance to the soma. We find a substantial AIS heterogeneity in visual cortical neurons, classified into three groups: (I) axons with somatic origin with proximal AIS at the axon hillock; (II) axons with somatic origin with distal AIS, with a discernible gap between the AIS and the soma; and (III) axons with dendritic origin (axon-carrying dendrite cell, AcD cell) and an AIS either starting directly at the axon origin or more distal to that point. Pyramidal cells have significantly longer AIS than interneurons. Interneurons with vertical columnar axonal projections have significantly more distal AIS locations than all other cells with their prevailing phenotype as an AcD cell. In contrast, neurons with perisomatic terminations display most often an axon originating from the soma. Our data contribute to the emerging understanding that AIS morphology is highly variable, and potentially a function of the cell type. PMID:29170630

A hydromorphological framework for the evaluation of e-flows

NASA Astrophysics Data System (ADS)

Bussettini, Martina; Rinaldi, Massimo; Grant, Gordon

2017-04-01

Anthropogenic alteration of hydromorphological processes in rivers is a major factor that diminishes river health and undermines environmental objectives envisaged by river protection policies. Specifying environmental flows to address those impacts can be a key strategy for the maintenance of functional river processes and the achievement of those objectives. Environmental flows are determined by various methods and approaches, based primarily on hydrological and/or hydraulic evaluations, although holistic methodologies, considering the many interacting factors that structure aquatic ecosystems, including sediments, are increasingly used. Hydrological and geomorphological processes are highly coupled and any change in one typically affects the other. The coupling varies over different spatial and temporal scales, and changing either hydrological or geomorphological processes can result in alteration of river habitats, ultimately impacting ecological processes. In spite of these linkages, current restoration approaches typically focus only on changes on hydrological regime as a means promoting ecological enhancements. Neglecting sediment transport and its interaction with flow in shaping riverine habitats is likely to results not only in minor or no enhancements in the ecology, but may also increase the costs of water use. A more integrated view of how human activities jointly affect sediment regime, river morphology and river flows is therefore needed in order to determine the most effective actions to rehabilitate river processes to desired states. These states involve considerations of the combination of intrinsic ("natural") conditions (e.g. river sensitivity and morphological potential, off-site conditions) and socio-economic constraints. The evaluation of such factors, the analysis of different scenarios, and the selection of appropriate actions require the contextualization of river reaches within a wider spatial-temporal hydromorphological framework. Here we present such a general multiscale, process-based hydromorphological framework, and discuss its application to the problem of how best to analyse and estimate e-flows.

Phenotypic plasticity in haptoral structures of Ligophorus cephali (Monogenea: Dactylogyridae) on the flathead mullet (Mugil cephalus): a geometric morphometric approach.

PubMed

Rodríguez-González, Abril; Míguez-Lozano, Raúl; Llopis-Belenguer, Cristina; Balbuena, Juan Antonio

2015-04-01

Evaluating phenotypic plasticity in attachment organs of parasites can provide information on the capacity to colonise new hosts and illuminate evolutionary processes driving host specificity. We analysed the variability in shape and size of the dorsal and ventral anchors of Ligophorus cephali from Mugil cephalus by means of geometric morphometrics and multivariate statistics. We also assessed the morphological integration between anchors and between the roots and points in order to gain insight into their functional morphology. Dorsal and ventral anchors showed a similar gradient of overall shape variation, but the amount of localised changes was much higher in the former. Statistical models describing variations in shape and size revealed clear differences between anchors. The dorsal anchor/bar complex seems more mobile than the ventral one in Ligophorus, and these differences may reflect different functional roles in attachment to the gills. The lower residual variation associated with the ventral anchor models suggests a tighter control of their shape and size, perhaps because these anchors seem to be responsible for firmer attachment and their size and shape would allow more effective responses to characteristics of the microenvironment within the individual host. Despite these putative functional differences, the high level of morphological integration indicates a concerted action between anchors. In addition, we found a slight, although significant, morphological integration between roots and points in both anchors, which suggests that a large fraction of the observed phenotypic variation does not compromise the functional role of anchors as levers. Given the low level of genetic variation in our sample, it is likely that much of the morphological variation reflects host-driven plastic responses. This supports the hypothesis of monogenean specificity through host-switching and rapid speciation. The present study demonstrates the potential of geometric morphometrics to provide new and previously unexplored insights into the functional morphology of attachment and evolutionary processes of host-parasite coevolution. Copyright © 2015 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

Mechanisms and consequences of action potential burst firing in rat neocortical pyramidal neurons

PubMed Central

Williams, Stephen R; Stuart, Greg J

1999-01-01

Electrophysiological recordings and pharmacological manipulations were used to investigate the mechanisms underlying the generation of action potential burst firing and its postsynaptic consequences in visually identified rat layer 5 pyramidal neurons in vitro.Based upon repetitive firing properties and subthreshold membrane characteristics, layer 5 pyramidal neurons were separated into three classes: regular firing and weak and strong intrinsically burst firing.High frequency (330 ± 10 Hz) action potential burst firing was abolished or greatly weakened by the removal of Ca2+ (n = 5) from, or by the addition of the Ca2+ channel antagonist Ni2+ (250–500 μm; n = 8) to, the perfusion medium.The blockade of apical dendritic sodium channels by the local dendritic application of TTX (100 nm; n = 5) abolished or greatly weakened action potential burst firing, as did the local apical dendritic application of Ni2+ (1 mm; n = 5).Apical dendritic depolarisation resulted in low frequency (157 ± 26 Hz; n = 6) action potential burst firing in regular firing neurons, as classified by somatic current injection. The intensity of action potential burst discharges in intrinsically burst firing neurons was facilitated by dendritic depolarisation (n = 11).Action potential amplitude decreased throughout a burst when recorded somatically, suggesting that later action potentials may fail to propagate axonally. Axonal recordings demonstrated that each action potential in a burst is axonally initiated and that no decrement in action potential amplitude is apparent in the axon > 30 μm from the soma.Paired recordings (n = 16) from synaptically coupled neurons indicated that each action potential in a burst could cause transmitter release. EPSPs or EPSCs evoked by a presynaptic burst of action potentials showed use-dependent synaptic depression.A postsynaptic, TTX-sensitive voltage-dependent amplification process ensured that later EPSPs in a burst were amplified when generated from membrane potentials positive to -60 mV, providing a postsynaptic mechanism that counteracts use-dependent depression at synapses between layer 5 pyramidal neurons. PMID:10581316

Induction and characterization of morphologic mutants in a natural Saccharomyces cerevisiae strain.

PubMed

Barberio, Claudia; Bianchi, Lucia; Pinzauti, Francesca; Lodi, Tiziana; Ferrero, Iliana; Polsinelli, Mario; Casalone, Enrico

2007-02-01

Saccharomyces cerevisiae is a good model with which to study the effects of morphologic differentiation on the ecological behaviour of fungi. In this work, 33 morphologic mutants of a natural strain of S. cerevisiae, obtained with UV mutagenesis, were selected for their streak shape and cell shape on rich medium. Two of them, showing both high sporulation proficiency and constitutive pseudohyphal growth, were analysed from a genetic and physiologic point of view. Each mutant carries a recessive monogenic mutation, and the two mutations reside in unlinked genes. Flocculation ability and responsiveness to different stimuli distinguished the two mutants. Growth at 37 degrees C affected the cell but not the colony morphology, suggesting that these two phenotypes are regulated differently. The effect of ethidium bromide, which affects mitochondrial DNA replication, suggested a possible "retrograde action" of mitochondria in pseudohyphal growth.

Evidence for Early Morphological Decomposition: Combining Masked Priming with Magnetoencephalography

ERIC Educational Resources Information Center

Lehtonen, Minna; Monahan, Philip J.; Poeppel, David

2011-01-01

Are words stored as morphologically structured representations? If so, when during word recognition are morphological pieces accessed? Recent masked priming studies support models that assume early decomposition of (potentially) morphologically complex words. The electrophysiological evidence, however, is inconsistent. We combined masked…

The human ether-a-go-go-related gene (hERG) current inhibition selectively prolongs action potential of midmyocardial cells to augment transmural dispersion.

PubMed

Yasuda, C; Yasuda, S; Yamashita, H; Okada, J; Hisada, T; Sugiura, S

2015-08-01

The majority of drug induced arrhythmias are related to the prolongation of action potential duration following inhibition of rapidly activating delayed rectifier potassium current (I(Kr)) mediated by the hERG channel. However, for arrhythmias to develop and be sustained, not only the prolongation of action potential duration but also its transmural dispersion are required. Herein, we evaluated the effect of hERG inhibition on transmural dispersion of action potential duration using the action potential clamp technique that combined an in silico myocyte model with the actual I(Kr) measurement. Whole cell I(Kr) current was measured in Chinese hamster ovary cells stably expressing the hERG channel. The measured current was coupled with models of ventricular endocardial, M-, and epicardial cells to calculate the action potentials. Action potentials were evaluated under control condition and in the presence of 1, 10, or 100 μM disopyramide, an hERG inhibitor. Disopyramide dose-dependently increased the action potential durations of the three cell types. However, action potential duration of M-cells increased disproportionately at higher doses, and was significantly different from that of epicardial and endocardial cells (dispersion of repolarization). By contrast, the effects of disopyramide on peak I(Kr) and instantaneous current-voltage relation were similar in all cell types. Simulation study suggested that the reduced repolarization reserve of M-cell with smaller amount of slowly activating delayed rectifier potassium current levels off at longer action potential duration to make such differences. The action potential clamp technique is useful for studying the mechanism of arrhythmogenesis by hERG inhibition through the transmural dispersion of repolarization.

Dynamics of Action Potential Initiation in the GABAergic Thalamic Reticular Nucleus In Vivo

PubMed Central

Muñoz, Fabián; Fuentealba, Pablo

2012-01-01

Understanding the neural mechanisms of action potential generation is critical to establish the way neural circuits generate and coordinate activity. Accordingly, we investigated the dynamics of action potential initiation in the GABAergic thalamic reticular nucleus (TRN) using in vivo intracellular recordings in cats in order to preserve anatomically-intact axo-dendritic distributions and naturally-occurring spatiotemporal patterns of synaptic activity in this structure that regulates the thalamic relay to neocortex. We found a wide operational range of voltage thresholds for action potentials, mostly due to intrinsic voltage-gated conductances and not synaptic activity driven by network oscillations. Varying levels of synchronous synaptic inputs produced fast rates of membrane potential depolarization preceding the action potential onset that were associated with lower thresholds and increased excitability, consistent with TRN neurons performing as coincidence detectors. On the other hand the presence of action potentials preceding any given spike was associated with more depolarized thresholds. The phase-plane trajectory of the action potential showed somato-dendritic propagation, but no obvious axon initial segment component, prominent in other neuronal classes and allegedly responsible for the high onset speed. Overall, our results suggest that TRN neurons could flexibly integrate synaptic inputs to discharge action potentials over wide voltage ranges, and perform as coincidence detectors and temporal integrators, supported by a dynamic action potential threshold. PMID:22279567

Decision making and action implementation: evidence for an early visually triggered motor activation specific to potential actions.

PubMed

Tandonnet, Christophe; Garry, Michael I; Summers, Jeffery J

2013-07-01

To make a decision may rely on accumulating evidence in favor of one alternative until a threshold is reached. Sequential-sampling models differ by the way of accumulating evidence and the link with action implementation. Here, we tested a model's prediction of an early action implementation specific to potential actions. We assessed the dynamics of action implementation in go/no-go and between-hand choice tasks by transcranial magnetic stimulation of the motor cortex (single- or paired-pulse TMS; 3-ms interstimulus interval). Prior to implementation of the selected action, the amplitude of the motor evoked potential first increased whatever the visual stimulus but only for the hand potentially involved in the to-be-produced action. These findings suggest that visual stimuli can trigger an early motor activation specific to potential actions, consistent with race-like models with continuous transmission between decision making and action implementation. Copyright © 2013 Society for Psychophysiological Research.

The effects of saxitoxin and tetrodotoxin on nerve conduction in the presence of lithium ions and of magnesium ions

PubMed Central

Evans, M. H.

1969-01-01

1. It has been shown that nerve fibres from rat cauda equina will conduct action potentials after immersion in saline in which lithium chloride is substituted for sodium chloride. 2. Both saxitoxin and tetrodotoxin inhibit lithium-generated action potentials. The concentration of toxin needed to inhibit the lithium-generated action potentials is similar to that needed to inhibit sodium-generated action potentials. 3. If magnesium chloride is added to the saline to give a concentration of 10-15 mM there is usually a slight fall in amplitude of the compound action potential. Saxitoxin and tetrodotoxin now inhibit the action potential to a greater degree than in the absence of magnesium ions. PMID:5789802

Properties of interstellar wind leading to shape morphology of the dust surrounding HD 61005

NASA Astrophysics Data System (ADS)

Pástor, P.

2017-08-01

Aims: A structure formed by dust particles ejected from the debris ring around HD 61005 is observed in the scattered light. The main aim here is to constrain interstellar wind parameters that lead to shape morphology in the vicinity of HD 61005 using currently available observational data for the debris ring. Methods: Equation of motion of 2 × 105 dust particles ejected from the debris ring under the action of the electromagnetic radiation, stellar wind, and interstellar wind is solved. A two-dimensional (2D) grid is placed in a given direction for accumulation of the light scattered on the dust particles in order to determine the shape morphology. The interaction of the interstellar wind and the stellar wind is considered. Results: Groups of unknown properties of the interstellar wind that create the observed morphology are determined. A relation between number densities of gas components in the interstellar wind and its relative velocity is found. Variations of the shape morphology caused by the interaction with the interstellar clouds of various temperatures are studied. When the interstellar wind velocity is tilted from debris ring axis a simple relation between the properties of the interstellar wind and an angle between the line of sight and the interstellar wind velocity exists. Dust particles that are most significantly influenced by stellar radiation move on the boundary of observed structure. Conclusions: Observed structure at HD 61005 can be explained as a result of dust particles moving under the action of the interstellar wind. Required number densities or velocities of the interstellar wind are much higher than that of the interstellar wind entering the solar system.

Modelling of sediment transport and morphological evolution under the combined action of waves and currents

NASA Astrophysics Data System (ADS)

Franz, Guilherme; Delpey, Matthias T.; Brito, David; Pinto, Lígia; Leitão, Paulo; Neves, Ramiro

2017-09-01

Coastal defence structures are often constructed to prevent beach erosion. However, poorly designed structures may cause serious erosion problems in the downdrift direction. Morphological models are useful tools to predict such impacts and assess the efficiency of defence structures for different scenarios. Nevertheless, morphological modelling is still a topic under intense research effort. The processes simulated by a morphological model depend on model complexity. For instance, undertow currents are neglected in coastal area models (2DH), which is a limitation for simulating the evolution of beach profiles for long periods. Model limitations are generally overcome by predefining invariant equilibrium profiles that are allowed to shift offshore or onshore. A more flexible approach is described in this paper, which can be generalised to 3-D models. The present work is based on the coupling of the MOHID modelling system and the SWAN wave model. The impacts of different designs of detached breakwaters and groynes were simulated in a schematic beach configuration following a 2DH approach. The results of bathymetry evolution are in agreement with the patterns found in the literature for several existing structures. The model was also tested in a 3-D test case to simulate the formation of sandbars by undertow currents. The findings of this work confirmed the applicability of the MOHID modelling system to study sediment transport and morphological changes in coastal zones under the combined action of waves and currents. The same modelling methodology was applied to a coastal zone (Costa da Caparica) located at the mouth of a mesotidal estuary (Tagus Estuary, Portugal) to evaluate the hydrodynamics and sediment transport both in calm water conditions and during events of highly energetic waves. The MOHID code is available in the GitHub repository.

Actions and mechanisms of action of novel analogues of sotalol on guinea-pig and rabbit ventricular cells.

PubMed Central

Connors, S. P.; Gill, E. W.; Terrar, D. A.

1992-01-01

1. The actions and mechanisms of action of novel analogues of sotalol which prolong cardiac action potentials were investigated in guinea-pig and rabbit isolated ventricular cells. 2. In guinea-pig and rabbit cells the compounds significantly prolonged action potential duration at 20% and 90% repolarization levels without affecting resting membrane potential. In guinea-pig but not rabbit cells there was an increase in action potential amplitude and in rabbit cells there was no change in the shape or position of the 'notch' in the action potential. 3. Possible mechanisms of action were studied in more detail in the case of compound II (1-(4-methanesulphonamidophenoxy)-3-(N-methyl 3,4 dichlorophenylethylamino)-2-propanol). Prolongation of action potential duration continued to occur in the presence of nisoldipine, and calcium currents recorded under voltage-clamp conditions were not reduced by compound II (1 microM). Action potential prolongation by compound II was also unaffected in the presence of 10 microM tetrodotoxin. 4. Compound II (1 microM) did not influence IK1 assessed from the current during ramp changes in membrane potential (20 mV s-1) over the range -90 to -10 mV. 5. Compound II (1 microM) blocked time-dependent delayed rectifier potassium current (IK) activated by step depolarizations and recorded as an outward tail following repolarization. When a submaximal concentration (50 nM) was applied there was no change in the apparent reversal potential of IK.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1393293

Phytotoxic effects of trichothecenes on the growth and morphology of Arabidopsis thaliana.

PubMed

Masuda, Daisuke; Ishida, Mamoru; Yamaguchi, Kazuo; Yamaguchi, Isamu; Kimura, Makoto; Nishiuchi, Takumi

2007-01-01

Non-volatile sesquiterpenoids, a trichothecene family of phytotoxins such as deoxynivalenol (DON) and T-2 toxin, contain numerous molecular species and are synthesized by phytopathogenic Fusarium species. Although trichothecene chemotypes might play a role in the virulence of individual Fusarium strains, the phytotoxic action of individual trichothecenes has not been systematically studied. To perform a comparative analysis of the phytotoxic action of representative trichothecenes, the growth and morphology of Arabidopsis thaliana growing on media containing these compounds was investigated. Both DON and diacetoxyscirpenol (DAS) preferentially inhibited root elongation. DON-treated roots were less organized compared with control roots. Moreover, preferential inhibition of root growth by DON was also observed in wheat plants. In addition, T-2 toxin-treated seedlings exhibited dwarfism with aberrant morphological changes (e.g. petiole shortening, curled dark-green leaves, and reduced cell size). These results imply that the phytotoxic action of trichothecenes differed among their molecular species. Cycloheximide (CHX)-treated seedlings displayed neither feature, although it is known that trichothecenes inhibit translation in eukaryotic ribosomes. Microarray analyses suggested that T-2 toxin caused a defence response, the inactivation of brassinosteroid (BR), and the generation of reactive oxygen species in Arabidopsis. This observation is in agreement with our previous reports in which trichothecenes such as T-2 toxin have an elicitor-like activity when infiltrated into the leaves of Arabidopsis. Since it has been reported that BR plays an important role in a broad range of disease resistance in tobacco and rice, inactivation of BR might affect pathogenicity during the infection of host plants by trichothecene-producing fungi.

Effect of alkali and oxidative treatments on the physicochemical, pasting, thermal and morphological properties of corn starch.

PubMed

Spier, Franciela; Zavareze, Elessandra da Rosa; Marques e Silva, Ricardo; Elias, Moacir Cardoso; Dias, Alvaro Renato Guerra

2013-07-01

Few studies on starch modifications using different chemical agents are available in the literature, and no reports were found on the combined effect of oxidation and alkaline treatment of corn starch. Thus this work evaluated the physicochemical, pasting, morphological, cystallinity and thermal properties of chemically modified corn starch, after either the isolated or combined action of alkaline (sodium hydroxide) and oxidative (sodium hypochlorite) treatments. The highest values for the sum of carbonyl and carboxyl and enzymatic hydrolysis occurred in starches submitted to oxidative treatment at high active chlorine concentrations. The alkali treatment in isolation modified the pasting properties, reduced the paste temperature and increased the peak viscosity, breakdown, final viscosity and setback of starches. Starch modified by the action of sodium hypochlorite and hydroxide in combination presented more severe damage on granule surfaces. The results show that corn starch modified by the combined action of oxidative and alkaline treatments should be studied more, especially at the concentration limit of sodium hydroxide where gelatinization occurs. Under these conditions the effect of oxidation can be more intense and thus allow the production of starches with different properties and an increase in their industrial applications. © 2013 Society of Chemical Industry.

Alteration of neural action potential patterns by axonal stimulation: the importance of stimulus location.

PubMed

Crago, Patrick E; Makowski, Nathaniel S

2014-10-01

Stimulation of peripheral nerves is often superimposed on ongoing motor and sensory activity in the same axons, without a quantitative model of the net action potential train at the axon endpoint. We develop a model of action potential patterns elicited by superimposing constant frequency axonal stimulation on the action potentials arriving from a physiologically activated neural source. The model includes interactions due to collision block, resetting of the neural impulse generator, and the refractory period of the axon at the point of stimulation. Both the mean endpoint firing rate and the probability distribution of the action potential firing periods depend strongly on the relative firing rates of the two sources and the intersite conduction time between them. When the stimulus rate exceeds the neural rate, neural action potentials do not reach the endpoint and the rate of endpoint action potentials is the same as the stimulus rate, regardless of the intersite conduction time. However, when the stimulus rate is less than the neural rate, and the intersite conduction time is short, the two rates partially sum. Increases in stimulus rate produce non-monotonic increases in endpoint rate and continuously increasing block of neurally generated action potentials. Rate summation is reduced and more neural action potentials are blocked as the intersite conduction time increases. At long intersite conduction times, the endpoint rate simplifies to being the maximum of either the neural or the stimulus rate. This study highlights the potential of increasing the endpoint action potential rate and preserving neural information transmission by low rate stimulation with short intersite conduction times. Intersite conduction times can be decreased with proximal stimulation sites for muscles and distal stimulation sites for sensory endings. The model provides a basis for optimizing experiments and designing neuroprosthetic interventions involving motor or sensory stimulation.

The role of Na-Ca exchange current in the cardiac action potential.

PubMed

Janvier, N C; Boyett, M R

1996-07-01

Since 1981, when Mullins published his provocative book proposing that the Na-Ca exchanger is electrogenic, it has been shown, first by computer simulation by Noble and later by experiment by various investigators, that inward iNaCa triggered by the Ca2+ transient is responsible for the low plateau of the atrial action potential and contributes to the high plateau of the ventricular action potential. Reduction or complete block of inward iNaCa by buffering intracellular Ca2+ with EGTA or BAPTA, by blocking SR Ca2+ release or by substituting extracellular Na+ with Li+ can result in a shortening of the action potential. The effect of block of outward iNaCa or complete block of both inward and outward iNaCa on the action potential has not been investigated experimentally, because of the lack of a suitable blocker, and remains a goal for the future. An increase in the intracellular Na+ concentration (after the application of cardiac glycoside or an increase in heart rate) or an increase in extracellular Ca2+ are believed to lead to an outward shift in iNaCa at plateau potentials and a shortening of the action potential. Changes in the Ca2+ transient are expected to result in changes in inward iNaCa and thus the action potential. This may explain the shortening of the premature action potential as well as the prolongation of the action potential when a muscle is allowed to shorten during the action potential. Inward iNaCa may play an important role in both normal and abnormal pacemaker activity in the heart.

Antibacterial activity of large-area monolayer graphene film manipulated by charge transfer

PubMed Central

Li, Jinhua; Wang, Gang; Zhu, Hongqin; Zhang, Miao; Zheng, Xiaohu; Di, Zengfeng; Liu, Xuanyong; Wang, Xi

2014-01-01

Graphene has attracted increasing attention for potential applications in biotechnology due to its excellent electronic property and biocompatibility. Here we use both Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative Escherichia coli (E. coli) to investigate the antibacterial actions of large-area monolayer graphene film on conductor Cu, semiconductor Ge and insulator SiO2. The results show that the graphene films on Cu and Ge can surprisingly inhibit the growth of both bacteria, especially the former. However, the proliferation of both bacteria cannot be significantly restricted by the graphene film on SiO2. The morphology of S. aureus and E. coli on graphene films further confirms that the direct contact of both bacteria with graphene on Cu and Ge can cause membrane damage and destroy membrane integrity, while no evident membrane destruction is induced by graphene on SiO2. From the viewpoint of charge transfer, a plausible mechanism is proposed here to explain this phenomenon. This study may provide new insights for the better understanding of antibacterial actions of graphene film and for the better designing of graphene-based antibiotics or other biomedical applications. PMID:24619247

Antibacterial activity of large-area monolayer graphene film manipulated by charge transfer.

PubMed

Li, Jinhua; Wang, Gang; Zhu, Hongqin; Zhang, Miao; Zheng, Xiaohu; Di, Zengfeng; Liu, Xuanyong; Wang, Xi

2014-03-12

Graphene has attracted increasing attention for potential applications in biotechnology due to its excellent electronic property and biocompatibility. Here we use both Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative Escherichia coli (E. coli) to investigate the antibacterial actions of large-area monolayer graphene film on conductor Cu, semiconductor Ge and insulator SiO2. The results show that the graphene films on Cu and Ge can surprisingly inhibit the growth of both bacteria, especially the former. However, the proliferation of both bacteria cannot be significantly restricted by the graphene film on SiO2. The morphology of S. aureus and E. coli on graphene films further confirms that the direct contact of both bacteria with graphene on Cu and Ge can cause membrane damage and destroy membrane integrity, while no evident membrane destruction is induced by graphene on SiO2. From the viewpoint of charge transfer, a plausible mechanism is proposed here to explain this phenomenon. This study may provide new insights for the better understanding of antibacterial actions of graphene film and for the better designing of graphene-based antibiotics or other biomedical applications.

Simulation of action potential propagation in plants.

PubMed

Sukhov, Vladimir; Nerush, Vladimir; Orlova, Lyubov; Vodeneev, Vladimir

2011-12-21

Action potential is considered to be one of the primary responses of a plant to action of various environmental factors. Understanding plant action potential propagation mechanisms requires experimental investigation and simulation; however, a detailed mathematical model of plant electrical signal transmission is absent. Here, the mathematical model of action potential propagation in plants has been worked out. The model is a two-dimensional system of excitable cells; each of them is electrically coupled with four neighboring ones. Ion diffusion between excitable cell apoplast areas is also taken into account. The action potential generation in a single cell has been described on the basis of our previous model. The model simulates active and passive signal transmission well enough. It has been used to analyze theoretically the influence of cell to cell electrical conductivity and H(+)-ATPase activity on the signal transmission in plants. An increase in cell to cell electrical conductivity has been shown to stimulate an increase in the length constant, the action potential propagation velocity and the temperature threshold, while the membrane potential threshold being weakly changed. The growth of H(+)-ATPase activity has been found to induce the increase of temperature and membrane potential thresholds and the reduction of the length constant and the action potential propagation velocity. Copyright © 2011 Elsevier Ltd. All rights reserved.

Computationally efficient simulation of electrical activity at cell membranes interacting with self-generated and externally imposed electric fields

NASA Astrophysics Data System (ADS)

Agudelo-Toro, Andres; Neef, Andreas

2013-04-01

Objective. We present a computational method that implements a reduced set of Maxwell's equations to allow simulation of cells under realistic conditions: sub-micron cell morphology, a conductive non-homogeneous space and various ion channel properties and distributions. Approach. While a reduced set of Maxwell's equations can be used to couple membrane currents to extra- and intracellular potentials, this approach is rarely taken, most likely because adequate computational tools are missing. By using these equations, and introducing an implicit solver, numerical stability is attained even with large time steps. The time steps are limited only by the time development of the membrane potentials. Main results. This method allows simulation times of tens of minutes instead of weeks, even for complex problems. The extracellular fields are accurately represented, including secondary fields, which originate at inhomogeneities of the extracellular space and can reach several millivolts. We present a set of instructive examples that show how this method can be used to obtain reference solutions for problems, which might not be accurately captured by the traditional approaches. This includes the simulation of realistic magnitudes of extracellular action potential signals in restricted extracellular space. Significance. The electric activity of neurons creates extracellular potentials. Recent findings show that these endogenous fields act back onto the neurons, contributing to the synchronization of population activity. The influence of endogenous fields is also relevant for understanding therapeutic approaches such as transcranial direct current, transcranial magnetic and deep brain stimulation. The mutual interaction between fields and membrane currents is not captured by today's concepts of cellular electrophysiology, including the commonly used activation function, as those concepts are based on isolated membranes in an infinite, isopotential extracellular space. The presented tool makes simulations with detailed morphology and implicit interactions of currents and fields available to the electrophysiology community.

[Loudness optimized registration of compound action potential in cochlear implant recipients].

PubMed

Berger, Klaus; Hocke, Thomas; Hessel, Horst

2017-11-01

Background Postoperative measurements of compound action potentials are not always possible due to the insufficient acceptance of the CI-recipients. This study investigated the impact of different parameters on the acceptance of the measurements. Methods Compound action potentials of 16 CI recipients were measured with different pulse-widths. Recipients performed a loudness rating at the potential thresholds with the different sequences. Results Compound action potentials obtained with higher pulse-widths were rated softer than those obtained with smaller pulse-widths. Conclusions Compound action potentials measured with higher pulse-widths generate a gap between loudest acceptable presentation level and potential threshold. This gap contributes to a higher acceptance of postoperative measurements. Georg Thieme Verlag KG Stuttgart · New York.

Enhancement of pharmacokinetic and pharmacological behavior of ocular dorzolamide after factorial optimization of self-assembled nanostructures

PubMed Central

Afify, Enas A. M. R.; Elsayed, Ibrahim; Gad, Mary K.; Mohamed, Magdy I.

2018-01-01

Dorzolamide hydrochloride is frequently administered for the control of the intra-ocular pressure associated with glaucoma. The aim of this study is to develop and optimize self-assembled nanostructures of dorzolamide hydrochloride and L-α-Phosphatidylcholine to improve the pharmacokinetic parameters and extend the drug pharmacological action. Self-assembled nanostructures were prepared using a modified thin-film hydration technique. The formulae compositions were designed based on response surface statistical design. The prepared self-assembled nanostructures were characterized by testing their drug content, particle size, polydispersity index, zeta potential, partition coefficient, release half-life and extent. The optimized formulae having the highest drug content, zeta potential, partition coefficient, release half-life and extent with the lowest particle size and polydispersity index were subjected to further investigations including investigation of their physicochemical, morphological characteristics, in vivo pharmacokinetic and pharmacodynamic profiles. The optimized formulae were prepared at pH 8.7 (F5 and F6) and composed of L-α-Phosphatidylcholine and drug mixed in a ratio of 1:1 and 2:1 w/w, respectively. They showed significantly higher Cmax, AUC024 and AUC0∞ at the aqueous humor with extended control over the intra-ocular pressure, when compared to the marketed product; Trusopt®. The study introduced novel and promising self-assembled formulae able to permeate higher drug amount through the cornea and achieve sustained pharmacological effect at the site of action. PMID:29401498

Murraya paniculata (L.) (Orange Jasmine): Potential Nutraceuticals with Ameliorative Effect in Alloxan-Induced Diabetic Rats.

PubMed

Menezes, Cicero Diego Almino; de Oliveira Garcia, Francisca Adilfa; de Barros Viana, Glauce Socorro; Pinheiro, Patricia Gonçalves; Felipe, Cícero Francisco Bezerra; de Albuquerque, Thaís Rodrigues; Moreira, Alisson Cordeiro; Santos, Enaide Soares; Cavalcante, Maynara Rodrigues; Garcia, Tatiana Rodrigues; Silva, Thiago Fonseca; Coutinho, Henrique Douglas Melo; de Menezes, Irwin Rose Alencar

2017-11-01

Orange jasmine, Murraya paniculata (Rutaceae), is a plant from India widely used in folk medicine as antinociceptive, antiinflammatory, and antioxidant. Although oral hypoglycemic agents and insulin are the mainstays of treatment of diabetes mellitus (DM), there is a significant demand for new natural products to reduce the development of diabetic complications. Alloxan-induced diabetic rats were treated for 60 days with a hydroalcoholic extract of M. paniculata (MPE), at doses of 100, 200, and 400 mg/kg. MPE decreased glycemia and also cholesterol and triglyceride levels, starting 1 week after treatments, as compared with the same group before treatments. Glucose values were reduced toward normality after 1 week of treatment. MPE hypoglycemic effects were potentiated by glibenclamide and metformin. MPE also decreased fructosamine and glycated hemoglobin values. MPE reduced diabetes-induced morphological alterations of the kidney, pancreas, and liver. MPE acts similarly to glibenclamide and metformin, and its glucose-lowering action is partly a consequence of ATP-sensitive K + channel inhibition. MPE may be a potential therapeutic alternative for the treatment of diabetes and its complications. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Proteomic and morphological changes produced by subinhibitory concentration of isoniazid in Mycobacterium tuberculosis.

PubMed

Campanerut-Sá, Paula Az; Ghiraldi-Lopes, Luciana D; Meneguello, Jean E; Fiorini, Adriana; Evaristo, Geisa Pc; Siqueira, Vera Ld; Scodro, Regiane Bl; Patussi, Eliana V; Donatti, Lucélia; Souza, Emanuel M; Cardoso, Rosilene F

2016-09-01

To study the proteomic and morphological changes in Mycobacterium tuberculosis H37Rv exposed to subinhibitory concentration of isoniazid (INH). The bacillus was exposed to ½ MIC of INH at 12, 24 and 48 h. The samples' cells were submitted to scanning electron microscopy. The proteins were separated by 2D gel electrophoresis and identified by MS. INH exposure was able to alter the format, the multiplication and causing a cell swelling in the bacillus. The major altered proteins were related to the virulence, detoxification, adaptation, intermediary metabolism and lipid metabolism. The protein and morphological changes in M. tuberculosis induced by ½ MIC INH were related to defense mechanism of the bacillus or the action of INH therein.

Inducing repetitive action potential firing in neurons via synthesized photoresponsive nanoscale cellular prostheses.

PubMed

Lu, Siyuan; Madhukar, Anupam

2013-02-01

Recently we reported an analysis that examined the potential of synthesized photovoltaic functional abiotic nanosystems (PVFANs) to modulate membrane potential and activate action potential firing in neurons. Here we extend the analysis to delineate the requirements on the electronic energy levels and the attendant photophysical properties of the PVFANs to induce repetitive action potential under continuous light, a capability essential for the proposed potential application of PVFANs as retinal cellular prostheses to compensate for loss of photoreceptors. We find that repetitive action potential firing demands two basic characteristics in the electronic response of the PVFANs: an exponential dependence of the PVFAN excited state decay rate on the membrane potential and a three-state system such that, following photon absorption, the electron decay from the excited state to the ground state is via intermediate state(s) whose lifetime is comparable to the refractory time following an action potential. In this study, the potential of synthetic photovoltaic functional abiotic nanosystems (PVFANs) is examined under continuous light to modulate membrane potential and activate action potential firing in neurons with the proposed potential application of PVFANs as retinal cellular prostheses. Copyright © 2013 Elsevier Inc. All rights reserved.

Effects of K(+) channel openers on spontaneous action potentials in detrusor smooth muscle of the guinea-pig urinary bladder.

PubMed

Takagi, Hiroaki; Hashitani, Hikaru

2016-10-15

The modulation of spontaneous excitability in detrusor smooth muscle (DSM) upon the pharmacological activation of different populations of K(+) channels was investigated. Effects of distinct K(+) channel openers on spontaneous action potentials in DSM of the guinea-pig bladder were examined using intracellular microelectrode techniques. NS1619 (10μM), a large conductance Ca(2+)-activated K(+) (BK) channel opener, transiently increased action potential frequency and then prevented their generation without hyperpolarizing the membrane in a manner sensitive to iberiotoxin (IbTX, 100nM). A higher concentration of NS1619 (30μM) hyperpolarized the membrane and abolished action potential firing. NS309 (10μM) and SKA31 (100μM), small conductance Ca(2+)-activated K(+) (SK) channel openers, dramatically increased the duration of the after-hyperpolarization and then abolished action potential firing in an apamin (100nM)-sensitive manner. Flupirtine (10μM), a Kv7 channel opener, inhibited action potential firing without hyperpolarizing the membrane in a manner sensitive to XE991 (10μM), a Kv7 channel blocker. BRL37344 (10μM), a β3-adrenceptor agonist, or rolipram (10nM), a phosphodiesterase 4 inhibitor, also inhibited action potential firing. A higher concentration of rolipram (100nM) hyperpolarized the DSM and abolished the action potentials. IbTX (100nM) prevented the rolipram-induced blockade of action potentials but not the hyperpolarization. BK and Kv7 channels appear to predominantly contribute to the stabilization of DSM excitability. Spare SK channels could be pharmacologically activated to suppress DSM excitability. BK channels appear to be involved in the cyclic AMP-induced inhibition of action potentials but not the membrane hyperpolarization. Copyright © 2016 Elsevier B.V. All rights reserved.

Potential role of green tea catechins in the management of oxidative stress-associated infertility.

PubMed

Roychoudhury, Shubhadeep; Agarwal, Ashok; Virk, Gurpriya; Cho, Chak-Lam

2017-05-01

Reactive oxygen species (ROS) are present in low concentrations in the genital tracts of males and females. Excessive ROS lead to oxidative stress, which damages DNA, lipids and proteins. Such molecular changes result in compromised vitality, increased morphological defects and decreased sperm motility in the male. In the female, oxidative stress interferes with oocyte maturation, and may inhibit in-vitro maturation of the oocyte. Recently, green tea supplementation has been reported to possess properties that may improve the quality of male and female gametes largely due to the ability of catechin polyphenols to quench ROS. Epigallocatechin-3-gallate (EGCG) is considered the most promising bioactive compound in green tea due to its strong antioxidant activity. The unique property of green tea catechins may potentially improve reproductive health and pose an important research area. We present a comprehensive overview on the effects and potential roles of green tea catechins on oxidative stress in male and female reproduction and fertility. In this review, possible mechanisms of action are highlighted to better understand the potential use of green tea catechins in the reduction of oxidative stress and its associated beneficial effects in the clinical setting. Copyright © 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Low-dimensional, morphologically accurate models of subthreshold membrane potential

PubMed Central

Kellems, Anthony R.; Roos, Derrick; Xiao, Nan; Cox, Steven J.

2009-01-01

The accurate simulation of a neuron’s ability to integrate distributed synaptic input typically requires the simultaneous solution of tens of thousands of ordinary differential equations. For, in order to understand how a cell distinguishes between input patterns we apparently need a model that is biophysically accurate down to the space scale of a single spine, i.e., 1 μm. We argue here that one can retain this highly detailed input structure while dramatically reducing the overall system dimension if one is content to accurately reproduce the associated membrane potential at a small number of places, e.g., at the site of action potential initiation, under subthreshold stimulation. The latter hypothesis permits us to approximate the active cell model with an associated quasi-active model, which in turn we reduce by both time-domain (Balanced Truncation) and frequency-domain (ℋ2 approximation of the transfer function) methods. We apply and contrast these methods on a suite of typical cells, achieving up to four orders of magnitude in dimension reduction and an associated speed-up in the simulation of dendritic democratization and resonance. We also append a threshold mechanism and indicate that this reduction has the potential to deliver an accurate quasi-integrate and fire model. PMID:19172386

Imaging Action Potential in Single Mammalian Neurons by Tracking the Accompanying Sub-Nanometer Mechanical Motion.

PubMed

Yang, Yunze; Liu, Xian-Wei; Wang, Hui; Yu, Hui; Guan, Yan; Wang, Shaopeng; Tao, Nongjian

2018-03-28

Action potentials in neurons have been studied traditionally by intracellular electrophysiological recordings and more recently by the fluorescence detection methods. Here we describe a label-free optical imaging method that can measure mechanical motion in single cells with a sub-nanometer detection limit. Using the method, we have observed sub-nanometer mechanical motion accompanying the action potential in single mammalian neurons by averaging the repeated action potential spikes. The shape and width of the transient displacement are similar to those of the electrically recorded action potential, but the amplitude varies from neuron to neuron, and from one region of a neuron to another, ranging from 0.2-0.4 nm. The work indicates that action potentials may be studied noninvasively in single mammalian neurons by label-free imaging of the accompanying sub-nanometer mechanical motion.

Pathological prolongation of action potential duration as a cause of the reduced alpha-adrenoceptor-mediated negative inotropy in streptozotocin-induced diabetic mice myocardium.

PubMed

Kanae, Haruna; Hamaguchi, Shogo; Wakasugi, Yumi; Kusakabe, Taichi; Kato, Keisuke; Namekata, Iyuki; Tanaka, Hikaru

2017-11-01

Effect of pathological prolongation of action potential duration on the α-adrenoceptor-mediated negative inotropy was studied in streptozotocin-induced diabetic mice myocardium. In streptozotocin-treated mouse ventricular myocardium, which had longer duration of action potential than that in control mice, the negative inotropic response induced by phenylephrine was smaller than that in control mice. 4-Aminopyridine prolonged the action potential duration and decreased the negative inotropy in control mice. Cromakalim shortened the action potential duration and increased the negative inotropy in streptozotocin-treated mice. These results suggest that the reduced α-adrenoceptor-mediated inotropy in the diabetic mouse myocardium is partly due to its prolonged action potential. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Determination of cable parameters in skeletal muscle fibres during repetitive firing of action potentials.

PubMed

Riisager, Anders; Duehmke, Rudy; Nielsen, Ole Bækgaard; Huang, Christopher L; Pedersen, Thomas Holm

2014-10-15

Recent studies in rat muscle fibres show that repetitive firing of action potentials causes changes in fibre resting membrane conductance (Gm) that reflect regulation of ClC-1 Cl(-) and KATP K(+) ion channels. Methodologically, these findings were obtained by inserting two microelectrodes at close proximity in the same fibres enabling measurements of fibre input resistance (Rin) in between action potential trains. Since the fibre length constant (λ) could not be determined, however, the calculation of Gm relied on the assumptions that the specific cytosolic resistivity (Ri) and muscle fibre volume remained constant during the repeated action potential firing. Here we present a three-microelectrode technique that enables determinations of multiple cable parameters in action potential-firing fibres including Rin and λ as well as waveform and conduction velocities of fully propagating action potentials. It is shown that in both rat and mouse extensor digitorum longus (EDL) fibres, action potential firing leads to substantial changes in both muscle fibre volume and Ri. The analysis also showed, however, that regardless of these changes, rat and mouse EDL fibres both exhibited initial decreases in Gm that were eventually followed by a ∼3-fold, fully reversible increase in Gm after the firing of 1450-1800 action potentials. Using this three-electrode method we further show that the latter rise in Gm was closely associated with excitation failures and loss of action potential signal above -20 mV. © 2014 The Authors. The Journal of Physiology © 2014 The Physiological Society.

Determination of cable parameters in skeletal muscle fibres during repetitive firing of action potentials

PubMed Central

Riisager, Anders; Duehmke, Rudy; Nielsen, Ole Bækgaard; Huang, Christopher L; Pedersen, Thomas Holm

2014-01-01

Recent studies in rat muscle fibres show that repetitive firing of action potentials causes changes in fibre resting membrane conductance (Gm) that reflect regulation of ClC-1 Cl− and KATP K+ ion channels. Methodologically, these findings were obtained by inserting two microelectrodes at close proximity in the same fibres enabling measurements of fibre input resistance (Rin) in between action potential trains. Since the fibre length constant (λ) could not be determined, however, the calculation of Gm relied on the assumptions that the specific cytosolic resistivity (Ri) and muscle fibre volume remained constant during the repeated action potential firing. Here we present a three-microelectrode technique that enables determinations of multiple cable parameters in action potential-firing fibres including Rin and λ as well as waveform and conduction velocities of fully propagating action potentials. It is shown that in both rat and mouse extensor digitorum longus (EDL) fibres, action potential firing leads to substantial changes in both muscle fibre volume and Ri. The analysis also showed, however, that regardless of these changes, rat and mouse EDL fibres both exhibited initial decreases in Gm that were eventually followed by a ∼3-fold, fully reversible increase in Gm after the firing of 1450–1800 action potentials. Using this three-electrode method we further show that the latter rise in Gm was closely associated with excitation failures and loss of action potential signal above −20 mV. PMID:25128573

Synaptic depolarization is more effective than back-propagating action potentials during induction of associative long-term potentiation in hippocampal pyramidal neurons.

PubMed

Hardie, Jason; Spruston, Nelson

2009-03-11

Long-term potentiation (LTP) requires postsynaptic depolarization that can result from EPSPs paired with action potentials or larger EPSPs that trigger dendritic spikes. We explored the relative contribution of these sources of depolarization to LTP induction during synaptically driven action potential firing in hippocampal CA1 pyramidal neurons. Pairing of a weak test input with a strong input resulted in large LTP (approximately 75% increase) when the weak and strong inputs were both located in the apical dendrites. This form of LTP did not require somatic action potentials. When the strong input was located in the basal dendrites, the resulting LTP was smaller (< or =25% increase). Pairing the test input with somatically evoked action potentials mimicked this form of LTP. Thus, back-propagating action potentials may contribute to modest LTP, but local synaptic depolarization and/or dendritic spikes mediate a stronger form of LTP that requires spatial proximity of the associated synaptic inputs.

Reduction of I(Ca,L) and I(to1) density in hypertrophied right ventricular cells by simulated high altitude in adult rats.

PubMed

Chouabe, C; Espinosa, L; Megas, P; Chakir, A; Rougier, O; Freminet, A; Bonvallet, R

1997-01-01

The present paper describes the effect of a simulated hypobaric condition (at the altitude of 4500 m) on morphological characteristics and on some ionic currents in ventricular cells of adult rats. According to current data, chronic high-altitude exposure led to mild right ventricular hypertrophy. Increase in right ventricular weight appeared to be due wholly or partly to an enlargement of myocytes. The whole-cell patch-clamp technique was used and this confirmed, by cell capacitance measurement, that chronic high-altitude exposure induced an increase in the size of the right ventricular cells. Hypertrophied cells showed prolongation of action potential (AP). Four ionic currents, playing a role along with many others in the precise balance of inward and outward currents that control the duration of cardiac AP, were investigated. We report a significant decrease in the transient outward (I(to1)) and in the L-type calcium current (I(Ca,L)) densities while there was no significant difference in the delayed rectifier current (I(K)) or in the inward rectifier current (I(K1)) densities in hypertrophied right ventricular cells compared to control cells. At a given potential the decrease in I(to 1) density was relatively more important than the decrease in I(Ca,L) density. In both cell types, all the currents displayed the same voltage dependence. The inactivation kinetics of I(to 1) and I(Ca,L) or the steady-state activation and inactivation relationships were not significantly modified by chronic high-altitude exposure. We conclude that chronic high-altitude exposure induced true right ventricular myocyte hypertrophy and that the decrease in I(to 1) density might account for the lengthened action potential, or have a partial effect.

Measurement and significance of sperm morphology

PubMed Central

Menkveld, Roelof; Holleboom, Cas AG; Rhemrev, Johann PT

2011-01-01

The measurement or evaluation and clinical significance of human sperm morphology has always been and still is a controversial aspect of the semen analysis for the determination of a male's fertility potential. In this review the background of the development of the evaluation criteria for sperm morphology will be discussed. Aspects of criticism on the strict criteria definition and use of the criteria for sperm morphology evaluation will be discussed as well as possible reasons for the decline in normal sperm morphology values and how we can compromise for this phenomenon resulting in the very low normal reference value as published in the 2010 WHO manual for the Examination and Processing of Human Semen. One of the possible solutions may be to give more attention to a limited number of abnormal sperm morphology categories and the inclusion of sperm morphology patterns. It is concluded in this review that if done correctly and with care and with strict application of existing guidelines as outlined in the 2010 WHO manual, sperm morphology measurement still has a very important role to play in the clinical evaluation of male fertility potential. PMID:21076438

Cardiac action potential imaging

NASA Astrophysics Data System (ADS)

Tian, Qinghai; Lipp, Peter; Kaestner, Lars

2013-06-01

Action potentials in cardiac myocytes have durations in the order of magnitude of 100 milliseconds. In biomedical investigations the documentation of the occurrence of action potentials is often not sufficient, but a recording of the shape of an action potential allows a functional estimation of several molecular players. Therefore a temporal resolution of around 500 images per second is compulsory. In the past such measurements have been performed with photometric approaches limiting the measurement to one cell at a time. In contrast, imaging allows reading out several cells at a time with additional spatial information. Recent developments in camera technologies allow the acquisition with the required speed and sensitivity. We performed action potential imaging on isolated adult cardiomyocytes of guinea pigs utilizing the fluorescent membrane potential sensor di-8-ANEPPS and latest electron-multiplication CCD as well as scientific CMOS cameras of several manufacturers. Furthermore, we characterized the signal to noise ratio of action potential signals of varying sets of cameras, dye concentrations and objective lenses. We ensured that di-8-ANEPPS itself did not alter action potentials by avoiding concentrations above 5 μM. Based on these results we can conclude that imaging is a reliable method to read out action potentials. Compared to conventional current-clamp experiments, this optical approach allows a much higher throughput and due to its contact free concept leaving the cell to a much higher degree undisturbed. Action potential imaging based on isolated adult cardiomyocytes can be utilized in pharmacological cardiac safety screens bearing numerous advantages over approaches based on heterologous expression of hERG channels in cell lines.

A simple model for the generation of the vestibular evoked myogenic potential (VEMP).

PubMed

Wit, Hero P; Kingma, Charlotte M

2006-06-01

To describe the mechanism by which the vestibular evoked myogenic potential is generated. Vestibular evoked myogenic potential generation is modeled by adding a large number of muscle motor unit action potentials. These action potentials occur randomly in time along a 100 ms long time axis. But because between approximately 15 and 20 ms after a loud short sound stimulus (almost) no action potentials are generated during VEMP measurements in human subjects, no action potentials are present in the model during this time. The evoked potential is the result of the lack of amplitude cancellation in the averaged surface electromyogram at the edges of this 5 ms long time interval. The relatively simple model describes generation and some properties of the vestibular evoked myogenic potential very well. It is shown that, in contrast with other evoked potentials (BAEPs, VERs), the vestibular evoked myogenic potential is the result of an interruption of activity and not that of summed synchronized neural action potentials.

A rabbit ventricular action potential model replicating cardiac dynamics at rapid heart rates.

PubMed

Mahajan, Aman; Shiferaw, Yohannes; Sato, Daisuke; Baher, Ali; Olcese, Riccardo; Xie, Lai-Hua; Yang, Ming-Jim; Chen, Peng-Sheng; Restrepo, Juan G; Karma, Alain; Garfinkel, Alan; Qu, Zhilin; Weiss, James N

2008-01-15

Mathematical modeling of the cardiac action potential has proven to be a powerful tool for illuminating various aspects of cardiac function, including cardiac arrhythmias. However, no currently available detailed action potential model accurately reproduces the dynamics of the cardiac action potential and intracellular calcium (Ca(i)) cycling at rapid heart rates relevant to ventricular tachycardia and fibrillation. The aim of this study was to develop such a model. Using an existing rabbit ventricular action potential model, we modified the L-type calcium (Ca) current (I(Ca,L)) and Ca(i) cycling formulations based on new experimental patch-clamp data obtained in isolated rabbit ventricular myocytes, using the perforated patch configuration at 35-37 degrees C. Incorporating a minimal seven-state Markovian model of I(Ca,L) that reproduced Ca- and voltage-dependent kinetics in combination with our previously published dynamic Ca(i) cycling model, the new model replicates experimentally observed action potential duration and Ca(i) transient alternans at rapid heart rates, and accurately reproduces experimental action potential duration restitution curves obtained by either dynamic or S1S2 pacing.

Action and object word writing in a case of bilingual aphasia.

PubMed

Kambanaros, Maria; Messinis, Lambros; Anyfantis, Emmanouil

2012-01-01

We report the spoken and written naming of a bilingual speaker with aphasia in two languages that differ in morphological complexity, orthographic transparency and script Greek and English. AA presented with difficulties in spoken picture naming together with preserved written picture naming for action words in Greek. In English, AA showed similar performance across both tasks for action and object words, i.e. difficulties retrieving action and object names for both spoken and written naming. Our findings support the hypothesis that cognitive processes used for spoken and written naming are independent components of the language system and can be selectively impaired after brain injury. In the case of bilingual speakers, such processes impact on both languages. We conclude grammatical category is an organizing principle in bilingual dysgraphia.

Fisetin as a promising antifungal agent against Cryptocococcus neoformans species complex.

PubMed

Reis, M P C; Carvalho, C R C; Andrade, F A; Fernandes, O F L; Arruda, W; Silva, M R R

2016-08-01

The aim of this study was to investigate the mechanisms of action of fisetin, a flavonol with antifungal activity previously evaluated against the Cryptococcus neoformans species complex. Ergosterol content and flow cytometry analysis were determined for the C. neoformans species complex in the presence of fisetin and ultrastructural analysis of morphology was performed on Cryptococcus gattii and C. neoformans. Decrease in the total cellular ergosterol content after exposure to fisetin ranged from 25·4% after exposure to 128 μg ml(-1) to 21·6% after exposure to 64 μg ml(-1) of fisetin compared with the control (without fisetin). The fisetin effects obtained with flow cytometry showed metabolic impairment, and alterations in its normal morphology caused by fisetin in C. neoformans cells were verified using scanning electron microscopy. Fisetin is a compound that acts in the biosynthesis of ergosterol. Flow cytometry showed that fisetin reduced viability of the metabolically active cells of C. gattii, while morphological changes explain the action of fisetin in inhibiting growth of these fungi. This study supports the idea that fisetin may represent a good starting point for the development of future therapeutic substances for cryptococcosis. © 2016 The Society for Applied Microbiology.

Typical gray matter axons in mammalian brain fail to conduct action potentials faithfully at fever-like temperatures.

PubMed

Pekala, Dobromila; Szkudlarek, Hanna; Raastad, Morten

2016-10-01

We studied the ability of typical unmyelinated cortical axons to conduct action potentials at fever-like temperatures because fever often gives CNS symptoms. We investigated such axons in cerebellar and hippocampal slices from 10 to 25 days old rats at temperatures between 30 and 43°C. By recording with two electrodes along axonal pathways, we confirmed that the axons were able to initiate action potentials, but at temperatures >39°C, the propagation of the action potentials to a more distal recording site was reduced. This temperature-sensitive conduction may be specific for the very thin unmyelinated axons because similar recordings from myelinated CNS axons did not show conduction failures. We found that the conduction fidelity improved with 1 mmol/L TEA in the bath, probably due to block of voltage-sensitive potassium channels responsible for the fast repolarization of action potentials. Furthermore, by recording electrically activated antidromic action potentials from the soma of cerebellar granule cells, we showed that the axons failed less if they were triggered 10-30 msec after another action potential. This was because individual action potentials were followed by a depolarizing after-potential, of constant amplitude and shape, which facilitated conduction of the following action potentials. The temperature-sensitive conduction failures above, but not below, normal body temperature, and the failure-reducing effect of the spike's depolarizing after-potential, are two intrinsic mechanisms in normal gray matter axons that may help us understand how the hyperthermic brain functions. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Cardiac structural changes and electrical remodeling in a thiamine-deficiency model in rats.

