Potential Role of Extracellular Vesicles in the Pathophysiology of Drug Addiction.

Science.gov (United States)

Rao, P S S; O'Connell, Kelly; Finnerty, Thomas Kyle

2018-01-23

Extracellular vesicles (EVs) are small vesicles secreted by cells and are known to carry sub-cellular components including microRNA, proteins, and lipids. Due to their ability to transport cargo between cells, EVs have been identified as important regulators of various pathophysiological conditions and can therefore influence treatment outcomes. In particular, the significance of microRNAs in EV-mediated cell-cell communication is well-documented. While the influence of EVs and the cargo delivered by EVs has been extensively reviewed in other neurological disorders, the available literature on the potential role of EVs in the pathophysiology of drug addiction has not been reviewed. Hence, in this article, the known effects of commonly abused drugs (ethanol, nicotine, opiates, cocaine, and cannabinoids) on EV secretion have been reviewed. In addition, the potential role of drugs of abuse in affecting the delivery of EV-packaged microRNAs, and the subsequent impact on neuronal health and continued drug dependence, has been discussed.

Robotics Potential Fields

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Jordi Lucero

2009-01-01

Full Text Available This problem was to calculate the path a robot would take to navigate an obstacle field and get to its goal. Three obstacles were given as negative potential fields which the robot avoided, and a goal was given a positive potential field that attracted the robot. The robot decided each step based on its distance, angle, and influence from every object. After each step, the robot recalculated and determined its next step until it reached its goal. The robot's calculations and steps were simulated with Microsoft Excel.

Focus on Extracellular Vesicles: Therapeutic Potential of Stem Cell-Derived Extracellular Vesicles

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Bin Zhang

2016-02-01

Full Text Available The intense research focus on stem and progenitor cells could be attributed to their differentiation potential to generate new cells to replace diseased or lost cells in many highly intractable degenerative diseases, such as Alzheimer disease, multiple sclerosis, and heart diseases. However, experimental and clinical studies have increasingly attributed the therapeutic efficacy of these cells to their secretion. While stem and progenitor cells secreted many therapeutic molecules, none of these molecules singly or in combination could recapitulate the functional effects of stem cell transplantations. Recently, it was reported that extracellular vesicles (EVs could recapitulate the therapeutic effects of stem cell transplantation. Based on the observations reported thus far, the prevailing hypothesis is that stem cell EVs exert their therapeutic effects by transferring biologically active molecules such as proteins, lipids, mRNA, and microRNA from the stem cells to injured or diseased cells. In this respect, stem cell EVs are similar to EVs from other cell types. They are both primarily vehicles for intercellular communication. Therefore, the differentiating factor is likely due to the composition of their cargo. The cargo of EVs from different cell types are known to include a common set of proteins and also proteins that reflect the cell source of the EVs and the physiological or pathological state of the cell source. Hence, elucidation of the stem cell EV cargo would provide an insight into the multiple physiological or biochemical changes necessary to affect the many reported stem cell-based therapeutic outcomes in a variety of experimental models and clinical trials.

Extracellular proteases of Trichoderma species. A review.

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Kredics, L; Antal, Zsuzsanna; Szekeres, A; Hatvani, L; Manczinger, L; Vágvölgyi, Cs; Nagy, Erzsébet

2005-01-01

Cellulolytic, xylanolytic, chitinolytic and beta-1,3-glucanolytic enzyme systems of species belonging to the filamentous fungal genus Trichoderma have been investigated in details and are well characterised. The ability of Trichoderma strains to produce extracellular proteases has also been known for a long time, however, the proteolytic enzyme system is relatively unknown in this genus. Fortunately, in the recent years more and more attention is focused on the research in this field. The role of Trichoderma proteases in the biological control of plant pathogenic fungi and nematodes has been demonstrated, and it is also suspected that they may be important for the competitive saprophytic ability of green mould isolates and may represent potential virulence factors of Trichoderma strains as emerging fungal pathogens of clinical importance. The aim of this review is to summarize the information available about the extracellular proteases of Trichoderma. Numerous studies are available about the extracellular proteolytic enzyme profiles of Trichoderma strains and about the effect of abiotic environmental factors on protease activities. A number of protease enzymes have been purified to homogeneity and some protease encoding genes have been cloned and characterized. These results will be reviewed and the role of Trichoderma proteases in biological control as well as their advantages and disadvantages in biotechnology will be discussed.

Update on controls for isolation and quantification methodology of extracellular vesicles derived from adipose tissue mesenchymal stem cells

NARCIS (Netherlands)

M. Franquesa (Marcella); M.J. Hoogduijn (Martin); E. Ripoll (Elia); F. Luk (Franka); M. Salih (Mahdi); M.G.H. Betjes (Michiel); J. Torras; C.C. Baan (Carla); J. Grinyo (Josep); A. Merino (Ana)

2014-01-01

textabstractThe research field on extracellular vesicles (EV) has rapidly expanded in recent years due to the therapeutic potential of EV. Adipose tissue human mesenchymal stem cells (ASC) may be a suitable source for therapeutic EV. A major limitation in the field is the lack of standardization of

Extracellular Signatures as Indicators of Processing Methods

Energy Technology Data Exchange (ETDEWEB)

Wahl, Karen L.

2012-01-09

As described in other chapters within this volume, many aspects of microbial cells vary with culture conditions and therefore can potentially be analyzed as forensic signatures of growth conditions. In addition to changes or variations in components of the microbes themselves, extracellular materials indicative of production processes may remain associated with the final bacterial product. It is well recognized that even with considerable effort to make pure products such as fine chemicals or pharmaceuticals, trace impurities from components or synthesis steps associated with production processes can be detected in the final product. These impurities can be used as indicators of production source or methods, such as to help connect drugs of abuse to supply chains. Extracellular residue associated with microbial cells could similarly help to characterize production processes. For successful growth of microorganisms on culture media there must be an available source of carbon, nitrogen, inorganic phosphate and sulfur, trace metals, water and vitamins. The pH, temperature, and a supply of oxygen or other gases must also be appropriate for a given organism for successful culture. The sources of these components and the range in temperature, pH and other variables has adapted over the years with currently a wide range of possible combinations of media components, recipes and parameters to choose from for a given organism. Because of this wide variability in components, mixtures of components, and other parameters, there is the potential for differentiation of cultured organisms based on changes in culture conditions. The challenge remains how to narrow the field of potential combinations and be able to attribute variations in the final bacterial product and extracellular signatures associated with the final product to information about the culture conditions or recipe used in the production of that product.

Activation of retinal glial (Müller cells by extracellular ATP induces pronounced increases in extracellular H+ flux.

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Boriana K Tchernookova

Full Text Available Small alterations in extracellular acidity are potentially important modulators of neuronal signaling within the vertebrate retina. Here we report a novel extracellular acidification mechanism mediated by glial cells in the retina. Using self-referencing H+-selective microelectrodes to measure extracellular H+ fluxes, we show that activation of retinal Müller (glial cells of the tiger salamander by micromolar concentrations of extracellular ATP induces a pronounced extracellular H+ flux independent of bicarbonate transport. ADP, UTP and the non-hydrolyzable analog ATPγs at micromolar concentrations were also potent stimulators of extracellular H+ fluxes, but adenosine was not. The extracellular H+ fluxes induced by ATP were mimicked by the P2Y1 agonist MRS 2365 and were significantly reduced by the P2 receptor blockers suramin and PPADS, suggesting activation of P2Y receptors. Bath-applied ATP induced an intracellular rise in calcium in Müller cells; both the calcium rise and the extracellular H+ fluxes were significantly attenuated when calcium re-loading into the endoplasmic reticulum was inhibited by thapsigargin and when the PLC-IP3 signaling pathway was disrupted with 2-APB and U73122. The anion transport inhibitor DIDS also markedly reduced the ATP-induced increase in H+ flux while SITS had no effect. ATP-induced H+ fluxes were also observed from Müller cells isolated from human, rat, monkey, skate and lamprey retinae, suggesting a highly evolutionarily conserved mechanism of potential general importance. Extracellular ATP also induced significant increases in extracellular H+ flux at the level of both the outer and inner plexiform layers in retinal slices of tiger salamander which was significantly reduced by suramin and PPADS. We suggest that the novel H+ flux mediated by ATP-activation of Müller cells and of other glia as well may be a key mechanism modulating neuronal signaling in the vertebrate retina and throughout the brain.

Effect of Ionic Diffusion on Extracellular Potentials in Neural Tissue.

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Geir Halnes

2016-11-01

Full Text Available Recorded potentials in the extracellular space (ECS of the brain is a standard measure of population activity in neural tissue. Computational models that simulate the relationship between the ECS potential and its underlying neurophysiological processes are commonly used in the interpretation of such measurements. Standard methods, such as volume-conductor theory and current-source density theory, assume that diffusion has a negligible effect on the ECS potential, at least in the range of frequencies picked up by most recording systems. This assumption remains to be verified. We here present a hybrid simulation framework that accounts for diffusive effects on the ECS potential. The framework uses (1 the NEURON simulator to compute the activity and ionic output currents from multicompartmental neuron models, and (2 the electrodiffusive Kirchhoff-Nernst-Planck framework to simulate the resulting dynamics of the potential and ion concentrations in the ECS, accounting for the effect of electrical migration as well as diffusion. Using this framework, we explore the effect that ECS diffusion has on the electrical potential surrounding a small population of 10 pyramidal neurons. The neural model was tuned so that simulations over ∼100 seconds of biological time led to shifts in ECS concentrations by a few millimolars, similar to what has been seen in experiments. By comparing simulations where ECS diffusion was absent with simulations where ECS diffusion was included, we made the following key findings: (i ECS diffusion shifted the local potential by up to ∼0.2 mV. (ii The power spectral density (PSD of the diffusion-evoked potential shifts followed a 1/f2 power law. (iii Diffusion effects dominated the PSD of the ECS potential for frequencies up to several hertz. In scenarios with large, but physiologically realistic ECS concentration gradients, diffusion was thus found to affect the ECS potential well within the frequency range picked up in

Intrinsic dendritic filtering gives low-pass power spectra of local field potentials

DEFF Research Database (Denmark)

Lindén, Henrik; Pettersen, Klas H; Einevoll, Gaute T

2010-01-01

of contributions to the LFP from a single layer-5 pyramidal neuron and a single layer-4 stellate neuron receiving synaptic input. An intrinsic dendritic low-pass filtering effect of the LFP signal, previously demonstrated for extracellular signatures of action potentials, is seen to strongly affect the LFP power...... spectra, even for frequencies as low as 10 Hz for the example pyramidal neuron. Further, the LFP signal is found to depend sensitively on both the recording position and the position of the synaptic input: the LFP power spectra recorded close to the active synapse are typically found to be less low......The local field potential (LFP) is among the most important experimental measures when probing neural population activity, but a proper understanding of the link between the underlying neural activity and the LFP signal is still missing. Here we investigate this link by mathematical modeling...

Participation of intracellular and extracellular pH changes in photosynthetic response development induced by variation potential in pumpkin seedlings.

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Sherstneva, O N; Vodeneev, V A; Katicheva, L A; Surova, L M; Sukhov, V S

2015-06-01

Electrical signals presented in plants by action potential and by variation potential (VP) can induce a reversible inactivation of photosynthesis. Changes in the intracellular and extracellular pH during VP generation are a potential mechanism of photosynthetic response induction; however, this hypothesis requires additional experimental investigation. The purpose of the present work was to analyze the influence of pH changes on induction of the photosynthetic response in pumpkin. It was shown that a burning of the cotyledon induced VP propagation into true leaves of pumpkin seedlings inducing a decrease in the photosynthetic CO2 assimilation and an increase in non-photochemical quenching of fluorescence, whereas respiration was activated insignificantly. The photosynthetic response magnitude depended linearly on the VP amplitude. The intracellular and extracellular concentrations of protons were analyzed using pH-sensitive fluorescent probes, and the VP generation was shown to be accompanied by apoplast alkalization (0.4 pH unit) and cytoplasm acidification (0.3 pH unit). The influence of changes in the incubation medium pH on the non-photochemical quenching of fluorescence of isolated chloroplasts was also investigated. It was found that acidification of the medium stimulated the non-photochemical quenching, and the magnitude of this increase depended on the decrease in pH. Our results confirm the contribution of changes in intracellular and extracellular pH to induction of the photosynthetic response caused by VP. Possible mechanisms of the influence of pH changes on photosynthesis are discussed.

Geobacter sulfurreducens adapts to low electrode potential for extracellular electron transfer

International Nuclear Information System (INIS)

Peng, Luo; Zhang, Xiao-Ting; Yin, Jie; Xu, Shuo-Yuan; Zhang, Yong; Xie, De-Ti; Li, Zhen-Lun

2016-01-01

Microbial extracellular electron transfer (EET) occurring in natural and engineering processes is attracting increasing interests. While a meaningful question for bioenergetics, microbial physiology and microbial electrochemical systems; less is known about the lower limit of electron acceptor reduction potential for EET. It is also unclear how microbes adapt to weak electron acceptors. This study evaluated Geobacter sulfurreducens biofilms grown with an electrode poised at −0.25 V vs. SHE. This potential was found to be sufficient for microbial metabolism and proliferation. The turnover cyclic voltammetries found that these biofilms had a half-saturation potential of −0.242 ± 0.004 V, in contrast to −0.151 ± 0.003 V for that of the biofilms grown under 0.2 V. For the biofilms grown under 0.2 V, differential pulse voltammetry showed that the metabolic current was mediated by interfacial cofactors with mid-point potential around −0.16 V performing single-electron electron transfer (ET). The major electron conduits for the biofilms respiring under −0.25 V had mid-point potentials of −0.22 V or −0.26 V, which appeared to perform two-electron ET. Under the non-turnover condition, both biofilms showed similar patterns in voltammograms and the low-potential conduits largely disappeared for the biofilms grown under −0.25 V. Transcriptome analysis identified 17 cytochrome-c genes significantly up-regulated for the biofilms grown under −0.25 V, together with many other genes linked to the ET system. It was also noted that, lowering the poised potential from −0.25 V to −0.28 V (the fuel standard oxidation potential) did not fully inhibit microbial respiration.

A model of extracellular enzymes in free-living microbes: which strategy pays off?

Science.gov (United States)

Traving, Sachia J; Thygesen, Uffe H; Riemann, Lasse; Stedmon, Colin A

2015-11-01

An initial modeling approach was applied to analyze how a single, nonmotile, free-living, heterotrophic bacterial cell may optimize the deployment of its extracellular enzymes. Free-living cells live in a dilute and complex substrate field, and to gain enough substrate, their extracellular enzymes must be utilized efficiently. The model revealed that surface-attached and free enzymes generate unique enzyme and substrate fields, and each deployment strategy has distinctive advantages. For a solitary cell, surface-attached enzymes are suggested to be the most cost-efficient strategy. This strategy entails potential substrates being reduced to very low concentrations. Free enzymes, on the other hand, generate a radically different substrate field, which suggests significant benefits for the strategy if free cells engage in social foraging or experience high substrate concentrations. Swimming has a slight positive effect for the attached-enzyme strategy, while the effect is negative for the free-enzyme strategy. The results of this study suggest that specific dissolved organic compounds in the ocean likely persist below a threshold concentration impervious to biological utilization. This could help explain the persistence and apparent refractory state of oceanic dissolved organic matter (DOM). Microbial extracellular enzyme strategies, therefore, have important implications for larger-scale processes, such as shaping the role of DOM in ocean carbon sequestration. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Improving Fructose Utilization and Butanol Production by Clostridium acetobutylicum via Extracellular Redox Potential Regulation and Intracellular Metabolite Analysis.

Science.gov (United States)

Chen, Li-Jie; Wu, You-Duo; Xue, Chuang; Bai, Feng-Wu

2017-10-01

Jerusalem artichoke (JA) can grow well in marginal lands with high biomass yield, and thus is a potential energy crop for biorefinery. The major biomass of JA is from tubers, which contain inulin that can be easily hydrolyzed into a mixture of fructose and glucose, but fructose utilization for producing butanol as an advanced biofuel is poor compared to glucose-based ABE fermentation by Clostridium acetobutylicum. In this article, the impact of extracellular redox potential (ORP) on the process is studied using a mixture of fructose and glucose to simulate the hydrolysate of JA tubers. When the extracellular ORP is controlled above -460 mV, 13.2 g L -1 butanol is produced from 51.0 g L -1 total sugars (40.1 g L -1 fructose and 10.9 g L -1 glucose), leading to dramatically increased butanol yield and butanol/ABE ratio of 0.26 g g -1 and 0.67, respectively. Intracellular metabolite and q-PCR analysis further indicate that intracellular ATP and NADH availabilities are significantly improved together with the fructose-specific PTS expression at the lag phase, which consequently facilitate fructose transport, metabolic shift toward solventogenesis and carbon flux redistribution for butanol biosynthesis. Therefore, the extracellular ORP control can be an effective strategy to improve butanol production from fructose-based feedstock. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Assessment of extracellular dehydration using saliva osmolality.

Science.gov (United States)

Ely, Brett R; Cheuvront, Samuel N; Kenefick, Robert W; Spitz, Marissa G; Heavens, Kristen R; Walsh, Neil P; Sawka, Michael N

2014-01-01

When substantial solute losses accompany body water an isotonic hypovolemia (extracellular dehydration) results. The potential for using blood or urine to assess extracellular dehydration is generally poor, but saliva is not a simple ultra-filtrate of plasma and the autonomic regulation of salivary gland function suggests the possibility that saliva osmolality (Sosm) may afford detection of extracellular dehydration via the influence of volume-mediated factors. This study aimed to evaluate the assessment of extracellular dehydration using Sosm. In addition, two common saliva collection methods and their effects on Sosm were compared. Blood, urine, and saliva samples were collected in 24 healthy volunteers during paired euhydration and dehydration trials. Furosemide administration and 12 h fluid restriction were used to produce extracellular dehydration. Expectoration and salivette collection methods were compared in a separate group of eight euhydrated volunteers. All comparisons were made using paired t-tests. The diagnostic potential of body fluids was additionally evaluated. Dehydration (3.1 ± 0.5% loss of body mass) decreased PV (-0.49 ± 0.12 L; -15.12 ± 3.94% change), but Sosm changes were marginal ( 0.05). Extracelluar dehydration was not detectable using plasma, urine, or saliva measures. Salivette and expectoration sampling methods produced similar, consistent results for Sosm, suggesting no methodological influence on Sosm.

Extracellular vesicles from parasitic helminths and their potential utility as vaccines.

Science.gov (United States)

Mekonnen, Gebeyaw Getnet; Pearson, Mark; Loukas, Alex; Sotillo, Javier

2018-03-01

Helminths are multicellular parasites affecting nearly three billion people worldwide. To orchestrate a parasitic existence, helminths secrete different molecules, either in soluble form or contained within extracellular vesicles (EVs). EVs are secreted by most cell types and organisms, and have varied roles in intercellular communication, including immune modulation and pathogenesis. Areas covered: In this review, we describe the nucleic acid and proteomic composition of EVs from helminths, with a focus on the protein vaccine candidates present on the EV surface membrane, and discuss the potential utility of helminth EVs and their constituent proteins in the fight against helminth infections. Expert commentary: A significant number of proteins present in helminth-secreted EVs are known vaccine candidates. The characterization of helminth EV proteomes will shed light on host-pathogen interactions, facilitate the discovery of new diagnostic biomarkers, and provide a novel approach for the development of new control measures against helminth infections.

Extracellular vesicles: fundamentals and clinical relevance

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Wael Nassar

2015-01-01

Full Text Available All types of cells of eukaryotic organisms produce and release small nanovesicles into their extracellular environment. Early studies have described these vesicles as ′garbage bags′ only to remove obsolete cellular molecules. Valadi and colleagues, in 2007, were the first to discover the capability of circulating extracellular vesicles (EVs to horizontally transfer functioning gene information between cells. These extracellular vesicles express components responsible for angiogenesis promotion, stromal remodeling, chemoresistance, genetic exchange, and signaling pathway activation through growth factor/receptor transfer. EVs represent an important mode of intercellular communication by serving as vehicles for transfer between cells of membrane and cytosolic proteins, lipids, signaling proteins, and RNAs. They contribute to physiology and pathology, and they have a myriad of potential clinical applications in health and disease. Moreover, vesicles can pass the blood-brain barrier and may perhaps even be considered as naturally occurring liposomes. These cell-derived EVs not only represent a central mediator of the disease microenvironment, but their presence in the peripheral circulation may serve as a surrogate for disease biopsies, enabling real-time diagnosis and disease monitoring. In this review, we′ll be addressing the characteristics of different types of extracellular EVs, as well as their clinical relevance and potential as diagnostic markers, and also define therapeutic options.

From neurons to circuits: linear estimation of local field potentials

Science.gov (United States)

Rasch, Malte; Logthetis, Nikos K.; Kreiman, Gabriel

2010-01-01

Extracellular physiological recordings are typically separated into two frequency bands: local field potentials (LFPs, a circuit property) and spiking multi-unit activity (MUA). There has been increased interest in LFPs due to their correlation with fMRI measurements and the possibility of studying local processing and neuronal synchrony. To further understand the biophysical origin of LFPs, we asked whether it is possible to estimate their time course based on the spiking activity from the same or nearby electrodes. We used Signal Estimation Theory to show that a linear filter operation on the activity of one/few neurons can explain a significant fraction of the LFP time course in the macaque primary visual cortex. The linear filter used to estimate the LFPs had a stereotypical shape characterized by a sharp downstroke at negative time lags and a slower positive upstroke for positve time lags. The filter was similar across neocortical regions and behavioral conditions including spontaneous activity and visual stimulation. The estimations had a spatial resolution of ~1 mm and a temporal resolution of ~200 ms. By considering a causal filter, we observed a temporal asymmetry such that the positive time lags in the filter contributed more to the LFP estimation than negative time lags. Additionally, we showed that spikes occurring within ~10 ms of spikes from nearby neurons yielded better estimation accuracies than nonsynchronous spikes. In sum, our results suggest that at least some circuit-level local properties of the field potentials can be predicted from the activity of one or a few neurons. PMID:19889990

Extracellular DNA metabolism in Haloferax volcanii

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Scott eChimileski

2014-02-01

Full Text Available Extracellular DNA is found in all environments and is a dynamic component of the micro-bial ecosystem. Microbial cells produce and interact with extracellular DNA through many endogenous mechanisms. Extracellular DNA is processed and internalized for use as genetic information and as a major source of macronutrients, and plays several key roles within prokaryotic biofilms. Hypersaline sites contain some of the highest extracellular DNA con-centrations measured in nature–a potential rich source of carbon, nitrogen and phosphorus for halophilic microorganisms. We conducted DNA growth studies for the halophilic archaeon Haloferax volcanii DS2 and show that this model Halobacteriales strain is capable of using exogenous double-stranded DNA as a nutrient. Further experiments with varying medium composition, DNA concentration and DNA types revealed that DNA is utilized primarily as a phosphorus source, that growth on DNA is concentration-dependent and that DNA isolated from different sources is metabolized selectively, with a bias against highly divergent methylated DNA sources. Additionally, fluorescence microscopy experiments showed that labeled DNA colocalized with Haloferax volcanii cells. The gene Hvo_1477 was also identified using a comparative genomic approach as a factor likely to be involved in extracellular DNA processing at the cell surface, and deletion of Hvo_1477 created an H. volcanii strain deficient in its ability to grow on extracellular DNA. Widespread distribution of Hvo_1477 homologs in archaea suggests metabolism of extracellular DNA may be of broad ecological and physiological relevance in this domain of life.

Electric field stimulation through a substrate influences Schwann cell and extracellular matrix structure

Science.gov (United States)

Nguyen, Hieu T.; Wei, Claudia; Chow, Jacqueline K.; Nguy, Lindsey; Nguyen, Hieu K.; Schmidt, Christine E.

2013-08-01

Objective. Electric field (EF) stimulation has been used to cue cell growth for tissue engineering applications. In this study, we explore the electrical parameters and extracellular mechanisms that elicit changes in cell behavior when stimulated through the substrate. Approach. Rat Schwann cell morphology was compared when exposed to EF through the media or a conductive indium tin oxide substrate. Ionic and structural effects were then analyzed on Matrigel and collagen I, respectively. Main results. When stimulating through media, cells had greater alignment perpendicular to the EF with higher current densities (106 mA cm-2 at 245 mV mm-1), and reached maximum alignment within 8 h. Stimulation through the substrate with EF (up to 110 mV mm-1) did not affect Schwann cell orientation, however the EF caused extracellular matrix (ECM) coatings on substrates to peel away, suggesting EF can physically change the ECM. Applying alternating current (ac) 2-1000 Hz signals through the media or substrate both caused cells to flatten and protrude many processes, without preferential alignment. Matrigel exposed to a substrate EF of 10 mV mm-1 for 2 h had a greater calcium concentration near the cathode, but quickly dissipated when the EF was removed. Schwann cells seeded 7 d after gels were exposed to substrate EF still aligned perpendicular to the EF direction. Microscopy of collagen I exposed to substrate EF shows alignment and bundling of fibrils. Significance. These findings demonstrate EF exposure can control Schwann cell alignment and morphology, change ECM bulk/surface architecture, and align ECM structures.

Standardization of sample collection, isolation and analysis methods in extracellular vesicle research

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Kenneth W. Witwer

2013-05-01

Full Text Available The emergence of publications on extracellular RNA (exRNA and extracellular vesicles (EV has highlighted the potential of these molecules and vehicles as biomarkers of disease and therapeutic targets. These findings have created a paradigm shift, most prominently in the field of oncology, prompting expanded interest in the field and dedication of funds for EV research. At the same time, understanding of EV subtypes, biogenesis, cargo and mechanisms of shuttling remains incomplete. The techniques that can be harnessed to address the many gaps in our current knowledge were the subject of a special workshop of the International Society for Extracellular Vesicles (ISEV in New York City in October 2012. As part of the “ISEV Research Seminar: Analysis and Function of RNA in Extracellular Vesicles (evRNA”, 6 round-table discussions were held to provide an evidence-based framework for isolation and analysis of EV, purification and analysis of associated RNA molecules, and molecular engineering of EV for therapeutic intervention. This article arises from the discussion of EV isolation and analysis at that meeting. The conclusions of the round table are supplemented with a review of published materials and our experience. Controversies and outstanding questions are identified that may inform future research and funding priorities. While we emphasize the need for standardization of specimen handling, appropriate normative controls, and isolation and analysis techniques to facilitate comparison of results, we also recognize that continual development and evaluation of techniques will be necessary as new knowledge is amassed. On many points, consensus has not yet been achieved and must be built through the reporting of well-controlled experiments.

Extracellular Vesicles in Heart Disease: Excitement for the Future?

Directory of Open Access Journals (Sweden)

Kirsty M. Danielson

2014-01-01

Full Text Available Extracellular vesicles (EV, including exosomes, microvesicles and apoptotic bodies, are released from numerous cell types and are involved in intercellular communication, physiological functions and the pathology of disease. They have been shown to carry and transfer a wide range of cargo including proteins, lipids and nucleic acids. The role of EVs in cardiac physiology and heart disease is an emerging field that has produced intriguing findings in recent years. This review will outline what is currently known about EVs in the cardiovascular system, including cellular origins, functional roles and utility as biomarkers and potential therapeutics.

Pulse electromagnetic fields enhance extracellular electron transfer in magnetic bioelectrochemical systems.

Science.gov (United States)

Zhou, Huihui; Liu, Bingfeng; Wang, Qisong; Sun, Jianmin; Xie, Guojun; Ren, Nanqi; Ren, Zhiyong Jason; Xing, Defeng

2017-01-01

Microbial extracellular electron transfer (EET) is essential in driving the microbial interspecies interaction and redox reactions in bioelectrochemical systems (BESs). Magnetite (Fe 3 O 4 ) and magnetic fields (MFs) were recently reported to promote microbial EET, but the mechanisms of MFs stimulation of EET and current generation in BESs are not known. This study investigates the behavior of current generation and EET in a state-of-the-art pulse electromagnetic field (PEMF)-assisted magnetic BES (PEMF-MBES), which was equipped with magnetic carbon particle (Fe 3 O 4 @N-mC)-coated electrodes. Illumina Miseq sequencing of 16S rRNA gene amplicons was also conducted to reveal the changes of microbial communities and interactions on the anode in response to magnetic field. PEMF had significant influences on current generation. When reactors were operated in microbial fuel cell (MFC) mode with pulse electromagnetic field (PEMF-MMFCs), power densities increased by 25.3-36.0% compared with no PEMF control MFCs (PEMF-OFF-MMFCs). More interestingly, when PEMF was removed, the power density dropped by 25.7%, while when PEMF was reintroduced, the value was restored to the previous level. Illumina sequencing of 16S rRNA gene amplicon and principal component analysis (PCA) based on operational taxonomic units (OTUs) indicate that PEMFs led to the shifts in microbial community and changes in species evenness that decreased biofilm microbial diversity. Geobacter spp. were found dominant in all anode biofilms, but the relative abundance in PEMF-MMFCs (86.1-90.0%) was higher than in PEMF-OFF-MMFCs (82.5-82.7%), indicating that the magnetic field enriched Geobacter on the anode. The current generation of Geobacter -inoculated microbial electrolysis cells (MECs) presented the same change regularity, the accordingly increase or decrease corresponding with switch of PEMF, which confirmed the reversible stimulation of PEMFs on microbial electron transfer. The pulse electromagnetic

Ribonucleic artefacts: are some extracellular RNA discoveries driven by cell culture medium components?

Science.gov (United States)

Tosar, Juan Pablo; Cayota, Alfonso; Eitan, Erez; Halushka, Marc K; Witwer, Kenneth W

2017-01-01

In a recently published study, Anna Krichevsky and colleagues raise the important question of whether results of in vitro extracellular RNA (exRNA) studies, including extracellular vesicle (EV) investigations, are confounded by the presence of RNA in cell culture medium components such as foetal bovine serum (FBS). The answer, according to their data, is a resounding "yes". Even after lengthy ultracentrifugation to remove bovine EVs from FBS, the majority of exRNA in FBS remained. Although technical factors may affect the degree of depletion, residual EVs and exRNA in FBS could influence the conclusions of in vitro studies: certainly, for secreted RNA, and possibly also for cell-associated RNA. In this commentary, we critically examine some of the literature in this field, including a recent study from some of the authors of this piece, in light of the Wei et al. study and explore how cell culture-derived RNAs may affect what we think we know about EV RNAs. These findings hold particular consequence as the field moves towards a deeper understanding of EV-RNA associations and potential functions.

Binding of matrix metalloproteinase inhibitors to extracellular matrix: 3D-QSAR analysis.

Science.gov (United States)

Zhang, Yufen; Lukacova, Viera; Bartus, Vladimir; Nie, Xiaoping; Sun, Guorong; Manivannan, Ethirajan; Ghorpade, Sandeep R; Jin, Xiaomin; Manyem, Shankar; Sibi, Mukund P; Cook, Gregory R; Balaz, Stefan

2008-10-01

Binding to the extracellular matrix, one of the most abundant human protein complexes, significantly affects drug disposition. Specifically, the interactions with extracellular matrix determine the free concentrations of small molecules acting in tissues, including signaling peptides, inhibitors of tissue remodeling enzymes such as matrix metalloproteinases, and other drug candidates. The nature of extracellular matrix binding was elucidated for 63 matrix metalloproteinase inhibitors, for which the association constants to an extracellular matrix mimic were reported here. The data did not correlate with lipophilicity as a common determinant of structure-nonspecific, orientation-averaged binding. A hypothetical structure of the binding site of the solidified extracellular matrix surrogate was analyzed using the Comparative Molecular Field Analysis, which needed to be applied in our multi-mode variant. This fact indicates that the compounds bind to extracellular matrix in multiple modes, which cannot be considered as completely orientation-averaged and exhibit structural dependence. The novel comparative molecular field analysis models, exhibiting satisfactory descriptive and predictive abilities, are suitable for prediction of the extracellular matrix binding for the untested chemicals, which are within applicability domains. The results contribute to a better prediction of the pharmacokinetic parameters such as the distribution volume and the tissue-blood partition coefficients, in addition to a more imminent benefit for the development of more effective matrix metalloproteinase inhibitors.

Expression of small leucine-rich extracellular matrix proteoglycans biglycan and lumican reveals oral lichen planus malignant potential.

Science.gov (United States)

Lončar-Brzak, Božana; Klobučar, Marko; Veliki-Dalić, Irena; Sabol, Ivan; Kraljević Pavelić, Sandra; Krušlin, Božo; Mravak-Stipetić, Marinka

2018-03-01

The aim of this study was to examine molecular alterations on the protein level in lesions of oral lichen planus (OLP), oral squamous cell carcinoma (OSCC) and healthy mucosa. Global protein profiling methods based on liquid chromatography coupled to mass spectrometry (LC-MS) were used, with a special emphasis on evaluation of deregulated extracellular matrix molecules expression, as well as on analyses of IG2F and IGFR2 expression in healthy mucosa, OLP and OSCC tissues by comparative semi-quantitative immunohistochemistry. Mass spectrometry-based proteomics profiling of healthy mucosa, OLP and OSCC tissues (and accompanied histologically unaltered tissues, respectively) identified 55 extracellular matrix proteins. Twenty among identified proteins were common to all groups of samples. Expression of small leucine-rich extracellular matrix proteoglycans lumican and biglycan was found both in OSCC and OLP and they were validated by Western blot analysis as putative biomarkers. A significant increase (p < 0.05) of biglycan expression in OLP-AT group was determined in comparison with OLP-T group, while lumican showed significant up-regulation (p < 0.05) in OLP-T and OSCC-T groups vs. adjacent and control tissue groups. Biglycan expression was only determined in OSCC-AT group. Immunohistochemical analysis of IGF2 and IG2FR expression revealed no significant difference among groups of samples. Biglycan and lumican were identified as important pathogenesis biomarkers of OLP that point to its malignant potential.

Spatial and frequency domain ring source models for the single muscle fiber action potential

DEFF Research Database (Denmark)

Henneberg, Kaj-åge; R., Plonsey

1994-01-01

In the paper, single-fibre models for the extracellular action potential are developed that will allow the potential to the evaluated at an arbitrary field point in the extracellular space. Fourier-domain models are restricted in that they evaluate potentials at equidistant points along a line...... parallel to the fibre axis. Consequently, they cannot easily evaluate the potential at the boundary nodes of a boundary-element electrode model. The Fourier-domain models employ axial-symmetric ring source models, and thereby provide higher accuracy that the line source model, where the source is lumped...... including anisotropy show that the spatial models require extreme care in the integration procedure owing to the singularity in the weighting functions. With adequate sampling, the spatial models can evaluate extracellular potentials with high accuracy....

Focus on Extracellular Vesicles: Physiological Role and Signalling Properties of Extracellular Membrane Vesicles

Directory of Open Access Journals (Sweden)

Nunzio Iraci

2016-02-01

Full Text Available Extracellular vesicles (EVs are a heterogeneous population of secreted membrane vesicles, with distinct biogenesis routes, biophysical properties and different functions both in physiological conditions and in disease. The release of EVs is a widespread biological process, which is conserved across species. In recent years, numerous studies have demonstrated that several bioactive molecules are trafficked with(in EVs, such as microRNAs, mRNAs, proteins and lipids. The understanding of their final impact on the biology of specific target cells remains matter of intense debate in the field. Also, EVs have attracted great interest as potential novel cell-free therapeutics. Here we describe the proposed physiological and pathological functions of EVs, with a particular focus on their molecular content. Also, we discuss the advances in the knowledge of the mechanisms regulating the secretion of EV-associated molecules and the specific pathways activated upon interaction with the target cell, highlighting the role of EVs in the context of the immune system and as mediators of the intercellular signalling in the brain.

Characterization of extracellular vitamin B12 producing Lactobacillus plantarum strains and assessment of the probiotic potentials.

Science.gov (United States)

Li, Ping; Gu, Qing; Yang, Lanlan; Yu, Yue; Wang, Yuejiao

2017-11-01

We investigated extracellular vitamin B 12 -producing Lactobacillus strains and their characteristics in tolerance to environmental stresses, gastric acid and bile salts. Two isolates, Lactobacillus plantarum LZ95 and CY2, showed high extracellular B 12 production, 98±15μg/L and 60±9μg/L respectively. Extracellular B 12 from LZ95 were identified as adenosylcobalamin and methylcobalamin using a combination of solid phase extraction and reverse-phase HPLC, while that from CY2 was adenosylcobalamin. Both strains grew under environmental stresses, and LZ95 exhibited better tolerance to low temperature and high ethanol concentration. LZ95 also showed good viability when exposed to gastric acid (pH 2.0 and 3.0) and bile salts (0.3%) as well as good adhesion to Caco-2 cells. The viability of CY2 was significantly reduced under low pH and exposure to bile salt. Together, extracellular B 12 producer LZ95 with good probiotic properties might be a candidate for in situ B 12 fortification in the food industry. Copyright © 2017 Elsevier Ltd. All rights reserved.

Skin Rejuvenation with Non-Invasive Pulsed Electric Fields

Science.gov (United States)

Golberg, Alexander; Khan, Saiqa; Belov, Vasily; Quinn, Kyle P.; Albadawi, Hassan; Felix Broelsch, G.; Watkins, Michael T.; Georgakoudi, Irene; Papisov, Mikhail; Mihm, Martin C., Jr.; Austen, William G., Jr.; Yarmush, Martin L.

2015-05-01

Degenerative skin diseases affect one third of individuals over the age of sixty. Current therapies use various physical and chemical methods to rejuvenate skin; but since the therapies affect many tissue components including cells and extracellular matrix, they may also induce significant side effects, such as scarring. Here we report on a new, non-invasive, non-thermal technique to rejuvenate skin with pulsed electric fields. The fields destroy cells while simultaneously completely preserving the extracellular matrix architecture and releasing multiple growth factors locally that induce new cells and tissue growth. We have identified the specific pulsed electric field parameters in rats that lead to prominent proliferation of the epidermis, formation of microvasculature, and secretion of new collagen at treated areas without scarring. Our results suggest that pulsed electric fields can improve skin function and thus can potentially serve as a novel non-invasive skin therapy for multiple degenerative skin diseases.

Quantum particle in a potential well field and in an electric field

International Nuclear Information System (INIS)

Gyunter, U.; Olejnik, V.P.

1990-01-01

Solutions of the Dirac equation in the field of δ-like potential well with arbitrary symmetry and in uniform electric field were obtained and analyzed. It is shown that wave function and energy of electron in bound state in the absence of electric field depend sufficiently on the type of potential well symmetry. 1 ref

Insertion of tetracysteine motifs into dopamine transporter extracellular domains.

Directory of Open Access Journals (Sweden)

Deanna M Navaroli

Full Text Available The neuronal dopamine transporter (DAT is a major determinant of extracellular dopamine (DA levels and is the primary target for a variety of addictive and therapeutic psychoactive drugs. DAT is acutely regulated by protein kinase C (PKC activation and amphetamine exposure, both of which modulate DAT surface expression by endocytic trafficking. In order to use live imaging approaches to study DAT endocytosis, methods are needed to exclusively label the DAT surface pool. The use of membrane impermeant, sulfonated biarsenic dyes holds potential as one such approach, and requires introduction of an extracellular tetracysteine motif (tetraCys; CCPGCC to facilitate dye binding. In the current study, we took advantage of intrinsic proline-glycine (Pro-Gly dipeptides encoded in predicted DAT extracellular domains to introduce tetraCys motifs into DAT extracellular loops 2, 3, and 4. [(3H]DA uptake studies, surface biotinylation and fluorescence microscopy in PC12 cells indicate that tetraCys insertion into the DAT second extracellular loop results in a functional transporter that maintains PKC-mediated downregulation. Introduction of tetraCys into extracellular loops 3 and 4 yielded DATs with severely compromised function that failed to mature and traffic to the cell surface. This is the first demonstration of successful introduction of a tetracysteine motif into a DAT extracellular domain, and may hold promise for use of biarsenic dyes in live DAT imaging studies.

Neurotransmitter modulation of extracellular H+ fluxes from isolated retinal horizontal cells of the skate

Science.gov (United States)

Molina, Anthony J A; Verzi, Michael P; Birnbaum, Andrea D; Yamoah, Ebenezer N; Hammar, Katherine; Smith, Peter J S; Malchow, Robert Paul

2004-01-01

Self-referencing H+-selective microelectrodes were used to measure extracellular H+ fluxes from horizontal cells isolated from the skate retina. A standing H+ flux was detected from quiescent cells, indicating a higher concentration of free hydrogen ions near the extracellular surface of the cell as compared to the surrounding solution. The standing H+ flux was reduced by removal of extracellular sodium or application of 5-(N-ethyl-N-isopropyl) amiloride (EIPA), suggesting activity of a Na+–H+ exchanger. Glutamate decreased H+ flux, lowering the concentration of free hydrogen ions around the cell. AMPA/kainate receptor agonists mimicked the response, and the AMPA/kainate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) eliminated the effects of glutamate and kainate. Metabotropic glutamate agonists were without effect. Glutamate-induced alterations in H+ flux required extracellular calcium, and were abolished when cells were bathed in an alkaline Ringer solution. Increasing intracellular calcium by photolysis of the caged calcium compound NP-EGTA also altered extracellular H+ flux. Immunocytochemical localization of the plasmalemma Ca2+–H+-ATPase (PMCA pump) revealed intense labelling within the outer plexiform layer and on isolated horizontal cells. Our results suggest that glutamate modulation of H+ flux arises from calcium entry into cells with subsequent activation of the plasmalemma Ca2+–H+-ATPase. These neurotransmitter-induced changes in extracellular pH have the potential to play a modulatory role in synaptic processing in the outer retina. However, our findings argue against the hypothesis that hydrogen ions released by horizontal cells normally act as the inhibitory feedback neurotransmitter onto photoreceptor synaptic terminals to create the surround portion of the centre-surround receptive fields of retinal neurones. PMID:15272044

Isolation and characterization of urinary extracellular vesicles: implications for biomarker discovery.

Science.gov (United States)

Merchant, Michael L; Rood, Ilse M; Deegens, Jeroen K J; Klein, Jon B

2017-12-01

Urine is a valuable diagnostic medium and, with the discovery of urinary extracellular vesicles, is viewed as a dynamic bioactive fluid. Extracellular vesicles are lipid-enclosed structures that can be classified into three categories: exosomes, microvesicles (or ectosomes) and apoptotic bodies. This classification is based on the mechanisms by which membrane vesicles are formed: fusion of multivesicular bodies with the plasma membranes (exosomes), budding of vesicles directly from the plasma membrane (microvesicles) or those shed from dying cells (apoptotic bodies). During their formation, urinary extracellular vesicles incorporate various cell-specific components (proteins, lipids and nucleic acids) that can be transferred to target cells. The rigour needed for comparative studies has fueled the search for optimal approaches for their isolation, purification, and characterization. RNA, the newest extracellular vesicle component to be discovered, has received substantial attention as an extracellular vesicle therapeutic, and compelling evidence suggests that ex vivo manipulation of microRNA composition may have uses in the treatment of kidney disorders. The results of these studies are building the case that urinary extracellular vesicles act as mediators of renal pathophysiology. As the field of extracellular vesicle studies is burgeoning, this Review focuses on primary data obtained from studies of human urine rather than on data from studies of laboratory animals or cultured immortalized cells.

Potential of Field Education as Signature Pedagogy: The Field Director Role

Science.gov (United States)

Lyter, Sharon C.

2012-01-01

In light of the assertion that field education is the signature pedagogy of social work education, this Internet-based study explores field director demographics and questions the fulfillment of this potential, examining BSW and MSW field education through the lens of the field director position. Field directors (159) and deans/directors (150)…

Shaping Synapses by the Neural Extracellular Matrix

Directory of Open Access Journals (Sweden)

Maura Ferrer-Ferrer

2018-05-01

Full Text Available Accumulating data support the importance of interactions between pre- and postsynaptic neuronal elements with astroglial processes and extracellular matrix (ECM for formation and plasticity of chemical synapses, and thus validate the concept of a tetrapartite synapse. Here we outline the major mechanisms driving: (i synaptogenesis by secreted extracellular scaffolding molecules, like thrombospondins (TSPs, neuronal pentraxins (NPs and cerebellins, which respectively promote presynaptic, postsynaptic differentiation or both; (ii maturation of synapses via reelin and integrin ligands-mediated signaling; and (iii regulation of synaptic plasticity by ECM-dependent control of induction and consolidation of new synaptic configurations. Particularly, we focused on potential importance of activity-dependent concerted activation of multiple extracellular proteases, such as ADAMTS4/5/15, MMP9 and neurotrypsin, for permissive and instructive events in synaptic remodeling through localized degradation of perisynaptic ECM and generation of proteolytic fragments as inducers of synaptic plasticity.

The role of extracellular conductivity profiles in compartmental models for neurons: particulars for layer 5 pyramidal cells.

Science.gov (United States)

Wang, Kai; Riera, Jorge; Enjieu-Kadji, Herve; Kawashima, Ryuta

2013-07-01

With the rapid increase in the number of technologies aimed at observing electric activity inside the brain, scientists have felt the urge to create proper links between intracellular- and extracellular-based experimental approaches. Biophysical models at both physical scales have been formalized under assumptions that impede the creation of such links. In this work, we address this issue by proposing a multicompartment model that allows the introduction of complex extracellular and intracellular resistivity profiles. This model accounts for the geometrical and electrotonic properties of any type of neuron through the combination of four devices: the integrator, the propagator, the 3D connector, and the collector. In particular, we applied this framework to model the tufted pyramidal cells of layer 5 (PCL5) in the neocortex. Our model was able to reproduce the decay and delay curves of backpropagating action potentials (APs) in this type of cell with better agreement with experimental data. We used the voltage drops of the extracellular resistances at each compartment to approximate the local field potentials generated by a PCL5 located in close proximity to linear microelectrode arrays. Based on the voltage drops produced by backpropagating APs, we were able to estimate the current multipolar moments generated by a PCL5. By adding external current sources in parallel to the extracellular resistances, we were able to create a sensitivity profile of PCL5 to electric current injections from nearby microelectrodes. In our model for PCL5, the kinetics and spatial profile of each ionic current were determined based on a literature survey, and the geometrical properties of these cells were evaluated experimentally. We concluded that the inclusion of the extracellular space in the compartmental models of neurons as an extra electrotonic medium is crucial for the accurate simulation of both the propagation of the electric potentials along the neuronal dendrites and the

Imaging and Quantification of Extracellular Vesicles by Transmission Electron Microscopy.

Science.gov (United States)

Linares, Romain; Tan, Sisareuth; Gounou, Céline; Brisson, Alain R

2017-01-01

Extracellular vesicles (EVs) are cell-derived vesicles that are present in blood and other body fluids. EVs raise major interest for their diverse physiopathological roles and their potential biomedical applications. However, the characterization and quantification of EVs constitute major challenges, mainly due to their small size and the lack of methods adapted for their study. Electron microscopy has made significant contributions to the EV field since their initial discovery. Here, we describe the use of two transmission electron microscopy (TEM) techniques for imaging and quantifying EVs. Cryo-TEM combined with receptor-specific gold labeling is applied to reveal the morphology, size, and phenotype of EVs, while their enumeration is achieved after high-speed sedimentation on EM grids.

The extracellular matrix: Structure, composition, age-related differences, tools for analysis and applications for tissue engineering.

Science.gov (United States)

Kular, Jaspreet K; Basu, Shouvik; Sharma, Ram I

2014-01-01

The extracellular matrix is a structural support network made up of diverse proteins, sugars and other components. It influences a wide number of cellular processes including migration, wound healing and differentiation, all of which is of particular interest to researchers in the field of tissue engineering. Understanding the composition and structure of the extracellular matrix will aid in exploring the ways the extracellular matrix can be utilised in tissue engineering applications especially as a scaffold. This review summarises the current knowledge of the composition, structure and functions of the extracellular matrix and introduces the effect of ageing on extracellular matrix remodelling and its contribution to cellular functions. Additionally, the current analytical technologies to study the extracellular matrix and extracellular matrix-related cellular processes are also reviewed.

Influx of extracellular Zn(2+) into the hippocampal CA1 neurons is required for cognitive performance via long-term potentiation.

Science.gov (United States)

Takeda, A; Suzuki, M; Tempaku, M; Ohashi, K; Tamano, H

2015-09-24

Physiological significance of synaptic Zn(2+) signaling was examined in the CA1 of young rats. In vivo CA1 long-term potentiation (LTP) was induced using a recording electrode attached to a microdialysis probe and the recording region was locally perfused with artificial cerebrospinal fluid (ACSF) via the microdialysis probe. In vivo CA1 LTP was inhibited under perfusion with CaEDTA and ZnAF-2DA, extracellular and intracellular Zn(2+) chelators, respectively, suggesting that the influx of extracellular Zn(2+) is required for in vivo CA1 LTP induction. The increase in intracellular Zn(2+) was chelated with intracellular ZnAF-2 in the CA1 1h after local injection of ZnAF-2DA into the CA1, suggesting that intracellular Zn(2+) signaling induced during learning is blocked with intracellular ZnAF-2 when the learning was performed 1h after ZnAF-2DA injection. Object recognition was affected when training of object recognition test was performed 1h after ZnAF-2DA injection. These data suggest that intracellular Zn(2+) signaling in the CA1 is required for object recognition memory via LTP. Surprisingly, in vivo CA1 LTP was affected under perfusion with 0.1-1μM ZnCl2, unlike the previous data that in vitro CA1 LTP was enhanced in the presence of 1-5μM ZnCl2. The influx of extracellular Zn(2+) into CA1 pyramidal cells has bidirectional action in CA1 LTP. The present study indicates that the degree of extracellular Zn(2+) influx into CA1 neurons is critical for LTP and cognitive performance. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Isolation, identification of an axenic fungal isolate of aspergillus sp. (mbl-1511) and its subsequent improvement for enhanced extracellular lipolytic potential through monoculture fermentation

International Nuclear Information System (INIS)

Iftikhar, T.; Sidra, A.; Ali, M.; Majeed, H.; Abdullah, R.

2017-01-01

The present investigation was conducted for extracellular lipases production. One hundred and forty samples of fungi were isolated from different environment and food samples. Among all the isolated cultures, an isolate obtained from chicken roasted in oil (MBL-1511) gave the highest extracellular lipase through SSF. Hyper producer strain (MBL-1511) was morphologically identified. A morphologically identified isolate of Aspergillus niger (MBL 1511) was verified by DNA barcoding marker like 18S rRNA gene sequence. The sequence of Aspergillus niger (MBL 1511) was registered with accession no. [GenBank: KP172477] in the public nucleotide library (genbank) of NCBI. The selected hyper producer of Aspergillus niger (MBL-1511) strain was subjected to physical and chemical mutagenic treatments to improve its lipolytic potential. Proximate analysis confirmed brassica meal as the best basal substrate with the lipases potential of 10.67+-0.01 IU/mL (wild) and 19.58+-0.04 IU/mL (mutant). The optimum conditions for the maximized extracellular lipases production were 1.0 mL inoculum at 30 degree C after 72 h at pH of 6.2. Finally, a potent mutant of A. niger [MBL-1511SA-4(150 min)] with an increased activity of 161 % over the wild strain was obtained when olive oil was used at 1% (v/v) concentration. (author)

The effect of nutrients on extracellular polymeric substance ...

African Journals Online (AJOL)

The effect of nutrients on extracellular polymeric substance (EPS) production and its impact on sludge properties and removal efficiencies were investigated in an in-depth field survey of wastewater treatment plants. Thereafter, laboratory studies were performed to evaluate the effect of a combination of nutrients - nitrogen ...

Minimal experimental requirements for definition of extracellular vesicles and their functions: a position statement from the International Society for Extracellular Vesicles.

Science.gov (United States)

Lötvall, Jan; Hill, Andrew F; Hochberg, Fred; Buzás, Edit I; Di Vizio, Dolores; Gardiner, Christopher; Gho, Yong Song; Kurochkin, Igor V; Mathivanan, Suresh; Quesenberry, Peter; Sahoo, Susmita; Tahara, Hidetoshi; Wauben, Marca H; Witwer, Kenneth W; Théry, Clotilde

2014-01-01

Secreted membrane-enclosed vesicles, collectively called extracellular vesicles (EVs), which include exosomes, ectosomes, microvesicles, microparticles, apoptotic bodies and other EV subsets, encompass a very rapidly growing scientific field in biology and medicine. Importantly, it is currently technically challenging to obtain a totally pure EV fraction free from non-vesicular components for functional studies, and therefore there is a need to establish guidelines for analyses of these vesicles and reporting of scientific studies on EV biology. Here, the International Society for Extracellular Vesicles (ISEV) provides researchers with a minimal set of biochemical, biophysical and functional standards that should be used to attribute any specific biological cargo or functions to EVs.

Skin Rejuvenation with Non-Invasive Pulsed Electric Fields

Science.gov (United States)

Golberg, Alexander; Khan, Saiqa; Belov, Vasily; Quinn, Kyle P.; Albadawi, Hassan; Felix Broelsch, G.; Watkins, Michael T.; Georgakoudi, Irene; Papisov, Mikhail; Mihm Jr., Martin C.; Austen Jr., William G.; Yarmush, Martin L.

2015-01-01

Degenerative skin diseases affect one third of individuals over the age of sixty. Current therapies use various physical and chemical methods to rejuvenate skin; but since the therapies affect many tissue components including cells and extracellular matrix, they may also induce significant side effects, such as scarring. Here we report on a new, non-invasive, non-thermal technique to rejuvenate skin with pulsed electric fields. The fields destroy cells while simultaneously completely preserving the extracellular matrix architecture and releasing multiple growth factors locally that induce new cells and tissue growth. We have identified the specific pulsed electric field parameters in rats that lead to prominent proliferation of the epidermis, formation of microvasculature, and secretion of new collagen at treated areas without scarring. Our results suggest that pulsed electric fields can improve skin function and thus can potentially serve as a novel non-invasive skin therapy for multiple degenerative skin diseases. PMID:25965851

Extracellular β-D-fructofuranosidase from Aspergillus parasiticus ...

African Journals Online (AJOL)

The β-D-fructofuranosidases are enzymes with biotechnological potential that can be used in different industrial sectors as food and beverage. In this context, microorganisms are important producers of these biomolecules, especially filamentous fungi. The production of extracellular β-Dfructofuranosidase from Aspergillus ...

The effective crystal field potential

CERN Document Server

Mulak, J

2000-01-01

As it results from the very nature of things, the spherical symmetry of the surrounding of a site in a crystal lattice or an atom in a molecule can never occur. Therefore, the eigenfunctions and eigenvalues of any bound ion or atom have to differ from those of spherically symmetric respective free ions. In this way, the most simplified concept of the crystal field effect or ligand field effect in the case of individual molecules can be introduced. The conventional notion of the crystal field potential is narrowed to its non-spherical part only through ignoring the dominating spherical part which produces only a uniform energy shift of gravity centres of the free ion terms. It is well understood that the non-spherical part of the effective potential "seen" by open-shell electrons localized on a metal ion plays an essential role in most observed properties. Light adsorption, electron paramagnetic resonance, inelastic neutron scattering and basic characteristics derived from magnetic and thermal measurements, ar...

Extracellular glycosylphosphatidylinositol-anchored mannoproteins and proteases of Cryptococcus neoformans.

Science.gov (United States)

Eigenheer, Richard A; Jin Lee, Young; Blumwald, Eduardo; Phinney, Brett S; Gelli, Angie

2007-06-01

Extracellular proteins of Cryptococcus neoformans are involved in the pathogenesis of cryptococcosis, and some are immunoreactive antigens that may potentially serve as candidates for vaccine development. To further study the extracellular proteome of the human fungal pathogen Cry. neoformans, we conducted a proteomic analysis of secreted and cell wall-bound proteins with an acapsular strain of Cry. neoformans. Proteins were identified from both intact cells and cell walls. In both cases, extracellular proteins were removed with trypsin or beta-glucanase, and then all proteins/peptides were purified by solid-phase extraction, spin dialysis, and HPLC, and identified by liquid chromatography-mass spectrometry. This study identified 29 extracellular proteins with a predicted N-terminal signal sequence and also a predicted glycosylphosphatidylinositol anchor motif in more than half. Among the novel proteins identified were five glycosylphosphatidylinositol-anchored proteins with extensive Ser/Thr-rich regions but no apparent functional domains, a glycosylphosphatidylinositol-anchored aspartic protease, and a metalloprotease with structural similarity to an elastinolytic metalloprotease of Aspergillus fumigatus. This study suggests that Cry. neoformans has the machinery required to target glycosylphosphatidylinositol-anchored proteins to the cell wall, and it confirms the extracellular proteolytic ability of Cry. neoformans.

The potential for targeting extracellular LOX proteins in human malignancy

DEFF Research Database (Denmark)

Mayorca Guiliani, Alejandro Enrique; Erler, Janine T

2013-01-01

The extracellular matrix (ECM) is the physical scaffold where cells are organized into tissues and organs. The ECM may be modified during cancer to allow and promote proliferation, invasion, and metastasis. The family of lysyl oxidase (LOX) enzymes cross-links collagens and elastin and, therefore......, is a central player in ECM deposition and maturation. Extensive research has revealed how the LOX proteins participate in every stage of cancer progression, and two family members, LOX and LOX-like 2, have been linked to metastasis, the final stage of cancer responsible for over 90% of cancer patient deaths...

Tumorigenic Potential of Extracellular Matrix Metalloproteinase Inducer

Science.gov (United States)

Zucker, Stanley; Hymowitz, Michelle; Rollo, Ellen E.; Mann, Richard; Conner, Cathleen E.; Cao, Jian; Foda, Hussein D.; Tompkins, David C.; Toole, Bryan P.

2001-01-01

Extracellular matrix metalloproteinase inducer (EMMPRIN), a glycoprotein present on the cancer cell plasma membrane, enhances fibroblast synthesis of matrix metalloproteinases (MMPs). The demonstration that peritumoral fibroblasts synthesize most of the MMPs in human tumors rather than the cancer cells themselves has ignited interest in the role of EMMPRIN in tumor dissemination. In this report we have demonstrated a role for EMMPRIN in cancer progression. Human MDA-MB-436 breast cancer cells, which are tumorigenic but slow growing in vivo, were transfected with EMMPRIN cDNA and injected orthotopically into mammary tissue of female NCr nu/nu mice. Green fluorescent protein was used to visualize metastases. In three experiments, breast cancer cell clones transfected with EMMPRIN cDNA were considerably more tumorigenic and invasive than plasmid-transfected cancer cells. Increased gelatinase A and gelatinase B expression (demonstrated by in situ hybridization and gelatin substrate zymography) was demonstrated in EMMPRIN-enhanced tumors. In contrast to de novo breast cancers in humans, human tumors transplanted into mice elicited minimal stromal or inflammatory cell reactions. Based on these experimental studies and our previous demonstration that EMMPRIN is prominently displayed in human cancer tissue, we propose that EMMPRIN plays an important role in cancer progression by increasing synthesis of MMPs. PMID:11395366

The potential of circulating extracellular small RNAs (smexRNA) in veterinary diagnostics-Identifying biomarker signatures by multivariate data analysis.

Science.gov (United States)

Melanie, Spornraft; Benedikt, Kirchner; Pfaffl, Michael W; Irmgard, Riedmaier

2015-09-01

Worldwide growth and performance-enhancing substances are used in cattle husbandry to increase productivity. In certain countries however e.g., in the EU, these practices are forbidden to prevent the consumers from potential health risks of substance residues in food. To maximize economic profit, 'black sheep' among farmers might circumvent the detection methods used in routine controls, which highlights the need for an innovative and reliable detection method. Transcriptomics is a promising new approach in the discovery of veterinary medicine biomarkers and also a missing puzzle piece, as up to date, metabolomics and proteomics are paramount. Due to increased stability and easy sampling, circulating extracellular small RNAs (smexRNAs) in bovine plasma were small RNA-sequenced and their potential to serve as biomarker candidates was evaluated using multivariate data analysis tools. After running the data evaluation pipeline, the proportion of miRNAs (microRNAs) and piRNAs (PIWI-interacting small non-coding RNAs) on the total sequenced reads was calculated. Additionally, top 10 signatures were compared which revealed that the readcount data sets were highly affected by the most abundant miRNA and piRNA profiles. To evaluate the discriminative power of multivariate data analyses to identify animals after veterinary drug application on the basis of smexRNAs, OPLS-DA was performed. In summary, the quality of miRNA models using all mapped reads for both treatment groups (animals treated with steroid hormones or the β-agonist clenbuterol) is predominant to those generated with combined data sets or piRNAs alone. Using multivariate projection methodologies like OPLS-DA have proven the best potential to generate discriminative miRNA models, supported by small RNA-Seq data. Based on the presented comparative OPLS-DA, miRNAs are the favorable smexRNA biomarker candidates in the research field of veterinary drug abuse.

Biological and bactericidal properties of Ag-doped bioactive glass in a natural extracellular matrix hydrogel with potential application in dentistry.

Science.gov (United States)

Wang, Y-Y; Chatzistavrou, X; Faulk, D; Badylak, S; Zheng, L; Papagerakis, S; Ge, L; Liu, H; Papagerakis, P

2015-06-20

The aim of this study was the fabrication and evaluation of a novel bioactive and bactericidal material, which could have applications in dentistry by supporting tissue regeneration and killing oral bacteria. Our hypothesis was that a new scaffold for pulp-dentin tissue engineering with enhanced antibacterial activity could be obtained by associating extracellular matrix derived from porcine bladder with an antibacterial bioactive glass. Our study combines in vitro approaches and ectopic implantation in scid mice. The novel material was fabricated by incorporating a sol-gel derived silver (Ag)-doped bioactive glass (BG) in a natural extracellular matrix (ECM) hydrogel in ratio 1:1 in weight % (Ag-BG/ECM). The biological properties of the Ag-BG/ECM were evaluated in culture with dental pulp stem cells (DPSCs). In particular, cell proliferation, cell apoptosis, stem cells markers profile, and cell differentiation potential were studied. Furthermore, the antibacterial activity against Streptococcus mutans and Lactobacillus casei was measured. Moreover, the capability of the material to enhance pulp/dentin regeneration in vivo was also evaluated. Our data show that Ag-BG/ECM significantly enhances DPSCs' proliferation, it does not affect cell morphology and stem cells markers profile, protects cells from apoptosis, and enhances in vitro cell differentiation and mineralisation potential as well as in vivo dentin formation. Furthermore, Ag-BG/ECM strongly inhibits S. mutans and L. casei growth suggesting that the new material has also anti-bacterial properties. This study provides foundation for future clinical applications in dentistry. It could potentially advance the currently available options of dental regenerative materials.

Non-potential Field Formation in the X-shaped Quadrupole Magnetic Field Configuration

Energy Technology Data Exchange (ETDEWEB)

Kawabata, Y.; Shimizu, T. [Department of Earth and Planetary Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan); Inoue, S., E-mail: kawabata.yusuke@ac.jaxa.jp [Max-Planck-Institute for Solar System Research, Justus-von-Liebig-Weg 3 D-37077 Göttingen (Germany)

2017-06-20

Some types of solar flares are observed in X-shaped quadrupolar field configuration. To understand the magnetic energy storage in such a region, we studied non-potential field formation in an X-shaped quadrupolar field region formed in the active region NOAA 11967, which produced three X-shaped M-class flares on 2014 February 2. Nonlinear force-free field modeling was applied to a time series of vector magnetic field maps from the Solar Optical Telescope on board Hinode and the Helioseismic and Magnetic Imager on board the Solar Dynamics Observatory . Our analysis of the temporal three-dimensional magnetic field evolution shows that the sufficient free energy had already been stored more than 10 hr before the occurrence of the first M-class flare and that the storage was observed in a localized region. In this localized region, quasi-separatrix layers (QSLs) started to develop gradually from 9 hr before the first M-class flare. One of the flare ribbons that appeared in the first M-class flare was co-spatial with the location of the QSLs, suggesting that the formation of the QSLs is important in the process of energy release. These QSLs do not appear in the potential field calculation, indicating that they were created by the non-potential field. The formation of the QSLs was associated with the transverse photospheric motion of the pre-emerged flux and the emergence of a new flux. This observation indicates that the occurrence of the flares requires the formation of QSLs in the non-potential field in which free magnetic energy is stored in advance.

Extracellular enzyme kinetics scale with resource availability

Science.gov (United States)

Sinsabaugh, Robert L.; Belnap, Jayne; Findlay, Stuart G.; Follstad Shah, Jennifer J.; Hill, Brian H.; Kuehn, Kevin A.; Kuske, Cheryl; Litvak, Marcy E.; Martinez, Noelle G.; Moorhead, Daryl L.; Warnock, Daniel D.

