Retrieval of ion distributions in RC from TWINS ENA images by CT technique

NASA Astrophysics Data System (ADS)

Ma, S.; Yan, W.; Xu, L.; Goldstein, J.; McComas, D. J.

2010-12-01

The Two Wide-angle Imaging Neutral-atom Spectrometers (TWINS) mission is the first constellation to employ imagers on two separate spacecraft to measure energetic neutral atoms (ENA) produced by charge exchange between ring current energetic ions and cold exospheric neutral atoms. By applying the 3-D volumetric pixel (voxel) computed tomography (CT) inversion method to TWINS images, parent ion populations in the ring current (RC) and auroral regions are retrieved from their ENA signals. This methodology is implemented for data obtained during the main phase of a moderate geomagnetic storm on 11 October 2008. For this storm the two TWINS satellites were located in nearly the same meridian plane at vantage points widely separated in magnetic local time, and both more than 5 RE geocentric distance from the Earth. In the retrieval process, the energetic ion fluxes to be retrieved are assumed being isotropic with respect to pitch angle. The ENA data used in this study are differential fluxes averaged over 12 sweeps (corresponding to an interval of 16 min.) at different energy levels ranging throughout the full 1--100 keV energy range of TWINS. The ENA signals have two main components: (1) a low-latitude/ high-altitude signal from trapped RC ions and (2) a low-altitude signal from precipitating ions in the auroral/subauroral ionosphere. In the retrieved ion distributions, the main part of the RC component is located around midnight toward dawn sector with L from 3 to 7 or farther, while the subauroral low-altitude component is mainly at pre-midnight. It seems that the dominant energy of the RC ions for this storm is at the lowest energy level of 1-2 keV, with another important energy band centered about 44 keV. The low-altitude component is consistent with in situ observations by DMSP/SSJ4. The result of this study demonstrates that with satellite constellations such as TWINS, using all-sky ENA imagers deployed at multiple vantage points, 3-D distribution of RC ion intensity may be reconstructed via the CT technique. Acknowledgement: This work is supported by NSFC (Grant No. 40674078).

IBEX Mission update: New discoveries and a new orbit

NASA Astrophysics Data System (ADS)

McComas, D. J.; IBEX Science Team

2011-12-01

The Interstellar Boundary Explorer (IBEX) mission has been remotely observing the global interaction of our heliosphere with the local interstellar medium for over two and a half years. Initially, IBEX generated the first all-sky maps of Energetic Neutral Atoms (ENAs) emanating in from the boundaries of our heliosphere over the energy range from ~0.1-6 keV. Using these observations, the IBEX team discovered a smoothly varying, globally distributed ENA flux overlaid by a narrow "ribbon" of significantly enhanced ENA emissions. Since the initial publications of these results in a special issue of Science magazine (November 2009), IBEX has completed four more energy-resolved sets of sky maps and discovered small but important time variations in the interaction, separated the ribbon from globally distributed ENA fluxes, measured the energy spectral shape and inferred ion source temperatures, and carried out many other observational and theoretical studies. In addition, IBEX made the first observations of ENAs produced by backscatter and neutralization of the solar wind from the lunar regolith and provided the first energy and angle resolved ENA images of the subsolar magnetosheath and magnetospheric cusps and plasma sheet. Most recently, direct IBEX observations of Interstellar Neutral (ISN) He show that the speed and direction (the motion of the heliosphere with respect to the interstellar medium) is different than that thought from prior Ulysses observations. These observations also show evidence for a previously unknown and unanticipated secondary population of Helium. In addition, IBEX is providing the first direct quantitative measurements of the ISN H parameters and the first direct measurements of interstellar Ne and the interstellar Neon/Oxygen abundance ratio; this ratio is significantly different than the solar abundance ratio. IBEX was recently maneuvered into a unique, long-term stable orbit and has several decades worth of fuel for routine operations. Thus, IBEX will likely continue to provide revolutionary observations of numerous heliospheric, magnetospheric, and planetary phenomena for many years to come!

Modulation of ENA in the heliosphere

NASA Astrophysics Data System (ADS)

Bzowski, Maciej; Kubiak, Marzena; Czechowski, Andrzej

Energetic Neutral Atoms (ENA), an important part of heliospheric physics, have recently en-joyed an increased interest because of the breakthrough observations by the NASA SMEX mission IBEX. Generally, ENA appear as a product of charge exchange reaction between an energetic ion and a neutral gas atom. Being insensitive to electromagnetic forces, ENA run away freely from their birth sites and can carry information on the physical state of the parent plasma on (somewhat energy-dependent) distances well in excess of 100 AU. The ENA fluxes exhibit modulation due to time variations of their source function due to modulation of solar wind on time scales from days to solar cycle and due to large-scale variation in the latitude structure of the solar wind, as well as to the variations in the loss rate due to re-ionization. Once created, the ENA flux suffers losses mostly due to photoionization by solar EUV photons, but also to charge exchange and electron impact. We will review the variation of survival prob-ability of the ENA created in the inner heliosheath and observed by spacecraft on Mars, Earth, and Venus orbits (like Mars Express, IBEX, and Venus Express) and solar-cycle modulation of the radially-expanding spectral flux of ENA consisting of the solar wind protons and alpha particles transcharged on the neutral interstellar gas inside the heliosphere.

TRACKING THE SOLAR CYCLE THROUGH IBEX OBSERVATIONS OF ENERGETIC NEUTRAL ATOM FLUX VARIATIONS AT THE HELIOSPHERIC POLES

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

Reisenfeld, D. B.; Janzen, P. H.; Bzowski, M., E-mail: dan.reisenfeld@umontana.edu, E-mail: paul.janzen@umontana.edu, E-mail: bzowski@cbk.waw.pl

With seven years of Interstellar Boundary Explorer ( IBEX ) observations, from 2009 to 2015, we can now trace the time evolution of heliospheric energetic neutral atoms (ENAs) through over half a solar cycle. At the north and south ecliptic poles, the spacecraft attitude allows for continuous coverage of the ENA flux; thus, signal from these regions has much higher statistical accuracy and time resolution than anywhere else in the sky. By comparing the solar wind dynamic pressure measured at 1 au with the heliosheath plasma pressure derived from the observed ENA fluxes, we show that the heliosheath pressure measuredmore » at the poles correlates well with the solar cycle. The analysis requires time-shifting the ENA measurements to account for the travel time out and back from the heliosheath, which allows us to estimate the scale size of the heliosphere in the polar directions. We arrive at an estimated distance to the center of the ENA source region in the north of 220 au and in the south a distance of 190 au. We also find a good correlation between the solar cycle and the ENA energy spectra at the poles. In particular, the ENA flux for the highest IBEX energy channel (4.3 keV) is quite closely correlated with the areas of the polar coronal holes, in both the north and south, consistent with the notion that polar ENAs at this energy originate from pickup ions of the very high speed wind (∼700 km s{sup −1}) that emanates from polar coronal holes.« less

ENA diagnostic of the solar wind interaction with Mars and Venus

NASA Astrophysics Data System (ADS)

Barabash, Stas

Charge - exchange of the solar wind ions flowing around non-magnetized Mars and Venus on their exospheres results in hydrogen energetic neutral atom (ENA) emissions. Accelerated planetary ions may also experience charge - exchange resulting in planetary ENAs, mainly oxygen. The ENAs carry information on the ion distribution functions integrated over the line-of-sight and are used for remote sensing of the original plasma populations. The ASPERA-3/4 instruments (Analyzer of Space Plasmas and Energetic Atoms) onboard Mars Express and Venus Express missions performed the first-ever measurements of ENAs from these bodies in the energy range 100 eV - 10 keV. ENAs are mostly emitted by the magnetospheath plasma flowing around the induced magnetosphere. Due to lower gravity the Martian exosphere extends further in the magnetosheath than at Venus that makes Mars a “brighter ENA source”. We thus focus mostly on Mars and only briefly discuss ENA observations at Venus. ENA emissions from an elementary emitting volume in the magnetosheath are highly anisotropic and occur along the tangential line to the stream-line in this point. That makes impossible to obtain a global ENA image of the object from a single vantage point contrary to, for example, “classical” ENA imaging of the terrestrial ring current. At Mars the statistically obtained emission pattern shows an increase in the ENA flux perpendicular to the sun direction resembling a thick layer or a wall. The emissions coming mostly from the sub-solar point show an increase in the direction opposite to the convective electric field indicating the induced magnetosphere boundary is not cylindrically symmetric and closer to planet in this direction. Measurements of ENAs turned out to be an effective way to reveal the global dynamics of an induced magnetosphere. Arrival of an interplanetary shock to Mars and the associated compression of the induced magnetosphere are clearly detected as an abrupt termination of the ENA signal because the ENA wall suddenly moved away from the spacecraft. When the spacecraft stays sufficiently long inside the ENA wall, oscillations of the ENA signal with a period of 30 sec - few min (~0.01 Hz) can be observed. The oscillations of the similar frequency are observed in the electron and ion fluxes in the magnetosheath as well as magnetic field. Their physics is not understood. Mars Express/ASPERA-3 detected a slight increase of the ENA emissions above the magnetic anomalies. It may be related to the increase of the neutral densities above these regions. Contrary to the predictions, Mars Express/ASPERA-3 did not detect any oxygen ENAs. That allowed to provide upper limits for the hydrogen exospheric densities which turned out to be much lower at the solar minimum than expected. Finally, we introduce a few “exotic” ideas of using ENAs for studies the near-Venus and near-Mars space. Using ENAs backscattered from the atmosphere one may obtain global precipitating maps. Using the neutral solar wind passing through the upper atmosphere at the terminate region, one may realize neutral solar wind occultation geometry and use the ENA signal variation for the upper atmosphere profiling.

Spatial distribution of Ion Precipitation into the High Latitude Inner Magnetosphere using Energetic Neutral Atom (ENA) images over the Declining Phase of Solar Cycle 23

NASA Astrophysics Data System (ADS)

Mackler, D. A.; Jahn, J.; Pollock, C. J.

2013-12-01

Plamasheet particles transported Earthward during times of active magnetic convection can interact with thermospheric neutrals through charge exchange. The resulting ENAs are free to leave the influence of the magnetosphere and can be remotely detected. ENAs associated with low altitude (300-800 km) ion precipitation in the high latitude inner mangetosphere are termed Low Altitude Emissions (LAEs). LAEs are highly non-isotropic in velocity space such that the pitch angle distribution at the time of charge exchange is near 90 degrees. The observed Geomagnetic Emission Cone (GEC) of LAEs can be mapped spatially, showing where energy is deposited during storm/sub-storm times. In this study we present a statistical look at the particulate albedo of LAEs over the declining phase of solar cycle 23. The particulate albedo is defined as the ratio of the emitting energetic neutrals to the precipitating ions. The precipitating ion differential directional flux maps are built up from combining NOAA 14/15/16 TED and DMSP 13/14/15 SSJ4 data. Low altitude ENA signatures are identified manually using IMAGE/MENA images and selected out. The geomagnetic location of each pixel representing a LAE source region in the neutral images is computed assuming an altitude of 650 km. Before taking the ratio of the resulting flux of neutrals and ions, the Magnetic Local Time (MLT) and Invariant Latitude (IL) bin sizes are changed such that each has less than 20% error in counting statistics. The particulate albedo maps are then evaluated over changes in geomagnetic storm activity.

Statistical correlation of low-altitude ENA emissions with geomagnetic activity from IMAGE/MENA observations

NASA Astrophysics Data System (ADS)

Mackler, D. A.; Jahn, J.-M.; Perez, J. D.; Pollock, C. J.; Valek, P. W.

2016-03-01

Plasma sheet particles transported Earthward during times of active magnetospheric convection can interact with exospheric/thermospheric neutrals through charge exchange. The resulting Energetic Neutral Atoms (ENAs) are free to leave the influence of the magnetosphere and can be remotely detected. ENAs associated with low-altitude (300-800 km) ion precipitation in the high-latitude atmosphere/ionosphere are termed low-altitude emissions (LAEs). Remotely observed LAEs are highly nonisotropic in velocity space such that the pitch angle distribution at the time of charge exchange is near 90°. The Geomagnetic Emission Cone of LAEs can be mapped spatially, showing where proton energy is deposited during times of varying geomagnetic activity. In this study we present a statistical look at the correlation between LAE flux (intensity and location) and geomagnetic activity. The LAE data are from the MENA imager on the IMAGE satellite over the declining phase of solar cycle 23 (2000-2005). The SYM-H, AE, and Kp indices are used to describe geomagnetic activity. The goal of the study is to evaluate properties of LAEs in ENA images and determine if those images can be used to infer properties of ion precipitation. Results indicate a general positive correlation to LAE flux for all three indices, with the SYM-H showing the greatest sensitivity. The magnetic local time distribution of LAEs is centered about midnight and spreads with increasing activity. The invariant latitude for all indices has a slightly negative correlation. The combined results indicate LAE behavior similar to that of ion precipitation.

Statistical Correlation of Low-Altitude ENA Emissions with Geomagnetic Activity from IMAGE MENA Observations

NASA Technical Reports Server (NTRS)

Mackler, D. A.; Jahn, J.- M.; Perez, J. D.; Pollock, C. J.; Valek, P. W.

2016-01-01

Plasma sheet particles transported Earthward during times of active magnetospheric convection can interact with exospheric/thermospheric neutrals through charge exchange. The resulting Energetic Neutral Atoms (ENAs) are free to leave the influence of the magnetosphere and can be remotely detected. ENAs associated with low-altitude (300-800 km) ion precipitation in the high-latitude atmosphere/ionosphere are termed low-altitude emissions (LAEs). Remotely observed LAEs are highly nonisotropic in velocity space such that the pitch angle distribution at the time of charge exchange is near 90deg. The Geomagnetic Emission Cone of LAEs can be mapped spatially, showing where proton energy is deposited during times of varying geomagnetic activity. In this study we present a statistical look at the correlation between LAE flux (intensity and location) and geomagnetic activity. The LAE data are from the MENA imager on the IMAGE satellite over the declining phase of solar cycle 23 (2000-2005). The SYM-H, AE, and Kp indices are used to describe geomagnetic activity. The goal of the study is to evaluate properties of LAEs in ENA images and determine if those images can be used to infer properties of ion precipitation. Results indicate a general positive correlation to LAE flux for all three indices, with the SYM-H showing the greatest sensitivity. The magnetic local time distribution of LAEs is centered about midnight and spreads with increasing activity. The invariant latitude for all indices has a slightly negative correlation. The combined results indicate LAE behavior similar to that of ion precipitation.

Hydration status regulates sodium flux and inflammatory pathways through epithelial sodium channel (ENaC) in the skin.

PubMed

Xu, Wei; Hong, Seok Jong; Zeitchek, Michael; Cooper, Garry; Jia, Shengxian; Xie, Ping; Qureshi, Hannan A; Zhong, Aimei; Porterfield, Marshall D; Galiano, Robert D; Surmeier, D James; Mustoe, Thomas A

2015-03-01

Although it is known that the inflammatory response that results from disruption of epithelial barrier function after injury results in excessive scarring, the upstream signals remain unknown. It has also been observed that epithelial disruption results in reduced hydration status and that the use of occlusive dressings that prevent water loss from wounds decreases scar formation. We hypothesized that hydration status changes sodium homeostasis and induces sodium flux in keratinocytes, which result in activation of pathways responsible for keratinocyte-fibroblast signaling and ultimately lead to activation of fibroblasts. Here, we demonstrate that perturbations in epithelial barrier function lead to increased sodium flux in keratinocytes. We identified that sodium flux in keratinocytes is mediated by epithelial sodium channels (ENaCs) and causes increased secretion of proinflammatory cytokines, which activate fibroblast via the cyclooxygenase 2 (COX-2)/prostaglandin E2 (PGE2) pathway. Similar changes in signal transduction and sodium flux occur by increased sodium concentration, which simulates reduced hydration, in the media in epithelial cultures or human ex vivo skin cultures. Blockade of ENaC, prostaglandin synthesis, or PGE2 receptors all reduce markers of fibroblast activation and collagen synthesis. In addition, employing a validated in vivo excessive scar model in the rabbit ear, we demonstrate that utilization of either an ENaC blocker or a COX-2 inhibitor results in a marked reduction in scarring. Other experiments demonstrate that the activation of COX-2 in response to increased sodium flux is mediated through the PIK3/Akt pathway. Our results indicate that ENaC responds to small changes in sodium concentration with inflammatory mediators and suggest that the ENaC pathway is a potential target for a strategy to prevent fibrosis.

3D tomographic reconstruction of the terrestrial exosphere and its time-dependent coupling to the magnetospheric ring current

NASA Astrophysics Data System (ADS)

Waldrop, L.; Cucho-Padin, G.; Ilie, R.

2017-12-01

Charge exchange collisions between ring current ions and hydrogen (H) atoms in the outer exosphere serve to dissipate magnetospheric energy, particularly during the slow recovery phase of geomagnetic storms, through the generation of energetic neutral atoms (ENAs) which escape the system. As a result, knowledge of the spatial distribution and temporal variability of exospheric H density is critical for reliable interpretation of ENA flux measurements as well as for accurate modeling of the ring current. Although numerous theoretical, numerical, and empirical H distributions have been used for such analyses, their reliance on ad hoc or unphysical assumptions, together with their inherently static formulations, is a source of significant uncertainty. Our recent development of a robust tomographic technique for the model-independent estimation of global exospheric H density from optical remote sensing data overcomes the limitations of past analysis and enables an unprecedented investigation of global exospheric and ring current dynamics. Here, we present sample results of our 3D, time-dependent reconstructions of exospheric structure, derived from measurements of resonantly scattered solar Lyman-alpha (121.6 nm) photons acquired by the Lyman-alpha detectors (LADs) onboard NASA's Two Wide-angle Imaging Neutral-atom Spectrometers (TWINS) mission. We use the Hot Electron and Ion Drift Integrator (HEIDI) kinetic model of the ring current to investigate the charge exchange interactions between the resulting H density distribution and ring current ions and generate synthetic images of ENA flux for comparison with those measured by TWINS.

A Test of the Interstellar Boundary EXplorer Ribbon Formation in the Outer Heliosheath

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

Gamayunov, Konstantin V.; Rassoul, Hamid; Heerikhuisen, Jacob, E-mail: kgamayunov@fit.edu

NASA’s Interstellar Boundary EXplorer ( IBEX ) mission is imaging energetic neutral atoms (ENAs) propagating to Earth from the outer heliosphere and local interstellar medium (LISM). A dominant feature in all ENA maps is a ribbon of enhanced fluxes that was not predicted before IBEX . While more than a dozen models of the ribbon formation have been proposed, consensus has gathered around the so-called secondary ENA model. Two classes of secondary ENA models have been proposed; the first class assumes weak scattering of the energetic pickup protons in the LISM, and the second class assumes strong but spatially localizedmore » scattering. Here we present a numerical test of the “weak scattering” version of the secondary ENA model using our gyro-averaged kinetic model for the evolution of the phase-space distribution of protons in the outer heliosheath. As input for our test, we use distributions of the primary ENAs from our MHD-plasma/kinetic-neutral model of the heliosphere-LISM interaction. The magnetic field spectrum for the large-scale interstellar turbulence and an upper limit for the amplitude of small-scale local turbulence (SSLT) generated by protons are taken from observations by Voyager 1 in the LISM. The hybrid simulations of energetic protons are also used to set the bounding wavenumbers for the spectrum of SSLT. Our test supports the “weak scattering” version. This makes an additional solid step on the way to understanding the origin and formation of the IBEX ribbon and thus to improving our understanding of the interaction between the heliosphere and the LISM.« less

Determining the Dimensions of the Heliosphere from the Time-Correlation of IBEX ENA Observations with Variations in the Solar Wind Dynamic Pressure

NASA Astrophysics Data System (ADS)

Reisenfeld, D. B.; Bzowski, M.; Funsten, H. O.; Janzen, P. H.; Kubiak, M. A.; McComas, D. J.; Schwadron, N.; Sokol, J. M.

2017-12-01

The IBEX mission has shown that variations in the ENA flux from the outer heliosphere are associated with the solar cycle. In particular, there is a good correlation between the dynamic pressure of the outbound solar wind and variations in the observed IBEX ENA flux (McComas et al, 2017; Reisenfeld et al., 2016). There is, of course, a time difference between observations of the outbound SW and the heliospheric ENAs with which they correlate, ranging from approximately two to four years, depending on ENA energy and look direction. In this study, we use this time difference as a means of "sounding" the heliosheath, that is, finding the average distance to the ENA source region in a particular direction. We use data from the first seven years of the IBEX mission. As each point in the sky is sampled once every six months, this gives us a time series of 14 points per look direction on which to time correlate. Fluxes are transformed from the spacecraft frame into a heliospheric inertial frame to remove the effects of spacecraft/Earth motion. Fluxes are also corrected for ENA extinction due to charge exchange. To improve statistics, we divide the sky into "macropixels" spanning 30 degrees in longitude and varying ranges of latitude to maintain comparable counting statistics per pixel. In calculating the response time, we account for the varying speed of the outbound solar wind by using a time and latitude dependent set of solar wind speeds derived from interplanetary scintillation data (Sokol et al. 2015). Consistent with heliospheric models, we determine the shortest distance to the heliopause is in the nose direction, with a flaring toward the flanks and poles.

Probing the Boundaries of the Heliosphere by Analyzing the Temporal Variation of the Polar ENA Flux

NASA Astrophysics Data System (ADS)

Reisenfeld, D. B.; Janzen, P. H.; Bzowski, M.; Dialynas, K.; Funsten, H. O.; Fuselier, S. A.; Karna, N.; Kubiak, M. A.; McComas, D. J.; Schwadron, N.; Sokol, J. M.

2015-12-01

With nearly seven years of IBEX observations, we can now trace the time evolution of heliospheric ENAs through over half a solar cycle. At the north and south ecliptic poles, the spacecraft attitude allows for continuous coverage of the ENA flux; thus, signal from these vantages have much higher statistical accuracy and time resolution than anywhere else in the sky. By assuming pressure balance across the termination shock, and comparing the solar wind dynamic pressure measured at 1 AU with the heliosheath plasma pressure derived from the observed ENA fluxes, we show that the heliosheath pressure measured at the poles correlates well with the solar cycle. The analysis requires time-shifting the ENA measurements to account for the travel time out and back from the heliosheath. The time shifts at the north pole range from 5.1 years at 700 eV, the low end of the IBEX-Hi energy range, to 3.2 years at 4.3 keV, the top IBEX-Hi energy. These time shifts assume a common mean distance to the ENA source region for all energies. For the south pole, the best-fit time shifts range from 4.1 to 2.6 years across the IBEX-Hi energy range. Hence, the ENA source at the south is somewhat closer than at the north, consistent with an asymmetric heliosphere model. We will present the details of this analysis, as well as estimates of the scale size of the heliosheath in the polar directions.

An observational study of the relationship between precipitating ions and ENAs emerging from the ion/atmosphere interaction region

NASA Astrophysics Data System (ADS)

Mackler, David A.

Plasmasheet particles transported Earthward during times of active magnetospheric convection can interact with thermospheric neutrals through charge exchange. The resulting Energetic Neutral Atoms (ENAs) are free to leave the influence of the magnetosphere and can be remotely detected. ENAs associated with low altitude (300--800 km) ion precipitation in the high latitude atmosphere/ionosphere are termed Low Altitude Emissions (LAEs). Remotely observed LAEs are highly non-isotropic in velocity space such that the pitch angle distribution at the time of charge exchange is near 90 degrees. The Geomagnetic Emission Cone (GEC) of LAEs can be mapped spatially, showing where proton energy is deposited during times of varying geomagnetic activity. In this study we present a statistical look at the correlation between LAE flux (intensity and location) and geomagnetic activity as well as comparisons of LAE signatures with in situ ion precipitation. The LAE data is from the MENA imager on the IMAGE satellite over the declining phase of solar cycle 23 (2000--2005). The SYM-H, AE, and Kp indices are used to describe geomagnetic activity. The in situ data is from the Defense Meteorological Satellite Program (DMSP). The goal of the study is to evaluate properties of LAEs in ENA images and determine if those images can be used to infer properties of ion precipitation. Results indicate a general positive correlation to LAE flux for all three indices, with the SYM-H showing the greatest non-linearity. The MLT distribution of LAEs are centered about midnight and spread with increasing activity. The Invariant Latitude for all indices has a slightly negative correlation. The combined results indicate that both LAE and DMSP data behave similarly to geomagnetic activity. LAEs are more spread out in latitude, possibly due to multiple charge exchange interactions, while the in situ data changes to lower latitudes dramatically with increasing flux. The bulk of the data indicates that the LAE latitude region is lower than that of the precipitating ions. The local time coverage of the DMSP constellation during the time of MENA is too limited to infer much information. The ratio of the fluxes (DMSP/LAE) is roughly constant over storm time parameters (LOG[-SYM-H]/Slope/Phase), with the possible exception of favoring Low Altitude Emissions at higher flux and lower latitudes. This may indicate that the change in flux intensity may respond equally between the two.

The Role of Pickup Ion Dynamics Outside of the Heliopause in the Limit of Weak Pitch Angle Scattering: Implications for the Source of the IBEX Ribbon.

PubMed

Zirnstein, E J; Heerikhuisen, J; Dayeh, M A

2018-01-01

We present a new model of the Interstellar Boundary Explorer ( IBEX ) ribbon based on the secondary energetic neutral atom (ENA) mechanism, under the assumption that there is negligible pitch angle scattering of pickup ions (PUIs) outside the heliopause. Using the results of an MHD-plasma/kinetic-neutral simulation of the heliosphere, we generate PUIs in the outer heliosheath, solve their transport using guiding center theory, and compute ribbon ENA fluxes at 1 AU. We implement several aspects of the PUI dynamics, including (1) parallel motion along the local interstellar magnetic field (ISMF), (2) advective transport with the interstellar plasma, (3) the mirror force acting on PUIs propagating along the ISMF, and (4) betatron acceleration of PUIs as they are advected within an increasing magnetic field towards the heliopause. We find that ENA fluxes at 1 AU are reduced when PUIs are allowed to move along the ISMF, and ENA fluxes are reduced even more by the inclusion of the mirror force, which pushes particles away from IBEX lines-of-sight. Inclusion of advection and betatron acceleration do not result in any significant change in the ribbon. Interestingly, the mirror force reduces the ENA fluxes from the inner edge of the ribbon more than its outer edge, effectively reducing the ribbon's width by ∼6° and increasing its radius projected on the sky. This is caused by the asymmetric draping of the ISMF around the heliopause, such that ENAs from the ribbon's inner edge originate closer to the heliopause, where the mirror force is strongest.

The Role of Pickup Ion Dynamics Outside of the Heliopause in the Limit of Weak Pitch Angle Scattering: Implications for the Source of the IBEX Ribbon

NASA Astrophysics Data System (ADS)

Zirnstein, E. J.; Heerikhuisen, J.; Dayeh, M. A.

2018-03-01

We present a new model of the Interstellar Boundary Explorer (IBEX) ribbon based on the secondary energetic neutral atom (ENA) mechanism, under the assumption that there is negligible pitch angle scattering of pickup ions (PUIs) outside the heliopause. Using the results of an MHD-plasma/kinetic-neutral simulation of the heliosphere, we generate PUIs in the outer heliosheath, solve their transport using guiding center theory, and compute ribbon ENA fluxes at 1 au. We implement several aspects of the PUI dynamics, including (1) parallel motion along the local interstellar magnetic field (ISMF), (2) advective transport with the interstellar plasma, (3) the mirror force acting on PUIs propagating along the ISMF, and (4) betatron acceleration of PUIs as they are advected within an increasing magnetic field toward the heliopause. We find that ENA fluxes at 1 au are reduced when PUIs are allowed to move along the ISMF, and ENA fluxes are reduced even more by the inclusion of the mirror force, which pushes particles away from IBEX lines of sight. Inclusion of advection and betatron acceleration do not result in any significant change in the ribbon. Interestingly, the mirror force reduces the ENA fluxes from the inner edge of the ribbon more than those from its outer edge, effectively reducing the ribbon’s width by ∼6° and increasing its radius projected on the sky. This is caused by the asymmetric draping of the ISMF around the heliopause, such that ENAs from the ribbon’s inner edge originate closer to the heliopause, where the mirror force is strongest.

Neutral atom imaging at Mercury

NASA Astrophysics Data System (ADS)

Mura, A.; Orsini, S.; Milillo, A.; Di Lellis, A. M.; De Angelis, E.

2006-02-01

The feasibility of neutral atom detection and imaging in the Hermean environment is discussed in this study. In particular, we consider those energetic neutral atoms (ENA) whose emission is directly related to solar wind entrance into Mercury's magnetosphere. In fact, this environment is characterised by a weak magnetic field; thus, cusp regions are extremely large if compared to the Earth's ones, and intense proton fluxes are expected there. Our study includes a model of H + distribution in space, energy and pitch angle, simulated by means of a single-particle, Monte-Carlo simulation. Among processes that could generate neutral atom emission, we focus our attention on charge-exchange and ion sputtering, which, in principle, are able to produce directional ENA fluxes. Simulated neutral atom images are investigated in the frame of the neutral particle analyser-ion spectrometer (NPA-IS) SERENA experiment, proposed to fly on board the ESA mission BepiColombo/MPO. The ELENA (emitted low-energy neutral atoms) unit, which is part of this experiment, will be able to detect such fluxes; instrumental details and predicted count rates are given.

Trapped Ring Current Ion Dynamics During the 17-18 March 2015 Geomagnetic Storm Obtained from TWINS ENA Images

NASA Astrophysics Data System (ADS)

Perez, J. D.; Goldstein, J.; McComas, D. J.; Valek, P. W.; Fok, M. C. H.; Hwang, K. J.

2015-12-01

On 17-18 March 2015, there was a large (minimum SYM/H < -200 nT) geomagnetic storm. The Two Wide-Angle Imaging Neutral Atom Spectrometers (TWINS) mission, the first stereoscopic ENA magnetospheric imager, provides global images of the inner magnetosphere from which global distributions of ion flux, energy spectra, and pitch angle distributions are obtained. We will show how the observed ion pressure correlates with SYM/H. Examples of multiple peaks in the ion spatial distribution which may be due to multiple injections and/or energy and pitch angle dependent drift will be illustrated. Energy spectra will be shown to be non-Maxwellian, frequently having two peaks, one in the 10 keV range and another near 40 keV. Pitch angle distributions will be shown to have generally perpendicular anisotropy and that this can be time, space and energy dependent. The results are consistent with Comprehensive Inner Magnetosphere-Ionosphere (CIMI) model simulations.

A three-coordinate system (ecliptic, galactic, ISMF) spectral analysis of heliospheric ENA emissions using CASSINI/INCA measurements

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

Dialynas, K.; Krimigis, S. M.; Mitchell, D. G.

2013-11-20

In the present study, we use all-sky energy-resolved energetic neutral atom (ENA) maps obtained by the Ion and Neutral CAmera (INCA) instrument on board Cassini that correspond to the time period from 2003 to 2009, in four discrete energy passbands (∼5.4 to ∼55 keV), to investigate the geometrical characteristics of the belt (a broad band of emission in the sky). The heliospheric ENA emissions are mapped in three different coordinate systems (ecliptic, Galactic, and interstellar magnetic field (ISMF)), and spectral analyses are performed to further examine the belt's possible energy dependence. Our conclusions are summarized as follows: (1) the highmore » flux ENA belt identified in the energy range of 8-42 keV is moderately well organized in Galactic coordinates, as the ENA minima appear in the vicinity of the north and south Galactic poles; (2) using minimization criteria ( B · R ∼ 0), the deviation of the ENA emissions from the equator is effectively minimized in a rotated frame, which we interpret as ISMF, where its north pole points toward 190° ecliptic longitude and 15° ecliptic latitude; (3) ENA spectra show a power-law form in energy that can be fitted with a single function presenting higher spectral slopes in the belt region and lower outside (3.4 < γ < 4.4); (4) the spectra are almost indistinguishable between the tail and the nose regions, i.e., no noticeable asymmetry is observed; (5) the consistency of the ENA distributions as a function of latitude among the different INCA channels indicates that the morphology of the belt (peak, width, and structure) is nearly energy independent from 8 keV to 30 keV (minor deviations start to appear at >35 keV); and (6) in the low count rate regions, the long-term ENA count rate profiles do not match the measured cosmic ray profiles, indicating that even the minimum ENA emissions detected by INCA are foreground ENAs.« less

Update on IBEX and the outer boundary of the space radiation environment

NASA Astrophysics Data System (ADS)

McComas, D. J.; IBEX Science Team

2012-11-01

The Interstellar Boundary Explorer (IBEX) mission has been remotely observing the global interaction of our heliosphere with the local interstellar medium for over three years. Initially, IBEX generated the first all-sky maps of Energetic Neutral Atoms (ENAs) emanating in from the boundaries of our heliosphere over the energy range from ˜0.1-6 keV. Using these observations, the IBEX team discovered a smoothly varying, globally distributed ENA flux overlaid by a narrow "ribbon" of significantly enhanced ENA emissions. Since the initial publication of these results in a special issue of Science magazine (November 2009), IBEX has completed five more energy-resolved sets of sky maps and discovered small but important time variations in the interaction, separated the ribbon from globally distributed ENA fluxes, measured the energy spectral shape and inferred ion source temperatures, and carried out many other observational and theoretical studies of the outer heliosphere. In a second major area of observations - direct measurements of Interstellar Neutral (ISN) atoms - just published, IBEX observations of ISN He atoms show that the speed and direction (the motion of the heliosphere with respect to the interstellar medium) is slower and from a somewhat different direction than that thought from prior Ulysses observations. These observations also show evidence for a previously unknown and unanticipated secondary population of Helium. In addition, IBEX is providing the first direct quantitative measurements of the ISN H parameters and the first direct measurements of interstellar Ne and the interstellar Neon/Oxygen abundance ratio; this ratio is significantly different than the solar abundance ratio. Finally, IBEX was recently maneuvered into a unique, long-term stable orbit, which has a very low radiation environment and requires no orbit maintenance. Thus, IBEX will likely continue to provide revolutionary observations of the outer heliosphere and local interstellar medium for many years to come.

On the stability of pick-up ion ring distributions in the outer heliosheath

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

Summerlin, Errol J.; Viñas, Adolfo F.; Moore, Thomas E.

The 'secondary energetic neutral atom (ENA)' hypothesis for the ribbon feature observed by the Interstellar Boundary Explorer (IBEX) posits that the neutral component of the solar wind continues beyond the heliopause and charge exchanges with interstellar ions in the Outer Heliosheath (OHS). This creates pick-up ions that gyrate about the draped interstellar magnetic field (ISMF) lines at pitch angles near 90° on the locus where the ISMF lies tangential to the heliopause and perpendicular to the heliocentric radial direction. This location closely coincides with the location of the ribbon feature according to the prevailing inferences of the ISMF orientation andmore » draping. The locally gyrating ions undergo additional charge exchange and escape as free-flying neutral atoms, many of which travel back toward the inner solar system and are imaged by IBEX as a ribbon tracing out the locus described above. For this mechanism to succeed, the pick-up ions must diffuse in pitch angle slowly enough to permit secondary charge exchange before their pitch angle distribution substantially broadens away from 90°. Previous work using linear Vlasov dispersion analysis of parallel propagating waves has suggested that the ring distribution in the OHS is highly unstable, which, if true, would make the secondary ENA hypothesis incapable of rendering the observed ribbon. In this paper, we extend this earlier work to more realistic ring distribution functions. We find that, at the low densities necessary to produce the observed IBEX ribbon via the secondary ENA hypothesis, growth rates are highly sensitive to the temperature of the beam and that even very modest temperatures of the ring beam corresponding to beam widths of <1° are sufficient to damp the self-generated waves associated with the ring beam. Thus, at least from the perspective of linear Vlasov dispersion analysis of parallel propagating waves, there is no reason to expect that the ring distributions necessary to produce the observed IBEX ENA flux via the secondary ENA hypothesis will be unstable to their own self-generated turbulence.« less

On the Stability of Pick-up Ion Ring Distributions in the Outer Heliosheath

NASA Astrophysics Data System (ADS)

Summerlin, Errol J.; Viñas, Adolfo F.; Moore, Thomas E.; Christian, Eric R.; Cooper, John F.

2014-10-01

The "secondary energetic neutral atom (ENA)" hypothesis for the ribbon feature observed by the Interstellar Boundary Explorer (IBEX) posits that the neutral component of the solar wind continues beyond the heliopause and charge exchanges with interstellar ions in the Outer Heliosheath (OHS). This creates pick-up ions that gyrate about the draped interstellar magnetic field (ISMF) lines at pitch angles near 90° on the locus where the ISMF lies tangential to the heliopause and perpendicular to the heliocentric radial direction. This location closely coincides with the location of the ribbon feature according to the prevailing inferences of the ISMF orientation and draping. The locally gyrating ions undergo additional charge exchange and escape as free-flying neutral atoms, many of which travel back toward the inner solar system and are imaged by IBEX as a ribbon tracing out the locus described above. For this mechanism to succeed, the pick-up ions must diffuse in pitch angle slowly enough to permit secondary charge exchange before their pitch angle distribution substantially broadens away from 90°. Previous work using linear Vlasov dispersion analysis of parallel propagating waves has suggested that the ring distribution in the OHS is highly unstable, which, if true, would make the secondary ENA hypothesis incapable of rendering the observed ribbon. In this paper, we extend this earlier work to more realistic ring distribution functions. We find that, at the low densities necessary to produce the observed IBEX ribbon via the secondary ENA hypothesis, growth rates are highly sensitive to the temperature of the beam and that even very modest temperatures of the ring beam corresponding to beam widths of <1° are sufficient to damp the self-generated waves associated with the ring beam. Thus, at least from the perspective of linear Vlasov dispersion analysis of parallel propagating waves, there is no reason to expect that the ring distributions necessary to produce the observed IBEX ENA flux via the secondary ENA hypothesis will be unstable to their own self-generated turbulence.

Energetic neutral atom imaging at low altitudes from the Swedish microsatellite Astrid: Images and spectral analysis

NASA Astrophysics Data System (ADS)

Brandt, Pontus C.:son; Barabash, Stas; Norberg, Olle; Lundin, Rickard; Roelof, Edmond C.; Chase, Christopher J.