PubMed

Roman-Campos, D; Campos, A C; Gioda, C R; Campos, P P; Medeiros, M A A; Cruz, J S

2009-06-05

Thiamine is an important cofactor present in many biochemical reactions, and its deprivation can lead to heart dysfunction. Little is known about the influence of thiamine deprivation on the electrophysiological behavior of the isolated heart cells and information about thiamine deficiency in heart morphology is controversial. Thus, we decided to investigate the major repolarizing conductances and their influence in the action potential (AP) waveform as well as the changes in the heart structure in a set of thiamine deficiency in rats. Using the patch-clamp technique, we investigated inward (I(K1)) and outward K(+) currents (I(to)), T-type and L-type Ca(2+) currents and APs. To evaluate heart morphology we used hematoxylin and eosin in transversal heart sections. Thiamine deficiency caused a marked decrease in left ventricle thickness, cardiomyocyte number, cell length and width, and membrane capacitance. When evaluating I(to) we did not find difference in current amplitude; however an acceleration of I(to) inactivation was observed. I(K1) showed a reduction in the amplitude and slope conductance, which implicated a less negative resting membrane potential in cardiac myocytes isolated from thiamine-deficient rats. We did not find any difference in L-type Ca(2+) current density. T-type Ca(2+) current was not observed. In addition, we did not observe significant changes in AP repolarization. Based on our study we can conclude that thiamine deficiency causes heart hypotrophy and not heart hypertrophy. Moreover, we provided evidence that there is no major electrical remodeling during thiamine deficiency, a feature of heart failure models.

Electrical Advantages of Dendritic Spines

PubMed Central

Gulledge, Allan T.; Carnevale, Nicholas T.; Stuart, Greg J.

2012-01-01

Many neurons receive excitatory glutamatergic input almost exclusively onto dendritic spines. In the absence of spines, the amplitudes and kinetics of excitatory postsynaptic potentials (EPSPs) at the site of synaptic input are highly variable and depend on dendritic location. We hypothesized that dendritic spines standardize the local geometry at the site of synaptic input, thereby reducing location-dependent variability of local EPSP properties. We tested this hypothesis using computational models of simplified and morphologically realistic spiny neurons that allow direct comparison of EPSPs generated on spine heads with EPSPs generated on dendritic shafts at the same dendritic locations. In all morphologies tested, spines greatly reduced location-dependent variability of local EPSP amplitude and kinetics, while having minimal impact on EPSPs measured at the soma. Spine-dependent standardization of local EPSP properties persisted across a range of physiologically relevant spine neck resistances, and in models with variable neck resistances. By reducing the variability of local EPSPs, spines standardized synaptic activation of NMDA receptors and voltage-gated calcium channels. Furthermore, spines enhanced activation of NMDA receptors and facilitated the generation of NMDA spikes and axonal action potentials in response to synaptic input. Finally, we show that dynamic regulation of spine neck geometry can preserve local EPSP properties following plasticity-driven changes in synaptic strength, but is inefficient in modifying the amplitude of EPSPs in other cellular compartments. These observations suggest that one function of dendritic spines is to standardize local EPSP properties throughout the dendritic tree, thereby allowing neurons to use similar voltage-sensitive postsynaptic mechanisms at all dendritic locations. PMID:22532875

Self-generated morphology in lagoon reefs

PubMed Central

Hamblin, Michael G.

2015-01-01

The three-dimensional form of a coral reef develops through interactions and feedbacks between its constituent organisms and their environment. Reef morphology therefore contains a potential wealth of ecological information, accessible if the relationships between morphology and ecology can be decoded. Traditionally, reef morphology has been attributed to external controls such as substrate topography or hydrodynamic influences. Little is known about inherent reef morphology in the absence of external control. Here we use reef growth simulations, based on observations in the cellular reefs of Western Australia’s Houtman Abrolhos Islands, to show that reef morphology is fundamentally determined by the mechanical behaviour of the reef-building organisms themselves—specifically their tendency to either remain in place or to collapse. Reef-building organisms that tend to remain in place, such as massive and encrusting corals or coralline algae, produce nodular reefs, whereas those that tend to collapse, such as branching Acropora, produce cellular reefs. The purest reef growth forms arise in sheltered lagoons dominated by a single type of reef builder, as in the branching Acropora-dominated lagoons of the Abrolhos. In these situations reef morphology can be considered a phenotype of the predominant reef building organism. The capacity to infer coral type from reef morphology can potentially be used to identify and map specific coral habitat in remotely sensed images. More generally, identifying ecological mechanisms underlying other examples of self-generated reef morphology can potentially improve our understanding of present-day reef ecology, because any ecological process capable of shaping a reef will almost invariably be an important process in real time on the living reef. PMID:26175962

Targeted cellular ablation based on the morphology of malignant cells

NASA Astrophysics Data System (ADS)

Ivey, Jill W.; Latouche, Eduardo L.; Sano, Michael B.; Rossmeisl, John H.; Davalos, Rafael V.; Verbridge, Scott S.

2015-11-01

Treatment of glioblastoma multiforme (GBM) is especially challenging due to a shortage of methods to preferentially target diffuse infiltrative cells, and therapy-resistant glioma stem cell populations. Here we report a physical treatment method based on electrical disruption of cells, whose action depends strongly on cellular morphology. Interestingly, numerical modeling suggests that while outer lipid bilayer disruption induced by long pulses (~100 μs) is enhanced for larger cells, short pulses (~1 μs) preferentially result in high fields within the cell interior, which scale in magnitude with nucleus size. Because enlarged nuclei represent a reliable indicator of malignancy, this suggested a means of preferentially targeting malignant cells. While we demonstrate killing of both normal and malignant cells using pulsed electric fields (PEFs) to treat spontaneous canine GBM, we proposed that properly tuned PEFs might provide targeted ablation based on nuclear size. Using 3D hydrogel models of normal and malignant brain tissues, which permit high-resolution interrogation during treatment testing, we confirmed that PEFs could be tuned to preferentially kill cancerous cells. Finally, we estimated the nuclear envelope electric potential disruption needed for cell death from PEFs. Our results may be useful in safely targeting the therapy-resistant cell niches that cause recurrence of GBM tumors.

Role of cytosolic calcium diffusion in cardiac purkinje cells.

PubMed

Limbu, Bijay; Shah, Kushal; Deo, Makarand

2016-08-01

The Cardiac Purkinje cells (PCs) exhibit distinct calcium (Ca2+) homeostasis than that in ventricular myocytes (VMs). Due to lack of t-tubules in PCs, the Ca2+ ions entering the cell have to diffuse through the cytoplasm to reach the sarcoplasmic reticulum (SR) before triggering Ca2+-induced-Ca2+-release (CICR). In recent experimental studies PCs have been shown to be more susceptible to action potential (AP) abnormalities than the VMs, however the exact mechanisms are poorly understood. In this study, we utilize morphologically realistic detailed biophysical mathematical model of a murine PC to systematically examine the role intracellular Ca2+ diffusion in the APs of PCs. A biphasic spatiotemporal Ca2+ diffusion process, as observed experimentally, was implemented in the model which includes radial Ca2+ wavelets and cell wide longitudinal Ca2+ diffusion wave (CWW). The AP morphology, specifically plateau, is affected due to changes in intracellular Ca2+ dynamics. When Ca2+ concentration in sarcolemmal region is elevated, it activated inward sodium Ca2+ exchanger (NCX) current resulting into prolongation of the plateau at faster diffusion rates. Our results demonstrate that the cytosolic Ca2+ diffusion waves play a significant role in shaping APs of PCs and could provide mechanistic insights into the increased arrhythmogeneity of PCs.

Targeted cellular ablation based on the morphology of malignant cells

PubMed Central

Ivey, Jill W.; Latouche, Eduardo L.; Sano, Michael B.; Rossmeisl, John H.; Davalos, Rafael V.; Verbridge, Scott S.

2015-01-01

Treatment of glioblastoma multiforme (GBM) is especially challenging due to a shortage of methods to preferentially target diffuse infiltrative cells, and therapy-resistant glioma stem cell populations. Here we report a physical treatment method based on electrical disruption of cells, whose action depends strongly on cellular morphology. Interestingly, numerical modeling suggests that while outer lipid bilayer disruption induced by long pulses (~100 μs) is enhanced for larger cells, short pulses (~1 μs) preferentially result in high fields within the cell interior, which scale in magnitude with nucleus size. Because enlarged nuclei represent a reliable indicator of malignancy, this suggested a means of preferentially targeting malignant cells. While we demonstrate killing of both normal and malignant cells using pulsed electric fields (PEFs) to treat spontaneous canine GBM, we proposed that properly tuned PEFs might provide targeted ablation based on nuclear size. Using 3D hydrogel models of normal and malignant brain tissues, which permit high-resolution interrogation during treatment testing, we confirmed that PEFs could be tuned to preferentially kill cancerous cells. Finally, we estimated the nuclear envelope electric potential disruption needed for cell death from PEFs. Our results may be useful in safely targeting the therapy-resistant cell niches that cause recurrence of GBM tumors. PMID:26596248

Calpains mediate axonal cytoskeleton disintegration during Wallerian degeneration

PubMed Central

Ma, Marek; Ferguson, Toby A.; Schoch, Kathleen M.; Li, Jian; Qian, Yaping; Shofer, Frances S.; Saatman, Kathryn E.; Neumar, Robert W.

2013-01-01

In both the central nervous system (CNS) and peripheral nervous system (PNS), transected axons undergo Wallerian degeneration. Even though Augustus Waller first described this process after transection of axons in 1850, the molecular mechanisms may be shared, at least in part, by many human diseases. Early pathology includes failure of synaptic transmission, target denervation, and granular disintegration of the axonal cytoskeleton (GDC). The Ca2+-dependent proteases calpains have been implicated in GDC but causality has not been established. To test the hypothesis that calpains play a causal role in axonal and synaptic degeneration in vivo, we studied transgenic mice that express human calpastatin (hCAST), the endogenous calpain inhibitor, in optic and sciatic nerve axons. Five days after optic nerve transection and 48 hours after sciatic nerve transection, robust neurofilament proteolysis observed in wild-type controls was reduced in hCAST transgenic mice. Protection of the axonal cytoskeleton in sciatic nerves of hCAST mice was nearly complete 48 hours post-transection. In addition, hCAST expression preserved the morphological integrity of neuromuscular junctions. However, compound muscle action potential amplitudes after nerve transection were similar in wild-type and hCAST mice. These results, in total, provide direct evidence that calpains are responsible for the morphological degeneration of the axon and synapse during Wallerian degeneration. PMID:23542511

Alteration of neural action potential patterns by axonal stimulation: the importance of stimulus location

PubMed Central

Crago, Patrick E; Makowski, Nathan S

2014-01-01

Objective Stimulation of peripheral nerves is often superimposed on ongoing motor and sensory activity in the same axons, without a quantitative model of the net action potential train at the axon endpoint. Approach We develop a model of action potential patterns elicited by superimposing constant frequency axonal stimulation on the action potentials arriving from a physiologically activated neural source. The model includes interactions due to collision block, resetting of the neural impulse generator, and the refractory period of the axon at the point of stimulation. Main Results Both the mean endpoint firing rate and the probability distribution of the action potential firing periods depend strongly on the relative firing rates of the two sources and the intersite conduction time between them. When the stimulus rate exceeds the neural rate, neural action potentials do not reach the endpoint and the rate of endpoint action potentials is the same as the stimulus rate, regardless of the intersite conduction time. However, when the stimulus rate is less than the neural rate, and the intersite conduction time is short, the two rates partially sum. Increases in stimulus rate produce non-monotonic increases in endpoint rate and continuously increasing block of neurally generated action potentials. Rate summation is reduced and more neural action potentials are blocked as the intersite conduction time increases.. At long intersite conduction times, the endpoint rate simplifies to being the maximum of either the neural or the stimulus rate. Significance This study highlights the potential of increasing the endpoint action potential rate and preserving neural information transmission by low rate stimulation with short intersite conduction times. Intersite conduction times can be decreased with proximal stimulation sites for muscles and distal stimulation sites for sensory endings. The model provides a basis for optimizing experiments and designing neuroprosthetic interventions involving motor or sensory stimulation. PMID:25161163

Alteration of neural action potential patterns by axonal stimulation: the importance of stimulus location

NASA Astrophysics Data System (ADS)

Crago, Patrick E.; Makowski, Nathaniel S.

2014-10-01

Objective. Stimulation of peripheral nerves is often superimposed on ongoing motor and sensory activity in the same axons, without a quantitative model of the net action potential train at the axon endpoint. Approach. We develop a model of action potential patterns elicited by superimposing constant frequency axonal stimulation on the action potentials arriving from a physiologically activated neural source. The model includes interactions due to collision block, resetting of the neural impulse generator, and the refractory period of the axon at the point of stimulation. Main results. Both the mean endpoint firing rate and the probability distribution of the action potential firing periods depend strongly on the relative firing rates of the two sources and the intersite conduction time between them. When the stimulus rate exceeds the neural rate, neural action potentials do not reach the endpoint and the rate of endpoint action potentials is the same as the stimulus rate, regardless of the intersite conduction time. However, when the stimulus rate is less than the neural rate, and the intersite conduction time is short, the two rates partially sum. Increases in stimulus rate produce non-monotonic increases in endpoint rate and continuously increasing block of neurally generated action potentials. Rate summation is reduced and more neural action potentials are blocked as the intersite conduction time increases. At long intersite conduction times, the endpoint rate simplifies to being the maximum of either the neural or the stimulus rate. Significance. This study highlights the potential of increasing the endpoint action potential rate and preserving neural information transmission by low rate stimulation with short intersite conduction times. Intersite conduction times can be decreased with proximal stimulation sites for muscles and distal stimulation sites for sensory endings. The model provides a basis for optimizing experiments and designing neuroprosthetic interventions involving motor or sensory stimulation.

Morphodynamic evolution of Laida beach (Oka estuary, Urdaibai Biosphere Reserve, southeastern Bay of Biscay) in response to supratidal beach nourishment actions

NASA Astrophysics Data System (ADS)

Monge-Ganuzas, M.; Gainza, J.; Liria, P.; Epelde, I.; Uriarte, A.; Garnier, R.; González, M.; Nuñez, P.; Jaramillo, C.; Medina, R.

2017-12-01

Laida beach, located at the Oka estuary mouth (Urdaibai Biosphere Reserve) in the southeastern region of the Bay of Biscay, suffered the impact of a severe succession of storms during the first months of 2014. As a result of the erosion induced by these events, the beach lost its supratidal zone almost completely. The absence of a supratidal beach generated an impact on the recreational use of the beach during the summer 2014, and represented a potential impact for the coming summer 2015. Furthermore, it resulted in an overexposure and damage of adjacent infrastructures due to impinging strong waves. Therefore, the competent authorities, in coordination, decided to take action in order to nourish the supratidal zone of this beach. The solution adopted combined two different actions. The first one accomplished in spring of 2015, consisted in the mobilization of 44,800 m3 of sand from an area of 35,200 m2 equal to the 7% of the intertidal zone of Laida beach interpreted as the existing surface between the average low and high tidal limits, to the zone next to the eastern rocky beach contour. This action successfully resulted in an increase of the supratidal beach for the entire summer 2015 without negatively perturbing the morphological system. The second action was somewhat experimental and consisted in the mechanical plough of the previously existing intertidal low-amplitude ridges with the aim of increasing the sand transport toward the supratidal beach. Although this action did not lead to the increase of the supratidal beach, it seems to have resulted in an acceleration of the natural onshore migration of the bars. The objective of this contribution is to describe the morphodynamical response of the estuarine mouth after the performed actions with special emphasis on the evolution of extracted sites and the supratidal Laida beach area. The information here presented represents an innovative step in the understanding of the complex mechanisms driving the supratidal beach formation at the mouth of Oka estuary and by extension of the majority of the estuaries of the southeastern Bay of Biscay.

Effect of an educational game on university students' learning about action potentials.

PubMed

Luchi, Kelly Cristina Gaviao; Montrezor, Luís Henrique; Marcondes, Fernanda K

2017-06-01

The aim of this study was to evaluate the effect of an educational game that is used for teaching the mechanisms of the action potentials in cell membranes. The game was composed of pieces representing the intracellular and extracellular environments, ions, ion channels, and the Na + -K + -ATPase pump. During the game activity, the students arranged the pieces to demonstrate how the ions move through the membrane in a resting state and during an action potential, linking the ion movement with a graph of the action potential. To test the effect of the game activity on student understanding, first-year dental students were given the game to play at different times in a series of classes teaching resting membrane potential and action potentials. In all experiments, students who played the game performed better in assessments. According to 98% of the students, the game supported the learning process. The data confirm the students' perception, indicating that the educational game improved their understanding about action potentials. Copyright © 2017 the American Physiological Society.

Understanding the electrical behavior of the action potential in terms of elementary electrical sources.

PubMed

Rodriguez-Falces, Javier

2015-03-01

A concept of major importance in human electrophysiology studies is the process by which activation of an excitable cell results in a rapid rise and fall of the electrical membrane potential, the so-called action potential. Hodgkin and Huxley proposed a model to explain the ionic mechanisms underlying the formation of action potentials. However, this model is unsuitably complex for teaching purposes. In addition, the Hodgkin and Huxley approach describes the shape of the action potential only in terms of ionic currents, i.e., it is unable to explain the electrical significance of the action potential or describe the electrical field arising from this source using basic concepts of electromagnetic theory. The goal of the present report was to propose a new model to describe the electrical behaviour of the action potential in terms of elementary electrical sources (in particular, dipoles). The efficacy of this model was tested through a closed-book written exam. The proposed model increased the ability of students to appreciate the distributed character of the action potential and also to recognize that this source spreads out along the fiber as function of space. In addition, the new approach allowed students to realize that the amplitude and sign of the extracellular electrical potential arising from the action potential are determined by the spatial derivative of this intracellular source. The proposed model, which incorporates intuitive graphical representations, has improved students' understanding of the electrical potentials generated by bioelectrical sources and has heightened their interest in bioelectricity. Copyright © 2015 The American Physiological Society.

Conditional immortalization of human thyroid epithelial cells: a tool for analysis of oncogene action.

PubMed Central

Wynford-Thomas, D; Bond, J A; Wyllie, F S; Burns, J S; Williams, E D; Jones, T; Sheer, D; Lemoine, N R

1990-01-01

To overcome the difficulty of assessing oncogene action in human epithelial cell types, such as thyroid, which have limited proliferative potential in culture, we have explored the use of temperature-sensitive (ts) mutants of simian virus 40 (SV40) early region to create conditionally immortalized epithelial cell lines. Normal primary cultures of human thyroid follicular cells were transfected with a plasmid containing the SV40 early region from mutant tsA58. Expanding epithelial colonies were observed after 2 to 3 months, all of which grew to greater than 200 population doublings without crisis. All showed tight temperature dependence for growth. After switch-up to the restrictive temperature (40.5 degrees C), no further increase in cell number was seen after 1 to 2 days. However, DNA synthesis declined much more slowly; the dissociation from cell division led to marked polyploidy. Viability was maintained for up to 2 weeks. Introduction of an inducible mutant ras gene into ts thyroid cells led, as expected, to morphological transformation at the permissive temperature when ras was induced. Interestingly, this was associated with a marked reduction in net growth rate. At the restrictive temperature, induction of mutant ras caused rapid cell death. These results demonstrate the utility of a ts SV40 mutant to permit the study of oncogene action in an otherwise nonproliferative target cell and reveal important differences in the interaction between ras and SV40 T in these epithelial cells compared with previously studied cell types. Images PMID:1697930

Selective activation of heteromeric SK channels contributes to action potential repolarization in mouse atrial myocytes.

PubMed

Hancock, Jane M; Weatherall, Kate L; Choisy, Stéphanie C; James, Andrew F; Hancox, Jules C; Marrion, Neil V

2015-05-01

Activation of small conductance calcium-activated potassium (SK) channels is proposed to contribute to repolarization of the action potential in atrial myocytes. This role is controversial, as these cardiac SK channels appear to exhibit an uncharacteristic pharmacology. The objectives of this study were to resolve whether activation of SK channels contributes to atrial action potential repolarization and to determine the likely subunit composition of the channel. The effect of 2 SK channel inhibitors was assessed on outward current evoked in voltage clamp and on action potential duration in perforated patch and whole-cell current clamp recording from acutely isolated mouse atrial myocytes. The presence of SK channel subunits was assessed using immunocytochemistry. A significant component of outward current was reduced by the SK channel blockers apamin and UCL1684. Block by apamin displayed a sensitivity indicating that this current was carried by homomeric SK2 channels. Action potential duration was significantly prolonged by UCL1684, but not by apamin. This effect was accompanied by an increase in beat-to-beat variability and action potential triangulation. This pharmacology was matched by that of expressed heteromeric SK2-SK3 channels in HEK293 cells. Immunocytochemistry showed that atrial myocytes express both SK2 and SK3 channels with an overlapping expression pattern. Only proposed heteromeric SK2-SK3 channels are physiologically activated to contribute to action potential repolarization, which is indicated by the difference in pharmacology of evoked outward current and prolongation of atrial action potential duration. The effect of blocking this channel on the action potential suggests that SK channel inhibition during cardiac function has the potential to be proarrhythmic. Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Urocortin2 prolongs action potential duration and modulates potassium currents in guinea pig myocytes and HEK293 cells.

PubMed

Yang, Li-Zhen; Zhu, Yi-Chun

2015-07-05

We previously reported that activation of corticotropin releasing factor receptor type 2 by urocortin2 up-regulates both L-type Ca(2+) channels and intracellular Ca(2+) concentration in ventricular myocytes and plays an important role in cardiac contractility and arrhythmogenesis. This study goal was to further test the hypothesis that urocortin2 may modulate action potentials as well as rapidly and slowly activating delayed rectifier potassium currents. With whole cell patch-clamp techniques, action potentials and slowly activating delayed rectifier potassium currents were recorded in isolated guinea pig ventricular myocytes, respectively. And rapidly activating delayed rectifier potassium currents were tested in hERG-HEK293 cells. Urocortin2 produced a time- and concentration-dependent prolongation of action potential duration. The EC50 values of action potential duration and action potential duration at 90% of repolarization were 14.73 and 24.3nM respectively. The prolongation of action potential duration of urocortin2 was almost completely or partly abolished by H-89 (protein kinase A inhibitor) or KB-R7943 (Na(+)/Ca(2+) exchange inhibitor) pretreatment respectively. And urocortin2 caused reduction of rapidly activating delayed rectifier potassium currents in hERG-HEK293 cells. In addition, urocortin2 slowed the rate of slowly activating delayed rectifier potassium channel activation, and rightward shifted the threshold of slowly activating delayed rectifier potassium currents to more positive potentials. Urocortin2 prolonged action potential duration via activation of protein kinase A and Na(+)/ Ca(2+) exchange in isolated guinea pig ventricular myocytes in a time- and concentration- dependent manner. In hERG-HEK293 cells, urocortin2 reduced rapidly activating delayed rectifier potassium current density which may contribute to action potential duration prolongation. Copyright © 2015 Elsevier B.V. All rights reserved.

Population of computational rabbit-specific ventricular action potential models for investigating sources of variability in cellular repolarisation.

PubMed

Gemmell, Philip; Burrage, Kevin; Rodriguez, Blanca; Quinn, T Alexander

2014-01-01

Variability is observed at all levels of cardiac electrophysiology. Yet, the underlying causes and importance of this variability are generally unknown, and difficult to investigate with current experimental techniques. The aim of the present study was to generate populations of computational ventricular action potential models that reproduce experimentally observed intercellular variability of repolarisation (represented by action potential duration) and to identify its potential causes. A systematic exploration of the effects of simultaneously varying the magnitude of six transmembrane current conductances (transient outward, rapid and slow delayed rectifier K(+), inward rectifying K(+), L-type Ca(2+), and Na(+)/K(+) pump currents) in two rabbit-specific ventricular action potential models (Shannon et al. and Mahajan et al.) at multiple cycle lengths (400, 600, 1,000 ms) was performed. This was accomplished with distributed computing software specialised for multi-dimensional parameter sweeps and grid execution. An initial population of 15,625 parameter sets was generated for both models at each cycle length. Action potential durations of these populations were compared to experimentally derived ranges for rabbit ventricular myocytes. 1,352 parameter sets for the Shannon model and 779 parameter sets for the Mahajan model yielded action potential duration within the experimental range, demonstrating that a wide array of ionic conductance values can be used to simulate a physiological rabbit ventricular action potential. Furthermore, by using clutter-based dimension reordering, a technique that allows visualisation of multi-dimensional spaces in two dimensions, the interaction of current conductances and their relative importance to the ventricular action potential at different cycle lengths were revealed. Overall, this work represents an important step towards a better understanding of the role that variability in current conductances may play in experimentally observed intercellular variability of rabbit ventricular action potential repolarisation.

Population of Computational Rabbit-Specific Ventricular Action Potential Models for Investigating Sources of Variability in Cellular Repolarisation

PubMed Central

Gemmell, Philip; Burrage, Kevin; Rodriguez, Blanca; Quinn, T. Alexander

2014-01-01

Variability is observed at all levels of cardiac electrophysiology. Yet, the underlying causes and importance of this variability are generally unknown, and difficult to investigate with current experimental techniques. The aim of the present study was to generate populations of computational ventricular action potential models that reproduce experimentally observed intercellular variability of repolarisation (represented by action potential duration) and to identify its potential causes. A systematic exploration of the effects of simultaneously varying the magnitude of six transmembrane current conductances (transient outward, rapid and slow delayed rectifier K+, inward rectifying K+, L-type Ca2+, and Na+/K+ pump currents) in two rabbit-specific ventricular action potential models (Shannon et al. and Mahajan et al.) at multiple cycle lengths (400, 600, 1,000 ms) was performed. This was accomplished with distributed computing software specialised for multi-dimensional parameter sweeps and grid execution. An initial population of 15,625 parameter sets was generated for both models at each cycle length. Action potential durations of these populations were compared to experimentally derived ranges for rabbit ventricular myocytes. 1,352 parameter sets for the Shannon model and 779 parameter sets for the Mahajan model yielded action potential duration within the experimental range, demonstrating that a wide array of ionic conductance values can be used to simulate a physiological rabbit ventricular action potential. Furthermore, by using clutter-based dimension reordering, a technique that allows visualisation of multi-dimensional spaces in two dimensions, the interaction of current conductances and their relative importance to the ventricular action potential at different cycle lengths were revealed. Overall, this work represents an important step towards a better understanding of the role that variability in current conductances may play in experimentally observed intercellular variability of rabbit ventricular action potential repolarisation. PMID:24587229

Post-Inhibitory Rebound Spikes in Rat Medial Entorhinal Layer II/III Principal Cells: In Vivo, In Vitro, and Computational Modeling Characterization

PubMed Central

Ferrante, Michele; Shay, Christopher F.; Tsuno, Yusuke; William Chapman, G.; Hasselmo, Michael E.

2017-01-01

Abstract Medial entorhinal cortex Layer-II stellate cells (mEC-LII-SCs) primarily interact via inhibitory interneurons. This suggests the presence of alternative mechanisms other than excitatory synaptic inputs for triggering action potentials (APs) in stellate cells during spatial navigation. Our intracellular recordings show that the hyperpolarization-activated cation current (Ih) allows post-inhibitory-rebound spikes (PIRS) in mEC-LII-SCs. In vivo, strong inhibitory-post-synaptic potentials immediately preceded most APs shortening their delay and enhancing excitability. In vitro experiments showed that inhibition initiated spikes more effectively than excitation and that more dorsal mEC-LII-SCs produced faster and more synchronous spikes. In contrast, PIRS in Layer-II/III pyramidal cells were harder to evoke, voltage-independent, and slower in dorsal mEC. In computational simulations, mEC-LII-SCs morphology and Ih homeostatically regulated the dorso-ventral differences in PIRS timing and most dendrites generated PIRS with a narrow range of stimulus amplitudes. These results suggest inhibitory inputs could mediate the emergence of grid cell firing in a neuronal network. PMID:26965902

Neuromuscular activity of the venoms of the Colombian coral snakes Micrurus dissoleucus and Micrurus mipartitus: an evolutionary perspective.

PubMed

Renjifo, Camila; Smith, Eric N; Hodgson, Wayne C; Renjifo, Juan M; Sanchez, Armando; Acosta, Rodrigo; Maldonado, Jairo H; Riveros, Alain

2012-01-01

The venoms of coral snakes (genus Micrurus) are known to induce a broad spectrum of pharmacological activities. While some studies have investigated their potential human effects, little is known about their mechanism of action in terms of the ecological diversity and evolutionary relationships among the group. In the current study we investigated the neuromuscular blockade of the venom of two sister species Micrurus mipartitus and Micrurus dissoleucus, which exhibit divergent ecological characteristics in Colombia, by using the chick biventer cervicis nerve-muscle preparation. We also undertook a phylogenetic analysis of these species and their congeners, in order to provide an evolutionary framework for the American coral snakes. The venom of M. mipartitus caused a concentration-dependant inhibition (3-10 μg/ml) of nerve-mediated twitches and significantly inhibited contractile responses to exogenous ACh (1 mM), but not KCl (40 mM), indicating a postsynaptic mechanism of action. The inhibition of indirect twitches at the lower venom dose (3 μg/ml) showed to be triphasic and the effect was further attenuated when PLA2 was inhibited. M. dissoleucus venom (10-50 μg/ml) failed to produce a complete blockade of nerve-mediated twitches within a 3 h time period and significantly inhibited contractile responses to exogenous ACh (1 mM) and KCl (40 mM), indicating both postsynaptic and myotoxic mechanisms of action. Myotoxic activity was confirmed by morphological studies of the envenomed tissues. Our results demonstrate a hitherto unsuspected diversity of pharmacological actions in closely related species which exhibit divergent ecological characteristics; these results have important implications for both the clinical management of Coral snake envenomings and the design of Micrurus antivenom. Copyright © 2011 Elsevier Ltd. All rights reserved.

Action potential propagation: ion current or intramembrane electric field?

PubMed

Martí, Albert; Pérez, Juan J; Madrenas, Jordi

2018-01-01

The established action potential propagation mechanisms do not satisfactorily explain propagation on myelinated axons given the current knowledge of biological channels and membranes. The flow across ion channels presents two possible effects: the electric potential variations across the lipid bilayers (action potential) and the propagation of an electric field through the membrane inner part. The proposed mechanism is based on intra-membrane electric field propagation, this propagation can explain the action potential saltatory propagation and its constant delay independent of distance between Ranvier nodes in myelinated axons.

Forward and Backward Pressure Waveform Morphology in Hypertension

PubMed Central

Li, Ye; Gu, Haotian; Fok, Henry; Alastruey, Jordi

2017-01-01

We tested the hypothesis that increased pulse wave reflection and altered backward waveform morphology contribute to increased pulse pressure in subjects with higher pulse pressure compared with lower pulse pressure and to actions of vasoactive drugs to increase pulse pressure. We examined the relationship of backward to forward wave morphology in 158 subjects who were evaluated for hypertension (including some normotensive subjects) divided into 3 groups by central pulse pressure: group 1, 33±6.5 mm Hg; group 2, 45±4.1 mm Hg; and group 3, 64±12.9 mm Hg (means±SD) and in healthy normotensive subjects during administration of inotropic and vasomotor drugs. Aortic pressure and flow in the aortic root were estimated by carotid tonometry and Doppler sonography, respectively. Morphology of the backward wave relative to the forward wave was similar in subjects in the lowest and highest tertiles of pulse pressure. Similar results were seen with the inotropic, vasopressor and vasodilator drugs, dobutamine, norepinephrine, and phentolamine, with the backward wave maintaining a constant ratio to the forward wave. However, nitroglycerin, a drug with a specific action to dilate muscular conduit arteries, reduced the amplitude of the backward wave relative to the forward wave from 0.26±0.018 at baseline to 0.19±0.019 during nitroglycerin 30 μg/min IV (P<0.01). These results are best explained by an approximately constant amount of reflection of the forward wave from the peripheral vasculature. The amount of reflection can be modified by dilation of peripheral muscular conduit arteries but contributes little to increased pulse pressure in hypertension. PMID:27920128

Antidromic propagation of action potentials in branched axons: implications for the mechanisms of action of deep brain stimulation.

PubMed

Grill, Warren M; Cantrell, Meredith B; Robertson, Matthew S

2008-02-01

Electrical stimulation of the central nervous system creates both orthodromically propagating action potentials, by stimulation of local cells and passing axons, and antidromically propagating action potentials, by stimulation of presynaptic axons and terminals. Our aim was to understand how antidromic action potentials navigate through complex arborizations, such as those of thalamic and basal ganglia afferents-sites of electrical activation during deep brain stimulation. We developed computational models to study the propagation of antidromic action potentials past the bifurcation in branched axons. In both unmyelinated and myelinated branched axons, when the diameters of each axon branch remained under a specific threshold (set by the antidromic geometric ratio), antidromic propagation occurred robustly; action potentials traveled both antidromically into the primary segment as well as "re-orthodromically" into the terminal secondary segment. Propagation occurred across a broad range of stimulation frequencies, axon segment geometries, and concentrations of extracellular potassium, but was strongly dependent on the geometry of the node of Ranvier at the axonal bifurcation. Thus, antidromic activation of axon terminals can, through axon collaterals, lead to widespread activation or inhibition of targets remote from the site of stimulation. These effects should be included when interpreting the results of functional imaging or evoked potential studies on the mechanisms of action of DBS.

Minocycline inhibits D-amphetamine-elicited action potential bursts in a central snail neuron.

PubMed

Chen, Y-H; Lin, P-L; Wong, R-W; Wu, Y-T; Hsu, H-Y; Tsai, M-C; Lin, M-J; Hsu, Y-C; Lin, C-H

2012-10-25

Minocycline is a second-generation tetracycline that has been reported to have powerful neuroprotective properties. In our previous studies, we found that d-amphetamine (AMPH) elicited action potential bursts in an identifiable RP4 neuron of the African snail, Achatina fulica Ferussac. This study sought to determine the effects of minocycline on the AMPH-elicited action potential pattern changes in the central snail neuron, using the two-electrode voltage clamping method. Extracellular application of AMPH at 300 μM elicited action potential bursts in the RP4 neuron. Minocycline dose-dependently (300-900 μM) inhibited the action potential bursts elicited by AMPH. The inhibitory effects of minocycline on AMPH-elicited action potential bursts were restored by forskolin (50 μM), an adenylate cyclase activator, and by dibutyryl cAMP (N(6),2'-O-Dibutyryladenosine 3',5'-cyclic monophosphate; 1mM), a membrane-permeable cAMP analog. Co-administration of forskolin (50 μM) plus tetraethylammonium chloride (TEA; 5mM) or co-administration of TEA (5mM) plus dibutyryl cAMP (1mM) also elicited action potential bursts, which were prevented and inhibited by minocycline. In addition, minocycline prevented and inhibited forskolin (100 μM)-elicited action potential bursts. Notably, TEA (50mM)-elicited action potential bursts in the RP4 neuron were not affected by minocycline. Minocycline did not affect steady-state outward currents of the RP4 neuron. However, minocycline did decrease the AMPH-elicited steady-state current changes. Similarly, minocycline decreased the effects of forskolin-elicited steady-state current changes. Pretreatment with H89 (N-[2-(p-Bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide dihydrochloride; 10 μM), a protein kinase A inhibitor, inhibited AMPH-elicited action potential bursts and decreased AMPH-elicited steady-state current changes. These results suggest that the cAMP-protein kinase A signaling pathway and the steady-state current are involved in the inhibitory effects of minocycline upon AMPH-elicited action potential bursts. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

Morphological Encoding in German Children's Language Production: Evidence from Event-Related Brain Potentials

ERIC Educational Resources Information Center

Jessen, Anna; Fleischhauer, Elisabeth; Clahsen, Harald

2017-01-01

This study reports developmental changes in morphological encoding across late childhood. We examined event-related brain potentials (ERPs) during the silent production of regularly vs. irregularly inflected verb forms (viz. "-t" vs. "-n" participles of German) in groups of eight- to ten-year-olds, eleven- to…

Selective effects of an octopus toxin on action potentials

PubMed Central

Dulhunty, Angela; Gage, Peter W.

1971-01-01

1. A lethal, water soluble toxin (Maculotoxin, MTX) with a molecular weight less than 540, can be extracted from the salivary glands of an octopus (Hapalochlaena maculosa). 2. MTX blocks action potentials in sartorius muscle fibres of toads without affecting the membrane potential. Delayed rectification is not inhibited by the toxin. 3. At low concentrations (10-6-10-5 g/ml.) MTX blocks action potentials only after a certain number have been elicited. The number of action potentials, which can be defined accurately, depends on the concentration of MTX and the concentration of sodium ions in the extracellular solution. 4. The toxin has no post-synaptic effect at the neuromuscular junction and it is concluded that it blocks neuromuscular transmission by inhibiting action potentials in motor nerve terminals. PMID:4330930

GENE EXPRESSION ANALYSIS IN THE VENTRAL PROSTATE OF RATS EXPOSED TO VINCLOZOLIN OR PROCYMIDONE

EPA Science Inventory

Vinclozolin and procymidone are antiandrogens that are thought to share a common androgen receptor (AR) mediated mechanism of action. This assessment is based primarily on morphological, AR binding, and in vitro transcriptional activation studies. Studies designed to evaluate t...

Relationship between size and latency of action potentials in human muscle sympathetic nerve activity.

PubMed

Salmanpour, Aryan; Brown, Lyndon J; Steinback, Craig D; Usselman, Charlotte W; Goswami, Ruma; Shoemaker, J Kevin

2011-06-01

We employed a novel action potential detection and classification technique to study the relationship between the recruitment of sympathetic action potentials (i.e., neurons) and the size of integrated sympathetic bursts in human muscle sympathetic nerve activity (MSNA). Multifiber postganglionic sympathetic nerve activity from the common fibular nerve was collected using microneurography in 10 healthy subjects at rest and during activation of sympathetic outflow using lower body negative pressure (LBNP). Burst occurrence increased with LBNP. Integrated burst strength (size) varied from 0.22 ± 0.07 V at rest to 0.28 ± 0.09 V during LBNP. Sympathetic burst size (i.e., peak height) was directly related to the number of action potentials within a sympathetic burst both at baseline (r = 0.75 ± 0.13; P < 0.001) and LBNP (r = 0.75 ± 0.12; P < 0.001). Also, the amplitude of detected action potentials within sympathetic bursts was directly related to the increased burst size at both baseline (r = 0.59 ± 0.16; P < 0.001) and LBNP (r = 0.61 ± 0.12; P < 0.001). In addition, the number of detected action potentials and the number of distinct action potential clusters within a given sympathetic burst were correlated at baseline (r = 0.7 ± 0.1; P < 0.001) and during LBNP (r = 0.74 ± 0.03; P < 0.001). Furthermore, action potential latency (i.e., an inverse index of neural conduction velocity) was decreased as a function of action potential size at baseline and LBNP. LBNP did not change the number of action potentials and unique clusters per sympathetic burst. It was concluded that there exists a hierarchical pattern of recruitment of additional faster conducting neurons of larger amplitude as the sympathetic bursts become stronger (i.e., larger amplitude bursts). This fundamental pattern was evident at rest and was not altered by the level of baroreceptor unloading applied in this study.

All optical experimental design for neuron excitation, inhibition, and action potential detection

NASA Astrophysics Data System (ADS)

Walsh, Alex J.; Tolstykh, Gleb; Martens, Stacey; Sedelnikova, Anna; Ibey, Bennett L.; Beier, Hope T.

2016-03-01

Recently, infrared light has been shown to both stimulate and inhibit excitatory cells. However, studies of infrared light for excitatory cell inhibition have been constrained by the use of invasive and cumbersome electrodes for cell excitation and action potential recording. Here, we present an all optical experimental design for neuronal excitation, inhibition, and action potential detection. Primary rat neurons were transfected with plasmids containing the light sensitive ion channel CheRiff. CheRiff has a peak excitation around 450 nm, allowing excitation of transfected neurons with pulsed blue light. Additionally, primary neurons were transfected with QuasAr2, a fast and sensitive fluorescent voltage indicator. QuasAr2 is excited with yellow or red light and therefore does not spectrally overlap CheRiff, enabling imaging and action potential activation, simultaneously. Using an optic fiber, neurons were exposed to blue light sequentially to generate controlled action potentials. A second optic fiber delivered a single pulse of 1869nm light to the neuron causing inhibition of the evoked action potentials (by the blue light). When used in concert, these optical techniques enable electrode free neuron excitation, inhibition, and action potential recording, allowing research into neuronal behaviors with high spatial fidelity.

Surface-potential undulation of Alq3 thin films prepared on ITO, Au, and n-Si.

PubMed

Ozasa, Kazunari; Ito, Hiromi; Maeda, Mizuo; Hara, Masahiko

2012-01-01

The surface potential (SP) morphology on thin films of tris(8-hydroxyquinolinato) aluminum (Alq3) was investigated with Kelvin probe force microscopy. Thin Alq3 films of 100 nm were prepared on ITO/glass substrates, Au/mica substrates, and n-Si substrates. Cloud-like morphologies of the SP undulation with 200-400 nm in lateral size were observed for all three types of the substrates. New larger peaks were observed in the cloud-like morphologies when the surfaces were exposed shortly to a light, while the SP average was reduced monotonically. The nonuniform distribution of charged traps and mobility was deduced from the SP undulation morphology and its photoexposure dependences.

Effect of Cu Alloying on S Poisoning of Ni Surfaces and Nanoparticle Morphologies Using Ab-Initio Thermodynamics Calculations.

PubMed

Kim, Ji-Su; Kim, Byung-Kook; Kim, Yeong-Cheol

2015-10-01

We investigated the effect of Cu alloying on S poisoning of Ni surfaces and nanoparticle morphologies using ab-initio thermodynamics calculations. Based on the Cu segregation energy and the S adsorption energy, the surface energy and nanoparticle morphology of pure Ni, pure Cu, and NiCu alloys were evaluated as functions of the chemical potential of S and the surface orientations of (100), (110), and (111). The constructed nanoparticle morphology was varied as a function of chemical potential of S. We find that the Cu added to Ni for NiCu alloys is strongly segregated into the top surface, and increases the S tolerance of the NiCu nanoparticles.

Functional morphology of the cranio-mandibular complex of the Guira cuckoo (Aves).

PubMed

Pestoni, Sofía; Degrange, Federico Javier; Tambussi, Claudia Patricia; Demmel Ferreira, María Manuela; Tirao, Germán Alfredo

2018-06-01

The cranio-mandibular complex is an important structure involved in food capture and processing. Its morphology is related to the nature of the food item. Jaw muscles enable the motion of this complex and their study is essential for functional and evolutionary analysis. The present study compares available behavioral and dietary data obtained from the literature with novel results from functional morphological analyses of the cranio-mandibular complex of the Guira cuckoo (Guira guira) to understand its relationship with the zoophagous trophic habit of this species. The bite force was estimated based on muscle dissections, measurements of the physiological cross-sectional area, and biomechanical modeling of the skull. The results were compared with the available functional morphological data for other birds. The standardized bite force of G. guira is higher than predicted for exclusively zoophagous birds, but lower than for granivorous and/or omnivorous birds. Guira guira possesses the generalized jaw muscular system of neognathous birds, but some features can be related to its trophic habit. The external adductor muscles act mainly during food item processing and multiple aspects of this muscle group are interpreted to increase bite force, that is, their high values of muscle mass, their mechanical advantage (MA), and their perpendicular orientation when the beak is closed. The m. depressor mandibulae and the m. pterygoideus dorsalis et ventralis are interpreted to prioritize speed of action (low MA values), being most important during prey capture. The supposed ecological significance of these traits is the potential to widen the range of prey size that can be processed and the possibility of rapidly capturing agile prey through changes in the leverage of the muscles involved in opening and closing of the bill. This contributes to the trophic versatility of the species and its ability to thrive in different habitats, including urban areas. © 2018 Wiley Periodicals, Inc.

Cortical Action Potential Backpropagation Explains Spike Threshold Variability and Rapid-Onset Kinetics

PubMed Central

Yu, Yuguo; Shu, Yousheng; McCormick, David A.

2008-01-01

Neocortical action potential responses in vivo are characterized by considerable threshold variability, and thus timing and rate variability, even under seemingly identical conditions. This finding suggests that cortical ensembles are required for accurate sensorimotor integration and processing. Intracellularly, trial-to-trial variability results not only from variation in synaptic activities, but also in the transformation of these into patterns of action potentials. Through simultaneous axonal and somatic recordings and computational simulations, we demonstrate that the initiation of action potentials in the axon initial segment followed by backpropagation of these spikes throughout the neuron results in a distortion of the relationship between the timing of synaptic and action potential events. In addition, this backpropagation also results in an unusually high rate of rise of membrane potential at the foot of the action potential. The distortion of the relationship between the amplitude time course of synaptic inputs and action potential output caused by spike back-propagation results in the appearance of high spike threshold variability at the level of the soma. At the point of spike initiation, the axon initial segment, threshold variability is considerably less. Our results indicate that spike generation in cortical neurons is largely as expected by Hodgkin—Huxley theory and is more precise than previously thought. PMID:18632930

Median and ulnar muscle and sensory evoked potentials.

PubMed

Felsenthal, G

1978-08-01

The medical literature was reviewed to find suggested clinical applications of the study of the amplitude of evoked muscle action potentials (MAP) and sensory action potentials (SAP). In addition, the literature was reviewed to ascertain the normal amplitude and duration of the evoked MAP and SAP as well as the factors affecting the amplitude: age, sex, temperature, ischemia. The present study determined the normal amplitude and duration of the median and ulnar MAP and SAP in fifty normal subjects. The amplitude of evoked muscle or sensory action potentials depends on multiple factors. Increased skin resistance, capacitance, and impedance at the surface of the recording electrode diminishes the amplitude. Similarly, increased distance from the source of the action potential diminishes its amplitude. Increased interelectrode distance increases the amplitude of the bipolarly recorded sensory action potential until a certain interelectrode distance is exceeded and the diphasic response becomes tri- or tetraphasic. Artifact or poor technique may reduce the potential difference between the recording electrodes or obscure the late positive phase of the action potential and thus diminish the peak to peak amplitude measurement. Intraindividual comparison indicated a marked difference of amplitude in opposite hands. The range of the MAP of the abductor pollicis brevis in one hand was 40.0--100% of the response in the opposite hand. For the abductor digiti minimi, the MAP was 58.5--100% of the response of the opposite hand. The median and ulnar SAP was between 50--100% of the opposite SAP. Consequent to these findings the effect of hand dominance on the amplitude of median and ulnar evoked muscle and sensory action potentials was studied in 41 right handed volunteers. The amplitudes of the median muscle action potential (p less than 0.02) and the median and ulnar sensory action potentials (p less than 0.001) were significantly less in the dominant hand. There was no significant difference between the ulnar muscle action potentials or for the median and ulnar distal motor and sensory latencies in the right and left hands of this group of volunteers.

Ionotropic glutamate receptor GluA4 and T-type calcium channel Cav 3.1 subunits control key aspects of synaptic transmission at the mouse L5B-POm giant synapse.

PubMed

Seol, Min; Kuner, Thomas

2015-12-01

The properties and molecular determinants of synaptic transmission at giant synapses connecting layer 5B (L5B) neurons of the somatosensory cortex (S1) with relay neurons of the posteriomedial nucleus (POm) of the thalamus have not been investigated in mice. We addressed this by using direct electrical stimulation of fluorescently labelled single corticothalamic terminals combined with molecular perturbations and whole-cell recordings from POm relay neurons. Consistent with their function as drivers, we found large-amplitude excitatory postsynaptic currents (EPSCs) and multiple postsynaptic action potentials triggered by a single presynaptic action potential. To study the molecular basis of these two features, ionotropic glutamate receptors and low voltage-gated T-type calcium channels were probed by virus-mediated genetic perturbation. Loss of GluA4 almost abolished the EPSC amplitude, strongly delaying the onset of action potential generation, but maintaining the number of action potentials generated per presynaptic action potential. In contrast, knockdown of the Cav 3.1 subunit abrogated the driver function of the synapse at a typical resting membrane potential of -70 mV. However, when depolarizing the membrane potential to -60 mV, the synapse relayed single action potentials. Hence, GluA4 subunits are required to produce an EPSC sufficiently large to trigger postsynaptic action potentials within a defined time window after the presynaptic action potential, while Cav 3.1 expression is essential to establish the driver function of L5B-POm synapses at hyperpolarized membrane potentials. © 2015 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Low concentrations of procaine and diethylaminoethanol reduce the excitability but not the action potential amplitude of hippocampal pyramidal cells.

PubMed

Butterworth, J F; Cole, L R

1990-10-01

To determine whether concentrations of diethylaminoethanol (DEAE) and procaine below those that reduce the amplitude of action potentials might alter the excitability of brain cells, a single microelectrode intracellular recording technique was used to measure firing threshold and action potential amplitude of pyramidal cells in rat hippocampal slices. At low concentrations of both DEAE (less than or equal to 5 mM) and procaine (less than or equal to 0.5 mM), firing threshold was significantly increased (P less than 0.01), whereas action potential spike amplitude was minimally altered. At higher concentrations, both drugs significantly decreased action potential spike amplitude (P less than 0.025) as well as increased firing threshold (P less than 0.001). Diethylaminoethanol tended to increase threshold relatively more than procaine, when drug concentrations that similarly reduced action potential amplitude were compared. All actions of DEAE and procaine were reversible. Inhibition of action potentials by DEAE and procaine was clearly concentration-dependent (P less than or equal to 0.015). Diethylaminoethanol effects on threshold were marginally concentration-dependent (P = 0.08); procaine did not demonstrate clear concentration-dependent effects (P = 0.33) over the concentrations tested in this study. These similar actions of procaine and DEAE on brain cells suggest a mechanism by which intravenous local anesthetics may contribute to the general anesthetic state. Moreover, it appears possible that procaine metabolism and DEAE accumulation may underlie the prolonged effects sometimes seen after intravenous procaine administration.

In vitro antitumor actions of extracts from endemic plant Helichrysum zivojinii

PubMed Central

2013-01-01

Background The aim of this research was to determine the intensity and mechanisms of the cytotoxic actions of five extracts isolated from the endemic plant species Helichrysum zivojinii Černjavski & Soška (family Asteraceae) against specific cancer cell lines. In order to evaluate the sensitivity of normal immunocompetent cells implicated in the antitumor immune response, the cytotoxicity of extracts was also tested against healthy peripheral blood mononuclear cells (PBMC). Methods The aerial parts of the plants were air-dried, powdered, and successively extracted with solvents of increasing polarity to obtain hexane, dichloromethane, ethyl-acetate, n-butanol and methanol extracts. The cytotoxic activities of the extracts against human cervix adenocarcinoma HeLa, human melanoma Fem-x, human myelogenous leukemia K562, human breast adenocarcinoma MDA-MB-361 cells and PBMC were evaluated by the MTT test. The mode of HeLa cell death was investigated by morphological analysis. Changes in the cell cycle of HeLa cells treated with the extracts were analyzed by flow cytometry. The apoptotic mechanisms induced by the tested extracts were determined using specific caspase inhibitors. Results The investigated Helichrysum zivojinii extracts exerted selective dose-dependent cytotoxic actions against selected cancer cell lines and healthy immunocompetent PBMC stimulated to proliferate, while the cytotoxic actions exerted on unstimulated PBMC were less pronounced. The tested extracts exhibited considerably stronger cytotoxic activities towards HeLa, Fem-x and K562 cells in comparison to resting and stimulated PBMC. It is worth noting that the cytotoxicity of the extracts was weaker against unstimulated PBMC in comparison to stimulated PBMC. Furthermore, each of the five extracts induced apoptosis in HeLa cells, through the activation of both intrinsic and extrinsic signaling pathways. Conclusion Extracts obtained from the endemic plant Helichrysum zivojinii may represent an important source of novel potential antitumor agents due to their pronounced and selective cytotoxic actions towards malignant cells. PMID:23414290

In vitro antitumor actions of extracts from endemic plant Helichrysum zivojinii.

PubMed

Matić, Ivana Z; Aljančić, Ivana; Žižak, Željko; Vajs, Vlatka; Jadranin, Milka; Milosavljević, Slobodan; Juranić, Zorica D

2013-02-18

The aim of this research was to determine the intensity and mechanisms of the cytotoxic actions of five extracts isolated from the endemic plant species Helichrysum zivojinii Černjavski & Soška (family Asteraceae) against specific cancer cell lines. In order to evaluate the sensitivity of normal immunocompetent cells implicated in the antitumor immune response, the cytotoxicity of extracts was also tested against healthy peripheral blood mononuclear cells (PBMC). The aerial parts of the plants were air-dried, powdered, and successively extracted with solvents of increasing polarity to obtain hexane, dichloromethane, ethyl-acetate, n-butanol and methanol extracts. The cytotoxic activities of the extracts against human cervix adenocarcinoma HeLa, human melanoma Fem-x, human myelogenous leukemia K562, human breast adenocarcinoma MDA-MB-361 cells and PBMC were evaluated by the MTT test. The mode of HeLa cell death was investigated by morphological analysis. Changes in the cell cycle of HeLa cells treated with the extracts were analyzed by flow cytometry. The apoptotic mechanisms induced by the tested extracts were determined using specific caspase inhibitors. The investigated Helichrysum zivojinii extracts exerted selective dose-dependent cytotoxic actions against selected cancer cell lines and healthy immunocompetent PBMC stimulated to proliferate, while the cytotoxic actions exerted on unstimulated PBMC were less pronounced. The tested extracts exhibited considerably stronger cytotoxic activities towards HeLa, Fem-x and K562 cells in comparison to resting and stimulated PBMC. It is worth noting that the cytotoxicity of the extracts was weaker against unstimulated PBMC in comparison to stimulated PBMC. Furthermore, each of the five extracts induced apoptosis in HeLa cells, through the activation of both intrinsic and extrinsic signaling pathways. Extracts obtained from the endemic plant Helichrysum zivojinii may represent an important source of novel potential antitumor agents due to their pronounced and selective cytotoxic actions towards malignant cells.