2014-01-01

Microbial community metabolism relies on external digestion, mediated by extracellular enzymes that break down complex organic matter into molecules small enough for cells to assimilate. We analyzed the kinetics of 40 extracellular enzymes that mediate the degradation and assimilation of carbon, nitrogen and phosphorus by diverse aquatic and terrestrial microbial communities (1160 cases). Regression analyses were conducted by habitat (aquatic and terrestrial), enzyme class (hydrolases and oxidoreductases) and assay methodology (low affinity and high affinity substrates) to relate potential reaction rates to substrate availability. Across enzyme classes and habitats, the scaling relationships between apparent Vmax and apparent Km followed similar power laws with exponents of 0.44 to 0.67. These exponents, called elasticities, were not statistically distinct from a central value of 0.50, which occurs when the Km of an enzyme equals substrate concentration, a condition optimal for maintenance of steady state. We also conducted an ecosystem scale analysis of ten extracellular hydrolase activities in relation to soil and sediment organic carbon (2,000–5,000 cases/enzyme) that yielded elasticities near 1.0 (0.9 ± 0.2, n = 36). At the metabolomic scale, the elasticity of extracellular enzymatic reactions is the proportionality constant that connects the C:N:P stoichiometries of organic matter and ecoenzymatic activities. At the ecosystem scale, the elasticity of extracellular enzymatic reactions shows that organic matter ultimately limits effective enzyme binding sites. Our findings suggest that one mechanism by which microbial communities maintain homeostasis is regulating extracellular enzyme expression to optimize the short-term responsiveness of substrate acquisition. The analyses also show that, like elemental stoichiometry, the fundamental attributes of enzymatic reactions can be extrapolated from biochemical to community and ecosystem scales.

Minimal experimental requirements for definition of extracellular vesicles and their functions: a position statement from the International Society for Extracellular Vesicles

Directory of Open Access Journals (Sweden)

Jan Lötvall

2014-12-01

Full Text Available Secreted membrane-enclosed vesicles, collectively called extracellular vesicles (EVs, which include exosomes, ectosomes, microvesicles, microparticles, apoptotic bodies and other EV subsets, encompass a very rapidly growing scientific field in biology and medicine. Importantly, it is currently technically challenging to obtain a totally pure EV fraction free from non-vesicular components for functional studies, and therefore there is a need to establish guidelines for analyses of these vesicles and reporting of scientific studies on EV biology. Here, the International Society for Extracellular Vesicles (ISEV provides researchers with a minimal set of biochemical, biophysical and functional standards that should be used to attribute any specific biological cargo or functions to EVs.

Dual functional extracellular recording using a light-addressable potentiometric sensor for bitter signal transduction.

Science.gov (United States)

Du, Liping; Wang, Jian; Chen, Wei; Zhao, Luhang; Wu, Chunsheng; Wang, Ping

2018-08-31

This paper presents a dual functional extracellular recording biosensor based on a light-addressable potentiometric sensor (LAPS). The design and fabrication of this biosensor make it possible to record both extracellular membrane potential changes and ATP release from a single taste bud cell for the first time. For detecting ATP release, LAPS chip was functionalized with ATP-sensitive DNA aptamer by covalent immobilization. Taste bud cells isolated from rat were cultured on LAPS surface. When the desired single taste bud cell was illuminated by modulated light, ATP release from single taste bud cells can be measured by recording the shifts of bias voltage-photocurrent curves (I-V curves) when the LAPS chip is working in discrete mode. On the other hand, extracellular membrane potential changes can be monitored by recording the fluctuation of LAPS photocurrent when the LAPS chip is working in continuous mode. The results show this biosensor can effectively record the enhancive effect of the bitter substance and inhibitory effect of the carbenoxolone (CBX) on the extracellular membrane potential changes and ATP release of single taste bud cells. In addition, the inhibitory effect of CBX also confirms LAPS extracellular recordings are originated from bitter signal transduction. It is proved this biosensor is suitable for extracellular recording of ATP release and membrane potential changes of single taste bud cells. It is suggested this biosensor could be applied to investigating taste signal transduction at the single-cell level as well as applied to other types of cells which have similar functions to taste bud cells. Copyright © 2018 Elsevier B.V. All rights reserved.

Biotechnological Aspects of Microbial Extracellular Electron Transfer

Science.gov (United States)

Kato, Souichiro

2015-01-01

Extracellular electron transfer (EET) is a type of microbial respiration that enables electron transfer between microbial cells and extracellular solid materials, including naturally-occurring metal compounds and artificial electrodes. Microorganisms harboring EET abilities have received considerable attention for their various biotechnological applications, in addition to their contribution to global energy and material cycles. In this review, current knowledge on microbial EET and its application to diverse biotechnologies, including the bioremediation of toxic metals, recovery of useful metals, biocorrosion, and microbial electrochemical systems (microbial fuel cells and microbial electrosynthesis), were introduced. Two potential biotechnologies based on microbial EET, namely the electrochemical control of microbial metabolism and electrochemical stimulation of microbial symbiotic reactions (electric syntrophy), were also discussed. PMID:26004795

Stabilizing effect of biochar on soil extracellular enzymes after a denaturing stress.

Science.gov (United States)

Elzobair, Khalid A; Stromberger, Mary E; Ippolito, James A

2016-01-01

Stabilizing extracellular enzymes may maintain enzymatic activity while protecting enzymes from proteolysis and denaturation. A study determined whether a fast pyrolysis hardwood biochar (CQuest™) would reduce evaporative losses, subsequently stabilizing soil extracellular enzymes and prohibiting potential enzymatic activity loss following a denaturing stress (microwaving). Soil was incubated in the presence of biochar (0%, 1%, 2%, 5%, or 10% by wt.) for 36 days and then exposed to microwave energies (0, 400, 800, 1600, or 3200 J g(-1) soil). Soil enzymes (β-glucosidase, β-d-cellobiosidase, N-acetyl-β-glucosaminidase, phosphatase, leucine aminopeptidase, β-xylosidase) were analyzed by fluorescence-based assays. Biochar amendment reduced leucine aminopeptidase and β-xylosidase potential activity after the incubation period and prior to stress exposure. The 10% biochar rate reduced soil water loss at the lowest stress level (400 J microwave energy g(-1) soil). Enzyme stabilization was demonstrated for β-xylosidase; intermediate biochar application rates prevented a complete loss of this enzyme's potential activity after soil was exposed to 400 (1% biochar treatment) or 1600 (5% biochar treatment) J microwave energy g(-1) soil. Remaining enzyme potential activities were not affected by biochar, and activities decreased with increasing stress levels. We concluded that biochar has the potential to reduce evaporative soil water losses and stabilize certain extracellular enzymes where activity is maintained after a denaturing stress; this effect was biochar rate and enzyme dependent. While biochar may reduce the potential activity of certain soil extracellular enzymes, this phenomenon was not universal as the majority of enzymes assayed in this study were unaffected by exposure to biochar. Copyright © 2015 Elsevier Ltd. All rights reserved.

An In Vitro Potency Assay for Monitoring the Immunomodulatory Potential of Stromal Cell-Derived Extracellular Vesicles

Directory of Open Access Journals (Sweden)

Karin Pachler

2017-07-01

Full Text Available The regenerative and immunomodulatory activity of mesenchymal stromal cells (MSCs is partially mediated by secreted vesicular factors. Extracellular vesicles (EVs exocytosed by MSCs are gaining increased attention as prospective non-cellular therapeutics for a variety of diseases. However, the lack of suitable in vitro assays to monitor the therapeutic potential of EVs currently restricts their application in clinical studies. We have evaluated a dual in vitro immunomodulation potency assay that reproducibly reports the inhibitory effect of MSCs on induced T-cell proliferation and the alloantigen-driven mixed leukocyte reaction of pooled peripheral blood mononuclear cells in a dose-dependent manner. Phytohemagglutinin-stimulated T-cell proliferation was inhibited by MSC-derived EVs in a dose-dependent manner comparable to MSCs. In contrast, inhibition of alloantigen-driven mixed leukocyte reaction was only observed for MSCs, but not for EVs. Our results support the application of a cell-based in vitro potency assay for reproducibly determining the immunomodulatory potential of EVs. Validation of this assay can help establish reliable release criteria for EVs for future clinical studies.

Method for isolation and molecular characterization of extracellular microvesicles released from brain endothelial cells

Directory of Open Access Journals (Sweden)

Haqqani Arsalan S

2013-01-01

Full Text Available Abstract Background In addition to possessing intracellular vesicles, eukaryotic cells also produce extracellular microvesicles, ranging from 50 to 1000 nm in diameter that are released or shed into the microenvironment under physiological and pathological conditions. These membranous extracellular organelles include both exosomes (originating from internal vesicles of endosomes and ectosomes (originating from direct budding/shedding of plasma membranes. Extracellular microvesicles contain cell-specific collections of proteins, glycoproteins, lipids, nucleic acids and other molecules. These vesicles play important roles in intercellular communication by acting as carrier for essential cell-specific information to target cells. Endothelial cells in the brain form the blood–brain barrier, a specialized interface between the blood and the brain that tightly controls traffic of nutrients and macromolecules between two compartments and interacts closely with other cells forming the neurovascular unit. Therefore, brain endothelial cell extracellular microvesicles could potentially play important roles in ‘externalizing’ brain-specific biomarkers into the blood stream during pathological conditions, in transcytosis of blood-borne molecules into the brain, and in cell-cell communication within the neurovascular unit. Methods To study cell-specific molecular make-up and functions of brain endothelial cell exosomes, methods for isolation of extracellular microvesicles using mass spectrometry-compatible protocols and the characterization of their signature profiles using mass spectrometry -based proteomics were developed. Results A total of 1179 proteins were identified in the isolated extracellular microvesicles from brain endothelial cells. The microvesicles were validated by identification of almost 60 known markers, including Alix, TSG101 and the tetraspanin proteins CD81 and CD9. The surface proteins on isolated microvesicles could potentially

Dynamic Artificial Potential Fields for Autonomous Camera Control

DEFF Research Database (Denmark)

Burelli, Paolo; Jhala, Arnav Harish

2009-01-01

the implementation and evaluation of Artificial Potential Fields for automatic camera placement. We first describe the re- casting of the frame composition problem as a solution to a two particles suspended in an Artificial Potential Field. We demonstrate the application of this technique to control both camera...

Highlights of the São Paulo ISEV workshop on extracellular vesicles in cross-kingdom communication

DEFF Research Database (Denmark)

Soares, Rodrigo P; Xander, Patrícia; Costa, Adriana Oliveira

2017-01-01

In the past years, extracellular vesicles (EVs) have become an important field of research since EVs have been found to play a central role in biological processes. In pathogens, EVs are involved in several events during the host–pathogen interaction, including invasion, immunomodulation, and pat......In the past years, extracellular vesicles (EVs) have become an important field of research since EVs have been found to play a central role in biological processes. In pathogens, EVs are involved in several events during the host–pathogen interaction, including invasion, immunomodulation...

Synergistic effect of defined artificial extracellular matrices and pulsed electric fields on osteogenic differentiation of human MSCs.

Science.gov (United States)

Hess, Ricarda; Jaeschke, Anna; Neubert, Holger; Hintze, Vera; Moeller, Stephanie; Schnabelrauch, Matthias; Wiesmann, Hans-Peter; Hart, David A; Scharnweber, Dieter

2012-12-01

In vivo, bone formation is a complex, tightly regulated process, influenced by multiple biochemical and physical factors. To develop a vital bone tissue engineering construct, all of these individual components have to be considered and integrated to gain an in vivo-like stimulation of target cells. The purpose of the present studies was to investigate the synergistic role of defined biochemical and physical microenvironments with respect to osteogenic differentiation of human mesenchymal stem cells (MSCs). Biochemical microenvironments have been designed using artificial extracellular matrices (aECMs), containing collagen I (coll) and glycosaminoglycans (GAGs) like chondroitin sulfate (CS), or a high-sulfated hyaluronan derivative (sHya), formulated as coatings on three-dimensional poly(caprolactone-co-lactide) (PCL) scaffolds. As part of the physical microenvironment, cells were exposed to pulsed electric fields via transformer-like coupling (TC). Results showed that aECM containing sHya enhanced osteogenic differentiation represented by increases in ALP activity and gene-expression (RT-qPCR) of several bone-related proteins (RUNX-2, ALP, OPN). Electric field stimulation alone did not influence cell proliferation, but osteogenic differentiation was enhanced if osteogenic supplements were provided, showing synergistic effects by the combination of sHya and electric fields. These results will improve the understanding of bone regeneration processes and support the development of effective tissue engineered bone constructs. Copyright © 2012 Elsevier Ltd. All rights reserved.

Dual-well potential field function for articulated manipulator trajectory planning

Directory of Open Access Journals (Sweden)

Ahmed Badawy

2016-06-01

Full Text Available A new attractive potential field function is proposed in this paper for manipulator trajectory planning. Existing attractive potential field constructs a global minimum through which maneuvering objects move down the gradient of the potential field toward this global minimum. The proposed method constructs a potential field with two minima. The purpose of these two minima is to create a dual attraction between links rather than affecting each link by the preceding one through kinematic constraints.

Modeling extracellular electrical stimulation: I. Derivation and interpretation of neurite equations.

Science.gov (United States)

Meffin, Hamish; Tahayori, Bahman; Grayden, David B; Burkitt, Anthony N

2012-12-01

Neuroprosthetic devices, such as cochlear and retinal implants, work by directly stimulating neurons with extracellular electrodes. This is commonly modeled using the cable equation with an applied extracellular voltage. In this paper a framework for modeling extracellular electrical stimulation is presented. To this end, a cylindrical neurite with confined extracellular space in the subthreshold regime is modeled in three-dimensional space. Through cylindrical harmonic expansion of Laplace's equation, we derive the spatio-temporal equations governing different modes of stimulation, referred to as longitudinal and transverse modes, under types of boundary conditions. The longitudinal mode is described by the well-known cable equation, however, the transverse modes are described by a novel ordinary differential equation. For the longitudinal mode, we find that different electrotonic length constants apply under the two different boundary conditions. Equations connecting current density to voltage boundary conditions are derived that are used to calculate the trans-impedance of the neurite-plus-thin-extracellular-sheath. A detailed explanation on depolarization mechanisms and the dominant current pathway under different modes of stimulation is provided. The analytic results derived here enable the estimation of a neurite's membrane potential under extracellular stimulation, hence bypassing the heavy computational cost of using numerical methods.

Extracellular matrix fluctuations during early embryogenesis

International Nuclear Information System (INIS)

Szabó, A; Rupp, P A; Rongish, B J; Little, C D; Czirók, A

2011-01-01

Extracellular matrix (ECM) movements and rearrangements were studied in avian embryos during early stages of development. We show that the ECM moves as a composite material, whereby distinct molecular components as well as spatially separated layers exhibit similar displacements. Using scanning wide field and confocal microscopy we show that the velocity field of ECM displacement is smooth in space and that ECM movements are correlated even at locations separated by several hundred micrometers. Velocity vectors, however, strongly fluctuate in time. The autocorrelation time of the velocity fluctuations is less than a minute. Suppression of the fluctuations yields a persistent movement pattern that is shared among embryos at equivalent stages of development. The high resolution of the velocity fields allows a detailed spatio-temporal characterization of important morphogenetic processes, especially tissue dynamics surrounding the embryonic organizer (Hensen's node)

Analytical formulation for φ4 field potential dynamics

International Nuclear Information System (INIS)

Javidan, Kurosh; Ghahraman, Arash

2011-01-01

An analytical model for adding a space dependent potential to the φ 4 field equation of motion is presented, by constructing a collective coordinate system for the solitary solutions of this model. The interaction of φ 4 solitons with a delta function potential barrier and also delta function potential well is investigated. Most of the characters of interaction are derived analytically while they are calculated by other models numerically. We will find that the behaviour of a solitary solution is like a point particle which is moved under the influence of a complicated effective potential. The effective potential is a function of the field initial conditions and also of parameters of the added potential. (author)

Self-constrained inversion of potential fields

Science.gov (United States)

Paoletti, V.; Ialongo, S.; Florio, G.; Fedi, M.; Cella, F.

2013-11-01

We present a potential-field-constrained inversion procedure based on a priori information derived exclusively from the analysis of the gravity and magnetic data (self-constrained inversion). The procedure is designed to be applied to underdetermined problems and involves scenarios where the source distribution can be assumed to be of simple character. To set up effective constraints, we first estimate through the analysis of the gravity or magnetic field some or all of the following source parameters: the source depth-to-the-top, the structural index, the horizontal position of the source body edges and their dip. The second step is incorporating the information related to these constraints in the objective function as depth and spatial weighting functions. We show, through 2-D and 3-D synthetic and real data examples, that potential field-based constraints, for example, structural index, source boundaries and others, are usually enough to obtain substantial improvement in the density and magnetization models.

Extracellular vesicles derived from mesenchymal stromal cells: a therapeutic option in respiratory diseases?

Science.gov (United States)

Abreu, Soraia C; Weiss, Daniel J; Rocco, Patricia R M

2016-04-14

Extracellular vesicles (EVs) are plasma membrane-bound fragments released from several cell types, including mesenchymal stromal cells (MSCs), constitutively or under stimulation. EVs derived from MSCs and other cell types transfer molecules (such as DNA, proteins/peptides, mRNA, microRNA, and lipids) and/or organelles with reparative and anti-inflammatory properties to recipient cells. The paracrine anti-inflammatory effects promoted by MSC-derived EVs have attracted significant interest in the regenerative medicine field, including for potential use in lung injuries. In the present review, we describe the characteristics, biological activities, and mechanisms of action of MSC-derived EVs. We also review the therapeutic potential of EVs as reported in relevant preclinical models of acute and chronic respiratory diseases, such as pneumonia, acute respiratory distress syndrome, asthma, and pulmonary arterial hypertension. Finally, we discuss possible approaches for potentiating the therapeutic effects of MSC-derived EVs so as to enable use of this therapy in clinical practice.

Nanoelectronics-biology frontier: From nanoscopic probes for action potential recording in live cells to three-dimensional cyborg tissues

OpenAIRE

Duan, Xiaojie; Fu, Tian-Ming; Liu, Jia; Lieber, Charles M.

2013-01-01

Semiconductor nanowires configured as the active channels of field-effect transistors (FETs) have been used as detectors for high-resolution electrical recording from single live cells, cell networks, tissues and organs. Extracellular measurements with substrate supported silicon nanowire (SiNW) FETs, which have projected active areas orders of magnitude smaller than conventional microfabricated multielectrode arrays (MEAs) and planar FETs, recorded action potential and field potential signa...

Methods for the physical characterization and quantification of extracellular vesicles in biological samples.

Science.gov (United States)

Rupert, Déborah L M; Claudio, Virginia; Lässer, Cecilia; Bally, Marta

2017-01-01

Our body fluids contain a multitude of cell-derived vesicles, secreted by most cell types, commonly referred to as extracellular vesicles. They have attracted considerable attention for their function as intercellular communication vehicles in a broad range of physiological processes and pathological conditions. Extracellular vesicles and especially the smallest type, exosomes, have also generated a lot of excitement in view of their potential as disease biomarkers or as carriers for drug delivery. In this context, state-of-the-art techniques capable of comprehensively characterizing vesicles in biological fluids are urgently needed. This review presents the arsenal of techniques available for quantification and characterization of physical properties of extracellular vesicles, summarizes their working principles, discusses their advantages and limitations and further illustrates their implementation in extracellular vesicle research. The small size and physicochemical heterogeneity of extracellular vesicles make their physical characterization and quantification an extremely challenging task. Currently, structure, size, buoyant density, optical properties and zeta potential have most commonly been studied. The concentration of vesicles in suspension can be expressed in terms of biomolecular or particle content depending on the method at hand. In addition, common quantification methods may either provide a direct quantitative measurement of vesicle concentration or solely allow for relative comparison between samples. The combination of complementary methods capable of detecting, characterizing and quantifying extracellular vesicles at a single particle level promises to provide new exciting insights into their modes of action and to reveal the existence of vesicle subpopulations fulfilling key biological tasks. Copyright © 2016 Elsevier B.V. All rights reserved.

Potential problems with interpolating fields

Energy Technology Data Exchange (ETDEWEB)

Birse, Michael C. [The University of Manchester, Theoretical Physics Division, School of Physics and Astronomy, Manchester (United Kingdom)

2017-11-15

A potential can have features that do not reflect the dynamics of the system it describes but rather arise from the choice of interpolating fields used to define it. This is illustrated using a toy model of scattering with two coupled channels. A Bethe-Salpeter amplitude is constructed which is a mixture of the waves in the two channels. The potential derived from this has a strong repulsive core, which arises from the admixture of the closed channel in the wave function and not from the dynamics of the model. (orig.)

Electric Potential and Electric Field Imaging with Applications

Science.gov (United States)

Generazio, Ed

2016-01-01

The technology and techniques for remote quantitative imaging of electrostatic potentials and electrostatic fields in and around objects and in free space is presented. Electric field imaging (EFI) technology may be applied to characterize intrinsic or existing electric potentials and electric fields, or an externally generated electrostatic field may be used for (illuminating) volumes to be inspected with EFI. The baseline sensor technology, electric field sensor (e-sensor), and its construction, optional electric field generation (quasistatic generator), and current e-sensor enhancements (ephemeral e-sensor) are discussed. Demonstrations for structural, electronic, human, and memory applications are shown. This new EFI capability is demonstrated to reveal characterization of electric charge distribution, creating a new field of study that embraces areas of interest including electrostatic discharge mitigation, crime scene forensics, design and materials selection for advanced sensors, dielectric morphology of structures, inspection of containers, inspection for hidden objects, tether integrity, organic molecular memory, and medical diagnostic and treatment efficacy applications such as cardiac polarization wave propagation and electromyography imaging.

Development of a Micronized Meniscus Extracellular Matrix Scaffold for Potential Augmentation of Meniscal Repair and Regeneration.

Science.gov (United States)

Monibi, Farrah A; Bozynski, Chantelle C; Kuroki, Keiichi; Stoker, Aaron M; Pfeiffer, Ferris M; Sherman, Seth L; Cook, James L

2016-12-01

Decellularized scaffolds composed of extracellular matrix (ECM) hold promise for repair and regeneration of the meniscus, given the potential for ECM-based biomaterials to aid in stem cell recruitment, infiltration, and differentiation. The objectives of this study were to decellularize canine menisci to fabricate a micronized, ECM-derived scaffold and to determine the cytocompatibility and repair potential of the scaffold ex vivo. Menisci were decellularized with a combination of physical agitation and chemical treatments. For scaffold fabrication, decellularized menisci were cryoground into a powder and the size and morphology of the ECM particles were evaluated using scanning electron microscopy. Histologic and biochemical analyses of the scaffold confirmed effective decellularization with loss of proteoglycan from the tissue but no significant reduction in collagen content. When washed effectively, the decellularized scaffold was cytocompatible to meniscal fibrochondrocytes, synoviocytes, and whole meniscal tissue based on the resazurin reduction assay and histologic evaluation. In an ex vivo model for meniscal repair, radial tears were augmented with the scaffold delivered with platelet-rich plasma as a carrier, and compared to nonaugmented (standard-of-care) suture techniques. Histologically, there was no evidence of cellular migration or proliferation noted in any of the untreated or standard-of-care treatment groups after 40 days of culture. Conversely, cellular infiltration and proliferation were noted in scaffold-augmented repairs. These data suggest the potential for the scaffold to promote cellular survival, migration, and proliferation ex vivo. Further investigations are necessary to examine the potential for the scaffold to induce cellular differentiation and functional meniscal fibrochondrogenesis.

Effective potentials for twisted fields

International Nuclear Information System (INIS)

Banach, R.

1981-01-01

Minus the density of the effective action, evaluated at the lowest eigenfunction of the (space-time) derivative part of the second (functional) derivative of the classical action, is proposed as a generalised definition of the effective potential, applicable to twisted as well as untwisted sectors of a field theory. The proposal is corroborated by several specific calculations in the twisted sector, namely phi 4 theory (real and complex) and wrong-sign-Gordon theory, in an Einstein cylinder, where the exact integrability of the static solutions confirms the effective potential predictions. Both models exhibit a phase transition, which the effective potential locates, and the one-loop quantum shift in the critical radius is computed for the real phi 4 model, being a universal result. Topological mass generation at the classical level is pointed out, and the exactness of the classical effective potential approximation for complex phi 4 is discussed. (author)

Magnetic fields, special relativity and potential theory elementary electromagnetic theory

CERN Document Server

Chirgwin, B H; Kilmister, C W

1972-01-01

Magnetic Fields, Special Relativity and Potential Theory is an introduction to electromagnetism, special relativity, and potential theory, with emphasis on the magnetic field of steady currents (magnetostatics). Topics covered range from the origin of the magnetic field and the magnetostatic scalar potential to magnetization, electromagnetic induction and magnetic energy, and the displacement current and Maxwell's equations. This volume is comprised of five chapters and begins with an overview of magnetostatics, followed by a chapter on the methods of solving potential problems drawn from elec

A regularization method for extrapolation of solar potential magnetic fields

Science.gov (United States)

Gary, G. A.; Musielak, Z. E.

1992-01-01

The mathematical basis of a Tikhonov regularization method for extrapolating the chromospheric-coronal magnetic field using photospheric vector magnetograms is discussed. The basic techniques show that the Cauchy initial value problem can be formulated for potential magnetic fields. The potential field analysis considers a set of linear, elliptic partial differential equations. It is found that, by introducing an appropriate smoothing of the initial data of the Cauchy potential problem, an approximate Fourier integral solution is found, and an upper bound to the error in the solution is derived. This specific regularization technique, which is a function of magnetograph measurement sensitivities, provides a method to extrapolate the potential magnetic field above an active region into the chromosphere and low corona.

Filament shape versus coronal potential magnetic field structure

Science.gov (United States)

Filippov, B.

2016-01-01

Solar filament shape in projection on disc depends on the structure of the coronal magnetic field. We calculate the position of polarity inversion lines (PILs) of coronal potential magnetic field at different heights above the photosphere, which compose the magnetic neutral surface, and compare with them the distribution of the filament material in Hα chromospheric images. We found that the most of the filament material is enclosed between two PILs, one at a lower height close to the chromosphere and one at a higher level, which can be considered as a height of the filament spine. Observations of the same filament on the limb by the Solar Terrestrial Relations Observatory spacecraft confirm that the height of the spine is really very close to the value obtained from the PIL and filament border matching. Such matching can be used for filament height estimations in on-disc observations. Filament barbs are housed within protruding sections of the low-level PIL. On the base of simple model, we show that the similarity of the neutral surfaces in potential and non-potential fields with the same sub-photospheric sources is the reason for the found tendency for the filament material to gather near the potential-field neutral surface.

Action potential propagation: ion current or intramembrane electric field?

Science.gov (United States)

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.

CORONAL MAGNETIC FIELDS DERIVED FROM SIMULTANEOUS MICROWAVE AND EUV OBSERVATIONS AND COMPARISON WITH THE POTENTIAL FIELD MODEL

Energy Technology Data Exchange (ETDEWEB)

Miyawaki, Shun; Nozawa, Satoshi [Department of Science, Ibaraki University, Mito, Ibaraki 310-8512 (Japan); Iwai, Kazumasa; Shibasaki, Kiyoto [Nobeyama Solar Radio Observatory, National Astronomical Observatory of Japan, Minamimaki, Nagano 384-1305 (Japan); Shiota, Daikou, E-mail: shunmi089@gmail.com [Solar-Terrestrial Environment Laboratory, Nagoya University, Nagoya, Aichi 464-8601 (Japan)

2016-02-10

We estimated the accuracy of coronal magnetic fields derived from radio observations by comparing them to potential field calculations and the differential emission measure measurements using EUV observations. We derived line-of-sight components of the coronal magnetic field from polarization observations of the thermal bremsstrahlung in the NOAA active region 11150, observed around 3:00 UT on 2011 February 3 using the Nobeyama Radioheliograph at 17 GHz. Because the thermal bremsstrahlung intensity at 17 GHz includes both chromospheric and coronal components, we extracted only the coronal component by measuring the coronal emission measure in EUV observations. In addition, we derived only the radio polarization component of the corona by selecting the region of coronal loops and weak magnetic field strength in the chromosphere along the line of sight. The upper limits of the coronal longitudinal magnetic fields were determined as 100–210 G. We also calculated the coronal longitudinal magnetic fields from the potential field extrapolation using the photospheric magnetic field obtained from the Helioseismic and Magnetic Imager. However, the calculated potential fields were certainly smaller than the observed coronal longitudinal magnetic field. This discrepancy between the potential and the observed magnetic field strengths can be explained consistently by two reasons: (1) the underestimation of the coronal emission measure resulting from the limitation of the temperature range of the EUV observations, and (2) the underestimation of the coronal magnetic field resulting from the potential field assumption.

Evaluation of viability and proliferative activity of human urothelial cells cultured onto xenogenic tissue-engineered extracellular matrices.

LENUS (Irish Health Repository)

Davis, Niall F

2011-04-01

To evaluate the viability and proliferative activity of human urothelial cells (HUCs) cultured on tissue-engineered extracellular matrix scaffolds and to assess the potential of extracellular matrixes to support the growth of HUCs in their expected in vivo urine environment.

Potential of extracellular microRNAs as biomarkers of acetaminophen toxicity in children

Energy Technology Data Exchange (ETDEWEB)

Yang, Xi, E-mail: Xi.Yang@fda.hhs.gov [Division of Systems Biology, National Center for Toxicological Research, Food and Drug Administration, 3900 NCTR Road, Jefferson, AR (United States); Salminen, William F., E-mail: Willie.Salminen@parexel.com [Division of Systems Biology, National Center for Toxicological Research, Food and Drug Administration, 3900 NCTR Road, Jefferson, AR (United States); Shi, Qiang, E-mail: Qiang.Shi@fda.hhs.gov [Division of Systems Biology, National Center for Toxicological Research, Food and Drug Administration, 3900 NCTR Road, Jefferson, AR (United States); Greenhaw, James, E-mail: James.Greenhaw@fda.hhs.gov [Division of Systems Biology, National Center for Toxicological Research, Food and Drug Administration, 3900 NCTR Road, Jefferson, AR (United States); Gill, Pritmohinder S., E-mail: PSGill@uams.edu [Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR (United States); Clinical Pharmacology and Toxicology Section, Arkansas Children' s Hospital, Little Rock, AR (United States); Bhattacharyya, Sudeepa, E-mail: SBhattacharyya2@uams.edu [Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR (United States); Clinical Pharmacology and Toxicology Section, Arkansas Children' s Hospital, Little Rock, AR (United States); Beger, Richard D., E-mail: Richard.Beger@fda.hhs.gov [Division of Systems Biology, National Center for Toxicological Research, Food and Drug Administration, 3900 NCTR Road, Jefferson, AR (United States); Mendrick, Donna L., E-mail: Donna.Mendrick@fda.hhs.gov [Division of Systems Biology, National Center for Toxicological Research, Food and Drug Administration, 3900 NCTR Road, Jefferson, AR (United States); Mattes, William B., E-mail: William.Mattes@fda.hhs.gov [Division of Systems Biology, National Center for Toxicological Research, Food and Drug Administration, 3900 NCTR Road, Jefferson, AR (United States); and others

2015-04-15

Developing biomarkers for detecting acetaminophen (APAP) toxicity has been widely investigated. Recent studies of adults with APAP-induced liver injury have reported human serum microRNA-122 (miR-122) as a novel biomarker of APAP-induced liver injury. The goal of this study was to examine extracellular microRNAs (miRNAs) as potential biomarkers for APAP liver injury in children. Global levels of serum and urine miRNAs were examined in three pediatric subgroups: 1) healthy children (n = 10), 2) hospitalized children receiving therapeutic doses of APAP (n = 10) and 3) children hospitalized for APAP overdose (n = 8). Out of 147 miRNAs detected in the APAP overdose group, eight showed significantly increased median levels in serum (miR-122, -375, -423-5p, -30d-5p, -125b-5p, -4732-5p, -204-5p, and -574-3p), compared to the other groups. Analysis of urine samples from the same patients had significantly increased median levels of four miRNAs (miR-375, -940, -9-3p and -302a) compared to the other groups. Importantly, correlation of peak serum APAP protein adduct levels (an indicator of the oxidation of APAP to the reactive metabolite N-acetyl-para-quinone imine) with peak miRNA levels showed that the highest correlation was observed for serum miR-122 (R = 0.94; p < 0.01) followed by miR-375 (R = 0.70; p = 0.05). Conclusion: Our findings demonstrate that miRNAs are increased in children with APAP toxicity and correlate with APAP protein adducts, suggesting a potential role as biomarkers of APAP toxicity. - Highlights: • Serum miR-122 and miR-375 levels were increased in children with APAP overdose. • Urine levels of miR-375 and miR-940 were increased in the APAP overdose group. • Peak serum miR-122 levels were correlated with peak serum APAP protein adducts.

Photospheric Driving of Non-Potential Coronal Magnetic Field Simulations

Science.gov (United States)

2016-09-19

synthesize observable emission . In future, the computational speed of the MF model makes it a potential avenue for near- real time and/or ensemble...AFRL-AFOSR-UK-TR-2016-0030 PHOTOSPHERIC DRIVING OF NON-POTENTIAL CORONAL MAGNETIC FIELD SIMULATIONS Anthony Yeates UNIVERSITY OF DURHAM Final Report...Final 3. DATES COVERED (From - To)  15 Sep 2014 to 14 Sep 2017 4. TITLE AND SUBTITLE PHOTOSPHERIC DRIVING OF NON-POTENTIAL CORONAL MAGNETIC FIELD

A cell-surface-anchored ratiometric fluorescent probe for extracellular pH sensing.

Science.gov (United States)

Ke, Guoliang; Zhu, Zhi; Wang, Wei; Zou, Yuan; Guan, Zhichao; Jia, Shasha; Zhang, Huimin; Wu, Xuemeng; Yang, Chaoyong James

2014-09-10

Accurate sensing of the extracellular pH is a very important yet challenging task in biological and clinical applications. This paper describes the development of an amphiphilic lipid-DNA molecule as a simple yet useful cell-surface-anchored ratiometric fluorescent probe for extracellular pH sensing. The lipid-DNA probe, which consists of a hydrophobic diacyllipid tail and a hydrophilic DNA strand, is modified with two fluorescent dyes; one is pH-sensitive as pH indicator and the other is pH-insensitive as an internal reference. The lipid-DNA probe showed sensitive and reversible response to pH change in the range of 6.0-8.0, which is suitable for most extracellular studies. In addition, based on simple hydrophobic interactions with the cell membrane, the lipid-DNA probe can be easily anchored on the cell surface with negligible cytotoxicity, excellent stability, and unique ratiometric readout, thus ensuring its accurate sensing of extracellular pH. Finally, this lipid-DNA-based ratiometric pH indicator was successfully used for extracellular pH sensing of cells in 3D culture environment, demonstrating the potential applications of the sensor in biological and medical studies.

Targeting Extracellular Histones with Novel RNA Bio drugs for the Treatment of Acute Lung Injury

Science.gov (United States)

2017-10-01

AWARD NUMBER: W81XWH-16-1-0179 TITLE: Targeting Extracellular Histones with Novel RNA Bio -drugs for the Treatment of Acute Lung Injury...4. TITLE AND SUBTITLE Targeting Extracellular Histones with Novel RNA Bio -drugs for the Treatment of Acute Lung Injury 5a. CONTRACT NUMBER 5b...and field situations. To accomplish this goal, we developed novel bio -reagents (RNA aptamers) that bind to those histones known to cause MODS/ARDS and

SPARC regulates extracellular matrix organization through its modulation of integrin-linked kinase activity.

Science.gov (United States)

Barker, Thomas H; Baneyx, Gretchen; Cardó-Vila, Marina; Workman, Gail A; Weaver, Matt; Menon, Priya M; Dedhar, Shoukat; Rempel, Sandra A; Arap, Wadih; Pasqualini, Renata; Vogel, Viola; Sage, E Helene

2005-10-28

SPARC, a 32-kDa matricellular glycoprotein, mediates interactions between cells and their extracellular matrix, and targeted deletion of Sparc results in compromised extracellular matrix in mice. Fibronectin matrix provides provisional tissue scaffolding during development and wound healing and is essential for the stabilization of mature extracellular matrix. Herein, we report that SPARC expression does not significantly affect fibronectin-induced cell spreading but enhances fibronectin-induced stress fiber formation and cell-mediated partial unfolding of fibronectin molecules, an essential process in fibronectin matrix assembly. By phage display, we identify integrin-linked kinase as a potential binding partner of SPARC and verify the interaction by co-immunoprecipitation and colocalization in vitro. Cells lacking SPARC exhibit diminished fibronectin-induced integrin-linked kinase activation and integrin-linked kinase-dependent cell-contractile signaling. Furthermore, induced expression of SPARC in SPARC-null fibroblasts restores fibronectin-induced integrin-linked kinase activation, downstream signaling, and fibronectin unfolding. These data further confirm the function of SPARC in extracellular matrix organization and identify a novel mechanism by which SPARC regulates extracellular matrix assembly.

Do field-free electromagnetic potentials play a role in biology?

Science.gov (United States)

Szasz, A; Vincze, G; Andocs, G; Szasz, O

2009-01-01

All bio-systems are imperfect dielectrics. Their general properties however cannot be described by conventional simple electrodynamics; the system is more complex. A central question in our present paper is centered on a controversial debate of the possible effect of the zero fields (only potentials exist). We show that the identical use of the "field-free," "curl-free," and "force-free" terminologies is incorrect, there have definitely different meanings. It is shown that the effective electro-dynamical parameters that describe and modify living systems are the potentials and not the fields. We discuss how the potentials have a role in biological processes even in field-free cases.

Off disk-center potential field calculations using vector magnetograms

Science.gov (United States)

Venkatakrishnan, P.; Gary, G. Allen

1989-01-01

A potential field calculation for off disk-center vector magnetograms that uses all the three components of the measured field is investigated. There is neither any need for interpolation of grid points between the image plane and the heliographic plane nor for an extension or a truncation to a heliographic rectangle. Hence, the method provides the maximum information content from the photospheric field as well as the most consistent potential field independent of the viewing angle. The introduction of polarimetric noise produces a less tolerant extrapolation procedure than using the line-of-sight extrapolation, but the resultant standard deviation is still small enough for the practical utility of this method.

Circulating extracellular vesicles with specific proteome and liver microRNAs are potential biomarkers for liver injury in experimental fatty liver disease.

Directory of Open Access Journals (Sweden)

Davide Povero

Full Text Available Nonalcoholic fatty liver disease (NAFLD is the most common chronic liver disease in both adult and children. Currently there are no reliable methods to determine disease severity, monitor disease progression, or efficacy of therapy, other than an invasive liver biopsy.Choline Deficient L-Amino Acid (CDAA and high fat diets were used as physiologically relevant mouse models of NAFLD. Circulating extracellular vesicles were isolated, fully characterized by proteomics and molecular analyses and compared to control groups. Liver-related microRNAs were isolated from purified extracellular vesicles and liver specimens.We observed statistically significant differences in the level of extracellular vesicles (EVs in liver and blood between two control groups and NAFLD animals. Time-course studies showed that EV levels increase early during disease development and reflect changes in liver histolopathology. EV levels correlated with hepatocyte cell death (r2 = 0.64, p<0.05, fibrosis (r2 = 0.66, p<0.05 and pathological angiogenesis (r2 = 0.71, p<0.05. Extensive characterization of blood EVs identified both microparticles (MPs and exosomes (EXO present in blood of NAFLD animals. Proteomic analysis of blood EVs detected various differentially expressed proteins in NAFLD versus control animals. Moreover, unsupervised hierarchical clustering identified a signature that allowed for discrimination between NAFLD and controls. Finally, the liver appears to be an important source of circulating EVs in NAFLD animals as evidenced by the enrichment in blood with miR-122 and 192--two microRNAs previously described in chronic liver diseases, coupled with a corresponding decrease in expression of these microRNAs in the liver.These findings suggest a potential for using specific circulating EVs as sensitive and specific biomarkers for the noninvasive diagnosis and monitoring of NAFLD.

Nanostructured gold microelectrodes for extracellular recording

Energy Technology Data Exchange (ETDEWEB)

Brueggemann, Dorothea; Wolfrum, Bernhard; Maybeck, Vanessa; Offenhaeusser, Andreas [CNI Center of Nanoelectronic Systems for Information Technology and Institute of Bio- and Nanosystems 2, Forschungszentrum Juelich (Germany)

2010-07-01

Electrophysiological activity of electrogenic cells is currently recorded with planar bioelectronic interfaces such as microelectrode arrays (MEAs). In this work, a novel concept of biocompatible nanostructured gold MEAs for extracellular signal recording is presented. MEAs were fabricated using clean room technologies, e.g. photolithography and metallization. Subsequently, they were modified with gold nanopillars of approximately 300 to 400 nm in height and 60 nm width. The nanostructuring process was carried out with a template-assisted approach using nanoporous aluminium oxide. Impedance spectroscopy of the resulting nanostructures showed higher capacitances compared to planar gold. This confirmed the expected increase of the surface area via nanostructuring. We used the nanostructured microelectrodes to record extracellular potentials from heart muscle cells (HL1), which were plated onto the chips. Good coupling between the HL1 cells and the nanostructured electrodes was observed. The resulting signal-to-noise ratio of nanopillar-MEAs was increased by a factor of 2 compared to planar MEAs. In future applications this nanopillar concept can be adopted for distinct interface materials and coupling to cellular and molecular sensing components.

Extracellular calcium controls the expression of two different forms of ripple-like hippocampal oscillations.

Science.gov (United States)

Aivar, Paloma; Valero, Manuel; Bellistri, Elisa; Menendez de la Prida, Liset

2014-02-19

Hippocampal high-frequency oscillations (HFOs) are prominent in physiological and pathological conditions. During physiological ripples (100-200 Hz), few pyramidal cells fire together coordinated by rhythmic inhibitory potentials. In the epileptic hippocampus, fast ripples (>200 Hz) reflect population spikes (PSs) from clusters of bursting cells, but HFOs in the ripple and the fast ripple range are vastly intermixed. What is the meaning of this frequency range? What determines the expression of different HFOs? Here, we used different concentrations of Ca(2+) in a physiological range (1-3 mM) to record local field potentials and single cells in hippocampal slices from normal rats. Surprisingly, we found that this sole manipulation results in the emergence of two forms of HFOs reminiscent of ripples and fast ripples recorded in vivo from normal and epileptic rats, respectively. We scrutinized the cellular correlates and mechanisms underlying the emergence of these two forms of HFOs by combining multisite, single-cell and paired-cell recordings in slices prepared from a rat reporter line that facilitates identification of GABAergic cells. We found a major effect of extracellular Ca(2+) in modulating intrinsic excitability and disynaptic inhibition, two critical factors shaping network dynamics. Moreover, locally modulating the extracellular Ca(2+) concentration in an in vivo environment had a similar effect on disynaptic inhibition, pyramidal cell excitability, and ripple dynamics. Therefore, the HFO frequency band reflects a range of firing dynamics of hippocampal networks.

Potential vorticity field in the Bay of Bengal during southwest monsoon

Digital Repository Service at National Institute of Oceanography (India)

Murty, V.S.N.; Rao, D.P.

theta), potential vorticity distribution is complex due to wind and freshwater forcings. The beta -effect dominates the potential vorticity field on 26.9 sigma theta isopycnal. The field of potential vorticity closely follows that of circulation...

Involvement of extracellular matrix constituents in breast cancer

Energy Technology Data Exchange (ETDEWEB)

Lochter, Andre; Bissell, Mina J

1995-06-01

It has recently been established that the extracellular matrix is required for normal functional differentiation of mammary epithelia not only in culture, but also in vivo. The mechanisms by which extracellular matrix affects differentiation, as well as the nature of extracellular matrix constituents which have major impacts on mammary gland function, have only now begun to be dissected. The intricate variety of extracellular matrix-mediated events and the remarkable degree of plasticity of extracellular matrix structure and composition at virtually all times during ontogeny, make such studies difficult. Similarly, during carcinogenesis, the extracellular matrix undergoes gross alterations, the consequences of which are not yet precisely understood. Nevertheless, an increasing amount of data suggests that the extracellular matrix and extracellular matrix-receptors might participate in the control of most, if not all, of the successive stages of breast tumors, from appearance to progression and metastasis.

Dermal extracellular lipid in birds.

Science.gov (United States)

Stromberg, M W; Hinsman, E J; Hullinger, R L

1990-01-01

A light and electron microscopic study of the skin of domestic chickens, seagulls, and antarctic penguins revealed abundant extracellular dermal lipid and intracellular epidermal lipid. Dermal lipid appeared ultrastructurally as extracellular droplets varying from less than 1 micron to more than 25 microns in diameter. The droplets were often irregularly contoured, sometimes round, and of relatively low electron density. Processes of fibrocytes were often seen in contact with extracellular lipid droplets. Sometimes a portion of such a droplet was missing, and this missing part appeared to have been "digested away" by the cell process. In places where cells or cell processes are in contact with fact droplets, there are sometimes extracellular membranous whorls or fragments which have been associated with the presence of fatty acids. Occasionally (in the comb) free fat particles were seen in intimate contact with extravasated erythrocytes. Fat droplets were seen in the lumen of small dermal blood and lymph vessels. We suggest that the dermal extracellular lipid originates in the adipocyte layer and following hydrolysis the free fatty acids diffuse into the epidermis. Here they become the raw material for forming the abundant neutral lipid contained in many of the epidermal cells of both birds and dolphins. The heretofore unreported presence and apparently normal utilization of abundant extracellular lipid in birds, as well as the presence of relatively large droplets of neutral lipid in dermal vessels, pose questions which require a thorough reappraisal of present concepts of the ways in which fat is distributed and utilized in the body.

Preservation and Significance of Extracellular DNA in Ferruginous Sediments from Lake Towuti, Indonesia

Directory of Open Access Journals (Sweden)

Aurèle Vuillemin

2017-07-01

Full Text Available Extracellular DNA is ubiquitous in soil and sediment and constitutes a dominant fraction of environmental DNA in aquatic systems. In theory, extracellular DNA is composed of genomic elements persisting at different degrees of preservation produced by processes occurring on land, in the water column and sediment. Extracellular DNA can be taken up as a nutrient source, excreted or degraded by microorganisms, or adsorbed onto mineral matrices, thus potentially preserving information from past environments. To test whether extracellular DNA records lacustrine conditions, we sequentially extracted extracellular and intracellular DNA from anoxic sediments of ferruginous Lake Towuti, Indonesia. We applied 16S rRNA gene Illumina sequencing on both fractions to discriminate exogenous from endogenous sources of extracellular DNA in the sediment. Environmental sequences exclusively found as extracellular DNA in the sediment originated from multiple sources. For instance, Actinobacteria, Verrucomicrobia, and Acidobacteria derived from soils in the catchment. Limited primary productivity in the water column resulted in few sequences of Cyanobacteria in the oxic photic zone, whereas stratification of the water body mainly led to secondary production by aerobic and anaerobic heterotrophs. Chloroflexi and Planctomycetes, the main degraders of sinking organic matter and planktonic sequences at the water-sediment interface, were preferentially preserved during the initial phase of burial. To trace endogenous sources of extracellular DNA, we used relative abundances of taxa in the intracellular DNA to define which microbial populations grow, decline or persist at low density with sediment depth. Cell lysis became an important additional source of extracellular DNA, gradually covering previous genetic assemblages as other microbial genera became more abundant with depth. The use of extracellular DNA as nutrient by active microorganisms led to selective removal of

Glioblastoma extracellular vesicles: reservoirs of potential biomarkers

Directory of Open Access Journals (Sweden)

Redzic JS

2014-02-01

Full Text Available Jasmina S Redzic,1 Timothy H Ung,2 Michael W Graner2 1Skaggs School of Pharmacy and Pharmaceutical Sciences, 2Department of Neurosurgery, School of Medicine, University of Colorado Denver, Aurora, CO, USA Abstract: Glioblastoma multiforme (GBM is the most frequent and most devastating of the primary central nervous system tumors, with few patients living beyond 2 years postdiagnosis. The damage caused by the disease and our treatments for the patients often leave them physically and cognitively debilitated. Generally, GBMs appear after very short clinical histories and are discovered by imaging (using magnetic resonance imaging [MRI], and the diagnosis is validated by pathology, following surgical resection. The treatment response and diagnosis of tumor recurrence are also tracked by MRI, but there are numerous problems encountered with these monitoring modalities, such as ambiguous interpretation and forms of pseudoprogression. Diagnostic, prognostic, and predictive biomarkers would be an immense boon in following treatment schemes and in determining recurrence, which often requires an invasive intracranial biopsy to verify imaging data. Extracellular vesicles (EVs are stable, membrane-enclosed, virus-sized particles released from either the cell surface or from endosomal pathways that lead to the systemic release of EVs into accessible biofluids, such as serum/plasma, urine, cerebrospinal fluid, and saliva. EVs carry a wide variety of proteins, nucleic acids, lipids, and other metabolites, with many common features but with enough individuality to be able to identify the cell of origin of the vesicles. These components, if properly interrogated, could allow for the identification of tumor-derived EVs in biofluids, indicating tumor progression, relapse, or treatment failure. That knowledge would allow clinicians to continue with treatment regimens that were actually effective or to change course if the therapies were failing. Here, we review

Field-aligned plasma-potential structure formed by local electron cyclotron resonance

International Nuclear Information System (INIS)

Hatakeyama, Rikizo; Kaneko, Toshiro; Sato, Noriyoshi

2001-01-01

The significance of basic experiments on field-aligned plasma-potential structure formed by local electron cyclotron resonance (ECR) is claimed based on the historical development of the investigation on electric double layer and electrostatic potential confinement of open-ended fusion-oriented plasmas. In the presence of a single ECR point in simple mirror-type configurations of magnetic field, a potential dip (thermal barrier) appears around this point, being followed by a subsequent potential hump (plug potential) along a collisionless plasma flow. The observed phenomenon gives a clear-cut physics to the formation of field-aligned plug potential with thermal barrier, which is closely related to the double layer formation triggered by a negative dip. (author)

Extracellular vesicles for personalized therapy decision support in advanced metastatic cancers and its potential impact for prostate cancer.

Science.gov (United States)

Soekmadji, Carolina; Corcoran, Niall M; Oleinikova, Irina; Jovanovic, Lidija; Ramm, Grant A; Nelson, Colleen C; Jenster, Guido; Russell, Pamela J

2017-10-01

The use of circulating tumor cells (CTCs) and circulating extracellular vesicles (EVs), such as exosomes, as liquid biopsy-derived biomarkers for cancers have been investigated. CTC enumeration using the CellSearch based platform provides an accurate insight on overall survival where higher CTC counts indicate poor prognosis for patients with advanced metastatic cancer. EVs provide information based on their lipid, protein, and nucleic acid content and can be isolated from biofluids and analyzed from a relatively small volume, providing a routine and non-invasive modality to monitor disease progression. Our pilot experiment by assessing the level of two subpopulations of small EVs, the CD9 positive and CD63 positive EVs, showed that the CD9 positive EV level is higher in plasma from patients with advanced metastatic prostate cancer with detectable CTCs. These data show the potential utility of a particular EV subpopulation to serve as biomarkers for advanced metastatic prostate cancer. EVs can potentially be utilized as biomarkers to provide accurate genotypic and phenotypic information for advanced prostate cancer, where new strategies to design a more personalized therapy is currently the focus of considerable investigation. © 2017 Wiley Periodicals, Inc.

Ratiometric Imaging of Extracellular pH in Dental Biofilms Using C-SNARF-4

DEFF Research Database (Denmark)

Dige, Irene

pH in dental biofilms plays a central role for the development of caries lesions. For decades, pH measurements in biofilms have been limited to recording pH with electrodes/microelectrodes that do not permit monitoring horizontal pH gradients in biofilms in real-time. Quantitative fluorescent...... microscopy can overcome these problems. Objective: The aim of this demonstration study was to monitor extracellular biofilm pH microscopically with the ratiometric pH-sensitive dye C-SNARF-4 in in-situ-grown dental biofilms. Methods: Using confocal microscopy, the dye C-SNARF-4 was employed both as p...... the microscopic images in order to exclusively determine extracellular pH. We monitored the pH drop at the biofilm-substratum interface in six microscopic fields of view per biofilm for 1h after exposure to 0.4% glucose. Results: Extracellular pH dropped rapidly in all specimens. In both individuals, analysis...

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

Science.gov (United States)

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.

Neutrophil Extracellular Traps in Ulcerative Colitis

DEFF Research Database (Denmark)

Bjerg Bennike, Tue; Carlsen, Thomas Gelsing; Ellingsen, Torkell

2015-01-01

microscopy and confocal microscopy. RESULTS: We identified and quantified 5711 different proteins with proteomics. The abundance of the proteins calprotectin and lactotransferrin in the tissue correlated with the degree of tissue inflammation as determined by histology. However, fecal calprotectin did...... not correlate. Forty-six proteins were measured with a statistically significant differences in abundances between the UC colon tissue and controls. Eleven of the proteins with increased abundances in the UC biopsies were associated with neutrophils and neutrophil extracellular traps. The findings were...... validated by microscopy, where an increased abundance of neutrophils and the presence of neutrophil extracellular traps by extracellular DNA present in the UC colon tissue were confirmed. CONCLUSIONS: Neutrophils, induced neutrophil extracellular traps, and several proteins that play a part in innate...

The Extracellular Matrix of Candida albicans Biofilms Impairs Formation of Neutrophil Extracellular Traps.

Science.gov (United States)

Johnson, Chad J; Cabezas-Olcoz, Jonathan; Kernien, John F; Wang, Steven X; Beebe, David J; Huttenlocher, Anna; Ansari, Hamayail; Nett, Jeniel E

2016-09-01

Neutrophils release extracellular traps (NETs) in response to planktonic C. albicans. These complexes composed of DNA, histones, and proteins inhibit Candida growth and dissemination. Considering the resilience of Candida biofilms to host defenses, we examined the neutrophil response to C. albicans during biofilm growth. In contrast to planktonic C. albicans, biofilms triggered negligible release of NETs. Time lapse imaging confirmed the impairment in NET release and revealed neutrophils adhering to hyphae and migrating on the biofilm. NET inhibition depended on an intact extracellular biofilm matrix as physical or genetic disruption of this component resulted in NET release. Biofilm inhibition of NETosis could not be overcome by protein kinase C activation via phorbol myristate acetate (PMA) and was associated with suppression of neutrophil reactive oxygen species (ROS) production. The degree of impaired NET release correlated with resistance to neutrophil attack. The clinical relevance of the role for extracellular matrix in diminishing NET production was corroborated in vivo using a rat catheter model. The C. albicans pmr1Δ/Δ, defective in production of matrix mannan, appeared to elicit a greater abundance of NETs by scanning electron microscopy imaging, which correlated with a decreased fungal burden. Together, these findings show that C. albicans biofilms impair neutrophil response through an inhibitory pathway induced by the extracellular matrix.

Extracellular Vesicles: How the External and Internal Environment Can Shape Cell-To-Cell Communication.

Science.gov (United States)

Neven, Kristof Y; Nawrot, Tim S; Bollati, Valentina

2017-03-01

To summarize the scientific evidence regarding the effects of environmental exposures on extracellular vesicle (EV) release and their contents. As environmental exposures might influence the aging phenotype in a very strict way, we will also report the role of EVs in the biological aging process. EV research is a new and quickly developing field. With many investigations conducted so far, only a limited number of studies have explored the potential role EVs play in the response and adaptation to environmental stimuli. The investigations available to date have identified several exposures or lifestyle factors able to modify EV trafficking including air pollutants, cigarette smoke, alcohol, obesity, nutrition, physical exercise, and oxidative stress. EVs are a very promising tool, as biological fluids are easily obtainable biological media that, if successful in identifying early alterations induced by the environment and predictive of disease, would be amenable to use for potential future preventive and diagnostic applications.

An inhibitory effect of extracellular Ca2+ on Ca2+-dependent exocytosis.

Directory of Open Access Journals (Sweden)

Wei Xiong

Full Text Available AIM: Neurotransmitter release is elicited by an elevation of intracellular Ca(2+ concentration ([Ca(2+](i. The action potential triggers Ca(2+ influx through Ca(2+ channels which causes local changes of [Ca(2+](i for vesicle release. However, any direct role of extracellular Ca(2+ (besides Ca(2+ influx on Ca(2+-dependent exocytosis remains elusive. Here we set out to investigate this possibility on rat dorsal root ganglion (DRG neurons and chromaffin cells, widely used models for studying vesicle exocytosis. RESULTS: Using photolysis of caged Ca(2+ and caffeine-induced release of stored Ca(2+, we found that extracellular Ca(2+ inhibited exocytosis following moderate [Ca(2+](i rises (2-3 µM. The IC(50 for extracellular Ca(2+ inhibition of exocytosis (ECIE was 1.38 mM and a physiological reduction (∼30% of extracellular Ca(2+ concentration ([Ca(2+](o significantly increased the evoked exocytosis. At the single vesicle level, quantal size and release frequency were also altered by physiological [Ca(2+](o. The calcimimetics Mg(2+, Cd(2+, G418, and neomycin all inhibited exocytosis. The extracellular Ca(2+-sensing receptor (CaSR was not involved because specific drugs and knockdown of CaSR in DRG neurons did not affect ECIE. CONCLUSION/SIGNIFICANCE: As an extension of the classic Ca(2+ hypothesis of synaptic release, physiological levels of extracellular Ca(2+ play dual roles in evoked exocytosis by providing a source of Ca(2+ influx, and by directly regulating quantal size and release probability in neuronal cells.

GABA-mediated synchronization in the human neocortex: elevations in extracellular potassium and presynaptic mechanisms.

Science.gov (United States)

Louvel, J; Papatheodoropoulos, C; Siniscalchi, A; Kurcewicz, I; Pumain, R; Devaux, B; Turak, B; Esposito, V; Villemeure, J G; Avoli, M

2001-01-01

Field potential and extracellular [K(+)] ([K(+)](o)) recordings were made in the human neocortex in an in vitro slice preparation to study the synchronous activity that occurs in the presence of 4-aminopyridine (50 microM) and ionotropic excitatory amino acid receptor antagonists. Under these experimental conditions, negative or negative-positive field potentials accompanied by rises in [K(+)](o) (up to 4.1 mM from a baseline of 3.25 mM) occurred spontaneously at intervals of 3-27 s. Both field potentials and [K(+)](o) elevations were largest at approximately 1000 microm from the pia. Similar events were induced by neocortical electrical stimuli. Application of medium containing low [Ca(2+)]/high [Mg(2+)] (n=3 slices), antagonism of the GABA(A) receptor (n=7) or mu-opioid receptor activation (n=4) abolished these events. Hence, they represented network, GABA-mediated potentials mainly reflecting the activation of type A receptors following GABA release from interneurons. The GABA(B) receptor agonist baclofen (10-100 microM, n=11) reduced and abolished the GABA-mediated potentials (ID(50)=18 microM). Baclofen effects were antagonized by the GABA(B) receptor antagonist CGP 35348 (0.1-1 mM, n=6; ID(50)=0.19 mM). CGP 38345 application to control medium increased the amplitude of the GABA-mediated potentials and the concomitant [K(+)](o) rises without modifying their rate of occurrence. The GABA-mediated potentials were not influenced by the broad-spectrum metabotropic glutamate agonist (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (100 microM, n=10), but decreased in rate with the group I receptor agonist (S)-3,5-dihydroxyphenylglycine (10-100 microM, n=9). Our data indicate that human neocortical networks challenged with 4-aminopyridine generate glutamatergic-independent, GABA-mediated potentials that are modulated by mu-opioid and GABA(B) receptors presumably located on interneuron terminals. These events are associated with [K(+)](o) elevations that may

Electrochemical Detection of Circadian Redox Rhythm in Cyanobacterial Cells via Extracellular Electron Transfer.

Science.gov (United States)

Nishio, Koichi; Pornpitra, Tunanunkul; Izawa, Seiichiro; Nishiwaki-Ohkawa, Taeko; Kato, Souichiro; Hashimoto, Kazuhito; Nakanishi, Shuji

2015-06-01

Recent research on cellular circadian rhythms suggests that the coupling of transcription-translation feedback loops and intracellular redox oscillations is essential for robust circadian timekeeping. For clarification of the molecular mechanism underlying the circadian rhythm, methods that allow for the dynamic and simultaneous detection of transcription/translation and redox oscillations in living cells are needed. Herein, we report that the cyanobacterial circadian redox rhythm can be electrochemically detected based on extracellular electron transfer (EET), a process in which intracellular electrons are exchanged with an extracellular electrode. As the EET-based method is non-destructive, concurrent detection with transcription/translation rhythm using bioluminescent reporter strains becomes possible. An EET pathway that electrochemically connected the intracellular region of cyanobacterial cells with an extracellular electrode was constructed via a newly synthesized electron mediator with cell membrane permeability. In the presence of the mediator, the open circuit potential of the culture medium exhibited temperature-compensated rhythm with approximately 24 h periodicity. Importantly, such circadian rhythm of the open circuit potential was not observed in the absence of the electron mediator, indicating that the EET process conveys the dynamic information regarding the intracellular redox state to the extracellular electrode. These findings represent the first direct demonstration of the intracellular circadian redox rhythm of cyanobacterial cells. © The Author 2015. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Extracellular Molecules Involved in Cancer Cell Invasion

International Nuclear Information System (INIS)

Stivarou, Theodora; Patsavoudi, Evangelia

2015-01-01

Nowadays it is perfectly clear that understanding and eradicating cancer cell invasion and metastasis represent the crucial, definitive points in cancer therapeutics. During the last two decades there has been a great interest in the understanding of the extracellular molecular mechanisms involved in cancer cell invasion. In this review, we highlight the findings concerning these processes, focusing in particular on extracellular molecules, including extracellular matrix proteins and their receptors, growth factors and their receptors, matrix metalloproteinases and extracellular chaperones. We report the molecular mechanisms underlying the important contribution of this pool of molecules to the complex, multi-step phenomenon of cancer cell invasion

Generating functionals for quantum field theories with random potentials

International Nuclear Information System (INIS)

Jain, Mudit; Vanchurin, Vitaly

2016-01-01

We consider generating functionals for computing correlators in quantum field theories with random potentials. Examples of such theories include cosmological systems in context of the string theory landscape (e.g. cosmic inflation) or condensed matter systems with quenched disorder (e.g. spin glass). We use the so-called replica trick to define two different generating functionals for calculating correlators of the quantum fields averaged over a given distribution of random potentials. The first generating functional is appropriate for calculating averaged (in-out) amplitudes and involves a single replica of fields, but the replica limit is taken to an (unphysical) negative one number of fields outside of the path integral. When the number of replicas is doubled the generating functional can also be used for calculating averaged probabilities (squared amplitudes) using the in-in construction. The second generating functional involves an infinite number of replicas, but can be used for calculating both in-out and in-in correlators and the replica limits are taken to only a zero number of fields. We discuss the formalism in details for a single real scalar field, but the generalization to more fields or to different types of fields is straightforward. We work out three examples: one where the mass of scalar field is treated as a random variable and two where the functional form of interactions is random, one described by a Gaussian random field and the other by a Euclidean action in the field configuration space.

Decoupling Action Potential Bias from Cortical Local Field Potentials

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Stephen V. David

2010-01-01

Full Text Available Neurophysiologists have recently become interested in studying neuronal population activity through local field potential (LFP recordings during experiments that also record the activity of single neurons. This experimental approach differs from early LFP studies because it uses high impendence electrodes that can also isolate single neuron activity. A possible complication for such studies is that the synaptic potentials and action potentials of the small subset of isolated neurons may contribute disproportionately to the LFP signal, biasing activity in the larger nearby neuronal population to appear synchronous and cotuned with these neurons. To address this problem, we used linear filtering techniques to remove features correlated with spike events from LFP recordings. This filtering procedure can be applied for well-isolated single units or multiunit activity. We illustrate the effects of this correction in simulation and on spike data recorded from primary auditory cortex. We find that local spiking activity can explain a significant portion of LFP power at most recording sites and demonstrate that removing the spike-correlated component can affect measurements of auditory tuning of the LFP.

Extracellular quaternary ammonium blockade of transient receptor potential vanilloid subtype 1 channels expressed in Xenopus laevis oocytes

DEFF Research Database (Denmark)

Rivera-Acevedo, Ricardo E; Pless, Stephan Alexander; Schwarz, Stephan K W

2012-01-01

expressed in Xenopus laevis oocytes, whereas the neutral local anesthetic, benzocaine, does not, suggesting that a titratable amine is required for high-affinity inhibition. Consistent with this possibility, extracellular tetraethylammonium (TEA) and tetramethylammonium application produces potent, voltage...