1999-02-01

Observations of energetic neutral atoms (ENA) in the energy range 26-52 keV are reported from four occasions during geomagnetically disturbed periods. The data were acquired by the ENA imager flown on the Swedish microsatellite Astrid in a 1000 km circular orbit with 83° inclination. The ENA imager separates charged particles from neutrals through an electrostatic deflection system in the energy range between 0.1 and 114 keV. ENA images obtained from vantage points in the polar cap and in the afternoon magnetic local time (MLT) hours looking into the antisunward hemisphere show intense ENA fluxes (~104(cm2srs)-1 over 26-37 keV) coming from the dusk region and low altitudes (~300 km). The morphology shows no relation to local magnetic field excluding the possibility of charged particle detection. It is concluded that the source of these ENAs are precipitating/mirroring ions from the ring current/trapped radiation interacting with the exobase on auroral L-shells and in the dusk region. The observed ENA fluxes show a relation with Kp and Dst geomagnetic indices. The observed ENA spectrum from a geomagnetic storm on February 8, 1995, is investigated in more detail and compared to the parent ion spectrum obtained by the Defense Meteorological Satellite Project (DMSP) satellite, F12, during the same period on L=6+/-2 around dusk. The observed ENA spectral slope is used to derive the parent ion spectral temperature. The derived ion temperatures range is 3.0-6.0 keV for H and 4.5-8.5 keV for O. The higher of these ion temperatures comes closest in agreement to the extrapolated DMSP spectrum leading us to favor O over H as the species of the detected ENAs. It is shown that the detected ENAs must have been produced at L>=6 to reach the detector without atmospheric attenuation and that the main energy dependence of the ENA spectrum, apart from the parent ion spectrum, is governed by the energy dependence of the charge exchange cross section between ions and exospheric oxygen.

Empirical Characterization of Low-Altitude Ion Flux Derived from TWINS

NASA Astrophysics Data System (ADS)

Goldstein, J.; LLera, K.; McComas, D. J.; Redfern, J.; Valek, P. W.

2018-05-01

In this study we analyze ion differential flux from 10 events between 2008 and 2015. The ion fluxes are derived from low-altitude emissions (LAEs) in energetic neutral atom (ENA) images obtained by Two Wide-angle Imaging Neutral-atom Spectrometers (TWINS). The data set comprises 119.44 hr of observations, including 4,284 per energy images with 128,277 values of differential ENA flux from pixels near Earth's limb. Limb pixel data are extracted and mapped to a common polar ionospheric grid and associated with values of the Dst index. Statistical analysis is restricted to pixels within 10% of the LAE emissivity peak. For weak Dst conditions we find a premidnight peak in the average ion precipitation, whose flux and location are relatively insensitive to energy. For moderate Dst, elevated flux levels appear over a wider magnetic local time (MLT) range, with a separation of peak locations by energy. Strong disturbances bring a dramatic flux increase across the entire nightside at all energies but strongest for low energies in the postmidnight sector. The arrival of low-energy ions can lower the average energy for strong Dst, even as it raises the total integral number flux. TWINS-derived ion fluxes provide a macroscale measurement of the average precipitating ion distribution and confirm that convection, either quasi-steady or bursty, is an important process controlling the spatial and spectral properties of precipitating ions. The premidnight peak (weak Dst), MLT widening and energy-versus-MLT dependence (moderate Dst), and postmidnight low-energy ion enhancement (strong Dst) are consistent with observations and models of steady or bursty convective transport.

WNK4 regulates activity of the epithelial Na+ channel in vitro and in vivo

PubMed Central

Ring, Aaron M.; Cheng, Sam X.; Leng, Qiang; Kahle, Kristopher T.; Rinehart, Jesse; Lalioti, Maria D.; Volkman, Heather M.; Wilson, Frederick H.; Hebert, Steven C.; Lifton, Richard P.

2007-01-01

Homeostasis of intravascular volume, Na+, Cl−, and K+ is interdependent and determined by the coordinated activities of structurally diverse mediators in the distal nephron and the distal colon. The behavior of these flux pathways is regulated by the renin–angiotensin–aldosterone system; however, the mechanisms that allow independent modulation of individual elements have been obscure. Previous work has shown that mutations in WNK4 cause pseudohypoaldosteronism type II (PHAII), a disease featuring hypertension with hyperkalemia, due to altered activity of specific Na-Cl cotransporters, K+ channels, and paracellular Cl− flux mediators of the distal nephron. By coexpression studies in Xenopus oocytes, we now demonstrate that WNK4 also inhibits the epithelial Na+ channel (ENaC), the major mediator of aldosterone-sensitive Na+ (re)absorption, via a mechanism that is independent of WNK4's kinase activity. This inhibition requires intact C termini in ENaC β- and γ-subunits, which contain PY motifs used to target ENaC for clearance from the plasma membrane. Importantly, PHAII-causing mutations eliminate WNK4's inhibition of ENaC, thereby paralleling other effects of PHAII to increase sodium balance. The relevance of these findings in vivo was studied in mice harboring PHAII-mutant WNK4. The colonic epithelium of these mice demonstrates markedly increased amiloride-sensitive Na+ flux compared with wild-type littermates. These studies identify ENaC as a previously unrecognized downstream target of WNK4 and demonstrate a functional role for WNK4 in the regulation of colonic Na+ absorption. These findings support a key role for WNK4 in coordinating the activities of diverse flux pathways to achieve integrated fluid and electrolyte homeostasis. PMID:17360470

Energetic Neutral Atom Emissions From Venus: VEX Observations and Theoretical Modeling

NASA Technical Reports Server (NTRS)

Fok, M.-C.; Galli, A.; Tanaka, T.; Moore, T. E.; Wurz, P.; Holmstrom, M.

2007-01-01

Venus has almost no intrinsic magnetic field to shield itself from its surrounding environment. The solar wind thus directly interacts with the planetary ionosphere and atmosphere. One of the by-products of this close encounter is the production of energetic neutral atom (ENA) emissions. Theoretical studies have shown that significant amount of ENAs are emanated from the planet. The launch of the Venus Express (VEX) in 2005 provided the first light ever of the Venus ENA emissions. The observed ENA flux level and structure are in pretty good agreement with the theoretical studies. In this paper, we present VEX ENA data and the comparison with numerical simulations. We seek to understand the solar wind interaction with the planet and the impacts on its atmospheres.

Influence of asymmetries in the magnetic draping pattern at Titan on the emission of energetic neutral atoms

NASA Astrophysics Data System (ADS)

Kabanovic, Slawa; Feyerabend, Moritz; Simon, Sven; Meeks, Zachary; Wulms, Veit

2018-03-01

We model the emission of energetic neutral atoms (ENAs) that are generated by the interaction between energetic ions from Saturn's magnetosphere and neutrals from the upper atmosphere of the giant planet's largest moon Titan. The trajectories of the parent ions and the resulting ENA emission morphology are highly sensitive to the electromagnetic field configuration near the moon. We therefore compare the ENA emission pattern for spatially homogeneous fields to the emission obtained from a magnetohydrodynamic (MHD) and a hybrid (kinetic ions, fluid electrons) model of Titan's magnetospheric interaction, by computing the trajectories of several billion energetic test particles. While the MHD model takes into account the draping of the magnetic field lines around Titan, the hybrid approach also considers the significant asymmetries in the electromagnetic fields due to the large gyroradii of pick-up ions from Titan's ionosphere. In all three models, the upstream parameters correspond to the conditions during Cassini's TA flyby of Titan. The shape, magnitude, and location of the ENA emission maxima vary considerably between these three field configurations. The magnetic pile-up region at Titan's ramside deflects a large number of the energetic parent ions, thereby reducing the ENA flux. However, the draped magnetic field lines in Titan's lobes rotate the gyration planes of the incident energetic ions, thereby facilitating the observable ENA production. Overall, the ENA flux calculated for the MHD model is weaker than the emission obtained for the electromagnetic fields from the hybrid code. In addition, we systematically investigate the dependency of the ENA emission morphology on the energy of the parent ions and on the upstream magnetic field strength.

Modeling Emission of Heavy Energetic Neutral Atoms from the Heliosphere

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

Swaczyna, Paweł; Bzowski, Maciej, E-mail: pswaczyna@cbk.waw.pl

2017-09-10

Observations of energetic neutral atoms (ENAs) are a fruitful tool for remote diagnosis of the plasma in the heliosphere and its vicinity. So far, instruments detecting ENAs from the heliosphere were configured for observations of hydrogen atoms. Here, we estimate emissions of ENAs of the heavy chemical elements helium, oxygen, nitrogen, and neon. A large portion of the heliospheric ENAs is created in the inner heliosheath from neutralized interstellar pick-up ions (PUIs). We modeled this process and calculated full-sky intensities of ENAs for energies 0.2–130 keV/nuc. We found that the largest fluxes among considered species are expected for helium, smallermore » for oxygen and nitrogen, and smallest for neon. The obtained intensities are 50–10{sup 6} times smaller than the hydrogen ENA intensities observed by IBEX . The detection of heavy ENAs will be possible if a future ENA detector is equipped with the capability to measure the masses of observed atoms. Because of different reaction cross-sections among the different species, observations of heavy ENAs can allow for a better understanding of global structure of the heliosphere as well as the transport and energization of PUIs in the heliosphere.« less

Modeling Emission of Heavy Energetic Neutral Atoms from the Heliosphere

NASA Astrophysics Data System (ADS)

Swaczyna, Paweł; Bzowski, Maciej

2017-09-01

Observations of energetic neutral atoms (ENAs) are a fruitful tool for remote diagnosis of the plasma in the heliosphere and its vicinity. So far, instruments detecting ENAs from the heliosphere were configured for observations of hydrogen atoms. Here, we estimate emissions of ENAs of the heavy chemical elements helium, oxygen, nitrogen, and neon. A large portion of the heliospheric ENAs is created in the inner heliosheath from neutralized interstellar pick-up ions (PUIs). We modeled this process and calculated full-sky intensities of ENAs for energies 0.2-130 keV/nuc. We found that the largest fluxes among considered species are expected for helium, smaller for oxygen and nitrogen, and smallest for neon. The obtained intensities are 50-106 times smaller than the hydrogen ENA intensities observed by IBEX. The detection of heavy ENAs will be possible if a future ENA detector is equipped with the capability to measure the masses of observed atoms. Because of different reaction cross-sections among the different species, observations of heavy ENAs can allow for a better understanding of global structure of the heliosphere as well as the transport and energization of PUIs in the heliosphere.

Neutralized solar energetic particles in the inner heliosphere: a parameter study

NASA Astrophysics Data System (ADS)

Wang, Xiao-Dong; Klecker, Berndt; Futaana, Yoshifumi; Cipriani, Fabrice; Barabash, Stas; Wieser, Martin

2016-04-01

The large fluxes of solar energetic particles (SEPs) in Gradual Events, dominated by protons, are believed to be produced by the acceleration of shocks driven by coronal mass ejections (CMEs). As SEPs propagate in the lower corona, there is a chance for them to be neutralized via the charge exchange and/or recombination processes and become energetic neutral atoms (ENAs). These ENAs retain the velocity of their parent SEPs and propagate in straight lines without the influence of the interplanetary magnetic field, and therefore might potentially serve as a new window to observe the particle acceleration processes in the solar corona. STEREO/Low Energy Telescope reported the first probable observation of hydrogen ENAs between 1.6 MeV - 5 MeV from the Sun prior to an X-class flare/CME [Mewaldt et al., 2009]. While such observations were somehow controversial, Wang et al. [2014] simulated the neutralization of solar energetic protons in the corona lower than 40 RS, and the result agreed with the STEREO observation. In this work, we further developed a production model of the ENA near the sun together with a transport model toward the inner planets, and explore the dependences of the ENA characteristics against the model parameters. These parameters include the angular width of the CME, its propagation direction with respect to the Sun-observer line, the propagation speed, the particle density in the corona, the abundances of O6+ and C4+, and the reaction rate of electron impact ionization in the loss of ENAs, and the heliospheric distance of the observer. The calculated ENA flux shows that at lower energy the expected ENA flux depends most sensitively on the CME apex angle and the CME propagation direction. At higher energy the dependence on the coronal density is more prominent. References Mewaldt, R. A., R. A. Leske, E. C. Stone, A. F. Barghouty, A. W. Labrador, C. M. S. Cohen, A. C. Cummings, A. J. Davis, T. T. von Rosenvinge, and M. E. Wiedenbeck (2009), STEREO Observations of Energetic Neutral Hydrogen Atoms During the 2006 December 5 Solar Flare, Astrophys. J. Lett., 693(1), L11. Wang, L., G. Li, A. Y. Shih, R. P. Lin, and R. F. Wimmer-Schweingruber (2014), Simulation of Energetic Neutral Atoms from Solar Energetic Particles, Astrophys. J. Lett., 793(2), L37.

CIRCULARITY OF THE INTERSTELLAR BOUNDARY EXPLORER RIBBON OF ENHANCED ENERGETIC NEUTRAL ATOM (ENA) FLUX

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

Funsten, H. O.; Higdon, D. M.; Larsen, B. A.

2013-10-10

As a sharp feature in the sky, the ribbon of enhanced energetic neutral atom (ENA) flux observed by the Interstellar Boundary Explorer (IBEX) mission is a key signature for understanding the interaction of the heliosphere and the interstellar medium through which we are moving. Over five nominal IBEX energy passbands (0.7, 1.1, 1.7, 2.7, and 4.3 keV), the ribbon is extraordinarily circular, with a peak location centered at ecliptic (λ{sub RC}, β{sub RC}) = (219.°2 ± 1.°3, 39.°9 ± 2.°3) and a half cone angle of φ{sub C} = 74.°5 ± 2.°0. A slight elongation of the ribbon, generally perpendicularmore » to the ribbon center-heliospheric nose vector and with eccentricity ∼0.3, is observed over all energies. At 4.3 keV, the ribbon is slightly larger and displaced relative to lower energies. For all ENA energies, a slice of the ribbon flux peak perpendicular to the circular arc is asymmetric and systematically skewed toward the ribbon center. We derive a spatial coherence parameter δ{sub C} ≤ 0.014 that characterizes the spatial uniformity of the ribbon over its extent in the sky and is a key constraint for understanding the underlying processes and structure governing the ribbon ENA emission.« less

Charge-exchange coupling between pickup ions across the heliopause and its effect on energetic neutral hydrogen flux

DOE PAGES

Zirnstein, Eric J.; Heerikhuisen, J.; Zank, G. P.; ...

2014-02-24

Pickup ions (PUIs) appear to play an integral role in the multi-component nature of the plasma in the interaction between the solar wind (SW) and local interstellar medium (LISM). Three-dimensional (3D) MHD simulations with a kinetic treatment for neutrals and PUIs are currently still not viable. In light of recent energetic neutral atom (ENA) observations by the Interstellar Boundary EXplorer, the purpose of this paper is to illustrate the complex coupling between PUIs across the heliopause (HP) as facilitated by ENAs using estimates of PUI properties extracted from a 3D MHD simulation of the SW-LISM interaction with kinetic neutrals. First,more » we improve upon the multi-component treatment of the inner heliosheath (IHS) plasma from Zank et al. by including the extinction of PUIs through charge-exchange. We find a significant amount of energy is transferred away from hot, termination shock-processed PUIs into a colder, "freshly injected" PUI population. Second, we extend the multi-component approach to estimate ENA flux from the outer heliosheath (OHS), formed from charge-exchange between interstellar hydrogen atoms and energetic PUIs. These PUIs are formed from ENAs in the IHS that crossed the HP and experienced charge-exchange. Lastly, our estimates, based on plasma-neutral simulations of the SW-LISM interaction and a post-processing analysis of ENAs and PUIs, suggest the majority of flux visible at 1 AU from the front of the heliosphere, between ~0.02 and 10 keV, originates from OHS PUIs, indicating strong coupling between the IHS and OHS plasmas through charge-exchange.« less

Epithelial sodium channel (ENaC) family: Phylogeny, structure-function, tissue distribution, and associated inherited diseases

PubMed Central

Hanukoglu, Israel; Hanukoglu, Aaron

2016-01-01

The epithelial sodium channel (ENaC) is composed of three homologous subunits and allows the flow of Na+ ions across high resistance epithelia, maintaining body salt and water homeostasis. ENaC dependent reabsorption of Na+ in the kidney tubules regulates extracellular fluid (ECF) volume and blood pressure by modulating osmolarity. In multi-ciliated cells, ENaC is located in cilia and plays an essential role in the regulation of epithelial surface liquid volume necessary for cilial transport of mucus and gametes in the respiratory and reproductive tracts respectively. The subunits that form ENaC (named as alpha, beta, gamma and delta, encoded by genes SCNN1A, SCNN1B, SCNN1G, and SCNN1D) are members of the ENaC/Degenerin superfamily. The earliest appearance of ENaC orthologs is in the genomes of the most ancient vertebrate taxon, Cyclostomata (jawless vertebrates) including lampreys, followed by earliest representatives of Gnathostomata (jawed vertebrates) including cartilaginous sharks. Among Euteleostomi (bony vertebrates), Actinopterygii (ray finned-fishes) branch has lost ENaC genes. Yet, most animals in the Sarcopterygii (lobe-finned fish) branch including Tetrapoda, amphibians and amniotes (lizards, crocodiles, birds, and mammals), have four ENaC paralogs. We compared the sequences of ENaC orthologs from 20 species and established criteria for the identification of ENaC orthologs and paralogs, and their distinction from other members of the ENaC/Degenerin superfamily, especially ASIC family. Differences between ENaCs and ASICs are summarized in view of their physiological functions and tissue distributions. Structural motifs that are conserved throughout vertebrate ENaCs are highlighted. We also present a comparative overview of the genotype-phenotype relationships in inherited diseases associated with ENaC mutations, including multisystem pseudohypoaldosteronism (PHA1B), Liddle syndrome, cystic fibrosis-like disease and essential hypertension. PMID:26772908

Domain-averaged, Shallow Precipitation Measurements During the Aerosol and Cloud Experiments in the Eastern North Atlantic (ACE-ENA)

NASA Astrophysics Data System (ADS)

Lamer, K.; Luke, E. P.; Kollias, P.; Oue, M.; Wang, J.

2017-12-01

The Atmospheric Radiation Measurement (ARM) Climate Research Facility operates a fixed observatory in the Eastern North Atlantic (ENA) on Graciosa Island in the Azores. Straddling the tropics and extratropics, the Azores receive air transported from North America, the Arctic and sometimes Europe. At the ARM ENA site, marine boundary layer clouds are frequently observed all year round. Estimates of drizzle mass flux from the surface to cloud base height are documented using a combination of high sensitivity profiling 35-GHz radar and ceilometer observations. Three years of drizzle mass flux retrievals reveal that statistically, directly over the ENA site, marine boundary layer cloud drizzle rates tend to be weak with few heavy drizzle events. In the summer of 2017, this site hosted the first phase of the Aerosol and Cloud Experiments in the Eastern North Atlantic (ACE-ENA) field campaign, which is motivated by the need for comprehensive in situ characterization of boundary layer structure, low clouds and aerosols. During this phase, the 35-GHz scanning ARM cloud radar was operated as a surveillance radar, providing regional context for the profiling observations. While less sensitive, the scanning radar measurements document a larger number of heavier drizzle events and provide domain-representative estimates of shallow precipitation. A best estimate, domain averaged, shallow precipitation rate for the region around the ARM ENA site is presented. The methodology optimally combines the ability of the profiling observations to detect the weak but frequently occurring drizzle events with the scanning cloud radar's ability to capture the less frequent heavier drizzle events. The technique is also evaluated using high resolution model output and a sophisticated forward radar operator.

Physical Processes in the Heliospheric Interface Region and their Implications for ENA Images

NASA Astrophysics Data System (ADS)

Gruntman, M.; Roelof, E. C.; McComas, D. J.; Funsten, H. O.; Krimigis, S. M.; Mitchell, D. G.

2009-12-01

The recent in situ measurements of particles and fields by Voyager 1 and 2 spacecraft and global heliospheric maps in fluxes of energetic neutral atoms (ENAs) obtained by IBEX and Cassini/INCA have challenged our established concepts of the heliosphere interaction with the surrounding local interstellar medium. We review the physics of the interaction in an attempt to identify most important processes determining the dynamics and properties of the heliospheric sheath region. The non-thermal ion component and interstellar magnetic field clearly play significant roles in the interaction, as well as the flow of the warm interstellar plasma. We stress here that the basic conservation laws for energetic ions and neutrals constrain the processes that must be included in any valid formulation of particle transport. The termination shock can be viewed as a continuous source of energetic ions that are transported throughout the inner heliosheath, through the heliopause, and outward through the outer heliosheath and into the local interstellar medium. ENA images integrate the ENA production by energetic ions along lines of sight (LOS) that extend in principle to infinity, and hence are quite sensitive to the way that energetic ions and ENAs eventually escape this huge (~1000AU) system. Non-thermal ion and ENA space densities can be changed by three mechanisms: spatial transport (which by itself only rearranges the numbers of energetic ions and ENAs), energy gain and loss of ions in electric field, and elastic and inelastic collisions. Thus, only if these mechanisms are properly included in computational models can the salient features observed ENA images be replicated by the model simulations.

Position of the IBEX ribbon as a key to understand its origin

NASA Astrophysics Data System (ADS)

Swaczyna, Pawel; Bzowski, Maciej; Sokół, Justyna M.; Christian, Eric R.; Funsten, Herbert O.; McComas, David J.; Schwadron, Nathan A.

2017-04-01

Observations of the energetic neutral atom (ENA) emission by the Interstellar Boundary Explorer (IBEX) allow for remote sensing of the plasma properties in heliosheath. The first IBEX results revealed an unexpected arc-like enhancement of the ENA flux in the sky, dubbed the IBEX ribbon. This discovery led to formulation of more than a dozen hypotheses on its origin. The emission source region proposed in these hypotheses span the heliospheric termination shock up to a hypothetical nearby interface between the Local Interstellar Cloud and a local bay in the Local Bubble. Among these hypotheses is the concept that the ribbon is produced by the secondary ENA mechanism, operating in the outer heliosheath. The observational strategy of IBEX allows observation of the same part of the sky from the opposite sides of the Sun every six months and thus provides parallax viewing with a baseline of 2 AU. After correcting the observations for the Compton-Getting effect and for gravitational deflection and radiation pressure, we use this parallax viewing to precisely determine the apparent position of the maximum flux associated with the ribbon. We find that the ribbon peak position differs semi-annually by an angle of 0.41±0.15 deg, which we interpret as the parallax effect. This angle corresponds to a distance of 140-38+84 AU, and thus suggests that most likely the ribbon's source is located just beyond the heliopause. Comparison of the IBEX ribbon position in five energy steps of IBEX-Hi shows a systematic shift, which changes the position of the ribbon center by ˜10 deg. We find that it can be explained using an analytic model of the secondary ENA mechanism with the neutralized supersonic solar wind as the source of the primary ENAs, which are ionized in the outer heliosheath, picked up by the ambient magnetic field, and eventually re-neutralized (as originally conceived, McComas et al. 2009). We use a realistic model of the solar wind evolution dependent on heliographic latitude, calculated the neutral solar wind flux and averaged it over the solar cycle, which was then used as the input in the analytic model of the secondary ENAs. The modeled ENA emission signal as observed at IBEX reproduces the observed features of the IBEX ribbon: the relative signal intensity along the ribbon in each energy channel and the shift of the ribbon center. The combination of the distance to the ribbon source obtained from parallax and the energy progression of the ribbon center location suggest that the secondary ENA mechanism is a plausible explanation for the ribbon origin. A better resolution of the ENA detectors expected on the IMAP mission will enable a more accurate determination of the ribbon's position and will extend observations to higher energies. In consequence, a better determination of its parallax should be possible, and time-dependent effects resulting from the evolution of the supersonic solar wind structure with time will provide additional, critical signatures of the ribbon origin.

Ly α Absorption at Transits of HD 209458b: A Comparative Study of Various Mechanisms Under Different Conditions

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

Khodachenko, M. L.; Lammer, H.; Kislyakova, K. G.

To shed more light on the nature of the observed Ly α absorption during transits of HD 209458b and to quantify the major mechanisms responsible for the production of fast hydrogen atoms (the so-called energetic neutral atoms, ENAs) around the planet, 2D hydrodynamic multifluid modeling of the expanding planetary upper atmosphere, which is driven by stellar XUV, and its interaction with the stellar wind has been performed. The model self-consistently describes the escaping planetary wind, taking into account the generation of ENAs due to particle acceleration by the radiation pressure and by the charge exchange between the stellar wind protonsmore » and planetary atoms. The calculations in a wide range of stellar wind parameters and XUV flux values showed that under typical Sun-like star conditions, the amount of generated ENAs is too small, and the observed absorption at the level of 6%–8% can be attributed only to the non-resonant natural line broadening. For lower XUV fluxes, e.g., during the activity minima, the number of planetary atoms that survive photoionization and give rise to ENAs increases, resulting in up to 10%–15% absorption at the blue wing of the Ly α line, caused by resonant thermal line broadening. A similar asymmetric absorption can be seen under the conditions realized during coronal mass ejections, when sufficiently high stellar wind pressure confines the escaping planetary material within a kind of bowshock around the planet. It was found that the radiation pressure in all considered cases has a negligible contribution to the production of ENAs and the corresponding absorption.« less

Energetic neutral atoms measured by the interstellar boundary explorer (IBEX): evidence for multiple heliosheath populations

DOE PAGES

Desai, M. I.; Allegrini, F. A.; Bzowski, M.; ...

2013-12-13

Energetic neutral atoms (ENAs) observed by the Interstellar Boundary Explorer (IBEX) provide powerful diagnostics about the origin of the progenitor ion populations and the physical mechanisms responsible for their production. In this paper, we extend the work of Desai et al. and Fuselier et al. and combine and compare ENA spectra from the first 3 yr of observations by the IBEX-Hi and -Lo ENA imagers along the lines-of-sight (LOSs) from the inner heliosphere through to the locations of Voyager 1 and 2 with results from an updated physics-based model of the three-dimensional heliosphere and its constituent ion populations. Our resultsmore » show that (1) IBEX ENA fluxes and spectra above ~0.7 keV measured along the LOSs of the Voyagers are consistent with several models in which the parent pickup ion (PUI) populations originate in the inner heliosheath, and (2) a significant fraction of lower energy ENAs between ~0.1-0.5 keV may originate from interstellar neutral gas charge-exchanging with a non-thermalized (hot) population of PUIs in the outer heliosheath beyond the heliopause. Here we discuss the implications of ENAs observed by IBEX originating from distinct parent populations as well as from two distinct locations in the heliospheric interface. In conclusion, these results indicate that ENA spectral measurements at various energies can be used to remotely probe distinct physical processes operating in vastly different regions of the distant heliosphere.« less

Energetic Neutral Atoms Measured by the Interstellar Boundary Explorer (IBEX): Evidence for Multiple Heliosheath Ion Populations

NASA Astrophysics Data System (ADS)

Desai, M. I.; Allegrini, F.; Bzowski, M.; Dayeh, M. A.; Funsten, H. O.; Fuselier, S.; Kubiak, M. A.; McComas, D. J.; Pogorelov, N. V.; Schwadron, N.; Sokol, J. M.; Zank, G. P.; Zirnstein, E. J.

2013-12-01

Energetic Neutral Atoms (ENAs) observed by the Interstellar Boundary Explorer (IBEX) provide powerful diagnostics about the origin of the progenitor ion populations and the physical mechanisms responsible for their production. In this paper, we extend the work of Desai et al. (2012) and Fuselier et al. (2012) and combine and compare ENA spectra from the first three years of observations by the IBEX-Hi and -Lo ENA imagers along the lines-of-sights (LOS) from the inner heliosphere through to the locations of Voyager 1 and 2 with results from an updated physics-based model of the 3D heliosphere and its constituent ion populations. Our results show that (1) IBEX ENA fluxes and spectra above ~0.7 keV measured along the LOS of the Voyagers are consistent with several models in which the parent pickup (PUI) populations originate in the inner heliosheath, and (2) a significant fraction of lower-energy ENAs between ~0.1-0.5 keV may originate from interstellar neutral gas charge-exchanging with a non-thermalized (hot) population of PUIs in the outer heliosheath beyond the heliopause. We discuss the implications of ENAs observed by IBEX originating from distinct parent populations as well as from two distinct locations in the heliospheric interface. These results indicate that ENA spectral measurements at various energies can be used to remotely probe distinct physical processes operating in vastly different regions of the distant heliosphere.

Energetic Neutral Atoms Measured by the Interstellar Boundary Explorer (IBEX): Evidence for Multiple Heliosheath Populations

NASA Astrophysics Data System (ADS)

Desai, M. I.; Allegrini, F. A.; Bzowski, M.; Dayeh, M. A.; Funsten, H.; Fuselier, S. A.; Heerikhuisen, J.; Kubiak, M. A.; McComas, D. J.; Pogorelov, N. V.; Schwadron, N. A.; Sokół, J. M.; Zank, G. P.; Zirnstein, E. J.

2014-01-01

Energetic neutral atoms (ENAs) observed by the Interstellar Boundary Explorer (IBEX) provide powerful diagnostics about the origin of the progenitor ion populations and the physical mechanisms responsible for their production. In this paper, we extend the work of Desai et al. and Fuselier et al. and combine and compare ENA spectra from the first 3 yr of observations by the IBEX-Hi and -Lo ENA imagers along the lines-of-sight (LOSs) from the inner heliosphere through to the locations of Voyager 1 and 2 with results from an updated physics-based model of the three-dimensional heliosphere and its constituent ion populations. Our results show that (1) IBEX ENA fluxes and spectra above ~0.7 keV measured along the LOSs of the Voyagers are consistent with several models in which the parent pickup ion (PUI) populations originate in the inner heliosheath, and (2) a significant fraction of lower energy ENAs between ~0.1-0.5 keV may originate from interstellar neutral gas charge-exchanging with a non-thermalized (hot) population of PUIs in the outer heliosheath beyond the heliopause. We discuss the implications of ENAs observed by IBEX originating from distinct parent populations as well as from two distinct locations in the heliospheric interface. These results indicate that ENA spectral measurements at various energies can be used to remotely probe distinct physical processes operating in vastly different regions of the distant heliosphere.

EXPLORING THE TIME DISPERSION OF THE IBEX-HI ENERGETIC NEUTRAL ATOM SPECTRA AT THE ECLIPTIC POLES

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

Allegrini, F.; Dayeh, M. A.; Desai, M. I.

2012-04-20

The Interstellar Boundary Explorer (IBEX) has observed energetic neutral atom (ENA) hydrogen emissions from the edge of the solar system for more than three years. The observations span energies from 0.01 to 6 keV FWHM. At energies greater than 0.5-6 keV, and for a travel distance of {approx}100 AU, the travel time difference between the slowest and the fastest ENA is more than a year. Therefore, we construct spectra including the effect that slower ENAs left the source at an earlier time than faster ones. If the source produces a steady rate of ENAs and the extinction does not vary,more » then we expect that the spectral shape would be time independent. However, while the extinction of ENAs has been fairly constant during the first two and a half years, the source appears to have changed, and thus the spectra at a single time may not represent the conditions at the source. IBEX's viewing allows continuous sampling of the ecliptic poles where fluxes can be continuously monitored. For a given source distance we construct spectra assuming that the measured ENAs left the source at roughly the same time. To accomplish this construction, we apply time lag corrections to the signal at different ENA energies that take into account the travel time difference. We show that the spectral shape at the poles exhibits a statistically significant change with time.« less

Seven Years of Imaging the Global Heliosphere with IBEX

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

McComas, D. J.; Zirnstein, E. J.; Bzowski, M.

2017-04-01

The Interstellar Boundary Explorer ( IBEX ) has now operated in space for 7 years and returned nearly continuous observations that have led to scientific discoveries and reshaped our entire understanding of the outer heliosphere and its interaction with the local interstellar medium. Here we extend prior work, adding the 2014–2015 data for the first time, and examine, validate, initially analyze, and provide a complete 7-year set of Energetic Neutral Atom (ENA) observations from ∼0.1 to 6 keV. The data, maps, and documentation provided here represent the 10th major release of IBEX data and include improvements to various prior correctionsmore » to provide the citable reference for the current version of IBEX data. We are now able to study time variations in the outer heliosphere and interstellar interaction over more than half a solar cycle. We find that the Ribbon has evolved differently than the globally distributed flux (GDF), with a leveling off and partial recovery of ENAs from the GDF, owing to solar wind output flattening and recovery. The Ribbon has now also lost its latitudinal ordering, which reflects the breakdown of solar minimum solar wind conditions and exhibits a greater time delay than for the surrounding GDF. Together, the IBEX observations strongly support a secondary ENA source for the Ribbon, and we suggest that this be adopted as the nominal explanation of the Ribbon going forward.« less

Scientific Achievements of Global ENA Imaging and Future Outlook

NASA Astrophysics Data System (ADS)

Brandt, P. C.; Stephens, G. K.; Hsieh, S. Y. W.; Demajistre, R.; Gkioulidou, M.

2017-12-01

Energetic Neutral Atom (ENA) imaging is the only technique that can capture the instantaneous global state of energetic ion distributions in planetary magnetospheres and from the heliosheath. In particular at Earth, ENA imaging has been used to diagnose the morphology and dynamics of the ring current and plasma sheet down to several minutes time resolution and is therefore a critical tool to validate global ring current physics models. However, this requires a detailed understanding for how ENAs are produced from the ring current and inversion techniques that are thoroughly validated against in-situ measurements. To date, several missions have carried out planetary and heliospheric ENA imaging including Cassini, JUICE, IBEX of the heliosphere, and POLAR, Astrid-1, Double Star, TWINS and IMAGE of the terrestrial magnetosphere. Because of their path-finding successes, a future global-imaging mission concept, MEDICI, has been recommended in the Heliophysics Decadal Survey. Its core mission consists of two satellites in one circular, near-polar orbit beyond the radiation belts at around 8 RE, with ENA, EUV and FUV cameras. This recommendation has driven the definition of smaller mission concepts that address specific science aspects of the MEDICI concept. In this presentation, we review the past scientific achievements of ENA imaging with a focus on the terrestrial magnetosphere from primarily the NASA IMAGE and the TWINS missions. The highlighted achievements include the storm, sub-storm and quiet-time morphology, dynamics and pitch-angle distributions of the ring current, global differential acceleration of protons versus O+ ions, the structure of the global electrical current systems associated with the plasma pressure of protons and O+ ions up to around 200 keV, and the relation between ring current and plasmasphere. We discuss the need for future global observations of the ring current, plasma sheet and magnetosheath ion distributions based and derive their measurement requirements, of which high-angular resolution (≤2˚) is critical. A significant aspect of the future science definition is the stability and accessibility of inversion algorithms that retrieve the 3D distribution from the 2D ENA images, that will also be discussed.

What We've Learned from IBEX ENA Imaging of the Heliosheath

NASA Astrophysics Data System (ADS)

Zirnstein, E.

2017-12-01

The Interstellar Boundary Explorer (IBEX) is an Earth-orbiting spacecraft equipped with two single-pixel cameras that detect neutral atoms produced by the interaction of the solar wind (SW) with the very local interstellar medium (VLISM), as well as neutral atoms flowing in from the VLISM itself. Since its launch in 2009, IBEX has provided us with over half a solar cycle of measurements of energetic neutral atom (ENA) fluxes produced in the heliosphere. In particular, a large number of these ENAs originate in the inner heliosheath, a region of nearly incompressible SW plasma that is slowed, compressed, and heated at the termination shock. As the heated SW plasma flows through the heliosheath and down the heliotail, charge-exchange with cold neutral atoms from the VLISM generates ENAs that travel on ballistic trajectories. Some of these ENAs travel to Earth and are detected by IBEX. IBEX all-sky observations of these ENAs show a unique energy and spatial dependence, revealing the structural and plasma properties of the heliosheath. One of the prime scientific objectives of the Interstellar Mapping and Acceleration Probe (IMAP) mission is to understand the SW-VLISM interaction, including the properties of the heliosheath and heliotail. This talk will review key IBEX observations of the inner heliosheath environment, the way they have shaped our understanding of the SW-VLISM interaction, and their implications for the upcoming IMAP mission.

Kinetic Simulation and Energetic Neutral Atom Imaging of the Magnetosphere

NASA Technical Reports Server (NTRS)

Fok, Mei-Ching H.

2011-01-01

Advanced simulation tools and measurement techniques have been developed to study the dynamic magnetosphere and its response to drivers in the solar wind. The Comprehensive Ring Current Model (CRCM) is a kinetic code that solves the 3D distribution in space, energy and pitch-angle information of energetic ions and electrons. Energetic Neutral Atom (ENA) imagers have been carried in past and current satellite missions. Global morphology of energetic ions were revealed by the observed ENA images. We have combined simulation and ENA analysis techniques to study the development of ring current ions during magnetic storms and substorms. We identify the timing and location of particle injection and loss. We examine the evolution of ion energy and pitch-angle distribution during different phases of a storm. In this talk we will discuss the findings from our ring current studies and how our simulation and ENA analysis tools can be applied to the upcoming TRIO-CINAMA mission.

Simulation and 'TWINS Observations of the 22 July 2009 Storm

NASA Technical Reports Server (NTRS)

Fok, Mei-Ching; Buzulukova, Natalia Y.; Chen, Sheng-Hsien; Valek, Phil; Goldstein, Jerry; McComas, David

2010-01-01

TWINS is the first mission to perform stereo imaging of the Earth's ring current. The magnetic storm on 22 July 2009 is the largest storm observed since TWINS began routine stereo imaging in June 2008. On 22 July 2009, the Dst dropped to nearly -80nT at 7:00 and 10:00 UT. During the main phase and at the peak of the storm, TWINS 1 and 2 were near apogee and moving from pre-dawn to post-dawn local time. The energetic neutral atom (ENA) imagers on the 2 spacecraft captured the storm intensification and the formation of the partial ring current. The peak of the ENA emissions was seen in the midnight-to-dawn local-time sector. The development of this storm has been simulated using the Comprehensive Ring Current Model (CRCM) to understand and interpret the observed signatures. We perform CRCM runs with constant and time-varying magnetic field. The model calculations are validated by comparing the simulated ENA and ion flux intensities with TWINS ENA images and in-situ ion data from THEMIS satellites. Simulation with static magnetic field produces a strong shielding electric field that skews the ion drift trajectories toward dawn. The model's corresponding peak ENA emissions are always eastward than those in the observed TWINS images. On the other hand, simulation with a dynamic magnetic field gives better spatial agreements with both ENA and insitu particle data, suggesting that temporal variations of the geomagnetic field exert a significant influence upon global ring current ion dynamics.

The Energetic Neutral Atoms of the "Croissant" Heliosphere with Jets

NASA Astrophysics Data System (ADS)

Kornbleuth, M. Z.; Opher, M.; Michael, A.