78 FR 34031 - Burned Area Emergency Response, Forest Service

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-06

...) Evaluate potential threats to critical values; (2) determine the risk level for each threat; (3) identify... actions that meet the objectives; (6) evaluate potential response actions on likelihood for timely... stabilization actions. Improved the descriptive guidelines for employing response actions involving...

SACE_5599, a putative regulatory protein, is involved in morphological differentiation and erythromycin production in Saccharopolyspora erythraea.

PubMed

Kirm, Benjamin; Magdevska, Vasilka; Tome, Miha; Horvat, Marinka; Karničar, Katarina; Petek, Marko; Vidmar, Robert; Baebler, Spela; Jamnik, Polona; Fujs, Štefan; Horvat, Jaka; Fonovič, Marko; Turk, Boris; Gruden, Kristina; Petković, Hrvoje; Kosec, Gregor

2013-12-17

Erythromycin is a medically important antibiotic, biosynthesized by the actinomycete Saccharopolyspora erythraea. Genes encoding erythromycin biosynthesis are organized in a gene cluster, spanning over 60 kbp of DNA. Most often, gene clusters encoding biosynthesis of secondary metabolites contain regulatory genes. In contrast, the erythromycin gene cluster does not contain regulatory genes and regulation of its biosynthesis has therefore remained poorly understood, which has for a long time limited genetic engineering approaches for erythromycin yield improvement. We used a comparative proteomic approach to screen for potential regulatory proteins involved in erythromycin biosynthesis. We have identified a putative regulatory protein SACE_5599 which shows significantly higher levels of expression in an erythromycin high-producing strain, compared to the wild type S. erythraea strain. SACE_5599 is a member of an uncharacterized family of putative regulatory genes, located in several actinomycete biosynthetic gene clusters. Importantly, increased expression of SACE_5599 was observed in the complex fermentation medium and at controlled bioprocess conditions, simulating a high-yield industrial fermentation process in the bioreactor. Inactivation of SACE_5599 in the high-producing strain significantly reduced erythromycin yield, in addition to drastically decreasing sporulation intensity of the SACE_5599-inactivated strains when cultivated on ABSM4 agar medium. In contrast, constitutive overexpression of SACE_5599 in the wild type NRRL23338 strain resulted in an increase of erythromycin yield by 32%. Similar yield increase was also observed when we overexpressed the bldD gene, a previously identified regulator of erythromycin biosynthesis, thereby for the first time revealing its potential for improving erythromycin biosynthesis. SACE_5599 is the second putative regulatory gene to be identified in S. erythraea which has positive influence on erythromycin yield. Like bldD, SACE_5599 is involved in morphological development of S. erythraea, suggesting a very close relationship between secondary metabolite biosynthesis and morphological differentiation in this organism. While the mode of action of SACE_5599 remains to be elucidated, the manipulation of this gene clearly shows potential for improvement of erythromycin production in S. erythraea in industrial setting. We have also demonstrated the applicability of the comparative proteomics approach for identifying new regulatory elements involved in biosynthesis of secondary metabolites in industrial conditions.

SACE_5599, a putative regulatory protein, is involved in morphological differentiation and erythromycin production in Saccharopolyspora erythraea

PubMed Central

2013-01-01

Background Erythromycin is a medically important antibiotic, biosynthesized by the actinomycete Saccharopolyspora erythraea. Genes encoding erythromycin biosynthesis are organized in a gene cluster, spanning over 60 kbp of DNA. Most often, gene clusters encoding biosynthesis of secondary metabolites contain regulatory genes. In contrast, the erythromycin gene cluster does not contain regulatory genes and regulation of its biosynthesis has therefore remained poorly understood, which has for a long time limited genetic engineering approaches for erythromycin yield improvement. Results We used a comparative proteomic approach to screen for potential regulatory proteins involved in erythromycin biosynthesis. We have identified a putative regulatory protein SACE_5599 which shows significantly higher levels of expression in an erythromycin high-producing strain, compared to the wild type S. erythraea strain. SACE_5599 is a member of an uncharacterized family of putative regulatory genes, located in several actinomycete biosynthetic gene clusters. Importantly, increased expression of SACE_5599 was observed in the complex fermentation medium and at controlled bioprocess conditions, simulating a high-yield industrial fermentation process in the bioreactor. Inactivation of SACE_5599 in the high-producing strain significantly reduced erythromycin yield, in addition to drastically decreasing sporulation intensity of the SACE_5599-inactivated strains when cultivated on ABSM4 agar medium. In contrast, constitutive overexpression of SACE_5599 in the wild type NRRL23338 strain resulted in an increase of erythromycin yield by 32%. Similar yield increase was also observed when we overexpressed the bldD gene, a previously identified regulator of erythromycin biosynthesis, thereby for the first time revealing its potential for improving erythromycin biosynthesis. Conclusions SACE_5599 is the second putative regulatory gene to be identified in S. erythraea which has positive influence on erythromycin yield. Like bldD, SACE_5599 is involved in morphological development of S. erythraea, suggesting a very close relationship between secondary metabolite biosynthesis and morphological differentiation in this organism. While the mode of action of SACE_5599 remains to be elucidated, the manipulation of this gene clearly shows potential for improvement of erythromycin production in S. erythraea in industrial setting. We have also demonstrated the applicability of the comparative proteomics approach for identifying new regulatory elements involved in biosynthesis of secondary metabolites in industrial conditions. PMID:24341557

Recovery of vestibular function following hair cell destruction by streptomycin

NASA Technical Reports Server (NTRS)

Jones, T. A.; Nelson, R. C.

1992-01-01

Can the vestibular periphery of warm-blooded vertebrates recover functionally from severe sensory hair cell loss? Recent findings in birds suggest a mechanism for recovery but in fact no direct functional evidence has been reported. We produced vestibular hair cell lesions using the ototoxic agent streptomycin sulfate (600 mg/kg/day, 8 days, chicks, Gallus domesticus). Compound action potentials of the vestibular nerve were used as a direct measure of peripheral vestibular function. Vestibular thresholds, neural activation latencies and amplitudes were documented. Eight days of drug treatment elevated thresholds significantly (P < 0.001) and eliminated all but remnants of vestibular activity. Virtually complete physiological recovery occurred in all animals studied over a period of 70 days following treatment. Thresholds recovered within two weeks of drug treatment whereas the return of response morphologies including activation latencies and amplitudes required an additional 6-8 weeks.

Activities of several benzimidazoles and tubulin inhibitors against Giardia spp. in vitro.

PubMed Central

Morgan, U M; Reynoldson, J A; Thompson, R C

1993-01-01

Previous studies in our laboratory have shown that albendazole is effective against Giardia spp. in vitro and in vivo, prompting an investigation of the effects of several related benzimidazoles (BZs) on the viability of this protozoan parasite. A range of BZs was tested, and their effects were compared with those of a number of microtubule inhibitors. The effects produced by the two types of drugs were markedly similar, namely, trophozoite detachment and distortion of morphology and general structure, indicating a potential antimicrotubule mode of action for BZs. Mebendazole, albendazole, and fenbendazole proved to be among the most effective BZs tested, exhibiting apparent irreversibility. Nocodazole, oxfendazole, and albendazole sulfoxide, among others, produced transient inhibitions only. Further studies are required to evaluate all available BZs and other antigiardial agents to ensure the development of the most effective and safest antigiardial agent possible. PMID:8452365

Fractional diffusion models of cardiac electrical propagation: role of structural heterogeneity in dispersion of repolarization

PubMed Central

Bueno-Orovio, Alfonso; Kay, David; Grau, Vicente; Rodriguez, Blanca; Burrage, Kevin

2014-01-01

Impulse propagation in biological tissues is known to be modulated by structural heterogeneity. In cardiac muscle, improved understanding on how this heterogeneity influences electrical spread is key to advancing our interpretation of dispersion of repolarization. We propose fractional diffusion models as a novel mathematical description of structurally heterogeneous excitable media, as a means of representing the modulation of the total electric field by the secondary electrical sources associated with tissue inhomogeneities. Our results, analysed against in vivo human recordings and experimental data of different animal species, indicate that structural heterogeneity underlies relevant characteristics of cardiac electrical propagation at tissue level. These include conduction effects on action potential (AP) morphology, the shortening of AP duration along the activation pathway and the progressive modulation by premature beats of spatial patterns of dispersion of repolarization. The proposed approach may also have important implications in other research fields involving excitable complex media. PMID:24920109

Cellular Reparative Mechanisms of Mesenchymal Stem Cells for Retinal Diseases.

PubMed

Ding, Suet Lee Shirley; Kumar, Suresh; Mok, Pooi Ling

2017-07-28

The use of multipotent mesenchymal stem cells (MSCs) has been reported as promising for the treatment of numerous degenerative disorders including the eye. In retinal degenerative diseases, MSCs exhibit the potential to regenerate into retinal neurons and retinal pigmented epithelial cells in both in vitro and in vivo studies. Delivery of MSCs was found to improve retinal morphology and function and delay retinal degeneration. In this review, we revisit the therapeutic role of MSCs in the diseased eye. Furthermore, we reveal the possible cellular mechanisms and identify the associated signaling pathways of MSCs in reversing the pathological conditions of various ocular disorders such as age-related macular degeneration (AMD), retinitis pigmentosa, diabetic retinopathy, and glaucoma. Current stem cell treatment can be dispensed as an independent cell treatment format or with the combination of other approaches. Hence, the improvement of the treatment strategy is largely subjected by our understanding of MSCs mechanism of action.

Cellular Reparative Mechanisms of Mesenchymal Stem Cells for Retinal Diseases

PubMed Central

Ding, Suet Lee Shirley; Kumar, Suresh; Mok, Pooi Ling

2017-01-01

The use of multipotent mesenchymal stem cells (MSCs) has been reported as promising for the treatment of numerous degenerative disorders including the eye. In retinal degenerative diseases, MSCs exhibit the potential to regenerate into retinal neurons and retinal pigmented epithelial cells in both in vitro and in vivo studies. Delivery of MSCs was found to improve retinal morphology and function and delay retinal degeneration. In this review, we revisit the therapeutic role of MSCs in the diseased eye. Furthermore, we reveal the possible cellular mechanisms and identify the associated signaling pathways of MSCs in reversing the pathological conditions of various ocular disorders such as age-related macular degeneration (AMD), retinitis pigmentosa, diabetic retinopathy, and glaucoma. Current stem cell treatment can be dispensed as an independent cell treatment format or with the combination of other approaches. Hence, the improvement of the treatment strategy is largely subjected by our understanding of MSCs mechanism of action. PMID:28788088

Catalytic control over supramolecular gel formation

NASA Astrophysics Data System (ADS)

Boekhoven, Job; Poolman, Jos M.; Maity, Chandan; Li, Feng; van der Mee, Lars; Minkenberg, Christophe B.; Mendes, Eduardo; van Esch, Jan H.; Eelkema, Rienk

2013-05-01

Low-molecular-weight gels show great potential for application in fields ranging from the petrochemical industry to healthcare and tissue engineering. These supramolecular gels are often metastable materials, which implies that their properties are, at least partially, kinetically controlled. Here we show how the mechanical properties and structure of these materials can be controlled directly by catalytic action. We show how in situ catalysis of the formation of gelator molecules can be used to accelerate the formation of supramolecular hydrogels, which drastically enhances their resulting mechanical properties. Using acid or nucleophilic aniline catalysis, it is possible to make supramolecular hydrogels with tunable gel-strength in a matter of minutes, under ambient conditions, starting from simple soluble building blocks. By changing the rate of formation of the gelator molecules using a catalyst, the overall rate of gelation and the resulting gel morphology are affected, which provides access to metastable gel states with improved mechanical strength and appearance despite an identical gelator composition.

Discordant U waves in the setting of hyperkalaemia.

PubMed

Chhabra, Lovely; Spodick, David H

2013-07-04

Physiological U wave genesis occurs likely secondary to either late repolarisation of Purkinje fibres, or late repolarisation of some myocardial cells and/or delayed after depolarisation of the ventricular wall occurring during ventricular filling. Hypokalaemia has a well-known association with pathological 'U wave' which actually combines with the T wave (TU complex) and results from slowing of phase 3 of the action potential with resultant electrical interaction between the three myocardial layers. U waves usually tend to disappear in the setting of hyperkalaemia. We report an unusual case where hyperkalaemia and discordant U waves coexisted. We believe that this may have occurred as a result of partial clinical adaptation of cardiac myocytes to the long-standing effects of hyperkalaemia as the patient had underlying history of chronic kidney disease. We also discuss the possible mechanisms of the U wave genesis and the importance of different U wave morphologies encountered in the real clinical practice.

In vitro evaluation of bioactive potential of Bacillus methylotrophicus YML008 against Propionibacterium acnes.

PubMed

Choi, Uk-Han; Nam, Eun Sook; Ahmad, Rather Irfan; Park, Yong-Ha

2016-05-01

Acne vulgaris is the most common skin diseases that people experience during their lives. Thirteen rhizosphere isolates were screened against Propionibacterium acnes. The bacterium exhibited the highest activity against P. acnes was identified as Bacillus methylotrophicus YML008 by 16S rRNA gene sequencing. Scanning electron microscopy was used to assess the changes in morphology of P. acnes. Preliminary studies on the antimicrobial substance demonstrated the hydrophilic nature of compound with MIC of 0.17mg/ml and MBC of 0.3mg/ml. The cytotoxic effect of the extract was least (80% survival) as compared to benzyperoxide (40% survival). These results suggest YML008 as a promising bioresource and may be useful as a lead bacterium to develop a new type of anti-acne skin care prep to cure or prevent acne. Further, mechanism of action and proper clinical trials may be promising for this research.

The Segregated Expression of Voltage-Gated Potassium and Sodium Channels in Neuronal Membranes: Functional Implications and Regulatory Mechanisms

PubMed Central

Duménieu, Maël; Oulé, Marie; Kreutz, Michael R.; Lopez-Rojas, Jeffrey

2017-01-01

Neurons are highly polarized cells with apparent functional and morphological differences between dendrites and axon. A critical determinant for the molecular and functional identity of axonal and dendritic segments is the restricted expression of voltage-gated ion channels (VGCs). Several studies show an uneven distribution of ion channels and their differential regulation within dendrites and axons, which is a prerequisite for an appropriate integration of synaptic inputs and the generation of adequate action potential (AP) firing patterns. This review article will focus on the signaling pathways leading to segmented expression of voltage-gated potassium and sodium ion channels at the neuronal plasma membrane and the regulatory mechanisms ensuring segregated functions. We will also discuss the relevance of proper ion channel targeting for neuronal physiology and how alterations in polarized distribution contribute to neuronal pathology. PMID:28484374

Conduction velocity of action potentials measured from unidimensional latency-topography in human and frog skeletal muscle fibers.

PubMed

Homma, S; Nakajima, Y; Hayashi, K; Toma, S

1986-01-01

Conduction of an action potential along skeletal muscle fibers was graphically displayed by unidimensional latency-topography, UDLT. Since the slopes of the equipotential line were linear and the width of the line was constant, it was possible to calculate conduction velocity from the slope. To determine conduction direction of the muscle action potential elicited by electric stimulation applied directly to the muscle, surface recording electrodes were placed on a two-dimensional plane over a human muscle. Thus a bi-dimensional topography was obtained. Then, twelve or sixteen surface electrodes were placed linearly along the longitudinal direction of the action potential conduction which was disclosed by the bi-dimensional topography. Thus conduction velocity of muscle action potential in man, calculated from the slope, was for m. brachioradialis, 3.9 +/- 0.4 m/s; for m. biceps brachii, 3.6 +/- 0.2 m/s; for m. sternocleidomastoideus, 3.6 +/- 0.4 m/s. By using a tungsten microelectrode to stimulate the motor axons, a convex-like equipotential line of an action potential in UDLT was obtained from human muscle fibers. Since a similar pattern of UDLT was obtained from experiments on isolated frog muscles, in which the muscle action potential was elicited by stimulating the motor axon, it was assumed that the maximum of the curve corresponds to the end-plate region, and that the slopes on both sides indicate bi-directional conduction of the action potential.

Active action potential propagation but not initiation in thalamic interneuron dendrites

PubMed Central

Casale, Amanda E.; McCormick, David A.

2012-01-01

Inhibitory interneurons of the dorsal lateral geniculate nucleus of the thalamus modulate the activity of thalamocortical cells in response to excitatory input through the release of inhibitory neurotransmitter from both axons and dendrites. The exact mechanisms by which release can occur from dendrites are, however, not well understood. Recent experiments using calcium imaging have suggested that Na/K based action potentials can evoke calcium transients in dendrites via local active conductances, making the back-propagating action potential a candidate for dendritic neurotransmitter release. In this study, we employed high temporal and spatial resolution voltage-sensitive dye imaging to assess the characteristics of dendritic voltage deflections in response to Na/K action potentials in interneurons of the mouse dorsal lateral geniculate nucleus. We found that trains or single action potentials elicited by somatic current injection or local synaptic stimulation led to action potentials that rapidly and actively back-propagated throughout the entire dendritic arbor and into the fine filiform dendritic appendages known to release GABAergic vesicles. Action potentials always appeared first in the soma or proximal dendrite in response to somatic current injection or local synaptic stimulation, and the rapid back-propagation into the dendritic arbor depended upon voltage-gated sodium and TEA-sensitive potassium channels. Our results indicate that thalamic interneuron dendrites integrate synaptic inputs that initiate action potentials, most likely in the axon initial segment, that then back-propagate with high-fidelity into the dendrites, resulting in a nearly synchronous release of GABA from both axonal and dendritic compartments. PMID:22171033

Event-Related Potentials Discriminate Familiar and Unusual Goal Outcomes in 5-Month-Olds and Adults

ERIC Educational Resources Information Center

Michel, Christine; Kaduk, Katharina; Ní Choisdealbha, Áine; Reid, Vincent M.

2017-01-01

Previous event-related potential (ERP) work has indicated that the neural processing of action sequences develops with age. Although adults and 9-month-olds use a semantic processing system, perceiving actions activates attentional processes in 7-month-olds. However, presenting a sequence of action context, action execution and action conclusion…

Multi-Parametric Analysis and Modeling of Relationships between Mitochondrial Morphology and Apoptosis

PubMed Central

Reis, Yara; Wolf, Thomas; Brors, Benedikt; Hamacher-Brady, Anne; Eils, Roland; Brady, Nathan R.

2012-01-01

Mitochondria exist as a network of interconnected organelles undergoing constant fission and fusion. Current approaches to study mitochondrial morphology are limited by low data sampling coupled with manual identification and classification of complex morphological phenotypes. Here we propose an integrated mechanistic and data-driven modeling approach to analyze heterogeneous, quantified datasets and infer relations between mitochondrial morphology and apoptotic events. We initially performed high-content, multi-parametric measurements of mitochondrial morphological, apoptotic, and energetic states by high-resolution imaging of human breast carcinoma MCF-7 cells. Subsequently, decision tree-based analysis was used to automatically classify networked, fragmented, and swollen mitochondrial subpopulations, at the single-cell level and within cell populations. Our results revealed subtle but significant differences in morphology class distributions in response to various apoptotic stimuli. Furthermore, key mitochondrial functional parameters including mitochondrial membrane potential and Bax activation, were measured under matched conditions. Data-driven fuzzy logic modeling was used to explore the non-linear relationships between mitochondrial morphology and apoptotic signaling, combining morphological and functional data as a single model. Modeling results are in accordance with previous studies, where Bax regulates mitochondrial fragmentation, and mitochondrial morphology influences mitochondrial membrane potential. In summary, we established and validated a platform for mitochondrial morphological and functional analysis that can be readily extended with additional datasets. We further discuss the benefits of a flexible systematic approach for elucidating specific and general relationships between mitochondrial morphology and apoptosis. PMID:22272225

Exposure to 1.8 GHz electromagnetic fields affects morphology, DNA-related Raman spectra and mitochondrial functions in human lympho-monocytes.

PubMed

Lasalvia, M; Scrima, R; Perna, G; Piccoli, C; Capitanio, N; Biagi, P F; Schiavulli, L; Ligonzo, T; Centra, M; Casamassima, G; Ermini, A; Capozzi, V

2018-01-01

Blood is a fluid connective tissue of human body, where it plays vital functions for the nutrition, defense and well-being of the organism. When circulating in peripheral districts, it is exposed to some physical stresses coming from outside the human body, as electromagnetic fields (EMFs) which can cross the skin. Such fields may interact with biomolecules possibly inducing non thermal-mediated biological effects at the cellular level. In this study, the occurrence of biochemical/biological modifications in human peripheral blood lympho-monocytes exposed in a reverberation chamber for times ranging from 1 to 20 h to EMFs at 1.8 GHz frequency and 200 V/m electric field strength was investigated. Morphological analysis of adherent cells unveiled, in some of these, appearance of an enlarged and deformed shape after EMFs exposure. Raman spectra of the nuclear compartment of cells exposed to EMFs revealed the onset of biochemical modifications, mainly consisting in the reduction of the DNA backbone-linked vibrational modes. Respirometric measurements of mitochondrial activity in intact lympho-monocytes resulted in increase of the resting oxygen consumption rate after 20 h of exposure, which was coupled to a significant increase of the FoF1-ATP synthase-related oxygen consumption. Notably, at lower time-intervals of EMFs exposure (i.e. 5 and 12 h) a large increase of the proton leak-related respiration was observed which, however, recovered at control levels after 20 h exposure. Confocal microscopy analysis of the mitochondrial membrane potential supported the respiratory activities whereas no significant variations in the mitochondrial mass/morphology was observed in EMFs-exposed lympho-monocytes. Finally, altered redox homeostasis was shown in EMFs-exposed lympho-monocytes, which progressed differently in nucleated cellular subsets. This results suggest the occurrence of adaptive mechanisms put in action, likely via redox signaling, to compensate for early impairments of the oxidative phosphorylation system caused by exposure to EMFs. Overall the data presented warn for health safety of people involved in long-term exposure to electromagnetic fields, although further studies are required to pinpoint the leukocyte cellular subset(s) selectively targeted by the EMFs action and the mechanisms by which it is achieved.

Understanding the Electrical Behavior of the Action Potential in Terms of Elementary Electrical Sources

ERIC Educational Resources Information Center

Rodriguez-Falces, Javier

2015-01-01

A concept of major importance in human electrophysiology studies is the process by which activation of an excitable cell results in a rapid rise and fall of the electrical membrane potential, the so-called action potential. Hodgkin and Huxley proposed a model to explain the ionic mechanisms underlying the formation of action potentials. However,…

Detachable glass microelectrodes for recording action potentials in active moving organs.

PubMed

Barbic, Mladen; Moreno, Angel; Harris, Tim D; Kay, Matthew W

2017-06-01

Here, we describe new detachable floating glass micropipette electrode devices that provide targeted action potential recordings in active moving organs without requiring constant mechanical constraint or pharmacological inhibition of tissue motion. The technology is based on the concept of a glass micropipette electrode that is held firmly during cell targeting and intracellular insertion, after which a 100-µg glass microelectrode, a "microdevice," is gently released to remain within the moving organ. The microdevices provide long-term recordings of action potentials, even during millimeter-scale movement of tissue in which the device is embedded. We demonstrate two different glass micropipette electrode holding and detachment designs appropriate for the heart (sharp glass microdevices for cardiac myocytes in rats, guinea pigs, and humans) and the brain (patch glass microdevices for neurons in rats). We explain how microdevices enable measurements of multiple cells within a moving organ that are typically difficult with other technologies. Using sharp microdevices, action potential duration was monitored continuously for 15 min in unconstrained perfused hearts during global ischemia-reperfusion, providing beat-to-beat measurements of changes in action potential duration. Action potentials from neurons in the hippocampus of anesthetized rats were measured with patch microdevices, which provided stable base potentials during long-term recordings. Our results demonstrate that detachable microdevices are an elegant and robust tool to record electrical activity with high temporal resolution and cellular level localization without disturbing the physiological working conditions of the organ. NEW & NOTEWORTHY Cellular action potential measurements within tissue using glass micropipette electrodes usually require tissue immobilization, potentially influencing the physiological relevance of the measurement. Here, we addressed this limitation with novel 100-µg detachable glass microelectrodes that can be precisely positioned to provide long-term measurements of action potential duration during unconstrained tissue movement. Copyright © 2017 the American Physiological Society.

The relationship between morphological and behavioral mimicry in hover flies (Diptera: Syrphidae).

PubMed

Penney, Heather D; Hassall, Christopher; Skevington, Jeffrey H; Lamborn, Brent; Sherratt, Thomas N

2014-02-01

Palatable (Batesian) mimics of unprofitable models could use behavioral mimicry to compensate for the ease with which they can be visually discriminated or to augment an already close morphological resemblance. We evaluated these contrasting predictions by assaying the behavior of 57 field-caught species of mimetic hover flies (Diptera: Syrphidae) and quantifying their morphological similarity to a range of potential hymenopteran models. A purpose-built phylogeny for the hover flies was used to control for potential lack of independence due to shared evolutionary history. Those hover fly species that engage in behavioral mimicry (mock stinging, leg waving, wing wagging) were all large wasp mimics within the genera Spilomyia and Temnostoma. While the behavioral mimics assayed were good morphological mimics, not all good mimics were behavioral mimics. Therefore, while the behaviors may have evolved to augment good morphological mimicry, they do not advantage all good mimics.

The surface stability and morphology of tobermorite 11 Å from first principles

NASA Astrophysics Data System (ADS)

Mutisya, Sylvia M.; Miranda, Caetano R.

2018-06-01

Tobermorite minerals are important in many industrial processes typically occurring in hydrous environment. Their functionality is therefore governed in various aspects by their morphology and surface stability/reactivity. Here, we present the results of the surface energies and morphology of normal tobermorite 11 Å in a water vapor environment investigated by employing first principles atomistic thermodynamic calculations. For the low index tobermorite surfaces studied, the calculated surface energies fall within a narrow range (0.41-0.97 J/m2) with the (0 0 4) surface being the most stable. The equilibrium morphology is a thin pseudohexagonal plate elongated along the b axis. The hydrated surfaces are more stable at high water vapor chemical potentials with the stability enhanced as the water partial pressures are varied from ambient to supercritical hydrothermal conditions. Increasing the water vapor chemical potential gives rise to a smaller size of the tobermorite crystal, with the equilibrium morphology remaining unaltered.

Extracellular matrix of collagen modulates arrhythmogenic activity of pulmonary veins through p38 MAPK activation.

PubMed

Lu, Yen-Yu; Chen, Yao-Chang; Kao, Yu-Hsun; Chen, Shih-Ann; Chen, Yi-Jen

2013-06-01

Atrial fibrillation (AF) is the most common sustained arrhythmia. Cardiac fibrosis with enhanced extracellular collagen plays a critical role in the pathophysiology of AF through structural and electrical remodeling. Pulmonary veins (PVs) are important foci for AF genesis. The purpose of this study was to evaluate whether collagen can directly modulate PV arrhythmogenesis. Action potentials and ionic currents were investigated in isolated male New Zealand rabbit PV cardiomyocytes with and without collagen incubation (10μg/ml, 5-7h) using the whole-cell patch-clamp technique. Compared to control PV cardiomyocytes (n=25), collagen-treated PV cardiomyocytes (n=22) had a faster beating rate (3.2±04 vs. 1.9±0.2Hz, p<0.005) and a larger amplitude of delayed afterdepolarization (16±2 vs. 10±1mV, p<0.01). Moreover, collagen-treated PV cardiomyocytes showed a larger transient outward potassium current, small-conductance Ca(2+)-activated K(+) current, inward rectifier potassium current, pacemaker current, and late sodium current than control PV cardiomyocytes, but amplitudes of the sodium current, sustained outward potassium current, and L-type calcium current were similar. Collagen increased the p38 MAPK phosphorylation in PV cardiomyocytes as compared to control. The change of the spontaneous activity and action potential morphology were ameliorated by SB203580 (the p38 MAPK catalytic activity inhibitor), indicating that collagen can directly increase PV cardiomyocyte arrhythmogenesis through p38 MAPK activation, which may contribute to the pathogenesis of AF. Copyright © 2013 Elsevier Ltd. All rights reserved.

Induction of apoptosis by pinostrobin in human cervical cancer cells: Possible mechanism of action.

PubMed

Jaudan, Alka; Sharma, Sapna; Malek, Sri Nurestri Abd; Dixit, Aparna

2018-01-01

Pinostrobin (PN) is a naturally occurring dietary bioflavonoid, found in various medicinal herbs/plants. Though anti-cancer potential of many such similar constituents has been demonstrated, critical biochemical targets and exact mechanism for their apoptosis-inducing actions have not been fully elucidated. The present study was aimed to investigate if PN induced apoptosis in cervical cancer cells (HeLa) of human origin. It is demonstrated that PN at increasing dose effectivity reduced the cell viability as well as GSH and NO2- levels. Condensed nuclei with fragmented chromatin and changes in mitochondrial matrix morphology clearly indicated the role of mitochondria in PN induced apoptosis. A marked reduction in mitochondrial membrane potential and increased ROS production after PN treatment showed involvement of free radicals, which in turn further augment ROS levels. PN treatment resulted in DNA damage, which could have been triggered by an increase in ROS levels. Decrease in apoptotic cells in the presence of caspase 3 inhibitor in PN-treated cells suggested that PN induced apoptosis via caspase dependent pathways. Additionally, a significant increase in the expression of proteins of extrinsic (TRAIL R1/DR4, TRAIL R2/DR5, TNF RI/TNFRSF1A, FADD, Fas/TNFRSF6) and intrinsic pathway (Bad, Bax, HTRA2/Omi, SMAC/Diablo, cytochrome C, Pro-Caspase-3, Cleaved Caspase-3) was observed in the cells exposed to PN. Taken together, these observations suggest that PN efficiently induces apoptosis through ROS mediated extrinsic and intrinsic dependent signaling pathways, as well as ROS mediated mitochondrial damage in HeLa cells.

The influence of metal Mg on micro-morphology and crystallinity of spherical hexagonal boron nitride

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Ning, E-mail: zhangning5832@163.com; Liu, Huan; Kan, Hongmin

2015-08-15

Highlights: • The action mechanism of Mg to the synthesis of spherical BN was explored. • The influence of Mg content on the crystallinity of h-BN powders was studied. • Even if not added any template, the spherical h-BN could be prepared. - Abstract: This search used the boric acid and borax as a source of boron, urea as a nitrogen source, Mg as metal catalyst, and thus prepared different micro-morphology and crystallinity hexagonal boron nitride powders under a flowing ammonia atmosphere at a nitriding temperature of 750 °C. The effect of Mg content on the crystallinity and micro-morphology ofmore » hexagonal boron nitride powders was studied, and the Mg action mechanism was explored. Without the added surfactant, the graphitization index (GI) was 6.87, and the diameter of the spherical h-BN was bigger. When the added Mg were 0.1 g, 0.3 g, 0.5 g and 0.7 g, the (GI) decreased to 6.04, 5.67, 4.62 and 4.84, respectively. When the Mg content was higher (0.9 g), GI value increased rapidly, and the crystallinity became bad. When the Mg content was 0.5 g, the dispersion of h-BN powders was at its optimum and refinement apparently, and the crystallinity at its highest.« less

Cultures-of-Use and Morphologies of Communicative Action

ERIC Educational Resources Information Center

Thorne, Steven L.

2016-01-01

In this article I revisit the cultures-of-use conceptual framework--that technologies, as forms and processes comprising human culture, mediate and assume variable meanings, values, and conventionalized functions for different communities (Thorne, 2003). I trace the antecedent arc of investigation and serendipitous encounters that led to the 2003…

[Gunshot wounds caused by non-lethal ammunition on the porcine model post-mortem].

PubMed

Jabrocký, Peter; Pivko, Juraj; Vondráková, Mária; Tažký, Boris

2013-10-01

In this article we focus on the effects of so called non-lethal ammunition. We studied possible mechanism of firearm injury formation as a consequence of using firearm on the body, to present a more comprehensive material in wound ballistics. We pointed out possible actions of a projectile causes on human, respectively other animal organisms, as well as to a manner in which an injury is caused by rifles or shotguns using non-lethal ammunition with rubber projectiles. In the experiment, we have focused on macroscopic analysis of the tissue penetrated by a rubber projectile fired from a long firearm and pump-action shotgun while focusing on the anatomical-morphological analysis of entry wounds to determine the effectiveness respectively, the wounding potential of the projectile. The results of the experiment based on the macroscopic analysis of entry wounds, cavities and exit wounds, show that when a rubber projectile penetrates the body it causes loss of the tissue (i.e. the minus effect) and mechanical disruption of the tissue similar to lethal projectile. Based on the measures and ballistic computations we concluded that in specific cases, like for example in a close range hit, a penetration of vital organs can cause serious or even lethal injuries.

Insights into the disparate action of osmolytes and macromolecular crowders on amyloid formation

PubMed Central

Sukenik, Shahar

2012-01-01

It is widely recognized that amyloid formation sensitively responds to conditions set by myriad cellular solutes. These cosolutes include two important classes: macromolecular crowders and compatible osmolytes. We have recently found that addition of macromolecular PEG only slightly affects fibril formation of a model peptide in vitro. Polyol osmolytes, in contrast, lengthen the lag time for aggregation, and lead to larger fibril mass at equilibrium. To further hypothesize on the molecular underpinnings of the disparate effect of the two cosolute classes, we have further analyzed the experiments using an available kinetic mechanism describing fibril aggregation. Model calculations suggest that all cosolutes similarly lengthen the time required for nucleation, possibly due to their excluded volume effect. However, PEGs may in addition promote fibril fragmentation, leading to lag times that are overall almost unvaried. Moreover, polyols effectively slow the monomer-fibril detachment rates, thereby favoring additional fibril formation. Our analysis provides first hints that cosolutes act not only by changing association or dissociation rates, but potentially also by directing the formation of fibrils of varied morphologies with different mechanical properties. Although additional experiments are needed to unambiguously resolve the action of excluded cosolutes on amyloid formation, it is becoming clear that these compounds are important to consider in the search for ways to modulate fibril formation. PMID:22453174

Tip off the HAT– Epigenetic control of learning and memory by Drosophila Tip60

PubMed Central

Xu, Songjun; Elefant, Felice

2015-01-01

Disruption of epigenetic gene control mechanisms involving histone acetylation in the brain causes cognitive impairment, a debilitating hallmark of most neurodegenerative disorders. Histone acetylation regulates cognitive gene expression via chromatin packaging control in neurons. Unfortunately, the histone acetyltransferases (HATs) that generate such neural epigenetic signatures and their mechanisms of action remain unclear. Our recent findings provide insight into this question by demonstrating that Tip60 HAT action is critical for morphology and function of the mushroom body (MB), the learning and memory center in the Drosophila brain. We show that Tip60 is robustly produced in MB Kenyon cells and extending axonal lobes and that targeted MB Tip60 HAT loss results in axonal outgrowth disruption. Functional consequences of loss and gain of Tip60 HAT levels in the MB are evidenced by defects in memory. Tip60 ChIP-Seq analysis reveals enrichment for genes that function in cognitive processes and accordingly, key genes representing these pathways are misregulated in the Tip60 HAT mutant fly brain. Remarkably, increasing levels of Tip60 in the MB rescues learning and memory deficits resulting from Alzheimer's disease associated amyloid precursor protein (APP) induced neurodegeneration. Our studies highlight the potential of HAT activators as a therapeutic option for cognitive disorders. PMID:26327426

Action of Coriandrum sativum L. Essential Oil upon Oral Candida albicans Biofilm Formation.

PubMed

Furletti, V F; Teixeira, I P; Obando-Pereda, G; Mardegan, R C; Sartoratto, A; Figueira, G M; Duarte, R M T; Rehder, V L G; Duarte, M C T; Höfling, J F

2011-01-01

The efficacy of extracts and essential oils from Allium tuberosum, Coriandrum sativum, Cymbopogon martini, Cymbopogon winterianus, and Santolina chamaecyparissus was evaluated against Candida spp. isolates from the oral cavity of patients with periodontal disease. The most active oil was fractionated and tested against C. albicans biofilm formation. The oils were obtained by water-distillation and the extracts were prepared with macerated dried plant material. The Minimal Inhibitory Concentration-MIC was determined by the microdilution method. Chemical characterization of oil constituents was performed using Gas Chromatography and Mass Spectrometry (GC-MS). C. sativum activity oil upon cell and biofilm morphology was evaluated by Scanning Electron Microscopy (SEM). The best activities against planktonic Candida spp. were observed for the essential oil and the grouped F(8-10) fractions from C. sativum. The crude oil also affected the biofilm formation in C. albicans causing a decrease in the biofilm growth. Chemical analysis of the F(8-10) fractions detected as major active compounds, 2-hexen-1-ol, 3-hexen-1-ol and cyclodecane. Standards of these compounds tested grouped provided a stronger activity than the oil suggesting a synergistic action from the major oil constituents. The activity of C. sativum oil demonstrates its potential for a new natural antifungal formulation.

A methodology for modeling barrier island storm-impact scenarios

USGS Publications Warehouse

Mickey, Rangley C.; Long, Joseph W.; Plant, Nathaniel G.; Thompson, David M.; Dalyander, P. Soupy

2017-02-16

A methodology for developing a representative set of storm scenarios based on historical wave buoy and tide gauge data for a region at the Chandeleur Islands, Louisiana, was developed by the U.S. Geological Survey. The total water level was calculated for a 10-year period and analyzed against existing topographic data to identify when storm-induced wave action would affect island morphology. These events were categorized on the basis of the threshold of total water level and duration to create a set of storm scenarios that were simulated, using a high-fidelity, process-based, morphologic evolution model, on an idealized digital elevation model of the Chandeleur Islands. The simulated morphological changes resulting from these scenarios provide a range of impacts that can help coastal managers determine resiliency of proposed or existing coastal structures and identify vulnerable areas within those structures.

TRPM4 non-selective cation channels influence action potentials in rabbit Purkinje fibres.

PubMed

Hof, Thomas; Sallé, Laurent; Coulbault, Laurent; Richer, Romain; Alexandre, Joachim; Rouet, René; Manrique, Alain; Guinamard, Romain

2016-01-15

The transient receptor potential melastatin 4 (TRPM4) inhibitor 9-phenanthrol reduces action potential duration in rabbit Purkinje fibres but not in ventricle. TRPM4-like single channel activity is observed in isolated rabbit Purkinje cells but not in ventricular cells. The TRPM4-like current develops during the notch and early repolarization phases of the action potential in Purkinje cells. Transient receptor potential melastatin 4 (TRPM4) Ca(2+)-activated non-selective cation channel activity has been recorded in cardiomyocytes and sinus node cells from mammals. In addition, TRPM4 gene mutations are associated with human diseases of cardiac conduction, suggesting that TRPM4 plays a role in this aspect of cardiac function. Here we evaluate the TRPM4 contribution to cardiac electrophysiology of Purkinje fibres. Ventricular strips with Purkinje fibres were isolated from rabbit hearts. Intracellular microelectrodes recorded Purkinje fibre activity and the TRPM4 inhibitor 9-phenanthrol was applied to unmask potential TRPM4 contributions to the action potential. 9-Phenanthrol reduced action potential duration measured at the point of 50 and 90% repolarization with an EC50 of 32.8 and 36.1×10(-6) mol l(-1), respectively, but did not modulate ventricular action potentials. Inside-out patch-clamp recordings were used to monitor TRPM4 activity in isolated Purkinje cells. TRPM4-like single channel activity (conductance = 23.8 pS; equal permeability for Na(+) and K(+); sensitivity to voltage, Ca(2+) and 9-phenanthrol) was observed in 43% of patches from Purkinje cells but not from ventricular cells (0/16). Action potential clamp experiments performed in the whole-cell configuration revealed a transient inward 9-phenanthrol-sensitive current (peak density = -0.65 ± 0.15 pA pF(-1); n = 5) during the plateau phases of the Purkinje fibre action potential. These results show that TRPM4 influences action potential characteristics in rabbit Purkinje fibres and thus could modulate cardiac conduction and be involved in triggering arrhythmias. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

14 CFR 1216.306 - Actions normally requiring an EIS.

Code of Federal Regulations, 2013 CFR

2013-01-01

... normally requiring an EIS. (a) NASA will prepare an EIS for actions with the potential to significantly... action or mitigation of its potentially significant impacts. (b) Typical NASA actions normally requiring... material greater than the quantity for which the NASA Nuclear Flight Safety Assurance Manager may grant...

The regulatory effect of SC-236 (4-[5-(4-chlorophenyl)-3-(trifluoromethyl)-1-pyrazol-1-l] benzenesulfonamide) on stem cell factor induced migration of mast cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Su-Jin; College of Oriental Medicine, Kyung Hee University, 1 Hoegi-Dong, Dongdaemun-Gu, Seoul 130-701; Jeong, Hyun-Ja

SC-236 (4-[5-(4-chlorophenyl)-3-(trifluoromethyl)-1-pyrazol-1-]benzenesulfonamide; C{sub 16}H{sub 11}ClF{sub 3}N{sub 3}O{sub 2}S), is a highly selective cyclooxygenase (COX)-2 inhibitor. Recently, there have been reports that SC-236 protects against cartilage damage in addition to reducing inflammation and pain in osteoarthritis. However, the mechanism involved in the inflammatory allergic reaction has not been examined. Mast cells accumulation can be related to inflammatory conditions, including allergic rhinitis, asthma, and rheumatoid arthritis. The aim of the present study is to investigate the effects of SC-236 on stem cell factor (SCF)-induced migration, morphological alteration, and cytokine production of rat peritoneal mast cells (RPMCs). We observed that SCF significantly inducedmore » the migration and morphological alteration. The ability of SCF to enhance migration and morphological alteration was abolished by treatment with SC-236. In addition, production of tumor necrosis factor (TNF)-{alpha}, interleukin (IL)-1{beta}, and vascular endothelial growth factor (VEGF) production induced by SCF was significantly inhibited by treatment with SC-236. Previous work has demonstrated that SCF-induced migration and cytokine production of mast cells require p38 MAPK activation. We also showed that SC-236 suppresses the SCF-induced p38 MAPK activation in RPMCs. These data suggest that SC-236 inhibits migration and cytokine production through suppression of p38 MAPK activation. These results provided new insight into the pharmacological actions of SC-236 and its potential therapeutic role in the treatment of inflammatory allergic diseases.« less

Effect of Processing Parameters on the Morphology of PVDF Electrospun Nanofiber

NASA Astrophysics Data System (ADS)

Zulfikar, M. A.; Afrianingsih, I.; Nasir, M.; Alni, A.

2018-03-01

Electrospinning is a process that produces continuous polymer fibers with diameters in the submicron range through the action of an external electric field imposed on a polymer solution or melt. Because of the tiny diameter in several hundreds of nanometers and the high porosity, electrospun membranes show potential applications in extensive areas such as filtration systems, biomedical tissue templates, drug delivery membranes, and so on. In the electrospinning process, some parameters such as polymer concentration, feeding rate of the polymer solution, additives, humidity, viscosity, surface tension, applied voltage, and nozzle-to ground collector distance will affect the fiber diameter and morphology. In this work, we have evaluated the effects of two processing parameters including the flow rate of the polymer solution and nozzle-to ground collector distance, on the morphology of the fibers formed. The solutions used in the electrospinning experiments were prepared using Poly(vinylidene fluoride) (PVDF). This material was dissolved in N,N-dimethylformamide (DMF) to make solutions with concentrations of 20 wt%. These solutions was electrospun using a 5 mL plastic syringe with an 8 gauge stainless needle at an applied voltage of 20.0 kV, a flow rate of 0.02-0.04 mL/min and nozzle-to ground collector distance of 12 and 15 cm. Electrospinning of PVDF polymer solution was performed in horizontal alignment having a grounded aluminum foil which serves as a collector. The nanofibers obtained were characterized by polarizing optical microscope. We find that the low flow rate of the polymer solution and nozzle-to ground collector distance are strongly correlated with the formation of bead defects in the fibers.

Structural and Functional Maturation of Cardiomyocytes Derived from Human Pluripotent Stem Cells

PubMed Central

Lundy, Scott D.; Zhu, Wei-Zhong

2013-01-01

Despite preclinical studies demonstrating the functional benefit of transplanting human pluripotent stem cell-derived cardiomyocytes (PSC-CMs) into damaged myocardium, the ability of these immature cells to adopt a more adult-like cardiomyocyte (CM) phenotype remains uncertain. To address this issue, we tested the hypothesis that prolonged in vitro culture of human embryonic stem cell (hESC)- and human induced pluripotent stem cell (hiPSC)-derived CMs would result in the maturation of their structural and contractile properties to a more adult-like phenotype. Compared to their early-stage counterparts (PSC-CMs after 20–40 days of in vitro differentiation and culture), late-stage hESC-CMs and hiPSC-CMs (80–120 days) showed dramatic differences in morphology, including increased cell size and anisotropy, greater myofibril density and alignment, sarcomeres visible by bright-field microscopy, and a 10-fold increase in the fraction of multinucleated CMs. Ultrastructural analysis confirmed improvements in the myofibrillar density, alignment, and morphology. We measured the contractile performance of late-stage hESC-CMs and hiPSC-CMs and noted a doubling in shortening magnitude with slowed contraction kinetics compared to the early-stage cells. We then examined changes in the calcium-handling properties of these matured CMs and found an increase in calcium release and reuptake rates with no change in the maximum amplitude. Finally, we performed electrophysiological assessments in hESC-CMs and found that late-stage myocytes have hyperpolarized maximum diastolic potentials, increased action potential amplitudes, and faster upstroke velocities. To correlate these functional changes with gene expression, we performed qPCR and found a robust induction of the key cardiac structural markers, including β-myosin heavy chain and connexin-43, in late-stage hESC-CMs and hiPSC-CMs. These findings suggest that PSC-CMs are capable of slowly maturing to more closely resemble the phenotype of adult CMs and may eventually possess the potential to regenerate the lost myocardium with robust de novo force-producing tissue. PMID:23461462

Genotoxic and teratogenic effect of freshwater sediment samples from the Rhine and Elbe River (Germany) in zebrafish embryo using a multi-endpoint testing strategy.

PubMed

Garcia-Käufer, M; Gartiser, S; Hafner, C; Schiwy, S; Keiter, S; Gründemann, C; Hollert, H

2015-11-01

The embryotoxic potential of three model sediment samples with a distinct and well-characterized pollutant burden from the main German river basins Rhine and Elbe was investigated. The Fish Embryo Contact Test (FECT) in zebrafish (Danio rerio) was applied and submitted to further development to allow for a comprehensive risk assessment of such complex environmental samples. As particulate pollutants are constructive constituents of sediments, they underlay episodic source-sink dynamics, becoming available to benthic organisms. As bioavailability of xenobiotics is a crucial factor for ecotoxicological hazard, we focused on the direct particle-exposure pathway, evaluating throughput-capable endpoints and considering toxicokinetics. Fish embryo and larvae were exposed toward reconstituted (freeze-dried) sediment samples on a microcosm-scale experimental approach. A range of different developmental embryonic stages were considered to gain knowledge of potential correlations with metabolic competence during the early embryogenesis. Morphological, physiological, and molecular endpoints were investigated to elucidate induced adverse effects, placing particular emphasis on genomic instability, assessed by the in vivo comet assay. Flow cytometry was used to investigate the extent of induced cell death, since cytotoxicity can lead to confounding effects. The implementation of relative toxicity indices further provides inter-comparability between samples and related studies. All of the investigated sediments represent a significant ecotoxicological hazard by disrupting embryogenesis in zebrafish. Beside the induction of acute toxicity, morphological and physiological embryotoxic effects could be identified in a concentration-response manner. Increased DNA strand break frequency was detected after sediment contact in characteristic non-monotonic dose-response behavior due to overlapping cytotoxic effects. The embryonic zebrafish toxicity model along with the in vivo comet assay and molecular biomarker analysis should prospectively be considered to assess the ecotoxicological potential of sediments allowing for a comprehensive hazard ranking. In order to elucidate mode of action, novel techniques such as flow cytometry have been adopted and proved to be valuable tools for advanced risk assessment and management.

Cell-type-dependent action potentials and voltage-gated currents in mouse fungiform taste buds.

PubMed

Kimura, Kenji; Ohtubo, Yoshitaka; Tateno, Katsumi; Takeuchi, Keita; Kumazawa, Takashi; Yoshii, Kiyonori

2014-01-01

Taste receptor cells fire action potentials in response to taste substances to trigger non-exocytotic neurotransmitter release in type II cells and exocytotic release in type III cells. We investigated possible differences between these action potentials fired by mouse taste receptor cells using in situ whole-cell recordings, and subsequently we identified their cell types immunologically with cell-type markers, an IP3 receptor (IP3 R3) for type II cells and a SNARE protein (SNAP-25) for type III cells. Cells not immunoreactive to these antibodies were examined as non-IRCs. Here, we show that type II cells and type III cells fire action potentials using different ionic mechanisms, and that non-IRCs also fire action potentials with either of the ionic mechanisms. The width of action potentials was significantly narrower and their afterhyperpolarization was deeper in type III cells than in type II cells. Na(+) current density was similar in type II cells and type III cells, but it was significantly smaller in non-IRCs than in the others. Although outwardly rectifying current density was similar between type II cells and type III cells, tetraethylammonium (TEA) preferentially suppressed the density in type III cells and the majority of non-IRCs. Our mathematical model revealed that the shape of action potentials depended on the ratio of TEA-sensitive current density and TEA-insensitive current one. The action potentials of type II cells and type III cells under physiological conditions are discussed. © 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

The optimal distance between two electrode tips during recording of compound nerve action potentials in the rat median nerve

PubMed Central

Li, Yongping; Lao, Jie; Zhao, Xin; Tian, Dong; Zhu, Yi; Wei, Xiaochun

2014-01-01

The distance between the two electrode tips can greatly influence the parameters used for recording compound nerve action potentials. To investigate the optimal parameters for these recordings in the rat median nerve, we dissociated the nerve using different methods and compound nerve action potentials were orthodromically or antidromically recorded with different electrode spacings. Compound nerve action potentials could be consistently recorded using a method in which the middle part of the median nerve was intact, with both ends dissociated from the surrounding fascia and a ground wire inserted into the muscle close to the intact part. When the distance between two stimulating electrode tips was increased, the threshold and supramaximal stimulating intensity of compound nerve action potentials were gradually decreased, but the amplitude was not changed significantly. When the distance between two recording electrode tips was increased, the amplitude was gradually increased, but the threshold and supramaximal stimulating intensity exhibited no significant change. Different distances between recording and stimulating sites did not produce significant effects on the aforementioned parameters. A distance of 5 mm between recording and stimulating electrodes and a distance of 10 mm between recording and stimulating sites were found to be optimal for compound nerve action potential recording in the rat median nerve. In addition, the orthodromic compound action potential, with a biphasic waveform that was more stable and displayed less interference (however also required a higher threshold and higher supramaximal stimulus), was found to be superior to the antidromic compound action potential. PMID:25206798

Modulation of hERG potassium channel gating normalizes action potential duration prolonged by dysfunctional KCNQ1 potassium channel

PubMed Central

Zhang, Hongkang; Zou, Beiyan; Yu, Haibo; Moretti, Alessandra; Wang, Xiaoying; Yan, Wei; Babcock, Joseph J.; Bellin, Milena; McManus, Owen B.; Tomaselli, Gordon; Nan, Fajun; Laugwitz, Karl-Ludwig; Li, Min

2012-01-01

Long QT syndrome (LQTS) is a genetic disease characterized by a prolonged QT interval in an electrocardiogram (ECG), leading to higher risk of sudden cardiac death. Among the 12 identified genes causal to heritable LQTS, ∼90% of affected individuals harbor mutations in either KCNQ1 or human ether-a-go-go related genes (hERG), which encode two repolarizing potassium currents known as IKs and IKr. The ability to quantitatively assess contributions of different current components is therefore important for investigating disease phenotypes and testing effectiveness of pharmacological modulation. Here we report a quantitative analysis by simulating cardiac action potentials of cultured human cardiomyocytes to match the experimental waveforms of both healthy control and LQT syndrome type 1 (LQT1) action potentials. The quantitative evaluation suggests that elevation of IKr by reducing voltage sensitivity of inactivation, not via slowing of deactivation, could more effectively restore normal QT duration if IKs is reduced. Using a unique specific chemical activator for IKr that has a primary effect of causing a right shift of V1/2 for inactivation, we then examined the duration changes of autonomous action potentials from differentiated human cardiomyocytes. Indeed, this activator causes dose-dependent shortening of the action potential durations and is able to normalize action potentials of cells of patients with LQT1. In contrast, an IKr chemical activator of primary effects in slowing channel deactivation was not effective in modulating action potential durations. Our studies provide both the theoretical basis and experimental support for compensatory normalization of action potential duration by a pharmacological agent. PMID:22745159

Short infrared laser pulses block action potentials in neurons

NASA Astrophysics Data System (ADS)

Walsh, Alex J.; Tolstykh, Gleb P.; Martens, Stacey L.; Ibey, Bennett L.; Beier, Hope T.

2017-02-01

Short infrared laser pulses have many physiological effects on cells including the ability to stimulate action potentials in neurons. Here we show that short infrared laser pulses can also reversibly block action potentials. Primary rat hippocampal neurons were transfected with the Optopatch2 plasmid, which contains both a blue-light activated channel rhodopsin (CheRiff) and a red-light fluorescent membrane voltage reporter (QuasAr2). This optogenetic platform allows robust stimulation and recording of action potential activity in neurons in a non-contact, low noise manner. For all experiments, QuasAr2 was imaged continuously on a wide-field fluorescent microscope using a Krypton laser (647 nm) as the excitation source and an EMCCD camera operating at 1000 Hz to collect emitted fluorescence. A co-aligned Argon laser (488 nm, 5 ms at 10Hz) provided activation light for CheRiff. A 200 mm fiber delivered infrared light locally to the target neuron. Reversible action potential block in neurons was observed following a short infrared laser pulse (0.26-0.96 J/cm2; 1.37-5.01 ms; 1869 nm), with the block persisting for more than 1 s with exposures greater than 0.69 J/cm2. Action potential block was sustained for 30 s with the short infrared laser pulsed at 1-7 Hz. Full recovery of neuronal activity was observed 5-30s post-infrared exposure. These results indicate that optogenetics provides a robust platform for the study of action potential block and that short infrared laser pulses can be used for non-contact, reversible action potential block.