Common time-frequency analysis of local field potential and pyramidal cell activity in seizure-like events of the rat hippocampus

Science.gov (United States)

Cotic, M.; Chiu, A. W. L.; Jahromi, S. S.; Carlen, P. L.; Bardakjian, B. L.

2011-08-01

To study cell-field dynamics, physiologists simultaneously record local field potentials and the activity of individual cells from animals performing cognitive tasks, during various brain states or under pathological conditions. However, apart from spike shape and spike timing analyses, few studies have focused on elucidating the common time-frequency structure of local field activity relative to surrounding cells across different periods of phenomena. We have used two algorithms, multi-window time frequency analysis and wavelet phase coherence (WPC), to study common intracellular-extracellular (I-E) spectral features in spontaneous seizure-like events (SLEs) from rat hippocampal slices in a low magnesium epilepsy model. Both algorithms were applied to 'pairs' of simultaneously observed I-E signals from slices in the CA1 hippocampal region. Analyses were performed over a frequency range of 1-100 Hz. I-E spectral commonality varied in frequency and time. Higher commonality was observed from 1 to 15 Hz, and lower commonality was observed in the 15-100 Hz frequency range. WPC was lower in the non-SLE region compared to SLE activity; however, there was no statistical difference in the 30-45 Hz band between SLE and non-SLE modes. This work provides evidence of strong commonality in various frequency bands of I-E SLEs in the rat hippocampus, not only during SLEs but also immediately before and after.

Solution to reinforcement learning problems with artificial potential field

Institute of Scientific and Technical Information of China (English)

XIE Li-juan; XIE Guang-rong; CHEN Huan-wen; LI Xiao-li

2008-01-01

A novel method was designed to solve reinforcement learning problems with artificial potential field. Firstly a reinforcement learning problem was transferred to a path planning problem by using artificial potential field(APF), which was a very appropriate method to model a reinforcement learning problem. Secondly, a new APF algorithm was proposed to overcome the local minimum problem in the potential field methods with a virtual water-flow concept. The performance of this new method was tested by a gridworld problem named as key and door maze. The experimental results show that within 45 trials, good and deterministic policies are found in almost all simulations. In comparison with WIERING's HQ-learning system which needs 20 000 trials for stable solution, the proposed new method can obtain optimal and stable policy far more quickly than HQ-learning. Therefore, the new method is simple and effective to give an optimal solution to the reinforcement learning problem.

Extracellular vesicles: Exosomes, microvesicles, and friends

NARCIS (Netherlands)

Raposo, G.; Stoorvogel, W.|info:eu-repo/dai/nl/074352385

2013-01-01

Cells release into the extracellular environment diverse types of membrane vesicles of endosomal and plasma membrane origin called exosomes and microvesicles, respectively. These extracellular vesicles (EVs) represent an important mode of intercellular communication by serving as vehicles for

Fabrication of highly modulable fibrous 3D extracellular microenvironments

KAUST Repository

Zhang, Xixiang; Han, Fangfei; Syed, Ahad; Bukhari, Ebtihaj M.; Siang, Basil Chew Joo; Yang, Shan; Zhou, Bingpu; Wen, Wei-jia; Jiang, Dechen

2017-01-01

Three-dimensional (3D) in vitro scaffolds that mimic the irregular fibrous structures of in vivo extracellular matrix (ECM) are critical for many important biological applications. However, structural properties modulation of fibrous 3D scaffolds remains a challenge. Here, we report the first highly modulable 3D fibrous scaffolds self-assembled by high-aspect-ratio (HAR) microfibers. The scaffolds structural properties can be easily tailored to incorporate various physical cues, including geometry, stiffness, heterogeneity and nanotopography. Moreover, the fibrous scaffolds are readily and accurately patterned on desired locations of the substrate. Cell culture exhibits that our scaffolds can elicit strong bidirectional cell-material interactions. Furthermore, a functional disparity between the two-dimensional substrate and our 3D scaffolds is identified by cell spreading and proliferation data. These results prove the potential of the proposed scaffold as a biomimetic extracellular microenvironment for cell study.

Fabrication of highly modulable fibrous 3D extracellular microenvironments

KAUST Repository

Zhang, Xixiang

2017-06-13

Three-dimensional (3D) in vitro scaffolds that mimic the irregular fibrous structures of in vivo extracellular matrix (ECM) are critical for many important biological applications. However, structural properties modulation of fibrous 3D scaffolds remains a challenge. Here, we report the first highly modulable 3D fibrous scaffolds self-assembled by high-aspect-ratio (HAR) microfibers. The scaffolds structural properties can be easily tailored to incorporate various physical cues, including geometry, stiffness, heterogeneity and nanotopography. Moreover, the fibrous scaffolds are readily and accurately patterned on desired locations of the substrate. Cell culture exhibits that our scaffolds can elicit strong bidirectional cell-material interactions. Furthermore, a functional disparity between the two-dimensional substrate and our 3D scaffolds is identified by cell spreading and proliferation data. These results prove the potential of the proposed scaffold as a biomimetic extracellular microenvironment for cell study.

A novel extracellular glycosidase activity from Rhodotorula mucilaginosa: its application potential in wine aroma enhancement.

Science.gov (United States)

Hu, K; Zhu, X L; Mu, H; Ma, Y; Ullah, N; Tao, Y S

2016-02-01

The aim of the work was to evaluate the application potential of a glycosidase extract of one indigenous non-Saccharomyces strain in wine aroma enhancement. The isolate was selected from a local winemaking region in China for its high β-glucosidase level and was identified as Rhodotorula mucilaginosa. The tolerance of the glycosidase extract to the typical winemaking conditions was assessed using the activity of its β-glucosidase. After that, the hydrolysis capacity of R. mucilaginosa glycosidase for liberation of grape aroma glycosides was characterized in comparison to commercial enzyme preparations. Results of this work revealed that glycosidase extract from R. mucilaginosa proved to be active in the presence of 0-20% (w/v) glucose, 0-20% (v/v) ethanol and at pH 3·0-5·0. In the hydrolysis of aroma precursors, enzymes obtained from different origins possessed various levels of specificity and activity, showing high origin dependence (α = 0·05). Compared to commercial enzymes, the indigenous R. mucilaginosa glycosidase extract presented better catalytic preference for the 'fruity and floral' glycosides of benzenic compounds and C13 -norisoprenoids, but less sensitivity to the glycosides of C6 compounds and volatile phenols. This work presents a novel extracellular glycosidase preparation from an indigenous Rhodotorula mucilaginosa strain selected from a local winemaking region in China. This enzyme extract exhibits strong tolerance towards winemaking conditions. It shows hydrolysis specificity for glycosides of benzenic compounds and C13 -norisoprenoids, proving a potential candidate for improving floral and fruity aroma characteristics of wine. © 2015 The Society for Applied Microbiology.

Sources of extracellular tau and its signaling.

Science.gov (United States)

Avila, Jesús; Simón, Diana; Díaz-Hernández, Miguel; Pintor, Jesús; Hernández, Félix

2014-01-01

The pathology associated with tau protein, tauopathy, has been recently analyzed in different disorders, leading to the suggestion that intracellular and extracellular tau may itself be the principal agent in the transmission and spreading of tauopathies. Tau pathology is based on an increase in the amount of tau, an increase in phosphorylated tau, and/or an increase in aggregated tau. Indeed, phosphorylated tau protein is the main component of tau aggregates, such as the neurofibrillary tangles present in the brain of Alzheimer's disease patients. It has been suggested that intracellular tau could be toxic to neurons in its phosphorylated and/or aggregated form. However, extracellular tau could also damage neurons and since neuronal death is widespread in Alzheimer's disease, mainly among cholinergic neurons, these cells may represent a possible source of extracellular tau. However, other sources of extracellular tau have been proposed that are independent of cell death. In addition, several ways have been proposed for cells to interact with, transmit, and spread extracellular tau, and to transduce signals mediated by this tau. In this work, we will discuss the role of extracellular tau in the spreading of the tau pathology.

Cancer-derived extracellular vesicles: friend and foe of tumour immunosurveillance.

Science.gov (United States)

Dörsam, Bastian; Reiners, Kathrin S; von Strandmann, Elke Pogge

2018-01-05

Extracellular vesicles (EVs) are important players of intercellular signalling mechanisms, including communication with and among immune cells. EVs can affect the surrounding tissue as well as peripheral cells. Recently, EVs have been identified to be involved in the aetiology of several diseases, including cancer. Tumour cell-released EVs or exosomes have been shown to promote a tumour-supporting environment in non-malignant tissue and, thus, benefit metastasis. The underlying mechanisms are numerous: loss of antigen expression, direct suppression of immune effector cells, exchange of nucleic acids, alteration of the recipient cells' transcription and direct suppression of immune cells. Consequently, tumour cells can subvert the host's immune detection as well as suppress the immune system. On the contrary, recent studies reported the existence of EVs able to activate immune cells, thus promoting the tumour-directed immune response. In this article, the immunosuppressive capabilities of EVs, on the one hand, and their potential use in immunoactivation and therapeutic potential, on the other hand, are discussed.This article is part of the discussion meeting issue 'Extracellular vesicles and the tumour microenvironment'. © 2017 The Authors.

Analysis of extracellular RNA by digital PCR

Directory of Open Access Journals (Sweden)

Kenji eTakahashi

2014-06-01

Full Text Available The transfer of extracellular RNA is emerging as an important mechanism for intracellular communication. The ability for the transfer of functionally active RNA molecules from one cell to another within vesicles such as exosomes enables a cell to modulate cellular signaling and biological processes within recipient cells. The study of extracellular RNA requires sensitive methods for the detection of these molecules. In this methods article, we will describe protocols for the detection of such extracellular RNA using sensitive detection technologies such as digital PCR. These protocols should be valuable to researchers interested in the role and contribution of extracellular RNA to tumor cell biology.

Extracellular Molecules Involved in Cancer Cell Invasion

Directory of Open Access Journals (Sweden)

Theodora Stivarou

2015-01-01

Full Text Available Nowadays it is perfectly clear that understanding and eradicating cancer cell invasion and metastasis represent the crucial, definitive points in cancer therapeutics. During the last two decades there has been a great interest in the understanding of the extracellular molecular mechanisms involved in cancer cell invasion. In this review, we highlight the findings concerning these processes, focusing in particular on extracellular molecules, including extracellular matrix proteins and their receptors, growth factors and their receptors, matrix metalloproteinases and extracellular chaperones. We report the molecular mechanisms underlying the important contribution of this pool of molecules to the complex, multi-step phenomenon of cancer cell invasion.

Step-wise potential development across the lipid bilayer under external electric fields

Science.gov (United States)

Majhi, Amit Kumar

2018-04-01

Pore formation across the bilayers under external electric field is an important phenomenon, which has numerous applications in biology and bio-engineering fields. However, it is not a ubiquitous event under all field applications. To initiate a pore in the bilayer a particular threshold electric field is required. The electric field alters the intrinsic potential distribution across the bilayer as we as it enhances total potential drop across the bilayer, which causes the pore formation. The intrinsic potential profile has a maximum peak value, which is 0.8 V and it gets enhanced under application of external field, 0.43 V/nm. The peak value becomes 1.4 V when a pore appears in the bilayer and it continues to evolve as along as the external electric field remains switched on.

Neuronal excitation and permeabilization by 200-ns pulsed electric field: An optical membrane potential study with FluoVolt dye.

Science.gov (United States)

Pakhomov, Andrei G; Semenov, Iurii; Casciola, Maura; Xiao, Shu

2017-07-01

Electric field pulses of nano- and picosecond duration are a novel modality for neurostimulation, activation of Ca 2+ signaling, and tissue ablation. However it is not known how such brief pulses activate voltage-gated ion channels. We studied excitation and electroporation of hippocampal neurons by 200-ns pulsed electric field (nsPEF), by means of time-lapse imaging of the optical membrane potential (OMP) with FluoVolt dye. Electroporation abruptly shifted OMP to a more depolarized level, which was reached within 10s), so cells remained above the resting OMP level for at least 20-30s. Activation of voltage-gated sodium channels (VGSC) enhanced the depolarizing effect of electroporation, resulting in an additional tetrodotoxin-sensitive OMP peak in 4-5ms after nsPEF. Omitting Ca 2+ in the extracellular solution did not reduce the depolarization, suggesting no contribution of voltage-gated calcium channels (VGCC). In 40% of neurons, nsPEF triggered a single action potential (AP), with the median threshold of 3kV/cm (range: 1.9-4kV/cm); no APs could be evoked by stimuli below the electroporation threshold (1.5-1.9kV/cm). VGSC opening could already be detected in 0.5ms after nsPEF, which is too fast to be mediated by the depolarizing effect of electroporation. The overlap of electroporation and AP thresholds does not necessarily reflect the causal relation, but suggests a low potency of nsPEF, as compared to conventional electrostimulation, for VGSC activation and AP induction. Copyright © 2017 Elsevier B.V. All rights reserved.

[Inhibitory proteins of neuritic regeneration in the extracellular matrix: structure, molecular interactions and their functions. Mechanisms of extracellular balance].

Science.gov (United States)

Vargas, Javier; Uribe-Escamilla, Rebeca; Alfaro-Rodríguez, Alfonso

2013-01-01

After injury of the central nervous system (CNS) in higher vertebrates, neurons neither grow nor reconnect with their targets because their axons or dendrites cannot regenerate within the injured site. In the CNS, the signal from the environment regulating neurite regeneration is not exclusively generated by one molecular group. This signal is generated by the interaction of various types of molecules such as extracellular matrix proteins, soluble factors and surface membrane molecules; all these elements interact with one another generating the matrix's biological state: the extracellular balance. Proteins in the balanced extracellular matrix, support and promote cellular physiological states, including neuritic regeneration. We have reviewed three types of proteins of the extracellular matrix possessing an inhibitory effect and that are determinant of neuritic regeneration failure in the CNS: chondroitin sulfate proteoglycans, keratan sulfate proteoglycans and tenascin. We also review some of the mechanisms involved in the balance of extracellular proteins such as isomerization, epimerization, sulfation and glycosylation as well as the assemblage of the extracellular matrix, the interaction between the matrix and soluble factors and its proteolytic degradation. In the final section, we have presented some examples of the matrix's role in development and in tumor propagation.

Extracellular Nucleotide Hydrolysis in Dermal and Limbal Mesenchymal Stem Cells: A Source of Adenosine Production.

Science.gov (United States)

Naasani, Liliana I Sous; Rodrigues, Cristiano; de Campos, Rafael Paschoal; Beckenkamp, Liziane Raquel; Iser, Isabele C; Bertoni, Ana Paula Santin; Wink, Márcia R

2017-08-01

Human Limbal (L-MSCs) and Dermal Mesenchymal Stem Cell (D-MSCs) possess many properties that increase their therapeutic potential in ophthalmology and dermatology. It is known that purinergic signaling plays a role in many aspects of mesenchymal stem cells physiology. They release and respond to purinergic ligands, altering proliferation, migration, differentiation, and apoptosis. Therefore, more information on these processes would be crucial for establishing future clinical applications using their differentiation potential, but without undesirable side effects. This study evaluated and compared the expression of ecto-nucleotidases, the enzymatic activity of degradation of extracellular nucleotides and the metabolism of extracellular ATP in D-MSCs and L-MSCs, isolated from discard tissues of human skin and sclerocorneal rims. The D-MSCs and L-MSCs showed a differentiation potential into osteogenic, adipogenic, and chondrogenic lineages and the expression of markers CD105 + , CD44 + , CD14 - , CD34 - , CD45 - , as expected. Both cells hydrolyzed low levels of extracellular ATP and high levels of AMP, leading to adenosine accumulation that can regulate inflammation and tissue repair. These cells expressed mRNA for ENTPD1, 2, 3, 5 and 6, and CD73 that corresponded to the observed enzymatic activities. Thus, considering the degradation of ATP and adenosine production, limbal MSCs are very similar to dermal MSCs, indicating that from the aspect of extracellular nucleotide metabolism L-MSCs are very similar to the characterized D-MSCs. J. Cell. Biochem. 118: 2430-2442, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Extracellular histones in tissue injury and inflammation.

Science.gov (United States)

Allam, Ramanjaneyulu; Kumar, Santhosh V R; Darisipudi, Murthy N; Anders, Hans-Joachim

2014-05-01

Neutrophil NETosis is an important element of host defense as it catapults chromatin out of the cell to trap bacteria, which then are killed, e.g., by the chromatin's histone component. Also, during sterile inflammation TNF-alpha and other mediators trigger NETosis, which elicits cytotoxic effects on host cells. The same mechanism should apply to other forms of regulated necrosis including pyroptosis, necroptosis, ferroptosis, and cyclophilin D-mediated regulated necrosis. Beyond these toxic effects, extracellular histones also trigger thrombus formation and innate immunity by activating Toll-like receptors and the NLRP3 inflammasome. Thereby, extracellular histones contribute to the microvascular complications of sepsis, major trauma, small vessel vasculitis as well as acute liver, kidney, brain, and lung injury. Finally, histones prevent the degradation of extracellular DNA, which promotes autoimmunization, anti-nuclear antibody formation, and autoimmunity in susceptible individuals. Here, we review the current evidence on the pathogenic role of extracellular histones in disease and discuss how to target extracellular histones to improve disease outcomes.

Characterization and biological activities of extracellular melanin produced by Schizophyllum commune (Fries).

Science.gov (United States)

Arun, G; Eyini, M; Gunasekaran, P

2015-06-01

Melanins are enigmatic pigments produced by a wide variety of microorganisms including bacteria and fungi. Here, we have isolated and characterized extracellular melanin from mushroom fungus, Schizophyllum commune. The extracellular dark pigment produced by the broth culture of S. commune, after 21 days of incubation was recovered by hot acid-alkali treatment. The melanin nature of the pigment was characterized by biochemical tests and further, confirmed by UV, IR, EPR, NMR and MALDI-TOF Mass Spectra. Extracellular melanin, at 100 μg/ml, showed significant antibacterial activity against Escherichia coli, Bacillus subtilis, Klebsiella pneumoniae and Pseudomonas fluorescens and antifungal activity against Trichophyton simii and T. rubrum. At a concentration of 50 μg/ml, melanin showed high free radical scavenging activity of DPPH (2,2-diphenyl-1-picrylhydrazyl) indicating its antioxidant potential. It showed concentration dependent inhibition of cell proliferation of Human Epidermoid Larynx Carcinoma Cell Line (HEP-2). This study has demonstrated characterization of melanin from basidiomycetes mushroom fungus, Schizophyllum commune and its applications.

Neuropeptide Y infusion into the shell region of the rat nucleus accumbens increases extracellular levels of dopamine

DEFF Research Database (Denmark)

Sørensen, Gunnar; Wegener, Gregers; Hasselstrøm, Jørgen

2009-01-01

Increases in extracellular dopamine in the shell region of the nucleus accumbens are centrally involved in mediating reinforcement of addictive drugs. Neuropeptide Y (NPY) and its receptors are present in the nucleus accumbens and have been implicated in addiction mechanisms. This study further...... explored the potential role of NPY in addiction mechanisms using microdialysis to measure extracellular dopamine in vivo after infusion of NPY directly into the accumbal shell region of adult rats. NPY was found to dose-dependently increase extracellular dopamine levels, indicating that NPY could play...... an important role in drug reinforcement by modulating accumbal dopamine levels...

Scalar field cosmologies with inverted potentials

Energy Technology Data Exchange (ETDEWEB)

Boisseau, B.; Giacomini, H. [Université de Tours, Laboratoire de Mathématiques et Physique Théorique, CNRS/UMR 7350, 37200 Tours (France); Polarski, D., E-mail: bruno.boisseau@lmpt.univ-tours.fr, E-mail: hector.giacomini@lmpt.univ-tours.fr, E-mail: david.polarski@umontpellier.fr [Université Montpellier and CNRS, Laboratoire Charles Coulomb, UMR 5221, F-34095 Montpellier (France)

2015-10-01

Regular bouncing solutions in the framework of a scalar-tensor gravity model were found in a recent work. We reconsider the problem in the Einstein frame (EF) in the present work. Singularities arising at the limit of physical viability of the model in the Jordan frame (JF) are either of the Big Bang or of the Big Crunch type in the EF. As a result we obtain integrable scalar field cosmological models in general relativity (GR) with inverted double-well potentials unbounded from below which possess solutions regular in the future, tending to a de Sitter space, and starting with a Big Bang. The existence of the two fixed points for the field dynamics at late times found earlier in the JF becomes transparent in the EF.

Scalar field cosmologies with inverted potentials

International Nuclear Information System (INIS)

Boisseau, B.; Giacomini, H.; Polarski, D.

2015-01-01

Regular bouncing solutions in the framework of a scalar-tensor gravity model were found in a recent work. We reconsider the problem in the Einstein frame (EF) in the present work. Singularities arising at the limit of physical viability of the model in the Jordan frame (JF) are either of the Big Bang or of the Big Crunch type in the EF. As a result we obtain integrable scalar field cosmological models in general relativity (GR) with inverted double-well potentials unbounded from below which possess solutions regular in the future, tending to a de Sitter space, and starting with a Big Bang. The existence of the two fixed points for the field dynamics at late times found earlier in the JF becomes transparent in the EF

POTENTIAL USE OF AN EXTRACELLULAR ENZYME OF a-AMYLASE FROM INDIGENOUS INDONESIAN MESOPHILIC BACTERIA

Directory of Open Access Journals (Sweden)

Puji Lestari

2013-04-01

Full Text Available Amylase enzyme has a great significance for industrial usages in  Indonesia. However, this enzyme is still imported. The use of bacteria in biotechnological process of industrial products such as enzyme production has stimulated the exploration of extracellular amylase producing  bacteria. This study aimed to identify and analyze the potential use of amylolytic bacterial enzymes for hydrolyzing cassava starch. Two bacterial isolates, i.e. MII-10 and DKW-8 originated from Indonesia soil were identified based on their morphological, physiological and biochemical properties according to the standard protocol. The isolates were then  cultivated on fermentation medium and their growth pattern and  enzymatic assays were observed. The acetone-precipitated crude enzyme harvested based on predetermined cultivation time was used for  enzymatic hydrolysis product characterization on cassava starch using thin layer chromatography (TLC. The results showed that the mesophilicbacteria isolates (MII-10 and DKW-8 were belonged to Bacillus licheniformis. The maximum bacterial cell growth and enzyme activity were reached at 48 hours after incubation. The MII-10 isolate was found more stable than DKW-8 in producing amylase enzyme. Amylase produced by the MII-10 and DKW- 8 isolates was identified to be an endo-a-amylase as confirmed by oligosaccharides and dextrin of the random hydrolysisproducts. Relatively high dextrose equivalence (DE value of a-amylase of MII-10 (DE of 9.96 suggests that the enzyme is prospective for  saccharification of starchy material in glucose syrup industry.

Transcriptome of extracellular vesicles released by hepatocytes.

Directory of Open Access Journals (Sweden)

Felix Royo

Full Text Available The discovery that the cells communicate through emission of vesicles has opened new opportunities for better understanding of physiological and pathological mechanisms. This discovery also provides a novel source for non-invasive disease biomarker research. Our group has previously reported that hepatocytes release extracellular vesicles with protein content reflecting the cell-type of origin. Here, we show that the extracellular vesicles released by hepatocytes also carry RNA. We report the messenger RNA composition of extracellular vesicles released in two non-tumoral hepatic models: primary culture of rat hepatocytes and a progenitor cell line obtained from a mouse foetal liver. We describe different subpopulations of extracellular vesicles with different densities and protein and RNA content. We also show that the RNA cargo of extracellular vesicles released by primary hepatocytes can be transferred to rat liver stellate-like cells and promote their activation. Finally, we provide in vitro and in vivo evidence that liver-damaging drugs galactosamine, acetaminophen, and diclofenac modify the RNA content of these vesicles. To summarize, we show that the extracellular vesicles secreted by hepatocytes contain various RNAs. These vesicles, likely to be involved in the activation of stellate cells, might become a new source for non-invasive identification of the liver toxicity markers.

Electric field effects in hyperexcitable neural tissue: A review

International Nuclear Information System (INIS)

Durand, D.M.

2003-01-01

Uniform electric fields applied to neural tissue can modulate neuronal excitability with a threshold value of about 1mV mm -1 in normal physiological conditions. However, electric fields could have a lower threshold in conditions where field sensitivity is enhanced, such as those simulating epilepsy. Uniform electrical fields were applied to hippocampal brain slices exposed to picrotoxin, high potassium or low calcium solutions. The results in the low calcium medium show that neuronal activity can be completely blocked in 10% of the 30 slices tested with a field amplitude of 1mV mm -1 . These results suggest that the threshold for this effect is clearly smaller than 1mV mm -1 . The hypothesis that the extracellular resistance could affect the sensitivity to the electrical fields was tested by measuring the effect of the osmolarity of the extracellular solution on the efficacy of the field. A 10% decrease on osmolarity resulted in a 56% decrease ( n =4) in the minimum field required for full suppression. A 14% in osmolarity produced an 81% increase in the minimum field required for full suppression. These results show that the extracellular volume can modulate the efficacy of the field and could lower the threshold field amplitudes to values lower than ∼1mmV mm -. (author)

Extracellular vesicles, tissue factor, cancer and thrombosis – discussion themes of the ISEV 2014 Educational Day

Directory of Open Access Journals (Sweden)

Chris Gardiner

2015-03-01

Full Text Available Although the association between cancer and venous thromboembolism (VTE has long been known, the mechanisms are poorly understood. Circulating tissue factor–bearing extracellular vesicles have been proposed as a possible explanation for the increased risk of VTE observed in some types of cancer. The International Society for Extracellular Vesicles (ISEV and International Society on Thrombosis and Haemostasis (ISTH held a joint Educational Day in April 2014 to discuss the latest developments in this field. This review discusses the themes of that event and the ISEV 2014 meeting that followed.

Impact of the strong electromagnetic field on the QCD effective potential for homogeneous Abelian gluon field configurations

International Nuclear Information System (INIS)

Galilo, Bogdan V.; Nedelko, Sergei N.

2011-01-01

The one-loop quark contribution to the QCD effective potential for the homogeneous Abelian gluon field in the presence of an external strong electromagnetic field is evaluated. The structure of extrema of the potential as a function of the angles between chromoelectric, chromomagnetic, and electromagnetic fields is analyzed. In this setup, the electromagnetic field is considered as an external one while the gluon field represents domain structured nonperturbative gluon configurations related to the QCD vacuum in the confinement phase. Two particularly interesting gluon configurations, (anti-)self-dual and crossed orthogonal chromomagnetic and chromoelectric fields, are discussed specifically. Within this simplified framework it is shown that the strong electromagnetic fields can play a catalyzing role for a deconfinement transition. At the qualitative level, the present consideration can be seen as a highly simplified study of an impact of the electromagnetic fields generated in relativistic heavy ion collisions on the strongly interacting hadronic matter.

A spectral element method with adaptive segmentation for accurately simulating extracellular electrical stimulation of neurons.

Science.gov (United States)

Eiber, Calvin D; Dokos, Socrates; Lovell, Nigel H; Suaning, Gregg J

2017-05-01

The capacity to quickly and accurately simulate extracellular stimulation of neurons is essential to the design of next-generation neural prostheses. Existing platforms for simulating neurons are largely based on finite-difference techniques; due to the complex geometries involved, the more powerful spectral or differential quadrature techniques cannot be applied directly. This paper presents a mathematical basis for the application of a spectral element method to the problem of simulating the extracellular stimulation of retinal neurons, which is readily extensible to neural fibers of any kind. The activating function formalism is extended to arbitrary neuron geometries, and a segmentation method to guarantee an appropriate choice of collocation points is presented. Differential quadrature may then be applied to efficiently solve the resulting cable equations. The capacity for this model to simulate action potentials propagating through branching structures and to predict minimum extracellular stimulation thresholds for individual neurons is demonstrated. The presented model is validated against published values for extracellular stimulation threshold and conduction velocity for realistic physiological parameter values. This model suggests that convoluted axon geometries are more readily activated by extracellular stimulation than linear axon geometries, which may have ramifications for the design of neural prostheses.

Heavy quark potential in a static and strong homogeneous magnetic field

Energy Technology Data Exchange (ETDEWEB)

Hasan, Mujeeb; Chatterjee, Bhaswar; Patra, Binoy Krishna [Indian Institute of Technology Roorkee, Department of Physics, Roorkee (India)

2017-11-15

We have investigated the properties of quarkonia in a thermal QCD medium in the background of strong magnetic field. For that purpose, we employ the Schwinger proper-time quark propagator in the lowest Landau level to calculate the one-loop gluon self-energy, which in the sequel gives the effective gluon propagator. As an artifact of strong magnetic field approximation (eB >> T{sup 2} and eB >> m{sup 2}), the Debye mass for massless flavors is found to depend only on the magnetic field which is the dominant scale in comparison to the scales prevalent in the thermal medium. However, for physical quark masses, it depends on both magnetic field and temperature in a low temperature and high magnetic field but the temperature dependence is very meager and becomes independent of the temperature beyond a certain temperature and magnetic field. With the above mentioned ingredients, the potential between heavy quark (Q) and anti-quark (anti Q) is obtained in a hot QCD medium in the presence of a strong magnetic field by correcting both short- and long-range components of the potential in the real-time formalism. It is found that the long-range part of the quarkonium potential is affected much more by magnetic field as compared to the short-range part. This observation facilitates us to estimate the magnetic field beyond which the potential will be too weak to bind Q anti Q together. For example, the J/ψ is dissociated at eB ∝ 10 m{sub π}{sup 2} and Υ is dissociated at eB ∝ 100 m{sub π}{sup 2} whereas its excited states, ψ{sup '} and Υ{sup '} are dissociated at smaller magnetic field eB = m{sub π}{sup 2}, 13 m{sub π}{sup 2}, respectively. (orig.)

Comparative proteomic analysis of extracellular vesicles isolated by acoustic trapping or differential centrifugation

NARCIS (Netherlands)

Rezeli, Melinda; Gidlöf, Olof; Evander, Mikael; Bryl-Górecka, Paulina; Sathanoori, Ramasri; Gilje, Patrik; Pawlowski, Krzysztof; Horvatovich, Péter; Erlinge, David; Marko-Varga, György; Laurell, Thomas

2016-01-01

Extracellular vesicles (ECVs), including microparticles (MPs) and exosomes, are submicron membrane vesicles released by diverse cell types upon activation or stress. Circulating ECVs are potential reservoirs of disease biomarkers, and the complexity of these vesicles is significantly lower compared

Potentiation of NMDA receptor-dependent cell responses by extracellular high mobility group box 1 protein.

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Marco Pedrazzi

Full Text Available BACKGROUND: Extracellular high mobility group box 1 (HMGB1 protein can operate in a synergistic fashion with different signal molecules promoting an increase of cell Ca(2+ influx. However, the mechanisms responsible for this effect of HMGB1 are still unknown. PRINCIPAL FINDINGS: Here we demonstrate that, at concentrations of agonist per se ineffective, HMGB1 potentiates the activation of the ionotropic glutamate N-methyl-D-aspartate receptor (NMDAR in isolated hippocampal nerve terminals and in a neuroblastoma cell line. This effect was abolished by the NMDA channel blocker MK-801. The HMGB1-facilitated NMDAR opening was followed by activation of the Ca(2+-dependent enzymes calpain and nitric oxide synthase in neuroblastoma cells, resulting in an increased production of NO, a consequent enhanced cell motility, and onset of morphological differentiation. We have also identified NMDAR as the mediator of HMGB1-stimulated murine erythroleukemia cell differentiation, induced by hexamethylenebisacetamide. The potentiation of NMDAR activation involved a peptide of HMGB1 located in the B box at the amino acids 130-139. This HMGB1 fragment did not overlap with binding sites for other cell surface receptors of HMGB1, such as the advanced glycation end products or the Toll-like receptor 4. Moreover, in a competition assay, the HMGB1((130-139 peptide displaced the NMDAR/HMGB1 interaction, suggesting that it comprised the molecular and functional site of HMGB1 regulating the NMDA receptor complex. CONCLUSION: We propose that the multifunctional cytokine-like molecule HMGB1 released by activated, stressed, and damaged or necrotic cells can facilitate NMDAR-mediated cell responses, both in the central nervous system and in peripheral tissues, independently of other known cell surface receptors for HMGB1.

Computation of 3-D magnetostatic fields using a reduced scalar potential

International Nuclear Information System (INIS)

Biro, O.; Preis, K.; Vrisk, G.; Richter, K.R.

1993-01-01

The paper presents some improvements to the finite element computation of static magnetic fields in three dimensions using a reduced magnetic scalar potential. New methods are described for obtaining an edge element representation of the rotational part of the magnetic field from a given source current distribution. In the case when the current distribution is not known in advance, a boundary value problem is set up in terms of a current vector potential. An edge element representation of the solution can be directly used in the subsequent magnetostatic calculation. The magnetic field in a D.C. arc furnace is calculated by first determining the current distribution in terms of a current vector potential. A three dimensional problem involving a permanent magnet as well as a coil is solved and the magnetic field in some points is compared with measurement results

Far-field potentials in cylindrical and rectangular volume conductors.

Science.gov (United States)

Dumitru, D; King, J C; Rogers, W E

1993-07-01

The occurrence of a transient dipole is one method of producing a far-field potential. This investigation qualitatively defines the characteristics of the near-field and far-field electrical potentials produced by a transient dipole in both cylindrical and rectangular volume conductors. Most body segments of electrophysiologic interest such as arms, legs, thorax, and neck are roughly cylindrical in shape. A centrally located dipole generator produces a nonzero equipotential region which is found to occur along the cylindrical wall at a distance from the dipole of approximately 1.4 times the cylinder's radius and 1.9 times the cylinder's radius for the center of the cylinder. This distance to the equi-potential zone along the surface wall expands but remains less than 3.0 times the cylindrical radius when the dipole is eccentrically placed. The magnitude of the equipotential region resulting from an asymmetrically placed dipole remains identical to that when the dipole is centrally located. This behavior is found to be very similar in rectangular shallow conducting volumes that model a longitudinal slice of the cylinder, thus allowing a simple experimental model of the cylinder to be utilized. Amplitudes of the equipotential region are inversely proportional to the cylindrical or rectangular volume's cross-sectional area at the location of dipolar imbalance. This study predicts that referential electrode montages, when placed at 3.0 times the radius or greater from a dipolar axially aligned far-field generator in cylindrical homogeneous volume conductors, will record only equipotential far-field effects.

Niche Extracellular Matrix Components and Their Influence on HSC.

Science.gov (United States)

Domingues, Mélanie J; Cao, Huimin; Heazlewood, Shen Y; Cao, Benjamin; Nilsson, Susan K

2017-08-01

Maintenance of hematopoietic stem cells (HSC) takes place in a highly specialized microenvironment within the bone marrow. Technological improvements, especially in the field of in vivo imaging, have helped unravel the complexity of the niche microenvironment and have completely changed the classical concept from what was previously believed to be a static supportive platform, to a dynamic microenvironment tightly regulating HSC homeostasis through the complex interplay between diverse cell types, secreted factors, extracellular matrix molecules, and the expression of different transmembrane receptors. To add to the complexity, non-protein based metabolites have also been recognized as a component of the bone marrow niche. The objective of this review is to discuss the current understanding on how the different extracellular matrix components of the niche regulate HSC fate, both during embryonic development and in adulthood. Special attention will be provided to the description of non-protein metabolites, such as lipids and metal ions, which contribute to the regulation of HSC behavior. J. Cell. Biochem. 118: 1984-1993, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Salivary extracellular vesicle-associated miRNAs as potential biomarkers in oral squamous cell carcinoma.

Science.gov (United States)

Gai, Chiara; Camussi, Francesco; Broccoletti, Roberto; Gambino, Alessio; Cabras, Marco; Molinaro, Luca; Carossa, Stefano; Camussi, Giovanni; Arduino, Paolo G

2018-04-18

Several studies in the past have investigated the expression of micro RNAs (miRNAs) in saliva as potential biomarkers. Since miRNAs associated with extracellular vesicles (EVs) are known to be protected from enzymatic degradation, we evaluated whether salivary EVs from patients with oral squamous cell carcinoma (OSCC) were enriched with specific subsets of miRNAs. OSCC patients and controls were matched with regards to age, gender and risk factors. Total RNA was extracted from salivary EVs and the differential expression of miRNAs was evaluated by qRT-PCR array and qRT-PCR. The discrimination power of up-regulated miRNAs as biomarkers in OSCC patients versus controls was evaluated by the Receiver Operating Characteristic (ROC) curves. A preliminary qRT-PCR array was performed on samples from 5 OSCC patients and 5 healthy controls whereby a subset of miRNAs were identified that were differentially expressed. On the basis of these results, a cohort of additional 16 patients and 6 controls were analyzed to further confirm the miRNAs that were up-regulated or selectively expressed in the previous pilot study. The following miRNAs: miR-302b-3p and miR-517b-3p were expressed only in EVs from OSCC patients and miR-512-3p and miR-412-3p were up-regulated in salivary EVs from OSCC patients compared to controls with the ROC curve showing a good discrimination power for OSCC diagnosis. The Kyoto Encyclopedia of Gene and Genomes (KEGG) pathway analysis suggested the possible involvement of the miRNAs identified in pathways activated in OSCC. In this work, we suggest that salivary EVs isolated by a simple charge-based precipitation technique can be exploited as a non-invasive source of miRNAs for OSCC diagnosis. Moreover, we have identified a subset of miRNAs selectively enriched in EVs of OSCC patients that could be potential biomarkers.

Effective potential for bilocal composite fields and its ambiguity

International Nuclear Information System (INIS)

Muta, T.

1988-01-01

It is discussed that an ambiguity exists in the definition of the effective potential for bilocal composite fields which is an indispensable tool to discuss dynamical symmetry breaking. The ambiguity gives warning to arguments on the stability of ground states based on the curvature of the effective potential

Electrochemical noise and impedance of Au electrode/electrolyte interfaces enabling extracellular detection of glioma cell populations.

Science.gov (United States)

Rocha, Paulo R F; Schlett, Paul; Kintzel, Ulrike; Mailänder, Volker; Vandamme, Lode K J; Zeck, Gunther; Gomes, Henrique L; Biscarini, Fabio; de Leeuw, Dago M

2016-10-06

Microelectrode arrays (MEA) record extracellular local field potentials of cells adhered to the electrodes. A disadvantage is the limited signal-to-noise ratio. The state-of-the-art background noise level is about 10 μVpp. Furthermore, in MEAs low frequency events are filtered out. Here, we quantitatively analyze Au electrode/electrolyte interfaces with impedance spectroscopy and noise measurements. The equivalent circuit is the charge transfer resistance in parallel with a constant phase element that describes the double layer capacitance, in series with a spreading resistance. This equivalent circuit leads to a Maxwell-Wagner relaxation frequency, the value of which is determined as a function of electrode area and molarity of an aqueous KCl electrolyte solution. The electrochemical voltage and current noise is measured as a function of electrode area and frequency and follow unambiguously from the measured impedance. By using large area electrodes the noise floor can be as low as 0.3 μVpp. The resulting high sensitivity is demonstrated by the extracellular detection of C6 glioma cell populations. Their minute electrical activity can be clearly detected at a frequency below about 10 Hz, which shows that the methodology can be used to monitor slow cooperative biological signals in cell populations.

Effects of Recurring Droughts on Extracellular Enzyme Activity in Mountain Grassland

Science.gov (United States)

Fuchslueger, L.; Bahn, M.; Kienzl, S.; Hofhansl, F.; Schnecker, J.; Richter, A.

2015-12-01

Water availability is a key factor for biogeochemical processes and determines microbial activity and functioning, and thereby organic matter decomposition in soils by affecting the osmotic potential, soil pore connectivity, substrate diffusion and nutrient availability. Low water availability during drought periods therefore directly affects microbial activity. Recurring drought periods likely induce shifts in microbial structure that might be reflected in altered responses of microbial turnover of organic matter by extracellular enzymes. To study this we measured a set of potential extracellular enzyme activity rates (cellobiohydrolase CBH; leucine-amino-peptidase LAP; phosphatase PHOS; phenoloxidase POX), in grassland soils that were exposed to extreme experimental droughts during the growing seasons of up to five subsequent years. During the first drought period after eight weeks of rain exclusion all measured potential enzyme activities were significantly decreased. In parallel, soil extractable organic carbon and nitrogen concentrations increased and microbial community structure, determined by phospholipid fatty acid analysis, changed. In soils that were exposed to two and three drought periods only PHOS decreased. After four years of drought again CBH, PHOS and POX decreased, while LAP was unaffected; after five years of drought PHOS and POX decreased and CBH and LAP remained stable. Thus, our results suggest that recurring extreme drought events can cause different responses of extracellular enzyme activities and that the responses change over time. We will discuss whether and to what degree these changes were related to shifts in microbial community composition. However, independent of whether a solitary or a recurrent drought was imposed, in cases when enzyme activity rates were altered during drought, they quickly recovered after rewetting. Overall, our data suggest that microbial functioning in mountain grassland is sensitive to drought, but highly

On-chip immunoelectrophoresis of extracellular vesicles released from human breast cancer cells.

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Takanori Akagi

Full Text Available Extracellular vesicles (EVs including exosomes and microvesicles have attracted considerable attention in the fields of cell biology and medicine. For a better understanding of EVs and further exploration of their applications, the development of analytical methods for biological nanovesicles has been required. In particular, considering the heterogeneity of EVs, methods capable of measuring individual vesicles are desired. Here, we report that on-chip immunoelectrophoresis can provide a useful method for the differential protein expression profiling of individual EVs. Electrophoresis experiments were performed on EVs collected from the culture supernatant of MDA-MB-231 human breast cancer cells using a measurement platform comprising a microcapillary electrophoresis chip and a laser dark-field microimaging system. The zeta potential distribution of EVs that reacted with an anti-human CD63 (exosome and microvesicle marker antibody showed a marked positive shift as compared with that for the normal immunoglobulin G (IgG isotype control. Thus, on-chip immunoelectrophoresis could sensitively detect the over-expression of CD63 glycoproteins on EVs. Moreover, to explore the applicability of on-chip immunoelectrophoresis to cancer diagnosis, EVs collected from the blood of a mouse tumor model were analyzed by this method. By comparing the zeta potential distributions of EVs after their immunochemical reaction with normal IgG, and the anti-human CD63 and anti-human CD44 (cancer stem cell marker antibodies, EVs of tumor origin circulating in blood were differentially detected in the real sample. The result indicates that the present method is potentially applicable to liquid biopsy, a promising approach to the low-invasive diagnosis of cancer.

Particle localization in a double-well potential by pseudo-supersymmetric fields

International Nuclear Information System (INIS)

Bagrov, V. G.; Samsonov, B. F.; Shamshutdinova, V. V.

2011-01-01

We study properties of a particle moving in a double-well potential in the two-level approximation placed in an additional external time-dependent field. Using previously established property (J. Phys. A 41, 244023 (2008)) that any two-level system possesses a pseudo-supersymmetry we introduce the notion of pseudo-supersymmetric field. It is shown that these fields, even if their time dependence is not periodical, may produce the effect of localization of the particle in one of the wells of the double-well potential.

Highlights of the São Paulo ISEV workshop on extracellular vesicles in cross-kingdom communication

DEFF Research Database (Denmark)

Soares, Rodrigo P.; Xander, Patrícia; Costa, Adriana Oliveira

2017-01-01

In the past years, extracellular vesicles (EVs) have become an important field of research since EVs have been found to play a central role in biological processes. In pathogens, EVs are involved in several events during the host–pathogen interaction, including invasion, immunomodulation, and pat...

Bacterial binding to extracellular proteins - in vitro adhesion

DEFF Research Database (Denmark)

Schou, C.; Fiehn, N.-E.

1999-01-01

Viridans streptococci, bacterial adherence, extracellular matrix proteins, surface receptors, endocarditis......Viridans streptococci, bacterial adherence, extracellular matrix proteins, surface receptors, endocarditis...

Bicarbonate sensing in mouse cortical astrocytes during extracellular acid/base disturbances

Science.gov (United States)

Naoshin, Zinnia; Defren, Sabrina; Schmaelzle, Jana; Weber, Tobias; Schneider, Hans‐Peter

2017-01-01

astrocytes from wild‐type (WT) and from NBCe1‐knockout (KO) mice, using ion‐selective dyes, during isocapnic acidosis, hypercapnic acidosis and hypocapnia. We also analysed NBCe1‐mediated membrane currents in Xenopus laevis oocytes under similar conditions. Comparing WT and NBCe1‐KO astrocytes, we could dissect the contribution of NBCe1, of diffusion of CO2 across the cell membrane and, after blocking carbonic anhydrase (CA) activity with ethoxyzolamide, of the role of CA, for the amplitude and rate of acid/base fluxes. Our results suggest that NBCe1 transport activity in astrocytes, supported by CA activity, renders astrocytes bicarbonate sensors in the mouse cortex. NBCe1 carried bicarbonate into and out of the cell by sensing the variations of transmembrane [HCO3 −], irrespective of the changes in intra‐ and extracellular pH, and played a major role in setting pHi responses to the extracellular acid/base challenges. We propose that bicarbonate sensing of astrocytes may have potential functional significance during extracellular acid/base alterations in the brain. PMID:27981578

Defining structural and functional dimensions of the extracellular thyrotropin receptor region.

Science.gov (United States)

Kleinau, Gunnar; Mueller, Sandra; Jaeschke, Holger; Grzesik, Paul; Neumann, Susanne; Diehl, Anne; Paschke, Ralf; Krause, Gerd

2011-06-24

The extracellular region of the thyrotropin receptor (TSHR) can be subdivided into the leucine-rich repeat domain (LRRD) and the hinge region. Both the LRRD and the hinge region interact with thyrotropin (TSH) or autoantibodies. Structural data for the TSHR LRRD were previously determined by crystallization (amino acids Glu(30)-Thr(257), 10 repeats), but the structure of the hinge region is still undefined. Of note, the amino acid sequence (Trp(258)-Tyr(279)) following the crystallized LRRD comprises a pattern typical for leucine-rich repeats with conserved hydrophobic side chains stabilizing the repeat fold. Moreover, functional data for amino acids between the LRRD and the transmembrane domain were fragmentary. We therefore investigated systematically these TSHR regions by mutagenesis to reveal insights into their functional contribution and potential structural features. We found that mutations of conserved hydrophobic residues between Thr(257) and Tyr(279) cause TSHR misfold, which supports a structural fold of this peptide, probably as an additional leucine-rich repeat. Furthermore, we identified several new mutations of hydrophilic amino acids in the entire hinge region leading to partial TSHR inactivation, indicating that these positions are important for intramolecular signal transduction. In summary, we provide new information regarding the structural features and functionalities of extracellular TSHR regions. Based on these insights and in context with previous results, we suggest an extracellular activation mechanism that supports an intramolecular agonistic unit as a central switch for activating effects at the extracellular region toward the serpentine domain.

The Analytical Potential Energy Function of NH Radical Molecule in External Electric Field

International Nuclear Information System (INIS)

Wu Dong-Lan; Tan Bin; Wan Hui-Jun; Xie An-Dong; Ding Da-Jun

2015-01-01

The geometric structures of an NH radical in different external electric fields are optimized by using the density functional B3P86/cc-PV5Z method, and the bond lengths, dipole moments, vibration frequencies and IR spectrum are obtained. The potential energy curves are gained by the CCSD (T) method with the same basis set. These results indicate that the physical property parameters and potential energy curves may change with the external electric field, especially in the reverse direction electric field. The potential energy function of zero field is fitted by the Morse potential, and the fitting parameters are in good accordance with the experimental data. The potential energy functions of different external electric fields are fitted adopting the constructed potential model. The fitted critical dissociation electric parameters are shown to be consistent with the numerical calculation, and the relative errors are only 0.27% and 6.61%, hence the constructed model is reliable and accurate. The present results provide an important reference for further study of the molecular spectrum, dynamics and molecular cooling with Stark effect. (paper)

Culture-dependent and culture-independent characterization of potentially functional biphenyl-degrading bacterial community in response to extracellular organic matter from Micrococcus luteus.

Science.gov (United States)

Su, Xiao-Mei; Liu, Yin-Dong; Hashmi, Muhammad Zaffar; Ding, Lin-Xian; Shen, Chao-Feng

2015-05-01

Biphenyl (BP)-degrading bacteria were identified to degrade various polychlorinated BP (PCB) congers in long-term PCB-contaminated sites. Exploring BP-degrading capability of potentially useful bacteria was performed for enhancing PCB bioremediation. In the present study, the bacterial composition of the PCB-contaminated sediment sample was first investigated. Then extracellular organic matter (EOM) from Micrococcus luteus was used to enhance BP biodegradation. The effect of the EOM on the composition of bacterial community was investigated by combining with culture-dependent and culture-independent methods. The obtained results indicate that Proteobacteria and Actinobacteria were predominant community in the PCB-contaminated sediment. EOM from M. luteus could stimulate the activity of some potentially difficult-to-culture BP degraders, which contribute to significant enhancement of BP biodegradation. The potentially difficult-to-culture bacteria in response to EOM addition were mainly Rhodococcus and Pseudomonas belonging to Gammaproteobacteria and Actinobacteria respectively. This study provides new insights into exploration of functional difficult-to-culture bacteria with EOM addition and points out broader BP/PCB degrading, which could be employed for enhancing PCB-bioremediation processes. © 2015 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.

Fuzzy Pheromone Potential Fields for Virtual Pedestrian Simulation

Directory of Open Access Journals (Sweden)

Meriem Mandar

2016-01-01

Full Text Available The study of collective movement of pedestrians is crucial in various situations, such as evacuation of buildings, stadiums, or external events like concerts or public events. In such situations and under panic conditions, several incidents and disasters may arise, resulting in loss of human lives. Hence, the study and modeling of the pedestrians behavior are imperative in both normal and panic situations. In a previous work, we developed a microscopic model for pedestrian movement based on the algorithm of Ant Colonies and the principles of cellular automata. We took advantage of a fuzzy model to better reflect the uncertainty and vagueness of the perception of space to pedestrians, especially to represent the desirability or blurred visibility of virtual pedestrians. This paper uses the mechanism of artificial potential fields. Said fields provide virtual pedestrians with better visibility of their surroundings and its various components (goals and obstacles. The predictions provided by the first-order traffic flow theory are confirmed by the results of the simulation. The advantage of this model lies in the combination of benefits provided by the model of ants and artificial potential fields in a fuzzy modeling, to better understand the perceptions of pedestrians.

Self-Potential Monitoring of Landslides on Field and Laboratory Scale

Science.gov (United States)

Heinze, T.; Limbrock, J. K.; Weigand, M.; Wagner, F. M.; Kemna, A.

2017-12-01

Among several other geophysical methods used to observe water movement in the ground, the electrical self-potential method has been applied to a broad range of monitoring studies, especially focusing on volcanism and dam leakage but also during hydraulic fracturing. Electrical self-potential signals may be caused by various mechanisms. Though, the most relevant source of the self-potential field in the given context of landslides is the streaming potential, caused by a flowing electrolyte through porous media with electrically charged internal surfaces. So far, existing models focus on monitoring water flow in non-deformable porous media. However, as the self-potential is sensitive to hydraulic parameters of the soil, any change in these parameters will cause an alteration of the electric signal. Mass movement will significantly influence the hydraulic parameters of the solid as well as the pressure field, assuming that fluid movement is faster than pressure diffusion. We present self-potential measurements from over a year of continuous monitoring at an old landslide site. Using a three-dimensional electric-resistivity underground model, the self-potential signal is analyzed with respect to precipitation and the resulting flow in the ground. Additional data from electrical measurements and conventional sensors are included to assess saturation. The field observations are supplemented by laboratory experiments in which we study the behavior of the self-potential during failure of a piled land slope. For the undrained scenarios, we observe a clear correlation between the mass movements and signals in the electric potential, which clearly differ from the underlying potential variations due to increased saturation and fluid flow. In the drained experiments, we do not observe any measurable change in the electric potential. We therefore assume that change in fluid properties and release of the load causes disturbances in flow and streaming potential. Our results

On the relation between fields and potentials in non abelian Gauge Theories

International Nuclear Information System (INIS)

Bollini, C.G.; Giambiagi, J.J.

1979-01-01

Some examples have been given in the literature of ambiguous gauge fields, i.e. those not having a unique potential (up to a gauge transformation). An example given by Deser and Wilczek is examined and found the condition (for any gauge group) that the group element generating the potentials must satisfy in order for the potentials not to be related by any gauge transformation. In three dimensions (for Su 2 ) there are other families of ambiguous fields characterized by arbitrary unit vector fields n vector (n vector) (n 2 vector =1). The example given by Wu and Yang belongs to a particular family with n vector = n vector. r vector / r vector. The sources of these fields and some interesting relations between them are also found [pt

Description of the Magnetic Field and Divergence of Multisolenoid Aharonov-Bohm Potential

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Araz R. Aliev

2016-01-01

Full Text Available Explicit formulas for the magnetic field and divergence of multisolenoid Aharonov-Bohm potential are obtained; the mathematical essence of this potential is explained. It is shown that the magnetic field and divergence of this potential are very singular generalized functions concentrated at a finite number of thin solenoids. Deficiency index is found for the minimal operator generated by the Aharonov-Bohm differential expression.

Extracellular vesicle-derived protein from Bifidobacterium longum alleviates food allergy through mast cell suppression.

Science.gov (United States)

Kim, Jung-Hwan; Jeun, Eun-Ji; Hong, Chun-Pyo; Kim, Seong-Hoon; Jang, Min Seong; Lee, Eun-Jung; Moon, Sook Jin; Yun, Chang Ho; Im, Sin-Hyeog; Jeong, Seok-Geun; Park, Beom-Young; Kim, Kyong-Tai; Seoh, Ju-Young; Kim, Yoon-Keun; Oh, Sung-Jong; Ham, Jun-Sang; Yang, Bo-Gie; Jang, Myoung Ho

2016-02-01

The incidence of food allergies has increased dramatically during the last decade. Recently, probiotics have been studied for the prevention and treatment of allergic disease. We examined whether Bifidobacterium longum KACC 91563 and Enterococcus faecalis KACC 91532 have the capacity to suppress food allergies. B longum KACC 91563 and E faecalis KACC 91532 were administered to BALB/c wild-type mice, in which food allergy was induced by using ovalbumin and alum. Food allergy symptoms and various immune responses were assessed. B longum KACC 91563, but not E faecalis KACC 91532, alleviated food allergy symptoms. Extracellular vesicles of B longum KACC 91563 bound specifically to mast cells and induced apoptosis without affecting T-cell immune responses. Furthermore, injection of family 5 extracellular solute-binding protein, a main component of extracellular vesicles, into mice markedly reduced the occurrence of diarrhea in a mouse food allergy model. B longum KACC 91563 induces apoptosis of mast cells specifically and alleviates food allergy symptoms. Accordingly, B longum KACC 91563 and family 5 extracellular solute-binding protein exhibit potential as therapeutic approaches for food allergies. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Efficient Extracellular Expression of Phospholipase D in Escherichia Coli with an Optimized Signal Peptide

Science.gov (United States)

Yang, Leyun; Xu, Yu; Chen, Yong; Ying, Hanjie

2018-01-01

New secretion vectors containing the synthetic signal sequence (OmpA’) was constructed for the secretory production of recombinant proteins in Escherichia coli. The E. coli Phospholipase D structural gene (Accession number:NC_018658) fused to various signal sequence were expressed from the Lac promoter in E. coli Rosetta strains by induction with 0.4mM IPTG at 28°C for 48h. SDS-PaGe analysis of expression and subcellular fractions of recombinant constructs revealed the translocation of Phospholipase D (PLD) not only to the medium but also remained in periplasm of E. coli with OmpA’ signal sequence at the N-terminus of PLD. Thus the study on the effects of various surfactants on PLD extracellular production in Escherichia coli in shake flasks revealed that optimal PLD extracellular production could be achieved by adding 0.4% Triton X-100 into the medium. The maximal extracellular PLD production and extracellular enzyme activity were 0.23mg ml-1 and 16U ml-1, respectively. These results demonstrate the possibility of efficient secretory production of recombinant PLD in E. coli should be a potential industrial applications.

Spontaneous and Widespread Electricity Generation in Natural Deep-Sea Hydrothermal Fields.

Science.gov (United States)

Yamamoto, Masahiro; Nakamura, Ryuhei; Kasaya, Takafumi; Kumagai, Hidenori; Suzuki, Katsuhiko; Takai, Ken

2017-05-15

Deep-sea hydrothermal vents discharge abundant reductive energy into oxidative seawater. Herein, we demonstrated that in situ measurements of redox potentials on the surfaces of active hydrothermal mineral deposits were more negative than the surrounding seawater potential, driving electrical current generation. We also demonstrated that negative potentials in the surface of minerals were widespread in the hydrothermal fields, regardless of the proximity to hydrothermal fluid discharges. Lab experiments verified that the negative potential of the mineral surface was induced by a distant electron transfer from the hydrothermal fluid through the metallic and catalytic properties of minerals. These results indicate that electric current is spontaneously and widely generated in natural mineral deposits in deep-sea hydrothermal fields. Our discovery provides important insights into the microbial communities that are supported by extracellular electron transfer and the prebiotic chemical and metabolic evolution of the ocean hydrothermal systems. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

An optimized absorbing potential for ultrafast, strong-field problems

Science.gov (United States)

Yu, Youliang; Esry, B. D.

2018-05-01

Theoretical treatments of strong-field physics have long relied on the numerical solution of the time-dependent Schrödinger equation. The most effective such treatments utilize a discrete spatial representation—a grid. Since most strong-field observables relate to the continuum portion of the wave function, the boundaries of the grid—which act as hard walls and thus cause reflection—can substantially impact the observables. Special care thus needs to be taken. While there exist a number of attempts to solve this problem—e.g., complex absorbing potentials and masking functions, exterior complex scaling, and coordinate scaling—none of them are completely satisfactory. The first of these is arguably the most popular, but it consumes a substantial fraction of the computing resources in any given calculation. Worse, this fraction grows with the dimensionality of the problem. In addition, no systematic way to design such a potential has been used in the strong-field community. In this work, we address these issues and find a much better solution. By comparing with previous widely used absorbing potentials, we find a factor of 3–4 reduction in the absorption range, given the same level of absorption over a specified energy interval.

Marine microorganisms as potential biofactories for synthesis of metallic nanoparticles.

Science.gov (United States)

Manivasagan, Panchanathan; Nam, Seung Yun; Oh, Junghwan

2016-11-01

The use of marine microorganisms as potential biofactories for green synthesis of metallic nanoparticles is a relatively new field of research with considerable prospects. This method is eco-friendly, time saving, and inexpensive and can be easily scaled up for large-scale synthesis. The increasing need to develop simple, nontoxic, clean, and environmentally safe production methods for nanoparticles and to decrease environmental impact, minimize waste, and increase energy productivity has become important in this field. Marine microorganisms are tiny organisms that live in marine ecosystems and account for >98% of biomass of the world's ocean. Marine microorganisms synthesize metallic nanoparticles either intracellularly or extracellularly. Marine microbially-produced metallic nanoparticles have received considerable attention in recent years because of their expected impact on various applications such as medicine, energy, electronic, and space industries. The present review discusses marine microorganisms as potential biofactories for the green synthesis of metallic nanoparticles and their potential applications.

Effective potential in Lorentz-breaking field theory models

Energy Technology Data Exchange (ETDEWEB)

Baeta Scarpelli, A.P. [Centro Federal de Educacao Tecnologica, Nova Gameleira Belo Horizonte, MG (Brazil); Setor Tecnico-Cientifico, Departamento de Policia Federal, Belo Horizonte, MG (Brazil); Brito, L.C.T. [Universidade Federal de Lavras, Departamento de Fisica, Lavras, MG (Brazil); Felipe, J.C.C. [Universidade Federal de Lavras, Departamento de Fisica, Lavras, MG (Brazil); Universidade Federal dos Vales do Jequitinhonha e Mucuri, Instituto de Engenharia, Ciencia e Tecnologia, Veredas, Janauba, MG (Brazil); Nascimento, J.R.; Petrov, A.Yu. [Universidade Federal da Paraiba, Departamento de Fisica, Joao Pessoa, Paraiba (Brazil)

2017-12-15

We calculate explicitly the one-loop effective potential in different Lorentz-breaking field theory models. First, we consider a Yukawa-like theory and some examples of Lorentz-violating extensions of scalar QED. We observe, for the extended QED models, that the resulting effective potential converges to the known result in the limit in which Lorentz symmetry is restored. Besides, the one-loop corrections to the effective potential in all the cases we study depend on the background tensors responsible for the Lorentz-symmetry violation. This has consequences for physical quantities like, for example, in the induced mass due to the Coleman-Weinberg mechanism. (orig.)

Effective potential in Lorentz-breaking field theory models

International Nuclear Information System (INIS)

Baeta Scarpelli, A.P.; Brito, L.C.T.; Felipe, J.C.C.; Nascimento, J.R.; Petrov, A.Yu.

2017-01-01

We calculate explicitly the one-loop effective potential in different Lorentz-breaking field theory models. First, we consider a Yukawa-like theory and some examples of Lorentz-violating extensions of scalar QED. We observe, for the extended QED models, that the resulting effective potential converges to the known result in the limit in which Lorentz symmetry is restored. Besides, the one-loop corrections to the effective potential in all the cases we study depend on the background tensors responsible for the Lorentz-symmetry violation. This has consequences for physical quantities like, for example, in the induced mass due to the Coleman-Weinberg mechanism. (orig.)

A combined vector potential-scalar potential method for FE computation of 3D magnetic fields in electrical devices with iron cores

Science.gov (United States)

Wang, R.; Demerdash, N. A.

1991-01-01

A method of combined use of magnetic vector potential based finite-element (FE) formulations and magnetic scalar potential (MSP) based formulations for computation of three-dimensional magnetostatic fields is introduced. In this method, the curl-component of the magnetic field intensity is computed by a reduced magnetic vector potential. This field intensity forms the basic of a forcing function for a global magnetic scalar potential solution over the entire volume of the region. This method allows one to include iron portions sandwiched in between conductors within partitioned current-carrying subregions. The method is most suited for large-scale global-type 3-D magnetostatic field computations in electrical devices, and in particular rotating electric machinery.

Extracellular mycosynthesis of gold nanoparticles using Fusarium solani

Science.gov (United States)

Gopinath, K.; Arumugam, A.

2014-08-01

The development of eco-friendly methods for the synthesis of nanomaterial shape and size is an important area of research in the field of nanotechnology. The present investigation deals with the extracellular rapid biosynthesis of gold nanoparticles using Fusarium solani culture filtrate. The UV-vis spectra of the fungal culture filtrate medium containing gold ion showed peak at 527 nm corresponding to the plasmon absorbance of gold nanoparticles. FTIR spectra provide an evidence for the presence of heterocyclic compound in the culture filtrate, which increases the stability of the synthesized gold nanoparticles. The X-ray analysis respects the Bragg's law and confirmed the crystalline nature of the gold nanoparticles. AFM analysis showed the results of particle sizes (41 nm). Transmission electron microscopy (TEM) showed that the gold nanoparticles are spherical in shape with the size range from 20 to 50 nm. The use of F. solani will offer several advantages since it is considered as a non-human pathogenic organism. The fungus F. solani has a fast growth rate, rapid capacity of metallic ions reduction, NPs stabilization and facile and economical biomass handling. Extracellular biosynthesis of gold nanoparticles could be highly advantageous from the point of view of synthesis in large quantities, time consumption, eco-friendly, non-toxic and easy downstream processing.

Sprifermin (rhFGF18) modulates extracellular matrix turnover in cartilage explants ex vivo

DEFF Research Database (Denmark)

Reker, Ditte; Kjelgaard-Petersen, Cecilie Freja; Siebuhr, Anne Sofie

2017-01-01

Background: Sprifermin (recombinant human fibroblast growth factor 18) is in clinical development as a potential disease-modifying osteoarthritis drug (DMOAD). In vitro studies have shown that cartilage regenerative properties of sprifermin involve chondrocyte proliferation and extracellular matrix...... or placebo at weekly intervals, similar to the dosing regimen used in clinical trials. Pre-culturing with oncostatin M and tumour necrosis factor-a, was also used to induce an inflammatory state before treatment. Metabolic activity was measured using AlamarBlue, and chondrocyte proliferation was visualized...... aggrecanase activity. Results: Sprifermin was able to reach the chondrocytes through the extracellular matrix, as it increased cell proliferation and metabolic activity of explants. ProC2 and CS846 was dose-dependently increased (P

Field and electric potential of conductors with fractal geometry

Energy Technology Data Exchange (ETDEWEB)

Assis, Thiago A de; Mota, Fernando de B; Miranda, Jose G V; Andrade, Roberto F S; Castilho, Caio M C de [Instituto de Fisica, Universidade Federal da Bahia, Campus Universitario da Federacao, 40210-340, Salvador (Brazil)

2007-11-28

In this study, the behavior of the electric field and its potential are investigated in a region bounded by a rough fractal surface and a distant plane. Both boundaries, maintained at distinct potential values, are assumed to be conductors and, as such, the electric potential is obtained by numerically solving Laplace's equation subject to the appropriate Dirichlet's condition. The rough boundaries, generated by the ballistic deposition and fractal Brownian motion methods, are characterized by the values of the surface roughness W and the local fractal dimension df = 3-{alpha}, where {alpha} is the usual roughness exponent. The equipotential surfaces, obtained from Laplace's equation, are characterized by these same parameters. Results presented show how df depends on the potential value, on the method used to generate the boundary and on W. The behavior of the electric field with respect to the equipotential surface is also considered. Its average intensity was found to increase as a function of the average distance from the equipotential to the fractal boundary; however, its intensity reaches a maximum before decreasing towards an asymptotic constant value, an effect that increases as the value of W increases.