2017-12-01

Opher et al. (2015) suggests the heliosphere may have two jets in the tail-ward direction driven to the north and south. This new model, the "Croissant Heliosphere", is in contrast to the classically accepted view of a comet-like tail. We investigate the effect of the heliosphere with jets model on energetic neutral atom (ENA) maps. Regardless of the existence of a split tail, other models show heliosheath plasma confined by the toroidal magnetic field in a "slinky" structure, similar to astrophysical jets bent by the interstellar medium. Therefore, the confinement of the plasma should appear in the ENA maps. ENA maps from the Interstellar Boundary Explorer (IBEX) have recently shown two high latitude lobes with excess ENA flux at higher energies in the tail of the heliosphere. These lobes could be a signature of the two jet structure of the heliosphere, while some have argued they are cause by the fast/slow solar wind profile. Here we present the ENA maps of the "Croissant Heliosphere" using initially a uniform solar wind. We incorporate pick-up ions (PUIs) into our model based on the kinetic modeling of Malama et al. (2006). We include the extinction of PUIs in the heliosheath and describe a locally created PUI population resulting from this extinction process. Additionally, we include the angular dependence of the PUIs based on the work of Vasyliunas & Siscoe (1976). With our model, we find that, in the presence of a uniform solar wind, the "heliosphere with jets" model is able to qualitatively reproduce the lobe structure of the tail seen in IBEX measurements. Turbulence also manifests itself within the lobes of the simulated ENA maps on the order of years. Finally we will present ENA maps using a time-dependent model of the heliosphere with the inclusion of solar cycle.

Simulation and Twins Observations of the 22 July 2009 Storm

NASA Technical Reports Server (NTRS)

Fok, M.-C.; Buzulukova, N.; Chen, S.-H.; Valek, P. W.; Goldstein, J.; McComas, D. J.

2011-01-01

TWINS is the first mission to perform stereo imaging of the Earth's ring current. The magnetic storm on 22 July 2009 was at the time the largest storm observed since TWINS began routine stereo imaging in June 2008. On 22 July 2009, the Dst dropped to nearly .80 nT at 0700 and 1000 UT. During the main phase, and at the peak of the storm, TWINS 1 and 2 were near apogee and moving between predawn and postdawn local time. The energetic neutral atom (ENA) imagers on the two spacecraft captured the storm intensification and the formation of the partial ring current. The peak of the high-altitude ENA emissions was seen in the midnight-to-dawn local time sector. The development of this storm has been simulated using the comprehensive ring current model (CRCM) to understand and interpret the observed signatures. We perform CRCM runs with constant and time-varying magnetic field. The model calculations are validated by comparing the simulated ENA and ion flux intensities with TWINS ENA images and in situ ion data from a THEMIS satellite. Simulation with a static magnetic field produces a strong shielding electric field that skews the ion drift trajectories toward dawn. The model's corresponding peak ENA emissions are always more eastward than those in the observed TWINS images. On the other hand, the simulation with a dynamic magnetic field gives better spatial agreement with both ENA and in situ particle data, suggesting that temporal variations of the geomagnetic field exert a significant influence upon global ring current ion dynamics.

Global Properties of the Heliospheric Termination Shock as inferred from Energetic Neutral Atoms measured by the Interstellar Boundary Explorer (IBEX)

NASA Astrophysics Data System (ADS)

Desai, Mihir; Heerikhuisen, Jacob; McComas, David; Pogorelov, Nikolai; Zank, Gary; Dayeh, Maher; Schwadron, Nathan; Allegrini, Frederic; Zirnstein, Eric

Energetic Neutral Atoms (ENAs) observed by the Interstellar Boundary Explorer (IBEX) provide powerful diagnostics about the origin of the progenitor ion populations and the physical mechanisms responsible for their production. Desai et al. (2012; 2013) combined and compared ENA spectra from the first three years of observations by the IBEX-Hi and -Lo ENA imagers along the lines-of-sights (LOS) from the inner heliosphere through to the locations of Voyager 1 and 2 with results from an updated physics-based model of the 3D heliosphere and its constituent ion populations. These results showed that (1) IBEX ENA fluxes and spectra above ˜0.7 keV measured along the LOS of the Voyagers are consistent with several models in which the parent pickup (PUI) populations originate in the inner heliosheath, and (2) a significant fraction of lower-energy ENAs between ˜0.1-0.5 keV may originate from interstellar neutral gas charge-exchanging with a non-thermalized (hot) population of PUIs in the outer heliosheath beyond the heliopause. We use these results and model the full sky IBEX-Hi energy spectra to probe the microphysical processes occurring in the inner heliospheath near the termination shock and then infer the global properties (e.g., latitudinal and longitudinal variations of the shock compression ratio) of the termination shock.

Inhaled ENaC antisense oligonucleotide ameliorates cystic fibrosis-like lung disease in mice.

PubMed

Crosby, Jeff R; Zhao, Chenguang; Jiang, Chong; Bai, Dong; Katz, Melanie; Greenlee, Sarah; Kawabe, Hiroshi; McCaleb, Michael; Rotin, Daniela; Guo, Shuling; Monia, Brett P

2017-11-01

Epithelial sodium channel (ENaC, Scnn1) hyperactivity in the lung leads to airway surface dehydration and mucus accumulation in cystic fibrosis (CF) patients and in mice with CF-like lung disease. We identified several potent ENaC specific antisense oligonucleotides (ASOs) and tested them by inhalation in mouse models of CF-like lung disease. The inhaled ASOs distributed into lung airway epithelial cells and decreased ENaC expression by inducing RNase H1-dependent degradation of the targeted Scnn1a mRNA. Aerosol delivered ENaC ASO down-regulated mucus marker expression and ameliorated goblet cell metaplasia, inflammation, and airway hyper-responsiveness. Lack of systemic activity of ASOs delivered via the aerosol route ensures the safety of this approach. Our results demonstrate that antisense inhibition of ENaC in airway epithelial cells could be an effective and safe approach for the prevention and reversal of lung symptoms in CF and potentially other inflammatory diseases of the lung. Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

γEpithelial Na(+) Channel (γENaC) and the Acid-Sensing Ion Channel 1 (ASIC1) expression in the urothelium of patients with neurogenic detrusor overactivity.

PubMed

Traini, Chiara; Del Popolo, Giulio; Lazzeri, Massimo; Mazzaferro, Katia; Nelli, Federico; Calosi, Laura; Vannucchi, Maria Giuliana

2015-11-01

To investigate the expression of two types of cation channels, γEpithelial Na(+) Channel (γENaC) and the Acid-Sensing Ion Channel 1 (ASIC1), in the urothelium of controls and in patients affected by neurogenic detrusor overactivity (NDO). In parallel, urodynamic parameters were collected and correlated to the immunohistochemical results. Four controls and 12 patients with a clinical diagnosis of NDO and suprasacral spinal cord lesion underwent urodynamic measurements and cystoscopy. Cold-cup biopsies were frozen and processed for immunohistochemistry and Western Blot. Spearman's correlation coefficient between morphological and urodynamic data was applied. One-way anova followed by Newman-Keuls multiple comparison post hoc test was applied for Western Blot results. In the controls, γENaC and ASIC1 were expressed in the urothelium with differences in their cell distribution and intensity. In patients with NDO, both markers showed consistent changes either in cell distribution and labelling intensity compared with the controls. A significant correlation between a higher intensity of γENaC expression in the urothelium of patients with NDO and lower values of bladder compliance was detected. The present findings show important changes in the expression of γENaC and ASIC1 in NDO human urothelium. Notably, while the changes in γENaC might impair the mechanosensory function of the urothelium, the increase of ASIC1 might represent an attempt to compensate for the excess in local sensitivity. © 2014 The Authors BJU International © 2014 BJU International Published by John Wiley & Sons Ltd.

Latittudinal and energy dependence of energetic neutral atom spectral indices measured by the Interstellar Boundary Explorer

DOE PAGES

Desai, M. I.; Allegrini, F.; Dayeh, M. A.; ...

2015-03-30

Here, we investigate the latitudinal and energy dependence of the globally distributed 0.5-6 keV energetic neutral atom (ENA) spectra measured by the Interstellar Boundary Explorer (IBEX) during the first 3 yrs of the mission. Our results are: (1) the ENA spectral indices at the two lowest energies (0.89 and 1.47 keV) exhibit no clear trend with ecliptic latitude θ, while those at ~2.29 and ~3.41 keV exhibit a clear latitudinal pattern; flatter spectra occur above 60° latitude and steeper spectra occur ±30° of the equator. (2) The latitudinal dependence of the spectral indices at different energies can be represented bymore » the cosine function γ =a 0 + a 1 cos (a 2θ) with unique offsets, amplitudes, and phase angles; the higher energy ENA indices transition to successively larger amplitudes within ±45° of the equator. The results confirm the previously reported latitudinal organization of the ENA spectra and their remarkable similarity to that of the solar wind (SW) speed observed by Ulysses in the inner heliosphere. And while earlier studies showed that the ~0.5-6 keV globally distributed ENA spectral indices could be represented as single power laws over much of the sky, our new results indicate that this is an over-simplification because the spectral indices have an energy and latitude dependence. Furthermore, this dependence is an important factor that must be taken into consideration by models and simulations that seek to map the IBEX ENA observations back to the latitudinal profile of the SW speed structure observed in the inner heliosphere.« less

Latitudinal and Energy Dependence of Energetic Neutral Atom Spectral Indices Measured by the Interstellar Boundary Explorer

NASA Astrophysics Data System (ADS)

Desai, M. I.; Allegrini, F.; Dayeh, M. A.; Funsten, H.; Heerikhuisen, J.; McComas, D. J.; Fuselier, S. A.; Pogorelov, N.; Schwadron, N. A.; Zank, G. P.; Zirnstein, E. J.

2015-04-01

We investigate the latitudinal and energy dependence of the globally distributed 0.5-6 keV energetic neutral atom (ENA) spectra measured by the Interstellar Boundary Explorer (IBEX) during the first 3 yrs of the mission. Our results are: (1) the ENA spectral indices at the two lowest energies (0.89 and 1.47 keV) exhibit no clear trend with ecliptic latitude θ, while those at ˜2.29 and ˜3.41 keV exhibit a clear latitudinal pattern; flatter spectra occur above 60° latitude and steeper spectra occur ±30° of the equator. (2) The latitudinal dependence of the spectral indices at different energies can be represented by the cosine function γ ={{a}0}+{{a}1}cos ({{a}2}θ ) with unique offsets, amplitudes, and phase angles; the higher energy ENA indices transition to successively larger amplitudes within ±45° of the equator. Our results confirm the previously reported latitudinal organization of the ENA spectra and their remarkable similarity to that of the solar wind (SW) speed observed by Ulysses in the inner heliosphere. While earlier studies showed that the ˜0.5-6 keV globally distributed ENA spectral indices could be represented as single power laws over much of the sky, our new results indicate that this is an over-simplification because the spectral indices have an energy and latitude dependence. This dependence is an important factor that must be taken into consideration by models and simulations that seek to map the IBEX ENA observations back to the latitudinal profile of the SW speed structure observed in the inner heliosphere.

The Moon observed in Energetic Neutral Atoms: Review of the Scientific Findings from SARA/CENA on board Chandrayaan-1

NASA Astrophysics Data System (ADS)

Vorburger, Audrey; Wurz, Peter; Barabash, Stas; Wieser, Martin; Futaana, Yoshifumi; Bhardwaj, Anil; Dhanya, Mb; Asamura, Kazushi

2017-04-01

The Sub-keV Atom Reflecting Analyzer (SARA) instrument on board Chandrayaan-1 was exceptionally successful. The instrument not only achieved all its set science goals but also revealed several hitherto unknown and unexpected properties of the solar wind interaction with the lunar surface. SARA's scientific findings can be divided into two groups based on the nature of the particles detected: The first group contains findings gained from ion measurements (from SWIM, SARA's ion sensor) whereas the second group contains findings gained from energetic neutral atom (ENA) measurements (from CENA, SARA's ENA sensor). Here, we present a review of all scientific findings based on ENA measurements. Since the Moon is constantly bombarded by solar wind ions. Until recently, it was tacitly assumed that the ions that impinge onto the lunar surface are almost completely absorbed, with less than 1% reflection, (e.g. Crider and Vondrak, Adv. Space Res., 2002; Feldman et al., JGR, 2000). However, recent observations conducted showed that on average 16% of the impinging solar wind ions are reflected as ENAs (e.g. McComas et al., GRL, 2009; Wieser et al., PSS, 2009; Vorburger et al., JGR, 2013). The energy spectrum of the reflected ENAs is broader than the spectrum of the incident solar wind protons (Futaana et al., JGR, 2012; Harada et al., JGR, 2014), and the characteristic energy is < 50% of the incident solar wind characteristic energy. This hints at multiple scattering processes taking place on the lunar surface. Determination of the ENA angular backscatter function showed that, contrary to expectations, as the solar zenith angle (SZA) increases, particles scatter more toward the sunward direction than in the anti-sunward direction (Vorburger et al., GRL, 2011; Lue et al., JGR, 2016). The ENA reflection ratio is rather featureless over the lunar surface (Vorburger et al., JGR., 2013), showing only strong variations at local crustal magnetic fields due to the interaction of the plasma with so-called mini-magnetospheres (e.g., Wieser et al., GRL, 2010; Vorburger et al., JGR, 2012; Vorburger et al., JGR, 2013). CENA measurements were also used to derive the electric potential above a lunar magnetic anomaly (Futaana et al., GRL, 2012, Järvinen et al. GRL, 2014). Electrical potentials are of scientific interest because they can influence the local plasma and dust environment near the magnetic anomaly. CENA also presented the first-ever measurements of sputtered lunar oxygen (Vorburger et al., JGR., 2012) as well as the first-ever observations of backscattered solar wind helium (Vorburger et al., JGR., 2012). With the backscattered proton signal being unexpectedly large, these signals are small in comparison, but persistent nevertheless. Finally, recent CENA data analyses showed that a significant fraction of the solar wind plasma is able to reach far into the lunar nightside surface: CENA measured a 30 deg broad ENA ring parallel to the terminator, with a total flux equal to 1.5% of the total dayside flux (Vorburger et al., GR., 2016). These measurements shed light onto the expansion of plasma into voids as they occur in planetary wakes.

Acute inhibition of NCC does not activate distal electrogenic Na+ reabsorption or kaliuresis.

PubMed

Hunter, Robert W; Craigie, Eilidh; Homer, Natalie Z M; Mullins, John J; Bailey, Matthew A

2014-02-15

Na(+) reabsorption from the distal renal tubule involves electroneutral and electrogenic pathways, with the latter promoting K(+) excretion. The relative activities of these two pathways are tightly controlled, participating in the minute-to-minute regulation of systemic K(+) balance. The pathways are interdependent: the activity of the NaCl cotransporter (NCC) in the distal convoluted tubule influences the activity of the epithelial Na(+) channel (ENaC) downstream. This effect might be mediated by changes in distal Na(+) delivery per se or by molecular and structural adaptations in the connecting tubule and collecting ducts. We hypothesized that acute inhibition of NCC activity would cause an immediate increase in Na(+) flux through ENaC, with a concomitant increase in renal K(+) excretion. We tested this using renal clearance methodology in anesthetized mice, by the administration of hydrochlorothiazide (HCTZ) and/or benzamil (BZM) to exert specific blockade of NCC and ENaC, respectively. Bolus HCTZ elicited a natriuresis that was sustained for up to 110 min; urinary K(+) excretion was not affected. Furthermore, the magnitude of the natriuresis was no greater during concomitant BZM administration. This suggests that ENaC-mediated Na(+) reabsorption was not normally limited by Na(+) delivery, accounting for the absence of thiazide-induced kaliuresis. After dietary Na(+) restriction, HCTZ elicited a kaliuresis, but the natiuretic effect of HCTZ was not enhanced by BZM. Our findings support a model in which inhibition of NCC activity does not increase Na(+) reabsorption through ENaC solely by increasing distal Na(+) delivery but rather by inducing a molecular and structural adaptation in downstream nephron segments.

Latitude, Energy, and Time Variations of Energetic Neutral Atom Spectral indices Measured by IBEX

NASA Astrophysics Data System (ADS)

Desai, M. I.; McComas, D. J.; Dayeh, M. A.; Funsten, H. O.; Schwadron, N.; Heerikhuisen, J.; Fuselier, S. A.; Allegrini, F.; Pogorelov, N.; Zank, G. P.

2015-12-01

We investigate the latitude, energy, and time variations of the globally distributed ~0.5-6 keV energetic neutral atom (ENA) spectra measured by the Interstellar Boundary Explorer (IBEX) during the first 5 years of the mission. Our previous results based on the first 3 years of IBEX observations showed that the ENA spectral indices at the two lowest energies (~0.89 and 1.47 keV) exhibit no clear trend with ecliptic latitude θ, while those at ~2.29 and ~3.41 keV exhibit a clear latitudinal pattern; flatter spectra occur above 60° latitude and steeper spectra occur ±30° of the equator. While these results confirmed the previously reported latitudinal organization of the ENA spectra and their remarkable similarity to that of the solar wind (SW) speed observed by Ulysses in the inner heliosphere, we also showed that, unlike previous reports, the ~0.5-6 keV globally distributed ENA spectral indices could not be represented as single power laws over much of the sky, and that they depend on energy and latitude. In this work we extend the above results to include years 4 and 5 of IBEX observations and investigate if the spectral indices vary as a function of time. Finally, we discuss implications of our results on models and simulations that seek to map the IBEX ENA observations back to the latitudinal profile of the SW speed structure observed in the inner heliosphere.

Latitude, Energy, and Time Variations of Energetic Neutral Atom Spectral indices Measured by IBEX

NASA Astrophysics Data System (ADS)

Desai, Mihir; Heerikhuisen, Jacob; McComas, David; Funsten, Herbert; Pogorelov, Nikolai; Zank, Gary; Schwadron, Nathan; Fuselier, Stephen; Allegrini, Frederic; Dayeh, Maher A.

2016-07-01

We investigate the latitude, energy, and time variations of the globally distributed 0.5-6 keV energetic neutral atom (ENA) spectra measured by the Interstellar Boundary Explorer (IBEX) during the first 5 years of the mission. Our previous results based on the first 3 years of IBEX observations showed that the ENA spectral indices at the two lowest energies (0.89 and 1.47 keV) exhibit no clear trend with ecliptic latitude θ, while those at ˜2.29 and ˜3.41 keV exhibit a clear latitudinal pattern; flatter spectra occur above 60° latitude and steeper spectra occur within ±30° of the equator. While these results confirmed the previously reported latitudinal organization of the ENA spectra and their remarkable similarity to that of the solar wind (SW) speed observed by Ulysses in the inner heliosphere, we also showed that, unlike previous reports, the ˜0.5-6 keV globally distributed ENA spectral indices could not be represented as single power laws over much of the sky, and that they depend on energy and latitude. In this paper we extend the above results to include years 4 and 5 of IBEX observations and investigate if the spectral indices vary as a function of time. Finally, we discuss implications of our results on models and simulations that seek to map the IBEX ENA observations back to the latitudinal profile of the SW speed structure observed in the inner heliosphere.

Imprint of the Sun’s Evolving Polar Winds on IBEX Energetic Neutral Atom All-sky Observations of the Heliosphere

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

Zirnstein, E. J.; McComas, D. J.; Dayeh, M. A.

2017-09-01

With 7 years of Interstellar Boundary Explorer ( IBEX ) measurements of energetic neutral atoms (ENAs), IBEX has shown a clear correlation between dynamic changes in the solar wind and the heliosphere’s response in the formation of ENAs. In this paper, we investigate temporal variations in the latitudinal-dependent ENA spectrum from IBEX and their relationship to the solar wind speed observed at 1 au. We find that the variation in latitude of the transition in ENA spectral indices between low (≲1.8) and high (≳1.8) values, as well as the distribution of ENA spectral indices at high and low latitudes, correlatesmore » well with the evolution of the fast and slow solar wind latitudinal structure observed near 1 au. This correlation includes a delay due to the time it takes the solar wind to propagate to the termination shock and into the inner heliosheath, and for ENAs to be generated via charge-exchange and travel back toward 1 au. Moreover, we observe a temporal asymmetry in the steepening of the ENA spectrum in the northern and southern hemispheres, consistent with asymmetries observed in the solar wind and polar coronal holes. While this asymmetry is observed near the upwind direction of the heliosphere, it is not yet observed in the tail direction, suggesting a longer line-of-sight integration distance or different processing of the solar wind plasma downstream of the termination shock.« less

Involvement of the exomer complex in the polarized transport of Ena1 required for Saccharomyces cerevisiae survival against toxic cations.

PubMed

Anton, Carlos; Zanolari, Bettina; Arcones, Irene; Wang, Congwei; Mulet, Jose Miguel; Spang, Anne; Roncero, Cesar

2017-12-01

Exomer is an adaptor complex required for the direct transport of a selected number of cargoes from the trans -Golgi network (TGN) to the plasma membrane in Saccharomyces cerevisiae However, exomer mutants are highly sensitive to increased concentrations of alkali metal cations, a situation that remains unexplained by the lack of transport of any known cargoes. Here we identify several HAL genes that act as multicopy suppressors of this sensitivity and are connected to the reduced function of the sodium ATPase Ena1. Furthermore, we find that Ena1 is dependent on exomer function. Even though Ena1 can reach the plasma membrane independently of exomer, polarized delivery of Ena1 to the bud requires functional exomer. Moreover, exomer is required for full induction of Ena1 expression after cationic stress by facilitating the plasma membrane recruitment of the molecular machinery involved in Rim101 processing and activation of the RIM101 pathway in response to stress. Both the defective localization and the reduced levels of Ena1 contribute to the sensitivity of exomer mutants to alkali metal cations. Our work thus expands the spectrum of exomer-dependent proteins and provides a link to a more general role of exomer in TGN organization. © 2017 Anton et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Ring Current Dynamics in Moderate and Strong Storms: Comparative Analysis of TWINS and IMAGE/HENA Data with the Comprehensive Ring Current Model

NASA Technical Reports Server (NTRS)

Buzulukova, N.; Fok, M.-C.; Goldstein, J.; Valek, P.; McComas, D. J.; Brandt, P. C.

2010-01-01

We present a comparative study of ring current dynamics during strong and moderate storms. The ring current during the strong storm is studied with IMAGE/HENA data near the solar cycle maximum in 2000. The ring current during the moderate storm is studied using energetic neutral atom (ENA) data from the Two Wide-Angle Imaging Neutral- Atom Spectrometers (TWINS) mission during the solar minimum in 2008. For both storms, the local time distributions of ENA emissions show signatures of postmidnight enhancement (PME) during the main phases. To model the ring current and ENA emissions, we use the Comprehensive Ring Current Model (CRCM). CRCM results show that the main-phase ring current pressure peaks in the premidnight-dusk sector, while the most intense CRCM-simulated ENA emissions show PME signatures. We analyze two factors to explain this difference: the dependence of charge-exchange cross section on energy and pitch angle distributions of ring current. We find that the IMF By effect (twisting of the convection pattern due to By) is not needed to form the PME. Additionally, the PME is more pronounced for the strong storm, although relative shielding and hence electric field skewing is well developed for both events.

Latitude, Energy, and Time Variations of Energetic Neutral Atom Spectral indices Measured by IBEX

NASA Astrophysics Data System (ADS)

Desai, Mihir; McComas, David; Dayeh, Maher; Funsten, Herbert; Schwadron, Nathan; Heerikhuisen, Jacob; Fuselier, Stephen; Pogorelov, Nikolai; Zank, Gary; Allegrini, Frederic

2016-04-01

We investigate the latitude, energy, and time variations of the globally distributed 0.5-6 keV energetic neutral atom (ENA) spectra measured by the Interstellar Boundary Explorer (IBEX) during the first 5 years of the mission. Our previous results based on the first 3 years of IBEX observations showed that the ENA spectral indices at the two lowest energies (0.89 and 1.47 keV) exhibit no clear trend with ecliptic latitude θ, while those at ˜2.29 and ˜3.41 keV exhibit a clear latitudinal pattern; flatter spectra occur above 60° latitude and steeper spectra occur ±30° of the equator. While these results confirmed the previously reported latitudinal organization of the ENA spectra and their remarkable similarity to that of the solar wind (SW) speed observed by Ulysses in the inner heliosphere, we also showed that, unlike previous reports, the ˜0.5-6 keV globally distributed ENA spectral indices could not be represented as single power laws over much of the sky, and that they depend on energy and latitude. In this work we extend the above results to include years 4 and 5 of IBEX observations and investigate if the spectral indices vary as a function of time. Finally, we discuss implications of our results on models and simulations that seek to map the IBEX ENA observations back to the latitudinal profile of the SW speed structure observed in the inner heliosphere. We also discuss the implications of these new results for observational requirements for upcoming missions like IMAP.

SELMA mission: revealing the origin of lunar water

NASA Astrophysics Data System (ADS)

Barabash, Stas; Selma Team

2013-04-01

We propose a very low cost lunar mission to cover a poorly investigated inter-disciplinary area in the lunar science. The mission SELMA (Surface, Environment, and Lunar Magnetic Anomalies) investigates the interaction of the neutral and plasma environment with the lunar surface and the impact of this interaction on the surface composition, in the first hand, on the presence of water. The mission focuses on the fundamental question: What is the origin of the water in the lunar soil? The mission also addresses the questions: What are the lunar exosphere content and composition and how does the exosphere interact with the surface? How do the lunar magnetic anomalies interact with the solar wind and affect the surface? SELMA investigates the origin of the water in the lunar soil via simultaneous measurements of the OH/H2O abundance in the soil, the proton flux deposited to the surface, and transient changes in the exospheric gas content and composition. The water content in the surface is mapped via measurements of the 2700 - 3300 nm OH/H2O/ice absorption lines. The proton flux at the surface is measured remotely via backscattered hydrogen flux (energetic neutral atoms, ENAs). The exospheric gas content and composition and possible transient changes due to micrometeoroid influx or outgassing are monitored by a neutral gas mass spectrometer. Little is known about the tenuous lunar exosphere, its composition, structure, and relation to the plasma environment. The reasons for the present poor knowledge of the lunar exosphere is the difficulty of observations due to the low number densities, and the complexity of models due to the multiplicity of the mechanisms responsible for the input and loss of exospheric species. To investigate the lunar exosphere SELMA is equipped with state-of-the-art time-of-flight neutral gas mass spectrometer with unprecedented sensitivity and mass resolution. The Moon does not have a global magnetic field but possesses local magnetizations. The magnetizations interact with the solar wind plasma creating highly variable mini-magnetospheres affecting, through an as yet unknown mechanism, the surface visible albedo. The electrodynamical interaction is very complex being one of the fundamental solar wind interactions in the solar system. SELMA studies how the magnetic anomaly interact with the solar wind and surface via simultaneous measurements of 3D ion and electron distribution functions, the local magnetic field, solar wind flux variations on the surface through ENA imaging of the backscattered hydrogen flux, imaging in the visible range, and measuring the surface IR spectrum. The SELMA results will be of critical importance for the interpretation of data from Mercury to be collected by the ESA BepiColombo mission in 2020 - 2022. To address its scientific objectives SELMA carries a highly focused suite of instruments including an IR spectrometer, an ENA telescope, an ion and electron spectrometer, a neutral gas mass spectrometer, a magnetometer, and a visible camera. SELMA is a spinning platform to be inserted on a low maintenance quasi-frozen polar orbit of 30 km x 216 km by a dedicated launch and a solid state fuel kick stage. SELMA was proposed to ESA as a candidate for the S-class mission.

The impact of exospheric neutral dynamics on ring current decay

NASA Astrophysics Data System (ADS)

Ilie, R.; Liemohn, M. W.; Skoug, R. M.; Funsten, H. O.; Gruntman, M.; Bailey, J. J.; Toth, G.

2015-12-01

The geocorona plays an important role in the energy budget of the Earth's inner magnetosphere since charge exchange of energetic ions with exospheric neutrals makes the exosphere act as an energy sink for ring current particles. Long-term ring current decay following a magnetic storm is mainly due to these electron transfer reactions, leading to the formation energetic neutral atoms (ENAs) that leave the ring current system on ballistic trajectories. The number of ENAs emitted from a given region of space depends on several factors, such as the energy and species of the energetic ion population in that region and the density of the neutral gas with which the ions undergo charge exchange. However, the density and structure of the exosphere are strongly dependent on changes in atmospheric temperature and density as well as charge exchange with the ions of plasmaspheric origin, which depletes the geocorona (by having a neutral removed from the system). Moreover, the radiation pressure exerted by solar far-ultraviolet photons pushes the geocoronal hydrogen away from the Earth in an anti-sunward direction to form a tail of neutral hydrogen. TWINS ENA images provide a direct measurement of these ENA losses and therefore insight into the dynamics of the ring current decay through interactions with the geocorona. We assess the influence of geocoronal neutrals on ring current formation and decay by analysis of the predicted ENA emissions using 6 different geocoronal models and simulations from the HEIDI ring current model during storm time. Comparison with TWINS ENA images shows that the location of the peak ENA enhancements is highly dependent on the distribution of geocoronal hydrogen density. We show that the neutral dynamics has a strong influence on the time evolution of the ring current populations as well as on the formation of energetic neutral atoms.

Boundary Layer Thermodynamics and Cloud Microphysics for a Mixed Stratocumulus and Cumulus Cloud Field Observed during ACE-ENA

NASA Astrophysics Data System (ADS)

Jensen, M. P.; Miller, M. A.; Wang, J.

2017-12-01

The first Intensive Observation Period of the DOE Aerosol and Cloud Experiments in the Eastern North Atlantic (ACE-ENA) took place from 21 June through 20 July 2017 involving the deployment of the ARM Gulfstream-159 (G-1) aircraft with a suite of in situ cloud and aerosol instrumentation in the vicinity of the ARM Climate Research Facility Eastern North Atlantic (ENA) site on Graciosa Island, Azores. Here we present preliminary analysis of the thermodynamic characteristics of the marine boundary layer and the variability of cloud properties for a mixed cloud field including both stratiform cloud layers and deeper cumulus elements. Analysis combines in situ atmospheric state observations from the G-1 with radiosonde profiles and surface meteorology from the ENA site in order to characterize the thermodynamic structure of the marine boundary layer including the coupling state and stability. Cloud/drizzle droplet size distributions measured in situ are combined with remote sensing observations from a scanning cloud radar, and vertically pointing cloud radar and lidar provide quantification of the macrophysical and microphysical properties of the mixed cloud field.

Analysis of Aprotinin, a Protease Inhibitor, Action on the Trafficking of Epithelial Na+ Channels (ENaC) in Renal Epithelial Cells Using a Mathematical Model.

PubMed

Sasamoto, Kouhei; Marunaka, Rie; Niisato, Naomi; Sun, Hongxin; Taruno, Akiyuki; Pezzotti, Giuseppe; Yamamoto, Toshiro; Kanamura, Narisato; Zhu, Wenliang; Nishio, Kyosuke; Inui, Toshio; Eaton, Douglas C; Marunaka, Yoshinori

2017-01-01

Epithelial Na+ channels (ENaC) play a crucial role in control of blood pressure by regulating renal Na+ reabsorption. Intracellular trafficking of ENaC is one of the key regulators of ENaC function, but a quantitative description of intracellular recycling of endogenously expressed ENaC is unavailable. We attempt here to provide a model for intracellular recycling after applying a protease inhibitor under hypotonic conditions. We simulated the ENaC-mediated Na+ transport in renal epithelial A6 cells measured as short-circuit currents using a four-state mathematical ENaC trafficking model. We developed a four-state mathematical model of ENaC trafficking in the cytosol of renal epithelial cells that consists of: an insertion state of ENaC that can be trafficked to the apical membrane state (insertion rate); an apical membrane state of ENaC conducting Na+ across the apical membrane; a recycling state containing ENaC that are retrieved from the apical membrane state (endocytotic rate) and then to the insertion state (recycling rate) communicating with the apical membrane state or to a degradation state (degradation rate). We studied the effect of aprotinin (a protease inhibitor) blocking protease-induced cleavage of the extracellular loop of γ ENaC subunit on the rates of intracellular ENaC trafficking using the above-defined four-state mathematical model of ENaC trafficking and the recycling number relative to ENaC staying in the apical membrane. We found that aprotinin significantly reduced the insertion rate of ENaC to the apical membrane by 40%, the recycling rate of ENaC by 81%, the cumulative time of an individual ENaC staying in the apical membrane by 32%, the cumulative life-time after the first endocytosis of ENaC by 25%, and the cumulative Na+ absorption by 31%. The most interesting result of the present study is that cleavage of ENaC affects the intracellular ENaC trafficking rate and determines the residency time of ENaC, indicating that more active cleaved ENaCs stay longer at the apical membrane contributing to transcellular Na+ transport via an increase in recycling of ENaC to the apical membrane. The extracellular protease-induced cleavage of the extracellular loop of γ ENaC subunit increases transcellular epithelial Na+ transport by elevating the recycling rate of ENaC due to an increase in the recycling rate of ENaCs associated with increases in the insertion rate of ENaC. © 2017 The Author(s). Published by S. Karger AG, Basel.

Hybrid Simulations for the Turbulence and the Wave-Particle Interaction in the Inner and the Outer Heliopause.

NASA Astrophysics Data System (ADS)

Kucharek, H.; Pogorelov, N. V.; Mueller, H. R.; Gamayunov, K. V.

2014-12-01

IBEX and the Voyager spacecraft provide unique data sets that enable us to study plasma conditions in the key regions of the heliosphere: the termination shock (TS), at the heliospause and beyond. Whereas Voyager provides in-situ plasma data IBEX uses neutral atoms to remote sense the plasma conditions in interstellar space, the heliopause, and the termination shock. The IBEX data sets revealed a ribbon feature which was unexpected and which formation mechanism is still unknown. Even the location of the source is not known considering the fact that IBEX measures neutral along a line of sight. Aside from the ribbon feature the distributed ENA flux shows temporal variations that are unexplained, in particular at solar wind energies. Furthermore, Voyager observations questioned the role of the termination shock being the main accelerator for high-energetic ions. All of these outstanding science questions are associated with wave-particle interaction and turbulence in most likely different key regions of the heliosphere. Hybrid simulations, which included all kinetic processes self-consistently on the ion level, are a proven to be a very powerful tool to investigate wave-particle interaction, turbulence, and phase-space evolution of pickup and solar wind ions. We performed 3D multi-species hybrid simulations for an ion/ion beam instability to study the temporal evolution of ion distributions, their stability, and the associated ENA generation under the influence of self-generated waves in the heliosheath. We investigated the energetization of ions downstream of the TS, the turbulence, and growth rate of instabilities in the heliosheath. The simulations show that ions can be accelerated downstream of the TS by trapping ions in coherent wave fronts.

Phylogenetic diversity anomaly in angiosperms between eastern Asia and eastern North America.

PubMed

Qian, Hong; Jin, Yi; Ricklefs, Robert E

2017-10-24

Although eastern Asia (EAS) and eastern North America (ENA) have similar climates, plant species richness in EAS greatly exceeds that in ENA. The degree to which this diversity difference reflects the ages of the floras or their rates of evolutionary diversification has not been quantified. Measures of species diversity that do not incorporate the ages of lineages disregard the evolutionary distinctiveness of species. In contrast, phylogenetic diversity integrates both the number of species and their history of evolutionary diversification. Here we compared species diversity and phylogenetic diversity in a large number of flowering plant (angiosperm) floras distributed across EAS and ENA, two regions with similar contemporary environments and broadly shared floristic history. After accounting for climate and sample area, we found both species diversity and phylogenetic diversity to be significantly higher in EAS than in ENA. When we controlled the number of species statistically, we found that phylogenetic diversity remained substantially higher in EAS than in ENA, although it tended to converge at high latitude. This pattern held independently for herbs, shrubs, and trees. The anomaly in species and phylogenetic diversity likely resulted from differences in regional processes, related in part to high climatic and topographic heterogeneity, and a strong monsoon climate, in EAS. The broad connection between tropical and temperate floras in southern Asia also might have played a role in creating the phylogenetic diversity anomaly.

STRUCTURE OF THE INTERSTELLAR BOUNDARY EXPLORER RIBBON FROM SECONDARY CHARGE-EXCHANGE AT THE SOLAR–INTERSTELLAR INTERFACE

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

Zirnstein, E. J.; McComas, D. J.; Heerikhuisen, J., E-mail: ezirnstein@swri.edu, E-mail: dmccomas@swri.edu, E-mail: jacob.heerikhuisen@uah.edu

2015-05-01

In 2009, the Interstellar Boundary Explorer discovered a bright “ribbon” of energetic neutral atom (ENA) flux in the energy range ≤0.4–6 keV, encircling a large portion of the sky. This observation was not previously predicted by any models or theories, and since its discovery, it has been the subject of numerous studies of its origin and properties. One of the most studied mechanisms for its creation is the “secondary ENA” process. Here, solar wind ions, neutralized by charge-exchange with interstellar atoms, propagate outside the heliopause; experience two charge-exchange events in the dense outer heliosheath; and then propagate back inside themore » heliosphere, preferentially in the direction perpendicular to the local interstellar magnetic field. This process has been extensively analyzed using state-of-the-art modeling and simulation techniques, but it has been difficult to visualize. In this Letter, we show the three-dimensional structure of the source of the ribbon, providing a physical picture of the spatial and energy scales over which the secondary ENA process occurs. These results help us understand how the ribbon is generated and further supports a secondary ENA process as the leading ribbon source mechanism.« less

Electrophysiological and biochemical evidence that DEG/ENaC cation channels are composed of nine subunits.

PubMed

Snyder, P M; Cheng, C; Prince, L S; Rogers, J C; Welsh, M J

1998-01-09

Members of the DEG/ENaC protein family form ion channels with diverse functions. DEG/ENaC subunits associate as hetero- and homomultimers to generate channels; however the stoichiometry of these complexes is unknown. To determine the subunit stoichiometry of the human epithelial Na+ channel (hENaC), we expressed the three wild-type hENaC subunits (alpha, beta, and gamma) with subunits containing mutations that alter channel inhibition by methanethiosulfonates. The data indicate that hENaC contains three alpha, three beta, and three gamma subunits. Sucrose gradient sedimentation of alphahENaC translated in vitro, as well as alpha-, beta-, and gammahENaC coexpressed in cells, was consistent with complexes containing nine subunits. FaNaCh and BNC1, two related DEG/ENaC channels, produced complexes of similar mass. Our results suggest a novel nine-subunit stoichiometry for the DEG/ENaC family of ion channels.

Localization of beta and gamma subunits of ENaC in sensory nerve endings in the rat foot pad.

PubMed

Drummond, H A; Abboud, F M; Welsh, M J

2000-11-24

The molecular mechanisms underlying mechanoelectrical transduction and the receptors that detect light touch remain uncertain. Studies in Caenorhabditis elegans suggest that members of the DEG/ENaC cation channel family may be mechanoreceptors. Therefore, we tested the hypothesis that subunits of the mammalian epithelial Na(+) channel (ENaC) family are expressed in touch receptors in rat hairless skin. We detected betaENaC and gammaENaC, but not alphaENaC transcripts in cervical and lumbar dorsal root ganglia (DRG). Using immunofluorescence, we found betaENaC and gammaENaC expressed in medium to large lumbar DRG neurons. Moreover, we detected these two subunits in Merkel cell-neurite complexes, Meissner-like corpuscles, and small lamellated corpuscles, specialized mechanosensory structures of the skin. Within these structures, betaENaC and gammaENaC were localized in the nerve fibers believed to contain the sensors responsive to mechanical stress. Thus beta and gammaENaC subunits are good candidates as components of the molecular sensor that detects touch.