Forward and Backward Pressure Waveform Morphology in Hypertension.

PubMed

Li, Ye; Gu, Haotian; Fok, Henry; Alastruey, Jordi; Chowienczyk, Philip

2017-02-01

We tested the hypothesis that increased pulse wave reflection and altered backward waveform morphology contribute to increased pulse pressure in subjects with higher pulse pressure compared with lower pulse pressure and to actions of vasoactive drugs to increase pulse pressure. We examined the relationship of backward to forward wave morphology in 158 subjects who were evaluated for hypertension (including some normotensive subjects) divided into 3 groups by central pulse pressure: group 1, 33±6.5 mm Hg; group 2, 45±4.1 mm Hg; and group 3, 64±12.9 mm Hg (means±SD) and in healthy normotensive subjects during administration of inotropic and vasomotor drugs. Aortic pressure and flow in the aortic root were estimated by carotid tonometry and Doppler sonography, respectively. Morphology of the backward wave relative to the forward wave was similar in subjects in the lowest and highest tertiles of pulse pressure. Similar results were seen with the inotropic, vasopressor and vasodilator drugs, dobutamine, norepinephrine, and phentolamine, with the backward wave maintaining a constant ratio to the forward wave. However, nitroglycerin, a drug with a specific action to dilate muscular conduit arteries, reduced the amplitude of the backward wave relative to the forward wave from 0.26±0.018 at baseline to 0.19±0.019 during nitroglycerin 30 μg/min IV (P<0.01). These results are best explained by an approximately constant amount of reflection of the forward wave from the peripheral vasculature. The amount of reflection can be modified by dilation of peripheral muscular conduit arteries but contributes little to increased pulse pressure in hypertension. © 2016 The Authors.

Surface modification of endovascular stents with rosuvastatin and heparin-loaded biodegradable nanofibers by electrospinning.

PubMed

Janjic, Milka; Pappa, Foteini; Karagkiozaki, Varvara; Gitas, Christakis; Ktenidis, Kiriakos; Logothetidis, Stergios

2017-01-01

This study describes the development of drug-loaded nanofibrous scaffolds as a nanocoating for endovascular stents for the local and sustained delivery of rosuvastatin (Ros) and heparin (Hep) to injured artery walls after endovascular procedures via the electrospinning process. The proposed hybrid covered stents can promote re-endothelialization; improve endothelial function; reduce inflammatory reaction; inhibit neointimal hyperplasia of the injured artery wall, due to well-known pleiotropic actions of Ros; and prevent adverse events such as in-stent restenosis (ISR) and stent thrombosis (ST), through the antithrombotic action of Hep. Biodegradable nanofibers were prepared by dissolving cellulose acetate (AC) and Ros in N , N -dimethylacetamide (DMAc) and acetone-based solvents. The polymeric solution was electrospun (e-spun) into drug-loaded AC nanofibers onto three different commercially available stents (Co-Cr stent, Ni-Ti stent, and stainless steel stent), resulting in nonwoven matrices of submicron-sized fibers. Accordingly, Hep solution was further used for fibrous coating onto the engineered Ros-loaded stent. The functional encapsulation of Ros and Hep drugs into polymeric scaffolds further underwent physicochemical analysis. Morphological characterization took place via scanning electron microscopy (SEM) and atomic force microscopy (AFM) analyses, while scaffolds' wettability properties were obtained by contact angle (CA) measurements. The morphology of the drug-loaded AC nanofibers was smooth, with an average diameter of 200-800 nm, and after CA measurement, we concluded to the superhydrophobic nature of the engineered scaffolds. In vitro release rates of the pharmaceutical drugs were determined using a high-performance liquid chromatography assay, which showed that after the initial burst, drug release was controlled slowly by the degradation of the polymeric materials. These results imply that AC nanofibers encapsulated with Ros and Hep drugs have great potential in the development of endovascular grafts with anti-thrombogenic properties that can accelerate the re-endothelialization, reduce the neointimal hyperplasia and inflammatory reaction, and improve the endothelial function.

Control of postharvest soft rot caused by Erwinia carotovora of vegetables by a strain of Bacillus amyloliquefaciens and its potential modes of action.

PubMed

Zhao, Yancun; Li, Pengxia; Huang, Kaihong; Wang, Yuning; Hu, Huali; Sun, Ya

2013-03-01

Erwinia carotovora subsp. carotovora (Ecc), the causal agent of bacterial soft rot, is one of the destructive pathogens of postharvest vegetables. In this study, a bacterial isolate (BGP20) from the vegetable farm soil showed strong antagonistic activity against Ecc in vitro, and its twofold cell-free culture filtrate showed excellent biocontrol effect in controlling the postharvest bacterial soft rot of potatoes at 25 °C. The anti-Ecc metabolites produced by the isolate BGP20 had a high resistance to high temperature, UV-light and protease K. Based on the colonial morphology, cellular morphology, sporulation, and partial nucleotide sequences of 16S rRNA and gyrB gene, the isolate BGP20 was identified as Bacillus amyloliquefaciens subsp. plantarum. Further in vivo assays showed that the BGP20 cell culture was more effective in controlling the postharvest bacterial soft rot of green peppers and Chinese cabbages than its twofold cell-free culture filtrate. In contrast, the biocontrol effect and safety of the BGP20 cell culture were very poor on potatoes. In the wounds of potatoes treated with both the antagonist BGP20 and the pathogen Ecc, the viable count of Ecc was 31,746 times that of BGP20 at 48 h of incubation at 25 °C. But in the wounds of green peppers, the viable count of BGP20 increased 182.3 times within 48 h, and that of Ecc increased only 51.3 %. In addition, the treatment with both BGP20 and Ecc induced higher activity of phenylalanine ammonia-lyase (PAL) than others in potatoes. But the same treatment did not induce an increase of PAL activity in green peppers. In conclusion, the present study demonstrated that the isolate BGP20 is a promising candidate in biological control of postharvest bacterial soft rot of vegetables, but its main mode of action is different among various vegetables.

Strategic formulation of apigenin-loaded PLGA nanoparticles for intracellular trafficking, DNA targeting and improved therapeutic effects in skin melanoma in vitro.

PubMed

Das, Sreemanti; Das, Jayeeta; Samadder, Asmita; Paul, Avijit; Khuda-Bukhsh, Anisur Rahman

2013-11-25

The aim of the present study was the evaluation of anti-proliferative potentials of apigenin (Ap), (a dietary flavonoid) loaded in poly (lactic-co-glycolide) nanoparticles (NAp) in A375 cells in vitro. NAp was characterized for particle size, morphology, zeta potential, drug release and encapsulation. Cellular entry and intracellular localization of NAp were assessed by transmission electron and confocal microscopies. Circular dichroic spectral analysis and stability curve for Gibb's free energy of dsDNA of A375 cells were also analyzed. DNA fragmentation, intracellular ROS accumulation, superoxide-dismutase activity, intracellular glutathione-reductase content and mitochondrial functioning through relevant markers like mitochondrial transmembrane potential, ATPase activity, ATP/ADP ratio, volume changes/swelling, cytochrome-c release, expressions of Apaf-1, bax, bcl-2, caspase-9, 3, and PARP cleavage were analyzed. NAp produced better effects due to their smaller size, faster mobility and site-specific action. Photostability studies revealed that PLGA encapsulations were efficient at preserving apigenin ultraviolet-light mediated photodegradation. NAp readily entered cancer cells, could intercalate with dsDNA, inducing conformational change. Corresponding increase in ROS accumulation and depletion of the antioxidant enzyme activities exacerbated DNA damage, mediating apoptosis through mitochondrial dysfunction. Overall results indicate that therapeutic efficacy of NAp may be enhanced by PLGA nanoparticle formulations to have better ameliorative potentials in combating skin melanoma. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Action potentials and ion conductances in wild-type and CALHM1-knockout type II taste cells

PubMed Central

Saung, Wint Thu; Foskett, J. Kevin

2017-01-01

Taste bud type II cells fire action potentials in response to tastants, triggering nonvesicular ATP release to gustatory neurons via voltage-gated CALHM1-associated ion channels. Whereas CALHM1 regulates mouse cortical neuron excitability, its roles in regulating type II cell excitability are unknown. In this study, we compared membrane conductances and action potentials in single identified TRPM5-GFP-expressing circumvallate papillae type II cells acutely isolated from wild-type (WT) and Calhm1 knockout (KO) mice. The activation kinetics of large voltage-gated outward currents were accelerated in cells from Calhm1 KO mice, and their associated nonselective tail currents, previously shown to be highly correlated with ATP release, were completely absent in Calhm1 KO cells, suggesting that CALHM1 contributes to all of these currents. Calhm1 deletion did not significantly alter resting membrane potential or input resistance, the amplitudes and kinetics of Na+ currents either estimated from action potentials or recorded from steady-state voltage pulses, or action potential threshold, overshoot peak, afterhyperpolarization, and firing frequency. However, Calhm1 deletion reduced the half-widths of action potentials and accelerated the deactivation kinetics of transient outward currents, suggesting that the CALHM1-associated conductance becomes activated during the repolarization phase of action potentials. NEW & NOTEWORTHY CALHM1 is an essential ion channel component of the ATP neurotransmitter release mechanism in type II taste bud cells. Its contribution to type II cell resting membrane properties and excitability is unknown. Nonselective voltage-gated currents, previously associated with ATP release, were absent in cells lacking CALHM1. Calhm1 deletion was without effects on resting membrane properties or voltage-gated Na+ and K+ channels but contributed modestly to the kinetics of action potentials. PMID:28202574

Somatic spikes regulate dendritic signaling in small neurons in the absence of backpropagating action potentials.

PubMed

Myoga, Michael H; Beierlein, Michael; Regehr, Wade G

2009-06-17

Somatic spiking is known to regulate dendritic signaling and associative synaptic plasticity in many types of large neurons, but it is unclear whether somatic action potentials play similar roles in small neurons. Here we ask whether somatic action potentials can also influence dendritic signaling in an electrically compact neuron, the cerebellar stellate cell (SC). Experiments were conducted in rat brain slices using a combination of imaging and electrophysiology. We find that somatic action potentials elevate dendritic calcium levels in SCs. There was little attenuation of calcium signals with distance from the soma in SCs from postnatal day 17 (P17)-P19 rats, which had dendrites that averaged 60 microm in length, and in short SC dendrites from P30-P33 rats. Somatic action potentials evoke dendritic calcium increases that are not affected by blocking dendritic sodium channels. This indicates that dendritic signals in SCs do not rely on dendritic sodium channels, which differs from many types of large neurons, in which dendritic sodium channels and backpropagating action potentials allow somatic spikes to control dendritic calcium signaling. Despite the lack of active backpropagating action potentials, we find that trains of somatic action potentials elevate dendritic calcium sufficiently to release endocannabinoids and retrogradely suppress parallel fiber to SC synapses in P17-P19 rats. Prolonged SC firing at physiologically realistic frequencies produces retrograde suppression when combined with low-level group I metabotropic glutamate receptor activation. Somatic spiking also interacts with synaptic stimulation to promote associative plasticity. These findings indicate that in small neurons the passive spread of potential within dendrites can allow somatic spiking to regulate dendritic calcium signaling and synaptic plasticity.

Action potentials and ion conductances in wild-type and CALHM1-knockout type II taste cells.

PubMed

Ma, Zhongming; Saung, Wint Thu; Foskett, J Kevin

2017-05-01

Taste bud type II cells fire action potentials in response to tastants, triggering nonvesicular ATP release to gustatory neurons via voltage-gated CALHM1-associated ion channels. Whereas CALHM1 regulates mouse cortical neuron excitability, its roles in regulating type II cell excitability are unknown. In this study, we compared membrane conductances and action potentials in single identified TRPM5-GFP-expressing circumvallate papillae type II cells acutely isolated from wild-type (WT) and Calhm1 knockout (KO) mice. The activation kinetics of large voltage-gated outward currents were accelerated in cells from Calhm1 KO mice, and their associated nonselective tail currents, previously shown to be highly correlated with ATP release, were completely absent in Calhm1 KO cells, suggesting that CALHM1 contributes to all of these currents. Calhm1 deletion did not significantly alter resting membrane potential or input resistance, the amplitudes and kinetics of Na + currents either estimated from action potentials or recorded from steady-state voltage pulses, or action potential threshold, overshoot peak, afterhyperpolarization, and firing frequency. However, Calhm1 deletion reduced the half-widths of action potentials and accelerated the deactivation kinetics of transient outward currents, suggesting that the CALHM1-associated conductance becomes activated during the repolarization phase of action potentials. NEW & NOTEWORTHY CALHM1 is an essential ion channel component of the ATP neurotransmitter release mechanism in type II taste bud cells. Its contribution to type II cell resting membrane properties and excitability is unknown. Nonselective voltage-gated currents, previously associated with ATP release, were absent in cells lacking CALHM1. Calhm1 deletion was without effects on resting membrane properties or voltage-gated Na + and K + channels but contributed modestly to the kinetics of action potentials. Copyright © 2017 the American Physiological Society.

Electrophysiology and Innervation of the Photosensitive Epistellar Body in the Lesser Octopus Eledone cirrhosa.

PubMed

Cobb, C S; Williamson, R

1998-08-01

The innervation and responses to light of the cephalopod epistellar body were investigated in preparations isolated from the stellate ganglia of the lesser or northern octopus, Eledone cirrhosa. Extracellular generator potentials in response to flashes of light were recorded from these photosensitive vesicles, with the amplitude of the response being found to be dependent upon the intensity of the flash and the level of ambient illumination. Intracellular recordings from photoreceptor cells of the epistellar body showed that they had resting potentials of about -49 +/- 7 mV (mean +/- SD, n = 43) and were depolarized by flashes of white, but not red (>650 nm) light. The evoked depolarization consisted of a transient component, followed by a steady plateau in which the amplitude of the depolarization was well correlated with the log of the stimulus intensity. The evoked depolarizations induced action potentials in the photoreceptor cells, with the frequency of firing being well correlated with the stimulus intensity. The morphologies of individual photoreceptor cells were visualized by intracellular injections of the fluorescent dye Lucifer yellow, and the path of the epistellar nerve across the stellate ganglion, into the pallial nerve, toward the brain was traced using the lipophilic dye Di-I. This pathway was confirmed physiologically by recording light-evoked responses from the cut end of the pallial nerve.

Effect of Tissue Heterogeneity on the Transmembrane Potential of Type-1 Spiral Ganglion Neurons: A Simulation Study.

PubMed

Sriperumbudur, Kiran Kumar; Pau, Hans Wilhelm; van Rienen, Ursula

2018-03-01

Electric stimulation of the auditory nerve by cochlear implants has been a successful clinical intervention to treat the sensory neural deafness. In this pathological condition of the cochlea, type-1 spiral ganglion neurons in Rosenthal's canal play a vital role in the action potential initiation. Various morphological studies of the human temporal bones suggest that the spiral ganglion neurons are surrounded by heterogeneous structures formed by a variety of cells and tissues. However, the existing simulation models have not considered the tissue heterogeneity in the Rosenthal's canal while studying the electric field interaction with spiral ganglion neurons. Unlike the existing models, we have implemented the tissue heterogeneity in the Rosenthal's canal using a computationally inexpensive image based method in a two-dimensional finite element model. Our simulation results suggest that the spatial heterogeneity of surrounding tissues influences the electric field distribution in the Rosenthal's canal, and thereby alters the transmembrane potential of the spiral ganglion neurons. In addition to the academic interest, these results are especially useful to understand how the latest tissue regeneration methods such as gene therapy and drug-induced resprouting of peripheral axons, which probably modify the density of the tissues in the Rosenthal's canal, affect the cochlear implant functionality.

Diversity of layer 5 projection neurons in the mouse motor cortex

PubMed Central

Oswald, Manfred J.; Tantirigama, Malinda L. S.; Sonntag, Ivo; Hughes, Stephanie M.; Empson, Ruth M.

2013-01-01

In the primary motor cortex (M1), layer 5 projection neurons signal directly to distant motor structures to drive movement. Despite their pivotal position and acknowledged diversity these neurons are traditionally separated into broad commissural and corticofugal types, and until now no attempt has been made at resolving the basis for their diversity. We therefore probed the electrophysiological and morphological properties of retrogradely labeled M1 corticospinal (CSp), corticothalamic (CTh), and commissural projecting corticostriatal (CStr) and corticocortical (CC) neurons. An unsupervised cluster analysis established at least four phenotypes with additional differences between lumbar and cervical projecting CSp neurons. Distinguishing parameters included the action potential (AP) waveform, firing behavior, the hyperpolarisation-activated sag potential, sublayer position, and soma and dendrite size. CTh neurons differed from CSp neurons in showing spike frequency acceleration and a greater sag potential. CStr neurons had the lowest AP amplitude and maximum rise rate of all neurons. Temperature influenced spike train behavior in corticofugal neurons. At 26°C CTh neurons fired bursts of APs more often than CSp neurons, but at 36°C both groups fired regular APs. Our findings provide reliable phenotypic fingerprints to identify distinct M1 projection neuron classes as a tool to understand their unique contributions to motor function. PMID:24137110

α-Synuclein fibril-induced paradoxical structural and functional defects in hippocampal neurons.

PubMed

Froula, Jessica M; Henderson, Benjamin W; Gonzalez, Jose Carlos; Vaden, Jada H; Mclean, John W; Wu, Yumei; Banumurthy, Gokulakrishna; Overstreet-Wadiche, Linda; Herskowitz, Jeremy H; Volpicelli-Daley, Laura A

2018-05-01

Neuronal inclusions composed of α-synuclein (α-syn) characterize Parkinson's Disease (PD) and Dementia with Lewy bodies (DLB). Cognitive dysfunction defines DLB, and up to 80% of PD patients develop dementia. α-Syn inclusions are abundant in the hippocampus, yet functional consequences are unclear. To determine if pathologic α-syn causes neuronal defects, we induced endogenous α-syn to form inclusions resembling those found in diseased brains by treating hippocampal neurons with α-syn fibrils. At seven days after adding fibrils, α-syn inclusions are abundant in axons, but there is no cell death at this time point, allowing us to assess for potential alterations in neuronal function that are not caused by neuron death. We found that exposure of neurons to fibrils caused a significant reduction in mushroom spine densities, adding to the growing body of literature showing that altered spine morphology is a major pathologic phenotype in synucleinopathies. The reduction in spine densities occurred only in wild type neurons and not in neurons from α-syn knockout mice, suggesting that the changes in spine morphology result from fibril-induced corruption of endogenously expressed α-syn. Paradoxically, reduced postsynaptic spine density was accompanied by increased frequency of miniature excitatory postsynaptic currents (EPSCs) and presynaptic docked vesicles, suggesting enhanced presynaptic function. Action-potential dependent activity was unchanged, suggesting compensatory mechanisms responding to synaptic defects. Although activity at the level of the synapse was unchanged, neurons exposed to α-syn fibrils, showed reduced frequency and amplitudes of spontaneous Ca 2+ transients. These findings open areas of research to determine the mechanisms that alter neuronal function in brain regions critical for cognition at time points before neuron death.

Hyperactivity of newborn Pten knock-out neurons results from increased excitatory synaptic drive.

PubMed

Williams, Michael R; DeSpenza, Tyrone; Li, Meijie; Gulledge, Allan T; Luikart, Bryan W

2015-01-21

Developing neurons must regulate morphology, intrinsic excitability, and synaptogenesis to form neural circuits. When these processes go awry, disorders, including autism spectrum disorder (ASD) or epilepsy, may result. The phosphatase Pten is mutated in some patients having ASD and seizures, suggesting that its mutation disrupts neurological function in part through increasing neuronal activity. Supporting this idea, neuronal knock-out of Pten in mice can cause macrocephaly, behavioral changes similar to ASD, and seizures. However, the mechanisms through which excitability is enhanced following Pten depletion are unclear. Previous studies have separately shown that Pten-depleted neurons can drive seizures, receive elevated excitatory synaptic input, and have abnormal dendrites. We therefore tested the hypothesis that developing Pten-depleted neurons are hyperactive due to increased excitatory synaptogenesis using electrophysiology, calcium imaging, morphological analyses, and modeling. This was accomplished by coinjecting retroviruses to either "birthdate" or birthdate and knock-out Pten in granule neurons of the murine neonatal dentate gyrus. We found that Pten knock-out neurons, despite a rapid onset of hypertrophy, were more active in vivo. Pten knock-out neurons fired at more hyperpolarized membrane potentials, displayed greater peak spike rates, and were more sensitive to depolarizing synaptic input. The increased sensitivity of Pten knock-out neurons was due, in part, to a higher density of synapses located more proximal to the soma. We determined that increased synaptic drive was sufficient to drive hypertrophic Pten knock-out neurons beyond their altered action potential threshold. Thus, our work contributes a developmental mechanism for the increased activity of Pten-depleted neurons. Copyright © 2015 the authors 0270-6474/15/350943-17$15.00/0.

Hypodermal delivery of cosmetic actives for improved facial skin morphology and functionality.

PubMed

Bojanowski, K

2013-12-01

Skin compartments traditionally targeted by cosmetic actives - epidermis and dermis - are anchored and nourished by the underlying hypodermis, which therefore should be a key target for skin-rejuvenating formulations. However, given the difficulty to reach even the superficial layers of the skin, and to its 'unglamorous' fatty composition, the regenerative potential of hypodermis remains largely untapped. Therefore, this study was to investigate the capacity of a cosmetic material to trigger a regenerative response in dermis and epidermis through a selective action on hypodermis. Furthermore, it aimed to establish the effect of such cosmetic material in transbuccal hypodermal delivery form, on the hypodermal precursor cells - the preadipocytes. A combination of grape seed extract and soy phospholipids was formulated and standardized for elastase activity and free radical inhibition. This formulation was then used to contact the hypodermal layer of human skin biopsies and - under a transbuccal delivery vehicle form - the 3T3-L1 preadipocytes, and its effects were quantified using PCR arrays and histochemistry. Application of the standardized grape/soy material to the hypodermal layer of skin triggered modulation of gene expression in the upper layers of the skin and resulted in the clear morphological improvement at the dermal and epidermal levels. Furthermore, when this material was formulated in a mucoadhesive, intraoral film and applied on 3T3-L1 preadipocytes, the resulting modulation of gene expression in these cells was consistent with differentiation and detoxification effects. These results suggest that transbuccal formulations of nutraceutical grade cosmetics have potential to induce signal transduction pathways in facial hypodermis, resulting in anti-aging effects throughout all skin compartments, including dermal and epidermal layers. © 2013 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

Alterations of sodium and potassium channels of RGCs in RCS rat with the development of retinal degeneration.

PubMed

Chen, Zhongshan; Song, Yanping; Yao, Junping; Weng, Chuanhuang; Yin, Zheng Qin

2013-11-01

All know that retinitis pigmentosa (RP) is a group of hereditary retinal degenerative diseases characterized by progressive dysfunction of photoreceptors and associated with progressive cells loss; nevertheless, little is known about how rods and cones loss affects the surviving inner retinal neurons and networks. Retinal ganglion cells (RGCs) process and convey visual information from retina to visual centers in the brain. The healthy various ion channels determine the normal reception and projection of visual signals from RGCs. Previous work on the Royal College of Surgeons (RCS) rat, as a kind of classical RP animal model, indicated that, at late stages of retinal degeneration in RCS rat, RGCs were also morphologically and functionally affected. Here, retrograde labeling for RGCs with Fluorogold was performed to investigate the distribution, density, and morphological changes of RGCs during retinal degeneration. Then, patch clamp recording, western blot, and immunofluorescence staining were performed to study the channels of sodium and potassium properties of RGCs, so as to explore the molecular and proteinic basis for understanding the alterations of RGCs membrane properties and firing functions. We found that the resting membrane potential, input resistance, and capacitance of RGCs changed significantly at the late stage of retinal degeneration. Action potential could not be evoked in a part of RGCs. Inward sodium current and outward potassium current recording showed that sodium current was impaired severely but only slightly in potassium current. Expressions of sodium channel protein were impaired dramatically at the late stage of retinal degeneration. The results suggested that the density of RGCs decreased, process ramification impaired, and sodium ion channel proteins destructed, which led to the impairment of electrophysiological functions of RGCs and eventually resulted in the loss of visual function.

Cannabinoid Receptors Modulate Neuronal Morphology and AnkyrinG Density at the Axon Initial Segment

PubMed Central

Tapia, Mónica; Dominguez, Ana; Zhang, Wei; del Puerto, Ana; Ciorraga, María; Benitez, María José; Guaza, Carmen; Garrido, Juan José

2017-01-01

Neuronal polarization underlies the ability of neurons to integrate and transmit information. This process begins early in development with axon outgrowth, followed by dendritic growth and subsequent maturation. In between these two steps, the axon initial segment (AIS), a subcellular domain crucial for generating action potentials (APs) and maintaining the morphological and functional polarization, starts to develop. However, the cellular/molecular mechanisms and receptors involved in AIS initial development and maturation are mostly unknown. In this study, we have focused on the role of the type-1 cannabinoid receptor (CB1R), a highly abundant G-protein coupled receptor (GPCR) in the nervous system largely involved in different phases of neuronal development and differentiation. Although CB1R activity modulation has been related to changes in axons or dendrites, its possible role as a modulator of AIS development has not been yet explored. Here we analyzed the potential role of CB1R on neuronal morphology and AIS development using pharmacological and RNA interference approaches in cultured hippocampal neurons. CB1R inhibition, at a very early developmental stage, has no effect on axonal growth, yet CB1R activation can promote it. By contrast, subsequent dendritic growth is impaired by CB1R inhibition, which also reduces ankyrinG density at the AIS. Moreover, our data show a significant correlation between early dendritic growth and ankyrinG density. However, CB1R inhibition in later developmental stages after dendrites are formed only reduces ankyrinG accumulation at the AIS. In conclusion, our data suggest that neuronal CB1R basal activity plays a role in initial development of dendrites and indirectly in AIS proteins accumulation. Based on the lack of CB1R expression at the AIS, we hypothesize that CB1R mediated modulation of dendritic arbor size during early development indirectly determines the accumulation of ankyrinG and AIS development. Further studies will be necessary to determine which CB1R-dependent mechanisms can coordinate these two domains, and what may be the impact of these early developmental changes once neurons mature and are embedded in a functional brain network. PMID:28179879

Morphological change in cranial shape following the transition to agriculture across western Eurasia.

PubMed

Cheronet, Olivia; Finarelli, John A; Pinhasi, Ron

2016-09-13

The Neolithic transition brought about fundamental social, dietary and behavioural changes in human populations, which, in turn, impacted skeletal morphology. Crania are shaped through diverse genetic, ontogenetic and environmental factors, reflecting various elements of an individual's life. To determine the transition's effect on cranial morphology, we investigated its potential impact on the face and vault, two elements potentially responding to different influences. Three datasets from geographically distant regions (Ukraine, Iberia, and the Levant plus Anatolia) were analysed. Craniometric measurements were used to compare the morphology of pre-transition populations with that of agricultural populations. The Neolithic transition corresponds to a statistically significant increase only in cranial breadth of the Ukrainian vaults, while facial morphology shows no consistent transformations, despite expected changes related to the modification of masticatory behaviour. The broadening of Ukrainian vaults may be attributable to dietary and/or social changes. However, the lack of change observed in the other geographical regions and the lack of consistent change in facial morphology are surprising. Although the transition from foraging to farming is a process that took place repeatedly across the globe, different characteristics of transitions seem responsible for idiosyncratic responses in cranial morphology.

Cortical astrocytes exposed to tributyltin undergo morphological changes in vitro.

PubMed

Mizuhashi, S; Ikegaya, Y; Nishiyama, N; Matsuki, N

2000-11-01

We investigated the effect of tributyltin (TBT), an endocrine-disrupting chemical, on the morphology and viability of cultured rat cortical astrocytes. Cultured astrocytes exhibited smooth and planiform morphology under normal conditions. Following exposure to TBT, however, they showed rapid morphological changes that are characterized by asteriated cell bodies and process formation in a time- and concentration-dependent manner. Higher concentrations of TBT produced progressive cell death of the astrocytes. In serum-free medium, TBT at a concentration as low as 200 nM induced the stellation. Pharmacological studies revealed that the morphological changes were alleviated by application of diverse free radical scavengers or antioxidants such as catalase, superoxide dismutase, Trolox, ascorbic acid and N-acetyl-L-cysteine, suggesting that TBT-induced stellation is caused by oxidative stress involving free radicals, particularly reactive oxygen species. Furthermore, we found that the astrocyte stellation was abolished by treatment with inhibitors of phospholipase C, mitogen-activated protein kinase kinase or tyrosine phosphatase. The data suggest that TBT causes the stellation through intracellular signaling cascades rather than its non-specific toxicity. These findings provide an important insight for reconciling the problems in assumed aversive actions of this environmental pollutant for mammals.

The activity of spontaneous action potentials in developing hair cells is regulated by Ca(2+)-dependence of a transient K+ current.

PubMed

Levic, Snezana; Lv, Ping; Yamoah, Ebenezer N

2011-01-01

Spontaneous action potentials have been described in developing sensory systems. These rhythmic activities may have instructional roles for the functional development of synaptic connections. The importance of spontaneous action potentials in the developing auditory system is underpinned by the stark correlation between the time of auditory system functional maturity, and the cessation of spontaneous action potentials. A prominent K(+) current that regulates patterning of action potentials is I(A). This current undergoes marked changes in expression during chicken hair cell development. Although the properties of I(A) are not normally classified as Ca(2+)-dependent, we demonstrate that throughout the development of chicken hair cells, I(A) is greatly reduced by acute alterations of intracellular Ca(2+). As determinants of spike timing and firing frequency, intracellular Ca(2+) buffers shift the activation and inactivation properties of the current to more positive potentials. Our findings provide evidence to demonstrate that the kinetics and functional expression of I(A) are tightly regulated by intracellular Ca(2+). Such feedback mechanism between the functional expression of I(A) and intracellular Ca(2+) may shape the activity of spontaneous action potentials, thus potentially sculpting synaptic connections in an activity-dependent manner in the developing cochlea. © 2011 Levic et al.

78 FR 23740 - Notice of Availability of a Swine Brucellosis and Pseudorabies Proposed Action Plan

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-22

...] Notice of Availability of a Swine Brucellosis and Pseudorabies Proposed Action Plan AGENCY: Animal and... proposed action plan describing a potential new approach to managing swine brucellosis and pseudorabies...-0086) a notice that made a proposed action plan describing a potential new approach to managing swine...

Paclitaxel and the dietary flavonoid fisetin: a synergistic combination that induces mitotic catastrophe and autophagic cell death in A549 non-small cell lung cancer cells.

PubMed

Klimaszewska-Wisniewska, Anna; Halas-Wisniewska, Marta; Tadrowski, Tadeusz; Gagat, Maciej; Grzanka, Dariusz; Grzanka, Alina

2016-01-01

The use of the dietary polyphenols as chemosensitizing agents to enhance the efficacy of conventional cytostatic drugs has recently gained the attention of scientists and clinicians as a plausible approach for overcoming the limitations of chemotherapy (e.g. drug resistance and cytotoxicity). The aim of this study was to investigate whether a naturally occurring diet-based flavonoid, fisetin, at physiologically attainable concentrations, could act synergistically with clinically achievable doses of paclitaxel to produce growth inhibitory and/or pro-death effects on A549 non-small cell lung cancer cells, and if it does, what mechanisms might be involved. The drug-drug interactions were analyzed based on the combination index method of Chou and Talalay and the data from MTT assays. To provide some insights into the mechanism underlying the synergistic action of fisetin and paclitaxel, selected morphological, biochemical and molecular parameters were examined, including the morphology of cell nuclei and mitotic spindles, the pattern of LC3-II immunostaining, the formation of autophagic vacuoles at the electron and fluorescence microscopic level, the disruption of cell membrane asymmetry/integrity, cell cycle progression and the expression level of LC3-II, Bax, Bcl-2 and caspase-3 mRNA. Here, we reported the first experimental evidence for the existence of synergism between fisetin and paclitaxel in the in vitro model of non-small cell lung cancer. This synergism was, at least partially, ascribed to the induction of mitotic catastrophe. The switch from the cytoprotective autophagy to the autophagic cell death was also implicated in the mechanism of the synergistic action of fisetin and paclitaxel in the A549 cells. In addition, we revealed that the synergism between fisetin and paclitaxel was cell line-specific as well as that fisetin synergizes with arsenic trioxide, but not with mitoxantrone and methotrexate in the A549 cells. Our results provide rationale for further testing of fisetin in the combination with paclitaxel or arsenic trioxide to obtain detailed insights into the mechanism of their synergistic action as well as to evaluate their toxicity towards normal cells in an animal model in vivo. We conclude that this study is potentially interesting for the development of novel chemotherapeutic approach to non-small cell lung cancer.

Low temperature–scanning electron microscopy to evaluate morphology and predation of Scolothrips sexmaculatus Pergande (Thysanoptera: Thripidae) against spider mites (Acari: Tetranychidae: Tetranychus species)

USDA-ARS?s Scientific Manuscript database

This paper evaluates the potential usefulness of low temperature-scanning electron microscopy (LT-SEM) to evaluate morphology and predation behavior of the six-spotted thrips (Scolothrips sexmaculatus Pergande) against the two-spotted spider mite (Tetranychus urticae (Koch)). Morphological features...

Modulating anosognosia for hemiplegia: The role of dangerous actions in emergent awareness.

PubMed

D'Imperio, Daniela; Bulgarelli, Cristina; Bertagnoli, Sara; Avesani, Renato; Moro, Valentina

2017-07-01

Anosognosia for hemiplegia is a lack of awareness of motor deficits following a right hemisphere lesion. Residual forms of awareness co-occur with an explicit denial of hemiplegia. The term emergent awareness refers to a condition in which awareness of motor deficits is reported verbally during the actual performance of an action involving the affected body part. In this study, two tasks were used to explore the potential effects of i) attempting actions which are impossible for sufferers of hemiplegia and ii) attempting actions which are potentially dangerous. Sixteen hemiplegic patients (8 anosognosic, and 8 non-anosognosic) were asked to perform both potentially dangerous and neutral actions. Our results confirm an increase in emergent awareness in anosognosic patients during the execution of both of these types of action. Moreover, actions that are potentially dangerous improved the degree of awareness. However, lesions in the fronto-temporal areas appear to be associated with a reduced effect of action execution (emergent awareness) while lesions in the basal ganglia and amygdale and the white matter underlying the insula and fronto-temporal areas are associated with a lesser degree of improvement resulting from attempting to perform dangerous actions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Nanovesicle encapsulation of antimicrobial peptide P34: physicochemical characterization and mode of action on Listeria monocytogenes

NASA Astrophysics Data System (ADS)

da Silva Malheiros, Patrícia; Sant'Anna, Voltaire; Micheletto, Yasmine Miguel Serafini; da Silveira, Nadya Pesce; Brandelli, Adriano

2011-08-01

Antimicrobial peptide P34, a substance showing antibacterial activity against pathogenic and food spoilage bacteria, was encapsulated in liposomes prepared from partially purified soybean phosphatidylcholine, and their physicochemical characteristics were evaluated. The antimicrobial activity was estimated by agar diffusion assay using Listeria monocytogenes ATCC 7644 as indicator strain. A concentration of 3,200 AU/mL of P34 was encapsulated in nanovesicles and stocked at 4 °C. No significant difference ( p > 0.05) in the biological activity of free and encapsulated P34 was observed through 24 days. Size and PDI of liposomes, investigated by light scattering analysis, were on average 150 nm and 0.22 respectively. Zeta potential was -27.42 mV. There was no significant change ( p > 0.05) in the physicochemical properties of liposomes during the time of evaluation. The liposomes presented closed spherical morphology as visualized by transmission electron microscopy (TEM). The mode of action of liposome-encapsulated P34 under L. monocytogenes cells was investigated by TEM. Liposomes appeared to adhere but not fuse with the bacterial cell wall, suggesting that the antimicrobial is released from nanovesicles to act against the microorganism. The effect of free and encapsulated P34 was tested against L. monocytogenes, showing that free bacteriocin inhibited the pathogen more quickly than the encapsulated P34. Liposomes prepared with low-cost lipid showed high encapsulation efficiency for a new antimicrobial peptide and were stable during storage. The mode of action against the pathogen L. monocytogenes was characterized.

[Effect of pulse magnetic field on distribution of neuronal action potential].

PubMed

Zheng, Yu; Cai, Di; Wang, Jin-Hai; Li, Gang; Lin, Ling

2014-08-25

The biological effect on the organism generated by magnetic field is widely studied. The present study was aimed to observe the change of sodium channel under magnetic field in neurons. Cortical neurons of Kunming mice were isolated, subjected to 15 Hz, 1 mT pulse magnetic stimulation, and then the currents of neurons were recorded by whole-cell patch clamp. The results showed that, under magnetic stimulation, the activation process of Na(+) channel was delayed, and the inactivation process was accelerated. Given the classic three-layer model, the polarization diagram of cell membrane potential distribution under pulse magnetic field was simulated, and it was found that the membrane potential induced was associated with the frequency and intensity of magnetic field. Also the effect of magnetic field-induced current on action potential was simulated by Hodgkin-Huxley (H-H) model. The result showed that the generation of action potential was delayed, and frequency and the amplitudes were decreased when working current was between -1.32 μA and 0 μA. When the working current was higher than 0 μA, the generation frequency of action potential was increased, and the change of amplitudes was not obvious, and when the working current was lower than -1.32 μA, the time of rising edge and amplitudes of action potential were decreased drastically, and the action potential was unable to generate. These results suggest that the magnetic field simulation can affect the distribution frequency and amplitude of action potential of neuron via sodium channel mediation.

Maternal creatine supplementation affects the morpho-functional development of hippocampal neurons in rat offspring.

PubMed

Sartini, S; Lattanzi, D; Ambrogini, P; Di Palma, M; Galati, C; Savelli, D; Polidori, E; Calcabrini, C; Rocchi, M B L; Sestili, P; Cuppini, R

2016-01-15

Creatine supplementation has been shown to protect neurons from oxidative damage due to its antioxidant and ergogenic functions. These features have led to the hypothesis of creatine supplementation use during pregnancy as prophylactic treatment to prevent CNS damage, such as hypoxic-ischemic encephalopathy. Unfortunately, very little is known on the effects of creatine supplementation during neuron differentiation, while in vitro studies revealed an influence on neuron excitability, leaving the possibility of creatine supplementation during the CNS development an open question. Using a multiple approach, we studied the hippocampal neuron morphological and functional development in neonatal rats born by dams supplemented with 1% creatine in drinking water during pregnancy. CA1 pyramidal neurons of supplemented newborn rats showed enhanced dendritic tree development, increased LTP maintenance, larger evoked-synaptic responses, and higher intrinsic excitability in comparison to controls. Moreover, a faster repolarizing phase of action potential with the appearance of a hyperpolarization were recorded in neurons of the creatine-treated group. Consistently, CA1 neurons of creatine exposed pups exhibited a higher maximum firing frequency than controls. In summary, we found that creatine supplementation during pregnancy positively affects morphological and electrophysiological development of CA1 neurons in offspring rats, increasing neuronal excitability. Altogether, these findings emphasize the need to evaluate the benefits and the safety of maternal intake of creatine in humans. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Wt-p53 action in human leukaemia cell lines corresponding to different stages of differentiation.

PubMed

Rizzo, M G; Zepparoni, A; Cristofanelli, B; Scardigli, R; Crescenzi, M; Blandino, G; Giuliacci, S; Ferrari, S; Soddu, S; Sacchi, A

1998-05-01

Recent studies support the potential application of the wt-p53 gene in cancer therapy. Expression of exogenous wt-p53 suppresses a variety of leukaemia phenotypes by acting on cell survival, proliferation and/or differentiation. As for tumour gene therapy, the final fate of the neoplastic cells is one of the most relevant points. We examined the effects of exogenous wt-p53 gene expression in several leukaemia cell lines to identify p53-responsive leukaemia. The temperature-sensitive p53Val135 mutant or the human wt-p53 cDNA was transduced in leukaemia cell lines representative of different acute leukaemia FAB subtypes, including M1 (KG1), M2 (HL-60), M3 (NB4), M5 (U937) and M6 (HEL 92.1.7), as well as blast crisis of chronic myelogenous leukaemia (BC-CML: K562, BV173) showing diverse differentiation features. By morphological, molecular and biochemical analyses, we have shown that exogenous wt-p53 gene expression induces apoptosis only in cells corresponding to M1, M2 and M3 of the FAB classification and in BC-CML showing morphological and cytochemical features of undifferentiated blast cells. In contrast, it promotes differentiation in the others. Interestingly, cell responsiveness was independent of the vector used and the status of the endogenous p53 gene.

Nanomechanical and topographical imaging of living cells by atomic force microscopy with colloidal probes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Puricelli, Luca; Galluzzi, Massimiliano; Schulte, Carsten

Atomic Force Microscopy (AFM) has a great potential as a tool to characterize mechanical and morphological properties of living cells; these properties have been shown to correlate with cells’ fate and patho-physiological state in view of the development of novel early-diagnostic strategies. Although several reports have described experimental and technical approaches for the characterization of cellular elasticity by means of AFM, a robust and commonly accepted methodology is still lacking. Here, we show that micrometric spherical probes (also known as colloidal probes) are well suited for performing a combined topographic and mechanical analysis of living cells, with spatial resolution suitablemore » for a complete and accurate mapping of cell morphological and elastic properties, and superior reliability and accuracy in the mechanical measurements with respect to conventional and widely used sharp AFM tips. We address a number of issues concerning the nanomechanical analysis, including the applicability of contact mechanical models and the impact of a constrained contact geometry on the measured Young’s modulus (the finite-thickness effect). We have tested our protocol by imaging living PC12 and MDA-MB-231 cells, in order to demonstrate the importance of the correction of the finite-thickness effect and the change in Young’s modulus induced by the action of a cytoskeleton-targeting drug.« less

Microscale Electrode Implantation during Nerve Repair: Effects on Nerve Morphology, Electromyography, and Recovery of Muscle Contractile Function

PubMed Central

Urbanchek, Melanie G; Wei, Benjamin; Egeland, Brent M; Abidian, Mohammad R; Kipke, Daryl R; Cederna, Paul S

2011-01-01

Background Our goal is to develop a peripheral nerve electrode with long-term stability and fidelity for use in nerve-machine interfaces. Microelectromechanical systems (MEMS) use silicon probes that contain multi-channel actuators, sensors, and electronics. We tested the null hypothesis that implantation of MEMS probes do not have a detrimental effect on peripheral nerve function or regeneration. Methods A rat hindlimb, peroneal nerve model was utilized in all experimental groups: a) intact nerve (Control, n= 10); b) nerve division and repair (Repair, n= 9); and c) Nerve division, insertion of MEMS probe, and repair (Repair + Probe, n=9). Nerve morphology, nerve to muscle compound action potential (CMAP) studies, walking tracks, and extensor digitorum longus (EDL) muscle function tests were evaluated following an 80 day recovery. Results Repair and Repair + Probe showed no differences in axon count, axon size, percent non-neural area, CMAP amplitude, latency, muscle mass, muscle force, or walking track scores. Though there was some local fibrosis around each MEMS probe, this did not lead to measurable detrimental effects in any anatomic or functional outcome measurements. Conclusions The lack of a significant difference between Repair and Repair + Probe groups in histology, CMAP, walking tracks, and muscle force suggests that MEMS electrodes are compatible with regenerating axons and show promise for establishing chemical and electrical interfaces with peripheral nerves. PMID:21921739

Nephro-protective action of P. santalinus against alcohol-induced biochemical alterations and oxidative damage in rats.

PubMed

Bulle, Saradamma; Reddy, Vaddi Damodara; Hebbani, Ananda Vardhan; Padmavathi, Pannuru; Challa, Chandrasekhar; Puvvada, Pavan Kumar; Repalle, Elisha; Nayakanti, Devanna; Aluganti Narasimhulu, Chandrakala; Nallanchakravarthula, Varadacharyulu

2016-12-01

The present study investigated the antioxidant potential of P. santalinus heartwood methanolic extract (PSE) against alcohol-induced nephro-toxicity. The results indicated an increase in the concentration of kidney damage plasma markers, urea and creatinine with a concomitant decrease in the concentration of uric acid in alcohol-administered rats. A significant decrease in plasma electrolytes and mineral levels with increased kidney thiobarbituric acid reactive substances (TBARS) and nitric oxide (NOx) levels was also observed. PSE treatment to alcohol-administered rats effectively prevented the elevation in TBARS and NOx levels. Decreased activity of Na + /K + -ATPase in alcohol administered rats was brought to near normal levels with treatment of PSE. Chronic alcohol consumption affects antioxidant enzymatic activity and reabsorption function of the kidney which is evident from the decreased level of GSH as well as the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione s-transferase (GST). However, treatment with PSE to alcohol-administered rats significantly enhanced these enzymatic activities and reduced glutathione (GSH) content close to normal level. Alcohol-induced organ damage was evident from morphological changes in the kidney. Nevertheless, administration of PSE effectively restored these morphological changes to normal. The flavonoid and tannoid compounds might have protective activity against alcohol-induced oxidative/nitrosative stress mediated kidney damage. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Intracellular recording of action potentials by nanopillar electroporation.

PubMed

Xie, Chong; Lin, Ziliang; Hanson, Lindsey; Cui, Yi; Cui, Bianxiao

2012-02-12

Action potentials have a central role in the nervous system and in many cellular processes, notably those involving ion channels. The accurate measurement of action potentials requires efficient coupling between the cell membrane and the measuring electrodes. Intracellular recording methods such as patch clamping involve measuring the voltage or current across the cell membrane by accessing the cell interior with an electrode, allowing both the amplitude and shape of the action potentials to be recorded faithfully with high signal-to-noise ratios. However, the invasive nature of intracellular methods usually limits the recording time to a few hours, and their complexity makes it difficult to simultaneously record more than a few cells. Extracellular recording methods, such as multielectrode arrays and multitransistor arrays, are non-invasive and allow long-term and multiplexed measurements. However, extracellular recording sacrifices the one-to-one correspondence between the cells and electrodes, and also suffers from significantly reduced signal strength and quality. Extracellular techniques are not, therefore, able to record action potentials with the accuracy needed to explore the properties of ion channels. As a result, the pharmacological screening of ion-channel drugs is usually performed by low-throughput intracellular recording methods. The use of nanowire transistors, nanotube-coupled transistors and micro gold-spine and related electrodes can significantly improve the signal strength of recorded action potentials. Here, we show that vertical nanopillar electrodes can record both the extracellular and intracellular action potentials of cultured cardiomyocytes over a long period of time with excellent signal strength and quality. Moreover, it is possible to repeatedly switch between extracellular and intracellular recording by nanoscale electroporation and resealing processes. Furthermore, vertical nanopillar electrodes can detect subtle changes in action potentials induced by drugs that target ion channels.

Intracellular recording of action potentials by nanopillar electroporation

NASA Astrophysics Data System (ADS)

Xie, Chong; Lin, Ziliang; Hanson, Lindsey; Cui, Yi; Cui, Bianxiao

2012-03-01

Action potentials have a central role in the nervous system and in many cellular processes, notably those involving ion channels. The accurate measurement of action potentials requires efficient coupling between the cell membrane and the measuring electrodes. Intracellular recording methods such as patch clamping involve measuring the voltage or current across the cell membrane by accessing the cell interior with an electrode, allowing both the amplitude and shape of the action potentials to be recorded faithfully with high signal-to-noise ratios. However, the invasive nature of intracellular methods usually limits the recording time to a few hours, and their complexity makes it difficult to simultaneously record more than a few cells. Extracellular recording methods, such as multielectrode arrays and multitransistor arrays, are non-invasive and allow long-term and multiplexed measurements. However, extracellular recording sacrifices the one-to-one correspondence between the cells and electrodes, and also suffers from significantly reduced signal strength and quality. Extracellular techniques are not, therefore, able to record action potentials with the accuracy needed to explore the properties of ion channels. As a result, the pharmacological screening of ion-channel drugs is usually performed by low-throughput intracellular recording methods. The use of nanowire transistors, nanotube-coupled transistors and micro gold-spine and related electrodes can significantly improve the signal strength of recorded action potentials. Here, we show that vertical nanopillar electrodes can record both the extracellular and intracellular action potentials of cultured cardiomyocytes over a long period of time with excellent signal strength and quality. Moreover, it is possible to repeatedly switch between extracellular and intracellular recording by nanoscale electroporation and resealing processes. Furthermore, vertical nanopillar electrodes can detect subtle changes in action potentials induced by drugs that target ion channels.

Action potential bursts in central snail neurons elicited by paeonol: roles of ionic currents

PubMed Central

Chen, Yi-hung; Lin, Pei-lin; Hsu, Hui-yu; Wu, Ya-ting; Yang, Han-yin; Lu, Dah-yuu; Huang, Shiang-suo; Hsieh, Ching-liang; Lin, Jaung-geng

2010-01-01

Aim: To investigate the effects of 2′-hydroxy-4′-methoxyacetophenone (paeonol) on the electrophysiological behavior of a central neuron (right parietal 4; RP4) of the giant African snail (Achatina fulica Ferussac). Methods: Intracellular recordings and the two-electrode voltage clamp method were used to study the effects of paeonol on the RP4 neuron. Results: The RP4 neuron generated spontaneous action potentials. Bath application of paeonol at a concentration of ≥500 μmol/L reversibly elicited action potential bursts in a concentration-dependent manner. Immersing the neurons in Co2+-substituted Ca2+-free solution did not block paeonol-elicited bursting. Pretreatment with the protein kinase A (PKA) inhibitor KT-5720 or the protein kinase C (PKC) inhibitor Ro 31-8220 did not affect the action potential bursts. Voltage-clamp studies revealed that paeonol at a concentration of 500 μmol/L had no remarkable effects on the total inward currents, whereas paeonol decreased the delayed rectifying K+ current (IKD) and the fast-inactivating K+ current (IA). Application of 4-aminopyridine (4-AP 5 mmol/L), an inhibitor of IA, or charybdotoxin 250 nmol/L, an inhibitor of the Ca2+-activated K+ current (IK(Ca)), failed to elicit action potential bursts, whereas tetraethylammonium chloride (TEA 50 mmol/L), an IKD blocker, successfully elicited action potential bursts. At a lower concentration of 5 mmol/L, TEA facilitated the induction of action potential bursts elicited by paeonol. Conclusion: Paeonol elicited a bursting firing pattern of action potentials in the RP4 neuron and this activity relates closely to the inhibitory effects of paeonol on the IKD. PMID:21042287

Consequences of converting graded to action potentials upon neural information coding and energy efficiency.

PubMed

Sengupta, Biswa; Laughlin, Simon Barry; Niven, Jeremy Edward

2014-01-01

Information is encoded in neural circuits using both graded and action potentials, converting between them within single neurons and successive processing layers. This conversion is accompanied by information loss and a drop in energy efficiency. We investigate the biophysical causes of this loss of information and efficiency by comparing spiking neuron models, containing stochastic voltage-gated Na(+) and K(+) channels, with generator potential and graded potential models lacking voltage-gated Na(+) channels. We identify three causes of information loss in the generator potential that are the by-product of action potential generation: (1) the voltage-gated Na(+) channels necessary for action potential generation increase intrinsic noise and (2) introduce non-linearities, and (3) the finite duration of the action potential creates a 'footprint' in the generator potential that obscures incoming signals. These three processes reduce information rates by ∼50% in generator potentials, to ∼3 times that of spike trains. Both generator potentials and graded potentials consume almost an order of magnitude less energy per second than spike trains. Because of the lower information rates of generator potentials they are substantially less energy efficient than graded potentials. However, both are an order of magnitude more efficient than spike trains due to the higher energy costs and low information content of spikes, emphasizing that there is a two-fold cost of converting analogue to digital; information loss and cost inflation.

Consequences of Converting Graded to Action Potentials upon Neural Information Coding and Energy Efficiency

PubMed Central

Sengupta, Biswa; Laughlin, Simon Barry; Niven, Jeremy Edward

2014-01-01

Information is encoded in neural circuits using both graded and action potentials, converting between them within single neurons and successive processing layers. This conversion is accompanied by information loss and a drop in energy efficiency. We investigate the biophysical causes of this loss of information and efficiency by comparing spiking neuron models, containing stochastic voltage-gated Na+ and K+ channels, with generator potential and graded potential models lacking voltage-gated Na+ channels. We identify three causes of information loss in the generator potential that are the by-product of action potential generation: (1) the voltage-gated Na+ channels necessary for action potential generation increase intrinsic noise and (2) introduce non-linearities, and (3) the finite duration of the action potential creates a ‘footprint’ in the generator potential that obscures incoming signals. These three processes reduce information rates by ∼50% in generator potentials, to ∼3 times that of spike trains. Both generator potentials and graded potentials consume almost an order of magnitude less energy per second than spike trains. Because of the lower information rates of generator potentials they are substantially less energy efficient than graded potentials. However, both are an order of magnitude more efficient than spike trains due to the higher energy costs and low information content of spikes, emphasizing that there is a two-fold cost of converting analogue to digital; information loss and cost inflation. PMID:24465197

Quenching influence of cell culture medium on photoluminescence and morphological structure of porous silicon

NASA Astrophysics Data System (ADS)

Unal, Bayram

2011-10-01

In this work, the degradation of visible photoluminescence of porous silicon (PSi) under the influential actions of cell culture medium has been mainly studied in order to comprehend the quenching mechanisms necessitating the cell growth on spongy-like-silicon structures, which could form either micro- and/or nano-dimensional morphologies after stain-etching of the poly- or single-crystalline Si surfaces. Quenching effect of the neuron culture medium on visibly luminescent and non-luminescent porous silicon is found to be quite obvious so that this step of the culture process, especially, over nanostructured silicon is extremely essential for a variety of bionanotechnological applications.

Synchronization of action potentials during low-magnesium-induced bursting

PubMed Central

Johnson, Sarah E.; Hudson, John L.