Field and electric potential of conductors with fractal geometry

International Nuclear Information System (INIS)

Assis, Thiago A de; Mota, Fernando de B; Miranda, Jose G V; Andrade, Roberto F S; Castilho, Caio M C de

2007-01-01

In this study, the behavior of the electric field and its potential are investigated in a region bounded by a rough fractal surface and a distant plane. Both boundaries, maintained at distinct potential values, are assumed to be conductors and, as such, the electric potential is obtained by numerically solving Laplace's equation subject to the appropriate Dirichlet's condition. The rough boundaries, generated by the ballistic deposition and fractal Brownian motion methods, are characterized by the values of the surface roughness W and the local fractal dimension df = 3-α, where α is the usual roughness exponent. The equipotential surfaces, obtained from Laplace's equation, are characterized by these same parameters. Results presented show how df depends on the potential value, on the method used to generate the boundary and on W. The behavior of the electric field with respect to the equipotential surface is also considered. Its average intensity was found to increase as a function of the average distance from the equipotential to the fractal boundary; however, its intensity reaches a maximum before decreasing towards an asymptotic constant value, an effect that increases as the value of W increases

Olfactory Fear Conditioning Induces Field Potential Potentiation in Rat Olfactory Cortex and Amygdala

Science.gov (United States)

Messaoudi, Belkacem; Granjon, Lionel; Mouly, Anne-Marie; Sevelinges, Yannick; Gervais, Remi

2004-01-01

The widely used Pavlovian fear-conditioning paradigms used for studying the neurobiology of learning and memory have mainly used auditory cues as conditioned stimuli (CS). The present work assessed the neural network involved in olfactory fear conditioning, using olfactory bulb stimulation-induced field potential signal (EFP) as a marker of…

secHsp70 as a tool to approach amyloid-β42 and other extracellular amyloids.

Science.gov (United States)

De Mena, Lorena; Chhangani, Deepak; Fernandez-Funez, Pedro; Rincon-Limas, Diego E

2017-07-03

Self-association of amyloidogenic proteins is the main pathological trigger in a wide variety of neurodegenerative disorders. These aggregates are deposited inside or outside the cell due to hereditary mutations, environmental exposures or even normal aging. Cumulative evidence indicates that the heat shock chaperone Hsp70 possesses robust neuroprotection against various intracellular amyloids in Drosophila and mouse models. However, its protective role against extracellular amyloids was largely unknown as its presence outside the cells is very limited. Our recent manuscript in PNAS revealed that an engineered form of secreted Hsp70 (secHsp70) is highly protective against toxicity induced by extracellular deposition of the amyloid-β42 (Aβ42) peptide. In this Extra View article, we extend our analysis to other members of the heat shock protein family. We created PhiC31-based transgenic lines for human Hsp27, Hsp40, Hsp60 and Hsp70 and compared their activities in parallel against extracellular Aβ42. Strikingly, only secreted Hsp70 exhibits robust protection against Aβ42-triggered toxicity in the extracellular milieu. These observations indicate that the ability of secHsp70 to suppress Aβ42 insults is quite unique and suggest that targeted secretion of Hsp70 may represent a new therapeutic approach against Aβ42 and other extracellular amyloids. The potential applications of this engineered chaperone are discussed.

Lipolytic Potential of Aspergillus japonicus LAB01: Production, Partial Purification, and Characterisation of an Extracellular Lipase

Science.gov (United States)

Souza, Lívia Tereza Andrade; Oliveira, Jamil S.; dos Santos, Vera L.; Regis, Wiliam C. B.; Santoro, Marcelo M.; Resende, Rodrigo R.

2014-01-01

Lipolytic potential of Aspergillus japonicus LAB01 was investigated by describing the catalytic properties and stability of a secreted extracellular lipase. Enzyme production was considered high under room temperature after 4 days using sunflower oil and a combination of casein with sodium nitrate. Lipase was partially purified by 3.9-fold, resulting in a 44.2% yield using ammonium sulphate precipitation (60%) quantified with Superose 12 HR gel filtration chromatography. The activity of the enzyme was maximised at pH 8.5, and the enzyme demonstrated stability under alkaline conditions. The optimum temperature was found to be 45°C, and the enzyme was stable for up to 100 minutes, with more than 80% of initial activity remaining after incubation at this temperature. Partially purified enzyme showed reasonable stability with triton X-100 and was activated in the presence of organic solvents (toluene, hexane, and methanol). Among the tested ions, only Cu2+, Ni2+, and Al3+ showed inhibitory effects. Substrate specificity of the lipase was higher for C14 among various p-nitrophenyl esters assayed. The KM and V max values of the purified enzyme for p-nitrophenyl palmitate were 0.13 mM and 12.58 umol/(L·min), respectively. These features render a novel biocatalyst for industrial applications. PMID:25530954

In vivo xenogeneic scaffold fate is determined by residual antigenicity and extracellular matrix preservation

OpenAIRE

Wong, Maelene L.; Wong, Janelle L.; Vapniarsky, Natalia; Griffiths, Leigh G.

2016-01-01

The immunological potential of animal-derived tissues and organs is the critical hurdle to increasing their clinical implementation. Glutaraldehyde-fixation cross-links proteins in xenogeneic tissues (e.g., bovine pericardium) to delay immune rejection, but also compromises the regenerative potential of the resultant biomaterial. Unfixed xenogeneic biomaterials in which xenoantigenicity has been ameliorated and native extracellular matrix (ECM) architecture has been maintained have the potent...

Potential scattering in the presence of a static magnetic field and a radiation field of arbitrary polarization

Science.gov (United States)

Ferrante, G.; Zarcone, M.; Nuzzo, S.; McDowell, M. R. C.

1982-05-01

Expressions are obtained for the total cross sections for scattering of a charged particle by a potential in the presence of a static uniform magnetic field and a radiation field of arbitrary polarization. For a Coulomb field this is closely related to the time reverse of photoionization of a neutral atom in a magnetic field, including multiphoton effects off-resonance. The model is not applicable when the radiation energy approaches one of the quasi-Landau state separations. The effects of radiation field polarization are examined in detail.

Extracellular RNAs: development as biomarkers of human disease

Directory of Open Access Journals (Sweden)

Joseph F. Quinn

2015-08-01

Full Text Available Ten ongoing studies designed to test the possibility that extracellular RNAs may serve as biomarkers in human disease are described. These studies, funded by the NIH Common Fund Extracellular RNA Communication Program, examine diverse extracellular body fluids, including plasma, serum, urine and cerebrospinal fluid. The disorders studied include hepatic and gastric cancer, cardiovascular disease, chronic kidney disease, neurodegenerative disease, brain tumours, intracranial haemorrhage, multiple sclerosis and placental disorders. Progress to date and the plans for future studies are outlined.

The modulation of TRPM7 currents by nafamostat mesilate depends directly upon extracellular concentrations of divalent cations

Directory of Open Access Journals (Sweden)

Chen Xuanmao

2010-12-01

Full Text Available Abstract Concentrations of extracellular divalent cations (Ca2+ and Mg2+ fall substantially during intensive synaptic transmission as well as during some pathophysiological conditions such as epilepsy and brain ischemia. Here we report that a synthetic serine protease inhibitor, nafamostat mesylate (NM, and several of its analogues, block recombinant TRPM7 currents expressed in HEK293T cells in inverse relationship to the concentration of extracellular divalent cations. Lowering extracellular Ca2+ and Mg2+ also evokes a divalent-sensitive non-selective cation current that is mediated by TRPM7 expression in hippocampal neurons. In cultured hippocampal neurons, NM blocked these TRPM7-mediated currents with an apparent affinity of 27 μM, as well as the paradoxical Ca2+ influx associated with lowering extracellular Ca2+. Unexpectedly, pre-exposure to NM strongly potentiated TRPM7 currents. In the presence of physiological concentrations of extracellular divalent cations, NM activates TRPM7. The stimulating effects of NM on TRPM7 currents are also inversely related to extracellular Ca2+ and Mg2+. DAPI and HSB but not netropsin, blocked and stimulated TRPM7. In contrast, mono-cationic, the metabolites of NM, p-GBA and AN, as well as protease inhibitor leupeptin and gabexate failed to substantially modulate TRPM7. NM thus provides a molecular template for the design of putative modulators of TRPM7.

Extracellular pH Modulates Neuroendocrine Prostate Cancer Cell Metabolism and Susceptibility to the Mitochondrial Inhibitor Niclosamide

Science.gov (United States)

Ippolito, Joseph E.; Brandenburg, Matthew W.; Ge, Xia; Crowley, Jan R.; Kirmess, Kristopher M.; Som, Avik; D’Avignon, D. Andre; Arbeit, Jeffrey M.; Achilefu, Samuel; Yarasheski, Kevin E.; Milbrandt, Jeffrey

2016-01-01

Neuroendocrine prostate cancer is a lethal variant of prostate cancer that is associated with castrate-resistant growth, metastasis, and mortality. The tumor environment of neuroendocrine prostate cancer is heterogeneous and characterized by hypoxia, necrosis, and numerous mitoses. Although acidic extracellular pH has been implicated in aggressive cancer features including metastasis and therapeutic resistance, its role in neuroendocrine prostate cancer physiology and metabolism has not yet been explored. We used the well-characterized PNEC cell line as a model to establish the effects of extracellular pH (pH 6.5, 7.4, and 8.5) on neuroendocrine prostate cancer cell metabolism. We discovered that alkalinization of extracellular pH converted cellular metabolism to a nutrient consumption-dependent state that was susceptible to glucose deprivation, glutamine deprivation, and 2-deoxyglucose (2-DG) mediated inhibition of glycolysis. Conversely, acidic pH shifted cellular metabolism toward an oxidative phosphorylation (OXPHOS)-dependent state that was susceptible to OXPHOS inhibition. Based upon this mechanistic knowledge of pH-dependent metabolism, we identified that the FDA-approved anti-helminthic niclosamide depolarized mitochondrial potential and depleted ATP levels in PNEC cells whose effects were enhanced in acidic pH. To further establish relevance of these findings, we tested the effects of extracellular pH on susceptibility to nutrient deprivation and OXPHOS inhibition in a cohort of castrate-resistant prostate cancer cell lines C4-2B, PC-3, and PC-3M. We discovered similar pH-dependent toxicity profiles among all cell lines with these treatments. These findings underscore a potential importance to acidic extracellular pH in the modulation of cell metabolism in tumors and development of an emerging paradigm that exploits the synergy of environment and therapeutic efficacy in cancer. PMID:27438712

Quantum effects in external fields determined by potentials with point-like support

International Nuclear Information System (INIS)

Mamev, S.G.; Trunov, N.N.

1982-01-01

Exact expressions are obtained for the vacuum expectation values of the energy-momentum tensor of a scalar field in external potentials of the delta-function type. The conditions for the onset of the vacuum instability are found and the properties of the resulting condensate are studied. Particle production in the field of a nonstationary delta potential is studied

Phosphoproteins in extracellular vesicles as candidate markers for breast cancer

OpenAIRE

Chen, I-Hsuan; Xue, Liang; Hsu, Chuan-Chih; Paez, Juan Sebastian Paez; Pan, Li; Andaluz, Hillary; Wendt, Michael K.; Iliuk, Anton B.; Zhu, Jian-Kang; Tao, W. Andy

2017-01-01

Protein phosphorylation is a major regulatory mechanism for many cellular functions, but no phosphoprotein in biofluids has been developed for disease diagnosis because of the presence of active phosphatases. This study presents a general strategy to isolate and identify phosphoproteins in extracellular vesicles (EVs) from human plasma as potential markers to differentiate disease from healthy states. We identified close to 10,000 unique phosphopeptides in EVs from small volumes of plasma sam...

Nanostructured gold microelectrodes for extracellular recording from electrogenic cells.

Science.gov (United States)

Brüggemann, D; Wolfrum, B; Maybeck, V; Mourzina, Y; Jansen, M; Offenhäusser, A

2011-07-01

We present a new biocompatible nanostructured microelectrode array for extracellular signal recording from electrogenic cells. Microfabrication techniques were combined with a template-assisted approach using nanoporous aluminum oxide to develop gold nanopillar electrodes. The nanopillars were approximately 300-400 nm high and had a diameter of 60 nm. Thus, they yielded a higher surface area of the electrodes resulting in a decreased impedance compared to planar electrodes. The interaction between the large-scale gold nanopillar arrays and cardiac muscle cells (HL-1) was investigated via focused ion beam milling. In the resulting cross-sections we observed a tight coupling between the HL-1 cells and the gold nanostructures. However, the cell membranes did not bend into the cleft between adjacent nanopillars due to the high pillar density. We performed extracellular potential recordings from HL-1 cells with the nanostructured microelectrode arrays. The maximal amplitudes recorded with the nanopillar electrodes were up to 100% higher than those recorded with planar gold electrodes. Increasing the aspect ratio of the gold nanopillars and changing the geometrical layout can further enhance the signal quality in the future.

Nanostructured gold microelectrodes for extracellular recording from electrogenic cells

Energy Technology Data Exchange (ETDEWEB)

Brueggemann, D; Wolfrum, B; Maybeck, V; Mourzina, Y; Jansen, M; Offenhaeusser, A, E-mail: a.offenhaeusser@fz-juelich.de [Institute of Complex Systems and Peter Gruenberg Institute: Bioelectronics (ICS8/PGI8), Forschungszentrum Juelich GmbH, Leo-Brandt-Strasse, 52428 Juelich (Germany); Juelich-Aachen Research Alliance-Fundamental of Future Information Technology (JARA-FIT) (Germany)

2011-07-01

We present a new biocompatible nanostructured microelectrode array for extracellular signal recording from electrogenic cells. Microfabrication techniques were combined with a template-assisted approach using nanoporous aluminum oxide to develop gold nanopillar electrodes. The nanopillars were approximately 300-400 nm high and had a diameter of 60 nm. Thus, they yielded a higher surface area of the electrodes resulting in a decreased impedance compared to planar electrodes. The interaction between the large-scale gold nanopillar arrays and cardiac muscle cells (HL-1) was investigated via focused ion beam milling. In the resulting cross-sections we observed a tight coupling between the HL-1 cells and the gold nanostructures. However, the cell membranes did not bend into the cleft between adjacent nanopillars due to the high pillar density. We performed extracellular potential recordings from HL-1 cells with the nanostructured microelectrode arrays. The maximal amplitudes recorded with the nanopillar electrodes were up to 100% higher than those recorded with planar gold electrodes. Increasing the aspect ratio of the gold nanopillars and changing the geometrical layout can further enhance the signal quality in the future.

Analytic solution of the potential and electric field of a jet type drift chamber

Energy Technology Data Exchange (ETDEWEB)

Weltin, A

1988-02-15

Starting from the known two-dimensional potential of a multiwire proportional chamber, the analytic expressions of the potential and the electric field are derived for a jet type drift chamber with a central wire plane of alternating sense and potential wires. The design goal of any jet chamber, namely the periodicity of the electric drift field, is imposed as a boundary condition at the beginning. In this way, the formulae are short and can be easily evaluated. In particular, expressions are given for the mean potential of the central wire plane, the drift field and the wire surface fields. Moreover, wire cathodes frequently used in jet chambers are described by analytic expressions. For a given drift field the difference of the potential as compared to a continuous metal cathode is presented. These results allowed to construct a two-dimensional computer simulation of the full OPAL jet chamber with no explicit periodicity but all its boundaries. Using field shaping electrodes a geometrically short yet quite satisfactory termination of a sense wire plane is demonstrated. Finally an example is presented, which is calculated in detail.

A standardized method to determine the concentration of extracellular vesicles using tunable resistive pulse sensing

NARCIS (Netherlands)

Vogel, Robert; Coumans, Frank A. W.; Maltesen, Raluca G.; Böing, Anita N.; Bonnington, Katherine E.; Broekman, Marike L.; Broom, Murray F.; Buzás, Edit I.; Christiansen, Gunna; Hajji, Najat; Kristensen, Søren R.; Kuehn, Meta J.; Lund, Sigrid M.; Maas, Sybren L. N.; Nieuwland, Rienk; Osteikoetxea, Xabier; Schnoor, Rosalie; Scicluna, Benjamin J.; Shambrook, Mitch; de Vrij, Jeroen; Mann, Stephen I.; Hill, Andrew F.; Pedersen, Shona

2016-01-01

Background: Understanding the pathogenic role of extracellular vesicles (EVs) in disease and their potential diagnostic and therapeutic utility is extremely reliant on in-depth quantification, measurement and identification of EV sub-populations. Quantification of EVs has presented several

Strategy for improving extracellular lipolytic activities by a novel thermotolerant Staphylococcus sp. strain

Directory of Open Access Journals (Sweden)

Cherif Slim

2011-11-01

Full Text Available Abstract Background Extracellular bacterial lipases received much attention for their substrate specificity and their ability to function under extreme environments (pH, temperature.... Many staphylococci produced lipases which were released into the culture medium. Reports of extracellular thermostable lipases from Staphylococcus sp. and active in alkaline conditions are not previously described. Results This study focused on novel strategies to increase extracellular lipolytic enzyme production by a novel Staphylococcus sp. strain ESW. The microorganism needed neutral or alkaline pH values between 7.0 and 12.0 for growth. For pH values outside this range, cell growth seemed to be significantly inhibited. Staphylococcus sp. culture was able to grow within a wide temperature range (from 30 to 55°C. The presence of oils in the culture medium leaded to improvements in cells growth and lipolytic enzyme activity. On the other hand, although chemical surfactants leaded to an almost complete inhibition of growth and lipolytic enzyme production, their addition along the culture could affect the location of the enzyme. In addition, our results showed that this novel Staphylococcus sp. strain produced biosurfactants simultaneously with lipolytic activity, when soapstock (The main co-product of the vegetable oil refining industry, was used as the sole carbon source. Conclusion A simultaneous biosurfactant and extracellular lipolytic enzymes produced bacterial strain with potential application in soap stock treatment

Electric Potential and Electric Field Imaging with Dynamic Applications & Extensions

Science.gov (United States)

Generazio, Ed

2017-01-01

The technology and methods for remote quantitative imaging of electrostatic potentials and electrostatic fields in and around objects and in free space is presented. Electric field imaging (EFI) technology may be applied to characterize intrinsic or existing electric potentials and electric fields, or an externally generated electrostatic field made be used for volumes to be inspected with EFI. The baseline sensor technology (e-Sensor) and its construction, optional electric field generation (quasi-static generator), and current e- Sensor enhancements (ephemeral e-Sensor) are discussed. Critical design elements of current linear and real-time two-dimensional (2D) measurement systems are highlighted, and the development of a three dimensional (3D) EFI system is presented. Demonstrations for structural, electronic, human, and memory applications are shown. Recent work demonstrates that phonons may be used to create and annihilate electric dipoles within structures. Phonon induced dipoles are ephemeral and their polarization, strength, and location may be quantitatively characterized by EFI providing a new subsurface Phonon-EFI imaging technology. Results from real-time imaging of combustion and ion flow, and their measurement complications, will be discussed. Extensions to environment, Space and subterranean applications will be presented, and initial results for quantitative characterizing material properties are shown. A wearable EFI system has been developed by using fundamental EFI concepts. These new EFI capabilities are demonstrated to characterize electric charge distribution creating a new field of study embracing areas of interest including electrostatic discharge (ESD) mitigation, manufacturing quality control, crime scene forensics, design and materials selection for advanced sensors, combustion science, on-orbit space potential, container inspection, remote characterization of electronic circuits and level of activation, dielectric morphology of

Superfield approach to calculation of effective potential in supersymmetric field theories

International Nuclear Information System (INIS)

Bukhbinder, I.L.; Kuzenko, S.M.; Yarevskaya, Zh.V.

1993-01-01

Superfield method of computing effective potential in supersymmetric field theories is suggested. The one-loop effective potential of the Wess-Zumino model is found. The prescription for obtaining multi-loop corrections is described

Thermodynamic potential with condensate fields in an SU(2) model of QCD

International Nuclear Information System (INIS)

Ebert, D.

1996-06-01

We calculate the thermodynamic potential of the quark-gluon plasma in an SU(2) model of QCD, taking into account the gluon condensate configuration with a constant A 4 -potential and a uniform chromomagnetic field H. Within this scheme the interplay of condensate fields, as well as the role of quarks in the possible dynamical stabilization of the system is investigated. (orig.)

Extracellular nucleotide derivatives protect cardiomyctes against hypoxic stress

DEFF Research Database (Denmark)

Golan, O; Issan, Y; Isak, A

2011-01-01

assures cardioprotection. Treatment with extracellular nucleotides, or with tri/di-phosphate, administered under normoxic conditions or during hypoxic conditions, led to a decrease in reactive oxygen species production. CONCLUSIONS: Extracellular tri/di-phosphates are apparently the molecule responsible...

Identification and statistical optimization of fermentation conditions for a newly isolated extracellular cholesterol oxidase-producing Streptomyces cavourensis strain NEAE-42

OpenAIRE

El-Naggar, Noura El-Ahmady; El-Shweihy, Nancy M.; El-Ewasy, Sara M.

2016-01-01

Background Due to broad range of clinical and industrial applications of cholesterol oxidase, isolation and screening of bacterial strains producing extracellular form of cholesterol oxidase is of great importance. Results One hundred and thirty actinomycete isolates were screened for their cholesterol oxidase activity. Among them, a potential culture, strain NEAE-42 is displayed the highest extracellular cholesterol oxidase activity. It was selected and identified as Streptomyces cavourensis...

Identification of electric-field-dependent steps in the Na(+),K(+)-pump cycle.

Science.gov (United States)

Mares, Laura J; Garcia, Alvaro; Rasmussen, Helge H; Cornelius, Flemming; Mahmmoud, Yasser A; Berlin, Joshua R; Lev, Bogdan; Allen, Toby W; Clarke, Ronald J

2014-09-16

The charge-transporting activity of the Na(+),K(+)-ATPase depends on its surrounding electric field. To isolate which steps of the enzyme's reaction cycle involve charge movement, we have investigated the response of the voltage-sensitive fluorescent probe RH421 to interaction of the protein with BTEA (benzyltriethylammonium), which binds from the extracellular medium to the Na(+),K(+)-ATPase's transport sites in competition with Na(+) and K(+), but is not occluded within the protein. We find that only the occludable ions Na(+), K(+), Rb(+), and Cs(+) cause a drop in RH421 fluorescence. We conclude that RH421 detects intramembrane electric field strength changes arising from charge transport associated with conformational changes occluding the transported ions within the protein, not the electric fields of the bound ions themselves. This appears at first to conflict with electrophysiological studies suggesting extracellular Na(+) or K(+) binding in a high field access channel is a major electrogenic reaction of the Na(+),K(+)-ATPase. All results can be explained consistently if ion occlusion involves local deformations in the lipid membrane surrounding the protein occurring simultaneously with conformational changes necessary for ion occlusion. The most likely origin of the RH421 fluorescence response is a change in membrane dipole potential caused by membrane deformation. Copyright © 2014 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Tissue-Derived Extracellular Matrix Bioscaffolds: Emerging Applications in Cartilage and Meniscus Repair.

Science.gov (United States)

Monibi, Farrah A; Cook, James L

2017-08-01

Musculoskeletal injuries are a common problem in orthopedic practice. Given the long-term consequences of unaddressed cartilage and meniscal pathology, a number of treatments have been attempted to stimulate repair or to replace the injured tissue. Despite advances in orthopedic surgery, effective treatments for cartilage and meniscus injuries remain a significant clinical challenge. Tissue engineering is a developing field that aims to regenerate injured tissues with a combination of cells, scaffolds, and signals. Many natural and synthetic scaffold materials have been developed and tested for the repair and restoration of a number of musculoskeletal tissues. Among these, biological scaffolds derived from cell and tissue-derived extracellular matrix (ECM) have shown great promise in tissue engineering given the critical role of the ECM for maintaining the biological and biomechanical properties, structure, and function of native tissues. This review article presents emerging applications for tissue-derived ECM scaffolds in cartilage and meniscus repair. We examine normal ECM composition and the current and future methods for potential treatment of articular cartilage and meniscal defects with decellularized scaffolds.

Extracellular Matrix-Mediated Maturation of Human Pluripotent Stem Cell-Derived Cardiac Monolayer Structure and Electrophysiological Function.

Science.gov (United States)

Herron, Todd J; Rocha, Andre Monteiro Da; Campbell, Katherine F; Ponce-Balbuena, Daniela; Willis, B Cicero; Guerrero-Serna, Guadalupe; Liu, Qinghua; Klos, Matt; Musa, Hassan; Zarzoso, Manuel; Bizy, Alexandra; Furness, Jamie; Anumonwo, Justus; Mironov, Sergey; Jalife, José

2016-04-01

Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) monolayers generated to date display an immature embryonic-like functional and structural phenotype that limits their utility for research and cardiac regeneration. In particular, the electrophysiological function of hPSC-CM monolayers and bioengineered constructs used to date are characterized by slow electric impulse propagation velocity and immature action potential profiles. Here, we have identified an optimal extracellular matrix for significant electrophysiological and structural maturation of hPSC-CM monolayers. hPSC-CM plated in the optimal extracellular matrix combination have impulse propagation velocities ≈2× faster than previously reported (43.6±7.0 cm/s; n=9) and have mature cardiomyocyte action potential profiles, including hyperpolarized diastolic potential and rapid action potential upstroke velocity (146.5±17.7 V/s; n=5 monolayers). In addition, the optimal extracellular matrix promoted hypertrophic growth of cardiomyocytes and the expression of key mature sarcolemmal (SCN5A, Kir2.1, and connexin43) and myofilament markers (cardiac troponin I). The maturation process reported here relies on activation of integrin signaling pathways: neutralization of β1 integrin receptors via blocking antibodies and pharmacological blockade of focal adhesion kinase activation prevented structural maturation. Maturation of human stem cell-derived cardiomyocyte monolayers is achieved in a 1-week period by plating cardiomyocytes on PDMS (polydimethylsiloxane) coverslips rather than on conventional 2-dimensional cell culture formats, such as glass coverslips or plastic dishes. Activation of integrin signaling and focal adhesion kinase is essential for significant maturation of human cardiac monolayers. © 2016 American Heart Association, Inc.

Temporal Profiles Dissociate Regional Extracellular Ethanol versus Dopamine Concentrations

Science.gov (United States)

2015-01-01

In vivo monitoring of dopamine via microdialysis has demonstrated that acute, systemic ethanol increases extracellular dopamine in regions innervated by dopaminergic neurons originating in the ventral tegmental area and substantia nigra. Simultaneous measurement of dialysate dopamine and ethanol allows comparison of the time courses of their extracellular concentrations. Early studies demonstrated dissociations between the time courses of brain ethanol concentrations and dopaminergic responses in the nucleus accumbens (NAc) elicited by acute ethanol administration. Both brain ethanol and extracellular dopamine levels peak during the first 5 min following systemic ethanol administration, but the dopamine response returns to baseline while brain ethanol concentrations remain elevated. Post hoc analyses examined ratios of the dopamine response (represented as a percent above baseline) to tissue concentrations of ethanol at different time points within the first 25–30 min in the prefrontal cortex, NAc core and shell, and dorsomedial striatum following a single intravenous infusion of ethanol (1 g/kg). The temporal patterns of these “response ratios” differed across brain regions, possibly due to regional differences in the mechanisms underlying the decline of the dopamine signal associated with acute intravenous ethanol administration and/or to the differential effects of acute ethanol on the properties of subpopulations of midbrain dopamine neurons. This Review draws on neurochemical, physiological, and molecular studies to summarize the effects of acute ethanol administration on dopamine activity in the prefrontal cortex and striatal regions, to explore the potential reasons for the regional differences observed in the decline of ethanol-induced dopamine signals, and to suggest directions for future research. PMID:25537116

High-speed centrifugation induces aggregation of extracellular vesicles.

Science.gov (United States)

Linares, Romain; Tan, Sisareuth; Gounou, Céline; Arraud, Nicolas; Brisson, Alain R

2015-01-01

Plasma and other body fluids contain cell-derived extracellular vesicles (EVs), which participate in physiopathological processes and have potential biomedical applications. In order to isolate, concentrate and purify EVs, high-speed centrifugation is often used. We show here, using electron microscopy, receptor-specific gold labelling and flow cytometry, that high-speed centrifugation induces the formation of EV aggregates composed of a mixture of EVs of various phenotypes and morphologies. The presence of aggregates made of EVs of different phenotypes may lead to erroneous interpretation concerning the existence of EVs harbouring surface antigens from different cell origins.

High-speed centrifugation induces aggregation of extracellular vesicles

Directory of Open Access Journals (Sweden)

Romain Linares

2015-12-01

Full Text Available Plasma and other body fluids contain cell-derived extracellular vesicles (EVs, which participate in physiopathological processes and have potential biomedical applications. In order to isolate, concentrate and purify EVs, high-speed centrifugation is often used. We show here, using electron microscopy, receptor-specific gold labelling and flow cytometry, that high-speed centrifugation induces the formation of EV aggregates composed of a mixture of EVs of various phenotypes and morphologies. The presence of aggregates made of EVs of different phenotypes may lead to erroneous interpretation concerning the existence of EVs harbouring surface antigens from different cell origins.

Neutrophil extracellular traps - the dark side of neutrophils

DEFF Research Database (Denmark)

Sørensen, Ole E.; Borregaard, Niels

2016-01-01

Neutrophil extracellular traps (NETs) were discovered as extracellular strands of decondensed DNA in complex with histones and granule proteins, which were expelled from dying neutrophils to ensnare and kill microbes. NETs are formed during infection in vivo by mechanisms different from those ori...

Potential of the test particle in the magnetic field. I

International Nuclear Information System (INIS)

Sestak, B.

1980-01-01

The problem of the test particle potential in an external homogeneous magnetic field is solved in an unmagnetized plasma. It is shown that for the case when the parallel velocity component of the test particle is greater than the thermal velocity of the background particles, the potential is of a Coulomb character while for the case where the parallel velocity component is less than the thermal velocity the potential is of a Debye character. The Larmor radius of the test particle appears as an additional parameter in these potentials. (author)

Separation of Electric Fields Into Potential and Inductive Parts, and Implications for Radial Diffusion

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Chan, A. A.; Ilie, R.; Elkington, S. R.; Albert, J.; Huie, W.

2017-12-01

It has been traditional to separate radiation belt radial-diffusion coefficients into two contributions: an "electrostatic" diffusion coefficient, which is assumed to be due to a potential (non-inductive) electric field, and an "electromagnetic" diffusion coefficient , which is assumed to be due to the combined effect of an inductive electric field and the corresponding time-dependent magnetic field. One difficulty in implementing this separation when using magnetospheric fields obtained from measurements, or from MHD simulations, is that only the total electric field is given; the separation of the electric field into potential and inductive parts is not readily available. In this work we separate the electric field using a numerical method based on the Helmholtz decomposition of the total motional electric field calculated by the BATS-R-US MHD code. The inner boundary for the electric potential is based on the Ridley Ionospheric Model solution and we assume floating boundary conditions in the solar wind. Using different idealized solar wind drivers, including a solar wind density that is oscillating at a single frequency or with a broad spectrum of frequencies, we calculate potential and inductive electric fields, electric and magnetic power spectral densities, and corresponding radial diffusion coefficients. Simulations driven by idealized solar wind conditions show a clear separation of the potential and inductive contributions to the power spectral densities and diffusion coefficients. Simulations with more realistic solar wind drivers are underway to better assess the use of electrostatic and electromagnetic diffusion coefficients in understanding ULF wave-particle interactions in Earth's radiation belts.

Ionization from short-range potential under action of electromagnetic field of complex configuration

CERN Document Server

Rodionov, V N; Kravtsova, G A

2002-01-01

The transcendental equation for the complex energy is obtained on the basis of the exactly solvable 3D model of the short-acting potential and the Green time function in the intensive electromagnetic field, constituting the combination of the constant magnetic field and the circular-polarization wave field. The electron quasistationary states parameters in the delta-potential with an account of the action of the intensive external field of complex configuration are calculated. The problem on the possibility of stabilizing the bound states decay of the spinor and scalar particles through the intensive magnetic field is clarified. It is established that the obtained results regime the reexamination of the accepted notion on the stabilizing role of the strong magnetic field by the atoms ionization

Assessment of small RNA sorting into different extracellular fractions revealed by high-throughput sequencing of breast cell lines

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Tosar, Juan Pablo; Gámbaro, Fabiana; Sanguinetti, Julia; Bonilla, Braulio; Witwer, Kenneth W.; Cayota, Alfonso

2015-01-01

Intercellular communication can be mediated by extracellular small regulatory RNAs (sRNAs). Circulating sRNAs are being intensively studied for their promising use as minimally invasive disease biomarkers. To date, most attention is centered on exosomes and microRNAs as the vectors and the secreted species, respectively. However, this field would benefit from an increased understanding of the plethora of sRNAs secreted by different cell types in different extracellular fractions. It is still not clear if specific sRNAs are selected for secretion, or if sRNA secretion is mostly passive. We sequenced the intracellular sRNA content (19–60 nt) of breast epithelial cell lines (MCF-7 and MCF-10A) and compared it with extracellular fractions enriched in microvesicles, exosomes and ribonucleoprotein complexes. Our results are consistent with a non-selective secretion model for most microRNAs, although a few showed secretion patterns consistent with preferential secretion. On the contrary, 5′ tRNA halves and 5′ RNA Y4-derived fragments of 31–33 were greatly and significantly enriched in the extracellular space (even in non-mammary cell lines), where tRNA halves were detected as part of ∼45 kDa ribonucleoprotein complexes. Overall, we show that different sRNA families have characteristic secretion patterns and open the question of the role of these sRNAs in the extracellular space. PMID:25940616

Extracellular electron transfer mechanisms between microorganisms and minerals

Energy Technology Data Exchange (ETDEWEB)

Shi, Liang; Dong, Hailiang; Reguera, Gemma; Beyenal, Haluk; Lu, Anhuai; Liu, Juan; Yu, Han-Qing; Fredrickson, James K.

2016-08-30

Electrons can be transferred from microorganisms to multivalent metal ions that are associated with minerals and vice versa. As the microbial cell envelope is neither physically permeable to minerals nor electrically conductive, microorganisms have evolved strategies to exchange electrons with extracellular minerals. In this Review, we discuss the molecular mechanisms that underlie the ability of microorganisms to exchange electrons, such as c-type cytochromes and microbial nanowires, with extracellular minerals and with microorganisms of the same or different species. Microorganisms that have extracellular electron transfer capability can be used for biotechnological applications, including bioremediation, biomining and the production of biofuels and nanomaterials.

Characterization of rat primary trigeminal satellite glial cells and associated extracellular vesicles under normal and inflammatory conditions

DEFF Research Database (Denmark)

Vinterhøj, Hye Sook Han; Stensballe, Allan; Duroux, Meg

2018-01-01

Satellite glial cells (SGCs) in sensory ganglia contribute to the pathogenesis of chronic pain, potentially through mediating extracellular or paracrine signaling. Recently, extracellular vesicles (EVs) in the form of exosomes have been found to play an important role in cell-cell communication....... Results demonstrated that SGCs shed vesicles in the size range of exosomes (>150 nm) but with altered protein expression upon LPS-activation. Proteomic profiling of SGCs-shed EVs showed that a number of proteins were differentially regulated upon LPS stimulation such as junction plakoglobin and myosin 9...

Extracellular calmodulin regulates growth and cAMP-mediated chemotaxis in Dictyostelium discoideum

International Nuclear Information System (INIS)

O’Day, Danton H.; Huber, Robert J.; Suarez, Andres

2012-01-01

Highlights: ► Extracellular calmodulin is present throughout growth and development in Dictyostelium. ► Extracellular calmodulin localizes within the ECM during development. ► Extracellular calmodulin inhibits cell proliferation and increases chemotaxis. ► Extracellular calmodulin exists in eukaryotic microbes. ► Extracellular calmodulin may be functionally as important as intracellular calmodulin. -- Abstract: The existence of extracellular calmodulin (CaM) has had a long and controversial history. CaM is a ubiquitous calcium-binding protein that has been found in every eukaryotic cell system. Calcium-free apo-CaM and Ca 2+ /CaM exert their effects by binding to and regulating the activity of CaM-binding proteins (CaMBPs). Most of the research done to date on CaM and its CaMBPs has focused on their intracellular functions. The presence of extracellular CaM is well established in a number of plants where it functions in proliferation, cell wall regeneration, gene regulation and germination. While CaM has been detected extracellularly in several animal species, including frog, rat, rabbit and human, its extracellular localization and functions are less well established. In contrast the study of extracellular CaM in eukaryotic microbes remains to be done. Here we show that CaM is constitutively expressed and secreted throughout asexual development in Dictyostelium where the presence of extracellular CaM dose-dependently inhibits cell proliferation but increases cAMP mediated chemotaxis. During development, extracellular CaM localizes within the slime sheath where it coexists with at least one CaMBP, the matricellular CaM-binding protein CyrA. Coupled with previous research, this work provides direct evidence for the existence of extracellular CaM in the Dictyostelium and provides insight into its functions in this model amoebozoan.

Eosinophilic Otitis Media: the Aftermath of Eosinophil Extracellular Trap Cell Death.

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Ueki, Shigeharu; Ohta, Nobuo; Takeda, Masahide; Konno, Yasunori; Hirokawa, Makoto

2017-05-01

Eosinophilic otitis media (EOM) is a refractory disease characterized by the accumulation of eosinophils in middle ear effusion and mucosa. We summarize current knowledge regarding the clinical characteristics and management of EOM. Although eosinophil activation in inflamed foci is involved in the pathogenesis of EOM, little is known about the fate of the eosinophils and aftermath of their cell death. We discuss the possibility that eosinophils undergo non-apoptotic cell death that worsens tissue damage and increases effusion viscosity. Unlike chronic otitis media, EOM is strongly associated with an allergic background. Corticosteroids are currently the only effective pharmacological treatment, and surgical intervention is often required. Mucosal eosinophils infiltrate extensively into the middle ear cavity where they are stimulated by locally produced activators including interleukin-5 and eotaxin. The eosinophils undergo cytolysis in the effusion, which represents a major fate of activated eosinophils in vivo. Recent data revealed cytolysis could be renamed as extracellular trap cell death (ETosis). ETosis represents suicidal cell death involving total cell degranulation and development of sticky chromatin structures (extracellular traps (ETs)). The characteristics of eosinophil- and neutrophil-derived ET polymers might contribute to the difference in viscosity of secretions between EOM and common chronic otitis media. The extracellular products remaining after eosinophil ETosis are an important aspect of EOM pathology. The concept of ETosis also has novel implications for potential therapeutic modalities in various eosinophilic disorders.

The role of extracellular histones in haematological disorders.

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Alhamdi, Yasir; Toh, Cheng-Hock

2016-06-01

Over the past decades, chromosomal alterations have been extensively investigated for their pathophysiological relevance in haematological malignancies. In particular, epigenetic modifications of intra-nuclear histones are now known as key regulators of healthy cell cycles that have also evolved into novel therapeutic targets for certain blood cancers. Thus, for most haematologists, histones are DNA-chained proteins that are buried deep within chromatin. However, the plot has deepened with recent revelations on the function of histones when unchained and released extracellularly upon cell death or from activated neutrophils as part of neutrophil extracellular traps (NETs). Extracellular histones and NETs are increasingly recognized for profound cytotoxicity and pro-coagulant effects. This article highlights the importance of recognizing this new paradigm of extracellular histones as a key player in host defence through its damage-associated molecular patterns, which could translate into novel diagnostic and therapeutic biomarkers in various haematological and critical disorders. © 2016 John Wiley & Sons Ltd.

A collagen-based scaffold delivering exogenous microrna-29B to modulate extracellular matrix remodeling.

Science.gov (United States)

Monaghan, Michael; Browne, Shane; Schenke-Layland, Katja; Pandit, Abhay

2014-04-01

Directing appropriate extracellular matrix remodeling is a key aim of regenerative medicine strategies. Thus, antifibrotic interfering RNA (RNAi) therapy with exogenous microRNA (miR)-29B was proposed as a method to modulate extracellular matrix remodeling following cutaneous injury. It was hypothesized that delivery of miR-29B from a collagen scaffold will efficiently modulate the extracellular matrix remodeling response and reduce maladaptive remodeling such as aggressive deposition of collagen type I after injury. The release of RNA from the scaffold was assessed and its ability to silence collagen type I and collagen type III expression was evaluated in vitro. When primary fibroblasts were cultured with scaffolds doped with miR-29B, reduced levels of collagen type I and collagen type III mRNA expression were observed for up to 2 weeks of culture. When the scaffolds were applied to full thickness wounds in vivo, reduced wound contraction, improved collagen type III/I ratios and a significantly higher matrix metalloproteinase (MMP)-8: tissue inhibitor of metalloproteinase (TIMP)-1 ratio were detected when the scaffolds were functionalized with miR-29B. Furthermore, these effects were significantly influenced by the dose of miR-29B in the collagen scaffold (0.5 versus 5 μg). This study shows a potential of combining exogenous miRs with collagen scaffolds to improve extracellular matrix remodeling following injury.

Field differential equations for a potential flow from a Hamilton type variational principle

International Nuclear Information System (INIS)

Fierros Palacios, A.

1992-01-01

The same theoretical frame that was used to solve the problem of the field equations for a viscous fluid is utilized in this work. The purpose is to obtain the differential field equations for a potential flow from the Lagrangian formalism as in classical field theory. An action functional is introduced as a space-time integral over a region of three-dimensional Euclidean space, of a Lagrangian density as a function of certain field variables. A Hamilton type extremum action principle is postulated with adequate boundary conditions, and a set of differential field equations is derived. A particular Lagrangian density of the T-V type leads to the wave equation for the velocity potential. (Author)

Mean Field Limits for Interacting Diffusions in a Two-Scale Potential

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Gomes, S. N.; Pavliotis, G. A.

2018-06-01

In this paper, we study the combined mean field and homogenization limits for a system of weakly interacting diffusions moving in a two-scale, locally periodic confining potential, of the form considered in Duncan et al. (Brownian motion in an N-scale periodic potential, arXiv:1605.05854, 2016b). We show that, although the mean field and homogenization limits commute for finite times, they do not, in general, commute in the long time limit. In particular, the bifurcation diagrams for the stationary states can be different depending on the order with which we take the two limits. Furthermore, we construct the bifurcation diagram for the stationary McKean-Vlasov equation in a two-scale potential, before passing to the homogenization limit, and we analyze the effect of the multiple local minima in the confining potential on the number and the stability of stationary solutions.

Large area, label-free imaging of extracellular matrix using telecentricity

Science.gov (United States)

Visbal Onufrak, Michelle A.; Konger, Raymond L.; Kim, Young L.

2017-02-01

Subtle alterations in stromal tissue structures and organizations within the extracellular matrix (ECM) have been observed in several types of tissue abnormalities, including early skin cancer and wounds. Current microscopic imaging methods often lack the ability to accurately determine the extent of malignancy over a large area, due to their limited field of view. In this research we focus on the development of simple mesoscopic (i.e. between microscopic and macroscopic) biomedical imaging device for non-invasive assessment of ECM alterations over a large, heterogeneous area. In our technology development, a telecentric lens, commonly used in machine vision systems but rarely used in biomedical imaging, serves as a key platform to visualize alterations in tissue microenvironments in a label-free manner over a clinically relevant area. In general, telecentric imaging represents a simple, alternative method for reducing unwanted scattering or diffuse light caused by the highly anisotropic scattering properties of biological tissue. In particular, under telecentric imaging the light intensity backscattered from biological tissue is mainly sensitive to the scattering anisotropy factor, possibly associated with the ECM. We demonstrate the inherent advantages of combining telecentric lens systems with hyperspectral imaging for providing optical information of tissue scattering in biological tissue of murine models, as well as light absorption of hemoglobin in blood vessel tissue phantoms. Thus, we envision that telecentric imaging could potentially serve for simple site-specific, tissue-based assessment of stromal alterations over a clinically relevant field of view in a label-free manner, for studying diseases associated with disruption of homeostasis in ECM.

Integrins and extracellular matrix in mechanotransduction

Directory of Open Access Journals (Sweden)

Ramage L

2011-12-01

Full Text Available Lindsay RamageQueen’s Medical Research Institute, University of Edinburgh, Edinburgh, UKAbstract: Integrins are a family of cell surface receptors which mediate cell–matrix and cell–cell adhesions. Among other functions they provide an important mechanical link between the cells external and intracellular environments while the adhesions that they form also have critical roles in cellular signal-transduction. Cell–matrix contacts occur at zones in the cell surface where adhesion receptors cluster and when activated the receptors bind to ligands in the extracellular matrix. The extracellular matrix surrounds the cells of tissues and forms the structural support of tissue which is particularly important in connective tissues. Cells attach to the extracellular matrix through specific cell-surface receptors and molecules including integrins and transmembrane proteoglycans. Integrins work alongside other proteins such as cadherins, immunoglobulin superfamily cell adhesion molecules, selectins, and syndecans to mediate cell–cell and cell–matrix interactions and communication. Activation of adhesion receptors triggers the formation of matrix contacts in which bound matrix components, adhesion receptors, and associated intracellular cytoskeletal and signaling molecules form large functional, localized multiprotein complexes. Cell–matrix contacts are important in a variety of different cell and tissue properties including embryonic development, inflammatory responses, wound healing, and adult tissue homeostasis. This review summarizes the roles and functions of integrins and extracellular matrix proteins in mechanotransduction.Keywords: ligand binding, α subunit, ß subunit, focal adhesion, cell differentiation, mechanical loading, cell–matrix interaction

Potential Magnetic Field around a Helical Flux-rope Current Structure in the Solar Corona

OpenAIRE

Petrie, G. J. D.

2007-01-01

We consider the potential magnetic field associated with a helical electric line current flow, idealizing the near-potential coronal field within which a highly localized twisted current structure is embedded. It is found that this field has a significant axial component off the helical magnetic axis where there is no current flow, such that the flux winds around the axis. The helical line current field, in including the effects of flux rope writhe, is therefore more topologically complex tha...

Extracellular Protease Inhibition Alters the Phenotype of Chondrogenically Differentiating Human Mesenchymal Stem Cells (MSCs) in 3D Collagen Microspheres.

Science.gov (United States)

Han, Sejin; Li, Yuk Yin; Chan, Barbara Pui

2016-01-01

Matrix remodeling of cells is highly regulated by proteases and their inhibitors. Nevertheless, how would the chondrogenesis of mesenchymal stem cells (MSCs) be affected, when the balance of the matrix remodeling is disturbed by inhibiting matrix proteases, is incompletely known. Using a previously developed collagen microencapsulation platform, we investigated whether exposing chondrogenically differentiating MSCs to intracellular and extracellular protease inhibitors will affect the extracellular matrix remodeling and hence the outcomes of chondrogenesis. Results showed that inhibition of matrix proteases particularly the extracellular ones favors the phenotype of fibrocartilage rather than hyaline cartilage in chondrogenically differentiating hMSCs by upregulating type I collagen protein deposition and type II collagen gene expression without significantly altering the hypertrophic markers at gene level. This study suggests the potential of manipulating extracellular proteases to alter the outcomes of hMSC chondrogenesis, contributing to future development of differentiation protocols for fibrocartilage tissues for intervertebral disc and meniscus tissue engineering.

Extracellular Protease Inhibition Alters the Phenotype of Chondrogenically Differentiating Human Mesenchymal Stem Cells (MSCs in 3D Collagen Microspheres.

Directory of Open Access Journals (Sweden)

Sejin Han

Full Text Available Matrix remodeling of cells is highly regulated by proteases and their inhibitors. Nevertheless, how would the chondrogenesis of mesenchymal stem cells (MSCs be affected, when the balance of the matrix remodeling is disturbed by inhibiting matrix proteases, is incompletely known. Using a previously developed collagen microencapsulation platform, we investigated whether exposing chondrogenically differentiating MSCs to intracellular and extracellular protease inhibitors will affect the extracellular matrix remodeling and hence the outcomes of chondrogenesis. Results showed that inhibition of matrix proteases particularly the extracellular ones favors the phenotype of fibrocartilage rather than hyaline cartilage in chondrogenically differentiating hMSCs by upregulating type I collagen protein deposition and type II collagen gene expression without significantly altering the hypertrophic markers at gene level. This study suggests the potential of manipulating extracellular proteases to alter the outcomes of hMSC chondrogenesis, contributing to future development of differentiation protocols for fibrocartilage tissues for intervertebral disc and meniscus tissue engineering.

Wetting and dewetting of extracellular matrix and glycocalix models

International Nuclear Information System (INIS)

Tanaka, Motomu; Rehfeldt, Florian; Schneider, Matthias F; Mathe, Gerald; Albersdoerfer, Antero; Neumaier, Klaus R; Purrucker, Oliver; Sackmann, Erich

2005-01-01

In this paper, we study wetting and dewetting of hydrated biopolymer layers mediating cell-cell and cell-tissue contacts, called the extracellular matrix and cell surface glycocalix, by the combination of various physical techniques. Here, the sum of the net effects of the various interfacial forces, which is referred to as the disjoining pressure, is used as a semi-quantitative measure to describe the thermodynamics of hydrated interlayers. The disjoining pressure can be measured by applying external forces to maintain the equilibrium distance between two parallel surfaces (in biology, two neighbouring plasma membranes). Using artificial models of the extracellular matrix and glycocalix, we describe stable cell-cell contacts in terms of the wetting (or spreading) of complex fluids on polymer surfaces. In fact, the adjustment of the wetting interaction via thin hydrating layers enables us to transform three-dimensional cell membranes into quasi-two-dimensional films on macroscopically large surfaces. Fine-tuning of local wetting conditions at the interface further allows for the selective wetting of native cell membranes on microstructured polysaccharide films, which has a large potential for individual detection of biological functions in confined geometries

Skeletal muscle expresses the extracellular cyclic AMP–adenosine pathway

Science.gov (United States)

Chiavegatti, T; Costa, V L; Araújo, M S; Godinho, R O

2007-01-01

Background and purpose: cAMP is a key intracellular signalling molecule that regulates multiple processes of the vertebrate skeletal muscle. We have shown that cAMP can be actively pumped out from the skeletal muscle cell. Since in other tissues, cAMP efflux had been associated with extracellular generation of adenosine, in the present study we have assessed the fate of interstitial cAMP and the existence of an extracellular cAMP-adenosine signalling pathway in skeletal muscle. Experimental approach: cAMP efflux and/or its extracellular degradation were analysed by incubating rat cultured skeletal muscle with exogenous cAMP, forskolin or isoprenaline. cAMP and its metabolites were quantified by radioassay or HPLC, respectively. Key results: Incubation of cells with exogenous cAMP was followed by interstitial accumulation of 5′-AMP and adenosine, a phenomenon inhibited by selective inhibitors of ecto-phosphodiesterase (DPSPX) and ecto-nucleotidase (AMPCP). Activation of adenylyl cyclase (AC) in cultured cells with forskolin or isoprenaline increased cAMP efflux and extracellular generation of 5′-AMP and adenosine. Extracellular cAMP-adenosine pathway was also observed after direct and receptor-dependent stimulation of AC in rat extensor muscle ex vivo. These events were attenuated by probenecid, an inhibitor of ATP binding cassette family transporters. Conclusions and implications: Our results show the existence of an extracellular biochemical cascade that converts cAMP into adenosine. The functional relevance of this extracellular signalling system may involve a feedback modulation of cellular response initiated by several G protein-coupled receptor ligands, amplifying cAMP influence to a paracrine mode, through its metabolite, adenosine. PMID:18157164

Extracellular histones play an inflammatory role in acid aspiration-induced acute respiratory distress syndrome.

Science.gov (United States)

Zhang, Yanlin; Wen, Zongmei; Guan, Li; Jiang, Ping; Gu, Tao; Zhao, Jinyuan; Lv, Xin; Wen, Tao

2015-01-01

Systemic inflammation is a key feature in acid aspiration-induced acute respiratory distress syndrome (ARDS), but the factors that trigger inflammation are unclear. The authors hypothesize that extracellular histones, a newly identified inflammatory mediator, play important roles in the pathogenesis of ARDS. The authors used a hydrochloric acid aspiration-induced ARDS model to investigate whether extracellular histones are pathogenic and whether targeting histones are protective. Exogenous histones and antihistone antibody were administered to mice. Heparin can bind to histones, so the authors studied whether heparin could protect from ARDS using cell and mouse models. Furthermore, the authors analyzed whether extracellular histones are clinically involved in ARDS patients caused by gastric aspiration. Extracellular histones in bronchoalveolar lavage fluid of acid-treated mice were significantly higher (1.832 ± 0.698) at 3 h after injury than in sham-treated group (0.63 ± 0.153; P = 0.0252, n = 5 per group). Elevated histones may originate from damaged lung cells and neutrophil infiltration. Exogenous histones aggravated lung injury, whereas antihistone antibody markedly attenuated the intensity of ARDS. Notably, heparin provided a similar protective effect against ARDS. Analysis of plasma from ARDS patients (n = 21) showed elevated histones were significantly correlated with the degree of ARDS and were higher in nonsurvivors (2.723 ± 0.2933, n = 7) than in survivors (1.725 ± 0.1787, P = 0.006, n = 14). Extracellular histones may play a contributory role toward ARDS by promoting tissue damage and systemic inflammation and may become a novel marker reflecting disease activity. Targeting histones by neutralizing antibody or heparin shows potent protective effects, suggesting a potentially therapeutic strategy.

The potential for hydrocarbon biodegradation and production of extracellular polymeric substances by aerobic bacteria isolated from a Brazilian petroleum reservoir.

Science.gov (United States)

Vasconcellos, S P; Dellagnezze, B M; Wieland, A; Klock, J-H; Santos Neto, E V; Marsaioli, A J; Oliveira, V M; Michaelis, W

2011-06-01

Extracellular polymeric substances (EPS) can contribute to the cellular degradation of hydrocarbons and have a huge potential for application in biotechnological processes, such as bioremediation and microbial enhanced oil recovery (MEOR). Four bacterial strains from a Brazilian petroleum reservoir were investigated for EPS production, emulsification ability and biodegradation activity when hydrocarbons were supplied as substrates for microbial growth. Two strains of Bacillus species had the highest EPS production when phenanthrene and n-octadecane were offered as carbon sources, either individually or in a mixture. While Pseudomonas sp. and Dietzia sp., the other two evaluated strains, had the highest hydrocarbon biodegradation indices, EPS production was not detected. Low EPS production may not necessarily be indicative of an absence of emulsifier activity, as indicated by the results of a surface tension reduction assay and emulsification indices for the strain of Dietzia sp. The combined results gathered in this work suggest that a microbial consortium consisting of bacteria with interdependent metabolisms could thrive in petroleum reservoirs, thus overcoming the limitations imposed on each individual species by the harsh conditions found in such environments.

Primordial black holes from polynomial potentials in single field inflation

Science.gov (United States)

Hertzberg, Mark P.; Yamada, Masaki

2018-04-01

Within canonical single field inflation models, we provide a method to reverse engineer and reconstruct the inflaton potential from a given power spectrum. This is not only a useful tool to find a potential from observational constraints, but also gives insight into how to generate a large amplitude spike in density perturbations, especially those that may lead to primordial black holes (PBHs). In accord with other works, we find that the usual slow-roll conditions need to be violated in order to generate a significant spike in the spectrum. We find that a way to achieve a very large amplitude spike in single field models is for the classical roll of the inflaton to overshoot a local minimum during inflation. We provide an example of a quintic polynomial potential that implements this idea and leads to the observed spectral index, observed amplitude of fluctuations on large scales, significant PBH formation on small scales, and is compatible with other observational constraints. We quantify how much fine-tuning is required to achieve this in a family of random polynomial potentials, which may be useful to estimate the probability of PBH formation in the string landscape.

Comparison of potential field solutions for Carrington Rotation 2144

Science.gov (United States)

Hayashi, Keiji; Yang, Shangbin; Deng, Yuagyong

2016-02-01

We examined differences among the coronal magnetic field structures derived with the potential field source surface (PFSS) model for Carrington Rotation 2144, from 21 November to 19 December 2013. We used the synoptic maps of solar photospheric magnetic field from four observatories, the Huairou Solar Observing Station (HSOS), Global Oscillation Network Group (GONG), Helioseismic Magnetic Imager (HMI), and Wilcox Solar Observatory (WSO). We tested two smoothing methods, Gaussian and boxcar averaging, and correction of unbalanced net magnetic flux. The solutions of three-dimensional coronal magnetic field are significantly different each other. An open-field region derived with HSOS data agrees best with the corresponding coronal hole observed by Solar Dynamics Observatories/Atmospheric Imaging Assembly, while HMI data yielded best agreements with the near-Earth OMNI database. The GONG data overall gave agreements as good as the HMI. The PFSS calculations using WSO data were least sensitive to the choices we examined in this work. Differences in PFSS solutions using different choices and parameters in smoothing imply that the photospheric magnetic field distributions with size of several degrees at midlatitude and low-latitude regions can be decisive, at least, in the examined period. To better determine the global solar corona, therefore, further evaluation of influences from compact bipolar magnetic field is needed.

Flat structure and potential vector fields related with algebraic solutions to Painlevé VI equation

Directory of Open Access Journals (Sweden)

Mitsuo Kato

2018-01-01

Full Text Available A potential vector field is a solution of an extended WDVV equation which is a generalization of a WDVV equation. It is expected that potential vector fields corresponding to algebraic solutions of Painlevé VI equation can be written by using polynomials or algebraic functions explicitly. The purpose of this paper is to construct potential vector fields corresponding to more than thirty non-equivalent algebraic solutions.

Extracellular Ca²⁺ acts as a mediator of communication from neurons to glia.

Science.gov (United States)

Torres, Arnulfo; Wang, Fushun; Xu, Qiwu; Fujita, Takumi; Dobrowolski, Radoslaw; Willecke, Klaus; Takano, Takahiro; Nedergaard, Maiken

2012-01-24

Defining the pathways through which neurons and astrocytes communicate may contribute to the elucidation of higher central nervous system functions. We investigated the possibility that decreases in extracellular calcium ion concentration ([Ca(2+)](e)) that occur during synaptic transmission might mediate signaling from neurons to glia. Using noninvasive photolysis of the photolabile Ca(2+) buffer diazo-2 {N-[2-[2-[2-[bis(carboxymethyl)amino]-5-(diazoacetyl)phenoxy]ethoxy]-4-methylphenyl]-N-(carboxymethyl)-, tetrapotassium salt} to reduce [Ca(2+)](e) or caged glutamate to simulate glutamatergic transmission, we found that a local decline in extracellular Ca(2+) triggered astrocytic adenosine triphosphate (ATP) release and astrocytic Ca(2+) signaling. In turn, activation of purinergic P2Y1 receptors on a subset of inhibitory interneurons initiated the generation of action potentials by these interneurons, thereby enhancing synaptic inhibition. Thus, astrocytic ATP release evoked by an activity-associated decrease in [Ca(2+)](e) may provide a negative feedback mechanism that potentiates inhibitory transmission in response to local hyperexcitability.

In vitro generation of polysialylated cervical mucins by bacterial polysialyltransferases to counteract cytotoxicity of extracellular histones.

Science.gov (United States)

Galuska, Sebastian P; Galuska, Christina E; Tharmalingam, Tharmala; Zlatina, Kristina; Prem, Gerlinde; Husejnov, Farzali C O; Rudd, Pauline M; Vann, Willie F; Reid, Colm; Vionnet, Justine; Gallagher, Mary E; Carrington, Faye A; Hassett, Sarah-Louise; Carrington, Stephen D

2017-06-01

Neutrophil extracellular traps (NET) are formed against pathogens. However, various diseases are directly linked to this meshwork of DNA. The cytotoxic properties of extracellular histones especially seem to be an important trigger during these diseases. Furthermore, NET accumulation on implants is discussed to result in an impaired efficiency or failure, depending on the category of implant. Interestingly, mucins have been investigated as surface coatings potentially capable of reducing neutrophil adhesion. Similarly, polysialic acid was shown to inactivate the cytotoxic properties of extracellular histones. We wanted to combine the probability to decrease the adhesion of neutrophils using mucins with the capability of sialic acid polymers to counteract histone-mediated cytotoxicity. To this end, we elongate cervical mucins using bacterial polysialyltransferases. Subsequent cell-based experiments demonstrated the activity of elongated mucins against histone-mediated cytotoxicity. Thus, polysialylated mucins may represent a novel component to coat implants or to combat diseases with exaggerated NET formation. © 2017 Federation of European Biochemical Societies.

Diversity of Two-Domain Laccase-Like Multicopper Oxidase Genes in Streptomyces spp.: Identification of Genes Potentially Involved in Extracellular Activities and Lignocellulose Degradation during Composting of Agricultural Waste

Science.gov (United States)

Lu, Lunhui; Zhang, Jiachao; Chen, Anwei; Chen, Ming; Jiang, Min; Yuan, Yujie; Wu, Haipeng; Lai, Mingyong; He, Yibin

2014-01-01

Traditional three-domain fungal and bacterial laccases have been extensively studied for their significance in various biotechnological applications. Growing molecular evidence points to a wide occurrence of more recently recognized two-domain laccase-like multicopper oxidase (LMCO) genes in Streptomyces spp. However, the current knowledge about their ecological role and distribution in natural or artificial ecosystems is insufficient. The aim of this study was to investigate the diversity and composition of Streptomyces two-domain LMCO genes in agricultural waste composting, which will contribute to the understanding of the ecological function of Streptomyces two-domain LMCOs with potential extracellular activity and ligninolytic capacity. A new specific PCR primer pair was designed to target the two conserved copper binding regions of Streptomyces two-domain LMCO genes. The obtained sequences mainly clustered with Streptomyces coelicolor, Streptomyces violaceusniger, and Streptomyces griseus. Gene libraries retrieved from six composting samples revealed high diversity and a rapid succession of Streptomyces two-domain LMCO genes during composting. The obtained sequence types cluster in 8 distinct clades, most of which are homologous with Streptomyces two-domain LMCO genes, but the sequences of clades III and VIII do not match with any reference sequence of known streptomycetes. Both lignocellulose degradation rates and phenol oxidase activity at pH 8.0 in the composting process were found to be positively associated with the abundance of Streptomyces two-domain LMCO genes. These observations provide important clues that Streptomyces two-domain LMCOs are potentially involved in bacterial extracellular phenol oxidase activities and lignocellulose breakdown during agricultural waste composting. PMID:24657870

The Role of Extracellular Histones in Influenza Virus Pathogenesis.

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Ashar, Harshini K; Mueller, Nathan C; Rudd, Jennifer M; Snider, Timothy A; Achanta, Mallika; Prasanthi, Maram; Pulavendran, Sivasami; Thomas, Paul G; Ramachandran, Akhilesh; Malayer, Jerry R; Ritchey, Jerry W; Rajasekhar, Rachakatla; Chow, Vincent T K; Esmon, Charles T; Teluguakula, Narasaraju

2018-01-01

Although exaggerated host immune responses have been implicated in influenza-induced lung pathogenesis, the etiologic factors that contribute to these events are not completely understood. We previously demonstrated that neutrophil extracellular traps exacerbate pulmonary injury during influenza pneumonia. Histones are the major protein components of neutrophil extracellular traps and are known to have cytotoxic effects. Here, we examined the role of extracellular histones in lung pathogenesis during influenza. Mice infected with influenza virus displayed high accumulation of extracellular histones, with widespread pulmonary microvascular thrombosis. Occluded pulmonary blood vessels with vascular thrombi often exhibited endothelial necrosis surrounded by hemorrhagic effusions and pulmonary edema. Histones released during influenza induced cytotoxicity and showed strong binding to platelets within thrombi in infected mouse lungs. Nasal wash samples from influenza-infected patients also showed increased accumulation of extracellular histones, suggesting a possible clinical relevance of elevated histones in pulmonary injury. Although histones inhibited influenza growth in vitro, in vivo treatment with histones did not yield antiviral effects and instead exacerbated lung pathology. Blocking with antihistone antibodies caused a marked decrease in lung pathology in lethal influenza-challenged mice and improved protection when administered in combination with the antiviral agent oseltamivir. These findings support the pathogenic effects of extracellular histones in that pulmonary injury during influenza was exacerbated. Targeting histones provides a novel therapeutic approach to influenza pneumonia. Copyright © 2018 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Extracellular deoxyribonuclease production by periodontal bacteria.