Bumetanide increases Cl--dependent short-circuit current in late distal colon: Evidence for the presence of active electrogenic Cl- absorption.

PubMed

Tang, Lieqi; Fang, Xiefan; Winesett, Steven P; Cheng, Catherine Y; Binder, Henry J; Rivkees, Scott A; Cheng, Sam X

2017-01-01

Mammalian colonic epithelia consist of cells that are capable of both absorbing and secreting Cl-. The present studies employing Ussing chamber technique identified two opposing short-circuit current (Isc) responses to basolateral bumetanide in rat distal colon. Apart from the transepithelial Cl--secretory Isc in early distal colon that was inhibited by bumetanide, bumetanide also stimulated Isc in late distal colon that had not previously been identified. Since bumetanide inhibits basolateral Na+-K+-2Cl- cotransporter (NKCC) in crypt cells and basolateral K+-Cl- cotransporter (KCC) in surface epithelium, we proposed this stimulatory Isc could represent a KCC-mediated Cl- absorptive current. In support of this hypothesis, ion substitution experiments established Cl- dependency of this absorptive Isc and transport inhibitor studies demonstrated the involvement of an apical Cl- conductance. Current distribution and RNA sequencing analyses revealed that this Cl- absorptive Isc is closely associated with epithelial Na+ channel (ENaC) but is not dependent on ENaC activity. Thus, inhibition of ENaC by 10 μM amiloride or benzamil neither altered the direction nor its activity. Physiological studies suggested that this Cl- absorptive Isc senses dietary Cl- content; thus when dietary Cl- was low, Cl- absorptive Isc was up-regulated. In contrast, when dietary Cl- was increased, Cl- absorptive Isc was down-regulated. We conclude that an active Cl- extrusion mechanism exists in ENaC-expressing late distal colon and likely operates in parallel with ENaC to facilitate NaCl absorption.

α-ENaC in bullfrog embryo: expression in cement gland, gills and skin.

PubMed

Fujimaki-Aoba, Kayo; Tanaka, Kayoko; Inomata, Reiko; Jensik, Philip J; Takada, Makoto

2014-01-01

The epithelial sodium channel (ENaC) is involved in Na(+) responses such as Na(+) absorption and salt taste. The alpha ENaC subunit (α-ENaC) is expressed in the skin of both the adult and larval (tadpole) bullfrog. α-ENaC expression in the developing bullfrog embryo has not been previously investigated. In this study, the expression of α-ENaC at various stages (Sts.) of bullfrog embryonic development is assessed by western blot and immunofluorescence analysis. Bullfrog α-ENaC (α-fENaC) protein was detected by western blot in embryos at Sts. (Gosner/Shumway) 19, 21 and 25. Immunofluorescence studies indicate that α-fENaC was localized to the embryonic cement glands at St. 18 (muscular response), St. 19 (heart beat) and St. 21 (mouth open and/or cornea transparent), to the external gills at St. 21 and to the outermost cell-layer of the skin at St. 25 (operculum complete). The function(s) of ENaC in these embryonic structures remain to be elucidated.

Analysis of Solar Wind Precipitation on Mars Using MAVEN/SWIA Observations of Spacecraft-Scattered Ions

NASA Astrophysics Data System (ADS)

Lue, C.; Halekas, J. S.

2017-12-01

Particle sensors on the MAVEN spacecraft (SWIA, SWEA, STATIC) observe precipitating solar wind ions during MAVEN's periapsis passes in the Martian atmosphere (at 120-250 km altitude). The signature is observed as positive and negative particles at the solar wind energy, traveling away from the Sun. The observations can be explained by the solar wind penetrating the Martian magnetic barrier in the form of energetic neutral atoms (ENAs) due to charge-exchange with the Martian hydrogen corona, and then being reionized in positive or negative form upon impact with the atmosphere (1). These findings have elucidated solar wind precipitation dynamics at Mars, and can also be used to monitor the solar wind even when MAVEN is at periapsis (2). In the present study, we focus on a SWIA instrument background signal that has been interpreted as spacecraft/instrument-scattered ions (2). We aim to model and subtract the scattered ion signal from the observations including those of reionized solar wind. We also aim to use the scattered ion signal to track hydrogen ENAs impacting the spacecraft above the reionization altitude. We characterize the energy spectrum and directional scattering function for solar wind scattering off the SWIA aperture structure, the radome and the spacecraft body. We find a broad scattered-ion energy spectrum up to the solar wind energy, displaying increased energy loss and reduced flux with increasing scattering angle, allowing correlations with the solar wind direction, energy, and flux. We develop models that can be used to predict the scattered signal based on the direct solar wind observations or to infer the solar wind properties based on the observed scattered signal. We then investigate deviations to the models when the spacecraft is in the Martian atmosphere and evaluate the plausibility of that these are caused by ENAs. We also perform SIMION modeling of the scattering process and the resulting signal detection by SWIA, to study the results from an instrument point-of-view and evaluate the instrument sensitivity to ENAs. 1. Halekas, J. S., et al. (2015), Geophys. Res. Lett., 42, doi:10.1002/2015GL064693 2. Halekas, J. S., et al. (2017), J. Geophys. Res., 122, doi:10.1002/2016JA023167

Derlin-1 promotes ubiquitylation and degradation of the epithelial Na+ channel, ENaC.

PubMed

You, Hui; Ge, Yamei; Zhang, Jian; Cao, Yizhi; Xing, Jing; Su, Dongming; Huang, Yujie; Li, Min; Qu, Shen; Sun, Fei; Liang, Xiubin

2017-03-15

Ubiquitylation of the epithelial Na + channel (ENaC) plays a critical role in cellular functions, including transmembrane transport of Na + , Na + and water balance, and blood pressure stabilization. Published studies have suggested that ENaC subunits are targets of ER-related degradation (ERAD) in yeast systems. However, the molecular mechanism underlying proteasome-mediated degradation of ENaC subunits remains to be established. Derlin-1, an E3 ligase mediator, links recognized target proteins to ubiquitin-mediated proteasomal degradation in the cytosol. In the present study, we found that derlin-1 suppressed the expression of ENaC at the protein level and that the subunit α-ENaC (also known as SCNN1A) physically interacted with derlin-1 at the membrane-anchored domains or the loop regions, and that derlin-1 initiated α-ENaC retrotranslocation. In addition, HUWE1, an endoplasmic reticulum (ER)-resident E3 ubiquitin ligase, was recruited and promoted K11-linked polyubiquitylation of α-ENaC and, hence, formation of an α-ENaC ubiquitin-mediated degradation complex. These findings suggest that derlin-1 promotes ENaC ubiquitylation and enhances ENaC ubiquitin- mediated proteasome degradation. The derlin-1 pathway therefore may represent a significant early checkpoint in the recognition and degradation of ENaC in mammalian cells. © 2017. Published by The Company of Biologists Ltd.

Synthesis of 2',4'-propylene-bridged (carba-ENA) thymidine and its analogues: the engineering of electrostatic and steric effects at the bottom of the minor groove for nuclease and thermodynamic stabilities and elicitation of RNase H.

PubMed

Liu, Yi; Xu, Jianfeng; Karimiahmadabadi, Mansoureh; Zhou, Chuanzheng; Chattopadhyaya, Jyoti

2010-11-05

2',4'-Propylene-bridged thymidine (carba-ENA-T) and five 8'-Me/NH(2)/OH modified carba-ENA-T analogues have been prepared through intramolecular radical addition to C═N of the tethered oxime-ether. These carba-ENA nucleosides have been subsequently incorporated into 15mer oligodeoxynucleotides (AON), and their affinity toward cDNA and RNA, nuclease resistance, and RNase H recruitment capability have been investigated in comparison with those of the native and ENA counterparts. These carba-ENAs modified AONs are highly RNA-selective since all of them led to slight thermal stabilization effect for the AON:RNA duplex, but quite large destabilization effect for the AON:DNA duplex. It was found that different C8' substituents (at the bottom of the minor groove) on carba-ENA-T only led to rather small variation of thermal stability of the AON:RNA duplexes. We, however, observed that the parent carba-ENA-T modified AONs exhibited higher nucleolytic stability than those of the ENA-T modified counterparts. The nucleolytic stability of carba-ENA-T modified AONs can be further modulated by C8' substituent to variable extents depending on not only the chemical nature but also the stereochemical orientation of the C8' substituents: Thus, (1) 8'S-Me on carba-ENA increases the nucleolytic stability but 8'R-Me leads to a decreased effect; (2) 8'R-OH on carba-ENA had little, if any, effect on nuclease resistance but 8'S-OH resulted in significantly decreased nucleolytic stability; and (3) 8'-NH(2) substituted carba-ENA leads to obvious loss in the nuclease resistance. The RNA strand in all of the carba-ENA derivatives modified AON:RNA hybrid duplexes can be digested by RNase H1 with high efficiency, even at twice the rate of those of the native and ENA modified counterpart.

Aerosol and Cloud Experiments in Eastern North Atlantic (ACE-ENA) Science Plan

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

Wang, Jian; Dong, Xiquan; Wood, Robert

With their extensive coverage, low clouds greatly impact global climate. Presently, low clouds are poorly represented in global climate models (GCMs), and the response of low clouds to changes in atmospheric greenhouse gases and aerosols remains the major source of uncertainty in climate simulations. The poor representations of low clouds in GCMs are in part due to inadequate observations of their microphysical and macrophysical structures, radiative effects, and the associated aerosol distribution and budget in regions where the aerosol impact is the greatest. The Eastern North Atlantic (ENA) is a region of persistent but diverse subtropical marine boundary-layer (MBL) clouds,more » whose albedo and precipitation are highly susceptible to perturbations in aerosol properties. Boundary-layer aerosol in the ENA region is influenced by a variety of sources, leading to strong variations in cloud condensation nuclei (CCN) concentration and aerosol optical properties. Recently a permanent ENA site was established by the U.S. Department of Energy (DOE)’s Atmospheric Radiation Measurement (ARM) Climate Research Facility on Graciosa Island in the Azores, providing invaluable information on MBL aerosol and low clouds. At the same time, the vertical structures and horizontal variabilities of aerosol, trace gases, cloud, drizzle, and atmospheric thermodynamics are critically needed for understanding and quantifying the budget of MBL aerosol, the radiative properties, precipitation efficiency, and lifecycle of MBL clouds, and the cloud response to aerosol perturbations. Much of this data can be obtained only through aircraft-based measurements. In addition, the interconnected aerosol and cloud processes are best investigated by a study involving simultaneous in situ aerosol, cloud, and thermodynamics measurements. Furthermore, in situ measurements are also necessary for validating and improving ground-based retrieval algorithms at the ENA site. This project is motivated by the need for comprehensive in situ characterizations of boundary-layer structure, and associated vertical distributions and horizontal variabilities of low clouds and aerosol over the Azores. ARM Aerial Facility (AAF) Gulfstream-1 (G-1) aircraft will be deployed at the ENA site during two intensive operational periods (IOPs) of early summer (June to July) of 2017 and winter (January to February) of 2018, respectively. Deployments during both seasons allow for examination of key aerosol and cloud processes under a variety of representative meteorological and cloud conditions. The science themes for the deployments include: 1) Budget of MBL CCN and its seasonal variation; 2) Effects of aerosol on cloud and precipitation; 3) Cloud microphysical and macrophysical structures, and entrainment mixing; 4) Advancing retrievals of turbulence, cloud, and drizzle; and 5) Model evaluation and processes studies. A key advantage of the deployments is the strong synergy between the measurements onboard the G-1 and the routine measurements at the ENA site, including state-of-the-art profiling and scanning radars. The 3D cloud structures provided by the scanning radars will put the detailed in situ measurements into mesoscale and cloud lifecycle contexts. On the other hand, high quality in situ measurements will enable validation and improvements of ground-based retrieval algorithms at the ENA site, leading to high-quality and statistically robust data sets from the routine measurements. The deployments, combined with the routine measurements at the ENA site, will have a long lasting impact on the research and modeling of low clouds and aerosols in the remote marine environment.« less

Global Images of Trapped Ring Current Ions During Main Phase of 17 March 2015 Geomagnetic Storm as Observed by TWINS

NASA Technical Reports Server (NTRS)

Perez, J. D.; Goldstein, J.; McComas, D. J.; Valek, P.; Fok, Mei-Ching; Hwang, Kyoung-Joo

2016-01-01

A unique view of the trapped particles in the inner magnetosphere provided by energetic neutral atom (ENA) imaging is used to observe the dynamics of the spatial structure and the pitch angle anisotropy on a global scale during the last 6 h of the main phase of a large geomagnetic storm (minimum SYM-H 230 nT) that began on 17 March 2015. Ion flux and pressure anisotropy obtained from Two Wide-angle Imaging Neutral-atom Spectrometers (TWINS) ENA images are shown. The ion flux shows two peaks, an inner one at approximately radii 34 RE in the dusk-to-midnight sector and an outer peak at radii 89 RE prior to midnight. The inner peak is relatively stationary during the entire period with some intensification during the final steep decline in SYM-H to its minimum. The outer peak shows the significant temporal variation brightening and dimming and finally disappearing at the end of the main phase. The pressure anisotropy shows the expected perpendicular pitch angles inside of L 6 but shows parallel pitch angles at greater L values. This is interpreted as consistent with pitch angle-dependent drift as modeled in the Tsy05 magnetic field and Comprehensive Inner Magnetosphere-Ionosphere simulations. The TWINS results are compared directly with Radiation Belt Storm Probes Ion Composition Experiment (RBSPICE)-A measurements. Using 15 min snapshots of flux and pressure anisotropy from TWINS along the path of RBSPICE-A during the 6 h focused upon in this study, the essential features displayed in the TWINS global images are supported.

Modulation of epithelial sodium channel trafficking and function by sodium 4-phenylbutyrate in human nasal epithelial cells.

PubMed

Prulière-Escabasse, Virginie; Planès, Carole; Escudier, Estelle; Fanen, Pascale; Coste, André; Clerici, Christine

2007-11-23

Sodium 4-phenylbutyrate (4-PBA) has been shown to correct the cellular trafficking of several mutant or nonmutant plasma membrane proteins such as cystic fibrosis transmembrane conductance regulator through the expression of 70-kDa heat shock proteins. The objective of the study was to determine whether 4-PBA may influence the functional expression of epithelial sodium channels (ENaC) in human nasal epithelial cells (HNEC). Using primary cultures of HNEC, we demonstrate that 4-PBA (5 mm for 6 h) markedly stimulated amiloride-sensitive sodium channel activity and that this was related to an increased abundance of alpha-, beta-, and gamma-ENaC subunits in the apical membrane. The increase in ENaC cell surface expression (i) was due to insertion of newly ENaC subunits as determined by brefeldin A experiments and (ii) was not associated with cell surface retention of ENaC subunits because endocytosis of ENaC subunits was unchanged. In addition, we find that ENaC co-immunoprecipitated with the heat shock protein constitutively expressed Hsc70, that has been reported to modulate ENaC trafficking, and that 4-PBA decreased Hsc70 protein level. Finally, we report that in cystic fibrosis HNEC obtained from two cystic fibrosis patients, 4-PBA increased functional expression of ENaC as demonstrated by the increase in amiloride-sensitive sodium transport and in alpha-, beta-, and gamma-ENaC subunit expression in the apical membrane. Our results suggest that in HNEC, 4-PBA increases the functional expression of ENaC through the insertion of new alpha-, beta-, and gamma-ENaC subunits into the apical membrane and also suggest that 4-PBA could modify ENaC trafficking by reducing Hsc70 protein expression.

Complex Evolutionary Dynamics of Massively Expanded Chemosensory Receptor Families in an Extreme Generalist Chelicerate Herbivore.

PubMed

Ngoc, Phuong Cao Thi; Greenhalgh, Robert; Dermauw, Wannes; Rombauts, Stephane; Bajda, Sabina; Zhurov, Vladimir; Grbić, Miodrag; Van de Peer, Yves; Van Leeuwen, Thomas; Rouzé, Pierre; Clark, Richard M

2016-12-14

While mechanisms to detoxify plant produced, anti-herbivore compounds have been associated with plant host use by herbivores, less is known about the role of chemosensory perception in their life histories. This is especially true for generalists, including chelicerate herbivores that evolved herbivory independently from the more studied insect lineages. To shed light on chemosensory perception in a generalist herbivore, we characterized the chemosensory receptors (CRs) of the chelicerate two-spotted spider mite, Tetranychus urticae, an extreme generalist. Strikingly, T. urticae has more CRs than reported in any other arthropod to date. Including pseudogenes, 689 gustatory receptors were identified, as were 136 degenerin/Epithelial Na+ Channels (ENaCs) that have also been implicated as CRs in insects. The genomic distribution of T. urticae gustatory receptors indicates recurring bursts of lineage-specific proliferations, with the extent of receptor clusters reminiscent of those observed in the CR-rich genomes of vertebrates or C. elegans Although pseudogenization of many gustatory receptors within clusters suggests relaxed selection, a subset of receptors is expressed. Consistent with functions as CRs, the genomic distribution and expression of ENaCs in lineage-specific T. urticae expansions mirrors that observed for gustatory receptors. The expansion of ENaCs in T. urticae to > 3-fold that reported in other animals was unexpected, raising the possibility that ENaCs in T. urticae have been co-opted to fulfill a major role performed by unrelated CRs in other animals. More broadly, our findings suggest an elaborate role for chemosensory perception in generalist herbivores that are of key ecological and agricultural importance. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Helium Energetic Neutral Atoms from the Heliosphere: Perspectives for Future Observations

NASA Astrophysics Data System (ADS)

Swaczyna, Paweł; Grzedzielski, Stan; Bzowski, Maciej

2017-05-01

Observations of energetic neutral atoms (ENAs) allow for remote sensing of plasma properties in distant regions of the heliosphere. So far, most of the observations have concerned only hydrogen atoms. In this paper, we present perspectives for observations of helium energetic neutral atoms (He ENAs). We calculated the expected intensities of He ENAs created by the neutralization of helium ions in the inner heliosheath and through the secondary ENA mechanism in the outer heliosheath. We found that the dominant source region for He ENAs is the inner heliosheath. The obtained magnitudes of intensity spectra suggest that He ENAs can be observed with future ENA detectors, as those planned on Interstellar Mapping and Acceleration Probe. Observing He ENAs is most likely for energies from a few to a few tens of keV/nuc. Estimates of the expected count rates show that the ratio of helium to hydrogen atoms registered in the detectors can be as low as 1:104. Consequently, the detectors need to be equipped with an appropriate mass spectrometer capability, allowing for recognition of chemical elements. Due to the long mean free paths of helium ions in the inner heliosheath, He ENAs are produced also in the distant heliospheric tail. This implies that observations of He ENAs can resolve its structure, which seems challenging from observations of hydrogen ENAs since energetic protons are neutralized before they progress deeper in the heliospheric tail.

Auroral, Polar Cap, and Polar Cusp Modeling and Data Analysis for the IMAGE Mission and LENA Instrument

NASA Technical Reports Server (NTRS)

Wilson, Gordon R.

2001-01-01

One of the chief mysteries in the LENA perigee pass data is the lack of an apparent auroral oval in the images. Another is that in some cases ENA are seen from any direction near the Earth regardless of the latitude of the spacecraft. These facts lead one to ask a fundamental question: Is the instrument responding to ENA primarily? One possible way to get out of the "ambiguity" of the data is to assume that at least part of the signal is produced by something other than ENA. The two main candidates for this "something else" are UV light and energetic charged particles. UV light could only effect the instrument when its fan shaped aperture points toward the source. The most intense of which will be the sun, with day glow being the second strongest and the auroral zone, the third. We can rule out UV light as a prime source of counts in the perigee pass data for the following reasons: 1) The perigee pass signal is different in form and much stronger than the sun pulse signal seen just before or just after perigee; 2) There is no indication of the auroral zone, which would produce at least two peaks in the counts versus spin phase curve; 3) Mike Colliers' analysis of the sun pulse signal shows that it varies with the flux of the solar wind and not with variations in the solar UV flux. Charge particles that enter the aperture of the instrument and produce counts would show up when the instrument looks in the direction from which they come. In all of the data I am analyzing voltages were being applied to the collimators so that most charged particles should have been excluded from the instrument but this effect could still show up where the flux of energetic particles is high enough. The most likely place would be in the auroral zone where energetic electrons and protons precipitate. If these particles are producing counts then they should be seen when the instrument looks in and near the zenith direction. In nearly all of the perigee passes the zenith direction is devoid of counts.

Helium Energetic Neutral Atoms from the Heliosphere: Perspectives for Future Observations

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

Swaczyna, Paweł; Grzedzielski, Stan; Bzowski, Maciej, E-mail: pswaczyna@cbk.waw.pl

2017-05-10

Observations of energetic neutral atoms (ENAs) allow for remote sensing of plasma properties in distant regions of the heliosphere. So far, most of the observations have concerned only hydrogen atoms. In this paper, we present perspectives for observations of helium energetic neutral atoms (He ENAs). We calculated the expected intensities of He ENAs created by the neutralization of helium ions in the inner heliosheath and through the secondary ENA mechanism in the outer heliosheath. We found that the dominant source region for He ENAs is the inner heliosheath. The obtained magnitudes of intensity spectra suggest that He ENAs can bemore » observed with future ENA detectors, as those planned on Interstellar Mapping and Acceleration Probe . Observing He ENAs is most likely for energies from a few to a few tens of keV/nuc. Estimates of the expected count rates show that the ratio of helium to hydrogen atoms registered in the detectors can be as low as 1:10{sup 4}. Consequently, the detectors need to be equipped with an appropriate mass spectrometer capability, allowing for recognition of chemical elements. Due to the long mean free paths of helium ions in the inner heliosheath, He ENAs are produced also in the distant heliospheric tail. This implies that observations of He ENAs can resolve its structure, which seems challenging from observations of hydrogen ENAs since energetic protons are neutralized before they progress deeper in the heliospheric tail.« less

Calmodulin and CaMKII modulate ENaC activity by regulating the association of MARCKS and the cytoskeleton with the apical membrane.

PubMed

Alli, Abdel A; Bao, Hui-Fang; Liu, Bing-Chen; Yu, Ling; Aldrugh, Summer; Montgomery, Darrice S; Ma, He-Ping; Eaton, Douglas C

2015-09-01

Phosphatidylinositol bisphosphate (PIP2) regulates epithelial sodium channel (ENaC) open probability. In turn, myristoylated alanine-rich C kinase substrate (MARCKS) protein or MARCKS-like protein 1 (MLP-1) at the plasma membrane regulates the delivery of PIP2 to ENaC. MARCKS and MLP-1 are regulated by changes in cytosolic calcium; increasing calcium promotes dissociation of MARCKS from the membrane, but the calcium-regulatory mechanisms are unclear. However, it is known that increased intracellular calcium can activate calmodulin and we show that inhibition of calmodulin with calmidazolium increases ENaC activity presumably by regulating MARCKS and MLP-1. Activated calmodulin can regulate MARCKS and MLP-1 in two ways. Calmodulin can bind to the effector domain of MARCKS or MLP-1, inactivating both proteins by causing their dissociation from the membrane. Mutations in MARCKS that prevent calmodulin association prevent dissociation of MARCKS from the membrane. Calmodulin also activates CaM kinase II (CaMKII). An inhibitor of CaMKII (KN93) increases ENaC activity, MARCKS association with ENaC, and promotes MARCKS movement to a membrane fraction. CaMKII phosphorylates filamin. Filamin is an essential component of the cytoskeleton and promotes association of ENaC, MARCKS, and MLP-1. Disruption of the cytoskeleton with cytochalasin E reduces ENaC activity. CaMKII phosphorylation of filamin disrupts the cytoskeleton and the association of MARCKS, MLP-1, and ENaC, thereby reducing ENaC open probability. Taken together, these findings suggest calmodulin and CaMKII modulate ENaC activity by destabilizing the association between the actin cytoskeleton, ENaC, and MARCKS, or MLP-1 at the apical membrane. Copyright © 2015 the American Physiological Society.

The effect of new interstellar medium parameters on the heliosphere and energetic neutral atoms from the interstellar boundary

DOE PAGES

Heerikhuisen, J.; Zirnstein, E. J.; Funsten, H. O.; ...

2014-03-05

Here we present new results from three-dimensional simulations of the solar wind interaction with the local interstellar medium (LISM) using recent observations by NASA's Interstellar Boundary EXplorer (IBEX) mission estimates of the velocity and temperature of the LISM. We investigate four strengths of the LISM magnetic field, from 1 to 4 μG, and adjust the LISM proton and hydrogen densities so that the distance to the termination shock (TS) in the directions of the Voyager spacecraft is just below 90 AU, and the density of hydrogen at the TS is close to 0.09 cm-3 in the nose direction. The orientationmore » of the magnetic field is chosen to point toward the center of the ribbon of enhanced energetic neutral atom (ENA) flux seen in the IBEX data. Our simulations show that the plasma and neutral properties in the outer heliosheath vary considerably as a function of the LISM magnetic field strength. We also show that the heliotail points downwind in all cases, though its structure is strongly affected by the external magnetic field. Lastly, comparison and consistency between the simulated ENA flux and the circularity of the ribbon as measured by IBEX are most consistent with a LISM magnetic field strength aligned with the center of the ribbon and a magnitude in the range 2.5-3 μG.« less

Endothelial epithelial sodium channel inhibition activates endothelial nitric oxide synthase via phosphoinositide 3-kinase/Akt in small-diameter mesenteric arteries.

PubMed

Pérez, Francisco R; Venegas, Fabiola; González, Magdalena; Andrés, Sergio; Vallejos, Catalina; Riquelme, Gloria; Sierralta, Jimena; Michea, Luis

2009-06-01

Recent studies have shown that the epithelial sodium channel (ENaC) is expressed in vascular tissue. However, the role that ENaC may play in the responses to vasoconstrictors and NO production has yet to be addressed. In this study, the contractile responses of perfused pressurized small-diameter rat mesenteric arteries to phenylephrine and serotonin were reduced by ENaC blockade with amiloride (75.1+/-3.2% and 16.9+/-2.3% of control values, respectively; P<0.01) that was dose dependent (EC(50)=88.9+/-1.6 nmol/L). Incubation with benzamil, another ENaC blocker, had similar effects. alpha, beta, and gamma ENaC were identified in small-diameter rat mesenteric arteries using RT-PCR and Western blot with specific antibodies. In situ hybridization and immunohistochemistry localized ENaC expression to the tunica media and endothelium of small-diameter rat mesenteric arteries. Patch-clamp experiments demonstrated that primary cultures of mesenteric artery endothelial cells expressed amiloride-sensitive sodium currents. Mechanical ablation of the endothelium or inhibition of eNOS with N(omega)-nitro-L-arginine inhibited the reduction in contractility caused by ENaC blockers. ENaC inhibitors increased eNOS phosphorylation (Ser 1177) and Akt phosphorylation (Ser 473). The presence of the phosphoinositide 3-kinase inhibitor LY294002 blunted Akt phosphorylation and eNOS phosphorylation and the decrease in the response to phenylephrine caused by blockers of ENaC, indicating that the phosphoinositide 3-kinase/Akt pathway was activated after ENaC inhibition. Finally, we observed that the effects of blockers of ENaC were flow dependent and that the vasodilatory response to shear stress was enhanced by ENaC blockade. Our results identify a previously unappreciated role for ENaC as a negative modulator of eNOS and NO production in resistance arteries.

Two cation transporters Ena1 and Nha1 cooperatively modulate ion homeostasis, antifungal drug resistance, and virulence of Cryptococcus neoformans via the HOG pathway

PubMed Central

Jung, Kwang-Woo; Strain, Anna K; Nielsen, Kirsten; Jung, Kwang-Hwan; Bahn, Yong-Sun

2012-01-01

Maintenance of cation homeostasis is essential for survival of all living organisms in their biological niches. It is also important for the survival of human pathogenic fungi in the host, where cation concentrations and pH will vary depending on different anatomical sites. However, the exact role of diverse cation transporters and ion channels in virulence of fungal pathogens remains elusive. In this study we functionally characterized ENA1 and NHA1, encoding a putative Na+/ATPase and Na+/H+ antiporter, respectively, in Cryptococcus neoformans, a basidiomycete fungal pathogen which causes fatal meningoencephalitis. Expression of NHA1 and ENA1 is induced in response to salt and osmotic shock mainly in a Hog1-dependent manner. Phenotypic analysis of the ena1, nha1, and ena1 nha1 mutants revealed that Ena1 controls cellular levels of toxic cations, such as Na+ and Li+ whereas both Ena1 and Nha1 are important for controlling less toxic K+ ions. Under alkaline conditions, Ena1 was highly induced and required for growth in the presence of low levels of Na+ or K+ salt and Nha1 played a role in survival under K+ stress. In contrast, Nha1, but not Ena1, was essential for survival at acidic conditions (pH 4.5) under high K+ stress. In addition, Ena1 and Nha1 were required for maintenance of plasma membrane potential and stability, which appeared to modulate antifungal drug susceptibility. Perturbation of ENA1 and NHA1 enhanced capsule production and melanin synthesis. However, Nha1 was dispensable for virulence of C. neoformans although Ena1 was essential. In conclusion, Ena1 and Nha1 play redundant and discrete roles in cation homeostasis, pH regulation, membrane potential, and virulence in C. neoformans, suggesting that these transporters could be novel antifungal drug targets for treatment of cryptococcosis. PMID:22343280

The carboxyl terminus of the alpha-subunit of the amiloride-sensitive epithelial sodium channel binds to F-actin.

PubMed

Mazzochi, Christopher; Bubien, James K; Smith, Peter R; Benos, Dale J

2006-03-10

The activity of the amiloride-sensitive epithelial sodium channel (ENaC) is modulated by F-actin. However, it is unknown if there is a direct interaction between alpha-ENaC and actin. We have investigated the hypothesis that the actin cytoskeleton directly binds to the carboxyl terminus of alpha-ENaC using a combination of confocal microscopy, co-immunoprecipitation, and protein binding studies. Confocal microscopy of Madin-Darby canine kidney cell monolayers stably transfected with wild type, rat isoforms of alpha-, beta-, and gamma-ENaC revealed co-localization of alpha-ENaC with the cortical F-actin cytoskeleton both at the apical membrane and within the subapical cytoplasm. F-actin was found to co-immunoprecipitate with alpha-ENaC from whole cell lysates of this cell line. Gel overlay assays demonstrated that F-actin specifically binds to the carboxyl terminus of alpha-ENaC. A direct interaction between F-actin and the COOH terminus of alpha-ENaC was further corroborated by F-actin co-sedimentation studies. This is the first study to report a direct and specific biochemical interaction between F-actin and ENaC.

Salt restriction induces pseudohypoaldosteronism type 1 in mice expressing low levels of the β-subunit of the amiloride-sensitive epithelial sodium channel

PubMed Central

Pradervand, Sylvain; Barker, Pierre M.; Wang, Qing; Ernst, Stephen A.; Beermann, Friedrich; Grubb, Barbara R.; Burnier, Michel; Schmidt, Andrea; Bindels, Rene J. M.; Gatzy, John T.; Rossier, Bernard C.; Hummler, Edith

1999-01-01

The amiloride-sensitive epithelial sodium channel (ENaC) is a heteromultimer of three homologous subunits (α-, β-, and γ-subunits). To study the role of the β-subunit in vivo, we analyzed mice in which the βENaC gene locus was disrupted. These mice showed low levels of βENaC mRNA expression in kidney (≈1%), lung (≈1%), and colon (≈4%). In homozygous mutant βENaC mice, no βENaC protein could be detected with immunofluorescent staining. At birth, there was a small delay in lung-liquid clearance that paralleled diminished amiloride-sensitive Na+ absorption in tracheal explants. With normal salt intake, these mice showed a normal growth rate. However, in vivo, adult βENaC m/m mice exhibited a significantly reduced ENaC activity in colon and elevated plasma aldosterone levels, suggesting hypovolemia and pseudohypoaldosteronism type 1. This phenotype was clinically silent, as βENaC m/m mice showed no weight loss, normal plasma Na+ and K+ concentrations, normal blood pressure, and a compensated metabolic acidosis. On low-salt diets, βENaC-mutant mice developed clinical symptoms of an acute pseudohypoaldosteronism type 1 (weight loss, hyperkalemia, and decreased blood pressure), indicating that βENaC is required for Na+ conservation during salt deprivation. PMID:9990093

The function and regulation of acid‐sensing ion channels (ASICs) and the epithelial Na+ channel (ENaC): IUPHAR Review 19

PubMed Central

Boscardin, Emilie; Alijevic, Omar; Hummler, Edith

2016-01-01

Acid‐sensing ion channels (ASICs) and the epithelial Na+ channel (ENaC) are both members of the ENaC/degenerin family of amiloride‐sensitive Na+ channels. ASICs act as proton sensors in the nervous system where they contribute, besides other roles, to fear behaviour, learning and pain sensation. ENaC mediates Na+ reabsorption across epithelia of the distal kidney and colon and of the airways. ENaC is a clinically used drug target in the context of hypertension and cystic fibrosis, while ASIC is an interesting potential target. Following a brief introduction, here we will review selected aspects of ASIC and ENaC function. We discuss the origin and nature of pH changes in the brain and the involvement of ASICs in synaptic signalling. We expose how in the peripheral nervous system, ASICs cover together with other ion channels a wide pH range as proton sensors. We introduce the mechanisms of aldosterone‐dependent ENaC regulation and the evidence for an aldosterone‐independent control of ENaC activity, such as regulation by dietary K+. We then provide an overview of the regulation of ENaC by proteases, a topic of increasing interest over the past few years. In spite of the profound differences in the physiological and pathological roles of ASICs and ENaC, these channels share many basic functional and structural properties. It is likely that further research will identify physiological contexts in which ASICs and ENaC have similar or overlapping roles. PMID:27278329

Ethanol stimulates epithelial sodium channels by elevating reactive oxygen species

PubMed Central

Bao, Hui-Fang; Song, John Z.; Duke, Billie J.; Ma, He-Ping; Denson, Donald D.

2012-01-01

Alcohol affects total body sodium balance, but the molecular mechanism of its effect remains unclear. We used single-channel methods to examine how ethanol affects epithelial sodium channels (ENaC) in A6 distal nephron cells. The data showed that ethanol significantly increased both ENaC open probability (Po) and the number of active ENaC in patches (N). 1-Propanol and 1-butanol also increased ENaC activity, but iso-alcohols did not. The effects of ethanol were mimicked by acetaldehyde, the first metabolic product of ethanol, but not by acetone, the metabolic product of 2-propanol. Besides increasing open probability and apparent density of active channels, confocal microscopy and surface biotinylation showed that ethanol significantly increased α-ENaC protein in the apical membrane. The effects of ethanol on ENaC Po and N were abolished by a superoxide scavenger, 4-hydroxy-2,2,6,6-tetramethylpiperidinyloxy (TEMPOL) and blocked by the phosphatidylinositol 3-kinase inhibitor LY294002. Consistent with an effect of ethanol-induced reactive oxygen species (ROS) on ENaC, primary alcohols and acetaldehyde elevated intracellular ROS, but secondary alcohols did not. Taken together with our previous finding that ROS stimulate ENaC, the current results suggest that ethanol stimulates ENaC by elevating intracellular ROS probably via its metabolic product acetaldehyde. PMID:22895258

Exclusion of Na+ via Sodium ATPase (PpENA1) Ensures Normal Growth of Physcomitrella patens under Moderate Salt Stress1

PubMed Central

Lunde, Christina; Drew, Damian P.; Jacobs, Andrew K.; Tester, Mark

2007-01-01

The bryophyte Physcomitrella patens is unlike any other plant identified to date in that it possesses a gene that encodes an ENA-type Na+-ATPase. To complement previous work in yeast (Saccharomyces cerevisiae), we determined the importance of having a Na+-ATPase in planta by conducting physiological analyses of PpENA1 in Physcomitrella. Expression studies showed that PpENA1 is up-regulated by NaCl and, to a lesser degree, by osmotic stress. Maximal induction is obtained after 8 h at 60 mm NaCl or above. No other abiotic stress tested led to significant increases in PpENA1 expression. In the gametophyte, strong expression was confined to the rhizoids, stem, and the basal part of the leaf. In the protonemata, expression was ubiquitous with a few filaments showing stronger expression. At 100 mm NaCl, wild-type plants were able to maintain a higher K+-to-Na+ ratio than the PpENA1 (ena1) knockout gene, but at higher NaCl concentrations no difference was observed. Although no difference in chlorophyll content was observed between ena1 and wild type at 100 mm NaCl, the impaired Na+ exclusion in ena1 plants led to an approximately 40% decrease in growth. PMID:17556514

Renal tubular NEDD4-2 deficiency causes NCC-mediated salt-dependent hypertension.

PubMed

Ronzaud, Caroline; Loffing-Cueni, Dominique; Hausel, Pierrette; Debonneville, Anne; Malsure, Sumedha Ram; Fowler-Jaeger, Nicole; Boase, Natasha A; Perrier, Romain; Maillard, Marc; Yang, Baoli; Stokes, John B; Koesters, Robert; Kumar, Sharad; Hummler, Edith; Loffing, Johannes; Staub, Olivier

2013-02-01

The E3 ubiquitin ligase NEDD4-2 (encoded by the Nedd4L gene) regulates the amiloride-sensitive epithelial Na+ channel (ENaC/SCNN1) to mediate Na+ homeostasis. Mutations in the human β/γENaC subunits that block NEDD4-2 binding or constitutive ablation of exons 6-8 of Nedd4L in mice both result in salt-sensitive hypertension and elevated ENaC activity (Liddle syndrome). To determine the role of renal tubular NEDD4-2 in adult mice, we generated tetracycline-inducible, nephron-specific Nedd4L KO mice. Under standard and high-Na+ diets, conditional KO mice displayed decreased plasma aldosterone but normal Na+/K+ balance. Under a high-Na+ diet, KO mice exhibited hypercalciuria and increased blood pressure, which were reversed by thiazide treatment. Protein expression of βENaC, γENaC, the renal outer medullary K+ channel (ROMK), and total and phosphorylated thiazide-sensitive Na+Cl- cotransporter (NCC) levels were increased in KO kidneys. Unexpectedly, Scnn1a mRNA, which encodes the αENaC subunit, was reduced and proteolytic cleavage of αENaC decreased. Taken together, these results demonstrate that loss of NEDD4-2 in adult renal tubules causes a new form of mild, salt-sensitive hypertension without hyperkalemia that is characterized by upregulation of NCC, elevation of β/γENaC, but not αENaC, and a normal Na+/K+ balance maintained by downregulation of ENaC activity and upregulation of ROMK.