2015-01-01

The relationship between mono- and polysynaptic strength and action potential synchronization was explored using a reduced external Mg2+ model. Single and dual whole cell patch-clamp recordings were performed in hippocampal cultures in three concentrations of external Mg2+. In decreased Mg2+ medium, the individual cells transitioned to spontaneous bursting behavior. In lowered Mg2+ media the larger excitatory synaptic events were observed more frequently and fewer transmission failures occurred, suggesting strengthened synaptic transmission. The event synchronization was calculated for the neural action potentials of the cell pairs, and it increased in media where Mg2+ concentration was lowered. Analysis of surrogate data where bursting was present, but no direct or indirect connections existed between the neurons, showed minimal action potential synchronization. This suggests the synchronization of action potentials is a product of the strengthening synaptic connections within neuronal networks. PMID:25609103

Synchronization of action potentials during low-magnesium-induced bursting.

PubMed

Johnson, Sarah E; Hudson, John L; Kapur, Jaideep

2015-04-01

The relationship between mono- and polysynaptic strength and action potential synchronization was explored using a reduced external Mg(2+) model. Single and dual whole cell patch-clamp recordings were performed in hippocampal cultures in three concentrations of external Mg(2+). In decreased Mg(2+) medium, the individual cells transitioned to spontaneous bursting behavior. In lowered Mg(2+) media the larger excitatory synaptic events were observed more frequently and fewer transmission failures occurred, suggesting strengthened synaptic transmission. The event synchronization was calculated for the neural action potentials of the cell pairs, and it increased in media where Mg(2+) concentration was lowered. Analysis of surrogate data where bursting was present, but no direct or indirect connections existed between the neurons, showed minimal action potential synchronization. This suggests the synchronization of action potentials is a product of the strengthening synaptic connections within neuronal networks. Copyright © 2015 the American Physiological Society.

Millisecond infrared laser pulses depolarize and elicit action potentials on in-vitro dorsal root ganglion neurons

PubMed Central

Paris, Lambert; Marc, Isabelle; Charlot, Benoit; Dumas, Michel; Valmier, Jean; Bardin, Fabrice

2017-01-01

This work focuses on the optical stimulation of dorsal root ganglion (DRG) neurons through infrared laser light stimulation. We show that a few millisecond laser pulse at 1875 nm induces a membrane depolarization, which was observed by the patch-clamp technique. This stimulation led to action potentials firing on a minority of neurons beyond an energy threshold. A depolarization without action potential was observed for the majority of DRG neurons, even beyond the action potential energy threshold. The use of ruthenium red, a thermal channel blocker, stops the action potential generation, but has no effects on membrane depolarization. Local temperature measurements reveal that the depolarization amplitude is sensitive to the amplitude of the temperature rise as well as to the time rate of change of temperature, but in a way which may not fully follow a photothermal capacitive mechanism, suggesting that more complex mechanisms are involved. PMID:29082085

[Effects of dauricine on action potentials and slow inward currents of guinea pig ventricular papillary muscles].

PubMed

Li, S N; Zhang, K Y

1992-11-01

Effects of dauricine (Dau) on the action potentials (AP), the slow action potentials (SAP), and the slow inward currents (Isi) of guinea pig ventricular papillary muscles were observed by means of intracellular microelectrode and single sucrose gap voltage clamp technique. In the early stage, Dau shortened action potential duration 100 (APD100) and effective refractory period (ERP) (ERP/APD < 1; P < 0.01), but did not affect APD20 and other parameters. In the late stage, Dau prolonged APD100, ERP, and APD20, significantly decreased action potential amplitude (APA), maximum velocity (Vmax), and overshot (OS) (ERP/APD > 1; P < 0.01), greatly diminished APA and OS of SAP induced by isoprenaline (P < 0.01), and remarkably inhibited Isi (P < 0.01). The results suggested that Dau exerted an inhibitory effect on Na+, Ca2+, and K+ channels.

Simulation of axonal excitability using a Spreadsheet template created in Microsoft Excel.

PubMed

Brown, A M

2000-08-01

The objective of this present study was to implement an established simulation protocol (A.M. Brown, A methodology for simulating biological systems using Microsoft Excel, Comp. Methods Prog. Biomed. 58 (1999) 181-90) to model axonal excitability. The simulation protocol involves the use of in-cell formulas directly typed into a spreadsheet and does not require any programming skills or use of the macro language. Once the initial spreadsheet template has been set up the simulations described in this paper can be executed with a few simple keystrokes. The model axon contained voltage-gated ion channels that were modeled using Hodgkin Huxley style kinetics. The basic properties of axonal excitability modeled were: (1) threshold of action potential firing, demonstrating that not only are the stimulus amplitude and duration critical in the generation of an action potential, but also the resting membrane potential; (2) refractoriness, the phenomenon of reduced excitability immediately following an action potential. The difference between the absolute refractory period, when no amount of stimulus will elicit an action potential, and relative refractory period, when an action potential may be generated by applying increased stimulus, was demonstrated with regard to the underlying state of the Na(+) and K(+) channels; (3) temporal summation, a process by which two sub-threshold stimuli can unite to elicit an action potential was shown to be due to conductance changes outlasting the first stimulus and summing with the second stimulus-induced conductance changes to drive the membrane potential past threshold; (4) anode break excitation, where membrane hyperpolarization was shown to produce an action potential by removing Na(+) channel inactivation that is present at resting membrane potential. The simulations described in this paper provide insights into mechanisms of axonal excitation that can be carried out by following an easily understood protocol.

Optical mapping of optogenetically shaped cardiac action potentials.

PubMed

Park, Sarah A; Lee, Shin-Rong; Tung, Leslie; Yue, David T

2014-08-19

Light-mediated silencing and stimulation of cardiac excitability, an important complement to electrical stimulation, promises important discoveries and therapies. To date, cardiac optogenetics has been studied with patch-clamp, multielectrode arrays, video microscopy, and an all-optical system measuring calcium transients. The future lies in achieving simultaneous optical acquisition of excitability signals and optogenetic control, both with high spatio-temporal resolution. Here, we make progress by combining optical mapping of action potentials with concurrent activation of channelrhodopsin-2 (ChR2) or halorhodopsin (eNpHR3.0), via an all-optical system applied to monolayers of neonatal rat ventricular myocytes (NRVM). Additionally, we explore the capability of ChR2 and eNpHR3.0 to shape action-potential waveforms, potentially aiding the study of short/long QT syndromes that result from abnormal changes in action potential duration (APD). These results show the promise of an all-optical system to acquire action potentials with precise temporal optogenetics control, achieving a long-sought flexibility beyond the means of conventional electrical stimulation.

Optical mapping of optogenetically shaped cardiac action potentials

PubMed Central

Park, Sarah A.; Lee, Shin-Rong; Tung, Leslie; Yue, David T.

2014-01-01

Light-mediated silencing and stimulation of cardiac excitability, an important complement to electrical stimulation, promises important discoveries and therapies. To date, cardiac optogenetics has been studied with patch-clamp, multielectrode arrays, video microscopy, and an all-optical system measuring calcium transients. The future lies in achieving simultaneous optical acquisition of excitability signals and optogenetic control, both with high spatio-temporal resolution. Here, we make progress by combining optical mapping of action potentials with concurrent activation of channelrhodopsin-2 (ChR2) or halorhodopsin (eNpHR3.0), via an all-optical system applied to monolayers of neonatal rat ventricular myocytes (NRVM). Additionally, we explore the capability of ChR2 and eNpHR3.0 to shape action-potential waveforms, potentially aiding the study of short/long QT syndromes that result from abnormal changes in action potential duration (APD). These results show the promise of an all-optical system to acquire action potentials with precise temporal optogenetics control, achieving a long-sought flexibility beyond the means of conventional electrical stimulation. PMID:25135113

Growth of elaborate microbial pinnacles in Lake Vanda, Antarctica.

PubMed

Sumner, D Y; Jungblut, A D; Hawes, I; Andersen, D T; Mackey, T J; Wall, K

2016-11-01

Microbial pinnacles in ice-covered Lake Vanda, McMurdo Dry Valleys, Antarctica, extend from the base of the ice to more than 50 m water depth. The distribution of microbial communities, their photosynthetic potential, and pinnacle morphology affects the local accumulation of biomass, which in turn shapes pinnacle morphology. This feedback, plus environmental stability, promotes the growth of elaborate microbial structures. In Lake Vanda, all mats sampled from greater than 10 m water depth contained pinnacles with a gradation in size from <1-mm-tall tufts to pinnacles that were centimeters tall. Small pinnacles were cuspate, whereas larger ones had variable morphology. The largest pinnacles were up to ~30 cm tall and had cylindrical bases and cuspate tops. Pinnacle biomass was dominated by cyanobacteria from the morphological and genomic groups Leptolyngbya, Phormidium, and Tychonema. The photosynthetic potential of these cyanobacterial communities was high to depths of several millimeters into the mat based on PAM fluorometry, and sufficient light for photosynthesis penetrated ~5 mm into pinnacles. The distribution of photosynthetic potential and its correlation to pinnacle morphology suggests a working model for pinnacle growth. First, small tufts initiate from random irregularities in prostrate mat. Some tufts grow into pinnacles over the course of ~3 years. As pinnacles increase in size and age, their interiors become colonized by a more diverse community of cyanobacteria with high photosynthetic potential. Biomass accumulation within this subsurface community causes pinnacles to swell, expanding laminae thickness and creating distinctive cylindrical bases and cuspate tops. This change in shape suggests that pinnacle morphology emerges from a specific distribution of biomass accumulation that depends on multiple microbial communities fixing carbon in different parts of pinnacles. Similarly, complex patterns of biomass accumulation may be reflected in the morphology of elaborate ancient stromatolites. © 2016 John Wiley & Sons Ltd.

Injury risk associated with playing actions during competitive soccer

PubMed Central

Rahnama, N; Reilly, T; Lees, A

2002-01-01

Objective: To assess the exposure of players to injury risk during English Premier League soccer matches in relation to selected factors. Methods: Injury risk was assessed by rating the injury potential of playing actions during competition with respect to (a) type of playing action, (b) period of the game, (c) zone of the pitch, and (d) playing either at home or away. In all, 10 games from the English Premier League 1999–2000 were chosen for analysis. A notation system was used whereby 16 soccer specific playing actions were classified into three categories: those inducing actual injury, those with a potential for injury (graded as mild, moderate, or high), and those deemed to have no potential for injury. The pitch was divided into 18 zones, and the position of each event was recorded along with time elapsed in the game, enabling six 15 minute periods to be defined. Results: Close to 18 000 actions were notated. On average (mean (SD)), 1788 (73) events (one every three seconds), 767 (99) events with injury potential (one every six seconds), and 2 (1) injuries (one every 45 minutes) per game were recorded. An overall injury incidence of 53 per 1000 playing hours was calculated. Receiving a tackle, receiving a "charge", and making a tackle were categorised as having a substantial injury risk, and goal catch, goal punch, kicking the ball, shot on goal, set kick, and heading the ball were all categorised as having a significant injury risk. All other actions were deemed low in risk. The first 15 minutes of each half contained the highest number of actions with mild injury potential, the last 15 minutes having the highest number of actions with moderate injury potential (p<0.01). The first and last 15 minutes of the game had the highest number of actions with high injury potential, although not significant. More actions with mild injury potential occurred in the goal area, and more actions with moderate and high injury potential occurred in the zone adjacent to the goal area (p<0.001). There was no significant difference between home and away with regard to injury potential. Conclusions: Playing actions with high injury risk were linked to contesting possession. Injury risk was highest in the first and last 15 minutes of the game, reflecting the intense engagements in the opening period and the possible effect of fatigue in the closing period. Injury risk was concentrated in the areas of the pitch where possession of the ball is most vigorously contested, which were specific attacking and defending zones close to the goal. Injury potential was no greater in away matches than at home. PMID:12351333

Protein Targeting: ER Leads the Way to the Inner Nuclear Envelope.

PubMed

Blackstone, Craig

2017-12-04

Efficient targeting of newly synthesized membrane proteins from the endoplasmic reticulum to the inner nuclear membrane depends on nucleotide hydrolysis. A new study shows that this dependence reflects critical actions of the atlastin family of GTPases in maintaining the morphology of the endoplasmic reticulum network. Published by Elsevier Ltd.

HYPERFORIN MODULATES DENDRITIC SPINE MORPHOLOGY IN HIPPOCAMPAL PYRAMIDAL NEURONS BY ACTIVATING Ca2+-PERMEABLE TRPC6 CHANNELS

PubMed Central

Leuner, Kristina; Li, Wei; Amaral, Michelle D.; Rudolph, Stephanie; Calfa, Gaston; Schuwald, Anita M.; Harteneck, Christian; Inoue, Takafumi; Pozzo-Miller, Lucas

2012-01-01

The standardized extract of the St. John’s wort plant (Hypericum perforatum) is commonly used to treat mild to moderate depression. Its active constituent is hyperforin, a phloroglucinol derivative that reduces the reuptake of serotonin and norepinephrine by increasing intracellular Na+ concentration through the activation of non-selective cationic TRPC6 channels. TRPC6 channels are also Ca2+-permeable, resulting in intracellular Ca2+ elevations. Indeed, hyperforin activates TRPC6-mediated currents and Ca2+ transients in rat PC12 cells, which induce their differentiation, mimicking the neurotrophic effect of NGF. Here, we show that hyperforin modulates dendritic spine morphology in CA1 and CA3 pyramidal neurons of hippocampal slice cultures through the activation of TRPC6 channels. Hyperforin also evoked intracellular Ca2+ transients and depolarizing inward currents sensitive to the TRPC channel blocker La3+, thus resembling the actions of the neurotrophin BDNF in hippocampal pyramidal neurons. These results suggest that the antidepressant actions of St. John’s wort are mediated by a mechanism similar to that engaged by BDNF. PMID:22815087

Spontaneous action potentials and neural coding in unmyelinated axons.

PubMed

O'Donnell, Cian; van Rossum, Mark C W

2015-04-01

The voltage-gated Na and K channels in neurons are responsible for action potential generation. Because ion channels open and close in a stochastic fashion, spontaneous (ectopic) action potentials can result even in the absence of stimulation. While spontaneous action potentials have been studied in detail in single-compartment models, studies on spatially extended processes have been limited. The simulations and analysis presented here show that spontaneous rate in unmyelinated axon depends nonmonotonically on the length of the axon, that the spontaneous activity has sub-Poisson statistics, and that neural coding can be hampered by the spontaneous spikes by reducing the probability of transmitting the first spike in a train.

Improving Cardiac Action Potential Measurements: 2D and 3D Cell Culture.

PubMed

Daily, Neil J; Yin, Yue; Kemanli, Pinar; Ip, Brian; Wakatsuki, Tetsuro

2015-11-01

Progress in the development of assays for measuring cardiac action potential is crucial for the discovery of drugs for treating cardiac disease and assessing cardiotoxicity. Recently, high-throughput methods for assessing action potential using induced pluripotent stem cell (iPSC) derived cardiomyocytes in both two-dimensional monolayer cultures and three-dimensional tissues have been developed. We describe an improved method for assessing cardiac action potential using an ultra-fast cost-effective plate reader with commercially available dyes. Our methods improve dramatically the detection of the fluorescence signal from these dyes and make way for the development of more high-throughput methods for cardiac drug discovery and cardiotoxicity.

Action potentials contribute to epileptic high-frequency oscillations recorded with electrodes remote from neurons.

PubMed

Kobayashi, Katsuhiro; Akiyama, Tomoyuki; Ohmori, Iori; Yoshinaga, Harumi; Gotman, Jean

2015-05-01

The importance of epileptic high-frequency oscillations (HFOs) in electroencephalogram (EEG) is growing. Action potentials generating some HFOs are observed in the vicinity of neurons in experimental animals. However electrodes that are remote from neurons, as in case of clinical situations, should not record action potentials. We propose to resolve this question by a realistic simulation of epileptic neuronal network. The rat dentate gyrus with sclerosis was simulated in silico. We computed the current dipole moment generated by each granule cell and the field potentials in a measurement area far from neurons. The dentate gyrus was stimulated through synaptic input to evoke discharges resembling interictal epileptiform discharges, which had superimposed HFOs⩽295Hz that were recordable with remote electrodes and represented bursts of action potentials of granule cells. The increase in power of HFOs was associated with the progression of sclerosis, the reduction of GABAergic inhibition, and the increase in cell connectivity. Spectral frequency of HFOs had similar tendencies. HFOs recorded with electrodes remote from neurons could actually be generated by clusters of action potentials. The phenomenon of action potentials recorded with remote electrodes can possibly extend the clinical meaning of EEG. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

A physical action potential generator: design, implementation and evaluation.

PubMed

Latorre, Malcolm A; Chan, Adrian D C; Wårdell, Karin

2015-01-01

The objective was to develop a physical action potential generator (Paxon) with the ability to generate a stable, repeatable, programmable, and physiological-like action potential. The Paxon has an equivalent of 40 nodes of Ranvier that were mimicked using resin embedded gold wires (Ø = 20 μm). These nodes were software controlled and the action potentials were initiated by a start trigger. Clinically used Ag-AgCl electrodes were coupled to the Paxon for functional testing. The Paxon's action potential parameters were tunable using a second order mathematical equation to generate physiologically relevant output, which was accomplished by varying the number of nodes involved (1-40 in incremental steps of 1) and the node drive potential (0-2.8 V in 0.7 mV steps), while keeping a fixed inter-nodal timing and test electrode configuration. A system noise floor of 0.07 ± 0.01 μV was calculated over 50 runs. A differential test electrode recorded a peak positive amplitude of 1.5 ± 0.05 mV (gain of 40x) at time 196.4 ± 0.06 ms, including a post trigger delay. The Paxon's programmable action potential like signal has the possibility to be used as a validation test platform for medical surface electrodes and their attached systems.

Electrodeposition of Rhodium Nanowires Arrays and Their Morphology-Dependent Hydrogen Evolution Activity

PubMed Central

Zhang, Liqiu; Liu, Lichun; Wang, Hongdan; Shen, Hongxia; Cheng, Qiong; Yan, Chao; Park, Sungho

2017-01-01

This work reports on the electrodeposition of rhodium (Rh) nanowires with a controlled surface morphology synthesized using an anodic aluminum oxide (AAO) template. Vertically aligned Rh nanowires with a smooth and coarse morphology were successfully deposited by adjusting the electrode potential and the concentration of precursor ions and by involving a complexing reagent in the electrolyte solution. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) analyses were used to follow the morphological evolution of Rh nanowires. As a heterogeneous electrocatalyst for hydrogen evolution reactions (HER), the coarse Rh nanowire array exhibited an enhanced catalytic performance respect to smooth ones due to the larger surface area to mass ratio and the higher density of catalytically active defects, as evidenced by voltammetric measurements and TEM. Results suggest that the morphology of metallic nanomaterials could be readily engineered by electrodeposition. The controlled electrodeposition offers great potential for the development of an effective synthesis tool for heterogeneous catalysts with a superior performance for wide applications. PMID:28467375

Effect of Students' Term and Educational Institution on the Arising of Indonesian Morphology-Syntactical Interference in ELLT

ERIC Educational Resources Information Center

Nurhayati, Dwi Astuti Wahyu; Djatmika; Santosa, Riyadi; Wiratno, Tri

2017-01-01

This research examines the two factors which effect on the raising of Indonesian morphology-syntactical interference. It aimed at delineating the potential effect of these two factors on the arising of Indonesian morphology-syntactical interference of undergraduate students majoring in English department of State Islamic Institute of Tulungagung…

Direct detection of a single evoked action potential with MRS in Lumbricus terrestris.

PubMed

Poplawsky, Alexander J; Dingledine, Raymond; Hu, Xiaoping P

2012-01-01

Functional MRI (fMRI) measures neural activity indirectly by detecting the signal change associated with the hemodynamic response following brain activation. In order to alleviate the temporal and spatial specificity problems associated with fMRI, a number of attempts have been made to detect neural magnetic fields (NMFs) with MRI directly, but have thus far provided conflicting results. In this study, we used MR to detect axonal NMFs in the median giant fiber of the earthworm, Lumbricus terrestris, by examining the free induction decay (FID) with a sampling interval of 0.32 ms. The earthworm nerve cords were isolated from the vasculature and stimulated at the threshold of action potential generation. FIDs were acquired shortly after the stimulation, and simultaneous field potential recordings identified the presence or absence of single evoked action potentials. FIDs acquired when the stimulus did not evoke an action potential were summed as background. The phase of the background-subtracted FID exhibited a systematic change, with a peak phase difference of (-1.2 ± 0.3) × 10(-5) radians occurring at a time corresponding to the timing of the action potential. In addition, we calculated the possible changes in the FID magnitude and phase caused by a simulated action potential using a volume conductor model. The measured phase difference matched the theoretical prediction well in both amplitude and temporal characteristics. This study provides the first evidence for the direct detection of a magnetic field from an evoked action potential using MR. Copyright © 2011 John Wiley & Sons, Ltd.

The Direct Detection of a Single Evoked Action Potential with Magnetic Resonance Spectroscopy in Lumbricus Terrestris

PubMed Central

Poplawsky, Alexander J.; Dingledine, Raymond

2011-01-01

Functional MRI (fMRI) indirectly measures neural activity by detecting the signal change associated with the hemodynamic response following brain activation. In order to alleviate the temporal and spatial specificity problems associated with fMRI, a number of attempts have been made to detect neural magnetic fields (NMFs) with MRI directly, but have thus far provided conflicting results. In the present study, we used magnetic resonance to detect axonal NMFs in the median giant fiber of the earthworm, Lumbricus terrestris, by examining the free-induction decay (FID) with a sampling interval of 0.32 ms. The earthworm nerve cords were isolated from the vasculature and stimulated at the threshold of action potential generation. FIDs were acquired shortly after the stimulation and simultaneous field potential recordings identified the presence or absence of single evoked action potentials. FIDs acquired when the stimulus did not evoke an action potential were summed as background. The phase of the background-subtracted FID exhibited a systematic change, with a peak phase difference of [-1.2 ± 0.3] ×10-5 radians occurring at a time corresponding to the timing of the action potential. In addition, we calculated the possible changes in the FID magnitude and phase due to a simulated action potential using a volume conductor model. The measured phase difference matched the theoretical prediction well in both amplitude and temporal characteristics. This study provides the first evidence for the direct detection of a magnetic field from an evoked action potential using magnetic resonance. PMID:21728204

Channel sialic acids limit hERG channel activity during the ventricular action potential.

PubMed

Norring, Sarah A; Ednie, Andrew R; Schwetz, Tara A; Du, Dongping; Yang, Hui; Bennett, Eric S

2013-02-01

Activity of human ether-a-go-go-related gene (hERG) 1 voltage-gated K(+) channels is responsible for portions of phase 2 and phase 3 repolarization of the human ventricular action potential. Here, we questioned whether and how physiologically and pathophysiologically relevant changes in surface N-glycosylation modified hERG channel function. Voltage-dependent hERG channel gating and activity were evaluated as expressed in a set of Chinese hamster ovary (CHO) cell lines under conditions of full glycosylation, no sialylation, no complex N-glycans, and following enzymatic deglycosylation of surface N-glycans. For each condition of reduced glycosylation, hERG channel steady-state activation and inactivation relationships were shifted linearly by significant depolarizing ∼9 and ∼18 mV, respectively. The hERG window current increased significantly by 50-150%, and the peak shifted by a depolarizing ∼10 mV. There was no significant change in maximum hERG current density. Deglycosylated channels were significantly more active (20-80%) than glycosylated controls during phases 2 and 3 of action potential clamp protocols. Simulations of hERG current and ventricular action potentials corroborated experimental data and predicted reduced sialylation leads to a 50-70-ms decrease in action potential duration. The data describe a novel mechanism by which hERG channel gating is modulated through physiologically and pathophysiologically relevant changes in N-glycosylation; reduced channel sialylation increases hERG channel activity during the action potential, thereby increasing the rate of action potential repolarization.

Mechanical and degradation properties of biodegradable Mg strengthened poly-lactic acid composite through plastic injection molding.

PubMed

Butt, Muhammad Shoaib; Bai, Jing; Wan, Xiaofeng; Chu, Chenglin; Xue, Feng; Ding, Hongyan; Zhou, Guanghong

2017-01-01

Full biodegradable magnesium alloy (AZ31) strengthened poly-lactic acid (PLA) composite rods for potential application for bone fracture fixation were prepared by plastic injection process in this work. Their surface/interfacial morphologies, mechanical properties and vitro degradation were studied. In comparison with untreated Mg rod, porous MgO ceramic coating on Mg surface formed by Anodizing (AO) and micro-arc-oxidation (MAO)treatment can significantly improve the interfacial binding between outer PLA cladding and inner Mg rod due to the micro-anchoring action, leading to better mechanical properties and degradation performance of the composite rods.With prolonging immersion time in simulated body fluid (SBF) solution until 8weeks, the MgO porous coating were corroded gradually, along with the disappearance of original pores and the formation of a relatively smooth surface. This resulted in a rapidly reduction in mechanical properties for corresponding composite rods owing to the weakening of interfacial binding capacity. The present results indicated that this new PLA-clad Mg composite rods show good potential biomedical applications for implants and instruments of orthopedic inner fixation. Copyright © 2016 Elsevier B.V. All rights reserved.

Simulation of Atrial Fibrosis Using Coupled Myocyte-Fibroblast Cellular and Human Atrial Models

PubMed Central

Gao, Yuan

2017-01-01

Atrial fibrosis is characterized by expansion of extracellular matrix and increase in the number of fibroblasts which has been associated with the development and maintenance of atrial arrhythmias. However, the mechanisms how the fibrosis contributes to atrial arrhythmia remain incompletely understood. In this study, we used a proposed fibroblast model coupled with the human atrial myocyte to investigate the effects of fibrosis on atrial excitability and repolarization at both cellular and macroscopic levels. The 12-lead electrocardiogram (ECG) was also simulated to explore the index of clinical diagnosis for fibrosis. The simulation results showed that the fibrosis can modify action potential morphology of human atrial myocyte, slow down wave propagation, and have rate adaptation, thus causing the atrial electrical heterogeneity. The fibrosis alone was sufficient to cause arrhythmia, induce reentry wave, and result in low amplitude and wide P waves at normal heart rate and significant prolonged and inverse P waves at high heart rate. All these symptoms aggravated when the level of fibrosis increased. Our simulations demonstrated that fibrosis is the substrate of atrial arrhythmia and thereby may be a potential target in the treatment of atrial arrhythmias. PMID:29441121

Central projections and entries of capsaicin-sensitive muscle afferents.

PubMed

Della Torre, G; Lucchi, M L; Brunetti, O; Pettorossi, V E; Clavenzani, P; Bortolami, R

1996-03-25

The entry pathway and central distribution of A delta and C muscle afferents within the central nervous system (CNS) were investigated by combining electron microscopy and electrophysiological analysis after intramuscular injection of capsaicin. The drug was injected into the rat lateral gastrocnemius (LG) and extraocular (EO) muscles. The compound action potentials of LG nerve and the evoked field potentials recorded in semilunar ganglion showed an immediate and permanent reduction in A delta and C components. The morphological data revealed degenerating unmyelinated axons and terminals in the inner sublamina II and in the border of laminae I-II of the dorsal horn at L4-L5 and C1-C2 (subnucleus caudalis trigemini) spinal cord segments. Most degenerating terminals were the central bouton (C) of type I and II synaptic glomeruli. Furthermore, degenerating peripheral axonal endings (V2) presynaptic to normal C were found. Since V2 were previously found degenerated after cutting the oculomotor nerve (ON) or L4 ventral root, we conclude that some A delta and C afferents from LG and EO muscles entering the CNS by ON or ventral roots make axoaxonic synapses on other primary afferents to promote an afferent control of sensory input.

Reversible electric-field manipulation of the adsorption morphology and magnetic anisotropy of small Fe and Co clusters on graphene

NASA Astrophysics Data System (ADS)

Tanveer, M.; Dorantes-Dávila, J.; Pastor, G. M.

2017-12-01

First-principles electronic calculations show how the adsorption morphology, orbital magnetism, and magnetic anisotropy energy (MAE) of small CoN and FeN clusters (N ≤3 ) on graphene (G) can be reversibly controlled under the action of an external electric field (EF). A variety of cluster-specific and EF-induced effects are revealed, including (i) perpendicular or canted adsorption configurations of the dimers and trimers, (ii) significant morphology-dependent permanent dipole moments and electric susceptibilities, (iii) EF-induced reversible transitions among the different metastable adsorption morphologies of Fe3 and Co3 on graphene, (iv) qualitative changes in the MAE landscape driven by structural changes, (v) colossal values of the magnetic anisotropy Δ E ≃45 meV per atom in Co2/G , (vi) EF-induced spin-reorientation transitions in Co3/G , and (vii) reversibly tunable coercive field and blocking temperatures, which in some cases allow a barrierless magnetization reversal of the cluster. These remarkable electric and magnetic fingerprints open new possibilities of characterizing and exploiting the size- and structural-dependent properties of magnetic nanostructures at surfaces.

Sodium and calcium currents shape action potentials in immature mouse inner hair cells

PubMed Central

Marcotti, Walter; Johnson, Stuart L; Rüsch, Alfons; Kros, Corné J

2003-01-01

Before the onset of hearing at postnatal day 12, mouse inner hair cells (IHCs) produce spontaneous and evoked action potentials. These spikes are likely to induce neurotransmitter release onto auditory nerve fibres. Since immature IHCs express both α1D (Cav1.3) Ca2+ and Na+ currents that activate near the resting potential, we examined whether these two conductances are involved in shaping the action potentials. Both had extremely rapid activation kinetics, followed by fast and complete voltage-dependent inactivation for the Na+ current, and slower, partially Ca2+-dependent inactivation for the Ca2+ current. Only the Ca2+ current is necessary for spontaneous and induced action potentials, and 29 % of cells lacked a Na+ current. The Na+ current does, however, shorten the time to reach the action-potential threshold, whereas the Ca2+ current is mainly involved, together with the K+ currents, in determining the speed and size of the spikes. Both currents increased in size up to the end of the first postnatal week. After this, the Ca2+ current reduced to about 30 % of its maximum size and persisted in mature IHCs. The Na+ current was downregulated around the onset of hearing, when the spiking is also known to disappear. Although the Na+ current was observed as early as embryonic day 16.5, its role in action-potential generation was only evident from just after birth, when the resting membrane potential became sufficiently negative to remove a sizeable fraction of the inactivation (half inactivation was at −71 mV). The size of both currents was positively correlated with the developmental change in action-potential frequency. PMID:12937295

Distinct roles of cell wall biogenesis in yeast morphogenesis as revealed by multivariate analysis of high-dimensional morphometric data

PubMed Central

Okada, Hiroki; Ohnuki, Shinsuke; Roncero, Cesar; Konopka, James B.; Ohya, Yoshikazu

2014-01-01

The cell wall of budding yeast is a rigid structure composed of multiple components. To thoroughly understand its involvement in morphogenesis, we used the image analysis software CalMorph to quantitatively analyze cell morphology after treatment with drugs that inhibit different processes during cell wall synthesis. Cells treated with cell wall–affecting drugs exhibited broader necks and increased morphological variation. Tunicamycin, which inhibits the initial step of N-glycosylation of cell wall mannoproteins, induced morphologies similar to those of strains defective in α-mannosylation. The chitin synthase inhibitor nikkomycin Z induced morphological changes similar to those of mutants defective in chitin transglycosylase, possibly due to the critical role of chitin in anchoring the β-glucan network. To define the mode of action of echinocandin B, a 1,3-β-glucan synthase inhibitor, we compared the morphology it induced with mutants of Fks1 that contains the catalytic domain for 1,3-β-glucan synthesis. Echinocandin B exerted morphological effects similar to those observed in some fks1 mutants, with defects in cell polarity and reduced glucan synthesis activity, suggesting that echinocandin B affects not only 1,3-β-glucan synthesis, but also another functional domain. Thus our multivariate analyses reveal discrete functions of cell wall components and increase our understanding of the pharmacology of antifungal drugs. PMID:24258022

Action of vanillin (Vanilla planifolia) on the morphology of tibialis anterior and soleus muscles after nerve injury.

PubMed

Peretti, Ana Luiza; Antunes, Juliana Sobral; Lovison, Keli; Kunz, Regina Inês; Castor, Lidyane Regina Gomes; Brancalhão, Rose Meire Costa; Bertolini, Gladson Ricardo Flor; Ribeiro, Lucinéia de Fátima Chasko

2017-01-01

To evaluate the action of vanillin (Vanilla planifolia) on the morphology of tibialis anterior and soleus muscles after peripheral nerve injury. Wistar rats were divided into four groups, with seven animals each: Control Group, Vanillin Group, Injury Group, and Injury + Vanillin Group. The Injury Group and the Injury + Vanillin Group animals were submitted to nerve injury by compression of the sciatic nerve; the Vanillin Group and Injury + Vanillin Group, were treated daily with oral doses of vanillin (150mg/kg) from the 3rd to the 21st day after induction of nerve injury. At the end of the experiment, the tibialis anterior and soleus muscles were dissected and processed for light microscopy and submitted to morphological analysis. The nerve compression promoted morphological changes, typical of denervation, and the treatment with vanillin was responsible for different responses in the studied muscles. For the tibialis anterior, there was an increase in the number of satellite cells, central nuclei and fiber atrophy, as well as fascicular disorganization. In the soleus, only increased vascularization was observed, with no exacerbation of the morphological alterations in the fibers. The treatment with vanillin promoted increase in intramuscular vascularization for the muscles studied, with pro-inflammatory potential for tibialis anterior, but not for soleus muscle. Avaliar a ação da vanilina (Vanilla planifolia) sobre a morfologia dos músculos tibial anterior e sóleo após lesão nervosa periférica. Ratos Wistar foram divididos em quatro grupos, com sete animais cada, sendo Grupo Controle, Grupo Vanilina, Grupo Lesão e Grupo Lesão + Vanilina. Os animais dos Grupos Lesão e Grupo Lesão + Vanilina foram submetidos à lesão nervosa por meio da compressão do nervo isquiático, e os Grupos Vanilina e Grupo Lesão + Vanilina foram tratados diariamente com doses orais de vanilina (150mg/kg) do 3o ao 21o dia após a indução da lesão nervosa. Ao término do experimento, os músculos tibial anterior e sóleo foram dissecados e seguiram o processamento de rotina em microscopia de luz, para posterior análise morfológica. A compressão nervosa promoveu alterações morfológicas características de denervação, sendo que o tratamento com vanilina foi responsável por respostas distintas nos músculos estudados. Para o tibial anterior, houve aumento do número de células satélites, núcleos centrais e atrofia das fibras, bem como desorganização fascicular. Já no sóleo, houve apenas aumento da vascularização, sem exacerbação das alterações morfológicas nas fibras. O tratamento com vanilina promoveu o aumento da vascularização intramuscular para os músculos estudados, com potencial pró-inflamatório para o tibial anterior, o que não ocorreu no músculo sóleo.

The dependence of the action potential of the frog's heart on the external and intracellular sodium concentration

PubMed Central

Niedergerke, R.; Orkand, R. K.

1966-01-01

1. The overshoot of the action potential of the frog's heart was reduced when external sodium chloride was replaced by sucrose. However, the potential decrement was only 17·3 mV for a 10-fold reduction of sodium as compared with 58 mV expected on the basis of the sodium hypothesis of excitation. 2. Replacement of up to 75% of the external sodium by choline did not reduce the overshoot, provided atropine was present in sufficient concentrations to suppress any parasympathomimetic action. 3. The maximum rate of rise of the action potential markedly declined in low sodium fluids whether sucrose or choline chloride was used to replace sodium chloride. 4. The maximum rate of rise was reduced to only a small extent when external sodium was replaced by lithium. 5. Increasing the intracellular sodium concentration in exchange for lost potassium caused overshoots to decline. The effects resembled those obtained in similar experiments with skeletal muscle fibres (Desmedt, 1953). 6. Action potentials occurring under certain conditions even in the presence of very low external sodium concentrations (≤ 5% normal) also declined in height when the intracellular sodium concentration was increased. 7. The behaviour of the action potential in low external sodium concentrations may be explained by an action of calcium on the excitable membrane. PMID:5921833

MreB drives de novo rod morphogenesis in Caulobacter crescentus via remodeling of the cell wall.

PubMed

Takacs, Constantin N; Poggio, Sebastian; Charbon, Godefroid; Pucheault, Mathieu; Vollmer, Waldemar; Jacobs-Wagner, Christine

2010-03-01

MreB, the bacterial actin-like cytoskeleton, is required for the rod morphology of many bacterial species. Disruption of MreB function results in loss of rod morphology and cell rounding. Here, we show that the widely used MreB inhibitor A22 causes MreB-independent growth inhibition that varies with the drug concentration, culture medium conditions, and bacterial species tested. MP265, an A22 structural analog, is less toxic than A22 for growth yet equally efficient for disrupting the MreB cytoskeleton. The action of A22 and MP265 is enhanced by basic pH of the culture medium. Using this knowledge and the rapid reversibility of drug action, we examined the restoration of rod shape in lemon-shaped Caulobacter crescentus cells pretreated with MP265 or A22 under nontoxic conditions. We found that reversible restoration of MreB function after drug removal causes extensive morphological changes including a remarkable cell thinning accompanied with elongation, cell branching, and shedding of outer membrane vesicles. We also thoroughly characterized the composition of C. crescentus peptidoglycan by high-performance liquid chromatography and mass spectrometry and showed that MreB disruption and recovery of rod shape following restoration of MreB function are accompanied by considerable changes in composition. Our results provide insight into MreB function in peptidoglycan remodeling and rod shape morphogenesis and suggest that MreB promotes the transglycosylase activity of penicillin-binding proteins.

Rapid Ca2+ flux through the transverse tubular membrane, activated by individual action potentials in mammalian skeletal muscle

PubMed Central

Launikonis, Bradley S; Stephenson, D George; Friedrich, Oliver

2009-01-01

Periods of low frequency stimulation are known to increase the net Ca2+ uptake in skeletal muscle but the mechanism responsible for this Ca2+ entry is not known. In this study a novel high-resolution fluorescence microscopy approach allowed the detection of an action potential-induced Ca2+ flux across the tubular (t-) system of rat extensor digitorum longus muscle fibres that appears to be responsible for the net uptake of Ca2+ in working muscle. Action potentials were triggered in the t-system of mechanically skinned fibres from rat by brief field stimulation and t-system [Ca2+] ([Ca2+]t-sys) and cytoplasmic [Ca2+] ([Ca2+]cyto) were simultaneously resolved on a confocal microscope. When initial [Ca2+]t-sys was ≥ 0.2 mm a Ca2+ flux from t-system to the cytoplasm was observed following a single action potential. The action potential-induced Ca2+ flux and associated t-system Ca2+ permeability decayed exponentially and displayed inactivation characteristics such that further Ca2+ entry across the t-system could not be observed after 2–3 action potentials at 10 Hz stimulation rate. When [Ca2+]t-sys was closer to 0.1 mm, a transient rise in [Ca2+]t-sys was observed almost concurrently with the increase in [Ca2+]cyto following the action potential. The change in direction of Ca2+ flux was consistent with changes in the direction of the driving force for Ca2+. This is the first demonstration of a rapid t-system Ca2+ flux associated with a single action potential in mammalian skeletal muscle. The properties of this channel are inconsistent with a flux through the L-type Ca2+ channel suggesting that an as yet unidentified t-system protein is conducting this current. This action potential-activated Ca2+ flux provides an explanation for the previously described Ca2+ entry and accumulation observed with prolonged, intermittent muscle activity. PMID:19332499

The potential influence of morphology on the evolutionary divergence of an acoustic signal

PubMed Central

Pitchers, W. R.; Klingenberg, C.P.; Tregenza, Tom; Hunt, J.; Dworkin, I.

2014-01-01

The evolution of acoustic behaviour and that of the morphological traits mediating its production are often coupled. Lack of variation in the underlying morphology of signalling traits has the potential to constrain signal evolution. This relationship is particularly likely in field crickets, where males produce acoustic advertisement signals to attract females by stridulating with specialized structures on their forewings. In this study, we characterise the size and geometric shape of the forewings of males from six allopatric populations of the black field cricket (Teleogryllus commodus) known to have divergent advertisement calls. We sample from each of these populations using both wild-caught and common-garden reared cohorts, allowing us to test for multivariate relationships between wing morphology and call structure. We show that the allometry of shape has diverged across populations. However, there was a surprisingly small amount of covariation between wing shape and call structure within populations. Given the importance of male size for sexual selection in crickets, the divergence we observe among populations has the potential to influence the evolution of advertisement calls in this species. PMID:25223712

A simultaneous multichannel monophasic action potential electrode array for in vivo epicardial repolarization mapping.

PubMed

Sahakian, A V; Peterson, M S; Shkurovich, S; Hamer, M; Votapka, T; Ji, T; Swiryn, S

2001-03-01

While the recording of extracellular monophasic action potentials (MAPs) from single epicardial or endocardial sites has been performed for over a century, we are unaware of any previous successful attempt to record MAPs simultaneously from a large number of sites in vivo. We report here the design and validation of an array of MAP electrodes which records both depolarization and repolarization simultaneously at up to 16 epicardial sites in a square array on the heart in vivo. The array consists of 16 sintered Ag-AgCl electrodes mounted in a common housing with individual suspensions allowing each electrode to exert a controlled pressure on the epicardial surface. The electrodes are arranged in a square array, with each quadrant of four having an additional recessed sintered Ag-AgCl reference electrode at its center. A saline-soaked sponge establishes ionic contact between the reference electrodes and the tissue. The array was tested on six anesthetized open-chested pigs. Simultaneous diagnostic-quality MAP recordings were obtained from up to 13 out of 16 ventricular sites. Ventricular MAPs had amplitudes of 10-40 mV with uniform morphologies and stable baselines for up to 30 min. MAP duration at 90% repolarization was measured and shown to vary as expected with cycle length during sustained pacing. The relationship between MAP duration and effective refractory period was also confirmed. The ability of the array to detect local differences in repolarization was tested in two ways. Placement of the array straddling the atrioventricular (AV) junction yielded simultaneous atrial or ventricular recordings at corresponding sites during 1:1 and 2:1 AV conduction. Localized ischemia via constriction of a coronary artery branch resulted in shortening of the repolarization phase at the ischemic, but not the nonischemic, sites. In conclusion, these results indicate that the simultaneous multichannel MAP electrode array is a viable method for in vivo epicardial repolarization mapping. The array has the potential to be expanded to increase the number of sites and spatial resolution.

A computational framework for testing arrhythmia marker sensitivities to model parameters in functionally calibrated populations of atrial cells

NASA Astrophysics Data System (ADS)

Vagos, Márcia R.; Arevalo, Hermenegild; de Oliveira, Bernardo Lino; Sundnes, Joakim; Maleckar, Mary M.

2017-09-01

Models of cardiac cell electrophysiology are complex non-linear systems which can be used to gain insight into mechanisms of cardiac dynamics in both healthy and pathological conditions. However, the complexity of cardiac models can make mechanistic insight difficult. Moreover, these are typically fitted to averaged experimental data which do not incorporate the variability in observations. Recently, building populations of models to incorporate inter- and intra-subject variability in simulations has been combined with sensitivity analysis (SA) to uncover novel ionic mechanisms and potentially clarify arrhythmogenic behaviors. We used the Koivumäki human atrial cell model to create two populations, representing normal Sinus Rhythm (nSR) and chronic Atrial Fibrillation (cAF), by varying 22 key model parameters. In each population, 14 biomarkers related to the action potential and dynamic restitution were extracted. Populations were calibrated based on distributions of biomarkers to obtain reasonable physiological behavior, and subjected to SA to quantify correlations between model parameters and pro-arrhythmia markers. The two populations showed distinct behaviors under steady state and dynamic pacing. The nSR population revealed greater variability, and more unstable dynamic restitution, as compared to the cAF population, suggesting that simulated cAF remodeling rendered cells more stable to parameter variation and rate adaptation. SA revealed that the biomarkers depended mainly on five ionic currents, with noted differences in sensitivities to these between nSR and cAF. Also, parameters could be selected to produce a model variant with no alternans and unaltered action potential morphology, highlighting that unstable dynamical behavior may be driven by specific cell parameter settings. These results ultimately suggest that arrhythmia maintenance in cAF may not be due to instability in cell membrane excitability, but rather due to tissue-level effects which promote initiation and maintenance of reentrant arrhythmia.

Human adipose tissue-derived stem cells exhibit proliferation potential and spontaneous rhythmic contraction after fusion with neonatal rat cardiomyocytes.

PubMed

Metzele, Roxana; Alt, Christopher; Bai, Xiaowen; Yan, Yasheng; Zhang, Zhi; Pan, Zhizhong; Coleman, Michael; Vykoukal, Jody; Song, Yao-Hua; Alt, Eckhard

2011-03-01

Various types of stem cells have been shown to have beneficial effects on cardiac function. It is still debated whether fusion of injected stem cells with local resident cardiomyocytes is one of the mechanisms. To better understand the role of fusion in stem cell-based myocardial regeneration, the present study was designed to investigate the fate of human adipose tissue-derived stem cells (hASCs) fused with neonatal rat cardiomyocytes in vitro. hASCs labeled with the green fluorescent probe Vybrant DiO were cocultured with neonatal rat cardiomyocytes labeled with the red fluorescent probe Vybrant DiI and then treated with fusion-inducing hemagglutinating virus of Japan (HVJ). Cells that incorporated both red and green fluorescent signals were considered to be hASCs that had fused with rat cardiomyocytes. Fusion efficiency was 19.86 ± 4.84% at 5 d after treatment with HVJ. Most fused cells displayed cardiomyocyte-like morphology and exhibited spontaneous rhythmic contraction. Both immunofluorescence staining and lentiviral vector labeling showed that fused cells contained separate rat cardiomyocyte and hASC nuclei. Immunofluorescence staining assays demonstrated that human nuclei in fused cells still expressed the proliferation marker Ki67. In addition, hASCs fused with rat cardiomyocytes were positive for troponin I. Whole-cell voltage-clamp analysis demonstrated action potentials in beating fused cells. RT-PCR analysis using rat- or human-specific myosin heavy chain primers revealed that the myosin heavy-chain expression in fused cells was derived from rat cardiomyocytes. Real-time PCR identified expression of human troponin T in fused cells and the presence of rat cardiomyocytes induced a cardiomyogenic protein expression of troponin T in human ASCs. This study illustrates that hASCs exhibit both stem cell (proliferation) and cardiomyocyte properties (action potential and spontaneous rhythmic beating) after fusion with rat cardiomyocytes, supporting the theory that fusion, even if artificially induced in our study, could indeed be a mechanism for cardiomyocyte renewal in the heart.

Vestibular Response to Electrical Stimulation of the Otolith Organs. Implications in the Development of A Vestibular Implant for the Improvement of the Sensation of Gravitoinertial Accelerations.

PubMed

Ramos de Miguel, Angel; Falcon Gonzalez, Juan Carlos; Ramos Macias, Angel

2017-08-01

Electrical stimulation of the utricular and saccular portions of the vestibular nerve improves stability in patients suffering from vestibular dysfunction. The main objective of this study was to evaluate a new technique, vestibular response telemetry (VRT), for measuring the electrically evoked vestibular compound action potential (saccular and utricular) after stimulating the otolith organ (saccular and utricular) in adults. This study used evidence that the otolith organ can be electrically stimulated in order to develop a new vestibular implant design to improve the sensation of gravitoinertial acceleration. Four adult patients were evaluated by using a variety of measurement procedures with novel VRT software. VRT values were obtained by stimulating with three full-band Nucleus CI24RE (ST) electrodes. Specific stimuli were used. Simultaneously, electrical ocular vestibular evoked myogenic potentials (eoVEMPs) were recorded in the contralateral side. Electrically evoked compound action potentials were obtained in 10 of the 12 electrodes tested, and eoVEMPs were recorded when VRT was present. In addition to the validation of this technique, a set of default clinical test parameters was established. The VRT response morphology consisted of a biphasic waveform with an initial negative peak (N1) followed by a positive peak (P1), and latencies were typically 400 μs for N1 and 800 μs for P1. The consequences for the development of a vestibular implant for the improvement of gravitoinertial acceleration sensation are also presented. The VRT measurement technique has been shown to be a useful tool to record neural response on the otolith organ, and thus it is a convenient tool to evaluate whether the implanted electrodes provide a neural response or not. This can be used for the early development of vestibular implants to improve gravitoinertial acceleration sensation.

29 CFR 1990.147 - Final action.

Code of Federal Regulations, 2014 CFR

2014-07-01

...) IDENTIFICATION, CLASSIFICATION, AND REGULATION OF POTENTIAL OCCUPATIONAL CARCINOGENS Regulation of Potential Occupational Carcinogens § 1990.147 Final action. (a) Within one hundred twenty (120) days from the last day of... is classified as a Category I Potential Carcinogen or as a Category II Potential Carcinogen. If the...

29 CFR 1990.147 - Final action.

Code of Federal Regulations, 2012 CFR

2012-07-01

...) IDENTIFICATION, CLASSIFICATION, AND REGULATION OF POTENTIAL OCCUPATIONAL CARCINOGENS Regulation of Potential Occupational Carcinogens § 1990.147 Final action. (a) Within one hundred twenty (120) days from the last day of... is classified as a Category I Potential Carcinogen or as a Category II Potential Carcinogen. If the...

29 CFR 1990.147 - Final action.

Code of Federal Regulations, 2013 CFR

2013-07-01

...) IDENTIFICATION, CLASSIFICATION, AND REGULATION OF POTENTIAL OCCUPATIONAL CARCINOGENS Regulation of Potential Occupational Carcinogens § 1990.147 Final action. (a) Within one hundred twenty (120) days from the last day of... is classified as a Category I Potential Carcinogen or as a Category II Potential Carcinogen. If the...

29 CFR 1990.147 - Final action.

Code of Federal Regulations, 2011 CFR

2011-07-01

...) IDENTIFICATION, CLASSIFICATION, AND REGULATION OF POTENTIAL OCCUPATIONAL CARCINOGENS Regulation of Potential Occupational Carcinogens § 1990.147 Final action. (a) Within one hundred twenty (120) days from the last day of... is classified as a Category I Potential Carcinogen or as a Category II Potential Carcinogen. If the...

Effect of Exogenous Extracellular Nicotinamide Adenine Dinucleotide (NAD⁺) on Bioelectric Activity of the Pacemaker and Conduction System of the Heart.

PubMed

Pustovit, K B; Kuz'min, V S; Sukhova, G S

2015-06-01

In rat sinoatrial node, NAD(+) (10 μM) reduced the rate of spontaneous action potentials, duration of action potentials, and the velocity of slow diastolic depolarization, but the rate of action potential front propagation increases. In passed rabbit Purkinje fibers, NAD(+) (10 μM) reduced the duration of action potentials. Under conditions of spontaneous activity of Purkinje fibers, NAD(+) reduced the fi ring rate and the rate of slow diastolic depolarization. The effects of extracellular NAD(+) on bioelectric activity of the pacemaker (sinoatrial node) and conduction system of the heart (Purkinje fibers) are probably related to activation of P1 and P2 purinoceptors.

Morphological Variability in Second Language Learners: An Examination of Electrophysiological and Production Data

ERIC Educational Resources Information Center

Alemán Bañón, José; Miller, David; Rothman, Jason

2017-01-01

We examined sources of morphological variability in second language (L2) learners of Spanish whose native language (L1) is English, with a focus on L1-L2 similarity, morphological markedness, and knowledge type (receptive vs. expressive). Experiment 1 uses event-related potentials to examine noun-adjective number (present in L1) and gender…

The Epoch of Disk Formation: z is Approximately l to Today

NASA Technical Reports Server (NTRS)

Kassin, Susan; Gardner, Jonathan; Weiner, Ben; Faber, Sandra

2012-01-01

We present data on galaxy kinematics, morphologies, and star-formation rates over 0.1 less than z less than 1.2 for approximately 500 blue galaxies. These data show how systems like our own Milky-Way have come into being. At redshifts around 1, about half the age of the Universe ago, Milky-Way mass galaxies were different beasts than today. They had a significant amount of disturbed motions, disturbed morphologies, shallower potential wells, higher specific star-formation rates, and likely higher gas fractions. Since redshift approximately 1, galaxies have decreased in disturbed motions, increased in rotation velocity and potential well depth, become more well-ordered morphologically, and decreased in specific star-formation rate. We find interrelationships between these measurements. Galaxy kinematics are correlated with morphology and specific star-formation rate such that galaxies with the fastest rotation velocities and the least amounts of disturbed motions have the most well-ordered morphologies and the lowest specific star-formation rates. The converse is true. Moreover, we find that the rate at which galaxies become more well-ordered kinematically (i.e., increased rotation velocity, decreased disturbed motions) and morphologically is directly proportional to their stellar mass.

Network Oscillations Drive Correlated Spiking of ON and OFF Ganglion Cells in the rd1 Mouse Model of Retinal Degeneration

PubMed Central

Margolis, David J.; Gartland, Andrew J.; Singer, Joshua H.; Detwiler, Peter B.

2014-01-01

Following photoreceptor degeneration, ON and OFF retinal ganglion cells (RGCs) in the rd-1/rd-1 mouse receive rhythmic synaptic input that elicits bursts of action potentials at ∼10 Hz. To characterize the properties of this activity, RGCs were targeted for paired recording and morphological classification as either ON alpha, OFF alpha or non-alpha RGCs using two-photon imaging. Identified cell types exhibited rhythmic spike activity. Cross-correlation of spike trains recorded simultaneously from pairs of RGCs revealed that activity was correlated more strongly between alpha RGCs than between alpha and non-alpha cell pairs. Bursts of action potentials in alpha RGC pairs of the same type, i.e. two ON or two OFF cells, were in phase, while bursts in dissimilar alpha cell types, i.e. an ON and an OFF RGC, were 180 degrees out of phase. This result is consistent with RGC activity being driven by an input that provides correlated excitation to ON cells and inhibition to OFF cells. A2 amacrine cells were investigated as a candidate cellular mechanism and found to display 10 Hz oscillations in membrane voltage and current that persisted in the presence of antagonists of fast synaptic transmission and were eliminated by tetrodotoxin. Results support the conclusion that the rhythmic RGC activity originates in a presynaptic network of electrically coupled cells including A2s via a Na+-channel dependent mechanism. Network activity drives out of phase oscillations in ON and OFF cone bipolar cells, entraining similar frequency fluctuations in RGC spike activity over an area of retina that migrates with changes in the spatial locus of the cellular oscillator. PMID:24489706

From Early Embryonic to Adult Stage: Comparative Study of Action Potentials of Native and Pluripotent Stem Cell-Derived Cardiomyocytes.