Science.gov (United States)

Palmer, L J; Chapple, I L C; Wright, H J; Roberts, A; Cooper, P R

2012-08-01

Whilst certain bacteria have long been known to secrete extracellular deoxyribonuclease (DNase), the purpose in microbial physiology was unclear. Recently, however, this enzyme has been demonstrated to confer enhanced virulence, enabling bacteria to evade the host's immune defence of extruded DNA/chromatin filaments, termed neutrophil extracellular traps (NETs). As NETs have recently been identified in infected periodontal tissue, the aim of this study was to screen periodontal bacteria for extracellular DNase activity. To determine whether DNase activity was membrane bound or secreted, 34 periodontal bacteria were cultured in broth and on agar plates. Pelleted bacteria and supernatants from broth cultures were analysed for their ability to degrade DNA, with relative activity levels determined using an agarose gel electrophoresis assay. Following culture on DNA-supplemented agar, expression was determined by the presence of a zone of hydrolysis and DNase activity related to colony size. Twenty-seven bacteria, including red and orange complex members Porphyromonas gingivalis, Tannerella forsythia, Fusobacterium nucleatum, Parvimonas micra, Prevotella intermedia, Streptococcus constellatus, Campylobacter rectus and Prevotella nigrescens, were observed to express extracellular DNase activity. Differences in DNase activity were noted, however, when bacteria were assayed in different culture states. Analysis of the activity of secreted DNase from bacterial broth cultures confirmed their ability to degrade NETs. The present study demonstrates, for the first time, that DNase activity is a relatively common property of bacteria associated with advanced periodontal disease. Further work is required to determine the importance of this bacterial DNase activity in the pathogenesis of periodontitis. © 2011 John Wiley & Sons A/S.

In vitro Determination of Extracellular Proteins from Xylella fastidiosa.

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Mendes, Juliano S; Santiago, André S; Toledo, Marcelo A S; Horta, Maria A C; de Souza, Alessandra A; Tasic, Ljubica; de Souza, Anete P

2016-01-01

The phytopathogen Xylella fastidiosa causes economic losses in important agricultural crops. Xylem vessel occlusion caused by biofilm formation is the major mechanism underlying the pathogenicity of distinct strains of X. fastidiosa . Here, we provide a detailed in vitro characterization of the extracellular proteins of X. fastidiosa . Based on the results, we performed a comparison with a strain J1a12, which cannot induce citrus variegated chlorosis symptoms when inoculated into citrus plants. We then extend this approach to analyze the extracellular proteins of X. fastidiosa in media supplemented with calcium. We verified increases in extracellular proteins concomitant with the days of growth and, consequently, biofilm development (3-30 days). Outer membrane vesicles carrying toxins were identified beginning at 10 days of growth in the 9a5c strain. In addition, a decrease in extracellular proteins in media supplemented with calcium was observed in both strains. Using mass spectrometry, 71 different proteins were identified during 30 days of X. fastidiosa biofilm development, including proteases, quorum-sensing proteins, biofilm formation proteins, hypothetical proteins, phage-related proteins, chaperones, toxins, antitoxins, and extracellular vesicle membrane components.

Intense laser field effects on a Woods-Saxon potential quantum well

Science.gov (United States)

Restrepo, R. L.; Morales, A. L.; Akimov, V.; Tulupenko, V.; Kasapoglu, E.; Ungan, F.; Duque, C. A.

2015-11-01

This paper presents the results of the theoretical study of the effects of non-resonant intense laser field and electric and magnetic fields on the optical properties in an quantum well (QW) make with Woods-Saxon potential profile. The electric field and intense laser field are applied along the growth direction of the Woods-Saxon quantum well and the magnetic field is oriented perpendicularly. To calculate the energy and the wave functions of the electron in the Woods-Saxon quantum well, the effective mass approximation and the method of envelope wave function are used. The confinement in the Woods-Saxon quantum well is changed drastically by the application of intense laser field or either the effect of electric and magnetic fields. The optical properties are calculated using the compact density matrix.

Sum rules for the ed - NN scattering reactions and microscopic potential field-theoretical approach

International Nuclear Information System (INIS)

Machivariani, A.I.

1996-01-01

The connections between the equal-time commutators of nucleon and photon field-operators and relativistic potential approach of ed - NN scattering equations is established. Namely, it is demonstrated that: 1) equal-time commutator between nucleon field operators generated completeness condition for NN interaction functions, 2) the off-mass shell contributions in γd - NN exchange currents or in microscopic NN potential are determined by equal time commutator between nucleon field operator and photon or nucleon source operators, and 3) equal-time commutators between source operators produce sum rules for same vertex functions and effective potentials [ru

Exosomes are fingerprints of originating cells: potential biomarkers for ovarian cancer

Directory of Open Access Journals (Sweden)

Kobayashi M

2015-03-01

Full Text Available Miharu Kobayashi, Gregory E Rice, Jorge Tapia, Murray D Mitchell, Carlos Salomon Exosome Biology Laboratory, Centre for Clinical Diagnostics, University of Queensland Centre for Clinical Research, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia. Abstract: The past decade has seen an extraordinary explosion of research in the field of extracellular vesicles, especially in a specific type of extracellular vesicles originating from endosomal compartments, called exosomes. Exosomes are a specific subtype of secreted vesicles that are defined as small (~30–120 nm but very stable membrane vesicles that are released from a wide range of cells, including normal and cancer cells. As the content of exosomes is cell type specific, it is believed that they are a "fingerprint" of the releasing cell and its metabolic status. We hypothesized that the exosomes and their specific exosomal content (eg, microribonucleic acid represent a precious biomedical tool and may be used as biomarkers for the diagnosis and prognosis of malignant tumors. In addition, exosomes may modify the phenotype of the parent and/or target cell by transferring pro-oncogenic molecules to induce cancerous phenotype of recipient cells and contribute to the formation of the premetastatic niche. The mechanism involved in these phenomena remains unclear; however, inclusion of signaling mediators into exosomes or exosome release may reduce their intracellular bioavailability in the parent cell, thereby altering cell phenotype and their metastatic potential. The aim of this review therefore is to analyze the biogenesis and role of exosomes from tumor cells, focusing primarily on ovarian cancer. Ovarian cancer is the most lethal gynecologic cancer, and an effective early diagnosis has the potential to improve patient survival. Ovarian cancer currently lacks a reliable method for early detection, however, exosomes have received great attention as potential biomarkers and mediators

A physics-based potential and electric field model of a nanoscale ...

Indian Academy of Sciences (India)

... paper, we have developed a physics-based model for surface potential, channel potential, electric field and drain current for AlGaN/GaN high electron mobility transistor with high-K gate dielectric using two-dimensional Poisson equation under full depletion approximation with the inclusion of effect of polarization charges.

CONSTRAINING THE NFW POTENTIAL WITH OBSERVATIONS AND MODELING OF LOW SURFACE BRIGHTNESS GALAXY VELOCITY FIELDS

International Nuclear Information System (INIS)

Kuzio de Naray, Rachel; McGaugh, Stacy S.; Mihos, J. Christopher

2009-01-01

We model the Navarro-Frenk-White (NFW) potential to determine if, and under what conditions, the NFW halo appears consistent with the observed velocity fields of low surface brightness (LSB) galaxies. We present mock DensePak Integral Field Unit (IFU) velocity fields and rotation curves of axisymmetric and nonaxisymmetric potentials that are well matched to the spatial resolution and velocity range of our sample galaxies. We find that the DensePak IFU can accurately reconstruct the velocity field produced by an axisymmetric NFW potential and that a tilted-ring fitting program can successfully recover the corresponding NFW rotation curve. We also find that nonaxisymmetric potentials with fixed axis ratios change only the normalization of the mock velocity fields and rotation curves and not their shape. The shape of the modeled NFW rotation curves does not reproduce the data: these potentials are unable to simultaneously bring the mock data at both small and large radii into agreement with observations. Indeed, to match the slow rise of LSB galaxy rotation curves, a specific viewing angle of the nonaxisymmetric potential is required. For each of the simulated LSB galaxies, the observer's line of sight must be along the minor axis of the potential, an arrangement that is inconsistent with a random distribution of halo orientations on the sky.

Predicting local field potentials with recurrent neural networks.

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Kim, Louis; Harer, Jacob; Rangamani, Akshay; Moran, James; Parks, Philip D; Widge, Alik; Eskandar, Emad; Dougherty, Darin; Chin, Sang Peter

2016-08-01

We present a Recurrent Neural Network using LSTM (Long Short Term Memory) that is capable of modeling and predicting Local Field Potentials. We train and test the network on real data recorded from epilepsy patients. We construct networks that predict multi-channel LFPs for 1, 10, and 100 milliseconds forward in time. Our results show that prediction using LSTM outperforms regression when predicting 10 and 100 millisecond forward in time.

Motion Planning for Omnidirectional Wheeled Mobile Robot by Potential Field Method

Directory of Open Access Journals (Sweden)

Weihao Li

2017-01-01

Full Text Available In this paper, potential field method has been used to navigate a three omnidirectional wheels’ mobile robot and to avoid obstacles. The potential field method is used to overcome the local minima problem and the goals nonreachable with obstacles nearby (GNRON problem. For further consideration, model predictive control (MPC has been used to incorporate motion constraints and make the velocity more realistic and flexible. The proposed method is employed based on the kinematic model and dynamics model of the mobile robot in this paper. To show the performance of proposed control scheme, simulation studies have been carried to perform the motion process of mobile robot in specific workplace.

A physics-based potential and electric field model of a nanoscale ...

Indian Academy of Sciences (India)

In this paper, we have developed a physics-based model for surface potential, channel potential, electric field and drain current for AlGaN/GaN high electron mobility transistor with high-K gate dielectric using two-dimensional Poisson equation under full depletion approximation with the inclusion of effect of polarization ...

Response of extracellular zinc in the ventral hippocampus against novelty stress.

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Takeda, Atsushi; Sakurada, Naomi; Kanno, Shingo; Minami, Akira; Oku, Naoto

2006-10-01

An extensive neuronal activity takes place in the hippocampus during exploratory behavior. However, the role of hippocampal zinc in exploratory behavior is poorly understood. To analyze the response of extracellular zinc in the hippocampus against novelty stress, rats were placed for 50 min in a novel environment once a day for 8 days. Extracellular glutamate in the hippocampus was increased during exploratory behavior on day 1, whereas extracellular zinc was decreased. The same phenomenon was observed during exploratory behavior on day 2 and extracellular zinc had returned to the basal level during exploratory behavior on day 8. To examine the significance of the decrease in extracellular zinc in exploratory activity, exploratory behavior was observed during perfusion with 1 mm CaEDTA, a membrane-impermeable zinc chelator. Locomotor activity in the novel environment was decreased by perfusion with CaEDTA. The decrease in extracellular zinc and the increase in extracellular glutamate in exploratory period were abolished by perfusion with CaEDTA. These results suggest that zinc uptake by hippocampal cells is linked to exploratory activity and is required for the activation of the glutamatergic neurotransmitter system. The zinc uptake may be involved in the response to painless psychological stress or in the cognitive processes.

Agmatine reduces extracellular glutamate during pentylenetetrazole-induced seizures in rat brain: A potential mechanism for the anticonvulsive effects

Science.gov (United States)

Feng, Yangzheng; LeBlanc, Michael H.; Regunathan, Soundar

2010-01-01

Glutamate has been implicated in the initiation and spread of seizure activity. Agmatine, an endogenous neuromodulator, is an antagonist of NMDA receptors and has anticonvulsive effects. Whether agmatine regulate glutamate release, as measured by in vivo microdialysis, is not known. In this study, we used pentylenetetrazole (PTZ)-induced seizure model to determine the effect of agmatine on extracellular glutamate in rat brain. We also determined the time course and the amount of agmatine that reached brain after peripheral injection. After i.p. injection of agmatine (50 mg/kg), increase of agmatine in rat cortex and hippocampus was observed in 15 min with levels returning to baseline in one hour. Rats, naïve and implanted with microdialysis cannula into the cortex, were administered PTZ (60 mg/kg, i.p.) with prior injection of agmatine (100 mg/kg, i.p.) or saline. Seizure grades were recorded and microdialysis samples were collected every 15 min for 75 min. Agmatine pre-treatment significantly reduced the seizure grade and increased the onset time. The levels of extracellular glutamate in frontal cortex rose two- to three-fold after PTZ injection and agmatine significantly inhibited this increase. In conclusion, the present data suggest that the anticonvulsant activity of agmatine, in part, could be related to the inhibition glutamate release. PMID:16125317

Focus on Extracellular Vesicles: Introducing the Next Small Big Thing

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Hina Kalra

2016-02-01

Full Text Available Intercellular communication was long thought to be regulated exclusively through direct contact between cells or via release of soluble molecules that transmit the signal by binding to a suitable receptor on the target cell, and/or via uptake into that cell. With the discovery of small secreted vesicular structures that contain complex cargo, both in their lumen and the lipid membrane that surrounds them, a new frontier of signal transduction was discovered. These “extracellular vesicles” (EV were initially thought to be garbage bags through which the cell ejected its waste. Whilst this is a major function of one type of EV, i.e., apoptotic bodies, many EVs have intricate functions in intercellular communication and compound exchange; although their physiological roles are still ill-defined. Additionally, it is now becoming increasingly clear that EVs mediate disease progression and therefore studying EVs has ignited significant interests among researchers from various fields of life sciences. Consequently, the research effort into the pathogenic roles of EVs is significantly higher even though their protective roles are not well established. The “Focus on extracellular vesicles” series of reviews highlights the current state of the art regarding various topics in EV research, whilst this review serves as an introductory overview of EVs, their biogenesis and molecular composition.

Extracellular Histones Increase Tissue Factor Activity and Enhance Thrombin Generation by Human Blood Monocytes.

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Gould, Travis J; Lysov, Zakhar; Swystun, Laura L; Dwivedi, Dhruva J; Zarychanski, Ryan; Fox-Robichaud, Alison E; Liaw, Patricia C

2016-12-01

Sepsis is characterized by systemic activation of inflammatory and coagulation pathways in response to infection. Recently, it was demonstrated that histones released into the circulation by dying/activated cells may contribute to sepsis pathology. Although the ability of extracellular histones to modulate the procoagulant activities of several cell types has been investigated, the influence of histones on the hemostatic functions of circulating monocytes is unknown. To address this, we investigated the ability of histones to modulate the procoagulant potential of THP-1 cells and peripheral blood monocytes, and examined the effects of plasmas obtained from septic patients to induce a procoagulant phenotype on monocytic cells. Tissue factor (TF) activity assays were performed on histone-treated THP-1 cells and blood monocytes. Exposure of monocytic cells to histones resulted in increases in TF activity, TF antigen, and phosphatidylserine exposure. Histones modulate the procoagulant activity via engagement of Toll-like receptors 2 and 4, and this effect was abrogated with inhibitory antibodies. Increased TF activity of histone-treated cells corresponded to enhanced thrombin generation in plasma determined by calibrated automated thrombography. Finally, TF activity was increased on monocytes exposed to plasma from septic patients, an effect that was attenuated in plasma from patients receiving unfractionated heparin (UFH). Our studies suggest that increased levels of extracellular histones found in sepsis contribute to dysregulated coagulation by increasing TF activity of monocytes. These procoagulant effects can be partially ameliorated in sepsis patients receiving UFH, thereby identifying extracellular histones as a potential therapeutic target for sepsis treatment.

Label-free imaging of arterial cells and extracellular matrix using a multimodal CARS microscope

Science.gov (United States)

Wang, Han-Wei; Le, Thuc T.; Cheng, Ji-Xin

2008-04-01

A multimodal nonlinear optical imaging system that integrates coherent anti-Stokes Raman scattering (CARS), sum-frequency generation (SFG), and two-photon excitation fluorescence (TPEF) on the same platform was developed and applied to visualize single cells and extracellular matrix in fresh carotid arteries. CARS signals arising from CH 2-rich membranes allowed visualization of endothelial cells and smooth muscle cells of the arterial wall. Additionally, CARS microscopy allowed vibrational imaging of elastin and collagen fibrils which are also rich in CH 2 bonds. The extracellular matrix organization was further confirmed by TPEF signals arising from elastin's autofluorescence and SFG signals arising from collagen fibrils' non-centrosymmetric structure. Label-free imaging of significant components of arterial tissues suggests the potential application of multimodal nonlinear optical microscopy to monitor onset and progression of arterial diseases.

Potential and flux field landscape theory. I. Global stability and dynamics of spatially dependent non-equilibrium systems.

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Wu, Wei; Wang, Jin

2013-09-28

We established a potential and flux field landscape theory to quantify the global stability and dynamics of general spatially dependent non-equilibrium deterministic and stochastic systems. We extended our potential and flux landscape theory for spatially independent non-equilibrium stochastic systems described by Fokker-Planck equations to spatially dependent stochastic systems governed by general functional Fokker-Planck equations as well as functional Kramers-Moyal equations derived from master equations. Our general theory is applied to reaction-diffusion systems. For equilibrium spatially dependent systems with detailed balance, the potential field landscape alone, defined in terms of the steady state probability distribution functional, determines the global stability and dynamics of the system. The global stability of the system is closely related to the topography of the potential field landscape in terms of the basins of attraction and barrier heights in the field configuration state space. The effective driving force of the system is generated by the functional gradient of the potential field alone. For non-equilibrium spatially dependent systems, the curl probability flux field is indispensable in breaking detailed balance and creating non-equilibrium condition for the system. A complete characterization of the non-equilibrium dynamics of the spatially dependent system requires both the potential field and the curl probability flux field. While the non-equilibrium potential field landscape attracts the system down along the functional gradient similar to an electron moving in an electric field, the non-equilibrium flux field drives the system in a curly way similar to an electron moving in a magnetic field. In the small fluctuation limit, the intrinsic potential field as the small fluctuation limit of the potential field for spatially dependent non-equilibrium systems, which is closely related to the steady state probability distribution functional, is

Apparatus and method for transfer of information by means of a curl-free magnetic vector potential field

International Nuclear Information System (INIS)

Gelinas, R.C.

1984-01-01

A system for transmission of information using a curl-free magnetic vector potential radiation field. The system includes current-carrying apparatus for generating a magnetic vector potential field with a curl-free component coupled to apparatus for modulating the current applied to the field generating apparatus. Receiving apparatus includes a detector with observable properties that vary with the application of an applied curl-free magnetic vector potential field. Analyzing apparatus for determining the information content of modulation imposed on the curl-free vector potential field can be established in materials that are not capable of transmitting more common electromagnetic radiation

Parallel computation of electrostatic potentials and fields in technical geometries on SUPRENUM

International Nuclear Information System (INIS)

Alef, M.

1990-02-01

The programs EPOTZR und EFLDZR have been developed in order to compute electrostatic potentials and the corresponding fields in technical geometries (example: Diode geometry for optimum focussing of ion beams in pulsed high-current ion diodes). The Poisson equation is discretized in a two-dimensional boundary-fitted grid in the (r,z)-plane and solved using multigrid methods. The z- and r-components of the field are determined by numerical differentiation of the potential. This report contains the user's guide of the SUPRENUM versions EPOTZR-P and EFLDZR-P. (orig./HP) [de

Agmatine reduces extracellular glutamate during pentylenetetrazole-induced seizures in rat brain: A potential mechanism for the anticonvulsive effects

OpenAIRE

Feng, Yangzheng; LeBlanc, Michael H.; Regunathan, Soundar

2005-01-01

Glutamate has been implicated in the initiation and spread of seizure activity. Agmatine, an endogenous neuromodulator, is an antagonist of NMDA receptors and has anticonvulsive effects. Whether agmatine regulate glutamate release, as measured by in vivo microdialysis, is not known. In this study, we used pentylenetetrazole (PTZ)-induced seizure model to determine the effect of agmatine on extracellular glutamate in rat brain. We also determined the time course and the amount of agmatine that...

Pathophysiologic Changes in Extracellular pH Modulate Parathyroid Calcium-Sensing Receptor Activity and Secretion via a Histidine-Independent Mechanism.

Science.gov (United States)

Campion, Katherine L; McCormick, Wanda D; Warwicker, Jim; Khayat, Mohd Ezuan Bin; Atkinson-Dell, Rebecca; Steward, Martin C; Delbridge, Leigh W; Mun, Hee-Chang; Conigrave, Arthur D; Ward, Donald T

2015-09-01

The calcium-sensing receptor (CaR) modulates renal calcium reabsorption and parathyroid hormone (PTH) secretion and is involved in the etiology of secondary hyperparathyroidism in CKD. Supraphysiologic changes in extracellular pH (pHo) modulate CaR responsiveness in HEK-293 (CaR-HEK) cells. Therefore, because acidosis and alkalosis are associated with altered PTH secretion in vivo, we examined whether pathophysiologic changes in pHo can significantly alter CaR responsiveness in both heterologous and endogenous expression systems and whether this affects PTH secretion. In both CaR-HEK and isolated bovine parathyroid cells, decreasing pHo from 7.4 to 7.2 rapidly inhibited CaR-induced intracellular calcium (Ca(2+)i) mobilization, whereas raising pHo to 7.6 potentiated responsiveness to extracellular calcium (Ca(2+)o). Similar pHo effects were observed for Ca(2+)o-induced extracellular signal-regulated kinase phosphorylation and actin polymerization and for L-Phe-induced Ca(2+)i mobilization. Intracellular pH was unaffected by acute 0.4-unit pHo changes, and the presence of physiologic albumin concentrations failed to attenuate the pHo-mediated effects. None of the individual point mutations created at histidine or cysteine residues in the extracellular domain of CaR attenuated pHo sensitivity. Finally, pathophysiologic pHo elevation reversibly suppressed PTH secretion from perifused human parathyroid cells, and acidosis transiently increased PTH secretion. Therefore, pathophysiologic pHo changes can modulate CaR responsiveness in HEK-293 and parathyroid cells independently of extracellular histidine residues. Specifically, pathophysiologic acidification inhibits CaR activity, thus permitting PTH secretion, whereas alkalinization potentiates CaR activity to suppress PTH secretion. These findings suggest that acid-base disturbances may affect the CaR-mediated control of parathyroid function and calcium metabolism in vivo. Copyright © 2015 by the American Society of

A Multiagent Potential Field-Based Bot for Real-Time Strategy Games

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Johan Hagelbäck

2009-01-01

Full Text Available Bots for real-time strategy (RTS games may be very challenging to implement. A bot controls a number of units that will have to navigate in a partially unknown environment, while at the same time avoid each other, search for enemies, and coordinate attacks to fight them down. Potential fields are a technique originating from the area of robotics where it is used in controlling the navigation of robots in dynamic environments. Although attempts have been made to transfer the technology to the gaming sector, assumed problems with efficiency and high costs for implementation have made the industry reluctant to adopt it. We present a multiagent potential field-based bot architecture that is evaluated in two different real-time strategy game settings and compare them, both in terms of performance, and in terms of softer attributes such as configurability with other state-of-the-art solutions. We show that the solution is a highly configurable bot that can match the performance standards of traditional RTS bots. Furthermore, we show that our approach deals with Fog of War (imperfect information about the opponent units surprisingly well. We also show that a multiagent potential field-based bot is highly competitive in a resource gathering scenario.

Dark production of extracellular superoxide by the coral Porites astreoides and representative symbionts

Directory of Open Access Journals (Sweden)

Tong Zhang

2016-11-01

superoxide externally, which is decoupled from photosynthetic activity and circadian control. Corals may therefore produce extracellular superoxide constitutively, highlighting an unclear yet potentially beneficial role for superoxide in coral physiology and health.

Crystal structure of glucagon-like peptide-1 in complex with the extracellular domain of the glucagon-like peptide-1 receptor.

Science.gov (United States)

Underwood, Christina Rye; Garibay, Patrick; Knudsen, Lotte Bjerre; Hastrup, Sven; Peters, Günther H; Rudolph, Rainer; Reedtz-Runge, Steffen

2010-01-01

GLP-1 (glucagon-like peptide-1) is an incretin released from intestinal L-cells in response to food intake. Activation of the GLP-1 receptor potentiates the synthesis and release of insulin from pancreatic beta-cells in a glucose-dependent manner. The GLP-1 receptor belongs to class B of the G-protein-coupled receptors, a subfamily characterized by a large N-terminal extracellular ligand binding domain. Exendin-4 and GLP-1 are 50% identical, and exendin-4 is a full agonist with similar affinity and potency for the GLP-1 receptor. We recently solved the crystal structure of the GLP-1 receptor extracellular domain in complex with the competitive antagonist exendin-4(9-39). Interestingly, the isolated extracellular domain binds exendin-4 with much higher affinity than the endogenous agonist GLP-1. Here, we have solved the crystal structure of the extracellular domain in complex with GLP-1 to 2.1 Aresolution. The structure shows that important hydrophobic ligand-receptor interactions are conserved in agonist- and antagonist-bound forms of the extracellular domain, but certain residues in the ligand-binding site adopt a GLP-1-specific conformation. GLP-1 is a kinked but continuous alpha-helix from Thr(13) to Val(33) when bound to the extracellular domain. We supplemented the crystal structure with site-directed mutagenesis to link the structural information of the isolated extracellular domain with the binding properties of the full-length receptor. The data support the existence of differences in the binding modes of GLP-1 and exendin-4 on the full-length GLP-1 receptor.

From the Cover: Selective Enhancement of Domoic Acid Toxicity in Primary Cultures of Cerebellar Granule Cells by Lowering Extracellular Na+ Concentration.

Science.gov (United States)

Pérez-Gómez, Anabel; Cabrera-García, David; Warm, Davide; Marini, Ann M; Salas Puig, Javier; Fernández-Sánchez, Maria Teresa; Novelli, Antonello

2018-01-01

Domoic acid (DOM) is an excitatory amino acid analog of kainic acid (KA) that acts through glutamic acid (GLU) receptors, inducing a fast and potent neurotoxic response. Here, we present evidence for an enhancement of excitotoxicity following exposure of cultured cerebellar granule cells to DOM in the presence of lower than physiological Na+ concentrations. The concentration of DOM that reduced by 50% neuronal survival was approximately 3 µM in Na+-free conditions and 16 µM in presence of a physiological concentration of extracellular Na+. The enhanced neurotoxic effect of DOM was fully prevented by AMPA/KA receptor antagonist, while N-methyl-D-aspartate-receptor-mediated neurotoxicity did not seem to be involved, as the absence of extracellular Na+ failed to potentiate GLU excitotoxicity under the same experimental conditions. Lowering of extracellular Na+ concentration to 60 mM eliminated extracellular recording of spontaneous electrophysiological activity from cultured neurons grown on a multi electrode array and prevented DOM stimulation of the electrical activity. Although changes in the extracellular Na+ concentration did not alter the magnitude of the rapid increase in intracellular Ca2+ levels associated to DOM exposure, they did change significantly the contribution of voltage-sensitive calcium channels (VScaCs) and the recovery time to baseline. The prevention of Ca2+ influx via VSCaCs by nifedipine failed to prevent DOM toxicity at any extracellular Na+ concentration, while the reduction of extracellular Ca2+ concentration ameliorated DOM toxicity only in the absence of extracellular Na+, enhancing it in physiological conditions. Our data suggest a crucial role for extracellular Na+ concentration in determining excitotoxicity by DOM. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Neutrophil extracellular traps promote deep vein thrombosis in mice

Science.gov (United States)

Brill, A.; Fuchs, T.A.; Savchenko, A.S.; Thomas, G.M.; Martinod, K.; De Meyer, S.F.; Bhandari, A.A.; Wagner, D.D.

2011-01-01

Summary Background Upon activation, neutrophils can release nuclear material known as neutrophil extracellular traps (NETs), which were initially described as a part of antimicrobial defense. Extracellular chromatin was recently reported to be pro-thrombotic in vitro and to accumulate in plasma and thrombi of baboons with experimental deep vein thrombosis (DVT). Objective To explore the source and role of extracellular chromatin in DVT. Methods We used an established murine model of DVT induced by flow restriction (stenosis) in the inferior vena cava (IVC). Results We demonstrate that the levels of extracellular DNA increase in plasma after 6 h IVC stenosis, compared to sham-operated mice. Immunohistochemical staining revealed the presence of Gr-1-positive neutrophils in both red (RBC-rich) and white (platelet-rich) parts of thrombi. Citrullinated histone H3 (CitH3), an element of NETs’ structure, was present only in the red part of thrombi and was frequently associated with the Gr-1 antigen. Immunofluorescent staining of thrombi showed proximity of extracellular CitH3 and von Willebrand factor (VWF), a platelet adhesion molecule crucial for thrombus development in this model. Infusion of Deoxyribonuclease 1 (DNase 1) protected mice from DVT after 6 h and also 48 h IVC stenosis. Infusion of an unfractionated mixture of calf thymus histones increased plasma VWF and promoted DVT early after stenosis application. Conclusions Extracellular chromatin, likely originating from neutrophils, is a structural part of a venous thrombus and both the DNA scaffold and histones appear to contribute to the pathogenesis of DVT in mice. NETs may provide new targets for DVT drug development. PMID:22044575

Brain Extracellular Space: The Final Frontier of Neuroscience.

Science.gov (United States)

Nicholson, Charles; Hrabětová, Sabina

2017-11-21

Brain extracellular space is the narrow microenvironment that surrounds every cell of the central nervous system. It contains a solution that closely resembles cerebrospinal fluid with the addition of extracellular matrix molecules. The space provides a reservoir for ions essential to the electrical activity of neurons and forms an intercellular chemical communication channel. Attempts to reveal the size and structure of the extracellular space using electron microscopy have had limited success; however, a biophysical approach based on diffusion of selected probe molecules has proved useful. A point-source paradigm, realized in the real-time iontophoresis method using tetramethylammonium, as well as earlier radiotracer methods, have shown that the extracellular space occupies ∼20% of brain tissue and small molecules have an effective diffusion coefficient that is two-fifths that in a free solution. Monte Carlo modeling indicates that geometrical constraints, including dead-space microdomains, contribute to the hindrance to diffusion. Imaging the spread of macromolecules shows them increasingly hindered as a function of size and suggests that the gaps between cells are predominantly ∼40 nm with wider local expansions that may represent dead-spaces. Diffusion measurements also characterize interactions of ions and proteins with the chondroitin and heparan sulfate components of the extracellular matrix; however, the many roles of the matrix are only starting to become apparent. The existence and magnitude of bulk flow and the so-called glymphatic system are topics of current interest and controversy. The extracellular space is an exciting area for research that will be propelled by emerging technologies. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Extracellular DNA as matrix component in microbial biofilms

DEFF Research Database (Denmark)

Chiang, Wen-Chi; Tolker-Nielsen, Tim

2010-01-01

Bacteria in nature primarily live in surface-associated communities commonly known as biofilms. Because bacteria in biofilms, in many cases, display tolerance to host immune systems, antibiotics, and biocides, they are often difficult or impossible to eradicate. Biofilm formation, therefore, leads...... to various persistent infections in humans and animals, and to a variety of complications in industry, where solid–water interfaces occur. Knowledge about the molecular mechanisms involved in biofilm formation is necessary for creating strategies to control biofilms. Recent studies have shown...... that extracellular DNA is an important component of the extracellular matrix of microbial biofilms. The present chapter is focussed on extracellular DNA as matrix component in biofilms formed by Pseudomonas aeruginosa as an example from the Gram-negative bacteria, and Streptococcus and Staphylococcus as examples...

Low-level ultrahigh-frequency and ultrashort-pulse blue laser irradiation enhances osteoblast extracellular calcification by upregulating proliferation and differentiation via transient receptor potential vanilloid 1.

Science.gov (United States)

Mikami, Risako; Mizutani, Koji; Aoki, Akira; Tamura, Yukihiko; Aoki, Kazuhiro; Izumi, Yuichi

2018-04-01

Low-level laser irradiation (LLLI) exerts various biostimulative effects, including promotion of wound healing and bone formation; however, few studies have examined biostimulation using blue lasers. The purpose of this study was to investigate the effects of low-level ultrahigh-frequency (UHF) and ultrashort-pulse (USP) blue laser irradiation on osteoblasts. The MC3T3-E1 osteoblast cell line was used in this study. Following LLLI with a 405 nm newly developed UHF-USP blue laser (80 MHz, 100 fs), osteoblast proliferation, and alkaline phosphatase (ALP) activity were assessed. In addition, mRNA levels of the osteoblast differentiation markers, runt-related transcription factor 2 (Runx2), osterix (Osx), alkaline phosphatase (Alp), and osteopontin (Opn) was evaluated, and extracellular calcification was quantified. To clarify the involvement of transient receptor potential (TRP) channels in LLLI-induced biostimulation, cells were treated prior to LLLI with capsazepine (CPZ), a selective inhibitor of TRP vanilloid 1 (TRPV1), and subsequent proliferation and ALP activity were measured. LLLI with the 405 nm UHF-USP blue laser significantly enhanced cell proliferation and ALP activity, compared with the non-irradiated control and LLLI using continuous-wave mode, without significant temperature elevation. LLLI promoted osteoblast proliferation in a dose-dependent manner up to 9.4 J/cm 2 and significantly accelerated cell proliferation in in vitro wound healing assay. ALP activity was significantly enhanced at doses up to 5.6 J/cm 2 , and expression of Osx and Alp mRNAs was significantly increased compared to that of the control on days 3 and 7 following LLLI at 5.6 J/cm 2 . The extent of extracellular calcification was also significantly higher as a result of LLLI 3 weeks after the treatment. Measurement of TRPV1 protein expression on 0, 3, and 7 days post-irradiation revealed no differences between the LLLI and control groups; however, promotion of cell

Extracellular matrix dynamics during vertebrate axis formation.

Science.gov (United States)

Czirók, András; Rongish, Brenda J; Little, Charles D

2004-04-01

The first evidence for the dynamics of in vivo extracellular matrix (ECM) pattern formation during embryogenesis is presented below. Fibrillin 2 filaments were tracked for 12 h throughout the avian intraembryonic mesoderm using automated light microscopy and algorithms of our design. The data show that these ECM filaments have a reproducible morphogenic destiny that is characterized by directed transport. Fibrillin 2 particles initially deposited in the segmental plate mesoderm are translocated along an unexpected trajectory where they eventually polymerize into an intricate scaffold of cables parallel to the anterior-posterior axis. The cables coalesce near the midline before the appearance of the next-formed somite. Moreover, the ECM filaments define global tissue movements with high precision because the filaments act as passive motion tracers. Quantification of individual and collective filament "behaviors" establish fate maps, trajectories, and velocities. These data reveal a caudally propagating traveling wave pattern in the morphogenetic movements of early axis formation. We conjecture that within vertebrate embryos, long-range mechanical tension fields are coupled to both large-scale patterning and local organization of the ECM. Thus, physical forces or stress fields are essential requirements for executing an emergent developmental pattern-in this case, paraxial fibrillin cable assembly.

Extracellular matrix organization in developing muscle: correlation with acetylcholine receptor aggregates.

Science.gov (United States)

Bayne, E K; Anderson, M J; Fambrough, D M

1984-10-01

Monoclonal antibodies recognizing laminin, heparan sulfate proteoglycan, fibronectin, and two apparently novel connective tissue components have been used to examine the organization of extracellular matrix of skeletal muscle in vivo and in vitro. Four of the five monoclonal antibodies are described for the first time here. Immunocytochemical experiments with frozen-sectioned muscle demonstrated that both the heparan sulfate proteoglycan and laminin exhibited staining patterns identical to that expected for components of the basal lamina. In contrast, the remaining matrix constituents were detected in all regions of muscle connective tissue: the endomysium, perimysium, and epimysium. Embryonic muscle cells developing in culture elaborated an extracellular matrix, each antigen exhibiting a unique distribution. Of particular interest was the organization of extracellular matrix on myotubes: the build-up of matrix components was most apparent in plaques overlying clusters of an integral membrane protein, the acetylcholine receptor (AChR). The heparan sulfate proteoglycan was concentrated at virtually all AChR clusters and showed a remarkable level of congruence with receptor organization; laminin was detected at 70-95% of AChR clusters but often was not completely co-distributed with AChR within the cluster; fibronectin and the two other extracellular matrix antigens occurred at approximately 20, 8, and 2% of the AChR clusters, respectively, and showed little or no congruence with AChR. From observations on the distribution of extracellular matrix components in tissue cultured fibroblasts and myogenic cells, several ideas about the organization of extracellular matrix are suggested. (a) Congruence between AChR clusters and heparan sulfate proteoglycan suggests the existence of some linkage between the two molecules, possibly important for regulation of AChR distribution within the muscle membrane. (b) The qualitatively different patterns of extracellular matrix

Production of extracellular fatty acid using engineered Escherichia coli

Directory of Open Access Journals (Sweden)

Liu Hui

2012-04-01

Full Text Available Abstract Background As an alternative for economic biodiesel production, the microbial production of extracellular fatty acid from renewable resources is receiving more concerns recently, since the separation of fatty acid from microorganism cells is normally involved in a series of energy-intensive steps. Many attempts have been made to construct fatty acid producing strains by targeting genes in the fatty acid biosynthetic pathway, while few studies focused on the cultivation process and the mass transfer kinetics. Results In this study, both strain improvements and cultivation process strategies were applied to increase extracellular fatty acid production by engineered Escherichia coli. Our results showed overexpressing ‘TesA and the deletion of fadL in E. coli BL21 (DE3 improved extracellular fatty acid production, while deletion of fadD didn’t strengthen the extracellular fatty acid production for an undetermined mechanism. Moreover, the cultivation process controls contributed greatly to extracellular fatty acid production with respect to titer, cell growth and productivity by adjusting the temperature, adding ampicillin and employing on-line extraction. Under optimal conditions, the E. coli strain (pACY-‘tesA-ΔfadL produced 4.8 g L−1 extracellular fatty acid, with the specific productivity of 0.02 g h−1 g−1dry cell mass, and the yield of 4.4% on glucose, while the ratios of cell-associated fatty acid versus extracellular fatty acid were kept below 0.5 after 15 h of cultivation. The fatty acids included C12:1, C12:0, C14:1, C14:0, C16:1, C16:0, C18:1, C18:0. The composition was dominated by C14 and C16 saturated and unsaturated fatty acids. Using the strain pACY-‘tesA, similar results appeared under the same culture conditions and the titer was also much higher than that ever reported previously, which suggested that the supposedly superior strain did not necessarily perform best for the efficient production of desired

Exploring uncertainty in the Earth Sciences - the potential field perspective

Science.gov (United States)

Saltus, R. W.; Blakely, R. J.

2013-12-01

Interpretation of gravity and magnetic anomalies is mathematically non-unique because multiple theoretical solutions are possible. The mathematical label of 'non-uniqueness' can lead to the erroneous impression that no single interpretation is better in a geologic sense than any other. The purpose of this talk is to present a practical perspective on the theoretical non-uniqueness of potential field interpretation in geology. There are multiple ways to approach and constrain potential field studies to produce significant, robust, and definitive results. For example, a smooth, bell-shaped gravity profile, in theory, could be caused by an infinite set of physical density bodies, ranging from a deep, compact, circular source to a shallow, smoothly varying, inverted bell-shaped source. In practice, however, we can use independent geologic or geophysical information to limit the range of possible source densities and rule out many of the theoretical solutions. We can further reduce the theoretical uncertainty by careful attention to subtle anomaly details. For example, short-wavelength anomalies are a well-known and theoretically established characteristic of shallow geologic sources. The 'non-uniqueness' of potential field studies is closely related to the more general topic of scientific uncertainty in the Earth sciences and beyond. Nearly all results in the Earth sciences are subject to significant uncertainty because problems are generally addressed with incomplete and imprecise data. The increasing need to combine results from multiple disciplines into integrated solutions in order to address complex global issues requires special attention to the appreciation and communication of uncertainty in geologic interpretation.

Effects of an electric field on the confined hydrogen atom in a parabolic potential well

International Nuclear Information System (INIS)

Xie Wenfang

2009-01-01

Using the perturbation method, the confined hydrogen atom by a parabolic potential well is investigated. The binding energy of the confined hydrogen atom in a parabolic potential well is calculated as a function of the confined potential radius and as a function of the intensity of an applied electric field. It is shown that the binding energy of the confined hydrogen atom is highly dependent on the confined potential radius and the intensity of an applied electric field.

In vivo EPR extracellular pH-metry in tumors using a triphosphonated trityl radical.

Science.gov (United States)

Marchand, Valérie; Levêque, Philippe; Driesschaert, Benoit; Marchand-Brynaert, Jacqueline; Gallez, Bernard

2017-06-01

The ability to assess the extracellular pH (pHe) is an important issue in oncology, because extracellular acidification is associated with tumor aggressiveness and resistance to cytotoxic therapies. In this study, a stable triphosphonated triarylmethyl (TPTAM) radical was qualified as a pHe electron paramagnetic resonance (EPR) molecular reporter. Calibration of hyperfine splitting as a function of pH was performed using a 1.2-GHz EPR spectrometer. Gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) was used as an extracellular paramagnetic broadening agent to assess the localization of TPTAM when incubated with cells. In vivo EPR pH-metry was performed in MDA, SiHa, and TLT tumor models and in muscle. Bicarbonate therapy was used to modulate the tumor pHe. EPR measurements were compared with microelectrode readouts. The hyperfine splitting of TPTAM was strongly pH-dependent around the pKa of the probe (pKa = 6.99). Experiments with Gd-DTPA demonstrated that TPTAM remained in the extracellular compartment. pHe was found to be more acidic in the MDA, SiHa, and TLT tumor models compared with muscle. Treatment of animals by bicarbonate induced an increase in pHe in tumors: similar variations in pHe were found when using in vivo EPR or invasive microelectrodes measurements. This study demonstrates the potential usefulness of TPTAM for monitoring pHe in tumors. Magn Reson Med 77:2438-2443, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

Production of extracellular laccase from the newly isolated Bacillus ...

African Journals Online (AJOL)

This study was carried out with aim of screening for extracellular thermostable laccase producing bacteria. Twenty-two (22) laccase positive strains were isolated from the selected environmental samples while extracellular laccase activity was detected only in six strains namely TM1, TMT1, PK4, PS1, TMS1 and ASP3.

Escaping Underground Nets: Extracellular DNases Degrade Plant Extracellular Traps and Contribute to Virulence of the Plant Pathogenic Bacterium Ralstonia solanacearum

Science.gov (United States)

Tran, Tuan Minh; MacIntyre, April; Hawes, Martha; Allen, Caitilyn

2016-01-01

Plant root border cells have been recently recognized as an important physical defense against soil-borne pathogens. Root border cells produce an extracellular matrix of protein, polysaccharide and DNA that functions like animal neutrophil extracellular traps to immobilize pathogens. Exposing pea root border cells to the root-infecting bacterial wilt pathogen Ralstonia solanacearum triggered release of DNA-containing extracellular traps in a flagellin-dependent manner. These traps rapidly immobilized the pathogen and killed some cells, but most of the entangled bacteria eventually escaped. The R. solanacearum genome encodes two putative extracellular DNases (exDNases) that are expressed during pathogenesis, suggesting that these exDNases contribute to bacterial virulence by enabling the bacterium to degrade and escape root border cell traps. We tested this hypothesis with R. solanacearum deletion mutants lacking one or both of these nucleases, named NucA and NucB. Functional studies with purified proteins revealed that NucA and NucB are non-specific endonucleases and that NucA is membrane-associated and cation-dependent. Single ΔnucA and ΔnucB mutants and the ΔnucA/B double mutant all had reduced virulence on wilt-susceptible tomato plants in a naturalistic soil-soak inoculation assay. The ΔnucA/B mutant was out-competed by the wild-type strain in planta and was less able to stunt root growth or colonize plant stems. Further, the double nuclease mutant could not escape from root border cells in vitro and was defective in attachment to pea roots. Taken together, these results demonstrate that extracellular DNases are novel virulence factors that help R. solanacearum successfully overcome plant defenses to infect plant roots and cause bacterial wilt disease. PMID:27336156

Escaping Underground Nets: Extracellular DNases Degrade Plant Extracellular Traps and Contribute to Virulence of the Plant Pathogenic Bacterium Ralstonia solanacearum.

Directory of Open Access Journals (Sweden)

Tuan Minh Tran

2016-06-01

Full Text Available Plant root border cells have been recently recognized as an important physical defense against soil-borne pathogens. Root border cells produce an extracellular matrix of protein, polysaccharide and DNA that functions like animal neutrophil extracellular traps to immobilize pathogens. Exposing pea root border cells to the root-infecting bacterial wilt pathogen Ralstonia solanacearum triggered release of DNA-containing extracellular traps in a flagellin-dependent manner. These traps rapidly immobilized the pathogen and killed some cells, but most of the entangled bacteria eventually escaped. The R. solanacearum genome encodes two putative extracellular DNases (exDNases that are expressed during pathogenesis, suggesting that these exDNases contribute to bacterial virulence by enabling the bacterium to degrade and escape root border cell traps. We tested this hypothesis with R. solanacearum deletion mutants lacking one or both of these nucleases, named NucA and NucB. Functional studies with purified proteins revealed that NucA and NucB are non-specific endonucleases and that NucA is membrane-associated and cation-dependent. Single ΔnucA and ΔnucB mutants and the ΔnucA/B double mutant all had reduced virulence on wilt-susceptible tomato plants in a naturalistic soil-soak inoculation assay. The ΔnucA/B mutant was out-competed by the wild-type strain in planta and was less able to stunt root growth or colonize plant stems. Further, the double nuclease mutant could not escape from root border cells in vitro and was defective in attachment to pea roots. Taken together, these results demonstrate that extracellular DNases are novel virulence factors that help R. solanacearum successfully overcome plant defenses to infect plant roots and cause bacterial wilt disease.

Extracellular polymer substance synthesized by a halophilic bacterium Chromohalobacter canadensis 28.

Science.gov (United States)

Radchenkova, Nadja; Boyadzhieva, Ivanka; Atanasova, Nikolina; Poli, Annarita; Finore, Ilaria; Di Donato, Paola; Nicolaus, Barbara; Panchev, Ivan; Kuncheva, Margarita; Kambourova, Margarita

2018-04-03

Halophilic microorganisms are producers of a lot of new compounds whose properties suggest promising perspectives for their biotechnological exploration. Moderate halophilic bacterium Chromohalobacter canadensis 28 was isolated from Pomorie salterns as an extracellular polymer substance (EP) producer. The best carbon source for extracellular polymer production was found to be lactose, a sugar received as a by-product from the dairy industry. After optimization of the culture medium and physicochemical conditions for cultivation, polymer biosynthesis increased more than 2-fold. The highest level of extracellular polymer synthesis by C. canadensis 28 was observed in an unusually high NaCl concentration (15% w/v). Chemical analysis of the purified polymer revealed the presence of an exopolysaccharide (EPS) fraction (14.3% w/w) and protein fraction (72% w/w). HPLC analysis of the protein fraction showed the main presence of polyglutamic acid (PGA) (75.7% w/w). EPS fraction analysis revealed the following sugar composition (% w/w): glucosamine 36.7, glucose 32.3, rhamnose 25.4, xylose 1.7, and not identified sugar 3.9. The hydrogel formed by PGA and EPS fractions showed high swelling behavior, very good emulsifying and stabilizing properties, and good foaming ability. This is the first report for halophilic bacterium able to synthesize a polymer containing PGA fraction. The synthesized biopolymer shows an extremely high hydrophilicity, due to the simultaneous presence of PGA and EPS. The analysis of its functional properties and the presence of glucosamine in the highest proportion in EPS fraction clearly determine the potential of EP synthesized by C. canadensis 28 for application in the cosmetics industry.

Evidence-Based Clinical Use of Nanoscale Extracellular Vesicles in Nanomedicine.

Science.gov (United States)

Fais, Stefano; O'Driscoll, Lorraine; Borras, Francesc E; Buzas, Edit; Camussi, Giovanni; Cappello, Francesco; Carvalho, Joana; Cordeiro da Silva, Anabela; Del Portillo, Hernando; El Andaloussi, Samir; Ficko Trček, Tanja; Furlan, Roberto; Hendrix, An; Gursel, Ihsan; Kralj-Iglic, Veronika; Kaeffer, Bertrand; Kosanovic, Maja; Lekka, Marilena E; Lipps, Georg; Logozzi, Mariantonia; Marcilla, Antonio; Sammar, Marei; Llorente, Alicia; Nazarenko, Irina; Oliveira, Carla; Pocsfalvi, Gabriella; Rajendran, Lawrence; Raposo, Graça; Rohde, Eva; Siljander, Pia; van Niel, Guillaume; Vasconcelos, M Helena; Yáñez-Mó, María; Yliperttula, Marjo L; Zarovni, Natasa; Zavec, Apolonija Bedina; Giebel, Bernd

2016-04-26

Recent research has demonstrated that all body fluids assessed contain substantial amounts of vesicles that range in size from 30 to 1000 nm and that are surrounded by phospholipid membranes containing different membrane microdomains such as lipid rafts and caveolae. The most prominent representatives of these so-called extracellular vesicles (EVs) are nanosized exosomes (70-150 nm), which are derivatives of the endosomal system, and microvesicles (100-1000 nm), which are produced by outward budding of the plasma membrane. Nanosized EVs are released by almost all cell types and mediate targeted intercellular communication under physiological and pathophysiological conditions. Containing cell-type-specific signatures, EVs have been proposed as biomarkers in a variety of diseases. Furthermore, according to their physical functions, EVs of selected cell types have been used as therapeutic agents in immune therapy, vaccination trials, regenerative medicine, and drug delivery. Undoubtedly, the rapidly emerging field of basic and applied EV research will significantly influence the biomedicinal landscape in the future. In this Perspective, we, a network of European scientists from clinical, academic, and industry settings collaborating through the H2020 European Cooperation in Science and Technology (COST) program European Network on Microvesicles and Exosomes in Health and Disease (ME-HAD), demonstrate the high potential of nanosized EVs for both diagnostic and therapeutic (i.e., theranostic) areas of nanomedicine.

Extracellular matrix as a driver for lung regeneration.

Science.gov (United States)

Balestrini, Jenna L; Niklason, Laura E

2015-03-01

Extracellular matrix has manifold roles in tissue mechanics, guidance of cellular behavior, developmental biology, and regenerative medicine. Over the past several decades, various pre-clinical and clinical studies have shown that many connective tissues may be replaced and/or regenerated using suitable extracellular matrix scaffolds. More recently, decellularization of lung tissue has shown that gentle removal of cells can leave behind a "footprint" within the matrix that may guide cellular adhesion, differentiation and homing following cellular repopulation. Fundamental issues like understanding matrix composition and micro-mechanics remain difficult to tackle, largely because of a lack of available assays and tools for systematically characterizing intact matrix from tissues and organs. This review will critically examine the role of engineered and native extracellular matrix in tissue and lung regeneration, and provide insights into directions for future research and translation.

Trash or Treasure: extracellular microRNAs and cell-to-cell communication

Directory of Open Access Journals (Sweden)

Nobuyoshi eKosaka

2013-09-01

Full Text Available Circulating RNAs in human body fluids are promising candidates for diagnostic purposes. However, the biological significance of circulating RNAs remains elusive. Recently, small non-coding RNAs, microRNAs (miRNAs, were isolated from multiple human body fluids, and these circulating miRNAs have been implicated as novel disease biomarkers. Concurrently, miRNAs were also identified in the extracellular space associated with extracellular vesicles (EVs, which are small membrane vesicles secreted from various types of cells. The function of these secreted miRNAs has been revealed in several papers. Circulating miRNAs have been experimentally found to be associated with EVs, however, other types of extracellular miRNAs were also described. This review discusses studies related to extracellular miRNAs, including circulating miRNAs and secreted miRNAs, to highlight the importance of studying not only secreted miRNAs but also circulating miRNAs to determine the contribution of extracellular miRNAs especially in cancer development.

Inversion of potential-field data for layers with uneven thickness

OpenAIRE

Caratori Tontini, F.; Cocchi, L.; Carmisciano, C.; Stefanelli, P.

2008-01-01

AB: Inversion of large-scale potential-field anomalies, aimed at determining density or magnetization, is usually made in the Fourier domain. The commonly adopted geometry is based on a layer of constant thickness, characterized by a bottom surface at a fixed distance from the top surface.....

An immunofluorescence assay for extracellular matrix components highlights the role of epithelial cells in producing a stable, fibrillar extracellular matrix

Directory of Open Access Journals (Sweden)

Omar S. Qureshi

2017-10-01

Full Text Available Activated fibroblasts are considered major drivers of fibrotic disease progression through the production of excessive extracellular matrix (ECM in response to signals from damaged epithelial and inflammatory cells. Nevertheless, epithelial cells are capable of expressing components of the ECM, cross-linking enzymes that increase its stability and are sensitive to factors involved in the early stages of fibrosis. We therefore wanted to test the hypothesis that epithelial cells can deposit ECM in response to stimulation in a comparable manner to fibroblasts. We performed immunofluorescence analysis of components of stable, mature extracellular matrix produced by primary human renal proximal tubular epithelial cells and renal fibroblasts in response to cytokine stimulation. Whilst fibroblasts produced a higher basal level of extracellular matrix components, epithelial cells were able to deposit significant levels of fibronectin, collagen I, III and IV in response to cytokine stimulation. In response to hypoxia, epithelial cells showed an increase in collagen IV deposition but not in response to the acute stress stimuli aristolochic acid or hydrogen peroxide. When epithelial cells were in co-culture with fibroblasts we observed significant increases in the level of matrix deposition which could be reduced by transforming growth factor beta (TGF-β blockade. Our results highlight the role of epithelial cells acting as efficient producers of stable extracellular matrix which could contribute to renal tubule thickening in fibrosis.

Mechanisms of astrocytic K(+) clearance and swelling under high extracellular K(+) concentrations.

Science.gov (United States)

Murakami, Shingo; Kurachi, Yoshihisa

2016-03-01

In response to the elevation of extracellular K(+) concentration ([K(+)]out), astrocytes clear excessive K(+) to maintain conditions necessary for neural activity. K(+) clearance in astrocytes occurs via two processes: K(+) uptake and K(+) spatial buffering. High [K(+)]out also induces swelling in astrocytes, leading to edema and cell death in the brain. Despite the importance of astrocytic K(+) clearance and swelling, the underlying mechanisms remain unclear. Here, we report results from a simulation analysis of astrocytic K(+) clearance and swelling. Astrocyte models were constructed by incorporating various mechanisms such as intra/extracellular ion concentrations of Na(+), K(+), and Cl(-), cell volume, and models of Na,K-ATPase, Na-K-Cl cotransporter (NKCC), K-Cl cotransporter, inwardly-rectifying K(+) (KIR) channel, passive Cl(-) current, and aquaporin channel. The simulated response of astrocyte models under the uniform distribution of high [K(+)]out revealed significant contributions of NKCC and Na,K-ATPase to increases of intracellular K(+) and Cl(-) concentrations, and swelling. Moreover, we found that, under the non-uniform distribution of high [K(+)]out, KIR channels localized at synaptic clefts absorbed excess K(+) by depolarizing the equivalent potential of K(+) (E K) above membrane potential, while K(+) released through perivascular KIR channels was enhanced by hyperpolarizing E K and depolarizing membrane potential. Further analysis of simulated drug effects revealed that astrocyte swelling was modulated by blocking each of the ion channels and transporters. Our simulation analysis revealed controversial mechanisms of astrocytic K(+) clearance and swelling resulting from complex interactions among ion channels and transporters.

Extracellular miRNA-21 as a novel biomarker in glioma: evidence from meta-analysis, clinical validation and experimental investigations

Science.gov (United States)

Liu, Tian; Wang, Zhixin; Tai, Minghui; Meng, Fandi; Zhang, Jingyao; Wan, Yong; Mao, Ping; Dong, Xiaoqun; Liu, Chang; Niu, Wenquan; Dong, Shunbin

2016-01-01

Evidence is accumulating highlighting the importance of extracellular miRNA as a novel biomarker for diagnosing various kinds of malignancies. MiR-21 is one of the most studied miRNAs and is over-expressed in cancer tissues. To explore the clinical implications and secretory mechanisms of extracellular miR-21, we firstly meta-analyzed the diagnostic efficiency of extracellular miR-21 in different cancer types. Eighty-one studies based on 59 articles were finally included. In our study, extracellular miR-21 was observed to exhibit an outstanding diagnostic accuracy in detecting brain cancer (area under the summary receiver operating characteristic curve or AUC = 0.94), and this accuracy was more obvious in glioma diagnosis (AUC = 0.95). Our validation study (n = 45) further confirmed the diagnostic and prognostic role of miR-21 in cerebrospinal fluid (CSF) for glioma. These findings inspired us to explore the biological function of miR-21. We next conducted mechanistic investigations to explain the secretory mechanisms of extracellular miR-21 in glioma. TGF-β/Smad3 signaling was identified to participate in mediating the release of miR-21 from glioma cells. Further targeting TGF-β/Smad3 signaling using galunisertib, an inhibitor of the TGF-β type I receptor kinase, can attenuate the secretion of miR-21 from glioma cells. Taken together, CSF-based miR-21 might serve as a potential biomarker for diagnosing brain cancer, especially for patients with glioma. Moreover, extracellular levels of miR-21 were affected by exogenous TGF-β activity and galunisertib treatment. PMID:27166186

Extracellular acidosis activates ASIC-like channels in freshly isolated cerebral artery smooth muscle cells.

Science.gov (United States)

Chung, Wen-Shuo; Farley, Jerry M; Swenson, Alyssa; Barnard, John M; Hamilton, Gina; Chiposi, Rumbidzayi; Drummond, Heather A

2010-05-01

Recent studies suggest that certain acid-sensing ion channels (ASIC) are expressed in vascular smooth muscle cells (VSMCs) and are required for VSMC functions. However, electrophysiological evidence of ASIC channels in VSMCs is lacking. The purpose of this study was to test the hypothesis that isolated cerebral artery VSMCs express ASIC-like channels. To address this hypothesis, we used RT-PCR, Western blotting, immunolabeling, and conventional whole cell patch-clamp technique. We found extracellular H(+)-induced inward currents in 46% of cells tested (n = 58 of 126 VSMCs, pH 6.5-5.0). The percentage of responsive cells and the current amplitude increased as the external H(+) concentration increased (pH(6.0), n = 28/65 VSMCs responsive, mean current density = 8.1 +/- 1.2 pA/pF). Extracellular acidosis (pH(6.0)) shifted the whole cell reversal potential toward the Nernst potential of Na(+) (n = 6) and substitution of extracellular Na(+) by N-methyl-d-glucamine abolished the inward current (n = 6), indicating that Na(+) is a major charge carrier. The broad-spectrum ASIC blocker amiloride (20 microM) inhibited proton-induced currents to 16.5 +/- 8.7% of control (n = 6, pH(6.0)). Psalmotoxin 1 (PcTx1), an ASIC1a inhibitor and ASIC1b activator, had mixed effects: PcTx1 either 1) abolished H(+)-induced currents (11% of VSMCs, 5/45), 2) enhanced or promoted activation of H(+)-induced currents (76%, 34/45), or 3) failed to promote H(+) activation in nonresponsive VSMCs (13%, 6/45). These findings suggest that freshly dissociated cerebral artery VSMCs express ASIC-like channels, which are predominantly formed by ASIC1b.

Local Field Potentials: Myths and Misunderstandings

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Oscar Herreras

2016-12-01

Full Text Available The intracerebral local field potential (LFP is a measure of brain activity that reflects the highly dynamic flow of information across neural networks. This is a composite signal that receives contributions from multiple neural sources, yet interpreting its nature and significance may be hindered by several confounding factors and technical limitations. By and large, the main factor defining the amplitude of LFPs is the geometry of the current sources, over and above the degree of synchronization or the properties of the media. As such, similar levels of activity may result in potentials that differ in several orders of magnitude in different populations. The geometry of these sources has been experimentally inaccessible until intracerebral high density recordings enabled the co-activating sources to be revealed. Without this information, it has proven difficult to interpret a century’s worth of recordings that used temporal cues alone, such as event or spike related potentials and frequency bands. As such, a collection of biophysically ill-founded concepts have been considered legitimate, which can now be corrected in the light of recent advances. The relationship of LFPs to their sources is often counterintuitive. For instance, most LFP activity is not local but remote, it may be larger further from rather than close to the source, the polarity does not define its excitatory or inhibitory nature, and the amplitude may increase when source’s activity is reduced. As technological developments foster the use of LFPs, the time is now ripe to raise awareness of the need to take into account spatial aspects of these signals and of the errors derived from neglecting to do so.

EXTRACELLULAR VESICLES: CLASSIFICATION, FUNCTIONS AND CLINICAL RELEVANCE

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A. V. Oberemko

2014-12-01

Full Text Available This review presents a generalized definition of vesicles as bilayer extracellular organelles of all celular forms of life: not only eu-, but also prokaryotic. The structure and composition of extracellular vesicles, history of research, nomenclature, their impact on life processes in health and disease are discussed. Moreover, vesicles may be useful as clinical instruments for biomarkers, and they are promising as biotechnological drug. However, many questions in this area are still unresolved and need to be addressed in the future. The most interesting from the point of view of practical health care represents a direction to study the effect of exosomes and microvesicles in the development and progression of a particular disease, the possibility of adjusting the pathological process by means of extracellular vesicles of a particular type, acting as an active ingredient. Relevant is the further elucidation of the role and importance of exosomes to the surrounding cells, tissues and organs at the molecular level, the prospects for the use of non-cellular vesicles as biomarkers of disease.

Glucagon-like peptide-1 receptor ligand interactions: structural cross talk between ligands and the extracellular domain.

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Graham M West

Full Text Available Activation of the glucagon-like peptide-1 receptor (GLP-1R in pancreatic β-cells potentiates insulin production and is a current therapeutic target for the treatment of type 2 diabetes mellitus (T2DM. Like other class B G protein-coupled receptors (GPCRs, the GLP-1R contains an N-terminal extracellular ligand binding domain. N-terminal truncations on the peptide agonist generate antagonists capable of binding to the extracellular domain, but not capable of activating full length receptor. The main objective of this study was to use Hydrogen/deuterium exchange (HDX to identify how the amide hydrogen bonding network of peptide ligands and the extracellular domain of GLP-1R (nGLP-1R were altered by binding interactions and to then use this platform to validate direct binding events for putative GLP-1R small molecule ligands. The HDX studies presented here for two glucagon-like peptide-1 receptor (GLP-1R peptide ligands indicates that the antagonist exendin-4[9-39] is significantly destabilized in the presence of nonionic detergents as compared to the agonist exendin-4. Furthermore, HDX can detect stabilization of exendin-4 and exendin-4[9-39] hydrogen bonding networks at the N-terminal helix [Val19 to Lys27] upon binding to the N-terminal extracellular domain of GLP-1R (nGLP-1R. In addition we show hydrogen bonding network stabilization on nGLP-1R in response to ligand binding, and validate direct binding events with the extracellular domain of the receptor for putative GLP-1R small molecule ligands.

Bacterial Extracellular Polysaccharides Involved in Biofilm Formation

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Elena P. Ivanova

2009-07-01

Full Text Available Extracellular polymeric substances (EPS produced by microorganisms are a complex mixture of biopolymers primarily consisting of polysaccharides, as well as proteins, nucleic acids, lipids and humic substances. EPS make up the intercellular space of microbial aggregates and form the structure and architecture of the biofilm matrix. The key functions of EPS comprise the mediation of the initial attachment of cells to different substrata and protection against environmental stress and dehydration. The aim of this review is to present a summary of the current status of the research into the role of EPS in bacterial attachment followed by biofilm formation. The latter has a profound impact on an array of biomedical, biotechnology and industrial fields including pharmaceutical and surgical applications, food engineering, bioremediation and biohydrometallurgy. The diverse structural variations of EPS produced by bacteria of different taxonomic lineages, together with examples of biotechnological applications, are discussed. Finally, a range of novel techniques that can be used in studies involving biofilm-specific polysaccharides is discussed.