Endothelin-1 Inhibits the Epithelial Na+ Channel through βPix/14-3-3/Nedd4-2

PubMed Central

Pavlov, Tengis S.; Chahdi, Ahmed; Ilatovskaya, Daria V.; Levchenko, Vladislav; Vandewalle, Alain; Pochynyuk, Oleh

2010-01-01

Epithelial Na+ channels (ENaCs) mediate sodium reabsorption in the cortical collecting duct (CCD), but the regulatory pathways that modulate the activity of these channels are incompletely understood. Here, we observed that endothelin-1 (ET-1) attenuates ENaC activity acutely by reducing the channel's open probability and chronically by decreasing the number of channels in the plasma membrane. To investigate whether β1Pix, a signaling protein activated by ET-1, mediates ENaC activity, we reconstituted ENaC in CHO cells with or without coexpressed β1Pix and found that β1Pix negatively regulates ENaC. Knockdown of βPix in native principal cells abolished the ET-1-induced decrease in ENaC channel number. Furthermore, we found that βPix does not decrease ENaC activity through its guanine nucleotide exchange factor (GEF) activity for Rac1 and Cdc42. Instead, coexpression of β1Pix mutant constructs revealed that β1Pix affects ENaC activity through binding 14-3-3 proteins. Coimmunoprecipitation experiments supported a physical interaction between β1Pix and 14-3-3β in cultured principal cells. Coexpression of 14-3-3β increased ENaC activity in CHO cells, but concomitant expression of β1Pix attenuated this increase. Recruitment of 14-3-3β by β1Pix impaired the interaction of 14-3-3β with the ubiquitin ligase Nedd4-2, thereby promoting ubiquitination and degradation of ENaC. Taken together, these results suggest that the inhibitory effects of chronic ET-1 on ENaC result from βPix interacting with the 14-3-3/Nedd4-2 pathway. PMID:20338996

Anti-ENA antibody profiles in patients with hepatitis C virus infection.

PubMed

Litwin, Christine M; Rourk, Angela R

2018-03-01

The presence of antinuclear antibodies (ANA) has been described following hepatitis C virus (HCV). Very few studies have investigated the presence of anti-extractable nuclear antigens (ENA) in HCV infection. The aim of this study was to assess the prevalence of ENA antibodies in 100 patients with HCV infection compared to the prevalence of ENA antibodies in 100 healthy control patients. Sera from patients were tested for ENA using a multiplex microbead immunoassay. Sera positive for ENA were subsequently tested for ANA using an indirect immunofluorescence assay and titered if positive. Fourteen (14%) of the 100 patients with HCV infection had anti-ENA antibodies: four each showed anti-SSA antibodies and anti-dsDNA antibodies, three each had RNP antibodies and Scl-70 antibodies, and one each had anti-SSB, centromere B, Sm, and Sm/RNP antibodies. Ten of the 14 patients positive for anti-ENA were positive by indirect immunofluorescence staining (IFA) with titers ranging from 1:40 to 1:160. Five had antinuclear patterns, one had combined antinuclear and cytoplasmic patterns, and four only had a cytoplasmic pattern. Three of the 100 healthy control patients had ANA positive titers (1:80 and 1:320) and anti-ENA antibodies: one anti-Scl-70 and two anti-RNP. The prevalence of anti-ENA antibodies was significantly higher in the patients with HCV infections than in the healthy controls. Other studies of anti-ENA profiles in patients with HCV infection have identified similar patterns of positivity for anti-SSA, anti-SSB, anti-dsDNA, anti-RNP, anti- Sm/RNP, Scl-70, centromere B, and anti-Sm. © 2017 Wiley Periodicals, Inc.

Effect of dietary salt intake on epithelial Na+ channels (ENaC) in vasopressin magnocellular neurosecretory neurons in the rat supraoptic nucleus.

PubMed

Sharma, Kaustubh; Haque, Masudul; Guidry, Richard; Ueta, Yoichi; Teruyama, Ryoichi

2017-09-01

A growing body of evidence suggests that epithelial Na + channels (ENaCs) in the brain play a significant role in the regulation of blood pressure; however, the brain structures that mediate the effect are not well understood. Because vasopressin (VP) neurons play a pivotal role in coordinating neuroendocrine and autonomic responses to maintain cardiovascular homeostasis, a basic understanding of the regulation and activity of ENaC in VP neurons is of great interest. We show that high dietary salt intake caused an increase in the expression and activity of ENaC which resulted in the steady state depolarization of VP neurons. The results help us understand one of the mechanisms underlying how dietary salt intake affects the activity of VP neurons via ENaC activity. All three epithelial Na + channel (ENaC) subunits (α, β and γ) are located in vasopressin (VP) magnocellular neurons in the hypothalamic supraoptic (SON) and paraventricular nuclei. Our previous study demonstrated that ENaC mediates a Na + leak current that affects the steady state membrane potential in VP neurons. In the present study, we evaluated the effect of dietary salt intake on ENaC regulation and activity in VP neurons. High dietary salt intake for 7 days caused an increase in expression of β- and γENaC subunits in the SON and the translocation of αENaC immunoreactivity towards the plasma membrane. Patch clamp experiments on hypothalamic slices showed that the mean amplitude of the putative ENaC currents was significantly greater in VP neurons from animals that were fed a high salt diet compared with controls. The enhanced ENaC current contributed to the more depolarized basal membrane potential observed in VP neurons in the high salt diet group. These findings indicate that high dietary NaCl intake enhances the expression and activity of ENaCs, which augments synaptic drive by depolarizing the basal membrane potential close to the action potential threshold during hormonal demand. However, ENaCs appear to have only a minor role in the regulation of the firing activity of VP neurons in the absence of synaptic inputs as neither the mean intraburst frequency, burst duration, nor interspike interval variability of phasic bursting activity was affected. Moreover, ENaC activity did not affect the initiation, sustention, or termination of the phasic bursting generated in an intrinsic manner without synaptic inputs. © 2017 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.

Point mutations in the post-M2 region of human alpha-ENaC regulate cation selectivity.

PubMed

Ji, H L; Parker, S; Langloh, A L; Fuller, C M; Benos, D J

2001-07-01

We tested the hypothesis that an arginine-rich region immediately following the second transmembrane domain may constitute part of the inner mouth of the epithelial Na+ channel (ENaC) pore and, hence, influence conduction and/or selectivity properties of the channel by expressing double point mutants in Xenopus oocytes. Double point mutations of arginines in this post-M2 region of the human alpha-ENaC (alpha-hENaC) led to a decrease and increase in the macroscopic conductance of alphaR586E,R587Ebetagamma- and alphaR589E,R591Ebetagamma-hENaC, respectively, but had no effect on the single-channel conductance of either double point mutant. However, the apparent equilibrium dissociation constant for Na+ was decreased for both alphaR586E,R587Ebetagamma- and alphaR589E,R591Ebetagamma-hENaC, and the maximum amiloride-sensitive Na+ current was decreased for alphaR586E,R587Ebetagamma-hENaC and increased for alphaR589E,R591Ebetagamma-hENaC. The relative permeabilities of Li+ and K+ vs. Na+ were increased 11.25- to 27.57-fold for alphaR586E,R587Ebetagamma-hENaC compared with wild type. The relative ion permeability of these double mutants and wild-type ENaC was inversely related to the crystal diameter of the permeant ions. Thus the region of positive charge is important for the ion permeation properties of the channel and may form part of the pore itself.

Identification of Extracellular Domain Residues Required for Epithelial Na+ Channel Activation by Acidic pH

PubMed Central

Collier, Daniel M.; Peterson, Zerubbabel J.; Blokhin, Ilya O.; Benson, Christopher J.; Snyder, Peter M.

2012-01-01

A growing body of evidence suggests that the extracellular domain of the epithelial Na+ channel (ENaC) functions as a sensor that fine tunes channel activity in response to changes in the extracellular environment. We previously found that acidic pH increases the activity of human ENaC, which results from a decrease in Na+ self-inhibition. In the current work, we identified extracellular domain residues responsible for this regulation. We found that rat ENaC is less sensitive to pH than human ENaC, an effect mediated in part by the γ subunit. We identified a group of seven residues in the extracellular domain of γENaC (Asp-164, Gln-165, Asp-166, Glu-292, Asp-335, His-439, and Glu-455) that, when individually mutated to Ala, decreased proton activation of ENaC. γE455 is conserved in βENaC (Glu-446); mutation of this residue to neutral amino acids (Ala, Cys) reduced ENaC stimulation by acidic pH, whereas reintroduction of a negative charge (by MTSES modification of Cys) restored pH regulation. Combination of the seven γENaC mutations with βE446A generated a channel that was not activated by acidic pH, but inhibition by alkaline pH was intact. Moreover, these mutations reduced the effect of pH on Na+ self-inhibition. Together, the data identify eight extracellular domain residues in human β- and γENaC that are required for regulation by acidic pH. PMID:23060445

Plasma Potassium Determines NCC Abundance in Adult Kidney-Specific γENaC Knockout.

PubMed

Boscardin, Emilie; Perrier, Romain; Sergi, Chloé; Maillard, Marc P; Loffing, Johannes; Loffing-Cueni, Dominique; Koesters, Robert; Rossier, Bernard C; Hummler, Edith

2018-03-01

The amiloride-sensitive epithelial sodium channel (ENaC) and the thiazide-sensitive sodium chloride cotransporter (NCC) are key regulators of sodium and potassium and colocalize in the late distal convoluted tubule of the kidney. Loss of the α ENaC subunit leads to a perinatal lethal phenotype characterized by sodium loss and hyperkalemia resembling the human syndrome pseudohypoaldosteronism type 1 (PHA-I). In adulthood, inducible nephron-specific deletion of α ENaC in mice mimics the lethal phenotype observed in neonates, and as in humans, this phenotype is prevented by a high sodium (HNa + )/low potassium (LK + ) rescue diet. Rescue reflects activation of NCC, which is suppressed at baseline by elevated plasma potassium concentration. In this study, we investigated the role of the γ ENaC subunit in the PHA-I phenotype. Nephron-specific γ ENaC knockout mice also presented with salt-wasting syndrome and severe hyperkalemia. Unlike mice lacking α ENaC or β ΕΝaC, an HNa + /LK + diet did not normalize plasma potassium (K + ) concentration or increase NCC activation. However, when K + was eliminated from the diet at the time that γ ENaC was deleted, plasma K + concentration and NCC activity remained normal, and progressive weight loss was prevented. Loss of the late distal convoluted tubule, as well as overall reduced β ENaC subunit expression, may be responsible for the more severe hyperkalemia. We conclude that plasma K + concentration becomes the determining and limiting factor in regulating NCC activity, regardless of Na + balance in γ ENaC-deficient mice. Copyright © 2018 by the American Society of Nephrology.

ENaC activity in collecting ducts modulates NCC in cirrhotic mice.

PubMed

Mordasini, David; Loffing-Cueni, Dominique; Loffing, Johannes; Beatrice, Rohrbach; Maillard, Marc P; Hummler, Edith; Burnier, Michel; Escher, Geneviève; Vogt, Bruno

2015-12-01

Cirrhosis is a frequent and severe disease, complicated by renal sodium retention leading to ascites and oedema. A better understanding of the complex mechanisms responsible for renal sodium handling could improve clinical management of sodium retention. Our aim was to determine the importance of the amiloride-sensitive epithelial sodium channel (ENaC) in collecting ducts in compensate and decompensate cirrhosis. Bile duct ligation was performed in control mice (CTL) and collecting duct-specific αENaC knockout (KO) mice, and ascites development, aldosterone plasma concentration, urinary sodium/potassium ratio and sodium transporter expression were compared. Disruption of ENaC in collecting ducts (CDs) did not alter ascites development, urinary sodium/potassium ratio, plasma aldosterone concentrations or Na,K-ATPase abundance in CCDs. Total αENaC abundance in whole kidney increased in cirrhotic mice of both genotypes and cleaved forms of α and γ ENaC increased only in ascitic mice of both genotypes. The sodium chloride cotransporter (NCC) abundance was lower in non-ascitic KO, compared to non-ascitic CTL, and increased when ascites appeared. In ascitic mice, the lack of αENaC in CDs induced an upregulation of total ENaC and NCC and correlated with the cleavage of ENaC subunits. This revealed compensatory mechanisms which could also take place when treating the patients with diuretics. These compensatory mechanisms should be considered for future development of therapeutic strategies.

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

Jeggle, Pia; Smith, Ewan St. J.; Stewart, Andrew P.

ASIC and ENaC are co-expressed in various cell types, and there is evidence for a close association between them. Here, we used atomic force microscopy (AFM) to determine whether ASIC1a and ENaC subunits are able to form cross-clade hybrid ion channels. ASIC1a and ENaC could be co-isolated from detergent extracts of tsA 201 cells co-expressing the two subunits. Isolated proteins were incubated with antibodies against ENaC and Fab fragments against ASIC1a. AFM imaging revealed proteins that were decorated by both an antibody and a Fab fragment with an angle of ∼120° between them, indicating the formation of ASIC1a/ENaC heterotrimers. -more » Highlights: • There is evidence for a close association between ASIC and ENaC. • We used AFM to test whether ASIC1a and ENaC subunits form cross-clade ion channels. • Isolated proteins were incubated with subunit-specific antibodies and Fab fragments. • Some proteins were doubly decorated at ∼120° by an antibody and a Fab fragment. • Our results indicate the formation of ASIC1a/ENaC heterotrimers.« less

Growth, Yield and Grain Nutritional Quality in Three Brazilian Pearl Millets (Pennisetum americanum L.) with African or Indian origins.

PubMed

Medici, Leonardo O; Gonçalves, Fabíola V; Fonseca, Marcos Paulo S DA; Gaziola, Salete A; Schmidt, Daiana; Azevedo, Ricardo A; Pimentel, Carlos

2018-05-14

In this study, we are presenting recommendations to the best agricultural use as well as for plant breeding of three millet cultivars namely ENA1 and ENA2, which have African origin, and BRS1501 originally from India. These cultivars were evaluated for growth, yield and grain quality traits. The morphological traits evaluated in this study indicated that the African genotypes ENA1 and ENA2 are better than the Indian genotype BRS1501 for no-till farming or to produce forage with 15% of crude protein at flowering and at harvest to produce stover (around 7% of crude protein content) for livestock feeding. The BRS1501 cultivar exhibited the highest values for total crude protein, albumins and prolamins, phytate and mineral contents in grains. ENA1 and ENA2 exhibited the highest values of globulin and glutelin contents. The electrophoretic patterns for storage proteins were similar across the three millets cultivars, except for a higher intensity of two glutelin bands with 21 and 24 kDa in BRS1501. Together, the results allow us to recommend BRS1501 for grain production and ENA1 and ENA2 for biomass production.

Controlling epithelial sodium channels with light using photoswitchable amilorides

NASA Astrophysics Data System (ADS)

Schönberger, Matthias; Althaus, Mike; Fronius, Martin; Clauss, Wolfgang; Trauner, Dirk

2014-08-01

Amiloride is a widely used diuretic that blocks epithelial sodium channels (ENaCs). These heterotrimeric transmembrane proteins, assembled from β, γ and α or δ subunits, effectively control water transport across epithelia and sodium influx into non-epithelial cells. The functional role of δβγENaC in various organs, including the human brain, is still poorly understood and no pharmacological tools are available for the functional differentiation between α- and δ-containing ENaCs. Here we report several photoswitchable versions of amiloride. One compound, termed PA1, enables the optical control of ENaC channels, in particular the δβγ isoform, by switching between blue and green light, or by turning on and off blue light. PA1 was used to modify functionally δβγENaC in amphibian and mammalian cells. We also show that PA1 can be used to differentiate between δβγENaC and αβγENaC in a model for the human lung epithelium.

Field Aligned Currents Derived from Pressure Profiles Obtained from TWINS ENA Images

NASA Astrophysics Data System (ADS)

Wood, K.; Perez, J. D.; McComas, D. J.; Goldstein, J.; Valek, P. W.

2015-12-01

Field aligned currents (FACs) that flow from the Earth's magnetosphere into the ionosphere are an important coupling mechanism in the interaction of the solar wind with the Earth's magnetosphere. Assuming pressure balance along with charge conservation yields an expression for the FACs in terms of plasma pressure gradients and pressure anisotropy. The Two Wide-Angle Imaging Neutral Atom Spectrometers (TWINS) mission, the first stereoscopic ENA magnetospheric imager, provides global images of the inner magnetosphere from which ion pressure distributions and pressure anisotropies can be obtained. Following the formulations in Heineman [1990] and using results from TWINS observations, we calculate the distribution of field aligned currents for the 17-18 March 2015 geomagnetic storm in which extended ionospheric precipitation was observed. Initial results for the field aligned currents will be generated assuming an isotropic pitch angle distribution. Global maps of field aligned currents during the main and recovery phase of the storm will be presented. Heinemann, H. (1990), Representations of Currents and Magnetic Fields in Anisotropic Magnetohydrostatic Plasma, J. Geophys. Res., 95, 7789.

TGF-β directs trafficking of the epithelial sodium channel ENaC which has implications for ion and fluid transport in acute lung injury.

PubMed

Peters, Dorothea M; Vadász, István; Wujak, Lukasz; Wygrecka, Malgorzata; Olschewski, Andrea; Becker, Christin; Herold, Susanne; Papp, Rita; Mayer, Konstantin; Rummel, Sebastian; Brandes, Ralph P; Günther, Andreas; Waldegger, Siegfried; Eickelberg, Oliver; Seeger, Werner; Morty, Rory E

2014-01-21

TGF-β is a pathogenic factor in patients with acute respiratory distress syndrome (ARDS), a condition characterized by alveolar edema. A unique TGF-β pathway is described, which rapidly promoted internalization of the αβγ epithelial sodium channel (ENaC) complex from the alveolar epithelial cell surface, leading to persistence of pulmonary edema. TGF-β applied to the alveolar airspaces of live rabbits or isolated rabbit lungs blocked sodium transport and caused fluid retention, which--together with patch-clamp and flow cytometry studies--identified ENaC as the target of TGF-β. TGF-β rapidly and sequentially activated phospholipase D1, phosphatidylinositol-4-phosphate 5-kinase 1α, and NADPH oxidase 4 (NOX4) to produce reactive oxygen species, driving internalization of βENaC, the subunit responsible for cell-surface stability of the αβγENaC complex. ENaC internalization was dependent on oxidation of βENaC Cys(43). Treatment of alveolar epithelial cells with bronchoalveolar lavage fluids from ARDS patients drove βENaC internalization, which was inhibited by a TGF-β neutralizing antibody and a Tgfbr1 inhibitor. Pharmacological inhibition of TGF-β signaling in vivo in mice, and genetic ablation of the nox4 gene in mice, protected against perturbed lung fluid balance in a bleomycin model of lung injury, highlighting a role for both proximal and distal components of this unique ENaC regulatory pathway in lung fluid balance. These data describe a unique TGF-β-dependent mechanism that regulates ion and fluid transport in the lung, which is not only relevant to the pathological mechanisms of ARDS, but might also represent a physiological means of acutely regulating ENaC activity in the lung and other organs.

ENA-78 is an important angiogenic factor in idiopathic pulmonary fibrosis.

PubMed

Keane, M P; Belperio, J A; Burdick, M D; Lynch, J P; Fishbein, M C; Strieter, R M

2001-12-15

Idiopathic pulmonary fibrosis (IPF) is a chronic and often fatal disorder. Fibroplasia and deposition of extracellular matrix are dependent, in part, on angiogenesis and vascular remodeling. We obtained open lung biopsies from patients undergoing thoracic surgery for reasons other than interstitial lung disease (control) (n = 78) and from patients with IPF (n = 91). We found that levels of epithelial neutrophil-activating peptide 78 (ENA-78) were greater from tissue specimens of IPF patients, as compared with control subjects. When ENA-78 was depleted from IPF tissue specimens, tissue-derived angiogenic activity was markedly reduced. Immunolocalization of ENA-78 demonstrated that hyperplastic Type II pneumocytes and macrophages were the predominant cellular sources of ENA-78. These findings support the notion that ENA-78 may be an important additional factor that regulates angiogenic activity in IPF.

Epithelial Sodium and Acid-Sensing Ion Channels

NASA Astrophysics Data System (ADS)

Kellenberger, Stephan

The epithelial Na+ channel (ENaC) and acid-sensing ion channels (ASICs) are non-voltage-gated Na+ channels that form their own subfamilies within the ENaC/degenerin ion channel family. ASICs are sensors of extracellular pH, and ENaC, whose main function is trans-epithelial Na+ transport, can sense extra- and intra-cellular Na+. In aldosterone-responsive epithelial cells of the kidney, ENaC plays a critical role in the control of sodium balance, blood volume and blood pressure. In airway epithelia, ENaC has a distinct role in controlling fluid reabsorption at the air-liquid interface, thereby determining the rate of mucociliary transport. In taste receptor cells of the tongue, ENaC is involved in salt taste sensation. ASICs have emerged as key sensors for extracellular protons in central and peripheral neurons. Although not all of their physiological and pathological functions are firmly established yet, there is good evidence for a role of ASICs in the brain in learning, expression of fear, and in neurodegeneration after ischaemic stroke. In sensory neurons, ASICs are involved in nociception and mechanosensation. ENaC and ASIC subunits share substantial sequence homology and the conservation of several functional domains. This chapter summarises our current understanding of the physiological functions and of the mechanisms of ion permeation, gating and regulation of ENaC and ASICs.

Selectivity in subunit composition of Ena/VASP tetramers

PubMed Central

Riquelme, Daisy N.; Meyer, Aaron S.; Barzik, Melanie; Keating, Amy; Gertler, Frank B.

2015-01-01

The members of the actin regulatory family of Ena/VASP proteins form stable tetramers. The vertebrate members of the Ena/VASP family, VASP, Mena and EVL, have many overlapping properties and expression patterns, but functional and regulatory differences between paralogues have been observed. The formation of mixed oligomers may serve a regulatory role to refine Ena/VASP activity. While it has been assumed that family members can form mixed oligomers, this possibility has not been investigated systematically. Using cells expressing controlled combinations of VASP, Mena and EVL, we evaluated the composition of Ena/VASP oligomers and found that VASP forms oligomers without apparent bias with itself, Mena or EVL. However, Mena and EVL showed only weak hetero-oligomerization, suggesting specificity in the association of Ena/VASP family members. Co-expression of VASP increased the ability of Mena and EVL to form mixed oligomers. Additionally, we found that the tetramerization domain (TD) at the C-termini of Ena/VASP proteins conferred the observed selectivity. Finally, we demonstrate that replacement of the TD with a synthetic tetramerizing coiled coil sequence supports homo-oligomerization and normal VASP subcellular localization. PMID:26221026

ENA/VASP downregulation triggers cell death by impairing axonal maintenance in hippocampal neurons.

PubMed

Franco, D Lorena; Rezával, Carolina; Cáceres, Alfredo; Schinder, Alejandro F; Ceriani, M Fernanda

2010-06-01

Neurodegenerative diseases encompass a broad variety of motor and cognitive disorders that are accompanied by death of specific neuronal populations or brain regions. Cellular and molecular mechanisms underlying these complex disorders remain largely unknown. In a previous work we searched for novel Drosophila genes relevant for neurodegeneration and singled out enabled (ena), which encodes a protein involved in cytoskeleton remodeling. To extend our understanding on the mechanisms of ENA-triggered degeneration we now investigated the effect of silencing ena ortholog genes in mouse hippocampal neurons. We found that ENA/VASP downregulation led to neurite retraction and concomitant neuronal cell death through an apoptotic pathway. Remarkably, this retraction initially affected the axonal structure, showing no effect on dendrites. Reduction in ENA/VASP levels blocked the neuritogenic effect of a specific RhoA kinase (ROCK) inhibitor, thus suggesting that these proteins could participate in the Rho-signaling pathway. Altogether these observations demonstrate that ENA/VASP proteins are implicated in the establishment and maintenance of the axonal structure and that a change on their expression levels triggers neuronal degeneration. 2010 Elsevier Inc. All rights reserved.

Regulation of Epithelial Sodium Transport via Epithelial Na+ Channel

PubMed Central

Marunaka, Yoshinori; Niisato, Naomi; Taruno, Akiyuki; Ohta, Mariko; Miyazaki, Hiroaki; Hosogi, Shigekuni; Nakajima, Ken-ichi; Kusuzaki, Katsuyuki; Ashihara, Eishi; Nishio, Kyosuke; Iwasaki, Yoshinobu; Nakahari, Takashi; Kubota, Takahiro

2011-01-01

Renal epithelial Na+ transport plays an important role in homeostasis of our body fluid content and blood pressure. Further, the Na+ transport in alveolar epithelial cells essentially controls the amount of alveolar fluid that should be kept at an appropriate level for normal gas exchange. The epithelial Na+ transport is generally mediated through two steps: (1) the entry step of Na+ via epithelial Na+ channel (ENaC) at the apical membrane and (2) the extrusion step of Na+ via the Na+, K+-ATPase at the basolateral membrane. In general, the Na+ entry via ENaC is the rate-limiting step. Therefore, the regulation of ENaC plays an essential role in control of blood pressure and normal gas exchange. In this paper, we discuss two major factors in ENaC regulation: (1) activity of individual ENaC and (2) number of ENaC located at the apical membrane. PMID:22028593

Potential Roles of Amiloride-Sensitive Sodium Channels in Cancer Development.

PubMed

Xu, Siguang; Liu, Cui; Ma, Yana; Ji, Hong-Long; Li, Xiumin

2016-01-01

The ENaC/degenerin ion channel superfamily includes the amiloride-sensitive epithelial sodium channel (ENaC) and acid sensitive ionic channel (ASIC). ENaC is a multimeric ion channel formed by heteromultimeric membrane glycoproteins, which participate in a multitude of biological processes by mediating the transport of sodium (Na(+)) across epithelial tissues such as the kidney, lungs, bladder, and gut. Aberrant ENaC functions contribute to several human disease states including pseudohypoaldosteronism, Liddle syndrome, cystic fibrosis, and salt-sensitive hypertension. Increasing evidence suggests that ion channels not only regulate ion homeostasis and electric signaling in excitable cells but also play important roles in cancer cell behaviors such as proliferation, apoptosis, invasion, and migration. Indeed, ENaCs/ASICs had been reported to be associated with cancer characteristics. Given their cell surface localization and pharmacology, pharmacological strategies to target ENaC/ASIC family members may be promising cancer therapeutics.

Characterization of interactions between Nedd4 and beta and gammaENaC using surface plasmon resonance.

PubMed

Asher, C; Chigaev, A; Garty, H

2001-09-07

Cell surface expression of the epithelial Na(+) channel ENaC is regulated by the ubiquitin ligase Nedd4. Binding of the WW domains of Nedd4 to the PY region in the carboxy tails of beta and gammaENaC, results in channel ubiquitination and degradation. Kinetic analysis of these interactions has been done using surface plasmon resonance. Synthetic peptides corresponding to the PY regions of beta and gammaENaC were immobilized on a sensor chip and "real-time" kinetics of their binding to recombinant WW proteins was determined. Specificity of the interactions was established by competition experiment, as well as by monitoring effects of a point mutation known to impair Nedd4/ENaC binding. These data provides the first determination of association, dissociation and equilibrium constants for the interactions between WW2 and beta or gammaENaC. Copyright 2001 Academic Press.

Chloride transport-driven alveolar fluid secretion is a major contributor to cardiogenic lung edema

PubMed Central

Solymosi, Esther A.; Kaestle-Gembardt, Stefanie M.; Vadász, István; Wang, Liming; Neye, Nils; Chupin, Cécile Julie Adrienne; Rozowsky, Simon; Ruehl, Ramona; Tabuchi, Arata; Schulz, Holger; Kapus, Andras; Morty, Rory E.; Kuebler, Wolfgang M.

2013-01-01

Alveolar fluid clearance driven by active epithelial Na+ and secondary Cl− absorption counteracts edema formation in the intact lung. Recently, we showed that impairment of alveolar fluid clearance because of inhibition of epithelial Na+ channels (ENaCs) promotes cardiogenic lung edema. Concomitantly, we observed a reversal of alveolar fluid clearance, suggesting that reversed transepithelial ion transport may promote lung edema by driving active alveolar fluid secretion. We, therefore, hypothesized that alveolar ion and fluid secretion may constitute a pathomechanism in lung edema and aimed to identify underlying molecular pathways. In isolated perfused lungs, alveolar fluid clearance and secretion were determined by a double-indicator dilution technique. Transepithelial Cl− secretion and alveolar Cl− influx were quantified by radionuclide tracing and alveolar Cl− imaging, respectively. Elevated hydrostatic pressure induced ouabain-sensitive alveolar fluid secretion that coincided with transepithelial Cl− secretion and alveolar Cl− influx. Inhibition of either cystic fibrosis transmembrane conductance regulator (CFTR) or Na+-K+-Cl− cotransporters (NKCC) blocked alveolar fluid secretion, and lungs of CFTR−/− mice were protected from hydrostatic edema. Inhibition of ENaC by amiloride reproduced alveolar fluid and Cl− secretion that were again CFTR-, NKCC-, and Na+-K+-ATPase–dependent. Our findings show a reversal of transepithelial Cl− and fluid flux from absorptive to secretory mode at hydrostatic stress. Alveolar Cl− and fluid secretion are triggered by ENaC inhibition and mediated by NKCC and CFTR. Our results characterize an innovative mechanism of cardiogenic edema formation and identify NKCC1 as a unique therapeutic target in cardiogenic lung edema. PMID:23645634

Increased renal alpha-epithelial sodium channel (ENAC) protein and increased ENAC activity in normal pregnancy.

PubMed

West, Crystal; Zhang, Zheng; Ecker, Geoffrey; Masilamani, Shyama M E

2010-11-01

Pregnancy-mediated sodium (Na) retention is required to provide an increase in plasma volume for the growing fetus. The mechanisms responsible for this Na retention are not clear. We first used a targeted proteomics approach and found that there were no changes in the protein abundance compared with virgin rats of the β or γ ENaC, type 3 Na(+)/H(+) exchanger (NHE3), bumetanide-sensitive cotransporter (NKCC2), or NaCl cotransporter (NCC) in mid- or late pregnancy. In contrast, we observed marked increases in the abundance of the α-ENaC subunit. The plasma volume increased progressively during pregnancy with the greatest plasma volume being evident in late pregnancy. ENaC inhibition abolished the difference in plasma volume status between virgin and pregnant rats. To determine the in vivo activity of ENaC, we conducted in vivo studies of rats in late pregnancy (days 18-20) and virgin rats to measure the natriuretic response to ENaC blockade (with benzamil). The in vivo activity of ENaC (U(Na)V postbenzamil-U(Na)V postvehicle) was markedly increased in late pregnancy, and this difference was abolished by pretreatment with the mineralocorticoid receptor antagonist, eplerenone. These findings demonstrate that the increased α-ENaC subunit of pregnancy is associated with an mineralocorticoid-dependent increase in ENaC activity. Further, we show that ENaC activity is a major contributor of plasma volume status in late pregnancy. These changes are likely to contribute to the renal sodium retention and plasma volume expansion required for an optimal pregnancy.

Affinity and specificity of interactions between Nedd4 isoforms and the epithelial Na+ channel.

PubMed

Henry, Pauline C; Kanelis, Voula; O'Brien, M Christine; Kim, Brian; Gautschi, Ivan; Forman-Kay, Julie; Schild, Laurent; Rotin, Daniela

2003-05-30

The epithelial Na+ channel (alphabetagammaENaC) regulates salt and fluid homeostasis and blood pressure. Each ENaC subunit contains a PY motif (PPXY) that binds to the WW domains of Nedd4, a Hect family ubiquitin ligase containing 3-4 WW domains and usually a C2 domain. It has been proposed that Nedd4-2, but not Nedd4-1, isoforms can bind to and suppress ENaC activity. Here we challenge this notion and show that, instead, the presence of a unique WW domain (WW3*) in either Nedd4-2 or Nedd4-1 determines high affinity interactions and the ability to suppress ENaC. WW3* from either Nedd4-2 or Nedd4-1 binds ENaC-PY motifs equally well (e.g. Kd approximately 10 microm for alpha- or betaENaC, 3-6-fold higher affinity than WW4), as determined by intrinsic tryptophan fluorescence. Moreover, dNedd4-1, which naturally contains a WW3* instead of WW2, is able to suppress ENaC function equally well as Nedd4-2. Homology models of the WW3*.betaENaC-PY complex revealed that a Pro and Ala conserved in all WW3*, but not other Nedd4-WW domains, help form the binding pocket for PY motif prolines. Extensive contacts are formed between the betaENaC-PY motif and the Pro in WW3*, and the small Ala creates a large pocket to accommodate the peptide. Indeed, mutating the conserved Pro and Ala in WW3* reduces binding affinity 2-3-fold. Additionally, we demonstrate that mutations in PY motif residues that form contacts with the WW domain based on our previously solved structure either abolish or severely reduce binding affinity to the WW domain and that the extent of binding correlates with the level of ENaC suppression. Independently, we show that a peptide encompassing the PY motif of sgk1, previously proposed to bind to Nedd4-2 and alter its ability to regulate ENaC, does not bind (or binds poorly) the WW domains of Nedd4-2. Collectively, these results suggest that high affinity of WW domain-PY-motif interactions rather than affiliation with Nedd4-1/Nedd-2 is critical for ENaC suppression by Nedd4 proteins.

Blood pressure regulation via the epithelial sodium channel: from gene to kidney and beyond.

PubMed

Büsst, Cara J

2013-08-01

The epithelial sodium channel (ENaC) has long been recognized as playing a vital role in blood pressure (BP) regulation due to its involvement in fluid balance. The genes encoding the three ENaC subunits are likewise important contributors to hypertension, both in rare monogenic diseases and in the general population. The unusually high numbers of genetic variants associated with complex traits, including BP, that are located in non-coding areas suggest an involvement of these variants in regulatory functions. This may involve differential regulation of expression in different tissues. Emerging evidence indicates that the ENaC plays an important role in BP determination not only via its actions in the kidney, but also in other tissues commonly involved in BP regulation. The ENaC in the central nervous system is proposed to regulate BP via sympathetic nervous system activity. Recent evidence suggests that the ENaC contributes to vascular function and the myogenic response. Additional roles potentially include initiation of the baroreceptor reflex via ENaC in the baroreceptors and driving high salt intake with a 'taste for salt' via ENaC in the tongue. The present review describes the involvement of the ENaC in the determination of BP at a genetic and physiological level, detailing recent evidence for its role in the kidney and in other pertinent tissues. © 2013 Wiley Publishing Asia Pty Ltd.

The interaction between rejection sensitivity and emotional maltreatment in borderline personality disorder.

PubMed

Chesin, Megan; Fertuck, Eric; Goodman, Jeanne; Lichenstein, Sarah; Stanley, Barbara

2015-01-01

Borderline personality disorder (BPD) is a prevalent psychiatric disorder associated with significant distress, dysfunction, and treatment utilization. Though, theoretically, BPD is posited to arise from a combination of trait and environmental risk factors, few studies have tested trait-by-environment interactions in BPD. We investigated the roles of rejection sensitivity (RS) and childhood emotional neglect and abuse (ENA) as well as their interaction in BPD. Eighty-five adults with a lifetime mood disorder who were recruited for outpatient studies in a psychiatric clinic were assessed for ENA using the Childhood Trauma Questionnaire and for RS with the Adult Rejection Sensitivity Questionnaire. BPD diagnoses were made by consensus using data collected on the Structured Clinical Interview for DSM-IV. Hierarchical logistic regression was used to test associations between RS, ENA, their interaction and BPD. RS and ENA interacted to predict co-occurring BPD in our sample of mood-disordered patients, with the strength of the relationship between RS and BPD depending on the severity of ENA. In the context of little or no ENA, RS and BPD were more strongly related than when ENA was more severe. Our results extend previous findings suggesting RS and ENA are risk factors for BPD. They also provide preliminary support for contemporary theories of BPD positing trait-by-environment interactions in the development of BPD. Prospective studies are needed to confirm these findings. © 2014 S. Karger AG, Basel.

Charge exchange, ENAs and the loss of planetary ions at Mars

NASA Astrophysics Data System (ADS)

Kallio, E.; Janhunen, P.; Säles, T.

Neither Mars nor Venus has a strong global intrinsic magnetic field and therefore the solar wind can flow close to the planets in high neutral density regions. Because of the formed direct interaction between the atmosphere/exosphere and the solar wind, the ionized atmospheric neutrals can be picked up by the solar wind. Charge exchange between solar wind protons and planetary neutrals, instead, produce energetic neutral hydrogen atoms (H-ENA) which are the manifestation of the direct interaction between the solar wind and planetary neutrals. Picked-up planetary O+ ions in turn form energetic neutral oxygen atoms (O-ENA) via charge exchange process. The ion escape, H-ENAs, O-ENAs and electrons will be investigated at Mars and Venus by two identical instruments: ASPERA-3 on MarsExpress (measurements started in Jan. 2004) and ASPERA-4 on VenusExpress (2006). We present a self-consistent, three-dimensional quasi-neutral hybrid (ions are particles, electrons a fluid) simulation to study Mars/Venus-solar wind interaction in general and ASPERA-3/4 measurements in particular. Our model includes three ion species (H+, O+, O2+), and contains charge exchange, ion-neutral and chemical reactions. We show results of quasi-neutral hybrid model runs that we have used to study the escape of planetary ions, the effects of planetary ions on the Martian plasma environment and the production and properties of fast hydrogen(H) and oxygen(O) ENAs near Mars. We also compare these hydrogen ENA images with the hydrogen ENA images that has been derived from an empirical flow model by line-of-sight integration. The advantage of the analytical gas dynamic like flow model is that it is computationally so fast that it provides a possibility to perform an ENA inversion, that is, to derive global plasma parameters from the measured ENA image.

Modeling the near-Earth interaction between ring current ions and exospheric neutrals: escape through energetic neutral atoms (ENAs)

NASA Astrophysics Data System (ADS)

LLera, K.; Goldstein, J.; McComas, D. J.; Valek, P. W.