PubMed

Peinkofer, Gabriel; Burkert, Karsten; Urban, Katja; Krausgrill, Benjamin; Hescheler, Jürgen; Saric, Tomo; Halbach, Marcel

2016-10-01

Cardiomyocytes (CMs) derived from induced pluripotent stem cells (iPS-CMs) are promising candidates for cell therapy, drug screening, and developmental studies. It is known that iPS-CMs possess immature electrophysiological properties, but an exact characterization of their developmental stage and subtype differentiation is hampered by a lack of knowledge of electrophysiological properties of native CMs from different developmental stages and origins within the heart. Thus, we sought to systematically investigate action potential (AP) properties of native murine CMs and to establish a database that allows classification of stem cell-derived CMs. Hearts from 129S2PasCrl mice were harvested at days 9-10, 12-14, and 16-18 postcoitum, as well as 1 day, 3-4 days, 1-2 weeks, 3-4 weeks, and 6 weeks postpartum. AP recordings in left and right atria and at apical, medial, and basal left and right ventricles were performed with sharp glass microelectrodes. Measurements revealed significant changes in AP morphology during pre- and postnatal murine development and significant differences between atria and ventricles, enabling a classification of developmental stage and subtype differentiation of stem cell-derived CMs based on their AP properties. For iPS-CMs derived from cell line TiB7.4, a typical ventricular phenotype was demonstrated at later developmental stages, while there were electrophysiological differences from atrial as well as ventricular native CMs at earlier stages. This finding supports that iPS-CMs can develop AP properties similar to native CMs, but points to differences in the maturation process between iPS-CMs and native CMs, which may be explained by dissimilar conditions during in vitro differentiation and in vivo development.

The statistics of calcium-mediated focal excitations on a one-dimensional cable.

PubMed

Chen, Wei; Asfaw, Mesfin; Shiferaw, Yohannes

2012-02-08

It is well known that various cardiac arrhythmias are initiated by an ill-timed excitation that originates from a focal region of the heart. However, up to now, it is not known what governs the timing, location, and morphology of these focal excitations. Recent studies have shown that these excitations can be caused by abnormalities in the calcium (Ca) cycling system. However, the cause-and-effect relationships linking subcellular Ca dynamics and focal activity in cardiac tissue is not completely understood. In this article, we present a minimal model of Ca-mediated focal excitations in cardiac tissue. This model accounts for the stochastic nature of spontaneous Ca release on a one-dimensional cable of cardiac cells. Using this model, we show that the timing of focal excitations is equivalent to a first passage time problem in a spatially extended system. In particular, we find that for a short cable the mean first passage time increases exponentially with the number of cells in tissue, and is critically dependent on the ratio of inward to outward currents near the threshold for an action potential. For long cables excitations occurs due to ectopic foci that occur on a length scale determined by the minimum length of tissue that can induce an action potential. Furthermore, we find that for long cables the mean first passage time decreases as a power law in the number cells. These results provide precise criteria for the occurrence of focal excitations in cardiac tissue, and will serve as a guide to determine the propensity of Ca-mediated triggered arrhythmias in the heart. Copyright © 2012 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Mechanisms of action of Coxiella burnetii effectors inferred from host-pathogen protein interactions.

PubMed

Wallqvist, Anders; Wang, Hao; Zavaljevski, Nela; Memišević, Vesna; Kwon, Keehwan; Pieper, Rembert; Rajagopala, Seesandra V; Reifman, Jaques

2017-01-01

Coxiella burnetii is an obligate Gram-negative intracellular pathogen and the etiological agent of Q fever. Successful infection requires a functional Type IV secretion system, which translocates more than 100 effector proteins into the host cytosol to establish the infection, restructure the intracellular host environment, and create a parasitophorous vacuole where the replicating bacteria reside. We used yeast two-hybrid (Y2H) screening of 33 selected C. burnetii effectors against whole genome human and murine proteome libraries to generate a map of potential host-pathogen protein-protein interactions (PPIs). We detected 273 unique interactions between 20 pathogen and 247 human proteins, and 157 between 17 pathogen and 137 murine proteins. We used orthology to combine the data and create a single host-pathogen interaction network containing 415 unique interactions between 25 C. burnetii and 363 human proteins. We further performed complementary pairwise Y2H testing of 43 out of 91 C. burnetii-human interactions involving five pathogen proteins. We used the combined data to 1) perform enrichment analyses of target host cellular processes and pathways, 2) examine effectors with known infection phenotypes, and 3) infer potential mechanisms of action for four effectors with uncharacterized functions. The host-pathogen interaction profiles supported known Coxiella phenotypes, such as adapting cell morphology through cytoskeletal re-arrangements, protein processing and trafficking, organelle generation, cholesterol processing, innate immune modulation, and interactions with the ubiquitin and proteasome pathways. The generated dataset of PPIs-the largest collection of unbiased Coxiella host-pathogen interactions to date-represents a rich source of information with respect to secreted pathogen effector proteins and their interactions with human host proteins.

Roles of specific Kv channel types in repolarization of the action potential in genetically identified subclasses of pyramidal neurons in mouse neocortex

PubMed Central

Pathak, Dhruba; Guan, Dongxu

2016-01-01

The action potential (AP) is a fundamental feature of excitable cells that serves as the basis for long-distance signaling in the nervous system. There is considerable diversity in the appearance of APs and the underlying repolarization mechanisms in different neuronal types (reviewed in Bean BP. Nat Rev Neurosci 8: 451–465, 2007), including among pyramidal cell subtypes. In the present work, we used specific pharmacological blockers to test for contributions of Kv1, Kv2, or Kv4 channels to repolarization of single APs in two genetically defined subpopulations of pyramidal cells in layer 5 of mouse somatosensory cortex (etv1 and glt) as well as pyramidal cells from layer 2/3. These three subtypes differ in AP properties (Groh A, Meyer HS, Schmidt EF, Heintz N, Sakmann B, Krieger P. Cereb Cortex 20: 826–836, 2010; Guan D, Armstrong WE, Foehring RC. J Neurophysiol 113: 2014–2032, 2015) as well as laminar position, morphology, and projection targets. We asked what the roles of Kv1, Kv2, and Kv4 channels are in AP repolarization and whether the underlying mechanisms are pyramidal cell subtype dependent. We found that Kv4 channels are critically involved in repolarizing neocortical pyramidal cells. There are also pyramidal cell subtype-specific differences in the role for Kv1 channels. Only Kv4 channels were involved in repolarizing the narrow APs of glt cells. In contrast, in etv1 cells and layer 2/3 cells, the broader APs are partially repolarized by Kv1 channels in addition to Kv4 channels. Consistent with their activation in the subthreshold range, Kv1 channels also regulate AP voltage threshold in all pyramidal cell subtypes. PMID:26864770

Rapid time course of action potentials in spines and remote dendrites of mouse visual cortex neurons.

PubMed

Holthoff, Knut; Zecevic, Dejan; Konnerth, Arthur

2010-04-01

Axonally initiated action potentials back-propagate into spiny dendrites of central mammalian neurons and thereby regulate plasticity at excitatory synapses on individual spines as well as linear and supralinear integration of synaptic inputs along dendritic branches. Thus, the electrical behaviour of individual dendritic spines and terminal dendritic branches is critical for the integrative function of nerve cells. The actual dynamics of action potentials in spines and terminal branches, however, are not entirely clear, mostly because electrode recording from such small structures is not feasible. Additionally, the available membrane potential imaging techniques are limited in their sensitivity and require substantial signal averaging for the detection of electrical events at the spatial scale of individual spines. We made a critical improvement in the voltage-sensitive dye imaging technique to achieve multisite recordings of backpropagating action potentials from individual dendritic spines at a high frame rate. With this approach, we obtained direct evidence that in layer 5 pyramidal neurons from the visual cortex of juvenile mice, the rapid time course of somatic action potentials is preserved throughout all cellular compartments, including dendritic spines and terminal branches of basal and apical dendrites. The rapid time course of the action potential in spines may be a critical determinant for the precise regulation of spike timing-dependent synaptic plasticity within a narrow time window.

22 CFR 161.8 - General description of the Department's NEPA process.

Code of Federal Regulations, 2010 CFR

2010-04-01

... § 161.8 General description of the Department's NEPA process. In reviewing proposed actions for potential environmental effects in the United States responsible action officers will follow the procedural... review the action to determine if it may cause potential significant environmental effects on the...

Prolonged action potential duration in cardiac ablation of PDK1 mice.

PubMed

Han, Zhonglin; Jiang, Yu; Yang, Zhongzhou; Cao, Kejiang; Wang, Dao W

2015-01-01

The involvement of the AGC protein kinase family in regulating arrhythmia has drawn considerable attention, but the underlying mechanisms are still not clear. The aim of this study is to explore the role of 3-phosphoinositide-dependent protein kinase-1 (PDK1), one of upstream protein kinases of the AGC protein kinase family, in the pathogenesis of dysregulated electrophysiological basis. PDK1(F/F) αMHC-Cre mice and PDK1(F/F) mice were divided into experiment group and control group. Using patch clamping technology, we explored action potential duration in both groups, and investigated the functions of transient outward potassium channel and L-type Ca(2+) channel to explain the abnormal action potential duration. Significant prolongation action potential duration was found in mice with PDK1 deletion. Further, the peak current of transient outward potassium current and L-type Ca(2+) current were decreased by 84% and 49% respectively. In addition, dysregulation of channel kinetics lead to action potential duration prolongation further. In conclusion, we have demonstrated that PDK1 participates in action potential prolongation in cardiac ablation of PDK1 mice. This effect is likely to be mediated largely through downregulation of transient outward potassium current. These findings indicate the modulation of the PDK1 pathway could provide a new mechanism for abnormal electrophysiological basis.

A phantom axon setup for validating models of action potential recordings.

PubMed

Rossel, Olivier; Soulier, Fabien; Bernard, Serge; Guiraud, David; Cathébras, Guy

2016-08-01

Electrode designs and strategies for electroneurogram recordings are often tested first by computer simulations and then by animal models, but they are rarely implanted for long-term evaluation in humans. The models show that the amplitude of the potential at the surface of an axon is higher in front of the nodes of Ranvier than at the internodes; however, this has not been investigated through in vivo measurements. An original experimental method is presented to emulate a single fiber action potential in an infinite conductive volume, allowing the potential of an axon to be recorded at both the nodes of Ranvier and the internodes, for a wide range of electrode-to-fiber radial distances. The paper particularly investigates the differences in the action potential amplitude along the longitudinal axis of an axon. At a short radial distance, the action potential amplitude measured in front of a node of Ranvier is two times larger than in the middle of two nodes. Moreover, farther from the phantom axon, the measured action potential amplitude is almost constant along the longitudinal axis. The results of this new method confirm the computer simulations, with a correlation of 97.6 %.

Action potentials in retinal ganglion cells are initiated at the site of maximal curvature of the extracellular potential.

PubMed

Eickenscheidt, Max; Zeck, Günther

2014-06-01

The initiation of an action potential by extracellular stimulation occurs after local depolarization of the neuronal membrane above threshold. Although the technique shows remarkable clinical success, the site of action and the relevant stimulation parameters are not completely understood. Here we identify the site of action potential initiation in rabbit retinal ganglion cells (RGCs) interfaced to an array of extracellular capacitive stimulation electrodes. We determine which feature of the extracellular potential governs action potential initiation by simultaneous stimulation and recording RGCs interfaced in epiretinal configuration. Stimulation electrodes were combined to areas of different size and were presented at different positions with respect to the RGC. Based on stimulation by electrodes beneath the RGC soma and simultaneous sub-millisecond latency measurement we infer axonal initiation at the site of maximal curvature of the extracellular potential. Stimulation by electrodes at different positions along the axon reveals a nearly constant threshold current density except for a narrow region close to the cell soma. These findings are explained by the concept of the activating function modified to consider a region of lower excitability close to the cell soma. We present a framework how to estimate the site of action potential initiation and the stimulus required to cross threshold in neurons tightly interfaced to capacitive stimulation electrodes. Our results underscore the necessity of rigorous electrical characterization of the stimulation electrodes and of the interfaced neural tissue.

Autonomous initiation and propagation of action potentials in neurons of the subthalamic nucleus.

PubMed

Atherton, Jeremy F; Wokosin, David L; Ramanathan, Sankari; Bevan, Mark D

2008-12-01

The activity of the subthalamic nucleus (STN) is intimately related to movement and is generated, in part, by voltage-dependent Na(+) (Na(v)) channels that drive autonomous firing. In order to determine the principles underlying the initiation and propagation of action potentials in STN neurons, 2-photon laser scanning microscopy was used to guide tight-seal whole-cell somatic and loose-seal cell-attached axonal/dendritic patch-clamp recordings and compartment-selective ion channel manipulation in rat brain slices. Action potentials were first detected in a region that corresponded most closely to the unmyelinated axon initial segment, as defined by Golgi and ankyrin G labelling. Following initiation, action potentials propagated reliably into axonal and somatodendritic compartments with conduction velocities of approximately 5 m s(-1) and approximately 0.7 m s(-1), respectively. Action potentials generated by neurons with axons truncated within or beyond the axon initial segment were not significantly different. However, axon initial segment and somatic but not dendritic or more distal axonal application of low [Na(+)] ACSF or the selective Na(v) channel blocker tetrodotoxin consistently depolarized action potential threshold. Finally, somatodendritic but not axonal application of GABA evoked large, rapid inhibitory currents in concordance with electron microscopic analyses, which revealed that the somatodendritic compartment was the principal target of putative inhibitory inputs. Together the data are consistent with the conclusions that in STN neurons the axon initial segment and soma express an excess of Na(v) channels for the generation of autonomous activity, while synaptic activation of somatodendritic GABA(A) receptors regulates the axonal initiation of action potentials.

Autonomous initiation and propagation of action potentials in neurons of the subthalamic nucleus

PubMed Central

Atherton, Jeremy F; Wokosin, David L; Ramanathan, Sankari; Bevan, Mark D

2008-01-01

The activity of the subthalamic nucleus (STN) is intimately related to movement and is generated, in part, by voltage-dependent Na+ (Nav) channels that drive autonomous firing. In order to determine the principles underlying the initiation and propagation of action potentials in STN neurons, 2-photon laser scanning microscopy was used to guide tight-seal whole-cell somatic and loose-seal cell-attached axonal/dendritic patch-clamp recordings and compartment-selective ion channel manipulation in rat brain slices. Action potentials were first detected in a region that corresponded most closely to the unmyelinated axon initial segment, as defined by Golgi and ankyrin G labelling. Following initiation, action potentials propagated reliably into axonal and somatodendritic compartments with conduction velocities of ∼5 m s−1 and ∼0.7 m s−1, respectively. Action potentials generated by neurons with axons truncated within or beyond the axon initial segment were not significantly different. However, axon initial segment and somatic but not dendritic or more distal axonal application of low [Na+] ACSF or the selective Nav channel blocker tetrodotoxin consistently depolarized action potential threshold. Finally, somatodendritic but not axonal application of GABA evoked large, rapid inhibitory currents in concordance with electron microscopic analyses, which revealed that the somatodendritic compartment was the principal target of putative inhibitory inputs. Together the data are consistent with the conclusions that in STN neurons the axon initial segment and soma express an excess of Nav channels for the generation of autonomous activity, while synaptic activation of somatodendritic GABAA receptors regulates the axonal initiation of action potentials. PMID:18832425

Influence of asymmetric attenuation of single and paired dendritic inputs on summation of synaptic potentials and initiation of action potentials.

PubMed

Fortier, Pierre A; Bray, Chelsea

2013-04-16

Previous studies revealed mechanisms of dendritic inputs leading to action potential initiation at the axon initial segment and backpropagation into the dendritic tree. This interest has recently expanded toward the communication between different parts of the dendritic tree which could preprocess information before reaching the soma. This study tested for effects of asymmetric voltage attenuation between different sites in the dendritic tree on summation of synaptic inputs and action potential initiation using the NEURON simulation environment. Passive responses due to the electrical equivalent circuit of the three-dimensional neuron architecture with leak channels were examined first, followed by the responses after adding voltage-gated channels and finally synaptic noise. Asymmetric attenuation of voltage, which is a function of asymmetric input resistance, was seen between all pairs of dendritic sites but the transfer voltages (voltage recorded at the opposite site from stimulation among a pair of dendritic sites) were equal and also summed linearly with local voltage responses during simultaneous stimulation of both sites. In neurons with voltage-gated channels, we reproduced the observations where a brief stimulus to the proximal ascending dendritic branch of a pyramidal cell triggers a local action potential but a long stimulus triggers a somal action potential. Combined stimulation of a pair of sites in this proximal dendrite did not alter this pattern. The attraction of the action potential onset toward the soma with a long stimulus in the absence of noise was due to the higher density of voltage-gated sodium channels at the axon initial segment. This attraction was, however, negligible at the most remote distal dendritic sites and was replaced by an effect due to high input resistance. Action potential onset occurred at the dendritic site of higher input resistance among a pair of remote dendritic sites, irrespective of which of these two sites received the synaptic input. Exploration of the parameter space showed how the gradient of voltage-gated channel densities and input resistances along a dendrite could draw the action potential onset away from the stimulation site. The attraction of action potential onset toward the higher density of voltage-gated channels in the soma during stimulation of the proximal dendrite was, however, reduced after the addition of synaptic noise. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

Effects of hyperbaric therapy on function and morphology of Guinea pig cochlea with endolymphatic hydrops.

PubMed

Chi, Fang-Lu; Liang, Qin; Wang, Zheng-Min

2004-07-01

The objective of this study was to investigate the effect on experimental endolymphatic hydrops in guinea pigs after hyperbaric therapy. The histopathologic character of Ménière's disease is the presence of endolymphatic hydrops. Endolymphatic hypertension could be one of the factors resulting from endolymphatic hydrops. Some treatments of Ménière's disease are aimed toward preventing the endolymphatic hypertension. Exposure to pressure change has risen in recent years. Thirty-two guinea pigs were operated on the right ears to induce endolymphatic hydrops by obliterating the endolymphatic sac through an extradural posterior cranial fossa approach. After 5 weeks' survival, 12 guinea pigs were put into a chamber with an absolute atmospheric pressure of 2.2 for 3 weeks (90 minutes once a day 5 times a week). We observed the morphologic and functional changes in guinea pig cochleae of the pressure group, 4-week hydrops group (n = 10), 8-week hydrops group (n = 10), and the normal group (n = 10). We measured the hearing threshold of the auditory brainstem response, the 70-dB SPL action potential (AP) latency, the ratio of 70-dB SPL summating potential magnitude to action potential magnitude (-SP/AP) of the electrocochleogram, and the maximum scala media area (SMA) ratio, respectively. The average 70-dB SPL-SP/AP magnitude of right ears (0.29 +/- 0.09) and the average maximum SMA ratio (2.23 +/- 0.20) in the pressure group were significantly less than that in the 8-week hydrops group (0.69 +/- 0.15 and 4.04 +/- 0.52, respectively) with the same survival time (p < 0.05). The results in the pressure group were almost as similar as that in the 4-week hydrops group (0.29 +/- 0.13 and 2.22 +/- 0.20, respectively) (p > 0.05). The average hearing threshold of ABR of right ears in the pressure group (36.67 +/- 14.30-dB SPL) was lower than that of the 8-week hydrops group (44 +/-1 4.30-dB SPL), but the difference was insignificant (p > 0.05). The average 70-dB SPL AP latency of right ears in the pressure group was not significantly different from those of the 8-week hydrops group, the 4-week hydrops group, or the normal group (p > 0.05). Our findings suggest hyperbaric therapy can significantly suppress the development of endolymphatic hydrops and improve cochlear function in guinea pigs. This study provided strong evidence for the development of pressure treatment of Ménière's disease without destroying the inner ear.

Ling's Adsorption Theory as a Mechanism of Membrane Potential Generation Observed in Both Living and Nonliving Systems.

PubMed

Tamagawa, Hirohisa; Funatani, Makoto; Ikeda, Kota

2016-01-26

The potential between two electrolytic solutions separated by a membrane impermeable to ions was measured and the generation mechanism of potential measured was investigated. From the physiological point of view, a nonzero membrane potential or action potential cannot be observed across the impermeable membrane. However, a nonzero membrane potential including action potential-like potential was clearly observed. Those observations gave rise to a doubt concerning the validity of currently accepted generation mechanism of membrane potential and action potential of cell. As an alternative theory, we found that the long-forgotten Ling's adsorption theory was the most plausible theory. Ling's adsorption theory suggests that the membrane potential and action potential of a living cell is due to the adsorption of mobile ions onto the adsorption site of cell, and this theory is applicable even to nonliving (or non-biological) system as well as living system. Through this paper, the authors emphasize that it is necessary to reconsider the validity of current membrane theory and also would like to urge the readers to pay keen attention to the Ling's adsorption theory which has for long years been forgotten in the history of physiology.

Different evolutionary pathways underlie the morphology of wrist bones in hominoids

PubMed Central

2013-01-01

Background The hominoid wrist has been a focus of numerous morphological analyses that aim to better understand long-standing questions about the evolution of human and hominoid hand use. However, these same analyses also suggest various scenarios of complex and mosaic patterns of morphological evolution within the wrist and potentially multiple instances of homoplasy that would benefit from require formal analysis within a phylogenetic context. We identify morphological features that principally characterize primate – and, in particular, hominoid (apes, including humans) - wrist evolution and reveal the rate, process and evolutionary timing of patterns of morphological change on individual branches of the primate tree of life. Linear morphological variables of five wrist bones – the scaphoid, lunate, triquetrum, capitate and hamate – are analyzed in a diverse sample of extant hominoids (12 species, 332 specimens), Old World (8 species, 43 specimens) and New World (4 species, 26 specimens) monkeys, fossil Miocene apes (8 species, 20 specimens) and Plio-Pleistocene hominins (8 species, 18 specimens). Result Results reveal a combination of parallel and synapomorphic morphology within haplorrhines, and especially within hominoids, across individual wrist bones. Similar morphology of some wrist bones reflects locomotor behaviour shared between clades (scaphoid, triquetrum and capitate) while others (lunate and hamate) indicate clade-specific synapomorphic morphology. Overall, hominoids show increased variation in wrist bone morphology compared with other primate clades, supporting previous analyses, and demonstrate several occurrences of parallel evolution, particularly between orangutans and hylobatids, and among hominines (extant African apes, humans and fossil hominins). Conclusions Our analyses indicate that different evolutionary processes can underlie the evolution of a single anatomical unit (the wrist) to produce diversity in functional and morphological adaptations across individual wrist bones. These results exemplify a degree of evolutionary and functional independence across different wrist bones, the potential evolvability of skeletal morphology, and help to contextualize the postcranial mosaicism observed in the hominin fossil record. PMID:24148262

Effects of acetylcholine and noradrenalin on action potentials of isolated rabbit sinoatrial and atrial myocytes.

PubMed

Verkerk, Arie O; Geuzebroek, Guillaume S C; Veldkamp, Marieke W; Wilders, Ronald

2012-01-01

The autonomic nervous system controls heart rate and contractility through sympathetic and parasympathetic inputs to the cardiac tissue, with acetylcholine (ACh) and noradrenalin (NA) as the chemical transmitters. In recent years, it has become clear that specific Regulators of G protein Signaling proteins (RGS proteins) suppress muscarinic sensitivity and parasympathetic tone, identifying RGS proteins as intriguing potential therapeutic targets. In the present study, we have identified the effects of 1 μM ACh and 1 μM NA on the intrinsic action potentials of sinoatrial (SA) nodal and atrial myocytes. Single cells were enzymatically isolated from the SA node or from the left atrium of rabbit hearts. Action potentials were recorded using the amphotericin-perforated patch-clamp technique in the absence and presence of ACh, NA, or a combination of both. In SA nodal myocytes, ACh increased cycle length and decreased diastolic depolarization rate, whereas NA decreased cycle length and increased diastolic depolarization rate. Both ACh and NA increased maximum upstroke velocity. Furthermore, ACh hyperpolarized the maximum diastolic potential. In atrial myocytes stimulated at 2 Hz, both ACh and NA hyperpolarized the maximum diastolic potential, increased the action potential amplitude, and increased the maximum upstroke velocity. Action potential duration at 50 and 90% repolarization was decreased by ACh, but increased by NA. The effects of both ACh and NA on action potential duration showed a dose dependence in the range of 1-1000 nM, while a clear-cut frequency dependence in the range of 1-4 Hz was absent. Intermediate results were obtained in the combined presence of ACh and NA in both SA nodal and atrial myocytes. Our data uncover the extent to which SA nodal and atrial action potentials are intrinsically dependent on ACh, NA, or a combination of both and may thus guide further experiments with RGS proteins.

Effects of Acetylcholine and Noradrenalin on Action Potentials of Isolated Rabbit Sinoatrial and Atrial Myocytes

PubMed Central

Verkerk, Arie O.; Geuzebroek, Guillaume S. C.; Veldkamp, Marieke W.; Wilders, Ronald

2012-01-01

The autonomic nervous system controls heart rate and contractility through sympathetic and parasympathetic inputs to the cardiac tissue, with acetylcholine (ACh) and noradrenalin (NA) as the chemical transmitters. In recent years, it has become clear that specific Regulators of G protein Signaling proteins (RGS proteins) suppress muscarinic sensitivity and parasympathetic tone, identifying RGS proteins as intriguing potential therapeutic targets. In the present study, we have identified the effects of 1 μM ACh and 1 μM NA on the intrinsic action potentials of sinoatrial (SA) nodal and atrial myocytes. Single cells were enzymatically isolated from the SA node or from the left atrium of rabbit hearts. Action potentials were recorded using the amphotericin-perforated patch-clamp technique in the absence and presence of ACh, NA, or a combination of both. In SA nodal myocytes, ACh increased cycle length and decreased diastolic depolarization rate, whereas NA decreased cycle length and increased diastolic depolarization rate. Both ACh and NA increased maximum upstroke velocity. Furthermore, ACh hyperpolarized the maximum diastolic potential. In atrial myocytes stimulated at 2 Hz, both ACh and NA hyperpolarized the maximum diastolic potential, increased the action potential amplitude, and increased the maximum upstroke velocity. Action potential duration at 50 and 90% repolarization was decreased by ACh, but increased by NA. The effects of both ACh and NA on action potential duration showed a dose dependence in the range of 1–1000 nM, while a clear-cut frequency dependence in the range of 1–4 Hz was absent. Intermediate results were obtained in the combined presence of ACh and NA in both SA nodal and atrial myocytes. Our data uncover the extent to which SA nodal and atrial action potentials are intrinsically dependent on ACh, NA, or a combination of both and may thus guide further experiments with RGS proteins. PMID:22754533

The effects of gentamicin and penicillin/streptomycin on the electrophysiology of human induced pluripotent stem cell-derived cardiomyocytes in manual patch clamp and multi-electrode array system.

PubMed

Hyun, Soo-Wang; Kim, Bo-Ram; Lin, Dan; Hyun, Sung-Ae; Yoon, Seong Shoon; Seo, Joung-Wook

Cell culture media usually contains antibiotics including gentamicin or penicillin/streptomycin (PS) to protect cells from bacterial contamination. However, little is known about the effects of antibiotics on action potential and field potential parameters in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). The present study examined the effects of gentamicin (10, 25, and 50μg/ml) and PS (50, 100, and 200U/μg/ml) on electrophysiological activity in spontaneously beating hiPSC-CMs using manual patch clamp and multi-electrode array. We also measured mRNA expression of cardiac ion channels in hiPSC-CMs grown in media with or without gentamicin (25μg/ml) using reverse transcription-polymerase chain reaction. We recorded action potential and field potential of hiPSC-CMs grown in the presence or absence of gentamicin or PS. We also observed action potential parameters in hiPSC-CMs after short-term treatment with these antibiotics. Changes in action potential and field potential parameters were observed in hiPSC-CMs grown in media containing gentamicin or PS. Treatment with PS also affected action potential parameters in hiPSC-CMs. In addition, the mRNA expression of cardiac sodium and potassium ion channels was significantly attenuated in hiPSC-CMs grown in the presence of gentamicin (25μg/ml). The present findings suggested that gentamicin should not be used in the culture media of hiPSC-CMs used for the measurement of electrophysiological parameters. Our findings also suggest that 100U/100μg/ml of PS are the maximum appropriate concentrations of these antibiotics for recording action potential waveform, because they did not influence action potential parameters in these cells. Copyright © 2017. Published by Elsevier Inc.

Beta Function Quintessence Cosmological Parameters and Fundamental Constants I: Power and Inverse Power Law Dark Energy Potentials

NASA Astrophysics Data System (ADS)

Thompson, Rodger I.

2018-04-01

This investigation explores using the beta function formalism to calculate analytic solutions for the observable parameters in rolling scalar field cosmologies. The beta function in this case is the derivative of the scalar ϕ with respect to the natural log of the scale factor a, β (φ )=d φ /d ln (a). Once the beta function is specified, modulo a boundary condition, the evolution of the scalar ϕ as a function of the scale factor is completely determined. A rolling scalar field cosmology is defined by its action which can contain a range of physically motivated dark energy potentials. The beta function is chosen so that the associated "beta potential" is an accurate, but not exact, representation of the appropriate dark energy model potential. The basic concept is that the action with the beta potential is so similar to the action with the model potential that solutions using the beta action are accurate representations of solutions using the model action. The beta function provides an extra equation to calculate analytic functions of the cosmologies parameters as a function of the scale factor that are that are not calculable using only the model action. As an example this investigation uses a quintessence cosmology to demonstrate the method for power and inverse power law dark energy potentials. An interesting result of the investigation is that the Hubble parameter H is almost completely insensitive to the power of the potentials and that ΛCDM is part of the family of quintessence cosmology power law potentials with a power of zero.

Beta function quintessence cosmological parameters and fundamental constants - I. Power and inverse power law dark energy potentials

NASA Astrophysics Data System (ADS)

Thompson, Rodger I.

2018-07-01

This investigation explores using the beta function formalism to calculate analytic solutions for the observable parameters in rolling scalar field cosmologies. The beta function in this case is the derivative of the scalar φ with respect to the natural log of the scale factor a, β (φ)=d φ/d ln (a). Once the beta function is specified, modulo a boundary condition, the evolution of the scalar φ as a function of the scale factor is completely determined. A rolling scalar field cosmology is defined by its action which can contain a range of physically motivated dark energy potentials. The beta function is chosen so that the associated `beta potential' is an accurate, but not exact, representation of the appropriate dark energy model potential. The basic concept is that the action with the beta potential is so similar to the action with the model potential that solutions using the beta action are accurate representations of solutions using the model action. The beta function provides an extra equation to calculate analytic functions of the cosmologies parameters as a function of the scale factor that are not calculable using only the model action. As an example, this investigation uses a quintessence cosmology to demonstrate the method for power and inverse power law dark energy potentials. An interesting result of the investigation is that the Hubble parameter H is almost completely insensitive to the power of the potentials and that Λ cold dark matter is part of the family of quintessence cosmology power-law potentials with a power of zero.

Pulsed magnetic stimulation modifies amplitude of action potentials in vitro via ionic channels-dependent mechanism.

PubMed

Ahmed, Zaghloul; Wieraszko, Andrzej

2015-07-01

This paper investigates the influence of pulsed magnetic fields (PMFs) on amplitude of evoked, compound action potential (CAP) recorded from the segments of sciatic nerve in vitro. PMFs were applied for 30 min at frequency of 0.16 Hz and intensity of 15 mT. In confirmation of our previous reports, PMF exposure enhanced amplitude of CAPs. The effect persisted beyond PMF activation period. As expected, CAP amplitude was attenuated by antagonists of sodium channel, lidocaine, and tetrodotoxin. Depression of the potential by sodium channels antagonists was reversed by subsequent exposure to PMFs. The effect of elevated potassium concentration and veratridine on the action potential was modified by exposure to PMFs as well. Neither inhibitors of protein kinase C and protein kinase A, nor known free radicals scavengers had any effects on PMF action. Possible mechanisms of PMF action are discussed. © 2015 Wiley Periodicals, Inc.

Effectiveness of acidic oxidative potential water in preventing bacterial infection in islet transplantation.

PubMed

Miyamoto, M; Inoue, K; Gu, Y; Hoki, M; Haji, S; Ohyanagi, H

1999-01-01

At a number of points in the current procedures of islet isolation and islet culture after the harvesting of donor pancreata, microorganisms could potentially infect the islet preparation. Furthermore, the use of islets from multiple donors can compound the risks of contamination of individual recipients. Acidic oxidative potential water (also termed electrolyzed strong acid solution, function water, or acqua oxidation water), which was developed in Japan, is a strong acid formed on the anode in the electrolysis of water containing a small amount of sodium chloride. It has these physical properties: pH, from 2.3 to 2.7; oxidative-reduction potential, from 1,000 to 1,100 mV; dissolved chlorine, from 30 to 40 ppm; and dissolved oxygen, from 10 to 30 ppm. Because of these properties, acidic oxidative potential water has strong bactericidal effects on all bacteria including methicillin-resistant Staphylococcus aureus (MRSA), viruses including HIV, HBV, HCV, CMV, and fungi as a result of the action of the active oxygen and active chlorine that it contains. We conducted this study to evaluate the effect of acidic oxidative potential water irrigation on bacterial contamination on the harvesting of porcine pancreata from slaughterhouses for islet xenotransplantation by counting the number of pancreatic surface bacteria using the Dip-slide method, and on the results of islet culture; and to evaluate the direct effect on isolated islets when it is used to prevent bacterial contamination by the static incubation test and by morphological examination. Direct irrigation of the pancreas by acidic oxidative potential water was found to be very effective in preventing bacterial contamination, but direct irrigation of isolated islets slightly decreased their viability and function.

Differential recall of derived and inflected word forms in working memory: examining the role of morphological information in simple and complex working memory tasks

PubMed Central

Service, Elisabet; Maury, Sini

2015-01-01

Working memory (WM) has been described as an interface between cognition and action, or a system for access to a limited amount of information needed in complex cognition. Access to morphological information is needed for comprehending and producing sentences. The present study probed WM for morphologically complex word forms in Finnish, a morphologically rich language. We studied monomorphemic (boy), inflected (boy+’s), and derived (boy+hood) words in three tasks. Simple span, immediate serial recall of words, in Experiment 1, is assumed to mainly rely on information in the focus of attention. Sentence span, a dual task combining sentence reading with recall of the last word (Experiment 2) or of a word not included in the sentence (Experiment 3) is assumed to involve establishment of a search set in long-term memory for fast activation into the focus of attention. Recall was best for monomorphemic and worst for inflected word forms with performance on derived words in between. However, there was an interaction between word type and experiment, suggesting that complex span is more sensitive to morphological complexity in derivations than simple span. This was explored in a within-subjects Experiment 4 combining all three tasks. An interaction between morphological complexity and task was replicated. Both inflected and derived forms increased load in WM. In simple span, recall of inflectional forms resulted in form errors. Complex span tasks were more sensitive to morphological load in derived words, possibly resulting from interference from morphological neighbors in the mental lexicon. The results are best understood as involving competition among inflectional forms when binding words from input into an output structure, and competition from morphological neighbors in secondary memory during cumulative retrieval-encoding cycles. Models of verbal recall need to be able to represent morphological as well as phonological and semantic information. PMID:25642181

Na and Ca components of action potentials in amphioxus muscle cells

PubMed Central

Hagiwara, S.; Kidokoro, Y.

1971-01-01

1. The ionic mechanism of the action potential produced in lamella-like muscle cells of amphioxus, Branchiostoma californiense, was investigated with intracellular recording and polarization techniques. 2. The resting potential and action potential overshoot in normal saline are -53±5 mV (S.D.) and +29±10 mV (S.D.) respectively. 3. The action potential is eliminated by tetrodotoxin (3 μM) and by replacing NaCl in the saline with Tris-chloride but maintained by replacing Na with Li. 4. After elimination of the normal action potential by tetrodotoxin or replacing Na with Tris, the addition of procaine (7·3 mM) to the external saline makes the membrane capable of producing a regenerative potential change. 5. The peak potential of the regenerative response depends on external Ca concentration in a manner predicted by the Nernst equation with Ca concentrations close to normal. 6. The Ca dependent response is reversibly suppressed by Co or La ions. 7. Similar regenerative responses are obtained when Ca is substituted with Sr or Ba. 8. It is concluded that two independent mechanisms of ionic permeability increase occur in the membrane of amphioxus muscle cell, one to Na and the other to Ca. PMID:5158595

7 CFR 1945.19 - Reporting potential natural disasters and initial actions.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 13 2012-01-01 2012-01-01 false Reporting potential natural disasters and initial... Assistance-General § 1945.19 Reporting potential natural disasters and initial actions. (a) Purpose. The purpose of reporting potential natural disasters is to provide a systematic procedure for rapid reporting...

7 CFR 1945.19 - Reporting potential natural disasters and initial actions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 13 2011-01-01 2009-01-01 true Reporting potential natural disasters and initial... Assistance-General § 1945.19 Reporting potential natural disasters and initial actions. (a) Purpose. The purpose of reporting potential natural disasters is to provide a systematic procedure for rapid reporting...

7 CFR 1945.19 - Reporting potential natural disasters and initial actions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 13 2010-01-01 2009-01-01 true Reporting potential natural disasters and initial... Assistance-General § 1945.19 Reporting potential natural disasters and initial actions. (a) Purpose. The purpose of reporting potential natural disasters is to provide a systematic procedure for rapid reporting...

Action potentials recorded from bundles of very thin, gray matter axons in rat cerebellar slices using a grease-gap method.

PubMed

Palani, Damodharan; Pekala, Dobromila; Baginskas, Armantas; Szkudlarek, Hanna; Raastad, Morten

2012-07-15

We investigated the ability of a grease-gap method to record fast and slow changes of the membrane potential from bundles of gray matter axons. Their membrane potentials are of particular interest because these axons are different from most axons that have been investigated using intra-axonal or gap techniques. One of the main differences is that gray matter axons typically have closely spaced presynaptic specializations, called boutons or varicosities, distributed along their entire paths. In response to electrical activation of bundles of parallel fiber axons we were able to record small (128-416μV) but stable signals that we show most likely represented a fraction of the trans-membrane action potentials. A less-than 100% fraction prevents measurements of absolute values for membrane potentials, but the good signal-to-noise ratio (typically 10-16) allows detection of changes in resting membrane potential, action potentials and their after-potentials. Because very little is known about the shape of action potentials and after-potentials in these axons we used several independent methods to make it likely that the grease-gap signal was of intra-axonal origin. We demonstrate the utility of the method by showing that the action potentials in cerebellar parallel fibers and hippocampal Schaffer collaterals had a slowly decaying, depolarized after-potential. The method is ideal for pharmacological tests, which we demonstrate by showing that the slow after-potential was sensitive to 4-AP, and that the membrane potential was reduced by 200μM Ba(2+). Copyright © 2012 Elsevier B.V. All rights reserved.

Downregulation of NF-κB and PCNA in the regulatory pathways of apoptosis by cyclooxygenase-2 inhibitors in experimental lung cancer.

PubMed

Setia, Shruti; Sanyal, Sankar Nath

2012-10-01

Non-steroidal anti-inflammatory drugs (NSAIDs) are emerging as novel chemopreventive agents against a variety of cancers owing to their capability in blocking the tumor development by cellular proliferation, angiogenesis and by promoting apoptosis. The present study further explored the comparative role of a traditional NSAID, indomethacin and a newly developed coxib, etoricoxib against 9,10-dimethylbenz(a)anthracene (DMBA)-induced lung carcinogenesis in rats. Morphological and histological analysis revealed the occurrence of tumors and lesions along with constricted alveolar spaces in the DMBA treated animals which were largely corrected both by indomethacin and etoricoxib. COX-1 was found to be uniformly expressed in all the groups while COX-2 levels were raised prominently in the DMBA treated animals. Proliferation, as studied by PCNA expression was found to be markedly increased in the DMBA group as compared to the others. Increased NF-κB expression in the DMBA group was found to correct with the co-administration of NSAIDs. Also, fluorescent co-staining of the isolated lung cells revealed a significantly decreased apoptosis and altered mitochondrial membrane potential. In conclusion, these parameters indicate to the chemopreventive action of the two NSAIDs studied in lung cancer and as their mechanism of action suggests, can be achievable both by COX-dependent and COX-independent pathways.

Biological mode of action of a nitrophenolates-based biostimulant: case study

PubMed Central

Przybysz, Arkadiusz; Gawrońska, Helena; Gajc-Wolska, Janina

2014-01-01

The challenges facing modern plant production involve (i) responding to the demand for food and resources of plant origin from the world's rapidly growing population, (ii) coping with the negative impact of stressful conditions mainly due to anthropopressure, and (iii) meeting consumers' new requirements and preferences for food that is high in nutritive value, natural, and free from harmful chemical additives. Despite employing the most modern plant cultivation technologies and the progress that has been made in breeding programs, the genetically-determined crop potential is still far from being fully exploited. Consequently yield and quality are often reduced, making production less, both profitable and attractive. There is an increasing desire to reduce the chemical input in agriculture and there has been a change toward integrated plant management and sustainable, environmentally-friendly systems. Biostimulants are a category of relatively new products of diverse formulations that positively affect a plant's vital processes and whose impact is usually more evident under stressful conditions. In this paper, information is provided on the mode of action of a nitrophenolates-based biostimulant, Atonik, in model species and economically important crops grown under both field and controlled conditions in a growth chamber. The effects of Atonik on plant morphology, physiology, biochemistry (crops and model plant) and yield and yield parameters (crops) is demonstrated. Effects of other biostimulants on studied in this work processes/parameters are also presented in discussion. PMID:25566287

Biological mode of action of a nitrophenolates-based biostimulant: case study.

PubMed

Przybysz, Arkadiusz; Gawrońska, Helena; Gajc-Wolska, Janina

2014-01-01

The challenges facing modern plant production involve (i) responding to the demand for food and resources of plant origin from the world's rapidly growing population, (ii) coping with the negative impact of stressful conditions mainly due to anthropopressure, and (iii) meeting consumers' new requirements and preferences for food that is high in nutritive value, natural, and free from harmful chemical additives. Despite employing the most modern plant cultivation technologies and the progress that has been made in breeding programs, the genetically-determined crop potential is still far from being fully exploited. Consequently yield and quality are often reduced, making production less, both profitable and attractive. There is an increasing desire to reduce the chemical input in agriculture and there has been a change toward integrated plant management and sustainable, environmentally-friendly systems. Biostimulants are a category of relatively new products of diverse formulations that positively affect a plant's vital processes and whose impact is usually more evident under stressful conditions. In this paper, information is provided on the mode of action of a nitrophenolates-based biostimulant, Atonik, in model species and economically important crops grown under both field and controlled conditions in a growth chamber. The effects of Atonik on plant morphology, physiology, biochemistry (crops and model plant) and yield and yield parameters (crops) is demonstrated. Effects of other biostimulants on studied in this work processes/parameters are also presented in discussion.

Nanomechanical clues from morphologically normal cervical squamous cells could improve cervical cancer screening

NASA Astrophysics Data System (ADS)

Geng, Li; Feng, Jiantao; Sun, Quanmei; Liu, Jing; Hua, Wenda; Li, Jing; Ao, Zhuo; You, Ke; Guo, Yanli; Liao, Fulong; Zhang, Youyi; Guo, Hongyan; Han, Jinsong; Xiong, Guangwu; Zhang, Lufang; Han, Dong

2015-09-01

Applying an atomic force microscope, we performed a nanomechanical analysis of morphologically normal cervical squamous cells (MNSCs) which are commonly used in cervical screening. Results showed that nanomechanical parameters of MNSCs correlate well with cervical malignancy, and may have potential in cancer screening to provide early diagnosis.Applying an atomic force microscope, we performed a nanomechanical analysis of morphologically normal cervical squamous cells (MNSCs) which are commonly used in cervical screening. Results showed that nanomechanical parameters of MNSCs correlate well with cervical malignancy, and may have potential in cancer screening to provide early diagnosis. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr03662c

Three-dimensional echocardiography of congenital abnormalities of the left atrioventricular valve.

PubMed

Rice, Kathryn; Simpson, John

2015-03-01

Congenital abnormalities of the left atrioventricular (AV) valve are a significant diagnostic challenge. Traditionally, reliance has been placed on two-dimensional echocardiographic (2DE) imaging to guide recognition of the specific morphological features. Real-time 3DE can provide unique views of the left AV valve with the potential to improve understanding of valve morphology and function to facilitate surgical planning. This review illustrates the features of congenital abnormalities of the left AV valve assessed by 3DE. The similarities and differences in morphology between different lesions are described, both with respect to the valve itself and supporting chordal apparatus. The potential advantages as well as limitations of this technique in clinical practice are outlined.

A device for emulating cuff recordings of action potentials propagating along peripheral nerves.

PubMed

Rieger, Robert; Schuettler, Martin; Chuang, Sheng-Chih

2014-09-01

This paper describes a device that emulates propagation of action potentials along a peripheral nerve, suitable for reproducible testing of bio-potential recording systems using nerve cuff electrodes. The system is a microcontroller-based stand-alone instrument which uses established nerve and electrode models to represent neural activity of real nerves recorded with a nerve cuff interface, taking into consideration electrode impedance, voltages picked up by the electrodes, and action potential propagation characteristics. The system emulates different scenarios including compound action potentials with selectable propagation velocities and naturally occurring nerve traffic from different velocity fiber populations. Measured results from a prototype implementation are reported and compared with in vitro recordings from Xenopus Laevis frog sciatic nerve, demonstrating that the electrophysiological setting is represented to a satisfactory degree, useful for the development, optimization and characterization of future recording systems.

Nerve Impulses in Plants

ERIC Educational Resources Information Center

Blatt, F. J.

1974-01-01

Summarizes research done on the resting and action potential of nerve impulses, electrical excitation of nerve cells, electrical properties of Nitella, and temperature effects on action potential. (GS)

Antibacterial Compounds of Canadian Honeys Target Bacterial Cell Wall Inducing Phenotype Changes, Growth Inhibition and Cell Lysis That Resemble Action of β-Lactam Antibiotics

PubMed Central

Brudzynski, Katrina; Sjaarda, Calvin

2014-01-01

Honeys show a desirable broad spectrum activity against Gram-positive and negative bacteria making antibacterial activity an intrinsic property of honey and a desirable source for new drug development. The cellular targets and underlying mechanism of action of honey antibacterial compounds remain largely unknown. To facilitate the target discovery, we employed a method of phenotypic profiling by directly comparing morphological changes in Escherichia coli induced by honeys to that of ampicillin, the cell wall-active β-lactam of known mechanism of action. Firstly, we demonstrated the purity of tested honeys from potential β-lactam contaminations using quantitative LC-ESI-MS. Exposure of log-phase E. coli to honey or ampicillin resulted in time- and concentration-dependent changes in bacterial cell shape with the appearance of filamentous phenotypes at sub-inhibitory concentrations and spheroplasts at the MBC. Cell wall destruction by both agents, clearly visible on microscopic micrographs, was accompanied by increased permeability of the lipopolysaccharide outer membrane as indicated by fluorescence-activated cell sorting (FACS). More than 90% E. coli exposed to honey or ampicillin became permeable to propidium iodide. Consistently with the FACS results, both honey-treated and ampicillin-treated E. coli cells released lipopolysaccharide endotoxins at comparable levels, which were significantly higher than controls (p<0.0001). E. coli cells transformed with the ampicillin-resistance gene (β–lactamase) remained sensitive to honey, displayed the same level of cytotoxicity, cell shape changes and endotoxin release as ampicillin-sensitive cells. As expected, β–lactamase protected the host cell from antibacterial action of ampicillin. Thus, both honey and ampicillin induced similar structural changes to the cell wall and LPS and that this ability underlies antibacterial activities of both agents. Since the cell wall is critical for cell growth and survival, honey active compounds would be highly applicable for therapeutic purposes while differences in the mode of action between honey and ampicillin may provide clinical advantage in eradicating β-lactam-resistant pathogens. PMID:25191847

Marinobufagin, a molecule from poisonous frogs, causes biochemical, morphological and cell cycle changes in human neoplasms and vegetal cells.

PubMed

Machado, Kátia da Conceição; Sousa, Lívia Queiroz de; Lima, Daisy Jereissati Barbosa; Soares, Bruno Marques; Cavalcanti, Bruno Coêlho; Maranhão, Sarah Sant'Anna; Noronha, Janaina da Costa de; Rodrigues, Domingos de Jesus; Militão, Gardenia Carmen Gadelha; Chaves, Mariana Helena; Vieira-Júnior, Gerardo Magela; Pessoa, Cláudia; Moraes, Manoel Odorico de; Sousa, João Marcelo de Castro E; Melo-Cavalcante, Ana Amélia de Carvalho; Ferreira, Paulo Michel Pinheiro

2018-03-15

Skin toad secretion present physiologically active molecules to protect them against microorganisms, predators and infections. This work detailed the antiproliferative action of marinobufagin on tumor and normal lines, investigate its mechanism on HL-60 leukemia cells and its toxic effects on Allium cepa meristematic cells. Initially, cytotoxic action was assessed by colorimetric assays. Next, HL-60 cells were analyzed by morphological and flow cytometry techniques and growing A. cepa roots were examined after 72 h exposure. Marinobufagin presented high antiproliferative action against all human tumor lines [IC 50 values ranging from 0.15 (leukemia) to 7.35 (larynx) μM] and it failed against human erythrocytes and murine lines. Human normal peripheral blood mononuclear cells (PBMC) were up to 72.5-fold less sensitive [IC 50: 10.88 μM] to marinobufagin than HL-60 line, but DNA strand breaks were no detected. Leukemia treaded cells exhibited cell viability reduction, DNA fragmentation, phosphatidylserine externalization, binucleation, nuclear condensation and cytoplasmic vacuoles. Marinobufagin also reduced the growth of A. cepa roots (EC 50 : 7.5 μM) and mitotic index, caused cell cycle arrest and chromosomal alterations (micronuclei, delays and C-metaphases) in meristematic cells. So, to find out partially targeted natural molecules on human leukemia cells, like marinobufagin, is an amazing and stimulating way to continue the battle against cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

Central Nervous System-Toxic Lidocaine Concentrations Unmask L-Type Ca²⁺ Current-Mediated Action Potentials in Rat Thalamocortical Neurons: An In Vitro Mechanism of Action Study.

PubMed

Putrenko, Igor; Ghavanini, Amer A; Meyer Schöniger, Katrin S; Schwarz, Stephan K W

2016-05-01

High systemic lidocaine concentrations exert well-known toxic effects on the central nervous system (CNS), including seizures, coma, and death. The underlying mechanisms are still largely obscure, and the actions of lidocaine on supraspinal neurons have received comparatively little study. We recently found that lidocaine at clinically neurotoxic concentrations increases excitability mediated by Na-independent, high-threshold (HT) action potential spikes in rat thalamocortical neurons. Our goal in this study was to characterize these spikes and test the hypothesis that they are generated by HT Ca currents, previously implicated in neurotoxicity. We also sought to identify and isolate the specific underlying subtype of Ca current. We investigated the actions of lidocaine in the CNS-toxic concentration range (100 μM-1 mM) on ventrobasal thalamocortical neurons in rat brain slices in vitro, using whole-cell patch-clamp recordings aided by differential interference contrast infrared videomicroscopy. Drugs were bath applied; action potentials were generated using current clamp protocols, and underlying currents were identified and isolated with ion channel blockers and electrolyte substitution. Lidocaine (100 μM-1 mM) abolished Na-dependent tonic firing in all neurons tested (n = 46). However, in 39 of 46 (85%) neurons, lidocaine unmasked evoked HT action potentials with lower amplitudes and rates of de-/repolarization compared with control. These HT action potentials remained during the application of tetrodotoxin (600 nM), were blocked by Cd (50 μM), and disappeared after superfusion with an extracellular solution deprived of Ca. These features implied that the unmasked potentials were generated by high-voltage-activated Ca channels and not by Na channels. Application of the L-type Ca channel blocker, nifedipine (5 μM), completely blocked the HT potentials, whereas the N-type Ca channel blocker, ω-conotoxin GVIA (1 μM), had little effect. At clinically CNS-toxic concentrations, lidocaine unmasked in thalamocortical neurons evoked HT action potentials mediated by the L-type Ca current while substantially suppressing Na-dependent excitability. On the basis of the known role of an increase in intracellular Ca in the pathogenesis of local anesthetic neurotoxicity, this novel action represents a plausible contributing candidate mechanism for lidocaine's CNS toxicity in vivo.

Morphological Plant Modeling: Unleashing Geometric and Topological Potential within the Plant Sciences

PubMed Central

Bucksch, Alexander; Atta-Boateng, Acheampong; Azihou, Akomian F.; Battogtokh, Dorjsuren; Baumgartner, Aly; Binder, Brad M.; Braybrook, Siobhan A.; Chang, Cynthia; Coneva, Viktoirya; DeWitt, Thomas J.; Fletcher, Alexander G.; Gehan, Malia A.; Diaz-Martinez, Diego Hernan; Hong, Lilan; Iyer-Pascuzzi, Anjali S.; Klein, Laura L.; Leiboff, Samuel; Li, Mao; Lynch, Jonathan P.; Maizel, Alexis; Maloof, Julin N.; Markelz, R. J. Cody; Martinez, Ciera C.; Miller, Laura A.; Mio, Washington; Palubicki, Wojtek; Poorter, Hendrik; Pradal, Christophe; Price, Charles A.; Puttonen, Eetu; Reese, John B.; Rellán-Álvarez, Rubén; Spalding, Edgar P.; Sparks, Erin E.; Topp, Christopher N.; Williams, Joseph H.; Chitwood, Daniel H.