Extracellular Vesicles From the Helminth Fasciola hepatica Prevent DSS-Induced Acute Ulcerative Colitis in a T-Lymphocyte Independent Mode

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Javier Roig

2018-05-01

Full Text Available The complexity of the pathogenesis of inflammatory bowel disease (ulcerative colitis and Crohn’s disease has led to the quest of empirically drug therapies, combining immunosuppressant agents, biological therapy and modulators of the microbiota. Helminth parasites have been proposed as an alternative treatment of these diseases based on the hygiene hypothesis, but ethical and medical problems arise. Recent reports have proved the utility of parasite materials, mainly excretory/secretory products as therapeutic agents. The identification of extracellular vesicles on those secreted products opens a new field of investigation, since they exert potent immunomodulating effects. To assess the effect of extracellular vesicles produced by helminth parasites to treat ulcerative colitis, we have analyzed whether extracellular vesicles produced by the parasitic helminth Fasciola hepatica can prevent colitis induced by chemical agents in a mouse model. Adult parasites were cultured in vitro and secreted extracellular vesicles were purified and used for immunizing both wild type C57BL/6 and RAG1-/- mice. Control and immunized mice groups were treated with dextran sulfate sodium 7 days after last immunization to promote experimental colitis. The severity of colitis was assessed by disease activity index and histopathological scores. Mucosal cytokine expression was evaluated by ELISA. The activation of NF-kB, COX-2, and MAPK were evaluated by immunoblotting. Administration of extracellular vesicles from F. hepatica ameliorates the pathological symptoms reducing the amount of pro-inflammatory cytokines and interfering with both MAPK and NF-kB pathways. Interestingly, the observed effects do not seem to be mediated by T-cells. Our results indicate that extracellular vesicles from parasitic helminths can modulate immune responses in dextran sulfate sodium (DSS-induced colitis, exerting a protective effect that should be mediated by other cells distinct from B

Crystal Structure of Glucagon-like Peptide-1 in Complex with the Extracellular Domain of the Glucagon-like Peptide-1 Receptor*

Science.gov (United States)

Underwood, Christina Rye; Garibay, Patrick; Knudsen, Lotte Bjerre; Hastrup, Sven; Peters, Günther H.; Rudolph, Rainer; Reedtz-Runge, Steffen

2010-01-01

GLP-1 (glucagon-like peptide-1) is an incretin released from intestinal L-cells in response to food intake. Activation of the GLP-1 receptor potentiates the synthesis and release of insulin from pancreatic β-cells in a glucose-dependent manner. The GLP-1 receptor belongs to class B of the G-protein-coupled receptors, a subfamily characterized by a large N-terminal extracellular ligand binding domain. Exendin-4 and GLP-1 are 50% identical, and exendin-4 is a full agonist with similar affinity and potency for the GLP-1 receptor. We recently solved the crystal structure of the GLP-1 receptor extracellular domain in complex with the competitive antagonist exendin-4(9–39). Interestingly, the isolated extracellular domain binds exendin-4 with much higher affinity than the endogenous agonist GLP-1. Here, we have solved the crystal structure of the extracellular domain in complex with GLP-1 to 2.1 Åresolution. The structure shows that important hydrophobic ligand-receptor interactions are conserved in agonist- and antagonist-bound forms of the extracellular domain, but certain residues in the ligand-binding site adopt a GLP-1-specific conformation. GLP-1 is a kinked but continuous α-helix from Thr13 to Val33 when bound to the extracellular domain. We supplemented the crystal structure with site-directed mutagenesis to link the structural information of the isolated extracellular domain with the binding properties of the full-length receptor. The data support the existence of differences in the binding modes of GLP-1 and exendin-4 on the full-length GLP-1 receptor. PMID:19861722

Extracellular space, blood volume, and the early dumping syndrome after total gastrectomy

Energy Technology Data Exchange (ETDEWEB)

Miholic, J.; Reilmann, L.; Meyer, H.J.; Koerber, H.K.; Kotzerke, J.; Hecker, H. (Medzinische Hochschule Hannover (Germany, F.R.))

1990-10-01

Extracellular space and blood volume were measured using 82Br dilution and 51Cr-tagged erythrocytes in 24 tumor-free patients after total gastrectomy. Eleven of the patients suffered from early dumping. Age, blood volume, and extracellular space were significantly smaller in dumpers (P less than 0.05). The dumping score could be predicted by a multiple regression model considering blood volume per lean body mass and extracellular space (r = 0.637; P = 0.0039). Rapid (t1/2 less than 360 seconds) emptying of the gastric substitute, assessed using a 99Tc-labeled solid test meal, was significantly associated with dumping in addition to extracellular space and blood volume (r = 0.876; P = 0.0018). Both rapid emptying and a narrow extracellular space seem to contribute to the early dumping syndrome.

The auxiliary field method and approximate analytical solutions of the Schroedinger equation with exponential potentials

Energy Technology Data Exchange (ETDEWEB)

Silvestre-Brac, Bernard [LPSC Universite Joseph Fourier, Grenoble 1, CNRS/IN2P3, Institut Polytechnique de Grenoble, Avenue des Martyrs 53, F-38026 Grenoble-Cedex (France); Semay, Claude; Buisseret, Fabien [Groupe de Physique Nucleaire Theorique, Universite de Mons-Hainaut, Academie universitaire Wallonie-Bruxelles, Place du Parc 20, B-7000 Mons (Belgium)], E-mail: silvestre@lpsc.in2p3.fr, E-mail: claude.semay@umh.ac.be, E-mail: fabien.buisseret@umh.ac.be

2009-06-19

The auxiliary field method is a new and efficient way to compute approximate analytical eigenenergies of the Schroedinger equation. This method has already been successfully applied to the case of central potentials of power-law and logarithmic forms. In the present work, we show that the Schroedinger equation with exponential potentials of the form -{alpha}r{sup {lambda}}exp(-{beta}r) can also be analytically solved by using the auxiliary field method. Closed formulae giving the critical heights and the energy levels of these potentials are presented. Special attention is drawn to the Yukawa potential and the pure exponential potential.

The auxiliary field method and approximate analytical solutions of the Schroedinger equation with exponential potentials

International Nuclear Information System (INIS)

Silvestre-Brac, Bernard; Semay, Claude; Buisseret, Fabien

2009-01-01

The auxiliary field method is a new and efficient way to compute approximate analytical eigenenergies of the Schroedinger equation. This method has already been successfully applied to the case of central potentials of power-law and logarithmic forms. In the present work, we show that the Schroedinger equation with exponential potentials of the form -αr λ exp(-βr) can also be analytically solved by using the auxiliary field method. Closed formulae giving the critical heights and the energy levels of these potentials are presented. Special attention is drawn to the Yukawa potential and the pure exponential potential

Regulation of pituitary hormones and cell proliferation by components of the extracellular matrix

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M. Paez-Pereda

2005-10-01

Full Text Available The extracellular matrix is a three-dimensional network of proteins, glycosaminoglycans and other macromolecules. It has a structural support function as well as a role in cell adhesion, migration, proliferation, differentiation, and survival. The extracellular matrix conveys signals through membrane receptors called integrins and plays an important role in pituitary physiology and tumorigenesis. There is a differential expression of extracellular matrix components and integrins during the pituitary development in the embryo and during tumorigenesis in the adult. Different extracellular matrix components regulate adrenocorticotropin at the level of the proopiomelanocortin gene transcription. The extracellular matrix also controls the proliferation of adrenocorticotropin-secreting tumor cells. On the other hand, laminin regulates the production of prolactin. Laminin has a dynamic pattern of expression during prolactinoma development with lower levels in the early pituitary hyperplasia and a strong reduction in fully grown prolactinomas. Therefore, the expression of extracellular matrix components plays a role in pituitary tumorigenesis. On the other hand, the remodeling of the extracellular matrix affects pituitary cell proliferation. Matrix metalloproteinase activity is very high in all types of human pituitary adenomas. Matrix metalloproteinase secreted by pituitary cells can release growth factors from the extracellular matrix that, in turn, control pituitary cell proliferation and hormone secretion. In summary, the differential expression of extracellular matrix components, integrins and matrix metalloproteinase contributes to the control of pituitary hormone production and cell proliferation during tumorigenesis.

Factors that affect leaf extracellular ascorbic acid content and redox status

Energy Technology Data Exchange (ETDEWEB)

Burkey, K.O.; Fiscus, E.L. [North Carolina State Univ., United States dept. og Agriculture-Agricultural Research Service and Dept. of Crop Science, Raleigh, NC (United States); Eason, G. [North Carolina, State Univ., United States Dept. of Plant Pathology, Raleigh, NC (United States)

2003-01-01

Leaf ascorbic acid content and redox status were compared in ozone-tolerant (Provider) and ozone-sensitive (S156) genotypes of snap bean (Phaseolus vulgaris L.). Plants were grown in pots for 24 days under charcoal-filtered air (CF) conditions in open-top field chambers and then maintained as CF controls (29 nmol mol{sup 1} ozone) or exposed to elevated ozone (71 nmol mol{sup 1} ozone). Following a 10-day treatment, mature leaves of the same age were harvested early in the morning (06:00-08:00 h) or in the afternoon (13:00-15:00 h) for analysis of ascorbic acid (AA) and dehydroascorbic acid (DHA). Vacuum infiltration methods were used to separate leaf AA into apoplast and symplast fractions. The total ascorbate content [AA + DHA] of leaf tissue averaged 28% higher in Provider relative to S156, and Provider exhibited a greater capacity to maintain [AA + DHA] content under ozone stress. Apoplast [AA + DHA] content was 2-fold higher in tolerant Provider (360 nmol g{sup 1} FW maximum) relative to sensitive S156 (160 nmol g1 FW maximum) regardless of sampling period or treatment, supporting the hypothesis that extracellular AA is a factor in ozone tolerance. Apoplast [AA + DHA] levels were significantly higher in the afternoon than early morning for both genotypes, evidence for short-term regulation of extracellular ascorbate content. Total leaf ascorbate was primarily reduced with AA/[AA + DHA] ratios of 0.81-0.90. In contrast, apoplast AA/[AA + DHA] ratios were 0.01-0.60 and depended on genotype and ozone treatment. Provider exhibited a greater capacity to maintain extracellular AA/[AA + DHA] ratios under ozone stress, suggesting that ozone tolerance is associated with apoplast ascorbate redox status. (au)

An analytical expression of electric potential and field of organic thin film transistors

International Nuclear Information System (INIS)

Pankalla, S; Glesner, M

2012-01-01

The two-dimensional electric potential and field of an organic thin-film transistor (OTFT) is derived by conformal mapping using the Schwarz-Christoffel-transformation of the Poisson equation. In this paper we compare this analytical closed-form solution to field simulation results from Silvaco TCAD. Inter alia the potential close to the surface is calculated and we found excellent accordance to the numerical simulations and thus proofed its usability for charge transport calculations. Thus, it is used for calculation of the drain-source-current in the channel.

Extracellular matrix in canine mammary tumors with special focus on versican, a versatile extracellular proteoglycan

NARCIS (Netherlands)

Erdélyi, Ildikó

2006-01-01

The extracellular matrix (ECM) research has become fundamental to understand cancer. This thesis focuses on the exploration of ECM composition and organization in canine mammary tumors, with a special interest in the large chondroitin-sulfate proteoglycan (PG), versican. Chapter 1 gives an

A bioelectrochemical approach to characterize extracellular electron transfer by Synechocystis sp. PCC6803.

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Angelo Cereda

Full Text Available Biophotovoltaic devices employ photosynthetic organisms at the anode of a microbial fuel cell to generate electrical power. Although a range of cyanobacteria and algae have been shown to generate photocurrent in devices of a multitude of architectures, mechanistic understanding of extracellular electron transfer by phototrophs remains minimal. Here we describe a mediatorless bioelectrochemical device to measure the electrogenic output of a planktonically grown cyanobacterium, Synechocystis sp. PCC6803. Light dependent production of current is measured, and its magnitude is shown to scale with microbial cell concentration and light intensity. Bioelectrochemical characterization of a Synechocystis mutant lacking Photosystem II demonstrates conclusively that production of the majority of photocurrent requires a functional water splitting aparatus and electrons are likely ultimately derived from water. This shows the potential of the device to rapidly and quantitatively characterize photocurrent production by genetically modified strains, an approach that can be used in future studies to delineate the mechanisms of cyanobacterial extracellular electron transport.

Variation in activity of root extracellular phytase between genotypes of barley

DEFF Research Database (Denmark)

Asmar, Mohammad Farouq

1997-01-01

Barley genotypes grown in nutrient solution under P nutrient stress and sterile conditions were compared in activity of root-associated and root-released extracellular phytase. The activity of root-associated phytase of all genotypes was about 10 times higher than that of root-released phytase...... and the genotypes performed differently with regard to the activity of the enzymes. The winter barley genotype, Marinka had the highest activity of root-associated extracellular phytase which differed significantly from Alexis and Senate, but not from Regatta. Alexis showed the lowest activity of root......-released extracellular phytase which differed significantly from those of Marinka and Regatta, but not from Senate. Generally, there was a significant correlation between the activity of root-associated and released extracellular phytase....

Extracellular enzyme activity in a willow sewage treatment system.

Science.gov (United States)

Brzezinska, Maria Swiontek; Lalke-Porczyk, Elżbieta; Kalwasińska, Agnieszka

2012-12-01

This paper presents the results of studies on the activity of extra-cellular enzymes in soil-willow vegetation filter soil which is used in the post-treatment of household sewage in an onsite wastewater treatment system located in central Poland. Wastewater is discharged from the detached house by gravity into the onsite wastewater treatment system. It flows through a connecting pipe into a single-chamber septic tank and is directed by the connecting pipe to a control well to be further channelled in the soil-willow filter by means of a subsurface leaching system. Soil samples for the studies were collected from two depths of 5 cm and 1 m from three plots: close to the wastewater inflow, at mid-length of the plot and close to its terminal part. Soil samples were collected from May to October 2009. The activity of the extra-cellular enzymes was assayed by the fluorometric method using 4-methylumbelliferyl and 7-amido-4-methylcoumarin substrate. The ranking of potential activity of the assayed enzymes was the same at 5 cm and 1 m soil depths, i.e. esterase > phosphmomoesterase > leucine-aminopeptidase > β-glucosidase > α-glucosidase. The highest values of enzymatic activity were recorded in the surface layer of the soil at the wastewater inflow and decreased with increasing distance from that point.

Extracellular matrix hydrogels from decellularized tissues: Structure and function.

Science.gov (United States)

Saldin, Lindsey T; Cramer, Madeline C; Velankar, Sachin S; White, Lisa J; Badylak, Stephen F

2017-02-01

Extracellular matrix (ECM) bioscaffolds prepared from decellularized tissues have been used to facilitate constructive and functional tissue remodeling in a variety of clinical applications. The discovery that these ECM materials could be solubilized and subsequently manipulated to form hydrogels expanded their potential in vitro and in vivo utility; i.e. as culture substrates comparable to collagen or Matrigel, and as injectable materials that fill irregularly-shaped defects. The mechanisms by which ECM hydrogels direct cell behavior and influence remodeling outcomes are only partially understood, but likely include structural and biological signals retained from the native source tissue. The present review describes the utility, formation, and physical and biological characterization of ECM hydrogels. Two examples of clinical application are presented to demonstrate in vivo utility of ECM hydrogels in different organ systems. Finally, new research directions and clinical translation of ECM hydrogels are discussed. More than 70 papers have been published on extracellular matrix (ECM) hydrogels created from source tissue in almost every organ system. The present manuscript represents a review of ECM hydrogels and attempts to identify structure-function relationships that influence the tissue remodeling outcomes and gaps in the understanding thereof. There is a Phase 1 clinical trial now in progress for an ECM hydrogel. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Extracellular proteolytic enzymes produced by human pathogenic Vibrio species

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Shin-Ichi eMiyoshi

2013-11-01

Full Text Available Bacteria in the genus Vibrio produce extracellular proteolytic enzymes to obtain nutrients via digestion of various protein substrates. However, the enzymes secreted by human pathogenic species have been documented to modulate the bacterial virulence. Several species including Vibrio cholerae and V. vulnificus are known to produce thermolysin-like metalloproteases termed vibriolysin. The vibriolysin from V. vulnificus, a causative agent of serious systemic infection, is a major toxic factor eliciting the secondary skin damage characterized by formation of the hemorrhagic brae. The vibriolysin from intestinal pathogens may play indirect roles in pathogenicity because it can activate protein toxins and hemagglutinin by the limited proteolysis and can affect the bacterial attachment to or detachment from the intestinal surface by degradation of the mucus layer. Two species causing wound infections, V. alginolyticus and V. parahaemolyticus, produce another metalloproteases so-called collagenases. Although the detailed pathological roles have not been studied, the collagenase is potent to accelerate the bacterial dissemination through digestion of the protein components of the extracellular matrix. Some species produce cymotrypsin-like serine proteases, which may also affect the bacterial virulence potential. The intestinal pathogens produce sufficient amounts of the metalloprotease at the small intestinal temperature; however, the metalloprotease production by extra-intestinal pathogens is much higher around the body surface temperature. On the other hand, the serine protease is expressed only in the absence of the metalloprotease.

A novel extracellular low-temperature active phytase from Bacillus aryabhattai RS1 with potential application in plant growth.

Science.gov (United States)

Pal Roy, Moushree; Datta, Subhabrata; Ghosh, Shilpi

2017-05-01

Bacillus aryabhattai RS1 isolated from rhizosphere produced an extracellular, low temperature active phytase. The cultural conditions for enzyme production were optimized to obtain 35 U mL -1 of activity. Purified phytase had specific activity and molecular weight of 72.97 U mg -1 and ∼40 kDa, respectively. The enzyme was optimally active at pH 6.5 and 40°C and was highly specific to phytate. It exhibited higher catalytic activity at low temperature, retaining over 40% activity at 10°C. Phytase was more thermostable in presence of Ca 2+ ion and retained 100% residual activity on preincubation at 20-50°C for 30 min. Partial phytase encoding gene, phy B (816 bp) was cloned and sequenced. The encoded amino acid sequence (272 aa) contained two conserved motifs, DA[A/T/E]DDPA[I/L/V]W and NN[V/I]D[I/L/V]R[Y/D/Q] of β-propellar phytase and had lower sequence homology with other Bacillus phytases, indicating its novelty. Phytase and the bacterial inoculum were effective in improving germination and growth of chickpea seedlings under phosphate limiting condition. Moreover, the potential applications of the enzyme with relatively high activity at lower temperatures (20-30°C) could also be extended to aquaculture and food processing. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:633-641, 2017. © 2017 American Institute of Chemical Engineers.

MHODE: a local-homogeneity theory for improved source-parameter estimation of potential fields

Science.gov (United States)

Fedi, Maurizio; Florio, Giovanni; Paoletti, Valeria

2015-08-01

We describe a multihomogeneity theory for source-parameter estimation of potential fields. Similar to what happens for random source models, where the monofractal scaling-law has been generalized into a multifractal law, we propose to generalize the homogeneity law into a multihomogeneity law. This allows a theoretically correct approach to study real-world potential fields, which are inhomogeneous and so do not show scale invariance, except in the asymptotic regions (very near to or very far from their sources). Since the scaling properties of inhomogeneous fields change with the scale of observation, we show that they may be better studied at a set of scales than at a single scale and that a multihomogeneous model is needed to explain its complex scaling behaviour. In order to perform this task, we first introduce fractional-degree homogeneous fields, to show that: (i) homogeneous potential fields may have fractional or integer degree; (ii) the source-distributions for a fractional-degree are not confined in a bounded region, similarly to some integer-degree models, such as the infinite line mass and (iii) differently from the integer-degree case, the fractional-degree source distributions are no longer uniform density functions. Using this enlarged set of homogeneous fields, real-world anomaly fields are studied at different scales, by a simple search, at any local window W, for the best homogeneous field of either integer or fractional-degree, this yielding a multiscale set of local homogeneity-degrees and depth estimations which we call multihomogeneous model. It is so defined a new technique of source parameter estimation (Multi-HOmogeneity Depth Estimation, MHODE), permitting retrieval of the source parameters of complex sources. We test the method with inhomogeneous fields of finite sources, such as faults or cylinders, and show its effectiveness also in a real-case example. These applications show the usefulness of the new concepts, multihomogeneity and

Protease inhibitors enhance extracellular collagen fibril deposition in human mesenchymal stem cells.

Science.gov (United States)

Han, Sejin; Li, Yuk Yin; Chan, Barbara Pui

2015-10-15

Collagen is a widely used naturally occurring biomaterial for scaffolding, whereas mesenchymal stem cells (MSCs) represent a promising cell source in tissue engineering and regenerative medicine. It is generally known that cells are able to remodel their environment by simultaneous degradation of the scaffolds and deposition of newly synthesized extracellular matrix. Nevertheless, the interactions between MSCs and collagen biomaterials are poorly known, and the strategies enhancing the extracellular matrix deposition are yet to be defined. In this study, we aim to investigate the fate of collagen when it is in contact with MSCs and hypothesize that protease inhibition will enhance their extracellular deposition of collagen fibrils. Specifically, human MSCs (hMSCs) were exposed to fluorescence-labeled collagen with and without intracellular or extracellular protease inhibitors (or both) before tracing the collagen at both intracellular and extracellular spaces. Collagen were internalized by hMSCs and degraded intracellularly in lysosomes. In the presence of protease inhibitors, both intracellular collagen fibril growth and extracellular deposition of collagen fibrils were enhanced. Moreover, protease inhibitors work synergistically with ascorbic acid, a well-known matrix deposition-enhancing reagent, in further enhancing collagen fibril deposition at the extracellular space. These findings provide a better understanding of the interactions between hMSCs and collagen biomaterials and suggest a method to manipulate matrix remodeling and deposition of hMSCs, contributing to better scaffolding for tissue engineering and regenerative medicine.

Quark number density and susceptibility calculation with one correction in mean field potential

International Nuclear Information System (INIS)

Singh, S. Somorendro

2016-01-01

We calculate quark number density and susceptibility of a model which has one loop correction in mean field potential. The calculation shows continuous increasing in the number density and susceptibility up to the temperature T = 0.4 GeV. Then the value of number density and susceptibility approach to the lattice result for higher value of temperature. The result indicates that the calculated values of the model fit well and the result increase the temperature to reach the lattice data with the one loop correction in the mean field potential. (author)

Green's functions potential fields on surfaces

CERN Document Server

Melnikov, Yuri A

2017-01-01

This book is comprehensive in its classical mathematical physics presentation, providing the reader with detailed instructions for obtaining Green's functions from scratch. Green's functions is an instrument easily accessible to practitioners who are engaged in design and exploitation of machines and structures in modern engineering practice. To date, there are no books available on the market that are devoted to the Green's function formalism for equations covered in this volume. The reader, with an undergraduate background in applied mathematics, can become an active user of the Green's function approach. For the first time, Green's functions are discussed for a specific class of problems dealing with potential fields induced in thin-wall structures and therefore, the reader will have first-hand access to a novel issue. This Work is accessible to researchers in applied mathematics, mechanics, and relevant disciplines such as engineering, as well as to upper level undergraduates and graduate students.

Coppicing potential of Eucalyptus nitens : results from a field survey ...

African Journals Online (AJOL)

In order to determine factors which could have a positive influence on the coppicing potential of Eucalyptus nitens , a field survey was carried out at Draycott, near Estcourt in the KwaZulu-Natal Midlands. Five measures of the ability to coppice (stump survival, height of coppice, number of dominant shoots, coppicing ...

Production of extracellular nucleic acids by genetically altered bacteria in aquatic-environment microcosms

International Nuclear Information System (INIS)

Paul, J.H.; David, A.W.

1989-01-01

The factors which affect the production of extracellular DNA by genetically altered strains of Escherichia coli, Pseudomonas aeruginosa, Pseudomonas cepacia, and Bradyrhizobium japonicum in aquatic environments were investigated. Cellular nucleic acids were labeled in vivo by incubation with [ 3 H]thymidine or [ 3 H]adenine, and production of extracellular DNA in marine waters, artificial seawater, or minimal salts media was determined by detecting radiolabeled macromolecules in incubation filtrates. The presence or absence of the ambient microbial community had little effect on the production of extracellular DNA. Three of four organisms produced the greatest amounts of extracellular nucleic acids when incubated in low-salinity media (2% artificial seawater) rather than high-salinity media (10 to 50% artificial seawater). The greatest production of extracellular nucleic acids by P. cepacia occurred at pH 7 and 37 degree C, suggesting that extracellular-DNA production may be a normal physiologic function of the cell. Incubation of labeled P. cepacia cells in water from Bimini Harbor, Bahamas, resulted in labeling of macromolecules of the ambient microbial population. Collectively these results indicate that (i) extracellular-DNA production by genetically altered bacteria released into aquatic environments is more strongly influenced by physicochemical factors than biotic factors, (ii) extracellular-DNA production rates are usually greater for organisms released in freshwater than marine environments, and (iii) ambient microbial populations can readily utilize materials released by these organisms

Plumbing the depths: extracellular water storage in specialized leaf structures and its functional expression in a three-domain pressure -volume relationship.

Science.gov (United States)

Nguyen, Hoa T; Meir, Patrick; Wolfe, Joe; Mencuccini, Maurizio; Ball, Marilyn C

2017-07-01

A three-domain pressure-volume relationship (PV curve) was studied in relation to leaf anatomical structure during dehydration in the grey mangrove, Avicennia marina. In domain 1, relative water content (RWC) declined 13% with 0.85 MPa decrease in leaf water potential, reflecting a decrease in extracellular water stored primarily in trichomes and petiolar cisternae. In domain 2, RWC decreased by another 12% with a further reduction in leaf water potential to -5.1 MPa, the turgor loss point. Given the osmotic potential at full turgor (-4.2 MPa) and the effective modulus of elasticity (~40 MPa), domain 2 emphasized the role of cell wall elasticity in conserving cellular hydration during leaf water loss. Domain 3 was dominated by osmotic effects and characterized by plasmolysis in most tissues and cell types without cell wall collapse. Extracellular and cellular water storage could support an evaporation rate of 1 mmol m -2 s -1 for up to 54 and 50 min, respectively, before turgor loss was reached. This study emphasized the importance of leaf anatomy for the interpretation of PV curves, and identified extracellular water storage sites that enable transient water use without substantive turgor loss when other factors, such as high soil salinity, constrain rates of water transport. © 2016 John Wiley & Sons Ltd.

Responses of the extracellular enzyme activities in hardwood forest to soil temperature and seasonality and the potential effects of climate change

Czech Academy of Sciences Publication Activity Database

Baldrian, Petr; Šnajdr, Jaroslav; Merhautová, Věra; Dobiášová, Petra; Cajthaml, Tomáš; Valášková, Vendula

2013-01-01

Roč. 56, JAN 2013 (2013), s. 60-68 ISSN 0038-0717 R&D Projects: GA MŠk(CZ) LA10001; GA MŠk(CZ) ME10152; GA MZe QH72216 Institutional support: RVO:61388971 Keywords : Extracellular enzymes * Forest soil * Lignocellulose Subject RIV: EE - Microbiology, Virology Impact factor: 4.410, year: 2013

Intercellular Resistance to BRAF Inhibition Can Be Mediated by Extracellular Vesicle–Associated PDGFRβ

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Laura J. Vella

2017-11-01

Full Text Available Treatment of BRAF mutant melanoma with kinase inhibitors has been associated with rapid tumor regression; however, this clinical benefit is short-lived, and most patients relapse. A number of studies suggest that the extracellular environment promotes BRAF inhibitor resistance and tumor progression. Extracellular vesicles, such as exosomes, are functional mediators in the extracellular environment. They are small vesicles known to carry a concentrated group of functional cargo and serve as intercellular communicators not only locally but also systemically. Increasingly, it is reported that extracellular vesicles facilitate the development of drug resistance in cancer; however, their role in BRAF inhibitor resistance in melanoma is unclear. Here we investigated if extracellular vesicles from BRAF inhibitor–resistant melanoma could influence drug sensitivity in recipient melanoma cells. We demonstrate that the resistance driver, PDGFRβ, can be transferred to recipient melanoma cells via extracellular vesicles, resulting in a dose-dependent activation of PI3K/AKT signaling and escape from MAPK pathway BRAF inhibition. These data suggest that the BRAF inhibitor–sensitive phenotype of metastatic melanoma can be altered by delivery of PDGFRβ by extracellular vesicles derived from neighboring drug-resistant melanoma cells.

The emerging role of skeletal muscle extracellular matrix remodelling in obesity and exercise.

Science.gov (United States)

Martinez-Huenchullan, S; McLennan, S V; Verhoeven, A; Twigg, S M; Tam, C S

2017-07-01

Skeletal muscle extracellular matrix remodelling has been proposed as a new feature associated with obesity and metabolic dysfunction. Exercise training improves muscle function in obesity, which may be mediated by regulatory effects on the muscle extracellular matrix. This review examined available literature on skeletal muscle extracellular matrix remodelling during obesity and the effects of exercise. A non-systematic literature review was performed on PubMed of publications from 1970 to 2015. A total of 37 studies from humans and animals were retained. Studies reported overall increases in gene and protein expression of different types of collagen, growth factors and enzymatic regulators of the skeletal muscle extracellular matrix in obesity. Only two studies investigated the effects of exercise on skeletal muscle extracellular matrix during obesity, with both suggesting a regulatory effect of exercise. The effects of exercise on muscle extracellular matrix seem to be influenced by the duration and type of exercise training with variable effects from a single session compared with a longer duration of exercise. More studies are needed to elucidate the mechanisms behind skeletal muscle extracellular matrix remodelling during obesity and the effects of exercise. © 2017 World Obesity Federation.

Modulation of sibutramine-induced increases in extracellular noradrenaline concentration in rat frontal cortex and hypothalamus by α2-adrenoceptors

Science.gov (United States)

Wortley, K E; Heal, D J; Stanford, S C

1999-01-01

The effects of sibutramine (0.25–10 mg kg−1 i.p.) on extracellular noradrenaline concentration in the frontal cortex and hypothalamus of freely-moving rats were investigated using microdialysis. The role of presynaptic α2-adrenoceptors in modulating the effects of sibutramine in these brain areas was also determined.Sibutramine induced an increase in extracellular noradrenaline concentration, the magnitude of which paralleled dose, in both brain areas. In the cortex, this increase was gradual and sustained, whereas in the hypothalamus it was more rapid and of shorter duration.In both the cortex and hypothalamus, pretreatment of rats with the α2-adrenoceptor antagonist RX821002 (3 mg kg−1 i.p.) potentiated increases in the accumulation of extracellular noradrenaline induced by sibutramine (10 mg kg−1 i.p.), by 7 and 10 fold respectively. RX821002 also reduced the latency of sibutramine to reach its maximum effect in the cortex, but not in the hypothalamus.Infusion of RX821002 (1 μM) via the probe increased the accumulation of extracellular noradrenaline induced by sibutramine (10 mg kg−1 i.p.) in both brain areas. In the hypothalamus, the effects of RX821002 on the accumulation of noradrenaline induced by sibutramine were 2 fold greater than those in the cortex.These findings support evidence that sibutramine inhibits the reuptake of noradrenaline in vivo, but that the accumulation of extracellular noradrenaline is limited by noradrenergic activation of presynaptic α2-adrenoceptors. Furthermore, the data suggest that terminal α2-adrenoceptors in the hypothalamus exert a greater inhibitory effect over the control of extracellular noradrenaline accumulation than do those in the cortex. PMID:10516646

Vacuum stability of a general scalar potential of a few fields

Energy Technology Data Exchange (ETDEWEB)

Kannike, Kristjan [NICPB, Tallinn (Estonia)

2016-06-15

We calculate analytical vacuum stability or bounded from below conditions for general scalar potentials of a few fields. After a brief review of copositivity, we show how to find positivity conditions for more complicated potentials. We discuss the vacuum stability conditions of the general potential of two real scalars, without and with the Higgs boson included in the potential. As further examples, we give explicit vacuum stability conditions for the two Higgs doublet model with no explicit CP breaking, and for the Z{sub 3} scalar dark matter with an inert doublet and a complex singlet. We give a short overview of positivity conditions for tensors of quartic couplings via tensor eigenvalues. (orig.)

Classification of hemispheric monthly mean stratospheric potential vorticity fields

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R. Huth

Full Text Available Monthly mean NCEP reanalysis potential vorticity fields at the 650 K isentropic level over the Northern and Southern Hemispheres between 1979 and 1997 were studied using multivariate analysis tools. Principal component analysis in the T-mode was applied to demonstrate the validity of such statistical techniques for the study of stratospheric dynamics and climatology. The method, complementarily applied to both the raw and anomaly fields, was useful in determining and classifying the characteristics of winter and summer PV fields on both hemispheres, in particular, the well-known differences in the behaviour and persistence of the polar vortices. It was possible to identify such features as sudden warming events in the Northern Hemisphere and final warming dates in both hemispheres. The stratospheric impact of other atmospheric processes, such as volcanic eruptions, also identified though the results, must be viewed at this stage as tentative. An interesting change in behaviour around 1990 was detected over both hemispheres.

Key words. Meteorology and atmospheric dynamics (middle atmosphere dynamics; general circulation; climatology

Right ventricular function after repair of tetralogy of Fallot: a comparison between bovine pericardium and porcine small intestinal extracellular matrix.

Science.gov (United States)

Naik, Ronak; Johnson, Jason; Kumar, T K S; Philip, Ranjit; Boston, Umar; Knott-Craig, Christopher J

2017-05-29

The porcine small intestinal extracellular matrix reportedly has the potential to differentiate into viable myocardial cells. When used in tetralogy of Fallot repair, it may improve right ventricular function. We evaluated right ventricular function after repair of tetralogy of Fallot with extracellular matrix versus bovine pericardium. Subjects with non-transannular repair of tetralogy of Fallot with at least 1 year of follow-up were selected. The extracellular matrix and bovine pericardium groups were compared. We used three-dimensional right ventricular ejection fraction, right ventricle global longitudinal strain, and tricuspid annular plane systolic excursion to assess right ventricular function. The extracellular matrix group had 11 patients, whereas the bovine pericardium group had 10 patients. No differences between the groups were found regarding sex ratio, age at surgery, and cardiopulmonary bypass time. The follow-up period was 28±12.6 months in the extracellular matrix group and 50.05±17.6 months in the bovine pericardium group (p=0.001). The mean three-dimensional right ventricular ejection fraction (55.7±5.0% versus 55.3±5.2%, p=0.73), right ventricular global longitudinal strain (-18.5±3.0% versus -18.0±2.2%, p=0.44), and tricuspid annular plane systolic excursions (1.59±0.16 versus 1.59±0.2, p=0.93) were similar in the extracellular matrix group and in the bovine pericardium group, respectively. Right ventricular global longitudinal strain in healthy children is reported at -29±3% in literature. In a small cohort of the patients undergoing non-transannular repair of tetralogy of Fallot, there was no significant difference in right ventricular function between groups having extracellular matrix versus bovine pericardium patches followed-up for more than 1 year. Lower right ventricular longitudinal strain noted in both the groups compared to healthy children.

Plasma Extracellular Vesicles Enriched for Neuronal Origin: A Potential Window into Brain Pathologic Processes

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Maja Mustapic

2017-05-01

Full Text Available Our team has been a pioneer in harvesting extracellular vesicles (EVs enriched for neuronal origin from peripheral blood and using them as a biomarker discovery platform for neurological disorders. This methodology has demonstrated excellent diagnostic and predictive performance for Alzheimer's and other neurodegenerative diseases in multiple studies, providing a strong proof of concept for this approach. Here, we describe our methodology in detail and offer further evidence that isolated EVs are enriched for neuronal origin. In addition, we present evidence that EVs enriched for neuronal origin represent a more sensitive and accurate base for biomarkers than plasma, serum, or non-enriched total plasma EVs. Finally, we proceed to investigate the protein content of EVs enriched for neuronal origin and compare it with other relevant enriched and non-enriched populations of plasma EVs. Neuronal-origin enriched plasma EVs contain higher levels of signaling molecules of great interest for cellular metabolism, survival, and repair, which may be useful as biomarkers and to follow response to therapeutic interventions in a mechanism-specific manner.

Delivery of viral vectors to tumor cells: extracellular transport, systemic distribution, and strategies for improvement.

Science.gov (United States)

Wang, Yong; Yuan, Fan

2006-01-01

It is a challenge to deliver therapeutic genes to tumor cells using viral vectors because (i) the size of these vectors are close to or larger than the space between fibers in extracellular matrix and (ii) viral proteins are potentially toxic in normal tissues. In general, gene delivery is hindered by various physiological barriers to virus transport from the site of injection to the nucleus of tumor cells and is limited by normal tissue tolerance of toxicity determined by local concentrations of transgene products and viral proteins. To illustrate the obstacles encountered in the delivery and yet limit the scope of discussion, this review focuses only on extracellular transport in solid tumors and distribution of viral vectors in normal organs after they are injected intravenously or intratumorally. This review also discusses current strategies for improving intratumoral transport and specificity of viral vectors.

The mitochondrial toxin, 3-nitropropionic acid, induces extracellular Zn2+ accumulation in rat hippocampus slices.

Science.gov (United States)

Wei, Guo; Hough, Christopher J; Sarvey, John M

2004-11-11

3-nitropropionic acid (3-NPA), a suicide inhibitor of succinate dehydrogenase (SDH; complex II), has been used to provide useful experimental models of Huntington's disease (HD) and "chemical hypoxia" in rodents. The trace ion Zn2+ has been shown to cause neurodegeneration. Employing real-time Newport Green fluorescence imaging of extracellular Zn2+, we found that 3-NPA (10-100 microM) caused a concentration-dependent increase in the concentration of extracellular Zn2+ ([Zn2+]o) in acute rat hippocampus slices. This increase in [Zn2+]o was abolished by 10 mM CaEDTA. The increase of [Zn2+]o was also accompanied by a rapid increase of cytoplasmic-free Zn2+ concentration ([Zn2+]i). The induction of Zn2+ release by 3-MPA in hippocampus slices points to a potential mechanism by which 3-NPA might induce neurodegeneration.

MR imaging of intracellular and extracellular deoxyhemoglobin

International Nuclear Information System (INIS)

Janick, P.A.; Grossman, R.I.; Asakura, T.

1989-01-01

MR imaging was performed on varying concentrations of intracellular and extracellular deoxyhemoglobin as well as varying proportions of deoxyhemoglobin and oxyhemoglobin in vitro at 1.5T with use of standard spin-echo and gradient-refocused spin sequences. This study indicates that susceptibility-induced T2 shortening occurs over a broad range of intracellular deoxyhemoglobin concentrations (maximal at hematocrits between 20% and 45%), reflecting diffusional effects at the cellular level. T2* gradient-echo imaging enhances the observed hypointensity in images of intracellular deoxyhemoglobin. The characteristic MR appearance of acute hemotomas can be modeled by the behavior of intracellular and extracellular deoxyhemoglobin and oxyhemoglobin

Electric Potential and Electric Field Imaging with Dynamic Applications: 2017 Research Award Innovation

Science.gov (United States)

Generazio, Ed

2017-01-01

The technology and methods for remote quantitative imaging of electrostatic potentials and electrostatic fields in and around objects and in free space is presented. Electric field imaging (EFI) technology may be applied to characterize intrinsic or existing electric potentials and electric fields, or an externally generated electrostatic field may be used for illuminating volumes to be inspected with EFI. The baseline sensor technology (e-Sensor) and its construction, optional electric field generation (quasi-static generator), and current e- Sensor enhancements (ephemeral e-Sensor) are discussed. Critical design elements of current linear and real-time two-dimensional (2D) measurement systems are highlighted, and the development of a three dimensional (3D) EFI system is presented. Demonstrations for structural, electronic, human, and memory applications are shown. Recent work demonstrates that phonons may be used to create and annihilate electric dipoles within structures. Phonon induced dipoles are ephemeral and their polarization, strength, and location may be quantitatively characterized by EFI providing a new subsurface Phonon-EFI imaging technology. Initial results from real-time imaging of combustion and ion flow, and their measurement complications, will be discussed. These new EFI capabilities are demonstrated to characterize electric charge distribution creating a new field of study embracing areas of interest including electrostatic discharge (ESD) mitigation, crime scene forensics, design and materials selection for advanced sensors, combustion science, on-orbit space potential, container inspection, remote characterization of electronic circuits and level of activation, dielectric morphology of structures, tether integrity, organic molecular memory, atmospheric science, and medical diagnostic and treatment efficacy applications such as cardiac polarization wave propagation and electromyography imaging.

Extracellular facile biosynthesis, characterization and stability of gold nanoparticles by Bacillus licheniformis.

Science.gov (United States)

Singh, Sneha; Vidyarthi, Ambarish Sharan; Nigam, Vinod Kumar; Dev, Abhimanyu

2014-02-01

The development of a reliable, eco-friendly process for synthesis of gold nanoparticles (AuNPs) has gained impetus in recent years to counter the drawbacks of chemical and physical methods. This study illustrates simple, green synthesis of AuNPs in vitro using cell lysate supernatant (CLS) of non-pathogenic bacteria and to investigate its potential antimicrobial activity. Gold nanoparticles were synthesized by the reduction of precursor AuCl4- ions using the CLS of Bacillus licheniformis at 37°C upon 24 h of incubation. The nanoparticles were characterized for their morphology, particle size, optical absorption, zeta potential, and stability. Further the antimicrobial activity was assayed using cup-plate method. The process of biosynthesis was extracellular and the gold ions were reduced to stable nanogold of average size 38 nm. However, upon storage of AuNPs for longer duration at room temperature stability was influenced in terms of increase in particle size and decrease in zeta potential with respect to as synthesized nanoparticles. SEM micrographs revealed the spherical shape of AuNPs and EDX analysis confirmed the presence of gold in the sample. Also clear zone of inhibition was observed against Bacilllus subtilis MTCC 8364, Pseudomonas aeruginosa MTCC 7925, and Escherichia coli MTCC 1698 confirming the antimicrobial activity of AuNPs. The bioprocess under study was simple and less time consuming as compared to other methods as the need for harvesting AuNPs from within the microbial cells via downstream process will be eliminated. Nanoparticles exhibited good stability even in absence of external stabilizing agents. AuNPs showed good antimicrobial activity against several Gram-negative and Gram-positive pathogenic bacteria. The extracellular biosynthesis from CLS may serve as a suitable alternative for large scale synthesis of gold nanoparticles in vitro. The synthesis from lysed bacterial cell strongly suggests that exposure of microbial whole cells to the

Exact time-dependent exchange-correlation potentials for strong-field electron dynamics

International Nuclear Information System (INIS)

Lein, Manfred; Kuemmel, Stephan

2005-01-01

By solving the time-dependent Schroedinger equation and inverting the time-dependent Kohn-Sham scheme we obtain the exact time-dependent exchange-correlation potential of density-functional theory for the strong-field dynamics of a correlated system. We demonstrate that essential features of the exact exchange-correlation potential can be related to derivative discontinuities in stationary density-functional theory. Incorporating the discontinuity in a time-dependent density-functional calculation greatly improves the description of the ionization process

Drift motion of a charged particle in the crossed axial magnetic and radial electric fields, and the electric field of a rotating potential wave

International Nuclear Information System (INIS)

Eliseev, Yu.N.; Stepanov, K.N.

1983-01-01

In the drift motion approximation solution of the problem is obtained on the motion of a nonrelativistic charged particle in the crossed axial magnetic and radial electric fields, and the electric field of a rotating potential wave under cherenkov and modified cyclotron resonances. The static radial electric field potential is supposed to be close to the parabolic one. The drift motion equations and their integrals are preseOted. The experimentally obtained effect of plasma ionic component division in the crossed fields under the excitation of ion cyclotron oscillations is explained with the help of the theory developed in the paper

* Tissue-Specific Extracellular Matrix Enhances Skeletal Muscle Precursor Cell Expansion and Differentiation for Potential Application in Cell Therapy.

Science.gov (United States)

Zhang, Deying; Zhang, Yong; Zhang, Yuanyuan; Yi, Hualin; Wang, Zhan; Wu, Rongpei; He, Dawei; Wei, Guanghui; Wei, Shicheng; Hu, Yun; Deng, Junhong; Criswell, Tracy; Yoo, James; Zhou, Yu; Atala, Anthony

2017-08-01

Skeletal muscle precursor cells (MPCs) are considered a key candidate for cell therapy in the treatment of skeletal muscle dysfunction due to injury, disease, or age. However, expansion of a sufficient number of functional skeletal muscle cells in vitro from a small tissue biopsy has been challenging due to changes in phenotypic expression of these cells under traditional culture conditions. Thus, the aim of the study was to develop a better culture system for the expansion and myo-differentiation of MPCs that could further be used for therapy. For this purpose, we developed an ideal method of tissue decellularization and compared the ability of different matrices to support MPC growth and differentiation. Porcine-derived skeletal muscle and liver and kidney extracellular matrix (ECM) were generated by decellularization methods consisting of distilled water, 0.2 mg/mL DNase, or 5% fetal bovine serum. Acellular matrices were further homogenized, dissolved, and combined with a hyaluronic acid-based hydrogel decorated with heparin (ECM-HA-HP). The cell proliferation and myogenic differentiation capacity of human MPCs were assessed when grown on gel alone, ECM, or each ECM-HA-HP substrate. Human MPC proliferation was significantly enhanced when cultured on the ECM-HA-HP substrates compared to the other substrates tested, with the greatest proliferation on the muscle ECM-HA-HP (mECM-HA-HP) substrate. The number of differentiated myotubes was significantly increased on the mECM-HA-HP substrate compared to the other gel-ECM substrates, as well as the numbers of MPCs expressing specific myogenic cell markers (i.e., myosin, desmin, myoD, and myf5). In conclusion, skeletal mECM-HA-HP as a culture substrate provided an optimal culture microenvironment potentially due to its similarity to the in vivo environment. These data suggest a potential use of skeletal muscle-derived ECM gel for the expansion and differentiation of human MPCs for cell-based therapy for skeletal muscle

Influence of external magnetic field, finite-size effects and chemical potential on the phase transition of a complex scalar field

Energy Technology Data Exchange (ETDEWEB)

Cavalcanti, E.; Castro, E.; Malbouisson, A.P.C. [Centro Brasileiro de Pesquisas Fisicas/MCTI, Rio de Janeiro, RJ (Brazil); Linhares, C.A. [Universidade do Estado do Rio de Janeiro, Instituto de Fisica, Rio de Janeiro, RJ (Brazil)

2017-10-15

A scalar model is built, as a quantum field theory defined on a toroidal topology, to describe a phase transition in films subjected to periodic boundary conditions and influenced by an external and constant magnetic field. Criticality is studied and the relations between the critical temperature, the film thickness, the magnetic field strength and the chemical potential are investigated. Since the model describes a second-order phase transition a comparison with the Ginzburg-Landau theory is made. (orig.)

Spherical Magnetic Vortex in an External Potential Field: A Dissipative Contraction

Science.gov (United States)

Solov'ev, A. A.

2013-09-01

We consider the dissipative evolution of a spherical magnetic vortex with a force-free internal structure, located in a resistive medium and held in equilibrium by the potential external field. The magnetic field inside the sphere is force-free (the model of Chandrasekhar in Proc. Natl. Acad. Sci. 42, 1, 1956). Topologically, it is a set of magnetic toroids enclosed in spherical layers. A new exact MHD solution has been derived, describing a slow, uniform, radial compression of a magnetic spheroid under the pressure of an ambient field, when the plasma density and pressure are growing inside it. There is no dissipation in the potential field outside the sphere, but inside the sphere, where the current density can be high enough, the magnetic energy is continuously converted into heat. Joule dissipation lowers the magnetic pressure inside the sphere, which balances the pressure of the ambient field. This results in radial contraction of the magnetic sphere with a speed defined by the conductivity of the plasma and the characteristic spatial scale of the magnetic field inside the sphere. Formally, the sphere shrinks to zero within a finite time interval (magnetic collapse). The time of compression can be relatively small, within a day, even for a sphere with a radius of about 1 Mm, if the magnetic helicity trapped initially in the sphere (which is proportional to the number of magnetic toroids in the sphere) is quite large. The magnetic system is open along its axis of symmetry. On this axis, the magnetic and electric fields are strictly radial and sign-variable along the radius, so the plasma will be ejected along the axis of magnetic sphere outwards in both directions (as jets) at a rate much higher than the diffusive one, and the charged particles will be accelerated unevenly, in spurts, creating quasi-regular X-ray spikes. The applications of the solution to solar flares are discussed.

Insights into the Diagnostic Potential of Extracellular Vesicles and Their miRNA Signature from Liquid Biopsy as Early Biomarkers of Diabetic Micro/Macrovascular Complications.

Science.gov (United States)

La Marca, Valeria; Fierabracci, Alessandra

2017-09-14

Extracellular vesicles (EVs) represent a heterogeneous population of small vesicles, consisting of a phospholipidic bilayer surrounding a soluble interior cargo. Almost all cell types release EVs, thus they are naturally present in all body fluids. Among the several potential applications, EVs could be used as drug delivery vehicles in disease treatment, in immune therapy because of their immunomodulatory properties and in regenerative medicine. In addition to general markers, EVs are characterized by the presence of specific biomarkers (proteins and miRNAs) that allow the identification of their cell or tissue origin. For these features, they represent a potential powerful diagnostic tool to monitor state and progression of specific diseases. A large body of studies supports the idea that endothelial derived (EMPs) together with platelet-derived microparticles (PMPs) are deeply involved in the pathogenesis of diseases characterized by micro- and macrovascular damages, including diabetes. Existing literature suggests that the detection of circulating EMPs and PMPs and their specific miRNA profile may represent a very useful non-invasive signature to achieve information on the onset of peculiar disease manifestations. In this review, we discuss the possible utility of EVs in the early diagnosis of diabetes-associated microvascular complications, specifically related to kidney.

Extracellular matrix organization in various regions of rat brain grey matter.

Science.gov (United States)

Brückner, G; Härtig, W; Kacza, J; Seeger, J; Welt, K; Brauer, K

1996-05-01

Previous studies revealed the concentration of extracellular matrix proteoglycans in the so-called perineuronal nets on the one hand and in certain zones of the neuropil on the other. This nonhomogeneous distribution suggested a non-random chemical and spatial heterogeneity of the extracellular space. In the present investigation, regions dominated by one of both distribution patterns, i.e. piriform and parietal cortex, reticular thalamic nucleus, medial septum/diagonal band complex and cerebellar nuclei, were selected for correlative light and electron microscopic analysis. The labelling was performed by the use of the N-acetylgalactosamine-binding plant lectin Wisteria floribunda agglutinin visualized by peroxidase staining and additionally by photoconversion of red carbocyanine fluorescence labelling for electron microscopy. The intense labelling of the neuropil of a superficial piriform region, presumably identical with sublayer Ia, was confined to a fine meshwork spreading over the extracellular space between non-myelinated axons, dendrites and glial profiles. In the reticular thalamic nucleus the neuronal cell bodies were embedded in zones of labelled neuropil. In contrast to these patterns, the labelled extracellular matrix in different cortical layers and in the other subcortical regions was concentrated in perineuronal nets as large accumulations at surface areas of the neuronal perikarya and dendrites and the attached presynaptic boutons. Astrocytic processes usually were separated from the neuronal surface by the interposed extracellular material. Despite a great variability, the width of the extracellular space containing the labelled matrix components in all perineuronal nets appeared to be considerably larger than that in the labelled zones of neuropil and the non-labelled microenvironment of other neurons. Our results support the view that differences expressed in topographical and spatial peculiarities of the extracellular matrix constituents are

Liver nodules. MR imaging using extracellular gadolinium agent

International Nuclear Information System (INIS)

Yoshimitsu, Kengo; Honda, Hiroshi

2009-01-01

Extracellular gadolinium (Gd)-containing contrast medium, including gadopentetate dimeglumine (Gd-DTPA), has been playing a main role in the diagnostic MR imaging of the liver. Its significance is two-fold: assessment of the degree of neovascularity or angiogenesis in its early dynamic phase, and that of bulk of interstitium in its equilibrium phase. With the advent of gadolinium ethoxybenzyl diethylenetriamine-pentaacetic acid (Gd-EOB-DTPA), which can be used as a dynamic study agent by bolus injection in addition to its original use as a tissue-specific agent, some possibility has been suggested that extracellular Gd agent would be no longer available in the near future in the field of liver MR imaging. Neovascularity or arterial supply of a lesion may well be assessed by Gd-EOB-DTPA, when carefully selected pulse sequence and well designed injection protocol are used, as well as by Gd-DTPA. However, the pertinent assessment of interstitium or stroma can never be achieved by Gd-EOB-DTPA or any other contrast medium present. The interstitium of neoplasm, typically called as stromal fibrosis, is generated through the interaction between the neoplasm per se and its host, and its clinicopathological significance related to disease prognosis has well been established in some disease entities. Extracellular Gd agent is the only contrast medium that can provide information regarding the tumor stroma in a simple, easy, safe and non-invasive fashion, when properly used. This review article discusses, dynamic MR imaging features of representative liver diseases, including several recent topics. From technical point of view, 3D gradient-echo sequence with fat suppression should be used for dynamic studies along with tailored injection protocol using autoinjector and saline flush. Vascularity of hepatocellular carcinoma (HCC) can now be properly assessed by dynamic MR with approximately 90% concordance with CT during hepatic arteriography. Portal phase images can be used to

Dopamine transporters govern diurnal variation in extracellular dopamine tone

OpenAIRE

Ferris, Mark J.; España, Rodrigo A.; Locke, Jason L.; Konstantopoulos, Joanne K.; Rose, Jamie H.; Chen, Rong; Jones, Sara R.

2014-01-01

The mechanism for diurnal (i.e., light/dark) oscillations in extracellular dopamine tone in mesolimbic and nigrostriatal systems is unknown. This is because, unlike other neurotransmitter systems, variation in dopamine tone does not correlate with variation in dopamine cell firing. The current research pinpoints the dopamine transporter as a critical governor of diurnal variation in both extracellular dopamine tone and the intracellular availability of releasable dopamine. These data describe...

Human galectins induce conversion of dermal fibroblasts into myofibroblasts and production of extracellular matrix: potential application in tissue engineering and wound repair

Czech Academy of Sciences Publication Activity Database

Dvořánková, B.; Szabo, P.; Lacina, L.; Gál, P.; Uhrová, J.; Zima, T.; Kaltner, H.; André, S.; Gabius, H. J.; Syková, Eva; Smetana Jr., K.

2011-01-01

Roč. 194, č. 6 (2011), s. 469-480 ISSN 1422-6405 Grant - others:GA MŠk(CZ) 1M0538 Program:1M Institutional research plan: CEZ:AV0Z50390703 Keywords : extracellular matrix * fibronectin * keratinocyte Subject RIV: FH - Neurology Impact factor: 2.203, year: 2011

Bubaline Cholecyst Derived Extracellular Matrix for Reconstruction of Full Thickness Skin Wounds in Rats

Directory of Open Access Journals (Sweden)

Poonam Shakya

2016-01-01

Full Text Available An acellular cholecyst derived extracellular matrix (b-CEM of bubaline origin was prepared using anionic biological detergent. Healing potential of b-CEM was compared with commercially available collagen sheet (b-CS and open wound (C in full thickness skin wounds in rats. Thirty-six clinically healthy adult Sprague Dawley rats of either sex were randomly divided into three equal groups. Under general anesthesia, a full thickness skin wound (20 × 20 mm2 was created on the dorsum of each rat. The defect in group I was kept as open wound and was taken as control. In group II, the defect was repaired with commercially available collagen sheet (b-CS. In group III, the defect was repaired with cholecyst derived extracellular matrix of bovine origin (b-CEM. Planimetry, wound contracture, and immunological and histological observations were carried out to evaluate healing process. Significantly (P<0.05 increased wound contraction was observed in b-CEM (III as compared to control (I and b-CS (II on day 21. Histologically, improved epithelization, neovascularization, fibroplasia, and best arranged collagen fibers were observed in b-CEM (III as early as on postimplantation day 21. These findings indicate that b-CEM have potential for biomedical applications for full thickness skin wound repair in rats.

The role of extracellular proteolysis in synaptic plasticity of the central nervous system 

Directory of Open Access Journals (Sweden)

Anna Konopka

2012-11-01

Full Text Available The extracellular matrix (ECM of the central nervous system has a specific structure and protein composition that are different from those in other organs. Today we know that the ECM not only provides physical scaffolding for the neurons and glia, but also actively modifies their functions. Over the last two decades, a growing body of research evidence has been collected, suggesting an important role of ECM proteolysis in synaptic plasticity of the brain. So far the majority of data concern two large families of proteases: the serine proteases and the matrix metalloproteinases. The members of these families are localized at the synapses, and are secreted into the extracellular space in an activity-dependent manner. The proteases remodel the local environment as well as influencing synapse structure and function. The structural modifications induced by proteases include shape and size changes, as well as synapse elimination, and synaptogenesis. The functional changes include modifications of receptor function in the postsynaptic part of the synapse, as well as the potentiation or depression of neurotransmitter secretion by the presynaptic site. The present review summarizes the current view on the role of extracellular proteolysis in the physiological synaptic plasticity underlying the phenomena of learning and memory, as well as in the pathological plasticity occurring during epileptogenesis or development of drug addiction. 

Extracellular acidification synergizes with PDGF to stimulate migration of mouse embryo fibroblasts through activation of p38MAPK with a PTX-sensitive manner

International Nuclear Information System (INIS)

An, Caiyan; Sato, Koichi; Wu, Taoya; Bao, Muqiri; Bao, Liang; Tobo, Masayuki; Damirin, Alatangaole

2015-01-01

The elucidation of the functional mechanisms of extracellular acidification stimulating intracellular signaling pathway is of great importance for developing new targets of treatment for solid tumors, and inflammatory disorders characterized by extracellular acidification. In the present study, we focus on the regulation of extracellular acidification on intracellular signaling pathways in mouse embryo fibroblasts (MEFs). We found extracellular acidification was at least partly involved in stimulating p38MAPK pathway through PTX-sensitive behavior to enhance cell migration in the presence or absence of platelet-derived growth factor (PDGF). Statistical analysis showed that the actions of extracellular acidic pH and PDGF on inducing enhancement of cell migration were not an additive effect. However, we also found extracellular acidic pH did inhibit the viability and proliferation of MEFs, suggesting that extracellular acidification stimulates cell migration probably through proton-sensing mechanisms within MEFs. Using OGR1-, GPR4-, and TDAG8-gene knock out technology, and real-time qPCR, we found known proton-sensing G protein-coupled receptors (GPCRs), transient receptor potential vanilloid subtype 1 (TRPV1), and acid-sensing ion channels (ASICs) were unlikely to be involved in the regulation of acidification on cell migration. In conclusion, our present study validates that extracellular acidification stimulates chemotactic migration of MEFs through activation of p38MAPK with a PTX-sensitive mechanism either by itself, or synergistically with PDGF, which was not regulated by the known proton-sensing GPCRs, TRPV1, or ASICs. Our results suggested that others proton-sensing GPCRs or ion channels might exist in MEFs, which mediates cell migration induced by extracellular acidification in the presence or absence of PDGF. - Highlights: • Acidic pH and PDGF synergize to stimulate MEFs migration via Gi/p38MAPK pathway. • Extracellular acidification inhibits the

Extracellular acidification synergizes with PDGF to stimulate migration of mouse embryo fibroblasts through activation of p38MAPK with a PTX-sensitive manner

Energy Technology Data Exchange (ETDEWEB)

An, Caiyan [Department of Biochemistry and Molecular Biology, College of Life Sciences, Inner Mongolia University, Hohhot, Inner Mongolia (China); Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi (Japan); Clinical Medicine Research Center of the Affiliated Hospital, Inner Mongolia Medical University, Hohhot, Inner Mongolia (China); Sato, Koichi [Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi (Japan); Wu, Taoya; Bao, Muqiri; Bao, Liang [Department of Biochemistry and Molecular Biology, College of Life Sciences, Inner Mongolia University, Hohhot, Inner Mongolia (China); Tobo, Masayuki [Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi (Japan); Damirin, Alatangaole, E-mail: bigaole@imu.edu.cn [Department of Biochemistry and Molecular Biology, College of Life Sciences, Inner Mongolia University, Hohhot, Inner Mongolia (China)

2015-05-01

The elucidation of the functional mechanisms of extracellular acidification stimulating intracellular signaling pathway is of great importance for developing new targets of treatment for solid tumors, and inflammatory disorders characterized by extracellular acidification. In the present study, we focus on the regulation of extracellular acidification on intracellular signaling pathways in mouse embryo fibroblasts (MEFs). We found extracellular acidification was at least partly involved in stimulating p38MAPK pathway through PTX-sensitive behavior to enhance cell migration in the presence or absence of platelet-derived growth factor (PDGF). Statistical analysis showed that the actions of extracellular acidic pH and PDGF on inducing enhancement of cell migration were not an additive effect. However, we also found extracellular acidic pH did inhibit the viability and proliferation of MEFs, suggesting that extracellular acidification stimulates cell migration probably through proton-sensing mechanisms within MEFs. Using OGR1-, GPR4-, and TDAG8-gene knock out technology, and real-time qPCR, we found known proton-sensing G protein-coupled receptors (GPCRs), transient receptor potential vanilloid subtype 1 (TRPV1), and acid-sensing ion channels (ASICs) were unlikely to be involved in the regulation of acidification on cell migration. In conclusion, our present study validates that extracellular acidification stimulates chemotactic migration of MEFs through activation of p38MAPK with a PTX-sensitive mechanism either by itself, or synergistically with PDGF, which was not regulated by the known proton-sensing GPCRs, TRPV1, or ASICs. Our results suggested that others proton-sensing GPCRs or ion channels might exist in MEFs, which mediates cell migration induced by extracellular acidification in the presence or absence of PDGF. - Highlights: • Acidic pH and PDGF synergize to stimulate MEFs migration via Gi/p38MAPK pathway. • Extracellular acidification inhibits the

Quantitative modeling of clinical, cellular, and extracellular matrix variables suggest prognostic indicators in cancer: a model in neuroblastoma.

Science.gov (United States)

Tadeo, Irene; Piqueras, Marta; Montaner, David; Villamón, Eva; Berbegall, Ana P; Cañete, Adela; Navarro, Samuel; Noguera, Rosa

2014-02-01

Risk classification and treatment stratification for cancer patients is restricted by our incomplete picture of the complex and unknown interactions between the patient's organism and tumor tissues (transformed cells supported by tumor stroma). Moreover, all clinical factors and laboratory studies used to indicate treatment effectiveness and outcomes are by their nature a simplification of the biological system of cancer, and cannot yet incorporate all possible prognostic indicators. A multiparametric analysis on 184 tumor cylinders was performed. To highlight the benefit of integrating digitized medical imaging into this field, we present the results of computational studies carried out on quantitative measurements, taken from stromal and cancer cells and various extracellular matrix fibers interpenetrated by glycosaminoglycans, and eight current approaches to risk stratification systems in patients with primary and nonprimary neuroblastoma. New tumor tissue indicators from both fields, the cellular and the extracellular elements, emerge as reliable prognostic markers for risk stratification and could be used as molecular targets of specific therapies. The key to dealing with personalized therapy lies in the mathematical modeling. The use of bioinformatics in patient-tumor-microenvironment data management allows a predictive model in neuroblastoma.

Gravitational and electromagnetic potentials of the stationary Einstein-Maxwell field equations

International Nuclear Information System (INIS)

Jones, T.C.

1979-01-01

Associated with the stationary Einstein-Maxwell field equations is an infinite hierarchy of potentials. The basic characteristics of these potentials are examined in general and then in greater detail for the particular case of the Reissner-Nordstrom metric. Thier essential utility in the process of solution generation is elucidated, and the necessary equations for solution generation are developed. Appropriate generating functions, which contain the complete infinite hierarchy of potentials, are developed and analyzed. Particular attention is paid to the inherent gauge freedom of these generating functions. Two methods of solution generation, which yield asymptotically flat solutions in vacuum, are generalized to include electromagnetism. One method, using potentials consistent with the Harrison transformation and the Reissner-Nordstrom metric, is discussed in detail, and its resultant difficulties are explored

EVpedia: an integrated database of high-throughput data for systemic analyses of extracellular vesicles

Directory of Open Access Journals (Sweden)

Dae-Kyum Kim

2013-03-01

Full Text Available Secretion of extracellular vesicles is a general cellular activity that spans the range from simple unicellular organisms (e.g. archaea; Gram-positive and Gram-negative bacteria to complex multicellular ones, suggesting that this extracellular vesicle-mediated communication is evolutionarily conserved. Extracellular vesicles are spherical bilayered proteolipids with a mean diameter of 20–1,000 nm, which are known to contain various bioactive molecules including proteins, lipids, and nucleic acids. Here, we present EVpedia, which is an integrated database of high-throughput datasets from prokaryotic and eukaryotic extracellular vesicles. EVpedia provides high-throughput datasets of vesicular components (proteins, mRNAs, miRNAs, and lipids present on prokaryotic, non-mammalian eukaryotic, and mammalian extracellular vesicles. In addition, EVpedia also provides an array of tools, such as the search and browse of vesicular components, Gene Ontology enrichment analysis, network analysis of vesicular proteins and mRNAs, and a comparison of vesicular datasets by ortholog identification. Moreover, publications on extracellular vesicle studies are listed in the database. This free web-based database of EVpedia (http://evpedia.info might serve as a fundamental repository to stimulate the advancement of extracellular vesicle studies and to elucidate the novel functions of these complex extracellular organelles.