2016-12-01

The two major loss processes for ring current decay are precipitation and energetic neutral atoms (ENAs). Since the exospheric neutral density increases with decreasing altitudes, precipitating ring current ions (reaching down to 200 - 800 km in altitude) also produce low-altitude ENA signatures that can be stronger than the ring current emission at equatorial distances ( 2 - 9 Re). The higher density results in multiple collisions between the ring current ions and exospheric oxygen. The affect on hydrogen ions is the focus of this study. Since the H particle sustains energy loss ( 36 eV) at each neutralizing or re-ionizing interaction, the escaped ENAs do not directly reflect the ring current properties. We model the energy loss due to multiple charge exchange and electron stripping interactions of 1 - 100 keV precipitating ring current ions undergo before emerging as low-altitude ENAs. The H particle is either an ion or an ENA throughout the simulation. Their lifetime is analytically determined by the length of one mean free path. We track the ion state with Lorentz motion while the ENA travels ballistically across the geomagnetic field. Our simulations show the energy loss is greater than 20% for hydrogen ring current ions below 30 keV (60 keV for the simulations that wander equatorward). This is the first quantification of the energy loss associated with the creation of low-altitude ENAs. Our model (currently constrained in the meridional plane) has revealed characteristics on how precipitation is affected by the near-Earth neutral exosphere. This ion-neutral interaction removes particles from the loss cone but promotes loss through ENA generation. These findings should be implemented in models predicting the ring current decay and used as an analysis tool to reconstruct the ring current population from observed low-altitude ENAs.

Effective silencing of ENaC by siRNA delivered with epithelial-targeted nanocomplexes in human cystic fibrosis cells and in mouse lung.

PubMed

Tagalakis, Aristides D; Munye, Mustafa M; Ivanova, Rositsa; Chen, Hanpeng; Smith, Claire M; Aldossary, Ahmad M; Rosa, Luca Z; Moulding, Dale; Barnes, Josephine L; Kafetzis, Konstantinos N; Jones, Stuart A; Baines, Deborah L; Moss, Guy W J; O'Callaghan, Christopher; McAnulty, Robin J; Hart, Stephen L

2018-05-10

Loss of the cystic fibrosis transmembrane conductance regulator in cystic fibrosis (CF) leads to hyperabsorption of sodium and fluid from the airway due to upregulation of the epithelial sodium channel (ENaC). Thickened mucus and depleted airway surface liquid (ASL) then lead to impaired mucociliary clearance. ENaC regulation is thus a promising target for CF therapy. Our aim was to develop siRNA nanocomplexes that mediate effective silencing of airway epithelial ENaC in vitro and in vivo with functional correction of epithelial ion and fluid transport. We investigated translocation of nanocomplexes through mucus and their transfection efficiency in primary CF epithelial cells grown at air-liquid interface (ALI).Short interfering RNA (SiRNA)-mediated silencing was examined by quantitative RT-PCR and western analysis of ENaC. Transepithelial potential (V t ), short circuit current (I sc ), ASL depth and ciliary beat frequency (CBF) were measured for functional analysis. Inflammation was analysed by histological analysis of normal mouse lung tissue sections. Nanocomplexes translocated more rapidly than siRNA alone through mucus. Transfections of primary CF epithelial cells with nanocomplexes targeting αENaC siRNA, reduced αENaC and βENaC mRNA by 30%. Transfections reduced V t , the amiloride-sensitive I sc and mucus protein concentration while increasing ASL depth and CBF to normal levels. A single dose of siRNA in mouse lung silenced ENaC by approximately 30%, which persisted for at least 7 days. Three doses of siRNA increased silencing to approximately 50%. Nanoparticle-mediated delivery of ENaCsiRNA to ALI cultures corrected aspects of the mucociliary defect in human CF cells and offers effective delivery and silencing in vivo. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

TGF-β directs trafficking of the epithelial sodium channel ENaC which has implications for ion and fluid transport in acute lung injury

PubMed Central

Peters, Dorothea M.; Vadász, István; Wujak, Łukasz; Wygrecka, Małgorzata; Olschewski, Andrea; Becker, Christin; Herold, Susanne; Papp, Rita; Mayer, Konstantin; Rummel, Sebastian; Brandes, Ralph P.; Günther, Andreas; Waldegger, Siegfried; Eickelberg, Oliver; Seeger, Werner; Morty, Rory E.

2014-01-01

TGF-β is a pathogenic factor in patients with acute respiratory distress syndrome (ARDS), a condition characterized by alveolar edema. A unique TGF-β pathway is described, which rapidly promoted internalization of the αβγ epithelial sodium channel (ENaC) complex from the alveolar epithelial cell surface, leading to persistence of pulmonary edema. TGF-β applied to the alveolar airspaces of live rabbits or isolated rabbit lungs blocked sodium transport and caused fluid retention, which—together with patch-clamp and flow cytometry studies—identified ENaC as the target of TGF-β. TGF-β rapidly and sequentially activated phospholipase D1, phosphatidylinositol-4-phosphate 5-kinase 1α, and NADPH oxidase 4 (NOX4) to produce reactive oxygen species, driving internalization of βENaC, the subunit responsible for cell-surface stability of the αβγENaC complex. ENaC internalization was dependent on oxidation of βENaC Cys43. Treatment of alveolar epithelial cells with bronchoalveolar lavage fluids from ARDS patients drove βENaC internalization, which was inhibited by a TGF-β neutralizing antibody and a Tgfbr1 inhibitor. Pharmacological inhibition of TGF-β signaling in vivo in mice, and genetic ablation of the nox4 gene in mice, protected against perturbed lung fluid balance in a bleomycin model of lung injury, highlighting a role for both proximal and distal components of this unique ENaC regulatory pathway in lung fluid balance. These data describe a unique TGF-β–dependent mechanism that regulates ion and fluid transport in the lung, which is not only relevant to the pathological mechanisms of ARDS, but might also represent a physiological means of acutely regulating ENaC activity in the lung and other organs. PMID:24324142

Evaluation of Electrospun Nanofiber-Anchored Silicone for the Degenerative Intervertebral Disc

PubMed Central

Riahanizad, S.

2017-01-01

The nucleus pulposus (NP) substitution by polymeric gel is one of the promising techniques for the repair of the degenerative intervertebral disc (IVD). Silicone gel is one of the potential candidates for a NP replacement material. Electrospun fiber anchorage to silicone disc, referred as ENAS disc, may not only improve the biomechanical performances of the gel but it can also improve restoration capability of the gel, which is unknown. This study successfully produced a novel process to anchor any size and shape of NP gel with electrospun fiber mesh. Viscoelastic properties of silicone and ENAS disc were measured using standard experimental techniques and compared with the native tissue properties. Ex vivo mechanical tests were conducted on ENAS disc-implanted rabbit tails to the compare the mechanical stability between intact and ENAS implanted spines. This study found that viscoelastic properties of ENAS disc are higher than silicone disc and comparable to the viscoelastic properties of human NP. The ex vivo studies found that the ENAS disc restore the mechanical functionality of rabbit tail spine, after discectomy of native NP and replacing the NP by ENAS disc. Therefore, the PCL ENF mesh anchoring technique to a NP implant can have clinical potential. PMID:29181144

Regulation of the epithelial Na+ channel by membrane tension.

PubMed

Awayda, M S; Subramanyam, M

1998-08-01

The sensitivity of alphabetagamma rat epithelial Na+ channel (rENaC) to osmotically or mechanically induced changes of membrane tension was investigated in the Xenopus oocyte expression system, using both dual electrode voltage clamp and cell-attached patch clamp methodologies. ENaC whole-cell currents were insensitive to mechanical cell swelling caused by direct injection of 90 or 180 nl of 100-mM KCl. Similarly, ENaC whole-cell currents were insensitive to osmotic cell swelling caused by a 33% decrease of bathing solution osmolarity. The lack of an effect of cell swelling on ENaC was independent of the status of the actin cytoskeleton, as ENaC remained insensitive to osmotic and mechanical cell swelling in oocytes pretreated with cytochalasin B for 2-5 h. This apparent insensitivity of ENaC to increased cell volume and changes of membrane tension was also observed at the single channel level in membrane patches subjected to negative or positive pressures of 5 or 10 in. of water. However, and contrary to the lack of an effect of cell swelling, ENaC currents were inhibited by cell shrinking. A 45-min incubation in a 260-mosmol solution (a 25% increase of solution osmolarity) caused a decrease of ENaC currents (at -100 mV) from -3.42 +/- 0.34 to -2.02 +/- 0.23 microA (n = 6). This decrease of current with cell shrinking was completely blocked by pretreatment of oocytes with cytochalasin B, indicating that these changes of current are not likely related to a direct effect of cell shrinking. We conclude that alpha beta gamma rENaC is not directly mechanosensitive when expressed in a system that can produce a channel with identical properties to those found in native epithelia.

Cytochalasin E alters the cytoskeleton and decreases ENaC activity in Xenopus 2F3 cells.

PubMed

Reifenberger, Matthew S; Yu, Ling; Bao, Hui-Fang; Duke, Billie Jeanne; Liu, Bing-Chen; Ma, He-Ping; Alli, Ahmed A; Eaton, Douglas C; Alli, Abdel A

2014-07-01

Numerous reports have linked cytoskeleton-associated proteins with the regulation of epithelial Na(+) channel (ENaC) activity. The purpose of the present study was to determine the effect of actin cytoskeleton disruption by cytochalasin E on ENaC activity in Xenopus 2F3 cells. Here, we show that cytochalasin E treatment for 60 min can disrupt the integrity of the actin cytoskeleton in cultured Xenopus 2F3 cells. We show using single channel patch-clamp experiments and measurements of short-circuit current that ENaC activity, but not its density, is altered by cytochalasin E-induced disruption of the cytoskeleton. In nontreated cells, 8 of 33 patches (24%) had no measurable ENaC activity, whereas in cytochalasin E-treated cells, 17 of 32 patches (53%) had no activity. Analysis of those patches that did contain ENaC activity showed channel open probability significantly decreased from 0.081 ± 0.01 in nontreated cells to 0.043 ± 0.01 in cells treated with cytochalasin E. Transepithelial current from mpkCCD cells treated with cytochalasin E, cytochalasin D, or latrunculin B for 60 min was decreased compared with vehicle-treated cells. The subcellular expression of fodrin changed significantly, and several protein elements of the cytoskeleton decreased at least twofold after 60 min of cytochalasin E treatment. Cytochalasin E treatment disrupted the association between ENaC and myristoylated alanine-rich C-kinase substrate. The results presented here suggest disruption of the actin cytoskeleton by different compounds can attenuate ENaC activity through a mechanism involving changes in the subcellular expression of fodrin, several elements of the cytoskeleton, and destabilization of the ENaC-myristoylated alanine-rich C-kinase substrate complex. Copyright © 2014 the American Physiological Society.

Cytochalasin E alters the cytoskeleton and decreases ENaC activity in Xenopus 2F3 cells

PubMed Central

Reifenberger, Matthew S.; Yu, Ling; Bao, Hui-Fang; Duke, Billie Jeanne; Liu, Bing-Chen; Ma, He-Ping; Eaton, Douglas C.; Alli, Abdel A.

2014-01-01

Numerous reports have linked cytoskeleton-associated proteins with the regulation of epithelial Na+ channel (ENaC) activity. The purpose of the present study was to determine the effect of actin cytoskeleton disruption by cytochalasin E on ENaC activity in Xenopus 2F3 cells. Here, we show that cytochalasin E treatment for 60 min can disrupt the integrity of the actin cytoskeleton in cultured Xenopus 2F3 cells. We show using single channel patch-clamp experiments and measurements of short-circuit current that ENaC activity, but not its density, is altered by cytochalasin E-induced disruption of the cytoskeleton. In nontreated cells, 8 of 33 patches (24%) had no measurable ENaC activity, whereas in cytochalasin E-treated cells, 17 of 32 patches (53%) had no activity. Analysis of those patches that did contain ENaC activity showed channel open probability significantly decreased from 0.081 ± 0.01 in nontreated cells to 0.043 ± 0.01 in cells treated with cytochalasin E. Transepithelial current from mpkCCD cells treated with cytochalasin E, cytochalasin D, or latrunculin B for 60 min was decreased compared with vehicle-treated cells. The subcellular expression of fodrin changed significantly, and several protein elements of the cytoskeleton decreased at least twofold after 60 min of cytochalasin E treatment. Cytochalasin E treatment disrupted the association between ENaC and myristoylated alanine-rich C-kinase substrate. The results presented here suggest disruption of the actin cytoskeleton by different compounds can attenuate ENaC activity through a mechanism involving changes in the subcellular expression of fodrin, several elements of the cytoskeleton, and destabilization of the ENaC-myristoylated alanine-rich C-kinase substrate complex. PMID:24829507

Gain-of-Function Mutation W493R in the Epithelial Sodium Channel Allosterically Reconfigures Intersubunit Coupling*♦

PubMed Central

Shobair, Mahmoud; Dagliyan, Onur; Kota, Pradeep; Dang, Yan L.; He, Hong; Stutts, M. Jackson; Dokholyan, Nikolay V.

2016-01-01

Sodium absorption in epithelial cells is rate-limited by the epithelial sodium channel (ENaC) activity in lung, kidney, and the distal colon. Pathophysiological conditions, such as cystic fibrosis and Liddle syndrome, result from water-electrolyte imbalance partly due to malfunction of ENaC regulation. Because the quaternary structure of ENaC is yet undetermined, the bases of pathologically linked mutations in ENaC subunits α, β, and γ are largely unknown. Here, we present a structural model of heterotetrameric ENaC α1βα2γ that is consistent with previous cross-linking results and site-directed mutagenesis experiments. By using this model, we show that the disease-causing mutation αW493R rewires structural dynamics of the intersubunit interfaces α1β and α2γ. Changes in dynamics can allosterically propagate to the channel gate. We demonstrate that cleavage of the γ-subunit, which is critical for full channel activation, does not mediate activation of ENaC by αW493R. Our molecular dynamics simulations led us to identify a channel-activating electrostatic interaction between α2Arg-493 and γGlu-348 at the α2γ interface. By neutralizing a sodium-binding acidic patch at the α1β interface, we reduced ENaC activation of αW493R by more than 2-fold. By combining homology modeling, molecular dynamics, cysteine cross-linking, and voltage clamp experiments, we propose a dynamics-driven model for the gain-of-function in ENaC by αW493R. Our integrated computational and experimental approach advances our understanding of structure, dynamics, and function of ENaC in its disease-causing state. PMID:26668308

Dietary salt blunts vasodilation by stimulating epithelial sodium channels in endothelial cells from salt-sensitive Dahl rats.

PubMed

Wang, Zi-Rui; Liu, Hui-Bin; Sun, Ying-Ying; Hu, Qing-Qing; Li, Yu-Xia; Zheng, Wei-Wan; Yu, Chang-Jiang; Li, Xin-Yuan; Wu, Ming-Ming; Song, Bin-Lin; Mu, Jian-Jun; Yuan, Zu-Yi; Zhang, Zhi-Ren; Ma, He-Ping

2018-04-01

Our recent studies show that the reduced activity of epithelial sodium channels (ENaC) in endothelial cells accounts for the adaptation of vasculature to salt in Sprague-Dawley rats. The present study examines a hypothesis that enhanced ENaC activity mediates the loss of vasorelaxation in Dahl salt-sensitive (SS) rats. We used the cell-attached patch-clamp technique to record ENaC activity in split-open mesenteric arteries. Western blot and immunofluorescence staining were used to evaluate the levels of aldosterone, ENaC, eNOS and NO. Blood pressure was measured with the tail-cuff method and the artery relaxation was measured with the wire myograph assay. High-salt (HS) diet significantly increased plasma aldosterone and ENaC activity in the endothelial cells of Dahl SS rats. The endothelium-dependent artery relaxation was blunted by HS challenge in these rats. Amiloride, a potent blocker of ENaC, increased both phosphorylated eNOS and NO and therefore prevented the HS-induced loss of vasorelaxation. As, in SS rats, endogenous aldosterone was already elevated by HS challenge, exogenous aldosterone did not further elevate ENaC activity in the rats fed with HS. Eplerenone, a mineralocorticoid receptor antagonist, attenuated the effects of HS on both ENaC activity and artery relaxation. These data suggest that HS diet blunts artery relaxation and causes hypertension via a pathway associated with aldosterone-dependent activation of ENaC in endothelial cells. This pathway provides one of the mechanisms by which HS causes hypertension in Dahl SS rats. This article is part of a themed section on Spotlight on Small Molecules in Cardiovascular Diseases. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.8/issuetoc. © 2017 The British Pharmacological Society.

Interaction of Serum- and Glucocorticoid Regulated Kinase 1 (SGK1) with the WW-Domains of Nedd4-2 Is Required for Epithelial Sodium Channel Regulation

PubMed Central

Wiemuth, Dominik; Lott, J. Shaun; Ly, Kevin; Ke, Ying; Teesdale-Spittle, Paul; Snyder, Peter M.; McDonald, Fiona J.

2010-01-01

Background The epithelial sodium channel (ENaC) is an integral component of the pathway for Na+ absorption in epithelial cells. The ubiquitin ligases Nedd4 and Nedd4-2 bind to ENaC and decrease its activity. Conversely, Serum- and Glucocorticoid regulated Kinase-1 (SGK1), a downstream mediator of aldosterone, increases ENaC activity. This effect is at least partly mediated by direct interaction between SGK and Nedd4-2. SGK binds both Nedd4 and Nedd4-2, but it is only able to phosphorylate Nedd4-2. Phosphorylation of Nedd4-2 reduces its ability to bind to ENaC, due to the interaction of phosphorylated Nedd4-2 with 14-3-3 proteins, and hence increases ENaC activity. WW-domains in Nedd4-like proteins bind PY-motifs (PPXY) present in ENaC subunits, and SGK also has a PY-motif. Principal Finding Here we show that single or tandem WW-domains of Nedd4 and Nedd4-2 mediate binding to SGK and that different WW-domains of Nedd4 and Nedd4-2 are involved. Our data also show that WW-domains 2 and 3 of Nedd4-2 mediate the interaction with SGK in a cooperative manner, that activated SGK has increased affinity for the WW-domains of Nedd4-2 in vitro, and a greater stimulatory effect on ENaC Na+ transport compared to wildtype SGK. Further, SGK lacking a PY motif failed to stimulate ENaC activity in the presence of Nedd4-2. Conclusions Binding of Nedd4-2 WW-domains to SGK is necessary for SGK-induced ENaC activity. PMID:20730100

Salt-Induced Hypertension in a Mouse Model of Liddle's Syndrome is Mediated by Epithelial Sodium Channels in the Brain

PubMed Central

Van Huysse, James W.; Amin, Md. Shahrier; Yang, Baoli; Leenen, Frans H. H.

2012-01-01

Neural precursor cell expressed and developmentally downregulated 4-2 protein (Nedd4-2) facilitates the endocytosis of epithelial Na channels (ENaC). Both mice and humans with a loss of regulation of ENaC by Nedd4-2 have salt-induced hypertension. ENaC is also expressed in the brain, where it is critical for hypertension on high salt diet in salt-sensitive rats. In the present studies we assessed whether Nedd4-2 knockout (−/−) mice have: 1) increased brain ENaC; 2) elevated CSF sodium on high salt diet; and 3) enhanced pressor responses to CSF sodium and hypertension on high salt diet, both mediated by brain ENaC. Prominent choroid plexus and neuronal ENaC staining was present in −/− but not in wild-type (W/T) mice. In chronically instrumented mice, intracerebroventricular (icv) infusion of Na-rich aCSF increased MAP 3-fold higher in −/− than W/T. Icv infusion of the ENaC blocker benzamil abolished this enhancement. In telemetered −/− mice on high salt diet (8% NaCl), CSF [Na+], MAP and HR increased significantly, MAP by 30-35 mmHg. These MAP and HR responses were largely prevented by icv benzamil, but only to a minor extent by sc benzamil at the icv rate. We conclude that increased ENaC expression in the brain of Nedd 4-2 −/− mice mediates their hypertensive response to high salt diet, by causing increased sodium levels in the CSF as well as hyper-responsiveness to CSF sodium. These findings highlight the possible causative contribution of CNS ENaC in the etiology of salt-induced hypertension. PMID:22802227

CFTR fails to inhibit the epithelial sodium channel ENaC expressed in Xenopus laevis oocytes

PubMed Central

Nagel, G; Barbry, P; Chabot, H; Brochiero, E; Hartung, K; Grygorczyk, R

2005-01-01

The cystic fibrosis transmembrane conductance regulator (CFTR) plays a crucial role in regulating fluid secretion by the airways, intestines, sweat glands and other epithelial tissues. It is well established that the CFTR is a cAMP-activated, nucleotide-dependent anion channel, but additional functions are often attributed to it, including regulation of the epithelial sodium channel (ENaC). The absence of CFTR-dependent ENaC inhibition and the resulting sodium hyperabsorption were postulated to be a major electrolyte transport abnormality in cystic fibrosis (CF)-affected epithelia. Several ex vivo studies, including those that used the Xenopus oocyte expression system, have reported ENaC inhibition by activated CFTR, but contradictory results have also been obtained. Because CFTR–ENaC interactions have important implications in the pathogenesis of CF, the present investigation was undertaken by our three independent laboratories to resolve whether CFTR regulates ENaC in oocytes and to clarify potential sources of previously reported dissimilar observations. Using different experimental protocols and a wide range of channel expression levels, we found no evidence that activated CFTR regulates ENaC when oocyte membrane potential was carefully clamped. We determined that an apparent CFTR-dependent ENaC inhibition could be observed when resistance in series with the oocyte membrane was not low enough or the feedback voltage gain was not high enough. We suggest that the inhibitory effect of CFTR on ENaC reported in some earlier oocyte studies could be attributed to problems arising from high levels of channel expression and suboptimal recording conditions, that is, large series resistance and/or insufficient feedback voltage gain. PMID:15746174

Aldosterone Modulates the Association between NCC and ENaC.

PubMed

Wynne, Brandi M; Mistry, Abinash C; Al-Khalili, Otor; Mallick, Rickta; Theilig, Franziska; Eaton, Douglas C; Hoover, Robert S

2017-06-23

Distal sodium transport is a final step in the regulation of blood pressure. As such, understanding how the two main sodium transport proteins, the thiazide-sensitive sodium chloride cotransporter (NCC) and the epithelial sodium channel (ENaC), are regulated is paramount. Both are expressed in the late distal nephron; however, no evidence has suggested that these two sodium transport proteins interact. Recently, we established that these two sodium transport proteins functionally interact in the second part of the distal nephron (DCT2). Given their co-localization within the DCT2, we hypothesized that NCC and ENaC interactions might be modulated by aldosterone (Aldo). Aldo treatment increased NCC and αENaC colocalization (electron microscopy) and interaction (coimmunoprecipitation). Finally, with co-expression of the Aldo-induced protein serum- and glucocorticoid-inducible kinase 1 (SGK1), NCC and αENaC interactions were increased. These data demonstrate that Aldo promotes increased interaction of NCC and ENaC, within the DCT2 revealing a novel method of regulation for distal sodium reabsorption.

Involvement of the exomer complex in the polarized transport of Ena1 required for Saccharomyces cerevisiae survival against toxic cations

PubMed Central

Anton, Carlos; Zanolari, Bettina; Arcones, Irene; Wang, Congwei; Mulet, Jose Miguel; Spang, Anne; Roncero, Cesar

2017-01-01

Exomer is an adaptor complex required for the direct transport of a selected number of cargoes from the trans-Golgi network (TGN) to the plasma membrane in Saccharomyces cerevisiae. However, exomer mutants are highly sensitive to increased concentrations of alkali metal cations, a situation that remains unexplained by the lack of transport of any known cargoes. Here we identify several HAL genes that act as multicopy suppressors of this sensitivity and are connected to the reduced function of the sodium ATPase Ena1. Furthermore, we find that Ena1 is dependent on exomer function. Even though Ena1 can reach the plasma membrane independently of exomer, polarized delivery of Ena1 to the bud requires functional exomer. Moreover, exomer is required for full induction of Ena1 expression after cationic stress by facilitating the plasma membrane recruitment of the molecular machinery involved in Rim101 processing and activation of the RIM101 pathway in response to stress. Both the defective localization and the reduced levels of Ena1 contribute to the sensitivity of exomer mutants to alkali metal cations. Our work thus expands the spectrum of exomer-dependent proteins and provides a link to a more general role of exomer in TGN organization. PMID:29021337

Ground Motion Prediction Trends For Eastern North America Based on the Next Generation Attenuation East Ground Motion Database

NASA Astrophysics Data System (ADS)

Cramer, C. H.; Kutliroff, J.; Dangkua, D.

2010-12-01

A five-year Next Generation Attenuation (NGA) East project to develop new ground motion prediction equations for stable continental regions (SCRs), including eastern North America (ENA), has begun at the Pacific Earthquake Engineering Research (PEER) Center funded by the Nuclear Regulatory Commission (NRC), the U.S. Geological Survey (USGS), the Electric Power Research Institute (EPRI), and the Department of Energy (DOE). The initial effort focused on database design and collection of appropriate M>4 ENA broadband and accelerograph records to populate the database. Ongoing work has focused on adding records from smaller ENA earthquakes and from other SCRs such as Europe, Australia, and India. Currently, over 6500 horizontal and vertical component records from 60 ENA earthquakes have been collected and prepared (instrument response removed, filtering to acceptable-signal band, determining peak and spectral parameter values, quality assurance, etc.) for the database. Geologic Survey of Canada (GSC) strong motion recordings, previously not available, have also been added to the NGA East database. The additional earthquakes increase the number of ground motion recordings in the 10 - 100 km range, particularly from the 2008 M5.2 Mt. Carmel, IL event, and the 2005 M4.7 Riviere du Loup and 2010 M5.0 Val des Bois earthquakes in Quebec, Canada. The goal is to complete the ENA database and make it available in 2011 followed by a SCR database in 2012. Comparisons of ground motion observations from four recent M5 ENA earthquakes with current ENA ground motion prediction equations (GMPEs) suggest that current GMPEs, as a group, reasonably agree with M5 observations at short periods, particularly at distances less than 200 km. However, at one second, current GMPEs over predict M5 ground motion observations. The 2001 M7.6 Bhuj, India, earthquake provides some constraint at large magnitudes, as geology and regional attenuation is analogous to ENA. Cramer and Kumar, 2003, have shown that ENA GMPE’s generally agree with the Bhuj dataset within 300 km at short and long periods. But the Bhuj earthquake does not exhibit the intermediate-period spectral sag (Atkinson, 1993) of larger ENA earthquakes and thus the Bhuj ground motions may be larger than what could be expected at one second for M7s in ENA.

Regulation of ENaC-mediated alveolar fluid clearance by insulin via PI3K/Akt pathway in LPS-induced acute lung injury.

PubMed

Deng, Wang; Li, Chang-Yi; Tong, Jin; Zhang, Wei; Wang, Dao-Xin

2012-03-30

Stimulation of epithelial sodium channel (ENaC) increases Na(+) transport, a driving force of alveolar fluid clearance (AFC) to keep alveolar spaces free of edema fluid that is beneficial for acute lung injury (ALI). It is well recognized that regulation of ENaC by insulin via PI3K pathway, but the mechanism of this signaling pathway to regulate AFC and ENaC in ALI remains unclear. The aim of this study was to investigate the effect of insulin on AFC in ALI and clarify the pathway in which insulin regulates the expression of ENaC in vitro and in vivo. A model of ALI (LPS at a dose of 5.0 mg/kg) with non-hyperglycemia was established in Sprague-Dawley rats receiving continuous exogenous insulin by micro-osmotic pumps and wortmannin. The lungs were isolated for measurement of bronchoalveolar lavage fluid(BALF), total lung water content(TLW), and AFC after ALI for 8 hours. Alveolar epithelial type II cells were pre-incubated with LY294002, Akt inhibitor and SGK1 inhibitor 30 minutes before insulin treatment for 2 hours. The expressions of α-,β-, and γ-ENaC were detected by immunocytochemistry, reverse transcriptase polymerase chain reaction (RT-PCR) and western blotting. In vivo, insulin decreased TLW, enchanced AFC, increased the expressions of α-,β-, and γ-ENaC and the level of phosphorylated Akt, attenuated lung injury and improved the survival rate in LPS-induced ALI, the effects of which were blocked by wortmannin. Amiloride, a sodium channel inhibitor, significantly reduced insulin-induced increase in AFC. In vitro, insulin increased the expressions of α-,β-, and γ-ENaC as well as the level of phosphorylated Akt but LY294002 and Akt inhibitor significantly prevented insulin-induced increase in the expression of ENaC and the level of phosphorylated Akt respectively. Immunoprecipitation studies showed that levels of Nedd4-2 binding to ENaC were decreased by insulin via PI3K/Akt pathway. Our study demonstrated that insulin alleviated pulmonary edema and enhanced AFC by increasing the expression of ENaC that dependent upon PI3K/Akt pathway by inhibition of Nedd4-2.

Acute ENaC Stimulation by cAMP in a Kidney Cell Line is Mediated by Exocytic Insertion from a Recycling Channel Pool

PubMed Central

Butterworth, Michael B.; Edinger, Robert S.; Johnson, John P.; Frizzell, Raymond A.

2005-01-01

Acute hormonal regulation of the epithelial sodium channel (ENaC) in tight epithelia increases transcellular Na+ transport via trafficking of intracellular channels to the apical surface. The fate of the channels removed from the apical surface following agonist washout is less clear. By repetitively stimulating polarized mouse cortical collecting duct (mCCD, MPKCCD14) epithelia, we evaluated the hypothesis that ENaC recycles through an intracellular pool to be available for reinsertion into the apical membrane. Short circuit current (ISC), membrane capacitance (CT), and conductance (GT) were recorded from mCCD epithelia mounted in modified Ussing chambers. Surface biotinylation of ENaC demonstrated an increase in channel number in the apical membrane following cAMP stimulation. This increase was accompanied by a 83 ± 6% (n = 31) increase in ISC and a 15.3 ± 1.5% (n = 15) increase in CT. Selective membrane permeabilization demonstrated that the CT increase was due to an increase in apical membrane capacitance. ISC and CT declined to basal levels on stimulus washout. Repetitive cAMP stimulation and washout (∼1 h each cycle) resulted in response fatigue; ΔISC decreased ∼10% per stimulation–recovery cycle. When channel production was blocked by cycloheximide, ΔISC decreased ∼15% per stimulation cycle, indicating that newly synthesized ENaC contributed a relatively small fraction of the channels mobilized to the apical membrane. Selective block of surface ENaC by benzamil demonstrated that channels inserted from a subapical pool made up >90% of the stimulated ISC, and that on restimulation a large proportion of channels retrieved from the apical surface were reinserted into the apical membrane. Channel recycling was disrupted by brefeldin A, which inhibited ENaC exocytosis, by chloroquine, which inhibited ENaC endocytosis and recycling, and by latrunculin A, which blocked ENaC exocytosis. A compartment model featuring channel populations in the apical membrane and intracellular recycling pool provided an adequate kinetic description of the ISC responses to repetitive stimulation. The model supports the concept of ENaC recycling in response to repetitive cAMP stimulation. PMID:15623897

Acute ENaC stimulation by cAMP in a kidney cell line is mediated by exocytic insertion from a recycling channel pool.

PubMed

Butterworth, Michael B; Edinger, Robert S; Johnson, John P; Frizzell, Raymond A

2005-01-01

Acute hormonal regulation of the epithelial sodium channel (ENaC) in tight epithelia increases transcellular Na(+) transport via trafficking of intracellular channels to the apical surface. The fate of the channels removed from the apical surface following agonist washout is less clear. By repetitively stimulating polarized mouse cortical collecting duct (mCCD, (MPK)CCD(14)) epithelia, we evaluated the hypothesis that ENaC recycles through an intracellular pool to be available for reinsertion into the apical membrane. Short circuit current (I(SC)), membrane capacitance (C(T)), and conductance (G(T)) were recorded from mCCD epithelia mounted in modified Ussing chambers. Surface biotinylation of ENaC demonstrated an increase in channel number in the apical membrane following cAMP stimulation. This increase was accompanied by a 83 +/- 6% (n = 31) increase in I(SC) and a 15.3 +/- 1.5% (n = 15) increase in C(T). Selective membrane permeabilization demonstrated that the C(T) increase was due to an increase in apical membrane capacitance. I(SC) and C(T) declined to basal levels on stimulus washout. Repetitive cAMP stimulation and washout (approximately 1 h each cycle) resulted in response fatigue; DeltaI(SC) decreased approximately 10% per stimulation-recovery cycle. When channel production was blocked by cycloheximide, DeltaI(SC) decreased approximately 15% per stimulation cycle, indicating that newly synthesized ENaC contributed a relatively small fraction of the channels mobilized to the apical membrane. Selective block of surface ENaC by benzamil demonstrated that channels inserted from a subapical pool made up >90% of the stimulated I(SC), and that on restimulation a large proportion of channels retrieved from the apical surface were reinserted into the apical membrane. Channel recycling was disrupted by brefeldin A, which inhibited ENaC exocytosis, by chloroquine, which inhibited ENaC endocytosis and recycling, and by latrunculin A, which blocked ENaC exocytosis. A compartment model featuring channel populations in the apical membrane and intracellular recycling pool provided an adequate kinetic description of the I(SC) responses to repetitive stimulation. The model supports the concept of ENaC recycling in response to repetitive cAMP stimulation.

Sodium 4-phenylbutyrate upregulates ENaC and sodium absorption in T84 cells.

PubMed

Iordache, Claudiu; Duszyk, Marek

2007-01-15

Butyrate and other short-chain fatty acids (SCFA), produced by colonic bacterial flora, affect numerous epithelial cell functions. To better understand how SCFA regulate ion transport, we investigated the effects of 4-phenylbutyrate (4-PBA) on Na(+) absorption in T84 cells. Under standard cell culture conditions, the short circuit current did not display any amiloride-sensitive Na(+) absorption and was wholly representative of Cl(-) secretion. However, when T84 cells were grown in the presence of 5 mM 4-PBA, a gradual appearance of amiloride-sensitive Na(+) channel (ENaC) activity was observed that reached a plateau after 24 h. Quantitative RT-PCR and Western blot studies of ENaC subunit expression indicated that 4-PBA stimulated alpha and gamma subunits. Trichostatin A, an inhibitor of histone deacetylase, mimicked the effects of 4-PBA, suggesting that 4-PBA affects ENaC expression by inhibiting deacetylases. 4-PBA had no effect on ENaC expression in airway epithelial cells indicating tissue-specific effect. We conclude that butyrate plays an important role in regulating colonic Na(+) absorption by increasing ENaC transcription and activity.

WAVE binds Ena/VASP for enhanced Arp2/3 complex–based actin assembly

PubMed Central

Havrylenko, Svitlana; Noguera, Philippe; Abou-Ghali, Majdouline; Manzi, John; Faqir, Fahima; Lamora, Audrey; Guérin, Christophe; Blanchoin, Laurent; Plastino, Julie

2015-01-01

The WAVE complex is the main activator of the Arp2/3 complex for actin filament nucleation and assembly in the lamellipodia of moving cells. Other important players in lamellipodial protrusion are Ena/VASP proteins, which enhance actin filament elongation. Here we examine the molecular coordination between the nucleating activity of the Arp2/3 complex and the elongating activity of Ena/VASP proteins for the formation of actin networks. Using an in vitro bead motility assay, we show that WAVE directly binds VASP, resulting in an increase in Arp2/3 complex–based actin assembly. We show that this interaction is important in vivo as well, for the formation of lamellipodia during the ventral enclosure event of Caenorhabditis elegans embryogenesis. Ena/VASP's ability to bind F-actin and profilin-complexed G-actin are important for its effect, whereas Ena/VASP tetramerization is not necessary. Our data are consistent with the idea that binding of Ena/VASP to WAVE potentiates Arp2/3 complex activity and lamellipodial actin assembly. PMID:25355952

Mechanism of action of novel lung edema therapeutic AP301 by activation of the epithelial sodium channel.

PubMed

Shabbir, Waheed; Scherbaum-Hazemi, Parastoo; Tzotzos, Susan; Fischer, Bernhard; Fischer, Hendrik; Pietschmann, Helmut; Lucas, Rudolf; Lemmens-Gruber, Rosa

2013-12-01

AP301 [Cyclo(CGQRETPEGAEAKPWYC)], a cyclic peptide comprising the human tumor necrosis factor lectin-like domain (TIP domain) sequence, is currently being developed as a treatment for lung edema and has been shown to reduce extravascular lung water and improve lung function in mouse, rat, and pig models. The current paradigm for liquid homeostasis in the adult mammalian lung is that passive apical uptake of sodium via the amiloride-sensitive epithelial Na⁺ channel (ENaC) and nonselective cyclic-nucleotide-gated cation channels creates the major driving force for reabsorption of water through the alveolar epithelium in addition to other ion channels such as potassium and chloride channels. AP301 can increase amiloride-sensitive current in A549 cells as well as in freshly isolated type II alveolar epithelial cells from different species. ENaC is expressed endogenously in all of these cell types. Consequently, this study was undertaken to determine whether ENaC is the specific target of AP301. The effect of AP301 in A549 cells as well as in human embryonic kidney cells and Chinese hamster ovary cells heterologously expressing human ENaC subunits (α, β, γ, and δ) was measured in patch clamp experiments. The congener TIP peptide AP318 [Cyclo(4-aminobutanoic acid-GQRETPEGAEAKPWYD)] activated ENaC by increasing single-channel open probability. AP301 increased current in proteolytically activated (cleaved) but not near-silent (uncleaved) ENaC in a reversible manner. αβγ- or δβγ-ENaC coexpression was required for maximal activity. No increase in current was observed after deglycosylation of extracellular domains of ENaC. Thus, our data suggest that the specific interaction of AP301 with both endogenously and heterologously expressed ENaC requires precedent binding to glycosylated extracellular loop(s).

Scaffold Protein Connector Enhancer of Kinase Suppressor of Ras Isoform 3 (CNK3) Coordinates Assembly of a Multiprotein Epithelial Sodium Channel (ENaC)-regulatory Complex*

PubMed Central

Soundararajan, Rama; Ziera, Tim; Koo, Eric; Ling, Karen; Wang, Jian; Borden, Steffen A.; Pearce, David

2012-01-01

Hormone regulation of ion transport in the kidney tubules is essential for fluid and electrolyte homeostasis in vertebrates. A large body of evidence has suggested that transporters and channels exist in multiprotein regulatory complexes; however, relatively little is known about the composition of these complexes or their assembly. The epithelial sodium channel (ENaC) in particular is tightly regulated by the salt-regulatory hormone aldosterone, which acts at least in part by increasing expression of the serine-threonine kinase SGK1. Here we show that aldosterone induces the formation of a 1.0–1.2-MDa plasma membrane complex, which includes ENaC, SGK1, and the ENaC inhibitor Nedd4-2, a key target of SGK1. We further show that this complex contains the PDZ domain-containing protein connector enhancer of kinase suppressor of Ras isoform 3 (CNK3). CNK3 physically interacts with ENaC, Nedd4-2, and SGK1; enhances the interactions among them; and stimulates ENaC function in a PDZ domain-dependent, aldosterone-induced manner. These results strongly suggest that CNK3 is a molecular scaffold, which coordinates the assembly of a multiprotein ENaC-regulatory complex and hence plays a central role in Na+ homeostasis. PMID:22851176

H2O2 Regulates Lung Epithelial Sodium Channel (ENaC) via Ubiquitin-like Protein Nedd8

PubMed Central

Downs, Charles A.; Kumar, Amrita; Kreiner, Lisa H.; Johnson, Nicholle M.; Helms, My N.