2017-01-01

The geometries and topologies of leaves, flowers, roots, shoots, and their arrangements have fascinated plant biologists and mathematicians alike. As such, plant morphology is inherently mathematical in that it describes plant form and architecture with geometrical and topological techniques. Gaining an understanding of how to modify plant morphology, through molecular biology and breeding, aided by a mathematical perspective, is critical to improving agriculture, and the monitoring of ecosystems is vital to modeling a future with fewer natural resources. In this white paper, we begin with an overview in quantifying the form of plants and mathematical models of patterning in plants. We then explore the fundamental challenges that remain unanswered concerning plant morphology, from the barriers preventing the prediction of phenotype from genotype to modeling the movement of leaves in air streams. We end with a discussion concerning the education of plant morphology synthesizing biological and mathematical approaches and ways to facilitate research advances through outreach, cross-disciplinary training, and open science. Unleashing the potential of geometric and topological approaches in the plant sciences promises to transform our understanding of both plants and mathematics. PMID:28659934

Associations between sperm abnormalities, breed, age, and scrotal circumference in beef bulls

PubMed Central

Menon, Ajitkumar G.; Barkema, Herman W.; Wilde, Randy; Kastelic, John P.; Thundathil, Jacob C.

2011-01-01

The objectives of this study were to determine the associations of breed, age, and scrotal circumference (SC), and their interaction, on the prevalence of sperm abnormalities in beef bulls in Alberta, Canada, and the percentage of satisfactory potential breeders identified during breeding soundness examination solely due to normal sperm morphology. Eosin-nigrosin stained semen smears and evaluation reports of 1642 bull breeding soundness evaluations were procured from 6 veterinary clinics in Alberta. Sperm morphology was determined for at least 100 sperm per bull. The most common defects were detached head [4.86% ± 5.71%; mean ± standard deviation (s)], distal midpiece reflex (6.19% ± 9.13%), and bent tail (1.01% ± 1.54%). Although breed, age, and SC did not significantly affect the prevalence of head or midpiece defects, morphologically normal or abnormal sperm, tail defects were more prevalent in Angus and Hereford bulls compared with other breeds. Overall, solely on the basis of sperm morphology, 1363 (83.0%) bulls were classified as satisfactory potential breeders and the remainder 279 (17.0%) as unsatisfactory (> 30% abnormal sperm, > 20% defective heads, or both). Although not significantly different, the breed with the highest percentage of satisfactory potential breeders was Limousin (90.6%) and the lowest was Hereford (78.8%). That 17% of bulls subjected to breeding soundness evaluation were designated as unsatisfactory solely on the basis of sperm morphology highlights its importance. PMID:22468020

An intracellular analysis of the visual responses of neurones in cat visual cortex.

PubMed Central

Douglas, R J; Martin, K A; Whitteridge, D

1991-01-01

1. Extracellular and intracellular recordings were made from neurones in the visual cortex of the cat in order to compare the subthreshold membrane potentials, reflecting the input to the neurone, with the output from the neurone seen as action potentials. 2. Moving bars and edges, generated under computer control, were used to stimulate the neurones. The membrane potential was digitized and averaged for a number of trials after stripping the action potentials. Comparison of extracellular and intracellular discharge patterns indicated that the intracellular impalement did not alter the neurones' properties. Input resistance of the neurone altered little during stable intracellular recordings (30 min-2 h 50 min). 3. Intracellular recordings showed two distinct patterns of membrane potential changes during optimal visual stimulation. The patterns corresponded closely to the division of S-type (simple) and C-type (complex) receptive fields. Simple cells had a complex pattern of membrane potential fluctuations, involving depolarizations alternating with hyperpolarizations. Complex cells had a simple single sustained plateau of depolarization that was often followed but not preceded by a hyperpolarization. In both simple and complex cells the depolarizations led to action potential discharges. The hyperpolarizations were associated with inhibition of action potential discharge. 4. Stimulating simple cells with non-optimal directions of motion produced little or no hyperpolarization of the membrane in most cases, despite a lack of action potential output. Directional complex cells always produced a single plateau of depolarization leading to action potential discharge in both the optimal and non-optimal directions of motion. The directionality could not be predicted on the basis of the position of the hyperpolarizing inhibitory potentials found in the optimal direction. 5. Stimulation of simple cells with non-optimal orientations occasionally produced slight hyperpolarizations and inhibition of action potential discharge. Complex cells, which had broader orientation tuning than simple cells, could show marked hyperpolarization for non-optimal orientations, but this was not generally the case. 6. The data do not support models of directionality and orientation that rely solely on strong inhibitory mechanisms to produce stimulus selectivity. PMID:1804981

In vivo imaging of cardiac development and function in zebrafish using light sheet microscopy.

PubMed

Weber, Michael; Huisken, Jan

2015-01-01

Detailed studies of heart development and function are crucial for our understanding of cardiac failures and pave the way for better diagnostics and treatment. However, the constant motion and close incorporation into the cardiovascular system prevent in vivo studies of the living, unperturbed heart. The complementary strengths of the zebrafish model and light sheet microscopy provide a useful platform to fill this gap. High-resolution images of the embryonic vertebrate heart are now recorded from within the living animal: deep inside the unperturbed heart we can follow cardiac contractions and measure action potentials and calcium transients. Three-dimensional reconstructions of the entire beating heart with cellular resolution give new insights into its ever-changing morphology and facilitate studies into how individual cells form the complex cardiac network. In addition, cardiac dynamics and robustness are now examined with targeted optical manipulation. Overall, the combination of zebrafish and light sheet microscopy represents a promising addition for cardiac research and opens the door to a better understanding of heart function and development.

On biogenicity criteria for endolithic microborings on early Earth and beyond.

PubMed

McLoughlin, Nicola; Brasier, Martin D; Wacey, David; Green, Owen R; Perry, Randall S

2007-02-01

Micron-sized cavities created by the actions of rock-etching microorganisms known as euendoliths are explored as a biosignature for life on early Earth and perhaps Mars. Rock-dwelling organisms can tolerate extreme environmental stresses and are excellent candidates for the colonization of early Earth and planetary surfaces. Here, we give a brief overview of the fossil record of euendoliths in both sedimentary and volcanic rocks. We then review the current understanding of the controls upon the distribution of euendolithic microborings and use these to propose three lines of approach for testing their biogenicity: first, a geological setting that demonstrates a syngenetic origin for the euendolithic microborings; second, microboring morphologies and distributions that are suggestive of biogenic behavior and distinct from ambient inclusion trails; and third, elemental and isotopic evidence suggestive of biological processing. We use these criteria and the fossil record of terrestrial euendoliths to outline potential environments and techniques to search for endolithic microborings on Mars.

1,3,4-Thiadiazole derivatives of R-(+)-limonene benzaldehyde-thiosemicarbazones cause death in Trypanosoma cruzi through oxidative stress.

PubMed

Martins, Solange C; Lazarin-Bidóia, Danielle; Desoti, Vânia C; Falzirolli, Hugo; da Silva, Cleuza C; Ueda-Nakamura, Tania; Silva, Sueli de O; Nakamura, Celso V

2016-12-01

This work evaluated the in vitro and in vivo activity of TDZ 2 on Trypanosoma cruzi amastigotes and determined the possible mechanism of action of this compound on T. cruzi death. TDZ 2 inhibited T. cruzi proliferation in vitro and had low haemolytic potential. It also induced morphological and ultrastructural alterations. We observed a reduction of cell volume, the depolarization of the mitochondrial membrane, an increase in ROS production, lipoperoxidation of the cell membrane, lipid bodies formation and production of nitric oxide, a decrease in reduced thiols levels and, presence of autophagic vacuoles. The in vivo study found a reduction of parasitemia in animals treated with TDZ 2 alone or combined with benznidazole. Altogether, the alterations induced by TDZ 2 point to an oxidative stress condition that lead to T. cruzi cell death. Copyright © 2016 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Synthesis characterization and catalytic action of hexagonal gold nanoparticles using essential oils extracted from Anacardium occidentale

NASA Astrophysics Data System (ADS)

Sheny, D. S.; Mathew, Joseph; Philip, Daizy

2012-11-01

A new phytochemical method for the synthesis of gold nanoparticles is reported. The essential oils extracted from the fresh leaves of Anacardium occidentale are used for the reduction of auric acid to Au nanoparticles (NPs). The formation and morphology of synthesized NPs are investigated with the help of UV-visible, TEM and FTIR spectroscopy. The NPs synthesized at room temperature are mono-dispersed and hexagonal in shape with an average size of 36 nm while those prepared at higher temperature are composed of a mixture of anisotropic particles. The UV-visible absorption spectra of these anisotropic NPs show asymmetry in the longer wavelength side. The quantity of oil is an important criterion modulating the shape of NPs. Possible biochemical mechanism leading to the formation of NPs is studied using FTIR spectroscopy. The potential of synthesized Au NPs as catalyst is explored for the hydrogenation of p-nitro phenol to p-amino phenol at room temperature.

The mechanisms of repetitive spike generation in an axonless retinal interneuron

PubMed Central

Cembrowski, Mark S.; Logan, Stephen M.; Tian, Miao; Jia, Li; Li, Wei; Kath, William L.; Riecke, Hermann; Singer, Joshua H.

2012-01-01

SUMMARY Several types of retinal interneurons exhibit spikes but lack axons. One such neuron is the AII amacrine cell, in which spikes recorded at the soma exhibit small amplitudes (<10 mV) and broad time courses (>5 ms). Here, we used electrophysiological recordings and computational analysis to examine the mechanisms underlying this atypical spiking. We found that somatic spikes likely represent large, brief action potential-like events initiated in a single, electrotonically-distal dendritic compartment. In this same compartment, spiking undergoes slow modulation, likely by an M-type K conductance. The structural correlate of this compartment is a thin neurite that extends from the primary dendritic tree: local application of TTX to this neurite, or excision of it, eliminates spiking. Thus, the physiology of the axonless AII is much more complex than would be anticipated from morphological descriptions and somatic recordings; in particular, the AII possesses a single dendritic structure that controls its firing pattern. PMID:22832164

Reversibility of electrophysiological changes induced by chronic high-altitude hypoxia in adult rat heart.

PubMed

Chouabe, C; Amsellem, J; Espinosa, L; Ribaux, P; Blaineau, S; Mégas, P; Bonvallet, R

2002-04-01

Recent studies indicate that regression of left ventricular hypertrophy normalizes membrane ionic current abnormalities. This work was designed to determine whether regression of right ventricular hypertrophy induced by permanent high-altitude exposure (4,500 m, 20 days) in adult rats also normalizes changes of ventricular myocyte electrophysiology. According to the current data, prolonged action potential, decreased transient outward current density, and increased inward sodium/calcium exchange current density normalized 20 days after the end of altitude exposure, whereas right ventricular hypertrophy evidenced by both the right ventricular weight-to-heart weight ratio and the right ventricular free wall thickness measurement normalized 40 days after the end of altitude exposure. This morphological normalization occurred at both the level of muscular tissue, as shown by the decrease toward control values of some myocyte parameters (perimeter, capacitance, and width), and the level of the interstitial collagenous connective tissue. In the chronic high-altitude hypoxia model, the regression of right ventricular hypertrophy would not be a prerequisite for normalization of ventricular electrophysiological abnormalities.

Synthesis characterization and catalytic action of hexagonal gold nanoparticles using essential oils extracted from Anacardium occidentale.

PubMed

Sheny, D S; Mathew, Joseph; Philip, Daizy

2012-11-01

A new phytochemical method for the synthesis of gold nanoparticles is reported. The essential oils extracted from the fresh leaves of Anacardium occidentale are used for the reduction of auric acid to Au nanoparticles (NPs). The formation and morphology of synthesized NPs are investigated with the help of UV-visible, TEM and FTIR spectroscopy. The NPs synthesized at room temperature are mono-dispersed and hexagonal in shape with an average size of 36 nm while those prepared at higher temperature are composed of a mixture of anisotropic particles. The UV-visible absorption spectra of these anisotropic NPs show asymmetry in the longer wavelength side. The quantity of oil is an important criterion modulating the shape of NPs. Possible biochemical mechanism leading to the formation of NPs is studied using FTIR spectroscopy. The potential of synthesized Au NPs as catalyst is explored for the hydrogenation of p-nitro phenol to p-amino phenol at room temperature. Copyright © 2012 Elsevier B.V. All rights reserved.

Phenotypic and genomic characterization of the antimicrobial producer Rheinheimera sp. EpRS3 isolated from the medicinal plant Echinacea purpurea: insights into its biotechnological relevance.

PubMed

Presta, Luana; Bosi, Emanuele; Fondi, Marco; Maida, Isabel; Perrin, Elena; Miceli, Elisangela; Maggini, Valentina; Bogani, Patrizia; Firenzuoli, Fabio; Di Pilato, Vincenzo; Rossolini, Gian Maria; Mengoni, Alessio; Fani, Renato

2017-04-01

In recent years, there has been increasing interest in plant microbiota; however, despite medicinal plant relevance, very little is known about their highly complex endophytic communities. In this work, we report on the genomic and phenotypic characterization of the antimicrobial compound producer Rheinheimera sp. EpRS3, a bacterial strain isolated from the rhizospheric soil of the medicinal plant Echinacea purpurea. In particular, EpRS3 is able to inhibit growth of different bacterial pathogens (Bcc, Acinetobacter baumannii, and Klebsiella pneumoniae) which might be related to the presence of gene clusters involved in the biosynthesis of different types of secondary metabolites. The outcomes presented in this work highlight the fact that the strain possesses huge biotechnological potential; indeed, it also shows antimicrobial effects upon well-described multidrug-resistant (MDR) human pathogens, and it affects plant root elongation and morphology, mimicking indole acetic acid (IAA) action. Copyright © 2016 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Morin protects gastric mucosa from nonsteroidal anti-inflammatory drug, indomethacin induced inflammatory damage and apoptosis by modulating NF-κB pathway.

PubMed

Sinha, Krishnendu; Sadhukhan, Pritam; Saha, Sukanya; Pal, Pabitra Bikash; Sil, Parames C

2015-04-01

Deregulation in prostaglandin (PG) biosynthesis, severe oxidative stress, inflammation and apoptosis contribute to the pathogenesis of nonsteroidal anti-inflammatory drug (NSAID)-induced gastropathy. Unfortunately, most of the prescribed anti-ulcer drugs generate various side effects. In this scenario, we could consider morin as a safe herbal potential agent against IND-gastropathy and rationalize its action systematically. Rats were pretreated with morin for 30 min followed by IND (48 mgkg(-1)) administration for 4 h. The anti-ulcerogenic nature of morin was assessed by morphological and histological analysis. Its effects on the inflammatory (MPO, cytokines, adhesion molecules), ulcer-healing (COXs, PGE(2)), and signaling parameters (NF-κB and apoptotic signaling) were assessed by biochemical, RP-HPLC, immunoblots, IHC, RT-PCR, and ELISA at the time points of their maximal changes due to IND administration. IND induced NF-κB and apoptotic signaling in rat's gastric mucosa. These increased proinflammatory responses, but reduced the antioxidant enzymes and other protective factors. Morin reversed all the adverse effects to prevent IND-induced gastric ulceration in a PGE2 independent manner. Also, it did not affect the absorption and/or primary pharmacological activity of IND. The gastroprotective action of morin is primarily attributed to its potent antioxidant nature that also helps in controlling several IND-induced inflammatory responses. For the first time, the study reveals a mechanistic basis of morin mediated protective action against IND-induced gastropathy. As morin is a naturally abundant safe antioxidant, future detailed pharmacokinetic and pharmacodynamic studies are expected to establish it as a gastroprotective agent. Copyright © 2015 Elsevier B.V. All rights reserved.

Profile of neuronal excitation following selective activation of the neurokinin-1 receptor in rat deep dorsal horn in vitro.

PubMed

King, A E; Ackley, M A; Slack, J R

1997-08-29

The excitatory actions of the selective neurokinin-1 receptor (NK1R) agonist [Sar9,Met(O2)11]substance P (SP) were tested on a sample (n = 50) of deep dorsal horn neurones in the isolated and hemisected young rat spinal cord. Superfusion of the NK1R agonist (2 microM) elicited a prolonged membrane depolarisation (6.6 +/- 0.5 mV) and an increase in action potential firing in 41/50 (82%) neurones. These [Sar9,Met(O2)11]SP-induced depolarisations were attenuated by the selective NK1R antagonist GR82334 (1 microM). An increased neuronal excitability after [Sar9,Met(O2)11]SP application was indicated by an augmented spike frequency generated in response to long duration, step depolarisations. In order to assess whether a direct excitatory action existed, [Sar9,Met(O2)11]SP was re-tested on a sample of TTX-treated neurones (n = 14). The majority (9/14) retained agonist sensitivity although the amplitude of the depolarisation was reduced to 48% of the control value. A sample of neurones (n = 7) that responded to the NK1R agonist were morphologically characterised after filling with the intracellular dye, biocytin. Dorsal dendrites that clearly penetrated lamina II and that could receive a direct C-afferent input, were identified in only 2/7 neurones. These electrophysiological and neuroanatomical data demonstrate that deep dorsal horn neurones possess functional NK1Rs. The implications of the existence of these NK1Rs in the context of spinal somatosensory systems and SP is considered.

Towards a glutamate hypothesis of depression

PubMed Central

Sanacora, Gerard; Treccani, Giulia; Popoli, Maurizio

2011-01-01

Half a century after the first formulation of the monoamine hypothesis, compelling evidence implies that long-term changes in an array of brain areas and circuits mediating complex cognitive-emotional behaviors represent the biological underpinnings of mood/anxiety disorders. A large number of clinical studies suggest that pathophysiology is associated with dysfunction of the predominant glutamatergic system, malfunction in the mechanisms regulating clearance and metabolism of glutamate, and cytoarchitectural/morphological maladaptive changes in a number of brain areas mediating cognitive-emotional behaviors. Concurrently, a wealth of data from animal models have shown that different types of environmental stress enhance glutamate release/transmission in limbic/cortical areas and exert powerful structural effects, inducing dendritic remodeling, reduction of synapses and possibly volumetric reductions resembling those observed in depressed patients. Because a vast majority of neurons and synapses in these areas and circuits use glutamate as neurotransmitter, it would be limiting to maintain that glutamate is in some way ‘involved’ in mood/anxiety disorders; rather it should be recognized that the glutamatergic system is a primary mediator of psychiatric pathology and, potentially, also a final common pathway for the therapeutic action of antidepressant agents. A paradigm shift from a monoamine hypothesis of depression to a neuroplasticity hypothesis focused on glutamate may represent a substantial advancement in the working hypothesis that drives research for new drugs and therapies. Importantly, despite the availability of multiple classes of drugs with monoamine-based mechanisms of action, there remains a large percentage of patients who fail to achieve a sustained remission of depressive symptoms. The unmet need for improved pharmacotherapies for treatment-resistant depression means there is a large space for the development of new compounds with novel mechanisms of action such as glutamate transmission and related pathways. PMID:21827775

Disruption of testosterone homeostasis as a mode of action for the reproductive toxicity of triazole fungicides in the male rat.

PubMed

Goetz, Amber K; Ren, Hongzu; Schmid, Judith E; Blystone, Chad R; Thillainadarajah, Inthirany; Best, Deborah S; Nichols, Harriette P; Strader, Lillian F; Wolf, Douglas C; Narotsky, Michael G; Rockett, John C; Dix, David J

2007-01-01

Triazole fungicides associated with a range of reported male reproductive effects in experimental animals were selected to assess potential toxic modes of action. Wistar Han rats were fed myclobutanil (M: 100, 500, or 2000 ppm), propiconazole (P: 100, 500, or 2500 ppm), or triadimefon (T: 100, 500, or 1800 ppm) from gestation day 6 to postnatal day (PND) 120. One male per litter was necropsied on PND1, 22, 50, or 92. Measurements included anogenital distance (AGD) at PND0, body and organ weights, serum hormone levels, age at preputial separation (PPS), sperm morphology and motility, and fertility and fecundity. AGD was increased by the high dose of all three triazoles, indicating hypervirilization. Triadimefon delayed PPS, consistent with delayed puberty, at 1800 ppm. Relative liver weights were increased at PND1, 50, and 92 by all three triazoles. Hepatocellular hypertrophy was present at PND50 from propiconazole and triadimefon and at PND92 from all three high-dose triazole treatments. Relative pituitary weights were decreased at PND92 by middle- and high-dose myclobutanil treatment. Absolute testis weights were increased at PND1 by myclobutanil, at PND22 by myclobutanil and triadimefon, and at PND50 by propiconazole and triadimefon treatment. Relative ventral prostate weights were increased at PND92 by myclobutanil and triadimefon treatment. Serum testosterone was increased at PND50 by triadimefon and at PND92/99 by all three triazole treatments. Insemination and fertility were impaired by myclobutanil and triadimefon treatment. In addition to the reproductive system effects, total serum thyroxine levels were decreased at PND92 by high-dose triadimefon. These reproductive effects are consistent with the disruption of testosterone homeostasis as a key event in the mode of action for triazole-induced reproductive toxicity.

Antitumor effectiveness and mechanism of action of Ru(II)/amino acid/diphosphine complexes in the peritoneal carcinomatosis progression.

PubMed

Mello-Andrade, Francyelli; da Costa, Wanderson Lucas; Pires, Wanessa Carvalho; Pereira, Flávia de Castro; Cardoso, Clever Gomes; Lino-Junior, Ruy de Souza; Irusta, Vicente Raul Chavarria; Carneiro, Cristiene Costa; de Melo-Reis, Paulo Roberto; Castro, Carlos Henrique; Almeida, Marcio Aurélio Pinheiro; Batista, Alzir Azevedo; Silveira-Lacerda, Elisângela de Paula

2017-10-01

Peritoneal carcinomatosis is considered as a potentially lethal clinical condition, and the therapeutic options are limited. The antitumor effectiveness of the [Ru(l-Met)(bipy)(dppb)]PF 6 (1) and the [Ru(l-Trp)(bipy)(dppb)]PF 6 (2) complexes were evaluated in the peritoneal carcinomatosis model, Ehrlich ascites carcinoma-bearing Swiss mice. This is the first study that evaluated the effect of Ru(II)/amino acid complexes for antitumor activity in vivo. Complexes 1 and 2 (2 and 6 mg kg -1 ) showed tumor growth inhibition ranging from moderate to high. The mean survival time of animal groups treated with complexes 1 and 2 was higher than in the negative and vehicle control groups. The induction of Ehrlich ascites carcinoma in mice led to alterations in hematological and biochemical parameters, and not the treatment with complexes 1 and 2. The treatment of Ehrlich ascites carcinoma-bearing mice with complexes 1 and 2 increased the number of Annexin V positive cells and cleaved caspase-3 levels and induced changes in the cell morphology and in the cell cycle phases by induction of sub-G1 and G0/G1 cell cycle arrest. In addition, these complexes reduce angiogenesis induced by Ehrlich ascites carcinoma cells in chick embryo chorioallantoic membrane model. The treatment with the LAT1 inhibitor decreased the sensitivity of the Ehrlich ascites carcinoma cells to complexes 1 and 2 in vitro-which suggests that the LAT1 could be related to the mechanism of action of amino acid/ruthenium(II) complexes, consequently decreasing the glucose uptake. Therefore, these complexes could be used to reduce tumor growth and increase mean survival time with less toxicity than cisplatin. Besides, these complexes induce apoptosis by combination of different mechanism of action.

Inhibition of metastatic potential of B16-F10 melanoma cell line in vivo and in vitro by biflorin.

PubMed

Andrade Carvalho, Adriana; da Costa, Patrícia Marçal; Da Silva Souza, Luciana Gregório; Lemos, Telma Leda G; Alves, Ana Paula Negreiros Nunes; Pessoa, Cláudia; de Moraes, Manoel Odorico

2013-08-14

The aim of this study was to determine the antimetastatic potential of biflorin using in vivo and in vitro approaches. Biflorin was isolated from Capraria biflora collected in Fortaleza, Ceará, Brazil. Adhesion, migration and invasion assays were performed to avail of the antimetastatic potential of this quinone. Experimental metastasis was performed to avail of the antimetastatic potential of bilflorin using in vivo assay. Treatment with biflorin (25 and 50mg/kg/day) was shown to be effective in reducing B16-F10 melanoma metastasis in C57BL/6 mice. The administration of biflorin at 25mg/kg/day intraperitoneally inhibited the formation of metastases by about 57% compared to untreated control animals. When the animals were treated with 50mg/kg/day intraperitoneally, there was a 71% decrease in the number of lung metastases. Morphological assays showed the presence of hemosiderin and erythrocytes in the lung parenchyma, indicating the occurrence of hemorrhage, probably a side effect of biflorin. Biflorin at non-toxic concentrations (0.5, 1.0 and 1.5g/mL) was tested directly on B16-F10 cells in vitro, and it inhibited cell adhesion to type I collagen and cell motility using the wound-healing assay. These data suggest that biflorin has a promising antimetastatic potential, as shown by its anti-adhesion, anti-migration and anti-invasion properties against a metastatic melanoma cell line. However, further studies are essential to elucidate its mechanism of action. Copyright © 2013 Elsevier Inc. All rights reserved.

Growth potential limits drought morphological plasticity in seedlings from six Eucalyptus provenances.

PubMed

Maseda, Pablo H; Fernández, Roberto J

2016-02-01

Water stress modifies plant above- vs belowground biomass allocation, i.e., morphological plasticity. It is known that all species and genotypes reduce their growth rate in response to stress, but in the case of water stress it is unclear whether the magnitude of such reduction is linked to the genotype's growth potential, and whether the reduction can be largely attributed to morphological adjustments such as plant allocation and leaf and root anatomy. We subjected seedlings of six seed sources, three from each of Eucalyptus camaldulensis (potentially fast growing) and E. globulus (inherently slow growing), to three experimental water regimes. Biomass, leaf area and root length were measured in a 6-month glasshouse experiment. We then performed functional growth analysis of relative growth rate (RGR), and aboveground (leaf area ratio (LAR), specific leaf area (SLA) and leaf mass ratio (LMR)) and belowground (root length ratio (RLR), specific root length (SRL) and root mass ratio (RMR)) morphological components. Total biomass, root biomass and leaf area were reduced for all Eucalyptus provenances according to drought intensity. All populations exhibited drought plasticity, while those of greater growth potential (RGRmax) had a larger reduction in growth (discounting the effect of size). A positive correlation was observed between drought sensitivity and RGRmax. Aboveground, drought reduced LAR and LMR; under severe drought a negative correlation was found between LMR and RGRmax. Belowground, drought reduced SRL but increased RMR, resulting in no change in RLR. Under severe drought, a negative correlation was found between RLR, SRL and RGRmax. Our evidence strongly supports the classic ecophysiological trade-off between growth potential and drought tolerance for woody seedlings. It also suggests that slow growers would have a low capacity to adjust their morphology. For shoots, this constraint on plasticity was best observed in partition (i.e., LMR) whereas for roots it was clearest in morphology/anatomy (i.e., SRL). Thus, a low RGRmax would limit plastic response to drought not only at the whole plant level but also at the organ and even the tissue level. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Effect of morphology on the non-ohmic conduction in ZnO nanostructures

NASA Astrophysics Data System (ADS)

Praveen, E.; Jayakumar, K.

2016-05-01

Nanostructures of ZnO is synthesized with nanoflower like morphology by simple wet chemical method. The structural, morphological and electrical characterization have been carried out. The temperature dependent electrical characterization of ZnO pellets of thickness 1150 µm is made by the application of 925MPa pressure. The morphological dependence of non-ohmic conduction beyond some arbitrary tunneling potential and grain boundary barrier thickness is compared with the commercially available bulk ZnO. Our results show the suitability of nano-flower like ZnO for the devices like sensors, rectifiers etc.

Staff Handbook on Natural Gas.

ERIC Educational Resources Information Center

Gorges, H. A., Ed.; Raine, L. P., Ed.

The Department of Commerce created a Natural Gas Action Group early in the fall of 1975 to assist industrial firms and the communities they serve to cope with the effects of potentially severe and crippling curtailment situations. This action group was trained to assess a specific local situation, review the potential for remedial action and…

75 FR 43072 - Trichoderma Hamatum Isolate 382; Exemption from the Requirement of a Tolerance

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-23

... Information A. Does this Action Apply to Me? You may be potentially affected by this action if you are an agricultural producer, food manufacturer, or pesticide manufacturer. Potentially affected entities may include... exhaustive, but rather provides a guide for readers regarding entities likely to be affected by this action...

Remodelling of action potential and intracellular calcium cycling dynamics during subacute myocardial infarction promotes ventricular arrhythmias in Langendorff-perfused rabbit hearts

PubMed Central

Chou, Chung-Chuan; Zhou, Shengmei; Hayashi, Hideki; Nihei, Motoki; Liu, Yen-Bin; Wen, Ming-Shien; Yeh, San-Jou; Fishbein, Michael C; Weiss, James N; Lin, Shien-Fong; Wu, Delon; Chen, Peng-Sheng

2007-01-01

We hypothesize that remodelling of action potential and intracellular calcium (Cai) dynamics in the peri-infarct zone contributes to ventricular arrhythmogenesis in the postmyocardial infarction setting. To test this hypothesis, we performed simultaneous optical mapping of Cai and membrane potential (Vm) in the left ventricle in 15 rabbit hearts with myocardial infarction for 1 week. Ventricular premature beats frequently originated from the peri-infarct zone, and 37% showed elevation of Cai prior to Vm depolarization, suggesting reverse excitation–contraction coupling as their aetiology. During electrically induced ventricular fibrillation, the highest dominant frequency was in the peri-infarct zone in 61 of 70 episodes. The site of highest dominant frequency had steeper action potential duration restitution and was more susceptible to pacing-induced Cai alternans than sites remote from infarct. Wavebreaks during ventricular fibrillation tended to occur at sites of persistently elevated Cai. Infusion of propranolol flattened action potential duration restitution, reduced wavebreaks and converted ventricular fibrillation to ventricular tachycardia. We conclude that in the subacute phase of myocardial infarction, the peri-infarct zone exhibits regions with steep action potential duration restitution slope and unstable Cai dynamics. These changes may promote ventricular extrasystoles and increase the incidence of wavebreaks during ventricular fibrillation. Whereas increased tissue heterogeneity after subacute myocardial infarction creates a highly arrhythmogenic substrate, dynamic action potential and Cai cycling remodelling also contribute to the initiation and maintenance of ventricular fibrillation in this setting. PMID:17272354

Components of action potential repolarization in cerebellar parallel fibres.

PubMed

Pekala, Dobromila; Baginskas, Armantas; Szkudlarek, Hanna J; Raastad, Morten

2014-11-15

Repolarization of the presynaptic action potential is essential for transmitter release, excitability and energy expenditure. Little is known about repolarization in thin, unmyelinated axons forming en passant synapses, which represent the most common type of axons in the mammalian brain's grey matter.We used rat cerebellar parallel fibres, an example of typical grey matter axons, to investigate the effects of K(+) channel blockers on repolarization. We show that repolarization is composed of a fast tetraethylammonium (TEA)-sensitive component, determining the width and amplitude of the spike, and a slow margatoxin (MgTX)-sensitive depolarized after-potential (DAP). These two components could be recorded at the granule cell soma as antidromic action potentials and from the axons with a newly developed miniaturized grease-gap method. A considerable proportion of fast repolarization remained in the presence of TEA, MgTX, or both. This residual was abolished by the addition of quinine. The importance of proper control of fast repolarization was demonstrated by somatic recordings of antidromic action potentials. In these experiments, the relatively broad K(+) channel blocker 4-aminopyridine reduced the fast repolarization, resulting in bursts of action potentials forming on top of the DAP. We conclude that repolarization of the action potential in parallel fibres is supported by at least three groups of K(+) channels. Differences in their temporal profiles allow relatively independent control of the spike and the DAP, whereas overlap of their temporal profiles provides robust control of axonal bursting properties.

Morphological alterations induced by boric acid and fipronil in the midgut of worker honeybee (Apis mellifera L.) larvae : Morphological alterations in the midgut of A. mellifera.

PubMed

da Silva Cruz, Aline; da Silva-Zacarin, Elaine C M; Bueno, Odair C; Malaspina, Osmar

2010-04-01

Morphological alterations, by means of histological and ultrastructural analysis, have been used to determine the effects of boric acid and fipronil on midgut tissues of honeybee worker, Apis mellifera L. larvae. In order to observe possible morphological alterations in the midgut, two groups of bioassays were performed. In the first one, the larvae were chronically treated with different concentrations of boric acid added to the food (1.0, 2.5 and 7.5 mg/g). In the second group, the larvae were fed with diets containing different concentrations of fipronil (0.1 and 1 microg/g) and compared with control groups without these chemical compounds. In the first bioassay, the larvae were collected on day 3 and in the second bioassay on day 4, when the mortality rate obtained in the toxicological bioassay was not very high. The larval midguts were removed and processed for morphological analyses using a light and transmission electron microscopy. We observed cytoplasmic vacuolizations, with the absence of autophagic vacuoles, and chromatinic compacting in most of the cells in the groups treated with pesticides. The morphological alterations were far greater in the larvae treated with boric acid than in the larvae treated with fipronil. Our data suggest that the midgut cell death observed was in response to boric acid and fipronil action. This study significantly improves the understanding of the toxicological effect of these insecticides from the ecotoxicological perspective.

Activation of cannabinoid CB1 receptors modulates evoked action potentials in rat retinal ganglion cells.

PubMed

Jiang, Shu-Xia; Li, Qian; Wang, Xiao-Han; Li, Fang; Wang, Zhong-Feng

2013-08-25

Activation of cannabinoid CB1 receptors (CB1Rs) regulates a variety of physiological functions in the vertebrate retina through modulating various types of ion channels. The aim of the present study was to investigate the effects of this receptor on cell excitability of rat retinal ganglion cells (RGCs) in retinal slices using whole-cell patch-clamp techniques. The results showed that under current-clamped condition perfusing WIN55212-2 (WIN, 5 μmol/L), a CB1R agonist, did not significantly change the spontaneous firing frequency and resting membrane potential of RGCs. In the presence of cocktail synaptic blockers, including excitatory postsynaptic receptor blockers CNQX and D-APV, and inhibitory receptor blockers bicuculline and strychnine, perfusion of WIN (5 μmol/L) hardly changed the frequencies of evoked action potentials by a series of positive current injection (from +10 to +100 pA). Phase-plane plot analysis showed that both average threshold voltage for triggering action potential and delay time to reach threshold voltage were not affected by WIN. However, WIN significantly decreased +dV/dtmax and -dV/dtmax of action potentials, suggestive of reduced rising and descending velocities of action potentials. The effects of WIN were reversed by co-application of SR141716, a CB1R selective antagonist. Moreover, WIN did not influence resting membrane potential of RGCs with synaptic inputs being blocked. These results suggest that activation of CB1Rs may regulate intrinsic excitability of rat RGCs through modulating evoked action potentials.

Strategies for improving neural signal detection using a neural-electronic interface.

PubMed

Szlavik, Robert B

2003-03-01

There have been various theoretical and experimental studies presented in the literature that focus on interfacing neurons with discrete electronic devices, such as transistors. From both a theoretical and experimental perspective, these studies have emphasized the variability in the characteristics of the detected action potential from the nerve cell. The demonstrated lack of reproducible fidelity of the nerve cell action potential at the device junction would make it impractical to implement these devices in any neural prosthetic application where reliable detection of the action potential was a prerequisite. In this study, the effects of several different physical parameters on the fidelity of the detected action potential at the device junction are investigated and discussed. The impact of variations in the extracellular resistivity, which directly affects the junction seal resistance, is studied along with the impact of variable nerve cell membrane capacitance and variations in the injected charge. These parameters are discussed in the context of their suitability to design manipulation for the purpose of improving the fidelity of the detected neural action potential. In addition to investigating the effects of variations in these parameters, the applicability of the linear equivalent circuit approach to calculating the junction potential is investigated.

Simulation of action potentials from metabolically impaired cardiac myocytes. Role of ATP-sensitive K+ current.

PubMed

Ferrero, J M; Sáiz, J; Ferrero, J M; Thakor, N V

1996-08-01

The role of the ATP-sensitive K+ current (IK-ATP) and its contribution to electrophysiological changes that occur during metabolic impairment in cardiac ventricular myocytes is still being discussed. The aim of this work was to quantitatively study this issue by using computer modeling. A model of IK-ATP is formulated and incorporated into the Luo-Rudy ionic model of the ventricular action potential. Action potentials under different degrees of activation of IK-ATP are simulated. Our results show that in normal ionic concentrations, only approximately 0.6% of the KATP channels, when open, should account for a 50% reduction in action potential duration. However, increased levels of intracellular Mg2+ counteract this shortening. Under conditions of high [K+]0, such as those found in early ischemia, the activation of only approximately 0.4% of the KATP channels could account for a 50% reduction in action potential duration. Thus, our results suggest that opening of IK-ATP channels should play a significant role in action potential shortening during hypoxic/ischemic episodes, with the fraction of open channels involved being very low ( < 1%). However, the results of the model suggest that activation of IK-ATP alone does not quantitatively account for the observed K+ efflux in metabolically impaired cardiac myocytes. Mechanisms other than KATP channel activation should be responsible for a significant part of the K+ efflux measured in hypoxic/ischemic situations.

Peripheral nerve recruitment curve using near-infrared stimulation

NASA Astrophysics Data System (ADS)

Dautrebande, Marie; Doguet, Pascal; Gorza, Simon-Pierre; Delbeke, Jean; Nonclercq, Antoine

2018-02-01

In the context of near-infrared neurostimulation, we report on an experimental hybrid electrode allowing for simultaneous photonic or electrical neurostimulation and for electrical recording of evoked action potentials. The electrode includes three contacts and one optrode. The optrode is an opening in the cuff through which the tip of an optical fibre is held close to the epineurium. Two contacts provide action potential recording. The remaining contact, together with a remote subcutaneous electrode, is used for electric stimulation which allows periodical assessment of the viability of the nerve during the experiment. A 1470 nm light source was used to stimulate a mouse sciatic nerve. Neural action potentials were not successfully recorded because of the electrical noise so muscular activity was used to reflect the motor fibres stimulation. A recruitment curve was obtained by stimulating with photonic pulses of same power and increasing duration and recording the evoked muscular action potentials. Motor fibres can be recruited with radiant exposures between 0.05 and 0.23 J/cm2 for pulses in the 100 to 500 μs range. Successful stimulation at short duration and at a commercial wavelength is encouraging in the prospect of miniaturisation and practical applications. Motor fibres recruitment curve is a first step in an ongoing research work. Neural action potential acquisition will be improved, with aim to shed light on the mechanism of action potential initiation under photonic stimulation.

Influence of surface morphology on adsorption of potassium stearate molecules on diamond-like carbon substrate: A molecular dynamics study

NASA Astrophysics Data System (ADS)

Guo, Shusen; Cao, Yongzhi; Sun, Tao; Zhang, Junjie; Gu, Le; Zhang, Chuanwei; Xu, Zhiqiang

2018-05-01

Molecular dynamics (MD) simulations were used to provide insights into the influence of nano-scale surface morphology on adsorptive behavior of Potassium stearate molecules on diamond-like carbon (DLC) substrates. Particular focus was given to explain that how the distinctive geometric properties of different surface morphologies affect the equilibrium structures and substrate-molecules interactions of monolayers, which was achieved through adsorptive analysis methods including adsorptive process, density profile, density distribution and surface potential energy. Analysis on surface potential energy demonstrated that the adsorptivity of amorphous smooth substrate is uniformly distributed over the surface, while DLC substrates with different surface morphologies appear to be more potentially corrugated, which improves the adsorptivity significantly. Because of the large distance of molecules from carbon atoms located at the square groove bottom, substrate-molecules interactions vanish significantly, and thus potassium stearate molecules cannot penetrate completely into the square groove. It can be observed that the equilibrium substrate-molecules interactions of triangle groove and semi-circle groove are much more powerful than that of square groove due to geometrically advantageous properties. These findings provided key information of optimally design of solid substrates with controllable adsorptivity.

Headless spermatozoa in infertile men.

PubMed

Sha, Y-W; Ding, L; Wu, J-X; Lin, S-B; Wang, X; Ji, Z-Y; Li, P

2017-10-01

Spermatozoa morphology, an important parameter in a semen specimen's potential fertility evaluation, is a significant factor for in vitro fertilisation in assisted reproductive technology. Eleven sterile men with headless spermatozoa, a type of human teratozoospermia, are presented. Their ejaculates' headless spermatozoa percentages were high with rare normal spermatozoa forms. Additionally, abnormal morphology (e.g. round-headed or microcephalic spermatozoa) was also found. Spermatozoa motility was somewhat affected, potentially because of the missing mitochondrial sheath at the sperm tail base. Patients who underwent assisted reproductive technology treatment experienced adverse pregnancy outcomes. Work types and corresponding environments seemed irrelevant, but specific family history may have prompted its genetic origin. Computer-assisted semen analysis systems easily mistake headless spermatozoa as oligozoospermia because of nonrecognition of the loose head. However, morphological testing, especially with an electronic microscope, clearly identifies abnormal spermatozoa. Future exploration requires more methods investigating the frequency and percentage of this morphological abnormality in different populations with varied fertility levels. Such research would estimate the probable correlation of the abnormality with other semen parameters and examine the potential developmental or genetic origins. During clinical work, medical staff should detect these cases, avoid misdiagnosis and provide proper consultation about diagnosis and assisted reproductive technology treatment. © 2016 Blackwell Verlag GmbH.

JPRS Report - Science & Technology USSR: Life Sciences.

DTIC Science & Technology

1988-06-17

No 6. Nov-Dec 87] 11 Electron Microscopic and Radioautographic Investigation of Bronchi in Chronic Inflammation Upon Exposure to Helium-Neon...87] 22 Functional and Morphological Characteristics of Stress-Protective Action of Piracetam [V. M. Vinogradov, A. A. Klishov et al; FARMAKOLOGIYA...I TOKSIKOLOGIYA No 6, Nov-Dec 87] 23 Comparative Neurophysiological Studies on Nootropic Agents Piracetam and Centrophenoxine [S. V Krapivin, T. A

Grounding Vision through Experimental Manipulation

DTIC Science & Technology

2002-01-01

Speculatrix" by their creator to emphasise their exploratory behaviour , described as: "it explores its environment actively, persistently, systematically...as most animals do" (Walter, 1950). These robots had very simple control circuitry, and their behaviour depended greatly on the morphology and...a long developing process. More studies are needed though to ascertain how the dorsal pathway (action) influences the ventral (perception) both in

Flow Modulation and Force Control of Flapping Wings

DTIC Science & Technology

2014-10-29

evolution of which reflect the wing morphology and kinematics. While the near-wake vortex system directly reflects the action of the wing on the...at 8 different stroke positions, which demonstrate the evolution of the vortex wake structure. The contour plot of Z vorticity at X-Y plane (Z...20 Figure 14. Smoke patterns showing the evolution of the flow structure in an

Chronic obstructive sleep apnea accelerates pulmonary remodeling via TGF-β/miR-185/CoLA1 signaling in a canine model.

PubMed

Ding, Xue; Yu, Chengyuan; Liu, Yang; Yan, Sen; Li, Wenpeng; Wang, Dingyu; Sun, Li; Han, Yu; Li, Minghui; Zhang, Song; Yun, Fengxiang; Zhao, Hongwei; Li, Yue

2016-09-06

Chronic obstructive sleep apnea syndrome (OSAS) is considered to be associated with pulmonary diseases. However, the roles and mechanisms of OSA in pulmonary remodeling remain ambiguous. Thus, this study was aimed to elucidate the morphological and mechanical action of OSA in lung remodeling. In the present study, we employed a novel OSA model to mimic the OSA patient and investigate the role of OSA in pulmonary remodeling. We showed that pulmonary artery pressure of OSA group has no significant increased compared with the sham group. Nevertheless, we found that fibrotic tissue was predominantly located around the bronchi and vascular in the lung. Additionally, inflammatory cell infiltration was also detected in the peribonchial and perivascular space. The morphological change in OSA canines was ascertained by ultrastructure variation characterized by mitochondrial swelling, lamellar bodies degeneration and vascular smooth muscle incrassation. Moreover, sympathetic nerve sprouting was markedly increased in OSA group. Mechanistically, we showed that several pivotal proteins including collagen type I(CoLA1), GAP-43, TH and NGF were highly expressed in OSA groups. Furthermore, we found OSA could activated the expression of TGF-β, which subsequently suppressed miR-185 and promoted CoL A1 expression. This signaling cascade leads to pulmonary remodeling. In conclusion, Our data demonstrates that OSA can accelerate the progression of pulmonary remodeling through TGF-β/miR-185/CoLA1 signaling, which would potentially provide therapeutic strategies for chronic OSAS.

Antimicrobial and Virulence-Modulating Effects of Clove Essential Oil on the Foodborne Pathogen Campylobacter jejuni

PubMed Central

Kovács, Judit K.; Felső, Péter; Makszin, Lilla; Pápai, Zoltán; Horváth, Györgyi; Ábrahám, Hajnalka; Palkovics, Tamás; Böszörményi, Andrea; Emődy, Levente

2016-01-01

ABSTRACT Our study investigated the antimicrobial action of clove (Syzygium aromaticum) essential oil (EO) on the zoonotic pathogen Campylobacter jejuni. After confirming the clove essential oil's general antibacterial effect, we analyzed the reference strain Campylobacter jejuni NCTC 11168. Phenotypic, proteomic, and transcriptomic methods were used to reveal changes in cell morphology and functions when exposed to sublethal concentrations of clove EO. The normally curved cells showed markedly straightened and shrunken morphology on the scanning electron micrographs as a result of stress. Although, oxidative stress, as a generally accepted response to essential oils, was also present, the dominance of a general stress response was demonstrated by reverse transcription-PCR (RT-PCR). The results of RT-PCR and two-dimensional (2D) PAGE revealed that clove oil perturbs the expression of virulence-associated genes taking part in the synthesis of flagella, PEB1, PEB4, lipopolysaccharide (LPS), and serine protease. Loss of motility was also detected by a phenotypic test. Bioautographic analysis revealed that besides its major component, eugenol, at least four other spots of clove EO possessed bactericidal activity against C. jejuni. Our findings show that clove EO has a marked antibacterial and potential virulence-modulating effect on C. jejuni. IMPORTANCE This study demonstrates that the components of clove essential oil influence not only the expression of general stress genes but also the expression of virulence-associated genes. Based on this finding, alternative strategies can be worked on to control this important foodborne pathogen. PMID:27520816

Effects of titania nanotubes with or without bovine serum albumin loaded on human gingival fibroblasts

PubMed Central

Liu, Xiangning; Zhou, Xiaosong; Li, Shaobing; Lai, Renfa; Zhou, Zhiying; Zhang, Ye; Zhou, Lei

2014-01-01

Modifying the surface of the transmucosal area is a key research area because this process positively affects the three functions of implants: attachment to soft tissue, inhibiting bacterial biofilm adhesion, and the preservation of the crestal bone. To exploit the potential of titania nanotube arrays (TNTs) with or without using bovine serum albumin (BSA) to modify the surface of a dental implant in contact with the transmucosal area, BSA was loaded into TNTs that were fabricated by anodizing Ti sheets; the physical characteristics of these arrays, including their morphology, chemical composition, surface roughness, contact angle, and surface free energy (SFE), were assessed. The effect of Ti surfaces with TNTs or TNTs-BSA on human gingival fibroblasts (HGFs) was determined by analyzing cell morphology, early adhesion, proliferation, type I collagen (COL-1) gene expression, and the extracellular secretion of COL-1. The results indicate that early HGF adhesion and spreading behavior is positively correlated with surface characteristics, including hydrophilicity, SFE, and surface roughness. Additionally, TNT surfaces not only promoted early HGF adhesion, but also promoted COL-1 secretion. BSA-loaded TNT surfaces promoted early HGF adhesion, while suppressing late proliferation and COL-1 secretion. Therefore, TNT-modified smooth surfaces are expected to be applicable for uses involving the transmucosal area. Further study is required to determine whether BSA-loaded TNT surfaces actually affect closed loop formation of connective tissue because BSA coating actions in vivo are very rapid. PMID:24623977

Antimicrobial activity of gallic acid against thermophilic Campylobacter is strain specific and associated with a loss of calcium ions.

PubMed

Sarjit, Amreeta; Wang, Yi; Dykes, Gary A

2015-04-01

Gallic acid has been suggested as a potential antimicrobial for the control of Campylobacter but its effectiveness is poorly studied. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of gallic acid against Campylobacter jejuni (n = 8) and Campylobacter coli (n = 4) strains was determined. Gallic acid inhibited the growth of five C. jejuni strains and three C. coli strains (MIC: 15.63-250 μg mL(-1)). Gallic acid was only bactericidal to two C. coli strains (MBC: 125 and 62.5 μg mL(-1)). The mechanism of the bactericidal effect against these two strains (and selected non-susceptible controls) was investigated by determining decimal reduction times and by monitoring the loss of cellular content and calcium ions, and changes in cell morphology. Gallic acid did not result in a loss of cellular content or morphological changes in the susceptible strains as compared to the controls. Gallic acid resulted in a loss of calcium ions (0.58-1.53 μg mL(-1) and 0.54-1.17 μg mL(-1), respectively, over a 180 min period) from the susceptible strains but not the controls. Gallic acid is unlikely to be an effective antimicrobial against Campylobacter in a practical sense unless further interventions to ensure an effective bactericidal mode of action against all strains are developed. Copyright © 2014 Elsevier Ltd. All rights reserved.

Rhizobium leguminosarum bv. viciae 3841 Adapts to 2,4-Dichlorophenoxyacetic Acid with "Auxin-Like" Morphological Changes, Cell Envelope Remodeling and Upregulation of Central Metabolic Pathways.

PubMed

Bhat, Supriya V; Booth, Sean C; McGrath, Seamus G K; Dahms, Tanya E S

2014-01-01

There is a growing need to characterize the effects of environmental stressors at the molecular level on model organisms with the ever increasing number and variety of anthropogenic chemical pollutants. The herbicide 2,4-dichlorophenoxyacetic acid (2,4-D), as one of the most widely applied pesticides in the world, is one such example. This herbicide is known to have non-targeted undesirable effects on humans, animals and soil microbes, but specific molecular targets at sublethal levels are unknown. In this study, we have used Rhizobium leguminosarum bv. viciae 3841 (Rlv) as a nitrogen fixing, beneficial model soil organism to characterize the effects of 2,4-D. Using metabolomics and advanced microscopy we determined specific target pathways in the Rlv metabolic network and consequent changes to its phenotype, surface ultrastructure, and physical properties during sublethal 2,4-D exposure. Auxin and 2,4-D, its structural analogue, showed common morphological changes in vitro which were similar to bacteroids isolated from plant nodules, implying that these changes are related to bacteroid differentiation required for nitrogen fixation. Rlv showed remarkable adaptation capabilities in response to the herbicide, with changes to integral pathways of cellular metabolism and the potential to assimilate 2,4-D with consequent changes to its physical and structural properties. This study identifies biomarkers of 2,4-D in Rlv and offers valuable insights into the mode-of-action of 2,4-D in soil bacteria.

Hyperforin modulates dendritic spine morphology in hippocampal pyramidal neurons by activating Ca(2+) -permeable TRPC6 channels.

PubMed

Leuner, Kristina; Li, Wei; Amaral, Michelle D; Rudolph, Stephanie; Calfa, Gaston; Schuwald, Anita M; Harteneck, Christian; Inoue, Takafumi; Pozzo-Miller, Lucas

2013-01-01

The standardized extract of the St. John's wort plant (Hypericum perforatum) is commonly used to treat mild to moderate depression. Its active constituent is hyperforin, a phloroglucinol derivative that reduces the reuptake of serotonin and norepinephrine by increasing intracellular Na(+) concentration through the activation of nonselective cationic TRPC6 channels. TRPC6 channels are also Ca(2+) -permeable, resulting in intracellular Ca(2+) elevations. Indeed, hyperforin activates TRPC6-mediated currents and Ca(2+) transients in rat PC12 cells, which induce their differentiation, mimicking the neurotrophic effect of nerve growth factor. Here, we show that hyperforin modulates dendritic spine morphology in CA1 and CA3 pyramidal neurons of hippocampal slice cultures through the activation of TRPC6 channels. Hyperforin also evoked intracellular Ca(2+) transients and depolarizing inward currents sensitive to the TRPC channel blocker La(3+) , thus resembling the actions of the neurotrophin brain-derived neurotrophic factor (BDNF) in hippocampal pyramidal neurons. These results suggest that the antidepressant actions of St. John's wort are mediated by a mechanism similar to that engaged by BDNF. Copyright © 2012 Wiley Periodicals, Inc.

Microscopy reveals disease control through novel effects on fungal development: a case study with an early-generation benzophenone fungicide.

PubMed

Schmitt, Mark R; Carzaniga, Raffaella; Cotter, H Van T; O'Connell, Richard; Hollomon, Derek

2006-05-01

The benzophenones are a new class of agricultural fungicides that demonstrate protectant, curative and eradicative/antisporulant activity against powdery mildews. The chemistry is represented in the marketplace by the fungicide metrafenone, recently introduced by BASF and discussed in the following paper. The benzophenones show no evidence of acting by previously identified biochemical mechanisms, nor do they show cross-resistance with existing fungicides. The value of microscopy in elucidating fungicide mode of action is demonstrated through identification of the effects of an early benzophenone, eBZO, on mildew development. eBZO caused profound alterations in the morphology of powdery mildews of both monocotyledons and dicotyledons, affecting multiple stages of fungal development, including spore germination, appressorial formation, penetration, surface hyphal morphology and sporogenesis. Identification of analogous effects of eBZO on sporulation in the model organism Aspergillus nidulans (Eidam) Winter provides a unique opportunity to elucidate important morphogenetic regulatory sites in the economically important obligate pathogens, the powdery mildews. Benzophenones provide a further example of the benefits of whole-organism testing in the search for novel fungicide modes of action. Copyright 2006 Society of Chemical Industry.

Method for estimating the morphological significance of simple forms of crystals from X-ray data

DOE Office of Scientific and Technical Information (OSTI.GOV)

Treivus, E. B., E-mail: sbobr1@bk.ru

2010-09-15

When developing V.I. Mikheev and I.I. Shafranovskii's method for estimating the morphological significance of faces of different simple forms from X-ray reflection intensities, a way to approximately evaluate the morphological significance of simple forms on crystals from the structure amplitudes of the corresponding atomic planes is proposed. The potential for this approach is demonstrated by the examples of marcasite and zircon.

Improved performance by morphology control via fullerenes in PBDT-TBT-alkoBT based organic solar cells

DOE PAGES

Khatiwada, Devendra; Venkatesan, Swaminathan; Chen, QIliang; ...