A genetically encoded ratiometric sensor to measure extracellular pH in microdomains bounded by basolateral membranes of epithelial cells.

Science.gov (United States)

Urra, Javier; Sandoval, Moisés; Cornejo, Isabel; Barros, L Felipe; Sepúlveda, Francisco V; Cid, L Pablo

2008-10-01

Extracellular pH, especially in relatively inaccessible microdomains between cells, affects transport membrane protein activity and might have an intercellular signaling role. We have developed a genetically encoded extracellular pH sensor capable of detecting pH changes in basolateral spaces of epithelial cells. It consists of a chimerical membrane protein displaying concatenated enhanced variants of cyan fluorescence protein (ECFP) and yellow fluorescence protein (EYFP) at the external aspect of the cell surface. The construct, termed pHCECSensor01, was targeted to basolateral membranes of Madin-Darby canine kidney (MDCK) cells by means of a sequence derived from the aquaporin AQP4. The fusion of pH-sensitive EYFP with pH-insensitive ECFP allows ratiometric pH measurements. The titration curve of pHCECSensor01 in vivo had a pK (a) value of 6.5 +/- 0.04. Only minor effects of extracellular chloride on pHCECSensor01 were observed around the physiological concentrations of this anion. In MDCK cells, the sensor was able to detect changes in pH secondary to H(+) efflux into the basolateral spaces elicited by an ammonium prepulse or lactate load. This genetically encoded sensor has the potential to serve as a noninvasive tool for monitoring changes in extracellular pH microdomains in epithelial and other tissues in vivo.

On-orbit assembly of a team of flexible spacecraft using potential field based method

Science.gov (United States)

Chen, Ti; Wen, Hao; Hu, Haiyan; Jin, Dongping

2017-04-01

In this paper, a novel control strategy is developed based on artificial potential field for the on-orbit autonomous assembly of four flexible spacecraft without inter-member collision. Each flexible spacecraft is simplified as a hub-beam model with truncated beam modes in the floating frame of reference and the communication graph among the four spacecraft is assumed to be a ring topology. The four spacecraft are driven to a pre-assembly configuration first and then to the assembly configuration. In order to design the artificial potential field for the first step, each spacecraft is outlined by an ellipse and a virtual leader of circle is introduced. The potential field mainly depends on the attitude error between the flexible spacecraft and its neighbor, the radial Euclidian distance between the ellipse and the circle and the classical Euclidian distance between the centers of the ellipse and the circle. It can be demonstrated that there are no local minima for the potential function and the global minimum is zero. If the function is equal to zero, the solution is not a certain state, but a set. All the states in the set are corresponding to the desired configurations. The Lyapunov analysis guarantees that the four spacecraft asymptotically converge to the target configuration. Moreover, the other potential field is also included to avoid the inter-member collision. In the control design of the second step, only small modification is made for the controller in the first step. Finally, the successful application of the proposed control law to the assembly mission is verified by two case studies.

Isolation and characterization of urinary extracellular vesicles: implications for biomarker discovery

NARCIS (Netherlands)

Merchant, M.L.; Rood, I.M.; Deegens, J.K.J.; Klein, J.B.

2017-01-01

Urine is a valuable diagnostic medium and, with the discovery of urinary extracellular vesicles, is viewed as a dynamic bioactive fluid. Extracellular vesicles are lipid-enclosed structures that can be classified into three categories: exosomes, microvesicles (or ectosomes) and apoptotic bodies.

The influence of extracellular superoxide on iron redox chemistry and bioavailability to aquatic microorganisms

Directory of Open Access Journals (Sweden)

Andrew eRose

2012-04-01

Full Text Available Superoxide, the one-electron reduced form of dioxygen, is produced in the extracellular milieu of aquatic microbes through a range of abiotic chemical processes and also by microbes themselves. Due to its ability to promote both oxidative and reductive reactions, superoxide may have a profound impact on the redox state of iron, potentially influencing iron solubility, complex speciation and bioavailability. The interplay between iron, superoxide and oxygen may also produce a cascade of other highly reactive transients in oxygenated natural waters. For microbes, the overall effect of reactions between superoxide and iron may be deleterious or beneficial, depending on the organism and its chemical environment. Here I critically discuss recent advances in understanding: (i sources of extracellular superoxide in natural waters, with a particular emphasis on microbial generation; (ii the chemistry of reactions between superoxide and iron; and (iii the influence of these processes on iron bioavailability and microbial iron nutrition.

A NEW TECHNIQUE FOR THE PHOTOSPHERIC DRIVING OF NON-POTENTIAL SOLAR CORONAL MAGNETIC FIELD SIMULATIONS

Energy Technology Data Exchange (ETDEWEB)

Weinzierl, Marion; Yeates, Anthony R. [Department of Mathematical Sciences, Durham University, South Road, Durham DH1 3LE (United Kingdom); Mackay, Duncan H. [School of Mathematics and Statistics, University of St. Andrews, North Haugh, St. Andrews, Fife KY16 9SS (United Kingdom); Henney, Carl J.; Arge, C. Nick, E-mail: marion.weinzierl@durham.ac.uk [Air Force Research Lab/Space Vehicles Directorate, 3550 Aberdeen Avenue SE, Kirtland AFB, NM (United States)

2016-05-20

In this paper, we develop a new technique for driving global non-potential simulations of the Sun’s coronal magnetic field solely from sequences of radial magnetic maps of the solar photosphere. A primary challenge to driving such global simulations is that the required horizontal electric field cannot be uniquely determined from such maps. We show that an “inductive” electric field solution similar to that used by previous authors successfully reproduces specific features of the coronal field evolution in both single and multiple bipole simulations. For these cases, the true solution is known because the electric field was generated from a surface flux-transport model. The match for these cases is further improved by including the non-inductive electric field contribution from surface differential rotation. Then, using this reconstruction method for the electric field, we show that a coronal non-potential simulation can be successfully driven from a sequence of ADAPT maps of the photospheric radial field, without including additional physical observations which are not routinely available.

High-level extracellular protein production in Bacillus subtilis using an optimized dual-promoter expression system.

Science.gov (United States)

Zhang, Kang; Su, Lingqia; Duan, Xuguo; Liu, Lina; Wu, Jing

2017-02-20

We recently constructed a Bacillus subtilis strain (CCTCC M 2016536) from which we had deleted the srfC, spoIIAC, nprE, aprE and amyE genes. This strain is capable of robust recombinant protein production and amenable to high-cell-density fermentation. Because the promoter is among the factors that influence the production of target proteins, optimization of the initial promoter, P amyQ from Bacillus amyloliquefaciens, should improve protein expression using this strain. This study was undertaken to develop a new, high-level expression system in B. subtilis CCTCC M 2016536. Using the enzyme β-cyclodextrin glycosyltransferase (β-CGTase) as a reporter protein and B. subtilis CCTCC M 2016536 as the host, nine plasmids equipped with single promoters were screened using shake-flask cultivation. The plasmid containing the P amyQ' promoter produced the greatest extracellular β-CGTase activity; 24.1 U/mL. Subsequently, six plasmids equipped with dual promoters were constructed and evaluated using this same method. The plasmid containing the dual promoter P HpaII -P amyQ' produced the highest extracellular β-CGTase activity (30.5 U/mL) and was relatively glucose repressed. The dual promoter P HpaII -P amyQ' also mediated substantial extracellular pullulanase (90.7 U/mL) and α-CGTase expression (9.5 U/mL) during shake-flask cultivation, demonstrating the general applicability of this system. Finally, the production of β-CGTase using the dual-promoter P HpaII -P amyQ' system was investigated in a 3-L fermenter. Extracellular expression of β-CGTase reached 571.2 U/mL (2.5 mg/mL), demonstrating the potential of this system for use in industrial applications. The dual-promoter P HpaII -P amyQ' system was found to support superior expression of extracellular proteins in B. subtilis CCTCC M 2016536. This system appears generally applicable and is amenable to scale-up.

Neutrophil Extracellular Trap-Related Extracellular Histones Cause Vascular Necrosis in Severe GN.

Science.gov (United States)

Kumar, Santhosh V R; Kulkarni, Onkar P; Mulay, Shrikant R; Darisipudi, Murthy N; Romoli, Simone; Thomasova, Dana; Scherbaum, Christina R; Hohenstein, Bernd; Hugo, Christian; Müller, Susanna; Liapis, Helen; Anders, Hans-Joachim

2015-10-01

Severe GN involves local neutrophil extracellular trap (NET) formation. We hypothesized a local cytotoxic effect of NET-related histone release in necrotizing GN. In vitro, histones from calf thymus or histones released by neutrophils undergoing NETosis killed glomerular endothelial cells, podocytes, and parietal epithelial cells in a dose-dependent manner. Histone-neutralizing agents such as antihistone IgG, activated protein C, or heparin prevented this effect. Histone toxicity on glomeruli ex vivo was Toll-like receptor 2/4 dependent, and lack of TLR2/4 attenuated histone-induced renal thrombotic microangiopathy and glomerular necrosis in mice. Anti-glomerular basement membrane GN involved NET formation and vascular necrosis, whereas blocking NET formation by peptidylarginine inhibition or preemptive anti-histone IgG injection significantly reduced all aspects of GN (i.e., vascular necrosis, podocyte loss, albuminuria, cytokine induction, recruitment or activation of glomerular leukocytes, and glomerular crescent formation). To evaluate histones as a therapeutic target, mice with established GN were treated with three different histone-neutralizing agents. Anti-histone IgG, recombinant activated protein C, and heparin were equally effective in abrogating severe GN, whereas combination therapy had no additive effects. Together, these results indicate that NET-related histone release during GN elicits cytotoxic and immunostimulatory effects. Furthermore, neutralizing extracellular histones is still therapeutic when initiated in established GN. Copyright © 2015 by the American Society of Nephrology.

The potential for satellite and marginal field developments on the Norwegian continental shelf

International Nuclear Information System (INIS)

Raustein, O.; Abrahamsen, L.E.; Einang, G.

1994-01-01

Norway is faced with decreasing field sizes in hostile waters. On the other hand, approximately 620 billion 1993-NOK have been invested in field installations and transport systems. These installations will have significant available processing and transport capacity in the future, and thus represent a valuable infrastructure. This paper describes the resource situation and the installed infrastructure on the Norwegian Continental Shelf. Then the potential of still maintaining a high activity level in field developments is outlined

Optimization of the production of extracellular α-amylase by Kluyveromyces marxianus IF0 0288 by response surface methodology

Directory of Open Access Journals (Sweden)

Panagiota-Yiolanda Stergiou

2014-06-01

Full Text Available The aim of this work was to study the production of extracellular α-amylase by Kluyveromyces marxianus IF0 0288 using optimized nutritional and cultural conditions in a complex yeast medium under aerobic batch fermentation. By applying the conventional "one-variable-at-a-time" approach and the response surface methodology, the effect of four fermentation parameters (type of carbon source, initial culture pH, temperature, and incubation time on the growth and α-amylase production was evaluated. The production of α-amylase during 60 h of fermentation increased 13-fold under optimized conditions (1% starch, pH 6.0, 30ºC in comparison to the conventional optimization method. The initial pH value of 6.13 and temperature of 30.3ºC were optimal conditions by the response surface methodology, leading to further improvement (up to 13-fold in the production of extracellular α-amylase. These results constituted first evidence that K. marxianus could be potentially used as an effective source of extracellular α-amylase.

DMPD: Fragments of extracellular matrix as mediators of inflammation. [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available 18243041 Fragments of extracellular matrix as mediators of inflammation. Adair-Kirk...l) Show Fragments of extracellular matrix as mediators of inflammation. PubmedID 18243041 Title Fragments of... extracellular matrix as mediators of inflammation. Authors Adair-Kirk TL, Senior

Structural, biochemical, cellular, and functional changes in skeletal muscle extracellular matrix with aging

DEFF Research Database (Denmark)

Kragstrup, T W; Kjaer, M; Mackey, A L

2011-01-01

The extracellular matrix (ECM) of skeletal muscle is critical for force transmission and for the passive elastic response of skeletal muscle. Structural, biochemical, cellular, and functional changes in skeletal muscle ECM contribute to the deterioration in muscle mechanical properties with aging....... Structural changes include an increase in the collagen concentration, a change in the elastic fiber system, and an increase in fat infiltration of skeletal muscle. Biochemical changes include a decreased turnover of collagen with potential accumulation of enzymatically mediated collagen cross...

Autocrine signal transmission with extracellular ligand degradation

International Nuclear Information System (INIS)

Muratov, C B; Posta, F; Shvartsman, S Y

2009-01-01

Traveling waves of cell signaling in epithelial layers orchestrate a number of important processes in developing and adult tissues. These waves can be mediated by positive feedback autocrine loops, a mode of cell signaling where binding of a diffusible extracellular ligand to a cell surface receptor can lead to further ligand release. We formulate and analyze a biophysical model that accounts for ligand-induced ligand release, extracellular ligand diffusion and ligand–receptor interaction. We focus on the case when the main mode for ligand degradation is extracellular and analyze the problem with the sharp threshold positive feedback nonlinearity. We derive expressions that link the speed of propagation and other characteristics of traveling waves to the parameters of the biophysical processes, such as diffusion rates, receptor expression level, etc. Analyzing the derived expressions we found that traveling waves in such systems can exhibit a number of unusual properties, e.g. non-monotonic dependence of the speed of propagation on ligand diffusivity. Our results for the fully developed traveling fronts can be used to analyze wave initiation from localized perturbations, a scenario that frequently arises in the in vitro models of epithelial wound healing, and guide future modeling studies of cell communication in epithelial layers

Autocrine signal transmission with extracellular ligand degradation

Science.gov (United States)

Muratov, C B; Posta, F; Shvartsman, S Y

2009-03-01

Traveling waves of cell signaling in epithelial layers orchestrate a number of important processes in developing and adult tissues. These waves can be mediated by positive feedback autocrine loops, a mode of cell signaling where binding of a diffusible extracellular ligand to a cell surface receptor can lead to further ligand release. We formulate and analyze a biophysical model that accounts for ligand-induced ligand release, extracellular ligand diffusion and ligand-receptor interaction. We focus on the case when the main mode for ligand degradation is extracellular and analyze the problem with the sharp threshold positive feedback nonlinearity. We derive expressions that link the speed of propagation and other characteristics of traveling waves to the parameters of the biophysical processes, such as diffusion rates, receptor expression level, etc. Analyzing the derived expressions we found that traveling waves in such systems can exhibit a number of unusual properties, e.g. non-monotonic dependence of the speed of propagation on ligand diffusivity. Our results for the fully developed traveling fronts can be used to analyze wave initiation from localized perturbations, a scenario that frequently arises in the in vitro models of epithelial wound healing, and guide future modeling studies of cell communication in epithelial layers.

Stability Analysis and Variational Integrator for Real-Time Formation Based on Potential Field

Directory of Open Access Journals (Sweden)

Shengqing Yang

2014-01-01

Full Text Available This paper investigates a framework of real-time formation of autonomous vehicles by using potential field and variational integrator. Real-time formation requires vehicles to have coordinated motion and efficient computation. Interactions described by potential field can meet the former requirement which results in a nonlinear system. Stability analysis of such nonlinear system is difficult. Our methodology of stability analysis is discussed in error dynamic system. Transformation of coordinates from inertial frame to body frame can help the stability analysis focus on the structure instead of particular coordinates. Then, the Jacobian of reduced system can be calculated. It can be proved that the formation is stable at the equilibrium point of error dynamic system with the effect of damping force. For consideration of calculation, variational integrator is introduced. It is equivalent to solving algebraic equations. Forced Euler-Lagrange equation in discrete expression is used to construct a forced variational integrator for vehicles in potential field and obstacle environment. By applying forced variational integrator on computation of vehicles' motion, real-time formation of vehicles in obstacle environment can be implemented. Algorithm based on forced variational integrator is designed for a leader-follower formation.

Towards traceable size determination of extracellular vesicles

Directory of Open Access Journals (Sweden)

Zoltán Varga

2014-02-01

Full Text Available Background: Extracellular vesicles (EVs have clinical importance due to their roles in a wide range of biological processes. The detection and characterization of EVs are challenging because of their small size, low refractive index, and heterogeneity. Methods: In this manuscript, the size distribution of an erythrocyte-derived EV sample is determined using state-of-the-art techniques such as nanoparticle tracking analysis, resistive pulse sensing, and electron microscopy, and novel techniques in the field, such as small-angle X-ray scattering (SAXS and size exclusion chromatography coupled with dynamic light scattering detection. Results: The mode values of the size distributions of the studied erythrocyte EVs reported by the different methods show only small deviations around 130 nm, but there are differences in the widths of the size distributions. Conclusion: SAXS is a promising technique with respect to traceability, as this technique was already applied for traceable size determination of solid nanoparticles in suspension. To reach the traceable measurement of EVs, monodisperse and highly concentrated samples are required.

Cross-field flow and electric potential in a plasma slab

Directory of Open Access Journals (Sweden)

J. De Keyser

2013-08-01

Full Text Available We consider cross-field plasma flow inside a field-aligned plasma slab embedded in a uniform background in a 1-dimensional geometry. This situation may arise, for instance, when long-lasting reconnection pulses inject plasma into the inner magnetosphere. The present paper presents a detailed analysis of the structure of the interfaces that separate the slab from the background plasma on either side; a fully kinetic model is used to do so. Since the velocity shear across both interfaces has opposite signs, and given the typical gyroradius differences between injected and background ions and electrons, the structure of both interfaces can be very different. The behaviour of the slab and its interfaces depends critically on the flow of the plasma transverse to the magnetic field; in particular, it is shown that there are bounds to the flow speed that can be supported by the magnetised plasma. Further complicating the picture is the effect of the potential difference between the slab and its environment.

Effective field theory approaches for tensor potentials

Energy Technology Data Exchange (ETDEWEB)

Jansen, Maximilian

2016-11-14

Effective field theories are a widely used tool to study physical systems at low energies. We apply them to systematically analyze two and three particles interacting via tensor potentials. Two examples are addressed: pion interactions for anti D{sup 0}D{sup *0} scattering to dynamically generate the X(3872) and dipole interactions for two and three bosons at low energies. For the former, the one-pion exchange and for the latter, the long-range dipole force induce a tensor-like structure of the potential. We apply perturbative as well as non-perturbative methods to determine low-energy observables. The X(3872) is of major interest in modern high-energy physics. Its exotic characteristics require approaches outside the range of the quark model for baryons and mesons. Effective field theories represent such methods and provide access to its peculiar nature. We interpret the X(3872) as a hadronic molecule consisting of neutral D and D{sup *} mesons. It is possible to apply an effective field theory with perturbative pions. Within this framework, we address chiral as well as finite volume extrapolations for low-energy observables, such as the binding energy and the scattering length. We show that the two-point correlation function for the D{sup *0} meson has to be resummed to cure infrared divergences. Moreover, next-to-leading order coupling constants, which were introduced by power counting arguments, appear to be essential to renormalize the scattering amplitude. The binding energy as well as the scattering length display a moderate dependence on the light quark masses. The X(3872) is most likely deeper bound for large light quark masses. In a finite volume on the other hand, the binding energy significantly increases. The dependence on the light quark masses and the volume size can be simultaneously obtained. For bosonic dipoles we apply a non-perturbative, numerical approach. We solve the Lippmann-Schwinger equation for the two-dipole system and the Faddeev

Extracellular Gd-CA

DEFF Research Database (Denmark)

Thomsen, Henrik S; Marckmann, Peter

2008-01-01

Until recently it was believed that extracellular gadolinium-based contrast agents were safe for both the kidneys and all other organs within the dose range up to 0.3 mmol/kg body weight. However, in 2006, it was demonstrated that some gadolinium-based contrast agents may trig the development...... gadolinium-based agent (3-7% versus 0-1% per injection) in patients with reduced renal function. Prevalence after exposure to two gadodiamide injections is as high as 36% in patients with chronic kidney disease (CKD) stage 5. No report of NSF after the most stable agents has been reported in the peer...

On radiation of electrons moving in braking electric fields with distributed potential

International Nuclear Information System (INIS)

Fedulov, V.I.; Suvorov, V.I.; Umirov, U.R.

2002-01-01

The characteristics of radiation of electron moving in flat structures with braking electric field created by an accelerating electrode and another electrode with distributed potential are investigated. The analytical expressions for definition of conditions for complete loss of energy by electron in structure with distributed potential and for arising the electron vibrations are received. Also expressions connecting the electron energy with the point of entry and its fluctuation frequency are received. The mathematical model of irradiation process is offered depending on energy and point of entry of the electron. The connection between a radiation wave length and position of point of entry of electrons in the braking electric field are found. A possibility of emerging the optical radiation in solid environments at passage of charge particles through substance is shown. (author)

Incorporation of tenascin-C into the extracellular matrix by periostin underlies an extracellular meshwork architecture.

Science.gov (United States)

Kii, Isao; Nishiyama, Takashi; Li, Minqi; Matsumoto, Ken-Ichi; Saito, Mitsuru; Amizuka, Norio; Kudo, Akira

2010-01-15

Extracellular matrix (ECM) underlies a complicated multicellular architecture that is subjected to significant forces from mechanical environment. Although various components of the ECM have been enumerated, mechanisms that evolve the sophisticated ECM architecture remain to be addressed. Here we show that periostin, a matricellular protein, promotes incorporation of tenascin-C into the ECM and organizes a meshwork architecture of the ECM. We found that both periostin null mice and tenascin-C null mice exhibited a similar phenotype, confined tibial periostitis, which possibly corresponds to medial tibial stress syndrome in human sports injuries. Periostin possessed adjacent domains that bind to tenascin-C and the other ECM protein: fibronectin and type I collagen, respectively. These adjacent domains functioned as a bridge between tenascin-C and the ECM, which increased deposition of tenascin-C on the ECM. The deposition of hexabrachions of tenascin-C may stabilize bifurcations of the ECM fibrils, which is integrated into the extracellular meshwork architecture. This study suggests a role for periostin in adaptation of the ECM architecture in the mechanical environment.

Incorporation of Tenascin-C into the Extracellular Matrix by Periostin Underlies an Extracellular Meshwork Architecture*

Science.gov (United States)

Kii, Isao; Nishiyama, Takashi; Li, Minqi; Matsumoto, Ken-ichi; Saito, Mitsuru; Amizuka, Norio; Kudo, Akira

2010-01-01

Extracellular matrix (ECM) underlies a complicated multicellular architecture that is subjected to significant forces from mechanical environment. Although various components of the ECM have been enumerated, mechanisms that evolve the sophisticated ECM architecture remain to be addressed. Here we show that periostin, a matricellular protein, promotes incorporation of tenascin-C into the ECM and organizes a meshwork architecture of the ECM. We found that both periostin null mice and tenascin-C null mice exhibited a similar phenotype, confined tibial periostitis, which possibly corresponds to medial tibial stress syndrome in human sports injuries. Periostin possessed adjacent domains that bind to tenascin-C and the other ECM protein: fibronectin and type I collagen, respectively. These adjacent domains functioned as a bridge between tenascin-C and the ECM, which increased deposition of tenascin-C on the ECM. The deposition of hexabrachions of tenascin-C may stabilize bifurcations of the ECM fibrils, which is integrated into the extracellular meshwork architecture. This study suggests a role for periostin in adaptation of the ECM architecture in the mechanical environment. PMID:19887451

Use of UV-irradiated bacteriophage T6 to kill extracellular bacteria in tissue culture infectivity assays

International Nuclear Information System (INIS)

Shaw, D.R.; Maurelli, A.T.; Goguen, J.D.; Straley, S.C.; Curtiss, R. III

1983-01-01

The authors have utilized 'lysis from without' mediated by UV-inactivated bacteriophage T6 to eliminate extracellular bacteria in experiments measuring the internalization, intracellular survival and replication of Yersinia pestis within mouse peritoneal macrophages and of Shigella flexneri within a human intestinal epithelial cell line. The technique described has the following characteristics: (a) bacterial killing is complete within 15 min at 37 0 C, with a >10 3 -fold reduction in colony-forming units (CFU); (b) bacteria within cultured mammalian cells are protected from killing by UV-inactivated T6; (c) the mammalian cells are not observably affected by exposure to UV-inactivated T6. This technique has several advantages over the use of antibiotics to eliminate extracellular bacteria and is potentially widely applicable in studies of the interactions between pathogenic bacteria and host phagocytic cells as well as other target tissues. (Auth.)

Extracellular small heat shock proteins: exosomal biogenesis and function.

Science.gov (United States)

Reddy, V Sudhakar; Madala, Satish K; Trinath, Jamma; Reddy, G Bhanuprakash

2018-05-01

Small heat shock proteins (sHsps) belong to the family of heat shock proteins (Hsps): some are induced in response to multiple stressful events to protect the cells while others are constitutively expressed. Until now, it was believed that Hsps, including sHsps, are present inside the cells and perform intracellular functions. Interestingly, several groups recently reported the extracellular presence of Hsps, and sHsps have also been detected in sera/cerebrospinal fluids in various pathological conditions. Secretion into the extracellular milieu during many pathological conditions suggests additional or novel functions of sHsps in addition to their intracellular properties. Extracellular sHsps are implicated in cell-cell communication, activation of immune cells, and promoting anti-inflammatory and anti-platelet responses. Interestingly, exogenous administration of sHsps showed therapeutic effects in multiple disease models implying that extracellular sHsps are beneficial in pathological conditions. sHsps do not possess signal sequence and, hence, are not exported through the classical Endoplasmic reticulum-Golgi complex (ER-Golgi) secretory pathway. Further, export of sHsps is not inhibited by ER-Golgi secretory pathway inhibitors implying the involvement of a nonclassical secretory pathway in sHsp export. In lieu, lysoendosomal and exosomal pathways have been proposed for the export of sHsps. Heat shock protein 27 (Hsp27), αB-crystallin (αBC), and Hsp20 are shown to be exported by exosomes. Exosomes packaged with sHsps have beneficial effects in in vivo disease models. However, secretion mechanisms and therapeutic use of sHsps have not been elucidated in detail. Therefore, this review aimed at highlighting the current understanding of sHsps (Hsp27, αBC, and Hsp20) in the extracellular medium.

Magnetophoretic potential at the movement of cluster products of electrochemical reactions in an inhomogeneous magnetic field

International Nuclear Information System (INIS)

Gorobets, O. Yu.; Gorobets, Yu. I.; Rospotniuk, V. P.

2015-01-01

An electric field arises from the influence of a nonuniform static magnetic field on charged colloid particles with magnetic susceptibility different from that of the surrounding liquid. It arises, for example, under the influence of a nonuniform static magnetic field in clusters of electrochemical reaction products created during metal etching, deposition, and corrosion processes without an external electric current passing through an electrolyte near a magnetized electrode surface. The corresponding potential consists of a Nernst potential of inhomogeneous distribution of concentration of colloid particles and a magnetophoretic potential (MPP). This potential has been calculated using a thermodynamic approach based on the equations of thermodynamics of nonequilibrium systems and the Onsager relations for a mass flow of correlated magnetic clusters under a gradient magnetic force in the electrolyte. The conditions under which the MPP contribution to the total electric potential may be significant are discussed with a reference to the example of a corroding spherical ferromagnetic steel electrode

Magnetophoretic potential at the movement of cluster products of electrochemical reactions in an inhomogeneous magnetic field

Energy Technology Data Exchange (ETDEWEB)

Gorobets, O. Yu., E-mail: pitbm@ukr.net; Gorobets, Yu. I., E-mail: Gorobets@imag.kiev.ua [National Technical University of Ukraine “KPI”, Peremogy Avenue 37, Kyiv 03056 (Ukraine); Institute of Magnetism NAS of Ukraine and National Academy of Sciences of Ukraine, Vernadsky Avenue, 36-b, Kyiv 03142 (Ukraine); Rospotniuk, V. P. [National Technical University of Ukraine “KPI”, Peremogy Avenue 37, Kyiv 03056 (Ukraine)

2015-08-21

An electric field arises from the influence of a nonuniform static magnetic field on charged colloid particles with magnetic susceptibility different from that of the surrounding liquid. It arises, for example, under the influence of a nonuniform static magnetic field in clusters of electrochemical reaction products created during metal etching, deposition, and corrosion processes without an external electric current passing through an electrolyte near a magnetized electrode surface. The corresponding potential consists of a Nernst potential of inhomogeneous distribution of concentration of colloid particles and a magnetophoretic potential (MPP). This potential has been calculated using a thermodynamic approach based on the equations of thermodynamics of nonequilibrium systems and the Onsager relations for a mass flow of correlated magnetic clusters under a gradient magnetic force in the electrolyte. The conditions under which the MPP contribution to the total electric potential may be significant are discussed with a reference to the example of a corroding spherical ferromagnetic steel electrode.

The dynamic extracellular matrix: intervention strategies during heart failure and atherosclerosis

NARCIS (Netherlands)

Heeneman, Sylvia; Cleutjens, Jack P.; Faber, Birgit C.; Creemers, Esther E.; van Suylen, Robert-Jan; Lutgens, Esther; Cleutjens, Kitty B.; Daemen, Mat J.

2003-01-01

The extracellular matrix is no longer seen as the static embedding in which cells reside; it has been shown to be involved in cell proliferation, migration and cell-cell interactions. Turnover of the different extracellular matrix components is an active process with multiple levels of regulation.

Nanoparticle orientation to control RNA loading and ligand display on extracellular vesicles for cancer regression

Science.gov (United States)

Pi, Fengmei; Binzel, Daniel W.; Lee, Tae Jin; Li, Zhefeng; Sun, Meiyan; Rychahou, Piotr; Li, Hui; Haque, Farzin; Wang, Shaoying; Croce, Carlo M.; Guo, Bin; Evers, B. Mark; Guo, Peixuan

2018-01-01

Nanotechnology offers many benefits, and here we report an advantage of applying RNA nanotechnology for directional control. The orientation of arrow-shaped RNA was altered to control ligand display on extracellular vesicle membranes for specific cell targeting, or to regulate intracellular trafficking of small interfering RNA (siRNA) or microRNA (miRNA). Placing membrane-anchoring cholesterol at the tail of the arrow results in display of RNA aptamer or folate on the outer surface of the extracellular vesicle. In contrast, placing the cholesterol at the arrowhead results in partial loading of RNA nanoparticles into the extracellular vesicles. Taking advantage of the RNA ligand for specific targeting and extracellular vesicles for efficient membrane fusion, the resulting ligand-displaying extracellular vesicles were capable of specific delivery of siRNA to cells, and efficiently blocked tumour growth in three cancer models. Extracellular vesicles displaying an aptamer that binds to prostate-specific membrane antigen, and loaded with survivin siRNA, inhibited prostate cancer xenograft. The same extracellular vesicle instead displaying epidermal growth-factor receptor aptamer inhibited orthotopic breast cancer models. Likewise, survivin siRNA-loaded and folate-displaying extracellular vesicles inhibited patient-derived colorectal cancer xenograft.

Applicability of Yeast Extracellular Proteinases in Brewing: Physiological and Biochemical Aspects

Science.gov (United States)

Bilinski, Carl A.; Russell, Inge; Stewart, Graham G.

1987-01-01

A general screening survey for expression of extracellular acid proteinase production was performed on over 100 cultures belonging to the genus Saccharomyces. Although two strains of Saccharomyces cerevisiae showed positive extracellular proteinase phenotypes in plate tests, it was not possible to demonstrate proteolytic activities in cell-free culture supernatants in assays performed at beer pH values. Of several yeasts from other genera examined, Saccharomycopsis fibuligera and Torulopsis magnoliae produced extracellular proteinases with desirable properties. Proteolytic activities were detected in assays performed at beer pH values and at lower temperature. Brewer's wort served as a highly inducing medium for extracellular proteinase production, with T. magnoliae yielding enzyme of highest specific activity. In fact, commencement of enzyme production was detected shortly after the onset of exponential growth in brewer's wort. Inclusion of crude enzyme preparations in brewer's wort inoculated simultaneously with brewer's yeast reduced final ethanol yields slightly and was found to be effective in reducing chill haze formation in bottled beer. PMID:16347298

Discussion on prospecting potential for rich uranium deposits in Xiazhuang uranium ore-field, northern Guangdong

International Nuclear Information System (INIS)

Wu Lieqin; Tan Zhengzhong

2004-01-01

Based on analyzing the prospecting potential for uranium deposits in Xiazhuang uranium ore field this paper discusses the prospecting for rich uranium deposits and prospecting potential in the region. Research achievements indicate: that the Xiazhuang ore-field is an ore-concentrated area where uranium has been highly enriched, and possesses good prospecting potential and perspective, becoming one of the most important prospecting areas for locating rich uranium deposits in northern Guangdong; that the 'intersection type', the alkaline metasomatic fractured rock type and the vein-group type uranium deposits are main targets and the prospecting direction for future uranium prospecting in this region

Stable Flocking of Multiple Agents Based on Molecular Potential Field and Distributed Receding Horizon Control

International Nuclear Information System (INIS)

Zhang Yun-Peng; Duan Hai-Bin; Zhang Xiang-Yin

2011-01-01

A novel distributed control scheme to generate stable flocking motion for a group of agents is proposed. In this control scheme, a molecular potential field model is applied as the potential field function because of its smoothness and unique shape. The approach of distributed receding horizon control is adopted to drive each agent to find its optimal control input to lower its potential at every step. Experimental results show that this proposed control scheme can ensure that all agents eventually converge to a stable flocking formation with a common velocity and the collisions can also be avoided at the same time. (general)

A short proof that the Coulomb-gauge potentials yield the retarded fields

Energy Technology Data Exchange (ETDEWEB)

Heras, Jose A, E-mail: herasgomez@gmail.co [Universidad Autonoma Metropolitana, Unidad Azcapotzalco, Av. San Pablo No. 180, Col. Reynosa, Mexico D. F. 02200 (Mexico)

2011-01-15

A short demonstration that the potentials in the Coulomb gauge yield the retarded electric and magnetic fields is presented. This demonstration is relatively simple and can be presented in an advanced undergraduate course of electromagnetic theory.

A short proof that the Coulomb-gauge potentials yield the retarded fields

International Nuclear Information System (INIS)

Heras, Jose A

2011-01-01

A short demonstration that the potentials in the Coulomb gauge yield the retarded electric and magnetic fields is presented. This demonstration is relatively simple and can be presented in an advanced undergraduate course of electromagnetic theory.

Multiplatform Mass Spectrometry-Based Approach Identifies Extracellular Glycolipids of the Yeast Rhodotorula babjevae UCDFST 04-877.

Science.gov (United States)

Cajka, Tomas; Garay, Luis A; Sitepu, Irnayuli R; Boundy-Mills, Kyria L; Fiehn, Oliver

2016-10-28

A multiplatform mass spectrometry-based approach was used for elucidating extracellular lipids with biosurfactant properties produced by the oleaginous yeast Rhodotorula babjevae UCDFST 04-877. This strain secreted 8.6 ± 0.1 g/L extracellular lipids when grown in a benchtop bioreactor fed with 100 g/L glucose in medium without addition of hydrophobic substrate, such as oleic acid. Untargeted reversed-phase liquid chromatography-quadrupole/time-of-flight mass spectrometry (QTOFMS) detected native glycolipid molecules with masses of 574-716 Da. After hydrolysis into the fatty acid and sugar components and hydrophilic interaction chromatography-QTOFMS analysis, the extracellular lipids were found to consist of hydroxy fatty acids and sugar alcohols. Derivatization and chiral separation gas chromatography-mass spectrometry (GC-MS) identified these components as d-arabitol, d-mannitol, (R)-3-hydroxymyristate, (R)-3-hydroxypalmitate, and (R)-3-hydroxystearate. In order to assemble these substructures back into intact glycolipids that were detected in the initial screen, potential structures were in-silico acetylated to match the observed molar masses and subsequently characterized by matching predicted and observed MS/MS fragmentation using the Mass Frontier software program. Eleven species of acetylated sugar alcohol esters of hydroxy fatty acids were characterized for this yeast strain.

Crystallization and preliminary crystallographic analysis of Gibberella zeae extracellular lipase

International Nuclear Information System (INIS)

Sun, Yuna; Li, Ming; Zhang, Yan; Liu, Lifang; Liu, Ye; Liu, Zheng; Li, Xumei; Lou, Zhiyong

2008-01-01

G. zeae extracellular lipase has been overexpressed, purified and crystallized. Diffraction data were collected to 2.8 Å resolution. Fusarium head blight, one of the most destructive crop diseases, is mainly caused by Fusarium graminearum (known in its sexual stage as Gibberella zeae). F. graminearum secretes various extracellular enzymes that have been hypothesized to be involved in host infection. One of the extracellular enzymes secreted by this organism is the G. zeae extracellular lipase (GZEL), which is encoded by the FGL1 gene. In order to solve the crystal structure of GZEL and to gain a better understanding of the biological functions of the protein and of possible inhibitory mechanisms of lipase inhibitors, recombinant GZEL was crystallized at 291 K using PEG 3350 as a precipitant. A data set was collected to 2.8 Å resolution from a single flash-cooled crystal (100 K). The crystal belonged to space group P2 1 2 1 2 1 , with unit-cell parameters a = 78.4, b = 91.0, c = 195.8 Å, α = β = γ = 90°. The presence of four molecules was assumed per asymmetric unit, which gave a Matthews coefficient of 2.6 Å 3 Da −1

Applying extracellular vesicles based therapeutics in clinical trials - an ISEV position paper

NARCIS (Netherlands)

Lener, Thomas; Gimona, Mario; Aigner, Ludwig; Börger, Verena; Buzas, Edit; Camussi, Giovanni; Chaput, Nathalie; Chatterjee, Devasis; Court, Felipe A; Del Portillo, Hernando A; O'Driscoll, Lorraine; Fais, Stefano; Falcon-Perez, Juan M; Felderhoff-Mueser, Ursula; Fraile, Lorenzo; Gho, Yong Song; Görgens, André; Gupta, Ramesh C; Hendrix, An; Hermann, Dirk M; Hill, Andrew F; Hochberg, Fred; Horn, Peter A; de Kleijn, Dominique; Kordelas, Lambros; Kramer, Boris W; Krämer-Albers, Eva-Maria; Laner-Plamberger, Sandra; Laitinen, Saara; Leonardi, Tommaso; Lorenowicz, Magdalena J; Lim, Sai Kiang; Lötvall, Jan; Maguire, Casey A; Marcilla, Antonio; Nazarenko, Irina; Ochiya, Takahiro; Patel, Tushar; Pedersen, Shona; Pocsfalvi, Gabriella; Pluchino, Stefano; Quesenberry, Peter; Reischl, Ilona G; Rivera, Francisco J; Sanzenbacher, Ralf; Schallmoser, Katharina; Slaper-Cortenbach, Ineke; Strunk, Dirk; Tonn, Torsten; Vader, Pieter; van Balkom, Bas W M; Wauben, Marca|info:eu-repo/dai/nl/112675735; Andaloussi, Samir El; Théry, Clotilde; Rohde, Eva; Giebel, Bernd

2015-01-01

Extracellular vesicles (EVs), such as exosomes and microvesicles, are released by different cell types and participate in physiological and pathophysiological processes. EVs mediate intercellular communication as cell-derived extracellular signalling organelles that transmit specific information

Extracellular matrix and tissue engineering applications

NARCIS (Netherlands)

Fernandes, H.A.M.; Moroni, Lorenzo; van Blitterswijk, Clemens; de Boer, Jan

2009-01-01

The extracellular matrix is a key component during regeneration and maintenance of tissues and organs, and it therefore plays a critical role in successful tissue engineering as well. Tissue engineers should recognise that engineering technology can be deduced from natural repair processes. Due to

Extracellular matrix of dental pulp stem cells: Applications in pulp tissue engineering using somatic MSCs

Directory of Open Access Journals (Sweden)

Sriram eRavindran

2014-01-01

Full Text Available Dental Caries affects approximately 90% of the world’s population. At present, the clinical treatment for dental caries is root canal therapy. This treatment results in loss of tooth sensitivity and vitality. Tissue engineering can potentially solve this problem by enabling regeneration of a functional pulp tissue. Dental pulp stem cells (DPSCs have been shown to be an excellent source for pulp regeneration. However, limited availability of these cells hinders its potential for clinical translation. We have investigated the possibility of using somatic mesenchymal stem cells from other sources for dental pulp tissue regeneration using a biomimetic dental pulp extracellular matrix (ECM incorporated scaffold. Human periodontal ligament stem cells (PDLSCs and human bone marrow stromal cells (HMSCs were investigated for their ability to differentiate towards an odontogenic lineage. In vitro real-time PCR results coupled with histological and immunohistochemical examination of the explanted tissues confirmed the ability of PDLSCs and HMSCs to form a vascularized pulp-like tissue. These findings indicate that the dental pulp stem derived ECM scaffold stimulated odontogenic differentiation of PDLSCs and HMSCs without the need for exogenous addition of growth and differentiation factors. This study represents a translational perspective toward possible therapeutic application of using a combination of somatic stem cells and extracellular matrix for pulp regeneration.

Improved ring potential of QED at finite temperature and in the presence of weak and strong magnetic fields

International Nuclear Information System (INIS)

Sadooghi, N.; Anaraki, K. Sohrabi

2008-01-01

Using the general structure of the vacuum polarization tensor Π μν (k 0 ,k) in the infrared (IR) limit, k 0 →0, the ring contribution to the QED effective potential at finite temperature and the nonzero magnetic field is determined beyond the static limit, (k 0 →0, k→0). The resulting ring potential is then studied in weak and strong magnetic field limits. In the weak magnetic field limit, at high temperature and for α→0, the improved ring potential consists of a term proportional to T 4 α 5/2 , in addition to the expected T 4 α 3/2 term arising from the static limit. Here, α is the fine structure constant. In the limit of the strong magnetic field, where QED dynamics is dominated by the lowest Landau level, the ring potential includes a novel term consisting of dilogarithmic function (eB)Li 2 (-(2α/π)(eB/m 2 )). Using the ring improved (one-loop) effective potential including the one-loop effective potential and ring potential in the IR limit, the dynamical chiral symmetry breaking of QED is studied at finite temperature and in the presence of the strong magnetic field. The gap equation, the dynamical mass and the critical temperature of QED in the regime of the lowest Landau level dominance are determined in the improved IR as well as in the static limit. For a given value of the magnetic field, the improved ring potential is shown to be more efficient in decreasing the critical temperature arising from the one-loop effective potential.

Endophytic Fungi from Frankincense Tree Improves Host Growth and Produces Extracellular Enzymes and Indole Acetic Acid.

Directory of Open Access Journals (Sweden)

Abdul Latif Khan

Full Text Available Boswellia sacra, an economically important frankincense-producing tree found in the desert woodlands of Oman, is least known for its endophytic fungal diversity and the potential of these fungi to produce extracellular enzymes and auxins. We isolated various fungal endophytes belonging to Eurotiales (11.8%, Chaetomiaceae (17.6%, Incertae sadis (29.5%, Aureobasidiaceae (17.6%, Nectriaceae (5.9% and Sporomiaceae (17.6% from the phylloplane (leaf and caulosphere (stem of the tree. Endophytes were identified using genomic DNA extraction, PCR amplification and sequencing the internal transcribed spacer regions, whereas a detailed phylogenetic analysis of the same gene fragment was made with homologous sequences. The endophytic colonization rate was significantly higher in the leaf (5.33% than the stem (0.262%. The Shannon-Weiner diversity index was H' 0.8729, while Simpson index was higher in the leaf (0.583 than in the stem (0.416. Regarding the endophytic fungi's potential for extracellular enzyme production, fluorogenic 4-methylumbelliferone standards and substrates were used to determine the presence of cellulases, phosphatases and glucosidases in the pure culture. Among fungal strains, Penicillum citrinum BSL17 showed significantly higher amounts of glucosidases (62.15±1.8 μM-1min-1mL and cellulases (62.11±1.6 μM-1min-1mL, whereas Preussia sp. BSL10 showed significantly higher secretion of glucosidases (69.4±0.79 μM-1min-1mL and phosphatases (3.46±0.31μM-1min-1mL compared to other strains. Aureobasidium sp. BSS6 and Preussia sp. BSL10 showed significantly higher potential for indole acetic acid production (tryptophan-dependent and independent pathways. Preussia sp. BSL10 was applied to the host B. sacra tree saplings, which exhibited significant improvements in plant growth parameters and accumulation of photosynthetic pigments. The current study concluded that endophytic microbial resources producing extracellular enzymes and auxin

Endophytic Fungi from Frankincense Tree Improves Host Growth and Produces Extracellular Enzymes and Indole Acetic Acid.

Science.gov (United States)

Khan, Abdul Latif; Al-Harrasi, Ahmed; Al-Rawahi, Ahmed; Al-Farsi, Zainab; Al-Mamari, Aza; Waqas, Muhammad; Asaf, Sajjad; Elyassi, Ali; Mabood, Fazal; Shin, Jae-Ho; Lee, In-Jung

2016-01-01

Boswellia sacra, an economically important frankincense-producing tree found in the desert woodlands of Oman, is least known for its endophytic fungal diversity and the potential of these fungi to produce extracellular enzymes and auxins. We isolated various fungal endophytes belonging to Eurotiales (11.8%), Chaetomiaceae (17.6%), Incertae sadis (29.5%), Aureobasidiaceae (17.6%), Nectriaceae (5.9%) and Sporomiaceae (17.6%) from the phylloplane (leaf) and caulosphere (stem) of the tree. Endophytes were identified using genomic DNA extraction, PCR amplification and sequencing the internal transcribed spacer regions, whereas a detailed phylogenetic analysis of the same gene fragment was made with homologous sequences. The endophytic colonization rate was significantly higher in the leaf (5.33%) than the stem (0.262%). The Shannon-Weiner diversity index was H' 0.8729, while Simpson index was higher in the leaf (0.583) than in the stem (0.416). Regarding the endophytic fungi's potential for extracellular enzyme production, fluorogenic 4-methylumbelliferone standards and substrates were used to determine the presence of cellulases, phosphatases and glucosidases in the pure culture. Among fungal strains, Penicillum citrinum BSL17 showed significantly higher amounts of glucosidases (62.15±1.8 μM-1min-1mL) and cellulases (62.11±1.6 μM-1min-1mL), whereas Preussia sp. BSL10 showed significantly higher secretion of glucosidases (69.4±0.79 μM-1min-1mL) and phosphatases (3.46±0.31μM-1min-1mL) compared to other strains. Aureobasidium sp. BSS6 and Preussia sp. BSL10 showed significantly higher potential for indole acetic acid production (tryptophan-dependent and independent pathways). Preussia sp. BSL10 was applied to the host B. sacra tree saplings, which exhibited significant improvements in plant growth parameters and accumulation of photosynthetic pigments. The current study concluded that endophytic microbial resources producing extracellular enzymes and auxin could

Surface potential at a ferroelectric grain due to asymmetric screening of depolarization fields

Energy Technology Data Exchange (ETDEWEB)

Genenko, Yuri A., E-mail: genenko@mm.tu-darmstadt.de; Hirsch, Ofer [Technische Universität Darmstadt, Darmstadt (Germany); Erhart, Paul [Chalmers University of Technology, Gothenburg (Sweden)

2014-03-14

Nonlinear screening of electric depolarization fields, generated by a stripe domain structure in a ferroelectric grain of a polycrystalline material, is studied within a semiconductor model of ferroelectrics. It is shown that the maximum strength of local depolarization fields is rather determined by the electronic band gap than by the spontaneous polarization magnitude. Furthermore, field screening due to electronic band bending and due to presence of intrinsic defects leads to asymmetric space charge regions near the grain boundary, which produce an effective dipole layer at the surface of the grain. This results in the formation of a potential difference between the grain surface and its interior of the order of 1 V, which can be of either sign depending on defect transition levels and concentrations. Exemplary acceptor doping of BaTiO{sub 3} is shown to allow tuning of the said surface potential in the region between 0.1 and 1.3 V.

Cat exposure induces both intra- and extracellular Hsp72: the role of adrenal hormones.

Science.gov (United States)

Fleshner, Monika; Campisi, Jay; Amiri, Leila; Diamond, David M

2004-10-01

Heat-shock proteins (Hsp) play an important role in stress physiology. Exposure to a variety of stressors will induce intracellular Hsp72, and this induction is believed to be beneficial for cell survival. In contrast, Hsp72 released during stress (extracellular Hsp72; eHsp72) activates pro-inflammatory responses. Clearly, physical stressors such as heat, cold, H(2)O(2), intense exercise and tail shock will induce both intra- and extracellular Hsp72. The current study tested whether a psychological stressor, cat exposure, would also trigger this response. In addition, the potential role of adrenal hormones in the Hsp72 response was examined. Adult, male Sprague Dawley rats were either adrenalectomized (ADX) or sham operated. Ten days post-recovery, rats were exposed to either a cat with no physical contact or control procedures (n = 5-6/group) for 2 h. Levels of intracellular Hsp72 were measured in the brain (frontal cortex, hippocampus, hypothalamus, dorsal vagal complex) and pituitary (ELISA). Levels of eHsp72 (ELISA) and corticosterone (RIA) were measured from serum obtained at the end of the 2-h stress period. Rats that were exposed to a cat had elevated intracellular Hsp72 in hypothalamus and dorsal vagal complex, and elevated eHsp72 and corticosterone in serum. Both the intra- and extracellular Hsp72 responses were blocked or attenuated by ADX. This study demonstrates that cat exposure can stimulate the Hsp72 response and that adrenal hormones contribute to this response.

Cathepsin K in Lymphangioleiomyomatosis: LAM Cell-Fibroblast Interactions Enhance Protease Activity by Extracellular Acidification.

Science.gov (United States)

Dongre, Arundhati; Clements, Debbie; Fisher, Andrew J; Johnson, Simon R

2017-08-01

Lymphangioleiomyomatosis (LAM) is a rare disease in which LAM cells and fibroblasts form lung nodules and it is hypothesized that LAM nodule-derived proteases cause cyst formation and tissue damage. On protease gene expression profiling in whole lung tissue, cathepsin K gene expression was 40-fold overexpressed in LAM compared with control lung tissue (P ≤ 0.0001). Immunohistochemistry confirmed cathepsin K protein was expressed in LAM but not control lungs. Cathepsin K gene expression and protein and protease activity were detected in LAM-associated fibroblasts but not the LAM cell line 621-101. In lung nodules, cathepsin K immunoreactivity predominantly co-localized with LAM-associated fibroblasts. In vitro, fibroblast extracellular cathepsin K activity was minimal at pH 7.5 but significantly enhanced at pH 7 and 6. 621-101 cells reduced extracellular pH with acidification dependent on 621-101 mechanistic target of rapamycin activity and net hydrogen ion exporters, particularly sodium bicarbonate co-transporters and carbonic anhydrases, which were also expressed in LAM lung tissue. In LAM cell-fibroblast co-cultures, acidification paralleled cathepsin K activity, and both were reduced by sodium bicarbonate co-transporter (P ≤ 0.0001) and carbonic anhydrase inhibitors (P = 0.0021). Our findings suggest that cathepsin K activity is dependent on LAM cell-fibroblast interactions, and inhibitors of extracellular acidification may be potential therapies for LAM. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Multistability in a neuron model with extracellular potassium dynamics

Science.gov (United States)

Wu, Xing-Xing; Shuai, J. W.

2012-06-01

Experiments show a primary role of extracellular potassium concentrations in neuronal hyperexcitability and in the generation of epileptiform bursting and depolarization blocks without synaptic mechanisms. We adopt a physiologically relevant hippocampal CA1 neuron model in a zero-calcium condition to better understand the function of extracellular potassium in neuronal seizurelike activities. The model neuron is surrounded by interstitial space in which potassium ions are able to accumulate. Potassium currents, Na+-K+ pumps, glial buffering, and ion diffusion are regulatory mechanisms of extracellular potassium. We also consider a reduced model with a fixed potassium concentration. The bifurcation structure and spiking frequency of the two models are studied. We show that, besides hyperexcitability and bursting pattern modulation, the potassium dynamics can induce not only bistability but also tristability of different firing patterns. Our results reveal the emergence of the complex behavior of multistability due to the dynamical [K+]o modulation on neuronal activities.

Effects of transforming growth factor-beta1 on cell motility, collagen gel contraction, myofibroblastic differentiation, and extracellular matrix expression of human adipose-derived stem cell.

Science.gov (United States)

Kakudo, Natsuko; Kushida, Satoshi; Suzuki, Kenji; Ogura, Tsunetaka; Notodihardjo, Priscilla Valentin; Hara, Tomoya; Kusumoto, Kenji

2012-12-01

Human adipose-derived stem cells (ASCs) are adult pluripotent stem cells, and their usefulness in plastic surgery has garnered attention in recent years. Although, there have been expectations that ASCs might function in wound repair and regeneration, no studies to date have examined the role of ASCs in the mechanism that promotes wound-healing. Transforming growth factor-beta1 (TGF-β1) is a strong candidate cytokine for the triggering of mesenchymal stem cell migration, construction of extracellular matrices, and differentiation of ASCs into myofibroblasts. Cell proliferation, motility, and differentiation, as well as extracellular matrix production, play an important role in wound-healing. We have evaluated the capacity of ASCs to proliferate and their potential to differentiate into phenotypic myofibroblasts, as well as their cell motility and collagen gel contraction ability, when cultured with TGF-β1. Cell motility was analyzed using a wound-healing assay. ASCs that differentiated into myofibroblasts expressed the gene for alpha-smooth muscle actin, and its protein expression was detected immunohistochemically. The extracellular matrix expression in ASCs was evaluated using real-time RT-PCR. Based on the results, we conclude that human ASCs have the potential for cell motility, extracellular matrix gene expression, gel contraction, and differentiation into myofibroblasts and, therefore, may play an important role in the wound-healing process.

Detection of extracellular enzymatic activity in microorganisms ...

African Journals Online (AJOL)

Detection of extracellular enzymatic activity in microorganisms isolated from waste vegetable oil contaminated soil using plate methodologies. Eugenia G. Ortiz Lechuga, Isela Quintero Zapata, Katiushka Arévalo Niño ...

Purification and characterization of extracellular amylolytic enzyme ...

African Journals Online (AJOL)

DOSS

2012-10-16

Oct 16, 2012 ... Available online at http://www.academicjournals.org/AJB ... characterization of extracellular amylases from four ... Somogyi-Nelson's method (Nelson, 1944; Somogyi, 1952). ... The mycelia dry weight of currently studied four.

The matricellular receptor LRP1 forms an interface for signaling and endocytosis in modulation of the extracellular tumor environment

Directory of Open Access Journals (Sweden)

Bart eVan Gool

2015-11-01

Full Text Available The membrane protein low-density lipoprotein receptor related-protein 1 (LRP1 has been attributed a role in cancer. However, its presumably often indirect involvement is far from understood. LRP1 has both endocytic and signaling activities. As a matricellular receptor it is involved in regulation, mostly by clearing, of various extracellular matrix degrading enzymes including matrix metalloproteinases, serine proteases, protease-inhibitor complexes and the endoglycosidase heparanase. Furthermore, by binding extracellular ligands including growth factors and subsequent intracellular interaction with scaffolding and adaptor proteins it is involved in regulation of various signaling cascades. LRP1 expression levels are often downregulated in cancer and some studies consider low LRP1 levels a poor prognostic factor. On the contrary, upregulation in brain cancers has been noted and clinical trials explore the use of LRP1 as cargo receptor to deliver cytotoxic agents.This mini-review focuses on LRP1’s role in tumor growth and metastasis especially by modulation of the extracellular tumor environment. In relation to this role its diagnostic, prognostic and therapeutic potential will be discussed.

Extracellular Polymeric Substances Govern the Surface Charge of Biogenic Elemental Selenium Nanoparticles

KAUST Repository

Jain, Rohan; Jordan, Norbert; Weiss, Stephan; Foerstendorf, Harald; Heim, Karsten; Kacker, Rohit; Hü bner, René ; Kramer, Herman; van Hullebusch, Eric D.; Farges, Franç ois; Lens, Piet N. L.

2015-01-01

investigated the presence of extracellular polymeric substances (EPS) on BioSeNPs. The role of EPS in capping the extracellularly available BioSeNPs was also examined. Fourier transform infrared (FT-IR) spectroscopy and colorimetric measurements confirmed

Internal and external potential-field estimation from regional vector data at varying satellite altitude

Science.gov (United States)

Plattner, Alain; Simons, Frederik J.

2017-10-01

When modelling satellite data to recover a global planetary magnetic or gravitational potential field, the method of choice remains their analysis in terms of spherical harmonics. When only regional data are available, or when data quality varies strongly with geographic location, the inversion problem becomes severely ill-posed. In those cases, adopting explicitly local methods is to be preferred over adapting global ones (e.g. by regularization). Here, we develop the theory behind a procedure to invert for planetary potential fields from vector observations collected within a spatially bounded region at varying satellite altitude. Our method relies on the construction of spatiospectrally localized bases of functions that mitigate the noise amplification caused by downward continuation (from the satellite altitude to the source) while balancing the conflicting demands for spatial concentration and spectral limitation. The `altitude-cognizant' gradient vector Slepian functions (AC-GVSF) enjoy a noise tolerance under downward continuation that is much improved relative to the `classical' gradient vector Slepian functions (CL-GVSF), which do not factor satellite altitude into their construction. Furthermore, venturing beyond the realm of their first application, published in a preceding paper, in the present article we extend the theory to being able to handle both internal and external potential-field estimation. Solving simultaneously for internal and external fields under the limitation of regional data availability reduces internal-field artefacts introduced by downward-continuing unmodelled external fields, as we show with numerical examples. We explain our solution strategies on the basis of analytic expressions for the behaviour of the estimation bias and variance of models for which signal and noise are uncorrelated, (essentially) space- and band-limited, and spectrally (almost) white. The AC-GVSF are optimal linear combinations of vector spherical harmonics

Effects on functional groups and zeta potential of SAP1pulsed electric field technology.

Science.gov (United States)

Liang, Rong; Li, Xuenan; Lin, Songyi; Wang, Jia

2017-01-01

SAP 1 pulsed electric field (PEF) technology. The effects of electric field intensity and pulse frequency on SAP 1 electric field intensity 15 kV cm -1 , pulse frequency 1600 Hz and flow velocity 2.93 mL min -1 ). Furthermore, the PEF-treated SAP 1 < MW < 3kDa under optimal conditions lacked the characteristic absorbance of N-H, C = C and the amide band and the zeta potential was reduced to -18.0 mV. Overall, the results of the present study suggest that the improvement of antioxidant activity of SAP 1 < MW < 3kDa is a result of the contribution of the functional groups and the change in zeta potential when treated with PEF. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Interaction potentials for multiquark states from instantons and other background gauge field configurations

International Nuclear Information System (INIS)

Warner, R.C.; Joshi, G.C.

1979-01-01

A simple rule is presented for calculating the contributions to the interaction potentials between constituent particles for a family of multiquark states, due to the presence of a semi-classical gauge field configuration which exists in a single SU(2) subgroup of colour SU(3). In multiquark states beyond the baryon many-body potential terms are found. The static (Wilson loop) limit is sufficient to elucidate the dependence of the potential on the colour structure of the multiquark state

The monophasic action potential upstroke: a means of characterizing local conduction.

Science.gov (United States)

Levine, J H; Moore, E N; Kadish, A H; Guarnieri, T; Spear, J F

1986-11-01

The upstrokes of monophasic action potentials (MAPs) recorded with an extracellular pressure electrode were characterized in isolated canine tissue preparations in vitro. The characteristics of the MAP upstroke were compared with those of the local action potential foot as well as with the characteristics of approaching electrical activation during uniform and asynchronous conduction. The upstroke of the MAP was exponential during uniform conduction. The time constant of rise of the MAP upstroke (TMAP) correlated with that of the action potential foot (Tfoot): TMAP + 1.01 Tfoot + 0.50; r2 = .80. Furthermore, changes in Tfoot with alterations in cycle length were associated with similar changes in TMAP: Tfoot = 1.06 TMAP - 0.11; r2 = .78. In addition, TMAP and Tfoot both deviated from exponential during asynchronous activation; the inflections that developed in the MAP upstroke correlated in time with intracellular action potential upstrokes that were asynchronous in onset in these tissues. Finally, the field of view of the MAP was determined and was found to be dependent in part on tissue architecture and the space constant. Specifically, the field of view of the MAP was found to be greater parallel compared with transverse to fiber orientation (6.02 +/- 1.74 vs 3.03 +/- 1.10 mm; p less than .01). These data suggest that the MAP upstroke may be used to define and characterize local electrical activation. The relatively large field of view of the MAP suggests that this technique may be a sensitive means to record focal membrane phenomena in vivo.

Extracellular pH modulates GABAergic neurotransmission in rat hypothalamus.

Science.gov (United States)

Chen, Z L; Huang, R Q

2014-06-20

Changes in extracellular pH have a modulatory effect on GABAA receptor function. It has been reported that pH sensitivity of the GABA receptor is dependent on subunit composition and GABA concentration. Most of previous investigations focused on GABA-evoked currents, which only reflect the postsynaptic receptors. The physiological relevance of pH modulation of GABAergic neurotransmission is not fully elucidated. In the present studies, we examined the influence of extracellular pH on the GABAA receptor-mediated inhibitory neurotransmission in rat hypothalamic neurons. The inhibitory postsynaptic currents (IPSCs), tonic currents, and the GABA-evoked currents were recorded with whole-cell patch techniques on the hypothalamic slices from Sprague-Dawley rats at 15-26 postnatal days. The amplitude and frequency of spontaneous GABA IPSCs were significantly increased while the external pH was changed from 7.3 to 8.4. In the acidic pH (6.4), the spontaneous GABA IPSCs were reduced in amplitude and frequency. The pH induced changes in miniature GABA IPSCs (mIPSCs) similar to that in spontaneous IPSCs. The pH effect on the postsynaptic GABA receptors was assessed with exogenously applied varying concentrations of GABA. The tonic currents and the currents evoked by sub-saturating concentration of GABA ([GABA]) (10 μM) were inhibited by acidic pH and potentiated by alkaline pH. In contrast, the currents evoked by saturating [GABA] (1mM) were not affected by pH changes. We also investigated the influence of pH buffers and buffering capacity on pH sensitivity of GABAA receptors on human recombinant α1β2γ2 GABAA receptors stably expressed in HEK 293 cells. The pH influence on GABAA receptors was similar in HEPES- and MES-buffered media, and not dependent on protonated buffers, suggesting that the observed pH effect on GABA response is a specific consequence of changes in extracellular protons. Our data suggest that the hydrogen ions suppress the GABAergic neurotransmission

Magnetic field effects on the open circuit potential of ferromagnetic electrodes in corroding solutions.

Science.gov (United States)

Dass, Amala; Counsil, Joseph A; Gao, Xuerong; Leventis, Nicholas

2005-06-02

Magnetic fields shift the open circuit potential (OCP) of ferromagnetic electrodes (Fe, Co, and Ni) in corroding solutions. The OCP changes we observe (a) follow the series Fe>Co>Ni; (b) increase with the magnetic flux density; (c) reach a maximum with disk electrodes approximately 1 mm in diameter; and (d) depend on the orientation of the electrode. We report that when the surface of the electrode is oriented parallel (theta = 90 degrees) or perpendicular (theta = 0 degrees) to the magnetic field, the open circuit potential moves in opposite directions (positive and negative, respectively) with the largest changes occurring when the electrode surface is parallel to the magnetic field. Nonconvective sleeve electrodes produce the same behavior. The overall experimental evidence suggests that the magnetic field changes the OCP by modifying the surface concentrations of the paramagnetic participants in the corrosion process of the ferromagnetic electrode by species in solution; this in turn is accomplished by imposing a field-gradient driven mode of mass transfer upon paramagnetic species in solution (magnetophoresis). Simulations of the magnetic field around the ferromagnetic electrode at the two extreme orientations considered here show that in one case (theta = 90 degrees) field gradients actually repel, while in the other case (theta = 0 degrees) they attract paramagnetic species in the vicinity of the electrode.