2013-01-01

Redundancies in both the ubiquitin and epithelial sodium transport pathways allude to their importance of proteolytic degradation and ion transport in maintaining normal cell function. The classical pathway implicated in ubiquitination of the epithelial sodium channel (ENaC) involves Nedd4-2 regulation of sodium channel subunit expression and has been studied extensively studied. However, less attention has been given to the role of the ubiquitin-like protein Nedd8. Here we show that Nedd8 plays an important role in the ubiquitination of ENaC in alveolar epithelial cells. We report that the Nedd8 pathway is redox-sensitive and that under oxidizing conditions Nedd8 conjugation to Cullin-1 is attenuated, resulting in greater surface expression of α-ENaC. This observation was confirmed in our electrophysiology studies in which we inhibited Nedd8-activating enzyme using MLN4924 (a specific Nedd8-activating enzyme inhibitor) and observed a marked increase in ENaC activity (measured as the product of the number of channels (N) and the open probability (Po) of a channel). These results suggest that ubiquitination of lung ENaC is redox-sensitive and may have significant implications for our understanding of the role of ENaC in pulmonary conditions where oxidative stress occurs, such as pulmonary edema and acute lung injury. PMID:23362276

Plasma surrounding the global heliosphere at large distances controlled by the solar cycle

NASA Astrophysics Data System (ADS)

Dialynas, Konstantinos; Krimigis, Stamatios; Mitchell, Donald; Decker, Robert; Roelof, Edmond

2016-04-01

The past decade can be characterized by a series of key, groundbreaking remote energetic neutral atom (ENA) images (INCA, IBEX) and in-situ ion (Voyager 1 & 2) observations concerning the characteristics and interactions of the heliosphere with the Local Interstellar Medium (LISM). Voyagers 1 and 2 (V1, V2) discovered the reservoir of ions and electrons that constitute the heliosheath (HS) after crossing the termination shock (TS) 35deg north and 32deg south of the ecliptic plane at 94 and 84 astronomical units (1 AU= 1.5 x108 km), respectively. The in situ measurements by each Voyager were placed in a global context by remote sensing images using ENA obtained with the Ion and Neutral Camera (INCA) onboard Cassini orbiting Saturn. The ENA images contain a 5.2-55 keV hydrogen (H) ENA region (Belt) that loops through the celestial sphere and contributes to balancing the pressure of the interstellar magnetic field (ISMF). The success of any future mission with dedicated ENA detectors (e.g. the IMAP mission), highly depends on the antecedent understanding of the details of the plasma processes in the Heliosphere as revealed by remote sensing of the plasma environment characteristics. Therefore, we address here one of the remaining and most important questions: "Where do the 5-55 keV ENAs that INCA measures come from?". We analyzed INCA all-sky maps from 2003 to 2015 and compare the solar cycle (SC) variation of the ENAs in both the nose (upstream) and anti-nose (downstream) directions with the intensities of > 30 keV ions (source of ENA through charge exchange-CE with H) measured in-situ by V1 and V2, in overlapping energy bands ~30-55 keV. ENA intensities decrease during the declining phase of SC23 by ~x3 from 2003 to 2011 but recover through 2014 (SC24); similarly, V1 and V2 ion intensities also decrease and then recover through 2014. The similarity of time profiles of remotely sensed ENA and locally measured ions are consistent with (a) ENA originating in the HS, and (b) the global HS responding promptly (within ~1-1.5 years) to outward-propagating solar wind changes throughout the SC. Further, recovery of the Belt during SC24 precedes asymmetrically from south to north in the general direction of the nose. This may be related to the non-symmetric evolution of solar coronal holes during SC recovery.

Hypotonic stress upregulates β- and γ-ENaC expression through suppression of ERK by inducing MKP-1

PubMed Central

Niisato, Naomi; Ohta, Mariko; Eaton, Douglas C.

2012-01-01

We investigated a physiological role for ERK, a member of the MAPK family, in the hypotonic stimulation of epithelial Na+ channel (ENaC)-mediated Na+ reabsorption in renal epithelial A6 cells. We show that hypotonic stress causes a major dephosphorylation of ERK following a rapid transient phosphorylation. PD98059 (a MEK inhibitor) increases dephosphorylated ERK and enhances the hypotonic-stress-stimulated Na+ reabsorption. ERK dephosphorylation is mediated by MAPK phosphatase (MKP). Hypotonic stress activates p38, which in turn induces MKP-1 and to a lesser extent MKP-3 mRNA expression. Inhibition of p38 suppresses MKP-1 induction, preventing hypotonic stress from dephosphorylating ERK. Inhibition of MKP-1 and -3 by the inhibitor NSC95397 also suppresses the hypotonicity-induced dephosphorylation of ERK. NSC95397 reduces both β- and γ-ENaC mRNA expression and ENaC-mediated Na+ reabsorption stimulated by hypotonic stress. In contrast, pretreatment with PD98059 significantly enhances mRNA and protein expression of β- and γ-ENaC even under isotonic conditions. However, PD98059 only stimulates Na+ reabsorption in response to hypotonic stress, suggesting that ERK inactivation by itself (i.e., under isotonic conditions) is not sufficient to stimulate Na+ reabsorption, even though ERK inactivation enhances β- and γ-ENaC expression. Based on these results, we conclude that hypotonic stress stimulates Na+ reabsorption through at least two signaling pathways: 1) induction of MKP-1 that suppresses ERK activity and induces β- and γ-ENaC expression, and 2) promotion of translocation of the newly synthesized ENaC to the apical membrane. PMID:22573375

NVP-QBE170: an inhaled blocker of the epithelial sodium channel with a reduced potential to induce hyperkalaemia

PubMed Central

Coote, K J; Paisley, D; Czarnecki, S; Tweed, M; Watson, H; Young, A; Sugar, R; Vyas, M; Smith, N J; Baettig, U; Groot-Kormelink, P J; Gosling, M; Lock, R; Ethell, B; Williams, G; Schumacher, A; Harris, J; Abraham, W M; Sabater, J; Poll, C T; Faller, T; Collingwood, S P; Danahay, H

2015-01-01

Background and Purpose Inhaled amiloride, a blocker of the epithelial sodium channel (ENaC), enhances mucociliary clearance (MCC) in cystic fibrosis (CF) patients. However, the dose of amiloride is limited by the mechanism-based side effect of hyperkalaemia resulting from renal ENaC blockade. Inhaled ENaC blockers with a reduced potential to induce hyperkalaemia provide a therapeutic strategy to improve mucosal hydration and MCC in the lungs of CF patients. The present study describes the preclinical profile of a novel ENaC blocker, NVP-QBE170, designed for inhaled delivery, with a reduced potential to induce hyperkalaemia. Experimental Approach The in vitro potency and duration of action of NVP-QBE170 were compared with amiloride and a newer ENaC blocker, P552-02, in primary human bronchial epithelial cells (HBECs) by short-circuit current. In vivo efficacy and safety were assessed in guinea pig (tracheal potential difference/hyperkalaemia), rat (hyperkalaemia) and sheep (MCC). Key Results In vitro, NVP-QBE170 potently inhibited ENaC function in HBEC and showed a longer duration of action to comparator molecules. In vivo, intratracheal (i.t.) instillation of NVP-QBE170 attenuated ENaC activity in the guinea pig airways with greater potency and duration of action than that of amiloride without inducing hyperkalaemia in either guinea pig or rat. Dry powder inhalation of NVP-QBE170 by conscious sheep increased MCC and was better than inhaled hypertonic saline in terms of efficacy and duration of action. Conclusions and Implications NVP-QBE170 highlights the potential for inhaled ENaC blockers to exhibit efficacy in the airways with a reduced risk of hyperkalaemia, relative to existing compounds. PMID:25573195

NVP-QBE170: an inhaled blocker of the epithelial sodium channel with a reduced potential to induce hyperkalaemia.

PubMed

Coote, K J; Paisley, D; Czarnecki, S; Tweed, M; Watson, H; Young, A; Sugar, R; Vyas, M; Smith, N J; Baettig, U; Groot-Kormelink, P J; Gosling, M; Lock, R; Ethell, B; Williams, G; Schumacher, A; Harris, J; Abraham, W M; Sabater, J; Poll, C T; Faller, T; Collingwood, S P; Danahay, H

2015-06-01

Inhaled amiloride, a blocker of the epithelial sodium channel (ENaC), enhances mucociliary clearance (MCC) in cystic fibrosis (CF) patients. However, the dose of amiloride is limited by the mechanism-based side effect of hyperkalaemia resulting from renal ENaC blockade. Inhaled ENaC blockers with a reduced potential to induce hyperkalaemia provide a therapeutic strategy to improve mucosal hydration and MCC in the lungs of CF patients. The present study describes the preclinical profile of a novel ENaC blocker, NVP-QBE170, designed for inhaled delivery, with a reduced potential to induce hyperkalaemia. The in vitro potency and duration of action of NVP-QBE170 were compared with amiloride and a newer ENaC blocker, P552-02, in primary human bronchial epithelial cells (HBECs) by short-circuit current. In vivo efficacy and safety were assessed in guinea pig (tracheal potential difference/hyperkalaemia), rat (hyperkalaemia) and sheep (MCC). In vitro, NVP-QBE170 potently inhibited ENaC function in HBEC and showed a longer duration of action to comparator molecules. In vivo, intratracheal (i.t.) instillation of NVP-QBE170 attenuated ENaC activity in the guinea pig airways with greater potency and duration of action than that of amiloride without inducing hyperkalaemia in either guinea pig or rat. Dry powder inhalation of NVP-QBE170 by conscious sheep increased MCC and was better than inhaled hypertonic saline in terms of efficacy and duration of action. NVP-QBE170 highlights the potential for inhaled ENaC blockers to exhibit efficacy in the airways with a reduced risk of hyperkalaemia, relative to existing compounds. © 2015 The British Pharmacological Society.

Kinetics of degradation of enalapril maleate in dosage forms.

PubMed

Stanisz, Beata

2004-01-01

The effect of humidity and temperature on the stability of enalapril maleate (ENA) in tablets have been studied. Tablets with ENA were stored in final packs (blisters) and without final packs in the atmosphere of increased humidity (76.4 % RH) and in the temperature range from 313 K to 333 K (forced degradation test). Degradation of ENA in tablets stored in final packs and without final packs followed the first order reaction model. During this study, the product of hydrolysis of the ester group and intramolecular cyclization have been observed. Thermodynamic parameters (activation energies, enthalpy and entropy) for the decomposition of ENA in tablets were calculated.

Charge Exchange Contribution to the Decay of the Ring Current, Measured by Energetic Neutral Atoms (ENAs)

NASA Technical Reports Server (NTRS)

Jorgensen, A. M.; Henderson, M. G.; Roelof, E. C.; Reeves, G. D.; Spence, H. E.

2001-01-01

In this paper we calculate the contribution of charge exchange to the decay of the ring current. Past works have suggested that charge exchange of ring current protons is primarily responsible for the decay of the ring current during the late recovery phase, but there is still much debate about the fast decay of the early recovery phase. We use energetic neutral atom (ENA) measurements from Polar to calculate the total ENA energy escape. To get the total ENA escape we apply a forward modeling technique, and to estimate the total ring current energy escape we use the Dessler-Parker-Sckopke relationship. We find that during the late recovery phase of the March 10, 1998 storm ENAs with energies greater than 17.5 keV can account for 75% of the estimated energy loss from the ring current. During the fast recovery the measured ENAs can only account for a small portion of the total energy loss. We also find that the lifetime of the trapped ions is significantly shorter during the fast recovery phase than during the late recovery phase, suggesting that different processes are operating during the two phases.

Novel small molecule epithelial sodium channel inhibitors as potential therapeutics in cystic fibrosis - a patent evaluation.

PubMed

Schoenberger, Matthias; Althaus, Mike

2013-10-01

Novel molecular platforms for epithelial sodium channel (ENaC) modulators are claimed in the following six patents: WO2012035158(A1); WO2009074575(A2); WO2011028740(A1); WO2009150137(A2); WO2011079087(A1); WO2008135557(A1). These ENaC inhibitors may be used in blocking transepithelial sodium and consequently water absorption across airway epithelia. This may result in airway rehydration and enhanced mucociliary clearance in patients with cystic fibrosis (CF) lung disease. All inhibitors resemble the classical ENaC blocker amiloride but follow different strategies to increase structural diversity in a sterically tolerant region. These substitutions can be modified to i) enhance potency of ENaC inhibition; ii) reduce epithelial permeability; and iii) broaden applicability in order to be used as potential drugs for CF therapy. Most of the claims and patent data are supported by the currently available literature. The patents deliver a solid chemical basis for a variety of chemical modifications of the ENaC inhibitor amiloride. These modifications may result in the development of a novel, applicable ENaC inhibitors which may have lasting effects on diseased airways and may achieve airway rehydration and enhanced mucociliary clearance in CF lung disease.

Single-channel analysis of functional epithelial sodium channel (ENaC) stability at the apical membrane of A6 distal kidney cells

PubMed Central

Yu, Ling; Helms, My N.; Yue, Qiang; Eaton, Douglas C.

2008-01-01

Epithelial sodium channels (ENaC) play an essential role in maintaining total body fluid and electrolyte homeostasis. As such, abnormal expression of ENaC at the cell surface is linked to several important human diseases. Although the stability of ENaC subunits has been extensively studied by protein biochemical analysis, the half-life of the functional channel in the apical membrane remains controversial. Because the functional stability of the multisubunit channel may be more physiologically relevant than the stability of individual subunit proteins, we performed studies of functional ENaC channels using A6 epithelial cells, a Xenopus laevis distal nephron cell line. We recorded single-channel activity in over 400 cells with the translation blockers cycloheximide (CHX) or puromycin, as well as the intracellular protein trafficking inhibitors brefeldin A (BFA) or nocodazole. Our cell-attached, single-channel recordings allow us to quantify the channel density in the apical membrane, as well as to determine channel open probability (Po) from control (untreated) cells and from cells at different times of drug treatment. The data suggest that the half-life of ENaC channels is ∼3.5 h following puromycin, BFA, and nocodazole treatment. Furthermore, these three drugs had no significant effect on the Po of ENaC for at least 6 h after exposure. A decrease in apical channel number and Po was observed following 2 h of CHX inhibition of protein synthesis, and the apparent channel half-life was closer to 1.5 h following CHX treatment. Treatment of cells with the translation inhibitors does not alter the expression of the protease furin, and therefore changes in protease activity cannot explain changes in ENaC Po. Confocal images show that BFA and nocodazole both disrupt most of the Golgi apparatus after 1-h exposure. In cells with the Golgi totally disrupted by overnight exposure to BFA, 20% of apical ENaC channels remained functional. This result suggests that ENaC is delivered to the apical membrane via a pathway that might bypass the Golgi vesicular trafficking pathway, or that there might be two pools of channels with markedly different half-lives in the apical membrane. PMID:18784262

Single-channel analysis of functional epithelial sodium channel (ENaC) stability at the apical membrane of A6 distal kidney cells.

PubMed

Yu, Ling; Helms, My N; Yue, Qiang; Eaton, Douglas C

2008-11-01

Epithelial sodium channels (ENaC) play an essential role in maintaining total body fluid and electrolyte homeostasis. As such, abnormal expression of ENaC at the cell surface is linked to several important human diseases. Although the stability of ENaC subunits has been extensively studied by protein biochemical analysis, the half-life of the functional channel in the apical membrane remains controversial. Because the functional stability of the multisubunit channel may be more physiologically relevant than the stability of individual subunit proteins, we performed studies of functional ENaC channels using A6 epithelial cells, a Xenopus laevis distal nephron cell line. We recorded single-channel activity in over 400 cells with the translation blockers cycloheximide (CHX) or puromycin, as well as the intracellular protein trafficking inhibitors brefeldin A (BFA) or nocodazole. Our cell-attached, single-channel recordings allow us to quantify the channel density in the apical membrane, as well as to determine channel open probability (Po) from control (untreated) cells and from cells at different times of drug treatment. The data suggest that the half-life of ENaC channels is approximately 3.5 h following puromycin, BFA, and nocodazole treatment. Furthermore, these three drugs had no significant effect on the Po of ENaC for at least 6 h after exposure. A decrease in apical channel number and Po was observed following 2 h of CHX inhibition of protein synthesis, and the apparent channel half-life was closer to 1.5 h following CHX treatment. Treatment of cells with the translation inhibitors does not alter the expression of the protease furin, and therefore changes in protease activity cannot explain changes in ENaC Po. Confocal images show that BFA and nocodazole both disrupt most of the Golgi apparatus after 1-h exposure. In cells with the Golgi totally disrupted by overnight exposure to BFA, 20% of apical ENaC channels remained functional. This result suggests that ENaC is delivered to the apical membrane via a pathway that might bypass the Golgi vesicular trafficking pathway, or that there might be two pools of channels with markedly different half-lives in the apical membrane.

Low Altitude Emission (LAE) of Energetic Neutral Atoms (ENA) Observed by TWINS and its Relation to the CINEMA CubeSat Mission

NASA Astrophysics Data System (ADS)

Bazell, D.; Sotirelis, T.; Nair, H.; Roelof, E. C.; Brandt, P. C.

2009-12-01

The brightest source of energetic neutral atoms (ENAs) at energies >1keV is low altitude emission (LAE) from ~200-400km near auroral latitudes where precipitating energetic ions undergo multiple atomic collisions with the monatomic (O) exosphere. This emission is many times brighter than that from the high-altitude ring current region where the energetic ions interact only weakly with the much less dense monatomic (H) hydrogen geocorona. The recently selected NSF CubeSat mission CINEMA [Lin et al., this special session] has, as part of its science payload (STEIN), an ENA imager covering energies 4-100keV. From a high-inclination ~800km orbit, STEIN will view the LAE four times during every 90 minutes. The NASA TWINS stereo ENA imagers (2-40keV) will also view the LAE from their Molniya orbits (apogee radius~7Re). We have been analyzing the TWINS ENA images of LAE and comparing them with in situ ion measurements (1-40keV) from DMSP spacecraft when their tracks take them under the ion precipitation regions imaged by TWINS. We have developed an ENA emissivity function that relates the directionally-dependent emergent ENA spectrum to that of the precipitating ions. The TWINS/DMSP direct comparisons show good agreement. We offer suggestions on joint observing strategies for CINEMA, TWINS and DMSP after the CINEMA launch in the second half of 2011.

Evans Blue is not a suitable inhibitor of the epithelial sodium channel δ-subunit.

PubMed

Perniss, Alexander; Wolf, Annemarie; Wichmann, Lukas; Schönberger, Matthias; Althaus, Mike

2015-10-23

The Epithelial Sodium Channel (ENaC) is a heterotrimeric ion channel which can be either formed by assembly of its α-, β- and γ-subunits or, alternatively, its δ-, β- and γ-subunits. The physiological function of αβγ-ENaC is well established, but the function of δβγ-ENaC remains elusive. The azo-dye Evans Blue (EvB) has been routinely used to discriminate between the two channel isoforms by decreasing transmembrane currents and amiloride-sensitive current fractions of δβγ-ENaC expressing Xenopus oocytes. Even though these results could be reproduced, it was found by precipitation experiments and spectroscopic methods that the cationic amiloride and the anionic EvB directly interact in solution, forming a strong complex. Thereby a large amount of pharmacologically available amiloride is removed from physiological buffer solutions and the effective amiloride concentration is reduced. This interaction did not occur in the presence of albumin. In microelectrode recordings, EvB was able to abrogate the block of δβγ-ENaC by amiloride or its derivative benzamil. In sum, EvB reduces amiloride-sensitive ion current fractions in electrophysiological experiments. This is not a result of a specific inhibition of δβγ-ENaC but rather represents a pharmacological artefact. EvB should therefore not be used as an inhibitor of δ-ENaC. Copyright © 2015 Elsevier Inc. All rights reserved.

THE IBEX RIBBON AND THE PICKUP ION RING STABILITY IN THE OUTER HELIOSHEATH. II. MONTE-CARLO AND PARTICLE-IN-CELL MODEL RESULTS

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

Niemiec, J.; Florinski, V.; Heerikhuisen, J.

2016-08-01

The nearly circular ribbon of energetic neutral atom (ENA) emission discovered by NASA’s Interplanetary Boundary EXplorer satellite ( IBEX ), is most commonly attributed to the effect of charge exchange of secondary pickup ions (PUIs) gyrating about the magnetic field in the outer heliosheath (OHS) and the interstellar space beyond. The first paper in the series (Paper I) presented a theoretical analysis of the pickup process in the OHS and hybrid-kinetic simulations, revealing that the kinetic properties of freshly injected proton rings depend sensitively on the details of their velocity distribution. It was demonstrated that only rings that are notmore » too narrow (parallel thermal spread above a few km s{sup −1}) and not too wide (parallel temperature smaller than the core plasma temperature) could remain stable for a period of time long enough to generate ribbon ENAs. This paper investigates the role of electron dynamics and the extra spatial degree of freedom in the ring ion scattering process with the help of two-dimensional full particle-in-cell (PIC) kinetic simulations. A good agreement is observed between ring evolution under unstable conditions in hybrid and PIC models, and the dominant modes are found to propagate parallel to the magnetic field. We also present more realistic ribbon PUI distributions generated using Monte Carlo simulations of atomic hydrogen in the global heliosphere and examine the effect of both the cold ring-like and the hot “halo” PUIs produced from heliosheath ENAs on the ring stability. It is shown that the second PUI population enhances the fluctuation growth rate, leading to faster isotropization of the solar-wind-derived ring ions.« less

The IBEX Ribbon and the Pickup Ion Ring Stability in the Outer Heliosheath II. Monte-Carlo and Particle-in-cell Model Results

NASA Astrophysics Data System (ADS)

Niemiec, J.; Florinski, V.; Heerikhuisen, J.; Nishikawa, K.-I.

2016-08-01

The nearly circular ribbon of energetic neutral atom (ENA) emission discovered by NASA’s Interplanetary Boundary EXplorer satellite (IBEX), is most commonly attributed to the effect of charge exchange of secondary pickup ions (PUIs) gyrating about the magnetic field in the outer heliosheath (OHS) and the interstellar space beyond. The first paper in the series (Paper I) presented a theoretical analysis of the pickup process in the OHS and hybrid-kinetic simulations, revealing that the kinetic properties of freshly injected proton rings depend sensitively on the details of their velocity distribution. It was demonstrated that only rings that are not too narrow (parallel thermal spread above a few km s-1) and not too wide (parallel temperature smaller than the core plasma temperature) could remain stable for a period of time long enough to generate ribbon ENAs. This paper investigates the role of electron dynamics and the extra spatial degree of freedom in the ring ion scattering process with the help of two-dimensional full particle-in-cell (PIC) kinetic simulations. A good agreement is observed between ring evolution under unstable conditions in hybrid and PIC models, and the dominant modes are found to propagate parallel to the magnetic field. We also present more realistic ribbon PUI distributions generated using Monte Carlo simulations of atomic hydrogen in the global heliosphere and examine the effect of both the cold ring-like and the hot “halo” PUIs produced from heliosheath ENAs on the ring stability. It is shown that the second PUI population enhances the fluctuation growth rate, leading to faster isotropization of the solar-wind-derived ring ions.

Characterization of a novel splice variant of δ ENaC subunit in human lungs

PubMed Central

Zhao, Run-Zhen; Nie, Hong-Guang; Su, Xue-Feng; Han, Dong-Yun; Lee, Andrew; Huang, Yao; Chang, Yongchang; Matalon, Sadis

2012-01-01

Salt absorption via apical epithelial sodium channels (ENaC) is a critical rate-limiting process in maintaining airway and lung lining fluid at the physiological level. δ ENaC (termed δ1 in this article) has been detected in human lung epithelial cells in addition to α, β, and γ subunits (Ji HL, Su XF, Kedar S, Li J, Barbry P, Smith PR, Matalon S, Benos DJ. J Biol Chem 281: 8233–8241, 2006; Nie HG, Chen L, Han DY, Li J, Song WF, Wei SP, Fang XH, Gu X, Matalon S, Ji HL, J Physiol 587: 2663–2676, 2009) and may contribute to the differences in the biophysical properties of amiloride-inhibitable cation channels in pulmonary epithelial cells. Here we cloned a splicing variant of the δ1 ENaC, namely, δ2 ENaC in human bronchoalveolar epithelial cells (16HBEo). δ2 ENaC possesses 66 extra amino acids attached to the distal amino terminal tail of the δ1 ENaC. δ2 ENaC was expressed in both alveolar type I and II cells of human lungs as revealed by in situ hybridization and real-time RT-PCR. To characterize the biophysical and pharmacological features of the splicing variant, we injected Xenopus oocytes with human ENaC cRNAs and measured whole cell and single channel currents of δ1βγ, δ2βγ, and αβγ channels. Oocytes injected with δ2βγ cRNAs exhibited whole cell currents significantly greater than those expressing δ1βγ and αβγ channels. Single channel activity, unitary conductance, and open probability of δ2βγ channels were significantly greater compared with δ1βγ and αβγ channels. In addition, δ2βγ and δ1βγ channels displayed significant differences in apparent Na+ affinity, dissociation constant for amiloride (Kiamil), the EC50 for capsazepine activation, and gating kinetics by protons. Channels comprising of this novel splice variant may contribute to the diversities of native epithelial Na+ channels. PMID:22505667

ENaC/DEG in Tumor Development and Progression

PubMed Central

Liu, Cui; Zhu, Li-Li; Xu, Si-Guang; Ji, Hong-Long; Li, Xiu-Min

2016-01-01

The epithelial Na+ channel/degenerin (ENaC/DEG) superfamily, including the acid-sensing ion channels (ASICs), is characterized by a high degree of similarity in structure but highly diverse in physiological functions. These ion channels have been shown to be important in several physiological functions of normal epithelial cells, including salt homeostasis, fluid transportation and cell mobility. There is increasing evidence suggesting that ENaC/DEG channels are critically engaged in cancer cell biology, such as proliferation, migration, invasion and apoptosis, playing a role in tumor development and progression. In this review, we will discuss recent studies showing the role of ENaC and ASIC channels in epithelial cells and its relationship to the oncogenesis. PMID:27698929

Reconstructing Ion Spectra from Low-Altitude ENAs: Moderate to Large Storms.

NASA Astrophysics Data System (ADS)

LLera, K.; Goldstein, J.; McComas, D. J.; Valek, P. W.

2015-12-01

Two Wide-angle Imaging Neutral-atom Spectrometers (TWINS) Energetic neutral atom (ENA) imagers regularly observe Low-altitude Emission (LAE) intensifications during geomagnetic storm intervals. Since LAEs are produced by the interaction between ions and the near-Earth exosphere (altitudes ~200-800 km), they are a global signature of how the ring current decays in response to solar wind conditions. In this "optically thick" region, an ENA readily becomes reionized, and an ion is readily neutralized. Therefore, emerging ENAs that contribute to the LAE signal (detectable several RE away) have undergone multiple charge exchange and electron stripping interactions. Accounting for the ~36 eV energy loss per interaction, we developed a model to quantify the total energy lost by emergent LAEs. The analytical tool is applied to an ensemble of moderate to large storms (including the recent 17 March and 23 June storms in 2015) to reconstruct the parent ion spectra from TWINS ENA images. We examine the ion spectra energy characteristics among the various storm events.

Caffeine intake antagonizes salt sensitive hypertension through improvement of renal sodium handling

PubMed Central

Yu, Hao; Yang, Tao; Gao, Peng; Wei, Xing; Zhang, Hexuan; Xiong, Shiqiang; Lu, Zongshi; Li, Li; Wei, Xiao; Chen, Jing; Zhao, Yu; Arendshorst, William J.; Shang, Qianhui; Liu, Daoyan; Zhu, Zhiming

2016-01-01

High salt intake is a major risk factor for hypertension. Although acute caffeine intake produces moderate diuresis and natriuresis, caffeine increases the blood pressure (BP) through activating sympathetic activity. However, the long-term effects of caffeine on urinary sodium excretion and blood pressure are rarely investigated. Here, we investigated whether chronic caffeine administration antagonizes salt sensitive hypertension by promoting urinary sodium excretion. Dahl salt-sensitive (Dahl-S) rats were fed with high salt diet with or without 0.1% caffeine in drinking water for 15 days. The BP, heart rate and locomotor activity of rats was analyzed and urinary sodium excretion was determined. The renal epithelial Na+ channel (ENaC) expression and function were measured by in vivo and in vitro experiments. Chronic consumption of caffeine attenuates hypertension induced by high salt without affecting sympathetic nerve activity in Dahl-S rats. The renal α-ENaC expression and ENaC activity of rats decreased after chronic caffeine administration. Caffeine increased phosphorylation of AMPK and decrease α-ENaC expression in cortical collecting duct cells. Inhibiting AMPK abolished the effect of caffeine on α-ENaC. Chronic caffeine intake prevented the development of salt-sensitive hypertension through promoting urinary sodium excretion, which was associated with activation of renal AMPK and inhibition of renal tubular ENaC. PMID:27173481

βENaC is a molecular component of a VSMC mechanotransducer that contributes to renal blood flow regulation, protection from renal injury, and hypertension.

PubMed

Drummond, Heather A

2012-01-01

Pressure-induced constriction (also known as the "myogenic response") is an important mechano-dependent response in certain blood vessels. The response is mediated by vascular smooth muscle cells (VSMCs) and characterized by a pressure-induced vasoconstriction in small arteries and arterioles in the cerebral, mesenteric, cardiac, and renal beds. The myogenic response has two important roles; it is a mechanism of blood flow autoregulation and provides protection against systemic blood pressure-induced damage to delicate microvessels. However, the molecular mechanism(s) underlying initiation of myogenic response is unclear. Degenerin proteins have a strong evolutionary link to mechanotransduction in the nematode. Our laboratory has addressed the hypothesis that these proteins may also act as mechanosensors in certain mammalian tissues such as VSMCs and arterial baroreceptor neurons. This article discusses the importance of a specific degenerin protein, β Epithelial Na(+) Channel (βENaC) in pressure-induced vasoconstriction in renal vessels and arterial baroreflex function as determined in a mouse model of reduced βENaC (βENaC m/m). We propose that loss of baroreflex sensitivity (due to loss of baroreceptor βENaC) increases blood pressure variability, increasing the likelihood and magnitude of upward swings in systemic pressure. Furthermore, loss of the myogenic constrictor response (due to loss of VSMC βENaC) will permit those pressure swings to be transmitted to the microvasculature in βENaC m/m mice, thus increasing the susceptibility to renal injury and hypertension.

RNA-seq Analysis Reveals Unique Transcriptome Signatures in Systemic Lupus Erythematosus Patients with Distinct Autoantibody Specificities

PubMed Central

Rai, Richa; Chauhan, Sudhir Kumar; Singh, Vikas Vikram; Rai, Madhukar; Rai, Geeta

2016-01-01

Systemic lupus erythematosus (SLE) patients exhibit immense heterogeneity which is challenging from the diagnostic perspective. Emerging high throughput sequencing technologies have been proved to be a useful platform to understand the complex and dynamic disease processes. SLE patients categorised based on autoantibody specificities are reported to have differential immuno-regulatory mechanisms. Therefore, we performed RNA-seq analysis to identify transcriptomics of SLE patients with distinguished autoantibody specificities. The SLE patients were segregated into three subsets based on the type of autoantibodies present in their sera (anti-dsDNA+ group with anti-dsDNA autoantibody alone; anti-ENA+ group having autoantibodies against extractable nuclear antigens (ENA) only, and anti-dsDNA+ENA+ group having autoantibodies to both dsDNA and ENA). Global transcriptome profiling for each SLE patients subsets was performed using Illumina® Hiseq-2000 platform. The biological relevance of dysregulated transcripts in each SLE subsets was assessed by ingenuity pathway analysis (IPA) software. We observed that dysregulation in the transcriptome expression pattern was clearly distinct in each SLE patients subsets. IPA analysis of transcripts uniquely expressed in different SLE groups revealed specific biological pathways to be affected in each SLE subsets. Multiple cytokine signaling pathways were specifically dysregulated in anti-dsDNA+ patients whereas Interferon signaling was predominantly dysregulated in anti-ENA+ patients. In anti-dsDNA+ENA+ patients regulation of actin based motility by Rho pathway was significantly affected. The granulocyte gene signature was a common feature to all SLE subsets; however, anti-dsDNA+ group showed relatively predominant expression of these genes. Dysregulation of Plasma cell related transcripts were higher in anti-dsDNA+ and anti-ENA+ patients as compared to anti-dsDNA+ ENA+. Association of specific canonical pathways with the uniquely expressed transcripts in each SLE subgroup indicates that specific immunological disease mechanisms are operative in distinct SLE patients’ subsets. This ‘sub-grouping’ approach could further be useful for clinical evaluation of SLE patients and devising targeted therapeutics. PMID:27835693

Gadolinium released by the linear gadolinium-based contrast-agent Gd-DTPA decreases the activity of human epithelial Na+ channels (ENaCs).

PubMed

Knoepp, Fenja; Bettmer, Joerg; Fronius, Martin

2017-05-01

Gadolinium-based-contrast-agents (GBCAs) are used for magnetic-resonance-imaging and associated with renal and cardiovascular adverse reactions caused by released Gd 3+ ions. Gd 3+ is also a modulator of mechano-gated ion channels, including the epithelial Na + channel (ENaC) that is expressed in kidney epithelium and the vasculature. ENaC is important for salt-/water homeostasis and blood pressure regulation and a likely target of released Gd 3+ from GBCAs causing the above-mentioned adverse reactions. Therefore this study examined the effect of Gd 3+ and GBCAs on ENaC's activity. Human αβγENaC was expressed in Xenopus laevis oocytes and exposed to Gd 3+ , linear (Gd-DTPA, Magnevist) or cyclic (Dotarem) GBCAs. Transmembrane ion-currents (I M ) were recorded by the two-electrode-voltage-clamp technique and Gd 3+ -release by Gd-DTPA was confirmed by inductively coupled plasma-mass spectrometry. Gd 3+ exerts biphasic effects on ENaC's activity: ≤0.3mmol/l decreased I M which was preventable by DEPC (modifies histidines). Strikingly Gd 3+ ≥0.4mmol/l increased I M and this effect was prevented by cysteine-modifying MTSEA. Linear Gd-DTPA and Magnevist mimicked the effect of ≤0.3mmol/l Gd 3+ , whereas the chelator DTPA showed no effect. Gd 3+ and Gd-DTPA increased the IC 50 for amiloride, but did not affect ENaC's self-inhibition. Interestingly, cyclic Gd-DOTA (Dotarem) increased I M to a similar extent as its chelator DOTA, suggesting that the chelator rather than released Gd 3+ is responsible for this effect. These results confirm Gd 3+ -release from linear Gd-DTPA and indicate that the released Gd 3+ amount is sufficient to interfere with ENaC's activity to provide putative explanations for GBCA-related adverse effects. Copyright © 2017 Elsevier B.V. All rights reserved.

Rab27a regulates epithelial sodium channel (ENaC) activity through synaptotagmin-like protein (SLP-5) and Munc13-4 effector mechanism

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

Saxena, Sunil K.; Horiuchi, Hisanori; Fukuda, Mitsunori

Liddle's syndrome (excessive absorption of sodium ions) and PHA-1 (pseudohypoaldosteronism type 1) with decreased sodium absorption are caused by the mutations in the amiloride-sensitive epithelial sodium channel ENaC. Rab proteins are small GTPases involved in vesicle transport, docking, and fusion. Earlier, we reported that Rab27a inhibits ENaC-mediated currents through protein-protein interaction in HT-29 cells. We hereby report that Rab27a-dependent inhibition is associated with the GTP/GDP status as constitutively active or GTPase-deficient mutant Q78L inhibits amiloride-sensitive currents whereas GDP-locked inactive mutant T23N showed no effect. In order to further explore the molecular mechanism of this regulation, we performed competitive assays withmore » two Rab27a-binding proteins: synaptotagmin-like protein (SLP-5) and Munc13-4 (a putative priming factor for exocytosis). Both proteins eliminate negative modulation of Rab27a on ENaC function. The SLP-5 reversal of Rab27a effect was restricted to C-terminal C2A/C2B domains assigned for putative phospholipids-binding function while the Rab27a-binding SHD motif imparted higher inhibition. The ENaC-mediated currents remain unaffected by Rab27a though SLP-5 appears to strongly bind it. The immunoprecipitation experiments suggest that in the presence of excessive Munc13-4 and SLP-5 proteins, Rab27a interaction with ENaC is diminished. Munc13-4 and SLP-5 limit the Rab27a availability to ENaC, thus minimizing its effect on channel function. These observations decisively prove that Rab27a inhibits ENaC function through a complex mechanism that involves GTP/GDP status, and protein-protein interactions involving Munc13-4 and SLP-5 effector proteins.« less

Observation and Interpretation of Energetic Neutral Hydrogen Atoms from the December 5, 2006 Solar Event

NASA Technical Reports Server (NTRS)

Mewaldt, R. A.; Leske, R. A.; Stone, E. C.; Barghouty, A. F.; Shih, A. Y.; von Rosenvinge, T. T.; Labrador, A. W.; Cohen, C. M. S.; Cummings, A. C.; Cummings, A. C.

2009-01-01

We report the first observations of energetic neutral atoms (ENAs) from a solar flare/coronal mass ejection event. The observations were made during the December 5, 2006 X9 solar flare, located at E79, by the Low Energy Telescopes (LETs) on the STEREO A and B spacecraft. Within 1-2 hours of the flare onset, both LETs observed a sudden burst of 1.6 to 15 MeV protons arriving hours before the onset of the main solar energetic particle (SEP) event at Earth. More than 70% of these particles arrived from a longitude within +-10 degrees of the Sun. The derived emission profile at the Sun lasted for more than an hour and had a profile remarkably similar to the GOES soft X-ray profile. The observed arrival directions and energy spectrum argue strongly that the particle events <5 MeV were due to energetic neutral hydrogen atoms that were stripped of their electrons upon entering the LET sensor. To our knowledge, this is the first reported observation of ENA emission from a solar flare/coronal mass ejection. We discuss possible origins for the production of ENAs in solar events, including charge-transfer reactions involving both flare and shock-accelerated protons. Assuming isotropic emission, we find that 2 x 10E28 ENAs escaped from the Sun in the upper hemisphere. Based on the 2.2 MeV gamma-ray emission observed by RHESSI in this event, and using measured and theoretical cross sections, we estimate that 3 x 10E31 ENAs with 1.8 - 5 MeV could be produced by protons accelerated in the flare. CME-driven shock acceleration is also a possible ENA source, but unfortunately there were no CME observations available from this event. Taking into account ENA losses, we conclude that the observed ENAs were most likely produced in the high corona at heliocentric distances 1.6 solar radii.