2015-07-03

In this work, we report improved performance by controlling morphology using different fullerene derivatives in poly{2-octyldodecyloxy-benzo[1,2-b;3,4-b]dithiophene-alt-5,6-bis(dodecyloxy)-4,7- di(thieno[3,2-b]thiophen-2-yl)-benzo[c][1,2,5]thiadiazole} (PBDT-TBT-alkoBT) based organic solar cells. PC60BM and PC70BM fullerenes were used to investigate the characteristic change in morphology and device performance. Fullerene affects device efficiency by changing active layer morphology. PC70BM with broader absorption than PC 60BM resulted in reduced device performance which was elucidated by the intermixed granular morphology separating each larger grain in the PC70BM/polymer composite layer which created higher density of traps. However after adding additive 1,8-diiodooctane (DIO), the fibrous morphology was observed due to reduced solubility of polymer andmore » increased solubility of PC 70BM in chloroform. The fibrous morphology improved charge transport leading to increase in overall device performance. Atomic force microscopies (AFM), photo induced charge extraction by linearly increasing voltage (photo-CELIV), and Kelvin prove force microscope (KPFM) were used to investigate nanoscale morphology of active layer with different fullerene derivatives. For PC 60BM based active layer, AFM images revealed dense fibrous morphology and more distinct fibrous morphology was observed by adding DIO. The PC 70BM based active layer only exhibited intermixed granular morphology instead of fibrous morphology observed in PC60BM based active layer. However, addition of DIO in PC 70BM based active layer led to fibrous morphology. When additive DIO was not used, a wider distribution of surface potential was observed for PC 70BM than PC 60BM based active layer by KPFM measurements, indicating 2 polymer and fullerene domains are separated. When DIO was used, narrower distribution of surface potential for both PC 70BM and PC 60BM based active layers was observed. Photo-CELIV experiment showed larger extracted charge carrier density and mobility in PC 70BM/DIO film.« less

Improved performance by morphology control via fullerenes in PBDT-TBT-alkoBT based organic solar cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Khatiwada, Devendra; Venkatesan, Swaminathan; Chen, QIliang

In this work, we report improved performance by controlling morphology using different fullerene derivatives in poly{2-octyldodecyloxy-benzo[1,2-b;3,4-b]dithiophene-alt-5,6-bis(dodecyloxy)-4,7- di(thieno[3,2-b]thiophen-2-yl)-benzo[c][1,2,5]thiadiazole} (PBDT-TBT-alkoBT) based organic solar cells. PC60BM and PC70BM fullerenes were used to investigate the characteristic change in morphology and device performance. Fullerene affects device efficiency by changing active layer morphology. PC70BM with broader absorption than PC 60BM resulted in reduced device performance which was elucidated by the intermixed granular morphology separating each larger grain in the PC70BM/polymer composite layer which created higher density of traps. However after adding additive 1,8-diiodooctane (DIO), the fibrous morphology was observed due to reduced solubility of polymer andmore » increased solubility of PC 70BM in chloroform. The fibrous morphology improved charge transport leading to increase in overall device performance. Atomic force microscopies (AFM), photo induced charge extraction by linearly increasing voltage (photo-CELIV), and Kelvin prove force microscope (KPFM) were used to investigate nanoscale morphology of active layer with different fullerene derivatives. For PC 60BM based active layer, AFM images revealed dense fibrous morphology and more distinct fibrous morphology was observed by adding DIO. The PC 70BM based active layer only exhibited intermixed granular morphology instead of fibrous morphology observed in PC60BM based active layer. However, addition of DIO in PC 70BM based active layer led to fibrous morphology. When additive DIO was not used, a wider distribution of surface potential was observed for PC 70BM than PC 60BM based active layer by KPFM measurements, indicating 2 polymer and fullerene domains are separated. When DIO was used, narrower distribution of surface potential for both PC 70BM and PC 60BM based active layers was observed. Photo-CELIV experiment showed larger extracted charge carrier density and mobility in PC 70BM/DIO film.« less

Exploring the nature of ecological specialization in a coral reef fish community: morphology, diet and foraging microhabitat use

PubMed Central

Brandl, Simon J.; Robbins, William D.; Bellwood, David R.

2015-01-01

Patterns of ecological specialization offer invaluable information about ecosystems. Yet, specialization is rarely quantified across several ecological niche axes and variables beyond the link between morphological and dietary specialization have received little attention. Here, we provide a quantitative evaluation of ecological specialization in a coral reef fish assemblage (f. Acanthuridae) along one fundamental and two realized niche axes. Specifically, we examined ecological specialization in 10 surgeonfish species with regards to morphology and two realized niche axes associated with diet and foraging microhabitat utilization using a recently developed multidimensional framework. We then investigated the potential relationships between morphological and behavioural specialization. These relationships differed markedly from the traditional ecomorphological paradigm. While morphological specialization showed no relationship with dietary specialization, it exhibited a strong relationship with foraging microhabitat specialization. However, this relationship was inverted: species with specialized morphologies were microhabitat generalists, whereas generalized morphotypes were microhabitat specialists. Interestingly, this mirrors relationships found in plant–pollinator communities and may also be applicable to other ecosystems, highlighting the potential importance of including niche axes beyond dietary specialization into ecomorphological frameworks. On coral reefs, it appears that morphotypes commonly perceived as most generalized may, in fact, be specialized in exploiting flat and easily accessible microhabitats. PMID:26354935

Locomotor activity influences muscle architecture and bone growth but not muscle attachment site morphology.

PubMed

Rabey, Karyne N; Green, David J; Taylor, Andrea B; Begun, David R; Richmond, Brian G; McFarlin, Shannon C

2015-01-01

The ability to make behavioural inferences from skeletal remains is critical to understanding the lifestyles and activities of past human populations and extinct animals. Muscle attachment site (enthesis) morphology has long been assumed to reflect muscle strength and activity during life, but little experimental evidence exists to directly link activity patterns with muscle development and the morphology of their attachments to the skeleton. We used a mouse model to experimentally test how the level and type of activity influences forelimb muscle architecture of spinodeltoideus, acromiodeltoideus, and superficial pectoralis, bone growth rate and gross morphology of their insertion sites. Over an 11-week period, we collected data on activity levels in one control group and two experimental activity groups (running, climbing) of female wild-type mice. Our results show that both activity type and level increased bone growth rates influenced muscle architecture, including differences in potential muscular excursion (fibre length) and potential force production (physiological cross-sectional area). However, despite significant influences on muscle architecture and bone development, activity had no observable effect on enthesis morphology. These results suggest that the gross morphology of entheses is less reliable than internal bone structure for making inferences about an individual's past behaviour. Copyright © 2014 Elsevier Ltd. All rights reserved.

Locomotor activity influences muscle architecture and bone growth but not muscle attachment site morphology

PubMed Central

Rabey, Karyne N.; Green, David J.; Taylor, Andrea B.; Begun, David R.; Richmond, Brian G.; McFarlin, Shannon C.

2014-01-01

The ability to make behavioural inferences from skeletal remains is critical to understanding the lifestyles and activities of past human populations and extinct animals. Muscle attachment site (enthesis) morphology has long been assumed to reflect muscle strength and activity during life, but little experimental evidence exists to directly link activity patterns with muscle development and the morphology of their attachments to the skeleton. We used a mouse model to experimentally test how the level and type of activity influences forelimb muscle architecture of spinodeltoideus, acromiodeltoideus, and superficial pectoralis, bone growth rate and gross morphology of their insertion sites. Over an 11-week period, we collected data on activity levels in one control group and two experimental activity groups (running, climbing) of female wild-type mice. Our results show that both activity type and level increased bone growth rates influenced muscle architecture, including differences in potential muscular excursion (fibre length) and potential force production (physiological cross-sectional area). However, despite significant influences on muscle architecture and bone development, activity had no observable effect on enthesis morphology. These results suggest that the gross morphology of entheses is less reliable than internal bone structure for making inferences about an individual’s past behaviour. PMID:25467113

Exploring the nature of ecological specialization in a coral reef fish community: morphology, diet and foraging microhabitat use.

PubMed

Brandl, Simon J; Robbins, William D; Bellwood, David R

2015-09-22

Patterns of ecological specialization offer invaluable information about ecosystems. Yet, specialization is rarely quantified across several ecological niche axes and variables beyond the link between morphological and dietary specialization have received little attention. Here, we provide a quantitative evaluation of ecological specialization in a coral reef fish assemblage (f. Acanthuridae) along one fundamental and two realized niche axes. Specifically, we examined ecological specialization in 10 surgeonfish species with regards to morphology and two realized niche axes associated with diet and foraging microhabitat utilization using a recently developed multidimensional framework. We then investigated the potential relationships between morphological and behavioural specialization. These relationships differed markedly from the traditional ecomorphological paradigm. While morphological specialization showed no relationship with dietary specialization, it exhibited a strong relationship with foraging microhabitat specialization. However, this relationship was inverted: species with specialized morphologies were microhabitat generalists, whereas generalized morphotypes were microhabitat specialists. Interestingly, this mirrors relationships found in plant-pollinator communities and may also be applicable to other ecosystems, highlighting the potential importance of including niche axes beyond dietary specialization into ecomorphological frameworks. On coral reefs, it appears that morphotypes commonly perceived as most generalized may, in fact, be specialized in exploiting flat and easily accessible microhabitats. © 2015 The Author(s).

Action Learning: Avoiding Conflict or Enabling Action

ERIC Educational Resources Information Center

Corley, Aileen; Thorne, Ann

2006-01-01

Action learning is based on the premise that action and learning are inextricably entwined and it is this potential, to enable action, which has contributed to the growth of action learning within education and management development programmes. However has this growth in action learning lead to an evolution or a dilution of Revan's classical…

Action Learning: Potential for Inner City Youth

ERIC Educational Resources Information Center

Epps, Edgar G.

1974-01-01

Working class and minority participation in action-learning poses potential problems likely to be overlooked by program planners. This presentation reveals the trouble spots and offers constructive suggestions. (Editor)

Onset dynamics of action potentials in rat neocortical neurons and identified snail neurons: quantification of the difference.

PubMed

Volgushev, Maxim; Malyshev, Aleksey; Balaban, Pavel; Chistiakova, Marina; Volgushev, Stanislav; Wolf, Fred

2008-04-09

The generation of action potentials (APs) is a key process in the operation of nerve cells and the communication between neurons. Action potentials in mammalian central neurons are characterized by an exceptionally fast onset dynamics, which differs from the typically slow and gradual onset dynamics seen in identified snail neurons. Here we describe a novel method of analysis which provides a quantitative measure of the onset dynamics of action potentials. This method captures the difference between the fast, step-like onset of APs in rat neocortical neurons and the gradual, exponential-like AP onset in identified snail neurons. The quantitative measure of the AP onset dynamics, provided by the method, allows us to perform quantitative analyses of factors influencing the dynamics.

Onset Dynamics of Action Potentials in Rat Neocortical Neurons and Identified Snail Neurons: Quantification of the Difference

PubMed Central

Volgushev, Maxim; Malyshev, Aleksey; Balaban, Pavel; Chistiakova, Marina; Volgushev, Stanislav; Wolf, Fred

2008-01-01

The generation of action potentials (APs) is a key process in the operation of nerve cells and the communication between neurons. Action potentials in mammalian central neurons are characterized by an exceptionally fast onset dynamics, which differs from the typically slow and gradual onset dynamics seen in identified snail neurons. Here we describe a novel method of analysis which provides a quantitative measure of the onset dynamics of action potentials. This method captures the difference between the fast, step-like onset of APs in rat neocortical neurons and the gradual, exponential-like AP onset in identified snail neurons. The quantitative measure of the AP onset dynamics, provided by the method, allows us to perform quantitative analyses of factors influencing the dynamics. PMID:18398478

Effect of Detergent on Electrical Properties of Squid Axon Membrane

PubMed Central

Kishimoto, Uichiro; Adelman, William J.

1964-01-01

The effects of detergents on squid giant axon action and resting potentials as well as membrane conductances in the voltage clamp have been studied. Anionic detergents (sodium lauryl sulfate, 0.1 to 1.0 mM; dimethyl benzene sulfonate, 1 to 20 mM, pH 7.6) cause a temporary increase and a later decrease of action potential height and the value of the resting potential. Cationic detergent (cetyl trimethyl ammonium chloride, 6 x 10-5 M or more, pH 7.6) generally brings about immediate and irreversible decreases in the action and resting potentials. Non-ionic detergent (tween 80, 0.1 M, pH 7.6) causes a slight reversible reduction of action potential height without affecting the value of the resting potential. Both anionic and cationic detergents generally decrease the sodium and potassium conductances irreversibly. The effect of non-ionic detergent is to decrease the sodium conductance reversibly, leaving the potassium conductance almost unchanged. PMID:14158665

The influence of action observation on action execution: Dissociating the contribution of action on perception, perception on action, and resolving conflict.

PubMed

Deschrijver, Eliane; Wiersema, Jan R; Brass, Marcel

2017-04-01

For more than 15 years, motor interference paradigms have been used to investigate the influence of action observation on action execution. Most research on so-called automatic imitation has focused on variables that play a modulating role or investigated potential confounding factors. Interestingly, furthermore, a number of functional magnetic resonance imaging (fMRI) studies have tried to shed light on the functional mechanisms and neural correlates involved in imitation inhibition. However, these fMRI studies, presumably due to poor temporal resolution, have primarily focused on high-level processes and have neglected the potential role of low-level motor and perceptual processes. In the current EEG study, we therefore aimed to disentangle the influence of low-level perceptual and motoric mechanisms from high-level cognitive mechanisms. We focused on potential congruency differences in the visual N190 - a component related to the processing of biological motion, the Readiness Potential - a component related to motor preparation, and the high-level P3 component. Interestingly, we detected congruency effects in each of these components, suggesting that the interference effect in an automatic imitation paradigm is not only related to high-level processes such as self-other distinction but also to more low-level influences of perception on action and action on perception. Moreover, we documented relationships of the neural effects with (autistic) behavior.

Three-dimensional echocardiography of congenital abnormalities of the left atrioventricular valve

PubMed Central

Rice, Kathryn

2015-01-01

Congenital abnormalities of the left atrioventricular (AV) valve are a significant diagnostic challenge. Traditionally, reliance has been placed on two-dimensional echocardiographic (2DE) imaging to guide recognition of the specific morphological features. Real-time 3DE can provide unique views of the left AV valve with the potential to improve understanding of valve morphology and function to facilitate surgical planning. This review illustrates the features of congenital abnormalities of the left AV valve assessed by 3DE. The similarities and differences in morphology between different lesions are described, both with respect to the valve itself and supporting chordal apparatus. The potential advantages as well as limitations of this technique in clinical practice are outlined. PMID:26693328

Associative, Bidirectional Changes in Neural Signaling Utilizing NMDA Receptor- and Endocannabinoid-Dependent Mechanisms

ERIC Educational Resources Information Center

Li, Qin; Burrell, Brian D.

2011-01-01

Persistent, bidirectional changes in synaptic signaling (that is, potentiation and depression of the synapse) can be induced by the precise timing of individual pre- and postsynaptic action potentials. However, far less attention has been paid to the ability of paired trains of action potentials to elicit persistent potentiation or depression. We…

Final Environmental Assessment: Addressing An Army and Air Force Exchange Service (AAFES) Lifestyle Center at Eglin Air Force Base, Florida

DTIC Science & Technology

2008-11-01

the proposed site has the potential for adverse effects on surface water bodies in the event of a spill or uncontrolled erosion. Implementation of...inclusion of a No Action Alternative against which potential effects can be compared. While the No Action Alternative would not satisfy the purpose... potential effects on project site and adjacent land uses. The foremost factor affecting a proposed action in terms of land use is its compliance

Localization of effective actions in open superstring field theory

NASA Astrophysics Data System (ADS)

Maccaferri, Carlo; Merlano, Alberto

2018-03-01

We consider the construction of the algebraic part of D-branes tree-level effective action from Berkovits open superstring field theory. Applying this construction to the quartic potential of massless fields carrying a specific worldsheet charge, we show that the full contribution to the potential localizes at the boundary of moduli space, reducing to elementary two-point functions. As examples of this general mechanism, we show how the Yang-Mills quartic potential and the instanton effective action of a Dp/D( p - 4) system are reproduced.

The Morphologies of the Semiconductor Oxides and Their Gas-Sensing Properties

PubMed Central

Lv, Xin; Li, Shuang; Wang, Qingji

2017-01-01

Semiconductor oxide chemoresistive gas sensors are widely used for detecting deleterious gases due to low cost, simple preparation, rapid response and high sensitivity. The performance of gas sensor is greatly affected by the morphology of the semiconductor oxide. There are many semiconductor oxide morphologies, including zero-dimensional, one-dimensional, two-dimensional and three-dimensional ones. The semiconductor oxides with different morphologies significantly enhance the gas-sensing performance. Among the various morphologies, hollow nanostructures and core-shell nanostructures are always the focus of research in the field of gas sensors due to their distinctive structural characteristics and superior performance. Herein the morphologies of semiconductor oxides and their gas-sensing properties are reviewed. This review also proposes a potential strategy for the enhancement of gas-sensing performance in the future. PMID:29189714

77 FR 45535 - Aldicarb; Proposed Tolerance Actions

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-01

... Aldicarb; Proposed Tolerance Actions AGENCY: Environmental Protection Agency (EPA). ACTION: Proposed rule... Information A. Does this action apply to me? You may be potentially affected by this action if you are an... exhaustive, but rather provides a guide for readers regarding entities likely to be affected by this action...

Reconstitution of the NF1 GAP-related domain in NF1-deficient human Schwann cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thomas, Stacey L.; Neuroscience Program, Loyola University Medical Center, Maywood, IL; Department of Anatomy and Cell Biology, University of Illinois Chicago, Chicago, IL

Schwann cells derived from peripheral nerve sheath tumors from individuals with Neurofibromatosis Type 1 (NF1) are deficient for the protein neurofibromin, which contains a GAP-related domain (NF1-GRD). Neurofibromin-deficient Schwann cells have increased Ras activation, increased proliferation in response to certain growth stimuli, increased angiogenic potential, and altered cell morphology. This study examined whether expression of functional NF1-GRD can reverse the transformed phenotype of neurofibromin-deficient Schwann cells from both benign and malignant peripheral nerve sheath tumors. We reconstituted the NF1-GRD using retroviral transduction and examined the effects on cell morphology, growth potential, and angiogenic potential. NF1-GRD reconstitution resulted in morphologic changes,more » a 16-33% reduction in Ras activation, and a 53% decrease in proliferation in neurofibromin-deficient Schwann cells. However, NF1-GRD reconstitution was not sufficient to decrease the in vitro angiogenic potential of the cells. This study demonstrates that reconstitution of the NF1-GRD can at least partially reverse the transformation of human NF1 tumor-derived Schwann cells.« less

Sodium and potassium conductance changes during a membrane action potential.

PubMed

Bezanilla, F; Rojas, E; Taylor, R E

1970-12-01

1. A method for turning a membrane potential control system on and off in less than 10 musec is described. This method was used to record membrane currents in perfused giant axons from Dosidicus gigas and Loligo forbesi after turning on the voltage clamp system at various times during the course of a membrane action potential.2. The membrane current measured just after the capacity charging transient was found to have an almost linear relation to the controlled membrane potential.3. The total membrane conductance taken from these current-voltage curves was found to have a time course during the action potential similar to that found by Cole & Curtis (1939).4. The instantaneous current voltage curves were linear enough to make it possible to obtain a good estimate of the individual sodium and potassium channel conductances, either algebraically or by clamping to the sodium, or potassium, reversal potentials. Good general agreement was obtained with the predictions of the Hodgkin-Huxley equations.5. We consider these results to constitute the first direct experimental demonstration of the conductance changes to sodium and potassium during the course of an action potential.

Calcium-Induced Calcium Release during Action Potential Firing in Developing Inner Hair Cells

PubMed Central

Iosub, Radu; Avitabile, Daniele; Grant, Lisa; Tsaneva-Atanasova, Krasimira; Kennedy, Helen J.

2015-01-01

In the mature auditory system, inner hair cells (IHCs) convert sound-induced vibrations into electrical signals that are relayed to the central nervous system via auditory afferents. Before the cochlea can respond to normal sound levels, developing IHCs fire calcium-based action potentials that disappear close to the onset of hearing. Action potential firing triggers transmitter release from the immature IHC that in turn generates experience-independent firing in auditory neurons. These early signaling events are thought to be essential for the organization and development of the auditory system and hair cells. A critical component of the action potential is the rise in intracellular calcium that activates both small conductance potassium channels essential during membrane repolarization, and triggers transmitter release from the cell. Whether this calcium signal is generated by calcium influx or requires calcium-induced calcium release (CICR) is not yet known. IHCs can generate CICR, but to date its physiological role has remained unclear. Here, we used high and low concentrations of ryanodine to block or enhance CICR to determine whether calcium release from intracellular stores affected action potential waveform, interspike interval, or changes in membrane capacitance during development of mouse IHCs. Blocking CICR resulted in mixed action potential waveforms with both brief and prolonged oscillations in membrane potential and intracellular calcium. This mixed behavior is captured well by our mathematical model of IHC electrical activity. We perform two-parameter bifurcation analysis of the model that predicts the dependence of IHCs firing patterns on the level of activation of two parameters, the SK2 channels activation and CICR rate. Our data show that CICR forms an important component of the calcium signal that shapes action potentials and regulates firing patterns, but is not involved directly in triggering exocytosis. These data provide important insights into the calcium signaling mechanisms involved in early developmental processes. PMID:25762313

Calcium-Induced calcium release during action potential firing in developing inner hair cells.

PubMed

Iosub, Radu; Avitabile, Daniele; Grant, Lisa; Tsaneva-Atanasova, Krasimira; Kennedy, Helen J

2015-03-10

In the mature auditory system, inner hair cells (IHCs) convert sound-induced vibrations into electrical signals that are relayed to the central nervous system via auditory afferents. Before the cochlea can respond to normal sound levels, developing IHCs fire calcium-based action potentials that disappear close to the onset of hearing. Action potential firing triggers transmitter release from the immature IHC that in turn generates experience-independent firing in auditory neurons. These early signaling events are thought to be essential for the organization and development of the auditory system and hair cells. A critical component of the action potential is the rise in intracellular calcium that activates both small conductance potassium channels essential during membrane repolarization, and triggers transmitter release from the cell. Whether this calcium signal is generated by calcium influx or requires calcium-induced calcium release (CICR) is not yet known. IHCs can generate CICR, but to date its physiological role has remained unclear. Here, we used high and low concentrations of ryanodine to block or enhance CICR to determine whether calcium release from intracellular stores affected action potential waveform, interspike interval, or changes in membrane capacitance during development of mouse IHCs. Blocking CICR resulted in mixed action potential waveforms with both brief and prolonged oscillations in membrane potential and intracellular calcium. This mixed behavior is captured well by our mathematical model of IHC electrical activity. We perform two-parameter bifurcation analysis of the model that predicts the dependence of IHCs firing patterns on the level of activation of two parameters, the SK2 channels activation and CICR rate. Our data show that CICR forms an important component of the calcium signal that shapes action potentials and regulates firing patterns, but is not involved directly in triggering exocytosis. These data provide important insights into the calcium signaling mechanisms involved in early developmental processes. Copyright © 2015 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Power-Law Dynamics of Membrane Conductances Increase Spiking Diversity in a Hodgkin-Huxley Model.

PubMed

Teka, Wondimu; Stockton, David; Santamaria, Fidel

2016-03-01

We studied the effects of non-Markovian power-law voltage dependent conductances on the generation of action potentials and spiking patterns in a Hodgkin-Huxley model. To implement slow-adapting power-law dynamics of the gating variables of the potassium, n, and sodium, m and h, conductances we used fractional derivatives of order η≤1. The fractional derivatives were used to solve the kinetic equations of each gate. We systematically classified the properties of each gate as a function of η. We then tested if the full model could generate action potentials with the different power-law behaving gates. Finally, we studied the patterns of action potential that emerged in each case. Our results show the model produces a wide range of action potential shapes and spiking patterns in response to constant current stimulation as a function of η. In comparison with the classical model, the action potential shapes for power-law behaving potassium conductance (n gate) showed a longer peak and shallow hyperpolarization; for power-law activation of the sodium conductance (m gate), the action potentials had a sharp rise time; and for power-law inactivation of the sodium conductance (h gate) the spikes had wider peak that for low values of η replicated pituitary- and cardiac-type action potentials. With all physiological parameters fixed a wide range of spiking patterns emerged as a function of the value of the constant input current and η, such as square wave bursting, mixed mode oscillations, and pseudo-plateau potentials. Our analyses show that the intrinsic memory trace of the fractional derivative provides a negative feedback mechanism between the voltage trace and the activity of the power-law behaving gate variable. As a consequence, power-law behaving conductances result in an increase in the number of spiking patterns a neuron can generate and, we propose, expand the computational capacity of the neuron.

Nuclear markers reveal that inter-lake cichlids' similar morphologies do not reflect similar genealogy.

PubMed

Kassam, Daud; Seki, Shingo; Horic, Michio; Yamaoka, Kosaku

2006-08-01

The apparent inter-lake morphological similarity among East African Great Lakes' cichlid species/genera has left evolutionary biologists asking whether such similarity is due to sharing of common ancestor or mere convergent evolution. In order to answer such question, we first used Geometric Morphometrics, GM, to quantify morphological similarity and then subsequently used Amplified Fragment Length Polymorphism, AFLP, to determine if similar morphologies imply shared ancestry or convergent evolution. GM revealed that not all presumed morphological similar pairs were indeed similar, and the dendrogram generated from AFLP data indicated distinct clusters corresponding to each lake and not inter-lake morphological similar pairs. Such results imply that the morphological similarity is due to convergent evolution and not shared ancestry. The congruency of GM and AFLP generated dendrograms imply that GM is capable of picking up phylogenetic signal, and thus GM can be potential tool in phylogenetic systematics.

Effect of captivity on morphology: negligible changes in external morphology mask significant changes in internal morphology

PubMed Central

Munn, Adam J.; Byrne, Phillip G.

2018-01-01

Captive breeding programmes are increasingly relied upon for threatened species management. Changes in morphology can occur in captivity, often with unknown consequences for reintroductions. Few studies have examined the morphological changes that occur in captive animals compared with wild animals. Further, the effect of multiple generations being maintained in captivity, and the potential effects of captivity on sexual dimorphism remain poorly understood. We compared external and internal morphology of captive and wild animals using house mouse (Mus musculus) as a model species. In addition, we looked at morphology across two captive generations, and compared morphology between sexes. We found no statistically significant differences in external morphology, but after one generation in captivity there was evidence for a shift in the internal morphology of captive-reared mice; captive-reared mice (two generations bred) had lighter combined kidney and spleen masses compared with wild-caught mice. Sexual dimorphism was maintained in captivity. Our findings demonstrate that captive breeding can alter internal morphology. Given that these morphological changes may impact organismal functioning and viability following release, further investigation is warranted. If the morphological change is shown to be maladaptive, these changes would have significant implications for captive-source populations that are used for reintroduction, including reduced survivorship.

Xylitol improves pancreatic islets morphology to ameliorate type 2 diabetes in rats: a dose response study.

PubMed

Rahman, Md Atiar; Islam, Md Shahdiul

2014-07-01

Xylitol has been reported as a potential antidiabetic sweetener in a number of recent studies; however, the most effective dietary dose and organ-specific effects are still unclear. Six-week-old male Sprague-Dawley rats were randomly divided into 5 groups: normal control (NC), diabetic control (DBC), diabetic xylitol 2.5% (DXL2.5), diabetic xylitol 5.0% (DXL5), and diabetic xylitol 10.0% (DXL10). Diabetes was induced only in the animals in DBC and DXL groups and considered diabetic when their nonfasting blood glucose level was >300 mg/dL. The DXL groups were fed with 2.5%, 5.0%, and 10% xylitol solution, whereas the NC and DBC groups were supplied with normal drinking water. After 4-wk intervention, body weight, food and fluid intake, blood glucose, serum fructosamine, liver glycogen, serum alanine transaminase, aspartate transaminase, lactate dehydrogenase, creatine kinase, uric acid, creatinine, and most serum lipids were significantly decreased, and serum insulin concentration, glucose tolerance ability, and pancreatic islets morphology were significantly improved in the DXL10 group compared to the DBC group. The data of this study suggest that 10% xylitol has the better antidiabetic effects compared to 2.5% and 5.0% and it can be used as an excellent antidiabetic sweetener and food supplement in antidiabetic foods. Xylitol is widely used as a potential anticariogenic and sweetening agent in a number of oral care and food products when many of its health benefits are still unknown. Due to its similar sweetening power but lower calorific value (2.5 compared with 4 kcal) and lower glycemic index (13 compared with 65) compared to sucrose, recently it has been widely used as a sugar substitute particularly by overweight, obese, and diabetic patients in order to reduce their calorie intake from sucrose. However, the potential antidiabetic effects of xylitol have been discovered recently. The results of this study confirmed the effective dietary dose of xylitol for diabetics with some of the mechanisms of actions behind its antidiabetic effects. © 2014 Institute of Food Technologists®

Nanoscale monitoring of drug actions on cell membrane using atomic force microscopy

PubMed Central

Li, Mi; Liu, Lian-qing; Xi, Ning; Wang, Yue-chao

2015-01-01

Knowledge of the nanoscale changes that take place in individual cells in response to a drug is useful for understanding the drug action. However, due to the lack of adequate techniques, such knowledge was scarce until the advent of atomic force microscopy (AFM), which is a multifunctional tool for investigating cellular behavior with nanometer resolution under near-physiological conditions. In the past decade, researchers have applied AFM to monitor the morphological and mechanical dynamics of individual cells following drug stimulation, yielding considerable novel insight into how the drug molecules affect an individual cell at the nanoscale. In this article we summarize the representative applications of AFM in characterization of drug actions on cell membrane, including topographic imaging, elasticity measurements, molecular interaction quantification, native membrane protein imaging and manipulation, etc. The challenges that are hampering the further development of AFM for studies of cellular activities are aslo discussed. PMID:26027658

Improved outcomes in auditory brainstem implantation with the use of near-field electrical compound action potentials.

PubMed

Mandalà, Marco; Colletti, Liliana; Colletti, Giacomo; Colletti, Vittorio

2014-12-01

To compare the outcomes (auditory threshold and open-set speech perception at 48-month follow-up) of a new near-field monitoring procedure, electrical compound action potential, on positioning the auditory brainstem implant electrode array on the surface of the cochlear nuclei versus the traditional far-field electrical auditory brainstem response. Retrospective study. Tertiary referral center. Among the 202 patients with auditory brainstem implants fitted and monitored with electrical auditory brainstem response during implant fitting, 9 also underwent electrical compound action potential recording. These subjects were matched retrospectively with a control group of 9 patients in whom only the electrical auditory brainstem response was recorded. Electrical compound action potentials were obtained using a cotton-wick recording electrode located near the surface of the cochlear nuclei and on several cranial nerves. Significantly lower potential thresholds were observed with the recording electrode located on the cochlear nuclei surface compared with the electrical auditory brainstem response (104.4 ± 32.5 vs 158.9 ± 24.2, P = .0030). Electrical brainstem response and compound action potentials identified effects on the neighboring cranial nerves on 3.2 ± 2.4 and 7.8 ± 3.2 electrodes, respectively (P = .0034). Open-set speech perception outcomes at 48-month follow-up had improved significantly in the near- versus far-field recording groups (78.9% versus 56.7%; P = .0051). Electrical compound action potentials during auditory brainstem implantation significantly improved the definition of the potential threshold and the number of auditory and extra-auditory waves generated. It led to the best coupling between the electrode array and cochlear nuclei, significantly improving the overall open-set speech perception. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2014.

Dofetilide promotes repolarization abnormalities in perfused Guinea-pig heart.

PubMed

Osadchii, Oleg E

2012-12-01

Dofetilide is class III antiarrhythmic agent which prolongs cardiac action potential duration because of selective inhibition of I (Kr), the rapid component of the delayed rectifier K(+) current. Although clinical studies reported on proarrhythmic risk associated with dofetilide treatment, the contributing electrophysiological mechanisms remain poorly understood. This study was designed to determine if dofetilide-induced proarrhythmia may be attributed to abnormalities in ventricular repolarization and refractoriness. The monophasic action potential duration and effective refractory periods (ERP) were assessed at distinct epicardial and endocardial sites along with volume-conducted ECG recordings in isolated, perfused guinea-pig heart preparations. Dofetilide was found to produce the reverse rate-dependent prolongation of ventricular repolarization, increased the steepness of action potential duration rate adaptation, and amplified transepicardial variability in electrical restitution kinetics. Dofetilide also prolonged the T peak-to-end interval on ECG, and elicited a greater prolongation of endocardial than epicardial ERP, thereby increasing transmural dispersion of refractoriness. At epicardium, dofetilide prolonged action potential duration to a greater extent than ERP, thus extending the critical interval for ventricular re-excitation. This change was associated with triangulation of epicardial action potential because of greater dofetilide-induced prolonging effect at 90 % than 30 % repolarization. Premature ectopic beats and spontaneous short-lasting episodes of monomorphic ventricular tachycardia were observed in 44 % of dofetilide-treated heart preparations. Proarrhythmic potential of dofetilide in guinea-pig heart is attributed to steepened electrical restitution, increased transepicardial variability in electrical restitution kinetics, amplified transmural dispersion of refractoriness, increased critical interval for ventricular re-excitation, and triangulation of epicardial action potential.

Semantic processing during morphological priming: an ERP study.

PubMed

Beyersmann, Elisabeth; Iakimova, Galina; Ziegler, Johannes C; Colé, Pascale

2014-09-04

Previous research has yielded conflicting results regarding the onset of semantic processing during morphological priming. The present study was designed to further explore the time-course of morphological processing using event-related potentials (ERPs). We conducted a primed lexical decision study comparing a morphological (LAVAGE - laver [washing - wash]), a semantic (LINGE - laver [laundry - wash]), an orthographic (LAVANDE - laver [lavender - wash]), and an unrelated control condition (HOSPICE - laver [nursing home - wash]), using the same targets across the four priming conditions. The behavioral data showed significant effects of morphological and semantic priming, with the magnitude of morphological priming being significantly larger than the magnitude of semantic priming. The ERP data revealed significant morphological but no semantic priming at 100-250 ms. Furthermore, a reduction of the N400 amplitude in the morphological condition compared to the semantic and orthographic condition demonstrates that the morphological priming effect was not entirely due to the semantic or orthographic overlap between the prime and the target. The present data reflect an early process of semantically blind morphological decomposition, and a later process of morpho-semantic decomposition, which we discuss in the context of recent morphological processing theories. Copyright © 2014 Elsevier B.V. All rights reserved.

ALS/FTLD-linked TDP-43 regulates neurite morphology and cell survival in differentiated neurons

DOE Office of Scientific and Technical Information (OSTI.GOV)

Han, Jeong-Ho; Yu, Tae-Hoon; Ryu, Hyun-Hee

2013-08-01

Tar-DNA binding protein of 43 kDa (TDP-43) has been characterized as a major component of protein aggregates in brains with neurodegenerative diseases such as frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). However, physiological roles of TDP-43 and early cellular pathogenic effects caused by disease associated mutations in differentiated neurons are still largely unknown. Here, we investigated the physiological roles of TDP-43 and the effects of missense mutations associated with diseases in differentiated cortical neurons. The reduction of TDP-43 by siRNA increased abnormal neurites and decreased cell viability. ALS/FTLD-associated missense mutant proteins (A315T, Q331K, and M337V) were partially mislocalizedmore » to the cytosol and neurites when compared to wild-type and showed abnormal neurites similar to those observed in cases of loss of TDP-43. Interestingly, cytosolic expression of wild-type TDP-43 with mutated nuclear localization signals also induced abnormal neurtie morphology and reduction of cell viability. However, there was no significant difference in the effects of cytosolic expression in neuronal morphology and cell toxicity between wild-type and missense mutant proteins. Thus, our results suggest that mislocalization of missense mutant TDP-43 may contribute to loss of TDP-43 function and affect neuronal morphology, probably via dominant negative action before severe neurodegeneration in differentiated cortical neurons. Highlights: • The function of nuclear TDP-43 in neurite morphology in mature neurons. • Partial mislocalization of TDP-43 missense mutants into cytosol from nucleus. • Abnormal neurite morphology caused by missense mutants of TDP-43. • The effect of cytosolic expression of TDP-43 in neurite morphology and in cell survival.« less

Ignition and Combustion Characteristics of Nanoscale Al/AgIO3: A Potential Energetic Biocidal System

DTIC Science & Technology

2011-01-01

the actual particle morphology consists of thin platelets , roughly 1 mm in diam- eter. Silver iodide was purchased from Sigma Aldrich, and the size was...2008), and shows that mixing is limited by clumping of both ingredients. The AgIO3 has a platelet -like morphology, and could potentially mix...in this study is 80 nm from NanoTechnologies. The CuO in this study is 45 nm from Technanogy. Each sample was fuel rich in this study with equivalency

Aqueous processes at Gusev crater inferred from physical properties of rocks and soils along the Spirit traverse

USGS Publications Warehouse

Cabrol, N.A.; Farmer, J.D.; Grin, E.A.; Ritcher, L.; Soderblom, L.; Li, R.; Herkenhoff, K.; Landis, G.A.; Arvidson, R. E.

2006-01-01

Gusev crater was selected as the landing site for Spirit on the basis of morphological evidence of long-lasting water activity, including possibly fluvial and lacustrine episodes. From the Columbia Memorial Station to the Columbia Hills, Spirit's traverse provides a journey back in time, from relatively recent volcanic plains showing little evidence for aqueous processes up to the older hills, where rock and soil composition are drastically different. For the first 156 sols, the only evidence of water action was weathering rinds, vein fillings, and soil crust cementation by salts. The trenches of Sols 112-145 marked the first significant findings of increased concentrations of sulfur and magnesium varying in parallel, suggesting that they be paired as magnesium-sulfate. Spirit's arrival at West Spur coincided with a shift in rock and soil composition with observations hinting at substantial amounts of water in Gusev's past. We used the Microscopic Imager data up to Sol 431 to analyze rock and soil properties and infer plausible types and magnitude of aqueous processes through time. We show the role played early by topography and structure. The morphology, texture, and deep alteration shown by the rocks in West Spur and the Columbia Hills Formation (CHF) suggest conditions that are not met in present-day Mars and required a wetter environment, which could have included transport of sulfur, chlorine, and bromine in water, vapor in volcanic gases, hydrothermal circulation, or saturation in a briny fluid containing the same elements. Changing conditions that might have affected flow circulation are suggested by different textural and morphological characteristics between the rocks in the CHF and those of the plains, with higher porosity proxy, higher void ratio, and higher water storage potential in the CHF. Soils were used to assess aqueous processes and water pathways in the top layers of modern soils. We conclude that infiltration might have become more difficult with time. Copyright 2006 by the American Geophysical Union.

DBI potential, DBI inflation action and general Lagrangian relative to phantom, K-essence and quintessence

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Qing; Huang, Yong-Chang, E-mail: ychuang@bjut.edu.cn

We derive a Dirac-Born-Infeld (DBI) potential and DBI inflation action by rescaling the metric. The determinant of the induced metric naturally includes the kinetic energy and the potential energy. In particular, the potential energy and kinetic energy can convert into each other in any order, which is in agreement with the limit of classical physics. This is quite different from the usual DBI action. We show that the Taylor expansion of the DBI action can be reduced into the form in the non-linear classical physics. These investigations are the support for the statement that the results of string theory aremore » consistent with quantum mechanics and classical physics. We deduce the Phantom, K-essence, Quintessence and Generalized Klein-Gordon Equation from the DBI model.« less

Simultaneous formation of multiscale hierarchical surface morphologies through sequential wrinkling and folding

NASA Astrophysics Data System (ADS)

Wang, Yu; Sun, Qingyang; Xiao, Jianliang

2018-02-01

Highly organized hierarchical surface morphologies possess various intriguing properties that could find important potential applications. In this paper, we demonstrate a facile approach to simultaneously form multiscale hierarchical surface morphologies through sequential wrinkling. This method combines surface wrinkling induced by thermal expansion and mechanical strain on a three-layer structure composed of an aluminum film, a hard Polydimethylsiloxane (PDMS) film, and a soft PDMS substrate. Deposition of the aluminum film on hard PDMS induces biaxial wrinkling due to thermal expansion mismatch, and recovering the prestrain in the soft PDMS substrate leads to wrinkling of the hard PDMS film. In total, three orders of wrinkling patterns form in this process, with wavelength and amplitude spanning 3 orders of magnitude in length scale. By increasing the prestrain in the soft PDMS substrate, a hierarchical wrinkling-folding structure was also obtained. This approach can be easily extended to other thin films for fabrication of multiscale hierarchical surface morphologies with potential applications in different areas.

An Integrated Circuit for Simultaneous Extracellular Electrophysiology Recording and Optogenetic Neural Manipulation.

PubMed

Chen, Chang Hao; McCullagh, Elizabeth A; Pun, Sio Hang; Mak, Peng Un; Vai, Mang I; Mak, Pui In; Klug, Achim; Lei, Tim C

2017-03-01

The ability to record and to control action potential firing in neuronal circuits is critical to understand how the brain functions. The objective of this study is to develop a monolithic integrated circuit (IC) to record action potentials and simultaneously control action potential firing using optogenetics. A low-noise and high input impedance (or low input capacitance) neural recording amplifier is combined with a high current laser/light-emitting diode (LED) driver in a single IC. The low input capacitance of the amplifier (9.7 pF) was achieved by adding a dedicated unity gain stage optimized for high impedance metal electrodes. The input referred noise of the amplifier is [Formula: see text], which is lower than the estimated thermal noise of the metal electrode. Thus, the action potentials originating from a single neuron can be recorded with a signal-to-noise ratio of at least 6.6. The LED/laser current driver delivers a maximum current of 330 mA, which is adequate for optogenetic control. The functionality of the IC was tested with an anesthetized Mongolian gerbil and auditory stimulated action potentials were recorded from the inferior colliculus. Spontaneous firings of fifth (trigeminal) nerve fibers were also inhibited using the optogenetic protein Halorhodopsin. Moreover, a noise model of the system was derived to guide the design. A single IC to measure and control action potentials using optogenetic proteins is realized so that more complicated behavioral neuroscience research and the translational neural disorder treatments become possible in the future.

Action Potential Dynamics in Fine Axons Probed with an Axonally Targeted Optical Voltage Sensor.

PubMed

Ma, Yihe; Bayguinov, Peter O; Jackson, Meyer B

2017-01-01

The complex and malleable conduction properties of axons determine how action potentials propagate through extensive axonal arbors to reach synaptic terminals. The excitability of axonal membranes plays a major role in neural circuit function, but because most axons are too thin for conventional electrical recording, their properties remain largely unexplored. To overcome this obstacle, we used a genetically encoded hybrid voltage sensor (hVOS) harboring an axonal targeting motif. Expressing this probe in transgenic mice enabled us to monitor voltage changes optically in two populations of axons in hippocampal slices, the large axons of dentate granule cells (mossy fibers) in the stratum lucidum of the CA3 region and the much finer axons of hilar mossy cells in the inner molecular layer of the dentate gyrus. Action potentials propagated with distinct velocities in each type of axon. Repetitive firing broadened action potentials in both populations, but at an intermediate frequency the degree of broadening differed. Repetitive firing also attenuated action potential amplitudes in both mossy cell and granule cell axons. These results indicate that the features of use-dependent action potential broadening, and possible failure, observed previously in large nerve terminals also appear in much finer unmyelinated axons. Subtle differences in the frequency dependences could influence the propagation of activity through different pathways to excite different populations of neurons. The axonally targeted hVOS probe used here opens up the diverse repertoire of neuronal processes to detailed biophysical study.

The marketing potential of corporate social responsibility activities: the case of the alcohol industry in Latin America and the Caribbean.

PubMed

Pantani, Daniela; Peltzer, Raquel; Cremonte, Mariana; Robaina, Katherine; Babor, Thomas; Pinsky, Ilana

2017-01-01

The aims were to: (1) identify, monitor and analyse the Corporate Social Responsibility (CSR) practices of the alcohol industry in Latin America and the Caribbean (LAC) and (2) examine whether the alcohol industry is using these actions to market their products and brands. Nine health experts from Argentina, Brazil and Uruguay conducted a content analysis of 218 CSR activities using a standardized protocol. A content rating procedure was used to evaluate the marketing potential of CSR activities as well as their probable population reach and effectiveness. The LEAD procedure (longitudinal, expert and all data) was applied to verify the accuracy of industry-reported descriptions. A total of 55.8% of the actions were found to have a marketing potential, based on evidence that they are likely to promote brands and products. Actions with marketing potential were more likely to reach a larger audience than actions classified with no marketing potential. Most actions did not fit into any category recommended by the World Health Organization; 50% of the actions involving classroom and college education for young people were found to have marketing potential; 62.3% were classified as meeting the definition of risk management CSR. Alcohol industry Corporate Social Responsibility activities in Latin America and the Caribbean appear to have a strategic marketing role beyond their stated philanthropic and public health purpose. © 2016 Society for the Study of Addiction.

76 FR 40811 - Maneb; Tolerance Actions

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-12

...; Tolerance Actions AGENCY: Environmental Protection Agency (EPA). ACTION: Final rule. SUMMARY: EPA is... established a docket for this action under docket identification (ID) number EPA-HQ-OPP-2010-0327. All... . SUPPLEMENTARY INFORMATION: I. General Information A. Does this action apply to me? You may be potentially...

Through a Feminist Poststructuralist Lens: Embodied Subjectivites and Participatory Action Research

ERIC Educational Resources Information Center

Chesnay, Catherine T.

2016-01-01

An emerging literature has been building bridges between poststructuralism and participatory action research, highlighting the latter's potential for transformative action. Using examples from participative action research projects with incarcerated or previously incarcerated women, this article discusses how participatory action research is a…

77 FR 18748 - Dicloran and Formetanate; Proposed Tolerance Actions

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-28

... Dicloran and Formetanate; Proposed Tolerance Actions AGENCY: Environmental Protection Agency (EPA). ACTION... . SUPPLEMENTARY INFORMATION: I. General Information A. Does this action apply to me? You may be potentially affected by this action if you are an agricultural producer, food manufacturer, or pesticide manufacturer...

Differential regulation of GnRH secretion in the preoptic area (POA) and the median eminence (ME) in male mice.

PubMed

Glanowska, Katarzyna M; Moenter, Suzanne M

2015-01-01

GnRH release in the median eminence (ME) is the central output for control of reproduction. GnRH processes in the preoptic area (POA) also release GnRH. We examined region-specific regulation of GnRH secretion using fast-scan cyclic voltammetry to detect GnRH release in brain slices from adult male mice. Blocking endoplasmic reticulum calcium reuptake to elevate intracellular calcium evokes GnRH release in both the ME and POA. This release is action potential dependent in the ME but not the POA. Locally applied kisspeptin induced GnRH secretion in both the ME and POA. Local blockade of inositol triphospate-mediated calcium release inhibited kisspeptin-induced GnRH release in the ME, but broad blockade was required in the POA. In contrast, kisspeptin-evoked secretion in the POA was blocked by local gonadotropin-inhibitory hormone, but broad gonadotropin-inhibitory hormone application was required in the ME. Although action potentials are required for GnRH release induced by pharmacologically-increased intracellular calcium in the ME and kisspeptin-evoked release requires inositol triphosphate-mediated calcium release, blocking action potentials did not inhibit kisspeptin-induced GnRH release in the ME. Kisspeptin-induced GnRH release was suppressed after blocking both action potentials and plasma membrane Ca(2+) channels. This suggests that kisspeptin action in the ME requires both increased intracellular calcium and influx from the outside of the cell but not action potentials. Local interactions among kisspeptin and GnRH processes in the ME could thus stimulate GnRH release without involving perisomatic regions of GnRH neurons. Coupling between action potential generation and hormone release in GnRH neurons is thus likely physiologically labile and may vary with region.

Amphetamine elevates nucleus accumbens dopamine via an action potential-dependent mechanism that is modulated by endocannabinoids

PubMed Central

Covey, Dan P.; Bunner, Kendra D.; Schuweiler, Douglas R.; Cheer, Joseph F.; Garris, Paul A.

2018-01-01

The reinforcing effects of abused drugs are mediated by their ability to elevate nucleus accumbens dopamine. Amphetamine (AMPH) was historically thought to increase dopamine by an action potential-independent, non-exocytotic type of release called efflux, involving reversal of dopamine transporter function and driven by vesicular dopamine depletion. Growing evidence suggests that AMPH also acts by an action potential-dependent mechanism. Indeed, fast-scan cyclic voltammetry demonstrates that AMPH activates dopamine transients, reward-related phasic signals generated by burst firing of dopamine neurons and dependent on intact vesicular dopamine. Not established for AMPH but indicating a shared mechanism, endocannabinoids facilitate this activation of dopamine transients by broad classes of abused drugs. Here, using fast-scan cyclic voltammetry coupled to pharmacological manipulations in awake rats, we investigated the action potential and endocannabinoid dependence of AMPH-induced elevations in nucleus accumbens dopamine. AMPH increased the frequency, amplitude and duration of transients, which were observed riding on top of slower dopamine increases. Surprisingly, silencing dopamine neuron firing abolished all AMPH-induced dopamine elevations, identifying an action potential-dependent origin. Blocking cannabinoid type 1 receptors prevented AMPH from increasing transient frequency, similar to reported effects on other abused drugs, but not from increasing transient duration and inhibiting dopamine uptake. Thus, AMPH elevates nucleus accumbens dopamine by eliciting transients via cannabinoid type 1 receptors and promoting the summation of temporally coincident transients, made more numerous, larger and wider by AMPH. Collectively, these findings are inconsistent with AMPH eliciting action potential-independent dopamine efflux and vesicular dopamine depletion, and support endocannabinoids facilitating phasic dopamine signalling as a common action in drug reinforcement. PMID:27038339

Amphetamine elevates nucleus accumbens dopamine via an action potential-dependent mechanism that is modulated by endocannabinoids.

PubMed

Covey, Dan P; Bunner, Kendra D; Schuweiler, Douglas R; Cheer, Joseph F; Garris, Paul A

2016-06-01

The reinforcing effects of abused drugs are mediated by their ability to elevate nucleus accumbens dopamine. Amphetamine (AMPH) was historically thought to increase dopamine by an action potential-independent, non-exocytotic type of release called efflux, involving reversal of dopamine transporter function and driven by vesicular dopamine depletion. Growing evidence suggests that AMPH also acts by an action potential-dependent mechanism. Indeed, fast-scan cyclic voltammetry demonstrates that AMPH activates dopamine transients, reward-related phasic signals generated by burst firing of dopamine neurons and dependent on intact vesicular dopamine. Not established for AMPH but indicating a shared mechanism, endocannabinoids facilitate this activation of dopamine transients by broad classes of abused drugs. Here, using fast-scan cyclic voltammetry coupled to pharmacological manipulations in awake rats, we investigated the action potential and endocannabinoid dependence of AMPH-induced elevations in nucleus accumbens dopamine. AMPH increased the frequency, amplitude and duration of transients, which were observed riding on top of slower dopamine increases. Surprisingly, silencing dopamine neuron firing abolished all AMPH-induced dopamine elevations, identifying an action potential-dependent origin. Blocking cannabinoid type 1 receptors prevented AMPH from increasing transient frequency, similar to reported effects on other abused drugs, but not from increasing transient duration and inhibiting dopamine uptake. Thus, AMPH elevates nucleus accumbens dopamine by eliciting transients via cannabinoid type 1 receptors and promoting the summation of temporally coincident transients, made more numerous, larger and wider by AMPH. Collectively, these findings are inconsistent with AMPH eliciting action potential-independent dopamine efflux and vesicular dopamine depletion, and support endocannabinoids facilitating phasic dopamine signalling as a common action in drug reinforcement. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

A Link No Longer Missing: New Evidence for the Cetotheriid Affinities of Caperea.

PubMed

Marx, Felix G; Fordyce, R Ewan

2016-01-01

The origins of the enigmatic pygmy right whale Caperea marginata, the only living member of its subfamily (Neobalaeninae), are an outstanding mystery of cetacean evolution. Its strikingly disparate morphology sets Caperea apart from all other whales, and has turned it into a wildcard taxon that holds the key to understanding modern baleen whale diversity. Morphological cladistics generally ally this species with right whales, whereas molecular analyses consistently cluster it with rorquals and grey whales (Balaenopteroidea). A recent study potentially resolved this conflict by proposing that Caperea belongs with the otherwise extinct Cetotheriidae, but has been strongly criticised on morphological grounds. Evidence from the neobalaenine fossil record could potentially give direct insights into morphological transitions, but is currently limited to just a single species: the Late Miocene Miocaperea pulchra, from Peru. We show that Miocaperea has a highly unusual morphology of the auditory region, resulting from a-presumably feeding-related-strengthening of the articulation of the hyoid apparatus with the skull. This distinctive arrangement is otherwise only found in the extinct Cetotheriidae, which makes Miocaperea a "missing link" that demonstrates the origin of pygmy right whales from cetotheriids, and confirms the latter's resurrection from the dead.

A Link No Longer Missing: New Evidence for the Cetotheriid Affinities of Caperea

PubMed Central

Marx, Felix G.; Fordyce, R. Ewan

2016-01-01

The origins of the enigmatic pygmy right whale Caperea marginata, the only living member of its subfamily (Neobalaeninae), are an outstanding mystery of cetacean evolution. Its strikingly disparate morphology sets Caperea apart from all other whales, and has turned it into a wildcard taxon that holds the key to understanding modern baleen whale diversity. Morphological cladistics generally ally this species with right whales, whereas molecular analyses consistently cluster it with rorquals and grey whales (Balaenopteroidea). A recent study potentially resolved this conflict by proposing that Caperea belongs with the otherwise extinct Cetotheriidae, but has been strongly criticised on morphological grounds. Evidence from the neobalaenine fossil record could potentially give direct insights into morphological transitions, but is currently limited to just a single species: the Late Miocene Miocaperea pulchra, from Peru. We show that Miocaperea has a highly unusual morphology of the auditory region, resulting from a–presumably feeding-related–strengthening of the articulation of the hyoid apparatus with the skull. This distinctive arrangement is otherwise only found in the extinct Cetotheriidae, which makes Miocaperea a “missing link” that demonstrates the origin of pygmy right whales from cetotheriids, and confirms the latter’s resurrection from the dead. PMID:27711216