THE POSSIBLE IMPACT OF L5 MAGNETOGRAMS ON NON-POTENTIAL SOLAR CORONAL MAGNETIC FIELD SIMULATIONS

Energy Technology Data Exchange (ETDEWEB)

Weinzierl, Marion; Yeates, Anthony R. [Department of Mathematical Sciences, Durham University South Road, Durham DH1 3LE (United Kingdom); Mackay, Duncan H. [School of Mathematics and Statistics, University of St. Andrews North Haugh, St. Andrews, Fife KY16 9SS (United Kingdom); Pevtsov, Alexei A., E-mail: marion.weinzierl@durham.ac.uk [National Solar Observatory 3010 Coronal Loop, sunspot NM 88349 (United States)

2016-09-10

The proposed Carrington-L5 mission would bring instruments to the L5 Lagrange point to provide us with crucial data for space weather prediction. To assess the importance of including a magnetograph, we consider the possible differences in non-potential solar coronal magnetic field simulations when magnetograph observations are available from the L5 point, compared with an L1-based field of view (FOV). A timeseries of synoptic radial magnetic field maps is constructed to capture the emergence of two active regions from the L5 FOV. These regions are initially absent in the L1 magnetic field maps, but are included once they rotate into the L1 FOV. Non-potential simulations for these two sets of input data are compared in detail. Within the bipolar active regions themselves, differences in the magnetic field structure can exist between the two simulations once the active regions are included in both. These differences tend to reduce within 5 days of the active region being included in L1. The delayed emergence in L1 can, however, lead to significant persistent differences in long-range connectivity between the active regions and the surrounding fields, and also in the global magnetic energy. In particular, the open magnetic flux and the location of open magnetic footpoints, are sensitive to capturing the real-time of emergence. These results suggest that a magnetograph at L5 could significantly improve predictions of the non-potential corona, the interplanetary magnetic field, and of solar wind source regions on the Sun.

Mesenchymal Stem/Stromal Cell-Derived Extracellular Vesicles and Their Potential as Novel Immunomodulatory Therapeutic Agents

Directory of Open Access Journals (Sweden)

Verena Börger

2017-07-01

Full Text Available Extracellular vesicles (EVs, such as exosomes and microvesicles, have been identified as mediators of a newly-discovered intercellular communication system. They are essential signaling mediators in various physiological and pathophysiological processes. Depending on their origin, they fulfill different functions. EVs of mesenchymal stem/stromal cells (MSCs have been found to promote comparable therapeutic activities as MSCs themselves. In a variety of in vivo models, it has been observed that they suppress pro-inflammatory processes and reduce oxidative stress and fibrosis. By switching pro-inflammatory into tolerogenic immune responses, MSC-EVs very likely promote tissue regeneration by creating a pro-regenerative environment allowing endogenous stem and progenitor cells to successfully repair affected tissues. Accordingly, MSC-EVs provide a novel, very promising therapeutic agent, which has already been successfully applied to humans. However, the MSC-EV production process has not been standardized, yet. Indeed, a collection of different protocols has been used for the MSC-EV production, characterization and application. By focusing on kidney, heart, liver and brain injuries, we have reviewed the major outcomes of published MSC-EV in vivo studies.

Extracellular nucleotide signaling in plants

Energy Technology Data Exchange (ETDEWEB)

Stacey, Gary [Univ. of Missouri, Columbia, MO (United States)

2016-09-08

Over the life of this funded project, our research group identified and characterized two key receptor proteins in plants; one mediating the innate immunity response to chitin and the other elucidating the key receptor for extracellular ATP. In the case of chitin recognition, we recently described the quaternary structure of this receptor, shedding light on how the receptor functions. Perhaps more importantly, we demonstrated that all plants have the ability to recognize both chitin oligomers and lipochitooligosacchardes, fundamentally changing how the community views the evolution of these systems and strategies that might be used, for example, to extend symbiotic nitrogen fixation to non-legumes. Our discovery of DORN1 opens a new chapter in plant physiology documenting conclusively that eATP is an important extracellular signal in plants, as it is in animals. At this point, we cannot predict just how far reaching this discovery may prove to be but we are convinced that eATP signaling is fundamental to plant growth and development and, hence, we believe that the future will be very exciting for the study of DORN1 and its overall function in plants.

Effect of Membrane Tension on the Electric Field and Dipole Potential of Lipid Bilayer Membrane

Science.gov (United States)

Warshaviak, Dora Toledo; Muellner, Michael J.; Chachisvilis, Mirianas

2011-01-01

The dipole potential of lipid bilayer membrane controls the difference in permeability of the membrane to oppositely charged ions. We have combined molecular dynamics (MD) simulations and experimental studies to determine changes in electric field and electrostatic potential of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) lipid bilayer in response to applied membrane tension. MD simulations based on CHARMM36 force field showed that electrostatic potential of DOPC bilayer decreases by ~45 mV in the physiologically relevant range of membrane tension values (0 to 15 dyn/cm). The electrostatic field exhibits a peak (~0.8×109 V/m) near the water/lipid interface which shifts by 0.9 Å towards the bilayer center at 15 dyn/cm. Maximum membrane tension of 15 dyn/cm caused 6.4% increase in area per lipid, 4.7% decrease in bilayer thickness and 1.4% increase in the volume of the bilayer. Dipole-potential sensitive fluorescent probes were used to detect membrane tension induced changes in DOPC vesicles exposed to osmotic stress. Experiments confirmed that dipole potential of DOPC bilayer decreases at higher membrane tensions. These results are suggestive of a potentially new mechanosensing mechanism by which mechanically induced structural changes in the lipid bilayer membrane could modulate the function of membrane proteins by altering electrostatic interactions and energetics of protein conformational states. PMID:21722624

Characterization of Extracellular Vesicles by Size-Exclusion High-Performance Liquid Chromatography (HPLC).

Science.gov (United States)

Huang, Tao; He, Jiang

2017-01-01

Extracellular vesicles (EVs) have recently attracted substantial attention due to the potential diagnostic and therapeutic relevance. Although a variety of techniques have been used to isolate and analyze EVs, it is still far away from satisfaction. Size-exclusion chromatography (SEC), which separates subjects by size, has been widely applied in protein purification and analysis. The purpose of this chapter is to show the applications of size-exclusion high-performance liquid chromatography (HPLC) as methods for EV characterization of impurities or contaminants of small size, and thus for quality assay for the purity of the samples of EVs.

On the unlikeliness of multi-field inflation: bounded random potentials and our vacuum

International Nuclear Information System (INIS)

Battefeld, Diana; Battefeld, Thorsten; Schulz, Sebastian

2012-01-01

Based on random matrix theory, we compute the likelihood of saddles and minima in a class of random potentials that are softly bounded from above and below, as required for the validity of low energy effective theories. Imposing this bound leads to a random mass matrix with non-zero mean of its entries. If the dimensionality of field-space is large, inflation is rare, taking place near a saddle point (if at all), since saddles are more likely than minima or maxima for common values of the potential. Due to the boundedness of the potential, the latter become more ubiquitous for rare low/large values respectively. Based on the observation of a positive cosmological constant, we conclude that the dimensionality of field-space after (and most likely during) inflation has to be low if no anthropic arguments are invoked, since the alternative, encountering a metastable deSitter vacuum by chance, is extremely unlikely

Sequential enzymatic derivatization coupled with online microdialysis sampling for simultaneous profiling of mouse tumor extracellular hydrogen peroxide, lactate, and glucose.

Science.gov (United States)

Su, Cheng-Kuan; Tseng, Po-Jen; Chiu, Hsien-Ting; Del Vall, Andrea; Huang, Yu-Fen; Sun, Yuh-Chang

2017-03-01

Probing tumor extracellular metabolites is a vitally important issue in current cancer biology. In this study an analytical system was constructed for the in vivo monitoring of mouse tumor extracellular hydrogen peroxide (H 2 O 2 ), lactate, and glucose by means of microdialysis (MD) sampling and fluorescence determination in conjunction with a smart sequential enzymatic derivatization scheme-involving a loading sequence of fluorogenic reagent/horseradish peroxidase, microdialysate, lactate oxidase, pyruvate, and glucose oxidase-for step-by-step determination of sampled H 2 O 2 , lactate, and glucose in mouse tumor microdialysate. After optimization of the overall experimental parameters, the system's detection limit reached as low as 0.002 mM for H 2 O 2 , 0.058 mM for lactate, and 0.055 mM for glucose, based on 3 μL of microdialysate, suggesting great potential for determining tumor extracellular concentrations of lactate and glucose. Spike analyses of offline-collected mouse tumor microdialysate and monitoring of the basal concentrations of mouse tumor extracellular H 2 O 2 , lactate, and glucose, as well as those after imparting metabolic disturbance through intra-tumor administration of a glucose solution through a prior-implanted cannula, were conducted to demonstrate the system's applicability. Our results evidently indicate that hyphenation of an MD sampling device with an optimized sequential enzymatic derivatization scheme and a fluorescence spectrometer can be used successfully for multi-analyte monitoring of tumor extracellular metabolites in living animals. Copyright © 2016 Elsevier B.V. All rights reserved.

Methods to isolate extracellular vesicles for diagnosis

Science.gov (United States)

Kang, Hyejin; Kim, Jiyoon; Park, Jaesung

2017-12-01

Extracellular vesicles (EVs) are small membrane-bound bodies that are released into extracellular space by diverse cells, and are found in body fluids like blood, urine and saliva. EVs contain RNA, DNA and proteins, which can be biomarkers for diagnosis. EVs can be obtained by minimally-invasive biopsy, so they are useful in disease diagnosis. High yield and purity contribute to precise diagnosis of disease, but damaged EVs and impurities can cause confu sed results. However, EV isolation methods have different yields and purities. Furthermore, the isolation method that is most suitable to maximize EV recovery efficiency depends on the experimental conditions. This review focuses on merits and demerits of several types of EV isolation methods, and provides examples of how to diagnose disease by exploiting information obtained by analysis of EVs.

Electric Mars: A large trans-terminator electric potential drop on closed magnetic field lines above Utopia Planitia

Science.gov (United States)

Collinson, Glyn; Mitchell, David; Xu, Shaosui; Glocer, Alex; Grebowsky, Joseph; Hara, Takuya; Lillis, Robert; Espley, Jared; Mazelle, Christian; Sauvaud, Jean-André; Fedorov, Andrey; Liemohn, Mike; Andersson, Laila; Jakosky, Bruce

2017-02-01

Parallel electric fields and their associated electric potential structures play a crucial role in ionospheric-magnetospheric interactions at any planet. Although there is abundant evidence that parallel electric fields play key roles in Martian ionospheric outflow and auroral electron acceleration, the fields themselves are challenging to directly measure due to their relatively weak nature. Using measurements by the Solar Wind Electron Analyzer instrument aboard the NASA Mars Atmosphere and Volatile EvolutioN (MAVEN) Mars Scout, we present the discovery and measurement of a substantial (ΦMars=7.7 ± 0.6 V) parallel electric potential drop on closed magnetic field lines spanning the terminator from day to night above the great impact basin of Utopia Planitia, a region largely free of crustal magnetic fields. A survey of the previous 26 orbits passing over a range of longitudes revealed similar signatures on seven orbits, with a mean potential drop (ΦMars) of 10.9 ± 0.8 V, suggestive that although trans-terminator electric fields of comparable strength are not ubiquitous, they may be common, at least at these northerly latitudes.

Electric Mars: A Large Trans-Terminator Electric Potential Drop on Closed Magnetic Field Lines Above Utopia Planitia

Science.gov (United States)

Collinson, Glyn; Mitchell, David; Xu, Shaosui; Glocer, Alex; Grebowsky, Joseph; Hara, Takuya; Lillis, Robert; Espley, Jared; Mazelle, Christian; Sauvaud, Jean-Andre

2017-01-01

Abstract Parallel electric fields and their associated electric potential structures play a crucial role inionospheric-magnetospheric interactions at any planet. Although there is abundant evidence that parallel electric fields play key roles in Martian ionospheric outflow and auroral electron acceleration, the fields themselves are challenging to directly measure due to their relatively weak nature. Using measurements by the Solar Wind Electron Analyzer instrument aboard the NASA Mars Atmosphere and Volatile EvolutioN(MAVEN) Mars Scout, we present the discovery and measurement of a substantial (Phi) Mars 7.7 +/-0.6 V) parallel electric potential drop on closed magnetic field lines spanning the terminator from day to night above the great impact basin of Utopia Planitia, a region largely free of crustal magnetic fields. A survey of the previous 26 orbits passing over a range of longitudes revealed similar signatures on seven orbits, with a mean potential drop (Phi) Mars of 10.9 +/- 0.8 V, suggestive that although trans-terminator electric fields of comparable strength are not ubiquitous, they may be common, at least at these northerly latitudes.

Evanescent field: A potential light-tool for theranostics application

Science.gov (United States)

Polley, Nabarun; Singh, Soumendra; Giri, Anupam; Pal, Samir Kumar

2014-03-01

A noninvasive or minimally invasive optical approach for theranostics, which would reinforce diagnosis, treatment, and preferably guidance simultaneously, is considered to be major challenge in biomedical instrument design. In the present work, we have developed an evanescent field-based fiber optic strategy for the potential theranostics application in hyperbilirubinemia, an increased concentration of bilirubin in the blood and is a potential cause of permanent brain damage or even death in newborn babies. Potential problem of bilirubin deposition on the hydroxylated fiber surface at physiological pH (7.4), that masks the sensing efficacy and extraction of information of the pigment level, has also been addressed. Removal of bilirubin in a blood-phantom (hemoglobin and human serum albumin) solution from an enhanced level of 77 μM/l (human jaundice >50 μM/l) to ˜30 μM/l (normal level ˜25 μM/l in human) using our strategy has been successfully demonstrated. In a model experiment using chromatography paper as a mimic of biological membrane, we have shown efficient degradation of the bilirubin under continuous monitoring for guidance of immediate/future course of action.

Extracellular matrix components direct porcine muscle stem cell behavior

International Nuclear Information System (INIS)

Wilschut, Karlijn J.; Haagsman, Henk P.; Roelen, Bernard A.J.

2010-01-01

In muscle tissue, extracellular matrix proteins, together with the vasculature system, muscle-residence cells and muscle fibers, create the niche for muscle stem cells. The niche is important in controlling proliferation and directing differentiation of muscle stem cells to sustain muscle tissue. Mimicking the extracellular muscle environment improves tools exploring the behavior of primary muscle cells. Optimizing cell culture conditions to maintain muscle commitment is important in stem cell-based studies concerning toxicology screening, ex vivo skeletal muscle tissue engineering and in the enhancement of clinical efficiency. We used the muscle extracellular matrix proteins collagen type I, fibronectin, laminin, and also gelatin and Matrigel as surface coatings of tissue culture plastic to resemble the muscle extracellular matrix. Several important factors that determine myogenic commitment of the primary muscle cells were characterized by quantitative real-time RT-PCR and immunofluorescence. Adhesion of high PAX7 expressing satellite cells was improved if the cells were cultured on fibronectin or laminin coatings. Cells cultured on Matrigel and laminin coatings showed dominant integrin expression levels and exhibited an activated Wnt pathway. Under these conditions both stem cell proliferation and myogenic differentiation capacity were superior if compared to cells cultured on collagen type I, fibronectin and gelatin. In conclusion, Matrigel and laminin are the preferred coatings to sustain the proliferation and myogenic differentiation capacity of the primary porcine muscle stem cells, when cells are removed from their natural environment for in vitro culture.

Nucleases from Prevotella intermedia can degrade neutrophil extracellular traps.

Science.gov (United States)

Doke, M; Fukamachi, H; Morisaki, H; Arimoto, T; Kataoka, H; Kuwata, H

2017-08-01

Periodontitis is an inflammatory disease caused by periodontal bacteria in subgingival plaque. These bacteria are able to colonize the periodontal region by evading the host immune response. Neutrophils, the host's first line of defense against infection, use various strategies to kill invading pathogens, including neutrophil extracellular traps (NETs). These are extracellular net-like fibers comprising DNA and antimicrobial components such as histones, LL-37, defensins, myeloperoxidase, and neutrophil elastase from neutrophils that disarm and kill bacteria extracellularly. Bacterial nuclease degrades the NETs to escape NET killing. It has now been shown that extracellular nucleases enable bacteria to evade this host antimicrobial mechanism, leading to increased pathogenicity. Here, we compared the DNA degradation activity of major Gram-negative periodontopathogenic bacteria, Porphyromonas gingivalis, Prevotella intermedia, Fusobacterium nucleatum, and Aggregatibacter actinomycetemcomitans. We found that Pr. intermedia showed the highest DNA degradation activity. A genome search of Pr. intermedia revealed the presence of two genes, nucA and nucD, putatively encoding secreted nucleases, although their enzymatic and biological activities are unknown. We cloned nucA- and nucD-encoding nucleases from Pr. intermedia ATCC 25611 and characterized their gene products. Recombinant NucA and NucD digested DNA and RNA, which required both Mg 2+ and Ca 2+ for optimal activity. In addition, NucA and NucD were able to degrade the DNA matrix comprising NETs. © 2016 The Authors Molecular Oral Microbiology Published by John Wiley & Sons Ltd.

Extracellular matrix components direct porcine muscle stem cell behavior

Energy Technology Data Exchange (ETDEWEB)

Wilschut, Karlijn J. [Department of Farm Animal Health, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 104, 3584 CM, Utrecht (Netherlands); Haagsman, Henk P. [Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 1, 3584 CL, Utrecht (Netherlands); Roelen, Bernard A.J., E-mail: b.a.j.roelen@uu.nl [Department of Farm Animal Health, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 104, 3584 CM, Utrecht (Netherlands)

2010-02-01

In muscle tissue, extracellular matrix proteins, together with the vasculature system, muscle-residence cells and muscle fibers, create the niche for muscle stem cells. The niche is important in controlling proliferation and directing differentiation of muscle stem cells to sustain muscle tissue. Mimicking the extracellular muscle environment improves tools exploring the behavior of primary muscle cells. Optimizing cell culture conditions to maintain muscle commitment is important in stem cell-based studies concerning toxicology screening, ex vivo skeletal muscle tissue engineering and in the enhancement of clinical efficiency. We used the muscle extracellular matrix proteins collagen type I, fibronectin, laminin, and also gelatin and Matrigel as surface coatings of tissue culture plastic to resemble the muscle extracellular matrix. Several important factors that determine myogenic commitment of the primary muscle cells were characterized by quantitative real-time RT-PCR and immunofluorescence. Adhesion of high PAX7 expressing satellite cells was improved if the cells were cultured on fibronectin or laminin coatings. Cells cultured on Matrigel and laminin coatings showed dominant integrin expression levels and exhibited an activated Wnt pathway. Under these conditions both stem cell proliferation and myogenic differentiation capacity were superior if compared to cells cultured on collagen type I, fibronectin and gelatin. In conclusion, Matrigel and laminin are the preferred coatings to sustain the proliferation and myogenic differentiation capacity of the primary porcine muscle stem cells, when cells are removed from their natural environment for in vitro culture.

Laminin and biomimetic extracellular elasticity enhance functional differentiation in mammary epithelia

Energy Technology Data Exchange (ETDEWEB)

Alcaraz, Jordi; Xu, Ren; Mori, Hidetoshi; Nelson, Celeste M.; Mroue, Rana; Spencer, Virginia A.; Brownfield, Doug; Radisky, Derek C.; Bustamante, Carlos; Bissell, Mina J.

2008-10-20

In the mammary gland, epithelial cells are embedded in a 'soft' environment and become functionally differentiated in culture when exposed to a laminin-rich extracellular matrix gel. Here, we define the processes by which mammary epithelial cells integrate biochemical and mechanical extracellular cues to maintain their differentiated phenotype. We used single cells cultured on top of gels in conditions permissive for {beta}-casein expression using atomic force microscopy to measure the elasticity of the cells and their underlying substrata. We found that maintenance of {beta}-casein expression required both laminin signalling and a 'soft' extracellular matrix, as is the case in normal tissues in vivo, and biomimetic intracellular elasticity, as is the case in primary mammary epithelial organoids. Conversely, two hallmarks of breast cancer development, stiffening of the extracellular matrix and loss of laminin signalling, led to the loss of {beta}-casein expression and non-biomimetic intracellular elasticity. Our data indicate that tissue-specific gene expression is controlled by both the tissues unique biochemical milieu and mechanical properties, processes involved in maintenance of tissue integrity and protection against tumorigenesis.

Involvement of amygdalar extracellular zinc in rat behavior for passive avoidance.

Science.gov (United States)

Takeda, Atsushi; Minami, Akira; Yamaide, Rie; Oku, Naoto

2004-03-25

On the basis of the evidence that zinc is released from glutamatergic neuron terminals in the amygdala, the effect of chelation of amygdalar extracellular zinc on glutamate release from the neuron terminals was studied by using in vivo microdialysis. When the amygdala was perfused with 100 microM CaEDTA to chelate extracellular zinc, glutamate concentration in the perfusate was decreased significantly, whereas that tended to be increased by perfusion with 100 microM ZnEDTA as a control. The effect of CaEDTA on extracellular glutamate levels was different between the amygdala and hippocampus, implying that modulation of glutamate signaling by zinc is different between them. To evaluate chelation of zinc in rat behavior, perfusion of the amygdala with CaEDTA was started 40 min before behavioral test for passive avoidance. The behavior for passive avoidance was impaired during perfusion with CaEDTA. On the other hand, the behavior during perfusion with ZnEDTA was more rapidly developed than that with vehicle only. These results suggest that amygdalar extracellular zinc is involved in the behavior for passive avoidance.

Extracellular secretion of recombinant proteins

Science.gov (United States)

Linger, Jeffrey G.; Darzins, Aldis

2014-07-22

Nucleic acids encoding secretion signals, expression vectors containing the nucleic acids, and host cells containing the expression vectors are disclosed. Also disclosed are polypeptides that contain the secretion signals and methods of producing polypeptides, including methods of directing the extracellular secretion of the polypeptides. Exemplary embodiments include cellulase proteins fused to secretion signals, methods to produce and isolate these polypeptides, and methods to degrade lignocellulosic biomass.

Solar system tests of scalar field models with an exponential potential

International Nuclear Information System (INIS)

Paramos, J.; Bertolami, O.

2008-01-01

We consider a scenario where the dynamics of a scalar field is ruled by an exponential potential, such as those arising from some quintessence-type models, and aim at obtaining phenomenological manifestations of this entity within our Solar System. To do so, we assume a perturbative regime, derive the perturbed Schwarzschild metric, and extract the relevant post-Newtonian parameters.

Unraveling nonadiabatic ionization and Coulomb potential effect in strong-field photoelectron holography.

Science.gov (United States)

Song, Xiaohong; Lin, Cheng; Sheng, Zhihao; Liu, Peng; Chen, Zhangjin; Yang, Weifeng; Hu, Shilin; Lin, C D; Chen, Jing

2016-06-22

Strong field photoelectron holography has been proposed as a means for interrogating the spatial and temporal information of electrons and ions in a dynamic system. After ionization, part of the electron wave packet may directly go to the detector (the reference wave), while another part may be driven back and scatters off the ion(the signal wave). The interference hologram of the two waves may be used to extract target information embedded in the collision process. Unlike conventional optical holography, however, propagation of the electron wave packet is affected by the Coulomb potential as well as by the laser field. In addition, electrons are emitted over the whole laser pulse duration, thus multiple interferences may occur. In this work, we used a generalized quantum-trajectory Monte Carlo method to investigate the effect of Coulomb potential and the nonadiabatic subcycle ionization on the photoelectron hologram. We showed that photoelectron hologram can be well described only when the effect of nonadiabatic ionization is accounted for, and Coulomb potential can be neglected only in the tunnel ionization regime. Our results help paving the way for establishing photoelectron holography for probing spatial and dynamic properties of atoms and molecules.

Extracellular Membrane Vesicles and Phytopathogenicity of Acholeplasma laidlawii PG8

Directory of Open Access Journals (Sweden)

Vladislav M. Chernov

2012-01-01

Full Text Available For the first time, the phytopathogenicity of extracellular vesicles of Acholeplasma laidlawii PG8 (a ubiquitous mycoplasma that is one of the five common species of cell culture contaminants and is a causative agent for phytomycoplasmoses in Oryza sativa L. plants was studied. Data on the ability of extracellular vesicles of Acholeplasma laidlawii PG8 to penetrate from the nutrient medium into overground parts of Oryza sativa L. through the root system and to cause alterations in ultrastructural organization of the plants were presented. As a result of the analysis of ultrathin leaf sections of plants grown in medium with A. laidlawii PG8 vesicles, we detected significant changes in tissue ultrastructure characteristic to oxidative stress in plants as well as their cultivation along with bacterial cells. The presence of nucleotide sequences of some mycoplasma genes within extracellular vesicles of Acholeplasma laidlawii PG8 allowed a possibility to use PCR (with the following sequencing to perform differential detection of cells and bacterial vesicles in samples under study. The obtained data may suggest the ability of extracellular vesicles of the mycoplasma to display in plants the features of infection from the viewpoint of virulence criteria—invasivity, infectivity—and toxigenicity—and to favor to bacterial phytopathogenicity.

Syndecans as receptors and organizers of the extracellular matrix

DEFF Research Database (Denmark)

Xian, Xiaojie; Gopal, Sandeep; Couchman, John

2009-01-01

, the collagens and glycoproteins of the extracellular matrix are prominent. Frequently, they do so in conjunction with other receptors, most notably the integrins. For this reason, they are often referred to as "co-receptors". However, just as with integrins, syndecans can interact with actin-associated proteins...... and signalling molecules, such as protein kinases. Some aspects of syndecan signalling are understood but much remains to be learned. The functions of syndecans in regulating cell adhesion and extracellular matrix assembly are described here. Evidence from null mice suggests that syndecans have roles...

MOTION MODELLINGUSINGCONCEPTS OF FUZZY ARTIFICIAL POTENTIAL FIELDS

Directory of Open Access Journals (Sweden)

O. Motlagh

2010-12-01

Full Text Available Artificial potential fields (APF are well established for reactive navigation of mobile robots. This paper describes a fast and robust fuzzy-APF on an ActivMedia AmigoBot. Obstacle-related information is fuzzified by using sensory fusion, which results in a shorter runtime. In addition, the membership functions of obstacle direction and range have been merged into one function, obtaining a smaller block of rules. The system is tested in virtual environments with non-concave obstacles. Then, the paper describes a new approach to motion modelling where the motion of intelligent travellers is modelled by consecutive path segments. In previous work, the authors described a reliable motion modelling technique using causal inference of fuzzy cognitive maps (FCM which has been efficiently modified for the purpose of this contribution. Results and analysis are given to demonstrate the efficiency and accuracy of the proposed motion modelling algorithm.

α1-Adrenoceptors in the hippocampal dentate gyrus involved in learning-dependent long-term potentiation during active-avoidance learning in rats.

Science.gov (United States)

Lv, Jing; Zhan, Su-Yang; Li, Guang-Xie; Wang, Dan; Li, Ying-Shun; Jin, Qing-Hua

2016-11-09

The hippocampus is the key structure for learning and memory in mammals and long-term potentiation (LTP) is an important cellular mechanism responsible for learning and memory. The influences of norepinephrine (NE) on the modulation of learning and memory, as well as LTP, through β-adrenoceptors are well documented, whereas the role of α1-adrenoceptors in learning-dependent LTP is not yet clear. In the present study, we measured extracellular concentrations of NE in the hippocampal dentate gyrus (DG) region using an in-vivo brain microdialysis and high-performance liquid chromatography techniques during the acquisition and extinction of active-avoidance behavior in freely moving conscious rats. Next, the effects of prazosin (an antagonist of α1-adrenoceptor) and phenylephrine (an agonist of the α1-adrenoceptor) on amplitudes of field excitatory postsynaptic potential were measured in the DG region during the active-avoidance behavior. Our results showed that the extracellular concentration of NE in the DG was significantly increased during the acquisition of active-avoidance behavior and gradually returned to the baseline level following extinction training. A local microinjection of prazosin into the DG significantly accelerated the acquisition of the active-avoidance behavior, whereas a local microinjection of phenylephrine retarded the acquisition of the active-avoidance behavior. Furthermore, in all groups, the changes in field excitatory postsynaptic potential amplitude were accompanied by corresponding changes in active-avoidance behavior. Our results suggest that NE activation of α1-adrenoceptors in the hippocampal DG inhibits active-avoidance learning by modulation of synaptic efficiency in rats.

The effect of membrane diffusion potential change on anionic drugs ...

African Journals Online (AJOL)

The effect of membrane potential change on anionic drugs Indomethacin and barbitone induced human erythrocyte shape change and red cell uptake of drug has been studied using microscopy and spectrophotometry techniques respectively. The membrane potential was changed by reducing the extracellular chloride ...

The extracellular matrix of plants: Molecular, cellular and developmental biology

Energy Technology Data Exchange (ETDEWEB)

NONE

1996-12-31

A symposium entitled ``The Extracellular Matrix of Plants: Molecular, Cellular and Developmental Biology was held in Tamarron, Colorado, March 15--21, 1996. The following topics were explored in addresses by 43 speakers: structure and biochemistry of cell walls; biochemistry, molecular biology and biosynthesis of lignin; secretory pathway and synthesis of glycoproteins; biosynthesis of matrix polysaccharides, callose and cellulose; role of the extracellular matrix in plant growth and development; plant cell walls in symbiosis and pathogenesis.

Extracellular space diffusion and extrasynaptic transmission

Czech Academy of Sciences Publication Activity Database

Vargová, Lýdia; Syková, Eva

2008-01-01

Roč. 57, Suppl.3 (2008), S89-S99 ISSN 0862-8408 R&D Projects: GA MŠk 1M0538; GA MŠk(CZ) LC554 Institutional research plan: CEZ:AV0Z50390512 Keywords : Diffusion * Extracellular volume * Tortuosity Subject RIV: FH - Neurology Impact factor: 1.653, year: 2008

Analysis of cellular and extracellular DNA in fingerprints

Energy Technology Data Exchange (ETDEWEB)

Button, Julie M. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

2014-09-09

It has been previously shown that DNA can be recovered from latent fingerprints left on various surfaces [R. A. H. van Oorschot and M. K. Jones, Nature 387, 767 (1997)]. However, the source of the DNA, extracellular versus cellular origin, is difficult to determine. If the DNA is cellular, it is believed to belong to skin cells while extracellular DNA is believed to originate from body fluids such as sweat [D. J. Daly et. al, Forensic Sci. Int. Genet. 6, 41-46 (2012); V. V. Vlassov et. al, BioEssays 29, 654-667 (2007)]. The origin of the DNA in fingerprints has implications for processing and interpretation of forensic evidence. The determination of the origin of DNA in fingerprints is further complicated by the fact that the DNA in fingerprints tends to be at a very low quantity [R. A. H. van Oorschot and M. K. Jones, Nature 387, 767 (1997)]. This study examined fingerprints from five volunteers left on sterilized glass slides and plastic pens. Three fingerprints were left on each glass slide (thumb, index, and middle fingers) while the pens were held as if one was writing with them. The DNA was collected from the objects using the wet swabbing technique (TE buffer). Following collection, the cellular and extracellular components of each sample were separated using centrifugation and an acoustofluidics system. Centrifugation is still the primary separation technique utilized in forensics laboratories, while acoustic focusing uses sound waves to focus large particles (cells) into low pressure nodes, separating them from the rest of the sample matrix. After separation, all samples were quantified using real-time quantitative PCR (qPCR). The overall trend is that there is more DNA in the extracellular fractions than cellular fractions for both centrifugation and acoustofluidic processing. Additionally, more DNA was generally collected from the pen samples than the samples left on glass slides.

miR-200–containing extracellular vesicles promote breast cancer cell metastasis

Science.gov (United States)

Le, Minh T.N.; Hamar, Peter; Guo, Changying; Basar, Emre; Perdigão-Henriques, Ricardo; Balaj, Leonora; Lieberman, Judy

2014-01-01

Metastasis is associated with poor prognosis in breast cancer patients. Not all cancer cells within a tumor are capable of metastasizing. The microRNA-200 (miR-200) family, which regulates the mesenchymal-to-epithelial transition, is enriched in the serum of patients with metastatic cancers. Ectopic expression of miR-200 can confer metastatic ability to poorly metastatic tumor cells in some settings. Here, we investigated whether metastatic capability could be transferred between metastatic and nonmetastatic cancer cells via extracellular vesicles. miR-200 was secreted in extracellular vesicles from metastatic murine and human breast cancer cell lines, and miR-200 levels were increased in sera of mice bearing metastatic tumors. In culture, murine and human metastatic breast cancer cell extracellular vesicles transferred miR-200 microRNAs to nonmetastatic cells, altering gene expression and promoting mesenchymal-to-epithelial transition. In murine cancer and human xenograft models, miR-200–expressing tumors and extracellular vesicles from these tumors promoted metastasis of otherwise weakly metastatic cells either nearby or at distant sites and conferred to these cells the ability to colonize distant tissues in a miR-200–dependent manner. Together, our results demonstrate that metastatic capability can be transferred by the uptake of extracellular vesicles. PMID:25401471

Royal Society Scientific Meeting: Extracellular vesicles in the tumour microenvironment.

Science.gov (United States)

Pink, Ryan Charles; Elmusrati, Areeg A; Lambert, Daniel; Carter, David Raul Francisco

2018-01-05

Cancer cells do not grow as an isolated homogeneous mass; tumours are, in fact, complex and heterogeneous collections of cancer and surrounding stromal cells, collectively termed the tumour microenvironment. The interaction between cancer cells and stromal cells in the tumour microenvironment has emerged as a key concept in the regulation of cancer progression. Understanding the intercellular dialogue in the tumour microenvironment is therefore an important goal. One aspect of this dialogue that has not been appreciated until recently is the role of extracellular vesicles (EVs). EVs are small vesicles released by cells under both normal and pathological conditions; they can transfer biological molecules between cells leading to changes in phenotype. EVs have emerged as important regulators of biological processes and can be dysregulated in diseases such as cancer; rapidly growing interest in their biology and therapeutic potential led to the Royal Society hosting a Scientific Meeting to explore the roles of EVs in the tumour microenvironment. This cross-disciplinary meeting explored examples of how aberrant crosstalk between tumour and stromal cells can promote cancer progression, and how such signalling can be targeted for diagnostic, prognostic and therapeutic benefit. In this review, and the special edition of Philosophical Transactions of the Royal Society B that follows, we will provide an overview of the content and outcomes of this exciting meeting.This article is part of the discussion meeting issue 'Extracellular vesicles and the tumour microenvironment'. © 2017 The Author(s).

Reconstruction of the Scalar Field Potential in Inflationary Models with a Gauss-Bonnet term

Science.gov (United States)

Koh, Seoktae; Lee, Bum-Hoon; Tumurtushaa, Gansukh

2017-06-01

We consider inflationary models with a Gauss-Bonnet term to reconstruct the scalar-field potentials and the Gauss-Bonnet coupling functions. Both expressions are derived from the observationally favored configurations of ns and r . Our result implies that, for the reconstructed potentials and coupling functions, the blue tilt of inflationary tensor fluctuations can be realized. To achieve a blue tilt for the inflationary tensor fluctuations, a scalar field must climb up its potential before rolling down. We further investigate the properties of propagation of the perturbation modes in Friedmann-Robertson-Walker spacetime. For the reconstructed configurations that give rise to the blue tilt for the inflationary tensor fluctuations, we show that the ghosts and instabilities are absent with the superluminal propagation speeds for the scalar perturbation modes, whereas the propagation speeds of the tensor perturbations are subluminal.

Time and space-correlated plasma potential measurements in the near field of a coaxial Hall plasma discharge

International Nuclear Information System (INIS)

Smith, A. W.; Cappelli, M. A.

2009-01-01

Space- and time-correlated measurements of floating and plasma potential are made in the near field, external flow cathode region of a coaxial Hall plasma discharge using an emissive probe synchronized to quasicoherent fluctuations in discharge current. The luminous axial feature frequently observed in the near field of operating plasma accelerators is found to be concomitant with a spike in the plasma potential (and electron temperature). The structure of the plasma potential allows for multiple avenues for back-streaming ions to accelerate toward the discharge front pole and may pull some classes of ions toward the central axis. The fluctuations in plasma properties exhibit a complex structure at frequencies on the order of the so-called 'breathing mode' ionization instability often seen in these types of discharges. Most notably, the plasma potential appears to fluctuate in a helical fashion, resembling tilted drift waves rotating about the central axis. A simple analysis of these waves draws attention to the possible role that they may play in driving anomalous cross-field electron transport in the near field region.

Current-current correlation function in presence of chemical potential and external magnetic field

International Nuclear Information System (INIS)

Apresyan, E.A.

2017-01-01

The (2+1)-dimensional electron system was observed, where relation between the Green functions and conductivity was used. The current-current correlation function Π_μ_ν(B) for the fermion system was calculated in presence of non-quantizing magnetic field B, chemical potential η and gap m. From this function it is possible to obtain the equation for polarization operator calculated without the magnetic field. The result is also applicable for graphene

Extracellular Alkalinization as a Defense Response in Potato Cells.

Science.gov (United States)

Moroz, Natalia; Fritch, Karen R; Marcec, Matthew J; Tripathi, Diwaker; Smertenko, Andrei; Tanaka, Kiwamu

2017-01-01

A quantitative and robust bioassay to assess plant defense response is important for studies of disease resistance and also for the early identification of disease during pre- or non-symptomatic phases. An increase in extracellular pH is known to be an early defense response in plants. In this study, we demonstrate extracellular alkalinization as a defense response in potatoes. Using potato suspension cell cultures, we observed an alkalinization response against various pathogen- and plant-derived elicitors in a dose- and time-dependent manner. We also assessed the defense response against a variety of potato pathogens, such as protists ( Phytophthora infestans and Spongospora subterranea ) and fungi ( Verticillium dahliae and Colletotrichum coccodes ). Our results show that extracellular pH increases within 30 min in proportion to the number of pathogen spores added. Consistently with the alkalinization effect, the higher transcription level of several defense-related genes and production of reactive oxygen species was observed. Our results demonstrate that the alkalinization response is an effective marker to study early stages of defense response in potatoes.

Influence of the Ambient Electric Field on Measurements of the Actively Controlled Spacecraft Potential by MMS

Science.gov (United States)

Torkar, K.; Nakamura, R.; Andriopoulou, M.; Giles, B. L.; Jeszenszky, H.; Khotyaintsev, Y. V.; Lindqvist, P.-A.; Torbert, R. B.

2017-12-01

Space missions with sophisticated plasma instrumentation such as Magnetospheric Multiscale, which employs four satellites to explore near-Earth space benefit from a low electric potential of the spacecraft, to improve the plasma measurements and therefore carry instruments to actively control the potential by means of ion beams. Without control, the potential varies in anticorrelation with plasma density and temperature to maintain an equilibrium between the plasma current and the one of photoelectrons produced at the surface and overcoming the potential barrier. A drawback of the controlled, almost constant potential is the difficulty to use it as convenient estimator for plasma density. This paper identifies a correlation between the spacecraft potential and the ambient electric field, both measured by double probes mounted at the end of wire booms, as the main responsible for artifacts in the potential data besides the known effect of the variable photoelectron production due to changing illumination of the surface. It is shown that the effect of density variations is too weak to explain the observed correlation with the electric field and that a correction of the artifacts can be achieved to enable the reconstruction of the uncontrolled potential and plasma density in turn. Two possible mechanisms are discussed: the asymmetry of the current-voltage characteristic determining the probe to plasma potential and the fact that a large equipotential structure embedded in an electric field results in asymmetries of both the emission and spatial distribution of photoelectrons, which results in an increase of the spacecraft potential.

Comparative evaluation of extracellular β-D-fructofuranosidase in submerged and solid-state fermentation produced by newly identified Bacillus subtilis strain.

Science.gov (United States)

Lincoln, Lynette; More, Sunil S

2018-04-17

To screen and identify a potential extracellular β-D-fructofuranosidase or invertase producing bacterium from soil, and comparatively evaluate the enzyme biosynthesis under submerged and solid-state fermentation. Extracellular invertase producing bacteria were screened from soil. Identification of the potent bacterium was performed based on microscopic examinations and 16S rDNA molecular sequencing. Bacillus subtilis LYN12 invertase secretion was surplus with wheat bran humidified with molasses medium (70%), with elevated activity at 48 h and 37 °C under solid-state fermentation, whereas under submerged conditions increased activity was observed at 24 h and 45 °C in the molasses medium. The study revealed a simple fermentative medium for elevated production of extracellular invertase from a fast growing Bacillus strain. Bacterial invertases are scarce and limited reports are available. By far, this is the first report on the comparative analysis of optimization of extracellular invertase synthesis from Bacillus subtilis strain by submerged and solid-state fermentation. The use of agricultural residues increased yields resulting in development of a cost-effective and stable approach. Bacillus subtilis LYN12 invertase possesses excellent fermenting capability to utilize agro-industrial residues under submerged and solid-state conditions. This could be a beneficial candidate in food and beverage processing industries. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Extracellular functions of glycolytic enzymes of parasites: unpredicted use of ancient proteins.

Science.gov (United States)

Gómez-Arreaza, Amaranta; Acosta, Hector; Quiñones, Wilfredo; Concepción, Juan Luis; Michels, Paul A M; Avilán, Luisana

2014-02-01

In addition of their usual intracellular localization where they are involved in catalyzing reactions of carbohydrate and energy metabolism by glycolysis, multiple studies have shown that glycolytic enzymes of many organisms, but notably pathogens, can also be present extracellularly. In the case of parasitic protists and helminths, they can be found either secreted or attached to the surface of the parasites. At these extracellular localizations, these enzymes have been shown to perform additional, very different so-called "moonlighting" functions, such as acting as ligands for a variety of components of the host. Due to this recognition, different extracellular glycolytic enzymes participate in various important parasite-host interactions such as adherence and invasion of parasites, modulation of the host's immune and haemostatic systems, promotion of angiogenesis, and acquisition of specific nutrients by the parasites. Accordingly, extracellular glycolytic enzymes are important for the invasion of the parasites and their establishment in the host, and in determining their virulence. Copyright © 2014 Elsevier B.V. All rights reserved.

The mannosylated extracellular domain of Her2/neu produced in P. pastoris induces protective antitumor immunity

International Nuclear Information System (INIS)

Dimitriadis, Alexios; Gontinou, Chrysanthi; Baxevanis, Constantin N; Mamalaki, Avgi

2009-01-01

Her2/neu is overexpressed in various human cancers of epithelial origin and is associated with increased metastatic potential and poor prognosis. Several attempts have been made using the extracellular domain of Her2/neu (ECD/Her2) as a prophylactic vaccine in mice with no success in tumor prevention. The extracellular domain of Her2/neu (ECD/Her2) was expressed in yeast P. pastoris, in a soluble highly mannosylated form. The immune response of the immunization with this recombinant ECD/Her2 was analyzed using immunoprecipitation and western blot analysis, proliferation and cytotoxicity assays as well as specific tumor growth assays. Mannosylated ECD/Her2 elicited a humoral response with HER2/neu specific antibodies in vaccinated mice, which were able to reduce the proliferation rate of cancer cells in vitro. Moreover, it elicited a cellular response with Her2/neu-specific CTL capable of lysing tumor cells, in vitro. When immunized Balb/c and HHD mice were challenged with Her2/neu-overexpressing cells, tumor growth was inhibited. Here we report on the efficacy of the extracellular domain of human Her2/neu produced in yeast P. pastoris, which confers mannosylation of the protein, to act as a potent anti-tumor vaccine against Her2/neu overexpressing tumors. Specific cellular and humoral responses were observed as well as efficacy

Extracellular Polymeric Substances Govern the Surface Charge of Biogenic Elemental Selenium Nanoparticles

KAUST Repository

Jain, Rohan

2015-02-03

© 2014 American Chemical Society. The origin of the organic layer covering colloidal biogenic elemental selenium nanoparticles (BioSeNPs) is not known, particularly in the case when they are synthesized by complex microbial communities. This study investigated the presence of extracellular polymeric substances (EPS) on BioSeNPs. The role of EPS in capping the extracellularly available BioSeNPs was also examined. Fourier transform infrared (FT-IR) spectroscopy and colorimetric measurements confirmed the presence of functional groups characteristic of proteins and carbohydrates on the BioSeNPs, suggesting the presence of EPS. Chemical synthesis of elemental selenium nanoparticles in the presence of EPS, extracted from selenite fed anaerobic granular sludge, yielded stable colloidal spherical selenium nanoparticles. Furthermore, extracted EPS, BioSeNPs, and chemically synthesized EPS-capped selenium nanoparticles had similar surface properties, as shown by ζ-potential versus pH profiles and isoelectric point measurements. This study shows that the EPS of anaerobic granular sludge form the organic layer present on the BioSeNPs synthesized by these granules. The EPS also govern the surface charge of these BioSeNPs, thereby contributing to their colloidal properties, hence affecting their fate in the environment and the efficiency of bioremediation technologies.

Extracellular matrix in lung development, homeostasis and disease.

Science.gov (United States)

Zhou, Yong; Horowitz, Jeffrey C; Naba, Alexandra; Ambalavanan, Namasivayam; Atabai, Kamran; Balestrini, Jenna; Bitterman, Peter B; Corley, Richard A; Ding, Bi-Sen; Engler, Adam J; Hansen, Kirk C; Hagood, James S; Kheradmand, Farrah; Lin, Qing S; Neptune, Enid; Niklason, Laura; Ortiz, Luis A; Parks, William C; Tschumperlin, Daniel J; White, Eric S; Chapman, Harold A; Thannickal, Victor J

2018-03-08

The lung's unique extracellular matrix (ECM), while providing structural support for cells, is critical in the regulation of developmental organogenesis, homeostasis and injury-repair responses. The ECM, via biochemical or biomechanical cues, regulates diverse cell functions, fate and phenotype. The composition and function of lung ECM become markedly deranged in pathological tissue remodeling. ECM-based therapeutics and bioengineering approaches represent promising novel strategies for regeneration/repair of the lung and treatment of chronic lung diseases. In this review, we assess the current state of lung ECM biology, including fundamental advances in ECM composition, dynamics, topography, and biomechanics; the role of the ECM in normal and aberrant lung development, adult lung diseases and autoimmunity; and ECM in the regulation of the stem cell niche. We identify opportunities to advance the field of lung ECM biology and provide a set recommendations for research priorities to advance knowledge that would inform novel approaches to the pathogenesis, diagnosis, and treatment of chronic lung diseases. Copyright © 2017. Published by Elsevier B.V.

Imaging hydrated microbial extracellular polymers: Comparative analysis by electron microscopy

Energy Technology Data Exchange (ETDEWEB)

Dohnalkova, A.C.; Marshall, M. J.; Arey, B. W.; Williams, K. H.; Buck, E. C.; Fredrickson, J. K.

2011-01-01

Microbe-mineral and -metal interactions represent a major intersection between the biosphere and geosphere but require high-resolution imaging and analytical tools for investigating microscale associations. Electron microscopy has been used extensively for geomicrobial investigations and although used bona fide, the traditional methods of sample preparation do not preserve the native morphology of microbiological components, especially extracellular polymers. Herein, we present a direct comparative analysis of microbial interactions using conventional electron microscopy approaches of imaging at room temperature and a suite of cryogenic electron microscopy methods providing imaging in the close-to-natural hydrated state. In situ, we observed an irreversible transformation of the hydrated bacterial extracellular polymers during the traditional dehydration-based sample preparation that resulted in their collapse into filamentous structures. Dehydration-induced polymer collapse can lead to inaccurate spatial relationships and hence could subsequently affect conclusions regarding nature of interactions between microbial extracellular polymers and their environment.

Potential Risk Assessment of Mountain Torrent Disasters on Sloping Fields in China

Science.gov (United States)

GAO, X.

2017-12-01

China's sloping fields have the problems of low production and serious soil erosion, and mountain torrent disasters will bring more serious soil and water loss to traditional extensive exploitation of sloping field resources. In this paper, China's sloping fields were classified into three grades, such as slightly steep, steep and very steep grade. According to the geological hazards prevention and control regulation, the historical data of China's mountain torrent disasters were spatially interpolated and divided into five classes, such as extremely low, low, middle, high and extremely high level. And the risk level map of mountain torrents was finished in ArcGIS. By using overlaying analysis on sloping fields and risk level map, the potential risk regionalization map of sloping fields in various slope grades was obtained finally. The results shows that the very steep and steep sloping fields are mainly distributed in the first or second stage terraces in China. With the increase of hazard risk level, the area of sloping fields decreases rapidly and the sloping fields in extremely low and low risk levels of mountain torrents reach 98.9%. With the increase of slope grade, the area of sloping fields in various risk levels also declines sharply. The sloping fields take up approximately 60 65% and 26 30% in slightly steep and steep grade areas separately at different risk level. The risk regionalization map can provide effective information for returning farmland to forests or grassland and reducing water and soil erosion of sloping fields in the future.

Porphyromonas gingivalis-mediated shedding of extracellular matrix metalloproteinase inducer (EMMPRIN) by oral epithelial cells: a potential role in inflammatory periodontal disease.

Science.gov (United States)

Feldman, Mark; La, Vu Dang; Lombardo Bedran, Telma Blanca; Palomari Spolidorio, Denise Madalena; Grenier, Daniel

2011-12-01

Extracellular matrix metalloproteinase inducer (EMMPRIN) or CD147 is a transmembrane glycoprotein expressed by various cell types, including oral epithelial cells. Recent studies have brought evidence that EMMPRIN plays a role in periodontitis. In the present study, we investigated the effect of Porphyromonas gingivalis, a major pathogen in chronic periodontitis, on the shedding of membrane-anchored EMMPRIN and on the expression of the EMMPRIN gene by oral epithelial cells. A potential contribution of shed EMMPRIN to the inflammatory process of periodontitis was analyzed by evaluating the effect of recombinant EMMPRIN on cytokine and matrix metalloproteinase (MMP) secretion by human gingival fibroblasts. ELISA and immunofluorescence analyses revealed that P. gingivalis mediated the shedding of epithelial cell-surface EMMPRIN in a dose- and time-dependent manner. Cysteine proteinase (gingipain)-deficient P. gingivalis mutants were used to demonstrate that both Arg- and Lys-gingipain activities are involved in EMMPRIN shedding. Real-time PCR showed that P. gingivalis had no significant effect on the expression of the EMMPRIN gene in epithelial cells. Recombinant EMMPRIN induced the secretion of IL-6 and MMP-3 by gingival fibroblasts, a phenomenon that appears to involve mitogen activated protein kinases. The present study brought to light a new mechanism by which P. gingivalis can promote the inflammatory response during periodontitis. Copyright © 2011 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Extracellular synthesis gold nanotriangles using biomass of Streptomyces microflavus.

Science.gov (United States)

Soltani Nejad, Meysam; Khatami, Mehrdad; Shahidi Bonjar, Gholam Hosein

2016-02-01

Applications of nanotechnology and nano-science have ever-expanding breakthroughs in medicine, agriculture and industries in recent years; therefore, synthesis of metals nanoparticle (NP) has special significance. Synthesis of NPs by chemical methods are long, costly and hazardous for environment so biosynthesis has been developing interest for researchers. In this regard, the extracellular biosynthesis of gold nanotriangles (AuNTs) performed by use of the soil Streptomycetes. Streptomycetes isolated from rice fields of Guilan Province, Iran, showed biosynthetic activity for producing AuNTs via in vitro experiments. Among all 15 Streptomyces spp. isolates, isolate No. 5 showed high biosynthesis activity. To determine the bacterium taxonomical identity at genus level, its colonies characterised morphologically by use of scanning electron microscope. The polymerase chain reaction (PCR) molecular analysis of active isolate represented its identity partially. In this regard, 16S rRNA gene of the isolate was amplified using universal bacterial primers FD1 and RP2. The PCR products were purified and sequenced. Sequence analysis of 16S rDNA was then conducted using National Center for Biotechnology Information Basic Local Alignment Search Tool method. The AuNTs obtained were characterised by ultraviolet-visible spectroscopy, atomic force microscopy, transmission electron microscopy and energy dispersive X-ray spectroscopy, Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction spectroscopy analyses. The authors results indicated that Streptomyces microflavus isolate 5 bio-synthesises extracellular AuNTs in the range of 10-100 nm. Synthesised SNPs size ranged from 10 to 100 nm. In comparison with chemical methods for synthesis of metal NPs, the biosynthesis of AuNTs by Streptomyces source is a fast, simple and eco-friendly method. The isolate is a good candidate for further investigations to optimise its production efficacy for further industrial goals in

Space-frequency analysis and reduction of potential field ambiguity

Directory of Open Access Journals (Sweden)

A. Rapolla

1997-06-01

Full Text Available Ambiguity of depth estimation of magnetic sources via spectral analysis can be reduced representing its field via a set of space-frequency atoms. This is obtained throughout a continuous wavelet transform using a Morlet analyzing wavelet. In the phase-plane representation even a weak contribution related to deep-seated sources is clearly distinguished with respect a more intense effect of a shallow source, also in the presence of a strong noise. Furthermore, a new concept of local power spectrum allows the depth to both the sources to be correctly interpreted. Neither result can be provided by standard Fourier analysis. Another method is proposed to reduce ambiguity by inversion of potential field data lying along the vertical axis. This method allows a depth resolution to gravity or the magnetic methods and below some conditions helps to reduce their inherent ambiguity. Unlike the case of monopoles, inversion of a vertical profile of gravity data above a cubic source gives correct results for the cube side and density.

The impact of extracellular syntaxin4 on HaCaT keratinocyte behavior

International Nuclear Information System (INIS)

Kadono, Nanako; Miyazaki, Takafumi; Okugawa, Yoji; Nakajima, Kiichiro; Hirai, Yohei

2012-01-01

Highlights: ► A subpopulation of syntaxin4 localizes extracellularly in the keratinocytes. ► Epimorphin and syntaxin4 confer the resistance to the oxidative stress. ► Epimorphin suppresses and syntaxin4 accelerates the CCE formation. ► The antagonistic peptide to syntaxin4 blocks the syntaxin4-dependent CCE formation. -- Abstract: Syntaxin4 belongs to t-SNARE protein family and functions as a vesicular fusion mediator in the plasma membrane in a wide variety of cell types. This protein resembles another family member, epimorphin, a subpopulation of which has been shown to be secreted extracellularly in order to exert signaling functions. Here, we demonstrate the secretion of syntaxin4 via a non-classical pathway and its extracellular functions by using the functionally normal keratinocyte HaCaT. Extracellularly presented syntaxin4 appeared to elicit many cell responses similar to epimorphin with an important exception: it clearly facilitated keratinocyte cornification. The circularized peptide ST4n1 was synthesized from the putative functional core of syntaxin4 (a.a. 103–108), which is equivalent to the previously generated antagonist of epimorphin, and neutralized this contradictory effect. Intriguingly, an epimorphin mutant (EP4M) in which the functional core was replaced by that of syntaxin4 behaved like epimorphin, which was again antagonized by ST4n1. Electrophoresis-based analyses demonstrated the distinct structure of syntaxin4 compared to epimorphin or EP4M. These results revealed, for the first time, the extracellular role of syntaxin4 and shed light on the division of the extracellular effects exerted by epimorphin and syntaxin4 on keratinocyte cornification.

Incorporation of Tenascin-C into the Extracellular Matrix by Periostin Underlies an Extracellular Meshwork Architecture*

OpenAIRE

Kii, Isao; Nishiyama, Takashi; Li, Minqi; Matsumoto, Ken-ichi; Saito, Mitsuru; Amizuka, Norio; Kudo, Akira

2009-01-01

Extracellular matrix (ECM) underlies a complicated multicellular architecture that is subjected to significant forces from mechanical environment. Although various components of the ECM have been enumerated, mechanisms that evolve the sophisticated ECM architecture remain to be addressed. Here we show that periostin, a matricellular protein, promotes incorporation of tenascin-C into the ECM and organizes a meshwork architecture of the ECM. We found that both periostin null mice and tenascin-C...

Extracellular vesicles as a platform for membrane-associated therapeutic protein delivery.

Science.gov (United States)

Yang, Yoosoo; Hong, Yeonsun; Cho, Eunji; Kim, Gi Beom; Kim, In-San

2018-01-01

Membrane proteins are of great research interest, particularly because they are rich in targets for therapeutic application. The suitability of various membrane proteins as targets for therapeutic formulations, such as drugs or antibodies, has been studied in preclinical and clinical studies. For therapeutic application, however, a protein must be expressed and purified in as close to its native conformation as possible. This has proven difficult for membrane proteins, as their native conformation requires the association with an appropriate cellular membrane. One solution to this problem is to use extracellular vesicles as a display platform. Exosomes and microvesicles are membranous extracellular vesicles that are released from most cells. Their membranes may provide a favourable microenvironment for membrane proteins to take on their proper conformation, activity, and membrane distribution; moreover, membrane proteins can cluster into microdomains on the surface of extracellular vesicles following their biogenesis. In this review, we survey the state-of-the-art of extracellular vesicle (exosome and small-sized microvesicle)-based therapeutics, evaluate the current biological understanding of these formulations, and forecast the technical advances that will be needed to continue driving the development of membrane protein therapeutics.

Collisional effects on interaction potential in complex plasma in presence of magnetic field

International Nuclear Information System (INIS)

Bezbaruah, Pratikshya; Das, Nilakshi

2016-01-01

Interaction potential in complex plasma with streaming ions is derived analytically in presence of ion-neutral collision and magnetic field. The linear dielectric response function obtained describes the behavior of charged micron sized dust particles in strong collisional limit. A new type of repulsive potential is found to be operative among the dust grains apart from the normal Debye–Hückel potential. The amplitude and shielding length involved in the potential are substantially affected by the parameters describing ion cyclotron frequency, collision frequency among ions and neutrals, and ion streaming. It is also observed that the usual mechanism of ion focusing surrounding the grain is inhibited due to collision. As a result, the attractive wake potential structure is destroyed in the ion flow direction. The horizontal interaction involves only Debye–Hückel potential.

Collisional effects on interaction potential in complex plasma in presence of magnetic field

Energy Technology Data Exchange (ETDEWEB)

Bezbaruah, Pratikshya, E-mail: pratphd@tezu.ernet.in; Das, Nilakshi [Department of Physics, Tezpur University, Tezpur, Assam 784028 (India)

2016-04-15

Interaction potential in complex plasma with streaming ions is derived analytically in presence of ion-neutral collision and magnetic field. The linear dielectric response function obtained describes the behavior of charged micron sized dust particles in strong collisional limit. A new type of repulsive potential is found to be operative among the dust grains apart from the normal Debye–Hückel potential. The amplitude and shielding length involved in the potential are substantially affected by the parameters describing ion cyclotron frequency, collision frequency among ions and neutrals, and ion streaming. It is also observed that the usual mechanism of ion focusing surrounding the grain is inhibited due to collision. As a result, the attractive wake potential structure is destroyed in the ion flow direction. The horizontal interaction involves only Debye–Hückel potential.

Extracellular membrane vesicles in blood products-biology and clinical relevance

Directory of Open Access Journals (Sweden)

Emilija Krstova Krajnc

2016-01-01

Full Text Available Extracellular membrane vesicles are fragments shed from plasma membranes off all cell types that are undergoing apoptosis or are being subjected to various types of stimulation or stress.  Even in the process of programmed cell death (apoptosis, cell fall apart of varying size vesicles. They expose phosphatidylserine (PS on the outer leaflet of their membrane, and bear surface membrane antigens reflecting their cellular origin. Extracellular membrane vesicles have been isolated from many types of biological fluids, including serum, cerebrospinal fluid, urine, saliva, tears and conditioned culture medium. Flow cytometry is one of the many different methodological approaches that have been used to analyze EMVs. The method attempts to characterize the EMVs cellular origin, size, population, number, and structure. EMVs are present and accumulate in blood products (erythrocytes, platelets as well as in fresh frozen plasma during storage. The aim of this review is to highlight the importance of extracellular vesicles as a cell-to-cell communication system and the role in the pathogenesis of different diseases. Special emphasis will be given to the implication of extracellular membrane vesicles in blood products and their clinical relevance. Although our understanding of the role of  EMVs in disease is far from comprehensive, they display promise as biomarkers for different diseases in the future and also as a marker of quality and safety in the quality control of blood products.

Concise review : Developing best-practice models for the therapeutic use of extracellular vesicles

NARCIS (Netherlands)

Reiner, Agnes T.; Witwer, Kenneth W.; Van Balkom, Bas W.M.; De Beer, Joel; Brodie, Chaya; Corteling, Randolph L.; Gabrielsson, Susanne; Gimona, Mario; Ibrahim, Ahmed G.; De Kleijn, Dominique; Lai, Charles P.; Tvall, Jan Lo; Del Portillo, Hernando A; Reischl, Ilona G; Riazifar, Milad; Salomon, Carlos; Tahara, Hidetoshi; Toh, Wei Seong; Wauben, Marca H M; Yang, Vicky K.; Yang, Yijun; Yeo, Ronne Wee Yeh; Yin, Hang; Giebel, Bernd; Rohde, Eva; Lim, Sai Kiang

2017-01-01

Growing interest in extracellular vesicles (EVs, including exosomes and microvesicles) as therapeutic entities, particularly in stem cell-related approaches, has underlined the need for standardization and coordination of development efforts. Members of the International Society for Extracellular

Increased level of extracellular ATP at tumor sites: in vivo imaging with plasma membrane luciferase.

Directory of Open Access Journals (Sweden)

Patrizia Pellegatti

2008-07-01

Full Text Available There is growing awareness that tumour cells build up a "self-advantageous" microenvironment that reduces effectiveness of anti-tumour immune response. While many different immunosuppressive mechanisms are likely to come into play, recent evidence suggests that extracellular adenosine acting at A2A receptors may have a major role in down-modulating the immune response as cancerous tissues contain elevated levels of adenosine and adenosine break-down products. While there is no doubt that all cells possess plasma membrane adenosine transporters that mediate adenosine uptake and may also allow its release, it is now clear that most of extracellularly-generated adenosine originates from the catabolism of extracellular ATP.Measurement of extracellular ATP is generally performed in cell supernatants by HPLC or soluble luciferin-luciferase assay, thus it generally turns out to be laborious and inaccurate. We have engineered a chimeric plasma membrane-targeted luciferase that allows in vivo real-time imaging of extracellular ATP. With this novel probe we have measured the ATP concentration within the tumour microenvironment of several experimentally-induced tumours.Our results show that ATP in the tumour interstitium is in the hundreds micromolar range, while it is basically undetectable in healthy tissues. Here we show that a chimeric plasma membrane-targeted luciferase allows in vivo detection of high extracellular ATP concentration at tumour sites. On the contrary, tumour-free tissues show undetectable extracellular ATP levels. Extracellular ATP may be crucial for the tumour not only as a stimulus for growth but also as a source of an immunosuppressive agent such as adenosine. Our approach offers a new tool for the investigation of the biochemical composition of tumour milieu and for development of novel therapies based on the modulation of extracellular purine-based signalling.

A novel assay for extracellular matrix remodeling associated with liver fibrosis

DEFF Research Database (Denmark)

Barascuk, N; Veidal, S S; Larsen, L

2010-01-01

Accumulation of extracellular matrix (ECM) components and increased matrix-metalloprotease (MMPs) activity are hallmarks of fibrosis. We developed an ELISA for quantification of MMP-9 derived collagen type III (CO3) degradation.......Accumulation of extracellular matrix (ECM) components and increased matrix-metalloprotease (MMPs) activity are hallmarks of fibrosis. We developed an ELISA for quantification of MMP-9 derived collagen type III (CO3) degradation....

Thyrotropin-luteinizing hormone/chorionic gonadotropin receptor extracellular domain chimeras as probes for thyrotropin receptor function

International Nuclear Information System (INIS)

Nagayama, Yuji; Wadsworth, H.L.; Chazenbalk, G.D.; Russo, D.; Seto, Pui; Rapoport, B.

1991-01-01

To define the sites in the extracellular domain of the human thyrotropin (TSH) receptor that are involved in TSH binding and signal transduction the authors constructed chimeric thyrotropin-luteinizing hormone/chorionic gonadotropin (TSH-LH/CG) receptors. The extracellular domain of the human TSH receptor was divided into five regions that were replaced, either singly or in various combinations, with homologous regions of the rat LH/CG receptor. The chimeric receptors were stably expressed in Chinese hamster ovary cells. The data obtained suggest that the carboxyl region of the extracellular domain (amino acid residues 261-418) and particularly the middle region (residues 171-260) play a role in signal transduction. The possibility is also raised of an interaction between the amino and carboxyl regions of the extracellular domain in the process of signal transduction. In summary, these studies suggest that the middle region and carboxyl half of the extracellular domain of the TSH receptor are involved in signal transduction and that the TSH-binding region is likely to span the entire extracellular domain, with multiple discontinuous contact sites