Regulation of ENaC and CFTR expression with K+ channel modulators and effect on fluid absorption across alveolar epithelial cells.

PubMed

Leroy, Claudie; Privé, Anik; Bourret, Jean-Charles; Berthiaume, Yves; Ferraro, Pasquale; Brochiero, Emmanuelle

2006-12-01

In a recent study (Leroy C, Dagenais A, Berthiaume Y, and Brochiero E. Am J Physiol Lung Cell Mol Physiol 286: L1027-L1037, 2004), we identified an ATP-sensitive K(+) (K(ATP)) channel in alveolar epithelial cells, formed by inwardly rectifying K(+) channel Kir6.1/sulfonylurea receptor (SUR)2B subunits. We found that short applications of K(ATP), voltage-dependent K(+) channel KvLQT1, and calcium-activated K(+) (K(Ca)) channel modulators modified Na(+) and Cl(-) currents in alveolar monolayers. In addition, it was shown previously that a K(ATP) opener increased alveolar liquid clearance in human lungs by a mechanism possibly related to epithelial sodium channels (ENaC). We therefore hypothesized that prolonged treatment with K(+) channel modulators could induce a sustained regulation of ENaC activity and/or expression. Alveolar monolayers were treated for 24 h with inhibitors of K(ATP), KvLQT1, and K(Ca) channels identified by PCR. Glibenclamide and clofilium (K(ATP) and KvLQT1 inhibitors) strongly reduced basal transepithelial current, amiloride-sensitive Na(+) current, and forskolin-activated Cl(-) currents, whereas pinacidil, a K(ATP) activator, increased them. Interestingly, K(+) inhibitors or membrane depolarization (induced by valinomycin in high-K(+) medium) decreased alpha-, beta-, and gamma-ENaC and CFTR mRNA. alpha-ENaC and CFTR proteins also declined after glibenclamide or clofilium treatment. Conversely, pinacidil augmented ENaC and CFTR mRNAs and proteins. Since alveolar fluid transport was found to be driven, at least in part, by Na(+) transport through ENaC, we tested the impact of K(+) channel modulators on fluid absorption across alveolar monolayers. We found that glibenclamide and clofilium reduced fluid absorption to a level similar to that seen in the presence of amiloride, whereas pinacidil slightly enhanced it. Long-term regulation of ENaC and CFTR expression by K(+) channel activity could benefit patients with pulmonary diseases affecting ion transport and fluid clearance.

Inhibition of Protease-Epithelial Sodium Channel Signaling Improves Mucociliary Function in Cystic Fibrosis Airways.

PubMed

Reihill, James A; Walker, Brian; Hamilton, Robert A; Ferguson, Timothy E G; Elborn, J Stuart; Stutts, M Jackson; Harvey, Brian J; Saint-Criq, Vinciane; Hendrick, Siobhan M; Martin, S Lorraine

2016-09-15

In cystic fibrosis (CF) a reduction in airway surface liquid (ASL) height compromises mucociliary clearance, favoring mucus plugging and chronic bacterial infection. Inhibitors of the epithelial sodium channel (ENaC) have therapeutic potential in CF airways to reduce hyperstimulated sodium and fluid absorption to levels that can restore airway hydration. To determine whether a novel compound (QUB-TL1) designed to inhibit protease/ENaC signaling in CF airways restores ASL volume and mucociliary function. Protease activity was measured using fluorogenic activity assays. Differentiated primary airway epithelial cell cultures (F508del homozygotes) were used to determined ENaC activity (Ussing chamber recordings), ASL height (confocal microscopy), and mucociliary function (by tracking the surface flow of apically applied microbeads). Cell toxicity was measured using a lactate dehydrogenase assay. QUB-TL1 inhibits extracellularly located channel activating proteases (CAPs), including prostasin, matriptase, and furin, the activities of which are observed at excessive levels at the apical surface of CF airway epithelial cells. QUB-TL1-mediated CAP inhibition results in diminished ENaC-mediated Na(+) absorption in CF airway epithelial cells caused by internalization of a prominent pool of cleaved (active) ENaCγ from the cell surface. Importantly, diminished ENaC activity correlates with improved airway hydration status and mucociliary clearance. We further demonstrate QUB-TL1-mediated furin inhibition, which is in contrast to other serine protease inhibitors (camostat mesylate and aprotinin), affords protection against neutrophil elastase-mediated ENaC activation and Pseudomonas aeruginosa exotoxin A-induced cell death. QUB-TL1 corrects aberrant CAP activities, providing a mechanism to delay or prevent the development of CF lung disease in a manner independent of CF transmembrane conductance regulator mutation.

Regional differences in rat conjunctival ion transport activities

PubMed Central

Yu, Dongfang; Thelin, William R.; Rogers, Troy D.; Stutts, M. Jackson; Randell, Scott H.; Grubb, Barbara R.

2012-01-01

Active ion transport and coupled osmotic water flow are essential to maintain ocular surface health. We investigated regional differences in the ion transport activities of the rat conjunctivas and compared these activities with those of cornea and lacrimal gland. The epithelial sodium channel (ENaC), sodium/glucose cotransporter 1 (Slc5a1), transmembrane protein 16 (Tmem16a, b, f, and g), cystic fibrosis transmembrane conductance regulator (Cftr), and mucin (Muc4, 5ac, and 5b) mRNA expression was characterized by RT-PCR. ENaC proteins were measured by Western blot. Prespecified regions (palpebral, fornical, and bulbar) of freshly isolated conjunctival tissues and cell cultures were studied electrophysiologically with Ussing chambers. The transepithelial electrical potential difference (PD) of the ocular surface was also measured in vivo. The effect of amiloride and UTP on the tear volume was evaluated in lacrimal gland excised rats. All selected genes were detected but with different expression patterns. We detected αENaC protein in all tissues, βENaC in palpebral and fornical conjunctiva, and γENaC in all tissues except lacrimal glands. Electrophysiological studies of conjunctival tissues and cell cultures identified functional ENaC, SLC5A1, CFTR, and TMEM16. Fornical conjunctiva exhibited the most active ion transport under basal conditions amongst conjunctival regions. PD measurements confirmed functional ENaC-mediated Na+ transport on the ocular surface. Amiloride and UTP increased tear volume in lacrimal gland excised rats. This study demonstrated that the different regions of the conjunctiva exhibited a spectrum of ion transport activities. Understanding the specific functions of distinct regions of the conjunctiva may foster a better understanding of the physiology maintaining hydration of the ocular surface. PMID:22814399

Regional differences in rat conjunctival ion transport activities.

PubMed

Yu, Dongfang; Thelin, William R; Rogers, Troy D; Stutts, M Jackson; Randell, Scott H; Grubb, Barbara R; Boucher, Richard C

2012-10-01

Active ion transport and coupled osmotic water flow are essential to maintain ocular surface health. We investigated regional differences in the ion transport activities of the rat conjunctivas and compared these activities with those of cornea and lacrimal gland. The epithelial sodium channel (ENaC), sodium/glucose cotransporter 1 (Slc5a1), transmembrane protein 16 (Tmem16a, b, f, and g), cystic fibrosis transmembrane conductance regulator (Cftr), and mucin (Muc4, 5ac, and 5b) mRNA expression was characterized by RT-PCR. ENaC proteins were measured by Western blot. Prespecified regions (palpebral, fornical, and bulbar) of freshly isolated conjunctival tissues and cell cultures were studied electrophysiologically with Ussing chambers. The transepithelial electrical potential difference (PD) of the ocular surface was also measured in vivo. The effect of amiloride and UTP on the tear volume was evaluated in lacrimal gland excised rats. All selected genes were detected but with different expression patterns. We detected αENaC protein in all tissues, βENaC in palpebral and fornical conjunctiva, and γENaC in all tissues except lacrimal glands. Electrophysiological studies of conjunctival tissues and cell cultures identified functional ENaC, SLC5A1, CFTR, and TMEM16. Fornical conjunctiva exhibited the most active ion transport under basal conditions amongst conjunctival regions. PD measurements confirmed functional ENaC-mediated Na(+) transport on the ocular surface. Amiloride and UTP increased tear volume in lacrimal gland excised rats. This study demonstrated that the different regions of the conjunctiva exhibited a spectrum of ion transport activities. Understanding the specific functions of distinct regions of the conjunctiva may foster a better understanding of the physiology maintaining hydration of the ocular surface.

An unusual presenting symptom of graves' disease: myalgia.

PubMed

Papanikolaou, N; Perros, P

2013-01-01

A 50-year-old female patient presented with severe myalgia involving her proximal muscles for 3-4 weeks. She also reported mild thyrotoxic symptoms over the same time period. Examination revealed mild thyrotoxicosis, a moderate diffuse goiter and no eye signs. The clinical picture was dominated by muscle pain and tenderness involving mainly her proximal arms and legs, her calves and her fingers, requiring opiate analgesia. Muscle power and tendon reflexes were normal. Laboratory evaluation revealed undetectable serum thyroid stimulating hormone (TSH) with raised FT4, FT3 and positive TSH receptor antibodies. Treatment with carbimazole was started. Additional laboratory investigations were negative (inflammatory markers, creatine kinase and antibodies to antinuclear antibodies, gastric parietal cell, smooth muscle, mitochondrial, dsDNA, centromere, extractable nuclear antigen (ENA) ribonucleoprotein, ENA Sm, ENA Ro, ENA Anti-La, ENA Scl70, ENA Jo-1, anti-CCP and rheumatoid factor). Further assessment in the rheumatology clinic confirmed there was no small joint tenderness or loss of range of movement of her limbs, but widespread and profound muscle tenderness of the common extensors of the forearms, biceps, trapezius, calves and thighs. She was treated symptomatically with analgesic medication and continued on carbimazole. A month later she was euthyroid and her myalgia had resolved. Hyperthyroidism has a profound effect on skeletal muscle and often leads to myopathy. Severe myalgia in association with Graves' disease is rare and resolves with the restoration of euthyroidism.

Expression and localization of taste receptor genes in the vallate papillae of rats: effect of zinc deficiency.

PubMed

Ikeda, Atsuo; Sekine, Hiroki; Takao, Kyoichi; Ikeda, Minoru

2013-09-01

We found a difference in expression sites between TAS2Rs and ENaC (epithelial sodium channels). The number of TAS2R-positive cells and ENaC-positive cells were decreased in zinc-deficient diet rats. These findings suggest that decreased expression of taste receptor genes may play an important role in the onset of zinc deficiency-associated taste disorder. The present study was aimed at histologically investigating the expression and localization of TAS2Rs and ENaC in the vallate taste buds of rats. Changes in expression of the taste receptor genes in zinc-deficient rats were also investigated. The vallate papillae of five rats fed a normal diet and five rats fed a zinc-deficient diet were used. In situ hybridization was performed to investigate the expression and localization of TAS2Rs and ENaC. TAS2R-positive cells per taste bud were counted, and differences in number between the normal and zinc-deficient diet rats were investigated. In the normal rats, expression of TAS2Rs was observed specifically in the taste bud cells. In contrast, ENaC-positive cells were observed in a part of the taste bud cells and a large number of epithelial cells. Fewer cells were positive for TAS2Rs and ENaC in the zinc-deficient diet rats.

THE ENERGY-DEPENDENT POSITION OF THE IBEX RIBBON DUE TO THE SOLAR WIND STRUCTURE

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

Swaczyna, Paweł; Bzowski, Maciej; Sokół, Justyna M., E-mail: pswaczyna@cbk.waw.pl

2016-08-10

Observations of energetic neutral atoms (ENAs) allow for remote studies of the condition of plasma in the heliosphere and the neighboring local interstellar medium. The first results from the Interstellar Boundary Explorer ( IBEX ) revealed an arc-like enhancement of the ENA intensity in the sky, known as the ribbon. The ribbon was not expected from the heliospheric models prior to the launch of IBEX . One proposed explanation for the ribbon is the mechanism of secondary ENA emission. The ribbon reveals energy-dependent structure in the relative intensity along its circumference and in its position. That is, the geometric centermore » of the ribbon varies systematically by about 10° in the energy range 0.7–4.3 keV. Here, we show by analytical modeling that this effect is a consequence of the helio-latitudinal structure of the solar wind reflected in the secondary ENAs. Along with a recently measured distance to the ribbon’s source just beyond the heliopause, our findings support the connection of the ribbon with the local interstellar magnetic field by the mechanism of secondary ENA emission. However, the magnitude of the center shift in the highest IBEX energy channel is much larger in the observations than expected from the modeling. This may be due to another, not currently recognized, process of ENA generation.« less

Inhibition of airway surface fluid absorption by cholinergic stimulation

PubMed Central

Joo, Nam Soo; Krouse, Mauri E.; Choi, Jae Young; Cho, Hyung-Ju; Wine, Jeffrey J.

2016-01-01

In upper airways airway surface liquid (ASL) depth and clearance rates are both increased by fluid secretion. Secretion is opposed by fluid absorption, mainly via the epithelial sodium channel, ENaC. In static systems, increased fluid depth activates ENaC and decreased depth inhibits it, suggesting that secretion indirectly activates ENaC to reduce ASL depth. We propose an alternate mechanism in which cholinergic input, which causes copious airway gland secretion, also inhibits ENaC-mediated absorption. The conjoint action accelerates clearance, and the increased transport of mucus out of the airways restores ASL depth while cleansing the airways. We were intrigued by early reports of cholinergic inhibition of absorption by airways in some species. To reinvestigate this phenomenon, we studied inward short-circuit currents (Isc) in tracheal mucosa from human, sheep, pig, ferret, and rabbit and in two types of cultured cells. Basal Isc was inhibited 20–70% by the ENaC inhibitor, benzamil. Long-lasting inhibition of ENaC-dependent Isc was also produced by basolateral carbachol in all preparations except rabbit and the H441 cell line. Atropine inhibition produced a slow recovery or prevented inhibition if added before carbachol. The mechanism for inhibition was not determined and is most likely multi-factorial. However, its physiological significance is expected to be increased mucus clearance rates in cholinergically stimulated airways. PMID:26846701

Heliospheric and Local Interstellar Space Weathering Environments of Extreme Kuiper Belt Objects

NASA Astrophysics Data System (ADS)

Cooper, J. F.; Sturner, S. J.

2017-12-01

Since the first direct detection of a Kuiper Belt Object (KBO), (15760) 1992 QB1, in 1992, observational evidence via direct detection has accumulated for thousands (and via inference for hundreds of thousands) of small to large icy bodies that populate the solar system from within the supersonic heliosphere out into the local interstellar medium (LISM). These objects have mainly been discovered when within the heliosphere but the orbits of the more extreme KBOs, fifteen percent of the total known KBO population, take them out into the heliosheath and about half of these continue further out into the LISM. Continuing observations will inevitably increase the known inventory of extreme KBOs, possibly including a few that may be accessible as near-encounter targets for a future interstellar probe mission directed beyond 200 AU into the upstream LISM. Here we review the known population of extreme KBOs and address the properties of the heliospheric and LISM environments that could potentially affect object visibility and surface composition. The twin Voyager spacecraft are our present source of in-situ measurements for the plasma and energetic particle environments, except that there are no plasma data from Voyager 1. Voyager 1 and 2 are now respectively in the LISM and the heliosheath after earlier passing through the outer regions of the supersonic heliosphere upstream of the solar wind termination shock. The Voyager data coverage is complemented by energetic neutral atom (ENA) measurements of the Interstellar Background Explorer (IBEX) and Cassini Orbiter spacecraft that can be used to infer proton flux spectra from models of ENA production in the outer heliosphere. High radiation background in the LISM has precluded sub-MeV energetic ion measurements by Voyager 1, so we use limits from Cummings et al. (ApJ, 2016) for molecular cloud ionization. This would be an important energy region to cover with interstellar probe measurements. These sources of plasma and energetic particle flux measurements are used to estimate values for space weathering parameters including surface energy flux and pressure, dosage vs. depth profiles for chemical processing of mixed ice surfaces, and ion sputtering rates. We further consider other space weathering processes including ultraviolet irradiation and meteoritic impact gardening.

The Low‐Energy Neutral Imager (LENI)

PubMed Central

Mitchell, D. G.; Brandt, P. C.‐son.; Andrews, B. G.; Clark, G.

2016-01-01

Abstract To achieve breakthroughs in the areas of heliospheric and magnetospheric energetic neutral atom (ENA) imaging, a new class of instruments is required. We present a high angular resolution ENA imager concept aimed at the suprathermal plasma populations with energies between 0.5 and 20 keV. This instrument is intended for understanding the spatial and temporal structure of the heliospheric boundary recently revealed by Interstellar Boundary Explorer instrumentation and the Cassini Ion and Neutral Camera. The instrument is also well suited to characterize magnetospheric ENA emissions from low‐altitude ENA emissions produced by precipitation of magnetospheric ions into the terrestrial upper atmosphere, or from the magnetosheath where solar wind protons are neutralized by charge exchange, or from portions of the ring current region. We present a new technique utilizing ultrathin carbon foils, 2‐D collimation, and a novel electron optical design to produce high angular resolution (≤2°) and high‐sensitivity (≥10−3 cm2 sr/pixel) ENA imaging in the 0.5–20 keV energy range. PMID:27867800

Particle Environment Package (PEP) for the ESA JUICE mission

NASA Astrophysics Data System (ADS)

Barabash, Stas; Brandt, Pontus; Wurz, Peter; PEP Team

2016-10-01

PEP is a suite of six (6) sensors arranged in 4 units to measure charged and neutral particles in the Jupiter magnetospheres and at the moons to answer four overarching science questions:1. How does the corotating magnetosphere of Jupiter interact with the complex and diverse environment of Ganymede?2. How does the rapidly rotating magnetosphere of Jupiter interact with the seemingly inert Callisto?3. What are the governing mechanisms and their global impacts of release of material into the Jovian magnetosphere from seemingly inert Europa and active Io?4. How do internal and solar wind drivers cause such energetic, time variable and multi-scale phenomena in the steadily rotating giant magnetosphere of Jupiter?PEP measures positive and negative ions, electrons, exospheric neutral gas, thermal plasma and energetic neutral atoms present in all domains of the Jupiter system over nine decades of energy from < 0.001 eV to > 1 MeV with full angular coverage.PEP provides instantaneous measurements of 3D flow of the ion plasma and composition to understand the magnetosphere and magnetosphere-moon interactions. It also measures instantaneously 3D electron plasma to investigate auroral processes at the moon and Jupiter. Measurements of the angular distributions of energetic electrons at sub-second resolution probe the acceleration mechanisms and magnetic field topology and boundaries.PEP combines global imaging via remote sensing using energetic neutral atoms (ENA) with in-situ measurements and performs global imaging of Europa/Io tori and magnetosphere combined with energetic ion measurements. Using low energy ENAs originating from the particle - surface interaction PEP investigate space weathering of the icy moons by precipitation particles. PEP will first-ever directly sample of the exospheres of Europa, Ganymede, and Callisto with extremely high mass resolution (M/ΔM > 1100).The PEP sensors are (1) an ion mass analyzer, (2) an electron spectrometer, (3) a low energy ENA imager, (4) a high energy ENA and energetic ions imager, (5) an energetic electron sensor, and (6) a neutral gas and ions mass spectrometer.

Imaging plasmas at the Earth and other planets

NASA Astrophysics Data System (ADS)

Mitchell, D. G.

2006-05-01

The field of space physics, both at Earth and at other planets, was for decades a science based on local observations. By stitching together measurements of plasmas and fields from multiple locations either simultaneously or for similar conditions over time, and by comparing those measurements against models of the physical systems, great progress was made in understanding the physics of Earth and planetary magnetospheres, ionospheres, and their interactions with the solar wind. However, the pictures of the magnetospheres were typically statistical, and the large-scale global models were poorly constrained by observation. This situation changed dramatically with global auroral imaging, which provided snapshots and movies of the effects of field aligned currents and particle precipitation over the entire auroral oval during quiet and disturbed times. And with the advent of global energetic neutral atom (ENA) and extreme ultraviolet (EUV) imaging, global constraints have similarly been added to ring current and plasmaspheric models, respectively. Such global constraints on global models are very useful for validating the physics represented in those models, physics of energy and momentum transport, electric and magnetic field distribution, and magnetosphere-ionosphere coupling. These techniques are also proving valuable at other planets. For example with Hubble Space Telescope imaging of Jupiter and Saturn auroras, and ENA imaging at Jupiter and Saturn, we are gaining new insights into the magnetic fields, gas-plasma interactions, magnetospheric dynamics, and magnetosphere-ionosphere coupling at the giant planets. These techniques, especially ENA and EUV imaging, rely on very recent and evolving technological capabilities. And because ENA and EUV techniques apply to optically thin media, interpretation of their measurements require sophisticated inversion procedures, which are still under development. We will discuss the directions new developments in imaging are taking, what technologies and mission scenarios might best take advantage of them, and how our understanding of the Earth's and other planets' plasma environments may benefit from such advancements.

Prenatal programming of rat cortical collecting tubule sodium transport.

PubMed

Cheng, Chih-Jen; Lozano, German; Baum, Michel

2012-03-15

Prenatal insults have been shown to lead to elevated blood pressure in offspring when they are studied as adults. Prenatal administration of dexamethasone and dietary protein deprivation have demonstrated that there is an increase in transporter abundance for a number of nephron segments but not the subunits of the epithelial sodium channel (ENaC) in the cortical collecting duct. Recent studies have shown that aldosterone is elevated in offspring of protein-deprived mothers when studied as adults, but the physiological importance of the increase in serum aldosterone is unknown. As an indirect measure of ENaC activity, we compared the natriuretic response to benzamil in offspring of mothers who ate a low-protein diet (6%) with those who ate a normal diet (20%) for the last half of pregnancy. The natriuretic response to benzamil was greater in the 6% group (821.1 ± 161.0 μmol/24 h) compared with the 20% group (279.1 ± 137.0 μmol/24 h), consistent with greater ENaC activity in vivo (P < 0.05). In this study, we also directly studied cortical collecting tubule function from adult rats using in vitro microperfusion. There was no difference in basal or vasopressin-stimulated osmotic water permeability. However, while cortical collecting ducts of adult offspring whose mothers ate a 20% protein diet had no sodium transport (-1.9 ± 3.1 pmol·mm(-1)·min(-1)), the offspring of rats that ate a 6% protein diet during the last half of pregnancy had a net sodium flux of 10.7 ± 2.6 pmol·mm(-1)·min(-1) (P = 0.01) in tubules perfused in vitro. Sodium transport was measured using ion-selective electrodes, a novel technique allowing measurement of sodium in nanoliter quantities of fluid. Thus we directly demonstrate that there is prenatal programming of cortical collecting duct sodium transport.

Aerosol, cloud, and precipitation interactions in Eastern North Atlantic

NASA Astrophysics Data System (ADS)

Wang, J.; Wood, R.; Dong, X.

2017-12-01

With their extensive coverage, marine low clouds greatly impact global climate. Presently, marine low clouds are poorly represented in global climate models, and the response of marine low clouds to changes in atmospheric greenhouse gases and aerosols remains the major source of uncertainty in climate simulations. The Eastern North Atlantic (ENA) is a region of persistent but diverse subtropical marine boundary layer clouds, whose albedo and precipitation are highly susceptible to perturbations in aerosol properties. In addition, ENA is periodically impacted by anthropogenic aerosol both from North American and from continental Europe, making it an excellent location to study the CCN budget in a remote marine region periodically perturbed by anthropogenic emissions, and to investigate the impacts of long-range transport of aerosols on remote marine clouds. Aerosol and Cloud Experiments in Eastern North Atlantic (ACE-ENA), funded by DOE Atmospheric Radiation Measurement (ARM) program, is designed to improve the understanding of marine boundary CCN budget, cloud and drizzle microphysics, and the impact of aerosol on marine low cloud and precipitation in the ENA by combining airborne observations and long term surface based measurements. The study has two airborne deployments. The first deployment took place from June 15 to July 25, 2017, and the second one will take place from January 10 to February 20, 2018. Flights during the first deployment were carried out in the Azores, near the ARM ENA site on Graciosa Island. The long term measurements at the ENA site provide important Climatological context for the airborne observations during the two deployments, and the cloud structures provided by the scanning radars at the ENA site put the detailed in-situ measurements into mesoscale and cloud lifecycle contexts. Another important aspect of this study is to provide high quality in-situ measurements for validating and improving ground-based retrieval algorithms at the ENA site. This presentation will describe the setup and strategies of the study, early results from the first deployment on vertical structures and horizontal variabilities of aerosol properties, cloud and drizzle microphysics, and insights into the processes that drive the properties and interactions of aerosol and marine low clouds.

Differences in attenuation among the stable continental regions

USGS Publications Warehouse

Bakun, W.H.; McGarr, A.

2002-01-01

There are systematic differences in the attenuation of damaging earthquake ground motions between different stable continental regions (SCRs). Seismic intensity and weak-motion data show that the attenuation in seismic waves for eastern North America (ENA) is less than for India, Africa, Australia, and northwest Europe. If ENA ground-motion attenuation relations are used in seismic hazard models for other SCRs, as is commonly done, then the estimated ground motions and resulting hazard may be too large. If an attenuation model that averages observations from ENA and the other SCRs is used to estimate the magnitudes of large historical earthquakes in ENA, as is the case for recent estimates of M for the 1811-1812 New Madrid, Missouri and the 1886 Charleston, South Carolina events, then the magnitude estimates for these events will be too large, as will be the resulting hazard.

The sodium chloride cotransporter (NCC) and epithelial sodium channel (ENaC) associate.

PubMed

Mistry, Abinash C; Wynne, Brandi M; Yu, Ling; Tomilin, Viktor; Yue, Qiang; Zhou, Yiqun; Al-Khalili, Otor; Mallick, Rickta; Cai, Hui; Alli, Abdel A; Ko, Benjamin; Mattheyses, Alexa; Bao, Hui-Fang; Pochynyuk, Oleh; Theilig, Franziska; Eaton, Douglas C; Hoover, Robert S

2016-10-01

The thiazide-sensitive sodium chloride cotransporter (NCC) and the epithelial sodium channel (ENaC) are two of the most important determinants of salt balance and thus systemic blood pressure. Abnormalities in either result in profound changes in blood pressure. There is one segment of the nephron where these two sodium transporters are coexpressed, the second part of the distal convoluted tubule. This is a key part of the aldosterone-sensitive distal nephron, the final regulator of salt handling in the kidney. Aldosterone is the key hormonal regulator for both of these proteins. Despite these shared regulators and coexpression in a key nephron segment, associations between these proteins have not been investigated. After confirming apical localization of these proteins, we demonstrated the presence of functional transport proteins and native association by blue native PAGE. Extensive coimmunoprecipitation experiments demonstrated a consistent interaction of NCC with α- and γ-ENaC. Mammalian two-hybrid studies demonstrated direct binding of NCC to ENaC subunits. Fluorescence resonance energy transfer and immunogold EM studies confirmed that these transport proteins are within appropriate proximity for direct binding. Additionally, we demonstrate that there are functional consequences of this interaction, with inhibition of NCC affecting the function of ENaC. This novel finding of an association between ENaC and NCC could alter our understanding of salt transport in the distal tubule. © 2016 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

First Results from the Interstellar Boundary Explorer (IBEX) Mission

NASA Astrophysics Data System (ADS)

McComas, David J.

2010-03-01

The Interstellar Boundary Explorer (IBEX) is a Small Explorer mission designed to study the global interaction between the heliosphere and the local interstellar medium. IBEX does this by measuring energetic neutral atoms (ENAs) created by both solar wind ions and pickup ions in the solar wind when they charge exchange with cold interstellar neutrals drifting in from the interstellar medium. Because the ENAs are not magnetically confined, some of them propagate back into the inner heliosphere, where IBEX can detect them. IBEX was launched October 19th 2008, using a new launch technique that was also developed as a part of the IBEX project. The first scientific observations from IBEX were of ENAs coming from the Moon-these represented the first ever lunar ENA observations from any spacecraft and provided important information about the universal physical processes of backscatter and neutralization from complex planetary surfaces like the lunar regolith. Since then, IBEX has been collecting its first all-sky maps of heliospheric ENAs and initial direct, in situ observations of interstellar H, He, and O. At the time of this writing, these observations have been submitted and are under review for a special IBEX section of Science magazine nominally scheduled to be published in October 2009.

Energetic neutral atoms from a trans-Europa gas torus at Jupiter.

PubMed

Mauk, B H; Mitchell, D G; Krimigis, S M; Roelof, E C; Paranicas, C P

2003-02-27

The space environments--or magnetospheres--of magnetized planets emit copious quantities of energetic neutral atoms (ENAs) at energies between tens of electron volts to hundreds of kiloelectron volts (keV). These energetic atoms result from charge exchange between magnetically trapped energetic ions and cold neutral atoms, and they carry significant amounts of energy and mass from the magnetospheres. Imaging their distribution allows us to investigate the structure of planetary magnetospheres. Here we report the analysis of 50-80 keV ENA images of Jupiter's magnetosphere, where two distinct emission regions dominate: the upper atmosphere of Jupiter itself, and a torus of emission residing just outside the orbit of Jupiter's satellite Europa. The trans-Europa component shows that, unexpectedly, Europa generates a gas cloud comparable in gas content to that associated with the volcanic moon Io. The quantity of gas found indicates that Europa has a much greater impact than hitherto believed on the structure of, and the energy flow within, Jupiter's magnetosphere.

A New Vision of Science and Strategy for an Interstellar Probe Mission

NASA Astrophysics Data System (ADS)

Gruntman, M.; McNutt, R. L.; Krimigis, S. M.; Wimmer-Schweingruber, R. F.; Gold, R. E.

2011-12-01

The recent in-situ and remote observations from the Voyager Interstellar Mission (VIM), the Interstellar Boundary Explorer (IBEX), and Ion and Neutral Camera (INCA) Cassini have revealed the interaction of the heliosphere with the very local interstellar medium (VLISM) to be much more complex than described by our present day concepts. These discoveries call for a major revision of the strategy for the Interstellar Probe, a mission to explore the interstellar medium surrounding the Solar System. Voyager 1 and Voyager 2 continue to reveal unanticipated flow patterns and significant fluxes of energetic particles in the heliosheath (beyond the solar wind termination shock) while pointing to a more remote location for the modulation region and source of the anomalous cosmic rays (ACRs). Remarkably, Voyager 1 has been reporting near-zero plasma flows (10's of km/s) beyond 115 AU for over the past year. One implication of this flow stagnation is that Voyager is already in a "transition layer" that could lead to the interstellar plasma. Consequently an Interstellar Probe Mission may "punch out" into the deflected interstellar plasma flow at a much smaller distance than previous models had predicted. Global imaging observations by IBEX and INCA of energetic neutral atoms (ENAs) originating from the interaction region(s) of the solar wind and the VLISM show unexpected structure and possible time dependence on a variety of scales. In addition to the general "glow" of the sky in ENAs, IBEX revealed a relatively narrow "ribbon" of enhanced atomic hydrogen emission from ~200 eV to ~6 keV. The neutrals from both the glow and ribbon are also characterized by non-thermal distribution functions. In addition, INCA on Cassini sees a "belt" of emission in ENAs, broader than the ribbon and tilted significantly away from it, at even higher energies (10s of keV). This evidence supports the idea that the bulk of the energy density in the heliosheath plasma resides in a non-thermal component that extends to very high energies. We have never sampled such a huge and dynamic plasma regime that is dominated by non-thermal pressure, but it must be representative of the astrospheres of stars similar to our Sun. These new quantitative and qualitative implications for the overall heliospheric structure already call for a new generation of measurements to understand the global nature of our Sun's interaction with the local galactic environment. An interstellar probe with modern instruments and measurement requirements better defined by these recent observations will certainly advance our understanding of the heliospheric interaction and VLISM. New launch vehicles in the evolving fleet, including the Atlas V, Delta IV and Falcon Heavy, offer new capabilities that can enable such a mission with an acceptable development and launch cost.

Investigating Global Ion and Neutral Atom Populations with IBEX and Voyager

NASA Technical Reports Server (NTRS)

Florinski, Vladimir

2016-01-01

The main objective of this project was to investigate pickup ion (PUI) production in the solar wind and heliosheath (the region between the termination shock and the heliopause) and compute the distributed energetic neutral atom fluxes throughout the helioshpere. The simulations were constrained by comparing the model output against observations from Ulysses, New Horizons, Voyager 1 and 2, and IBEX space probes. As evidenced by the number of peer reviewed journal publications resulting from the project (13 plus three submitted) and their citation rate (156 citations over three years), the project has made a lasting contribution to the field. The outcome is a significant improvement of our understanding of the pickup ion production and distribution in the distant heliosphere. The team has accomplished the entire set of tasks A-H set forth in the proposal. Namely, the transport modeling framework has been augmented with two populations of pickup ions (PUIs), the boundary conditions for the plasma and interstellar neutral hydrogen were verified against Ulysses and New Horizons PUI and an optimal set of velocity diffusion parameters established. The multi-component fluxes of PUIs were computed and isotropic velocity distributions generated for each cell in the computer simulation that covered the heliosphere from 1.5 AU to the heliopause. The distributions were carefully compared with in situ measurements at 3 AU (Ulysses), 12 AU (New Horizons), and 80-90 AU (Voyager 1 and 2) as well as those inferred from ENA fluxes measured by Cassini and IBEX (Wu et al., 2016). Some examples of modeldata comparison are shown in Figure 1. We have used coupled MHD-plasma and kinetic-neutral code to investigate the likely range of plasma and magnetic field parameters in the local interstellar medium (LISM), based on the assumption that the shape of the IBEX ribbon could be used to determine the orientation of the interstellar magnetic field. While the magnetic field is believed to be oriented toward the center of the ribbon, constraining its strength requires comparing the model-predicted angular diameter and circularity of the ribbon with the observations. The study, published in Heerikhuisen et al. (2014), found that the most likely range for the LISM magnetic field strength is between 0.2 and 0.3 nT, which is less than previously thought. Figure 2 shows the IBEX data (left) and compares it to the simulation with a 0.2 nT interstellar magnetic field (center) and a 0.4 nT (right).

Cysteine palmitoylation of the γ subunit has a dominant role in modulating activity of the epithelial sodium channel.

PubMed

Mukherjee, Anindit; Mueller, Gunhild M; Kinlough, Carol L; Sheng, Nan; Wang, Zhijian; Mustafa, S Atif; Kashlan, Ossama B; Kleyman, Thomas R; Hughey, Rebecca P

2014-05-16

The epithelial sodium channel (ENaC) is composed of three homologous subunits (α, β, and γ) with cytoplasmic N and C termini. Our previous work revealed that two cytoplasmic Cys residues in the β subunit, βCys-43 and βCys-557, are Cys-palmitoylated. ENaCs with mutant βC43A/C557A exhibit normal surface expression but enhanced Na(+) self-inhibition and reduced channel open probability. Although the α subunit is not palmitoylated, we now show that the two cytoplasmic Cys residues in the γ subunit are palmitoylated. ENaCs with mutant γC33A, γC41A, or γC33A/C41A exhibit reduced activity compared with wild type channels but normal surface expression and normal levels of α and γ subunit-activating cleavage. These mutant channels have significantly enhanced Na(+) self-inhibition and reduced open probability compared with wild type ENaCs. Channel activity was enhanced by co-expression with the palmitoyltransferase DHHC2 that also co-immunoprecipitates with ENaCs. Secondary structure prediction of the N terminus of the γ subunit places γCys-33 within an α-helix and γCys-44 on a coil before the first transmembrane domain within a short tract that includes a well conserved His-Gly motif, where mutations have been associated with altered channel gating. Our current and previous results suggest that palmitoylation of the β and γ subunits of ENaCs enhances interactions of their respective cytoplasmic domains with the plasma membrane and stabilizes the open state of the channel. Comparison of activities of channels lacking palmitoylation sites in individual or multiple subunits revealed that γ subunit palmitoylation has a dominant role over β subunit palmitoylation in modulating ENaC gating. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Energetic Neutral Atom (ENA) Imaging of Mercury's Magnetosphere Onboard BepiColombo

NASA Astrophysics Data System (ADS)

Barabash, S.; Wieser, M.; Futaana, Y.; Holmström, M.; Asamura, K.; Saito, Y.; Wurz, P.

2018-05-01

We describe how energetic neutral atoms (ENA) are produced in Mercury’s magnetosphere, how they can be used to image the magnetosphere and surface, and how they are measured onboard the BepiColombo mission.

Regulation of blood pressure and renal function by NCC and ENaC: lessons from genetically engineered mice.

PubMed

Verouti, Sophia N; Boscardin, Emilie; Hummler, Edith; Frateschi, Simona

2015-04-01

The activity of the thiazide-sensitive Na(+)/Cl(-) cotransporter (NCC) and of the amiloride-sensitive epithelial Na(+) channel (ENaC) is pivotal for blood pressure regulation. NCC is responsible for Na(+) reabsorption in the distal convoluted tubule (DCT) of the nephron, while ENaC reabsorbs the filtered Na(+) in the late DCT and in the cortical collecting ducts (CCD) providing the final renal adjustment to Na(+) balance. Here, we aim to highlight the recent advances made using transgenic mouse models towards the understanding of the regulation of NCC and ENaC function relevant to the control of sodium balance and blood pressure. We thus like to pave the way for common mechanisms regulating these two sodium-transporting proteins and their potential implication in structural remodeling of the nephron segments and Na(+) and Cl(-) reabsorption. Copyright © 2015 Elsevier Ltd. All rights reserved.

The Downwind Hemisphere of the Heliosphere: Eight Years of IBEX-Lo Observations

NASA Astrophysics Data System (ADS)

Galli, A.; Wurz, P.; Schwadron, N. A.; Kucharek, H.; Möbius, E.; Bzowski, M.; Sokół, J. M.; Kubiak, M. A.; Fuselier, S. A.; Funsten, H. O.; McComas, D. J.

2017-12-01

We present a comprehensive study of energetic neutral atoms (ENAs) of 10 eV to 2.5 keV from the downwind hemisphere of the heliosphere. These ENAs are believed to originate mostly from pickup protons and solar-wind protons in the inner heliosheath. This study includes all low-energy observations made with the Interstellar Boundary Explorer over the first eight years. Because the protons around 0.1 keV dominate the plasma pressure within the inner heliosheath in downwind direction, these ENA observations offer the unique opportunity to constrain the plasma properties and dimensions of the heliosheath where no in situ observations are available. We first derive energy spectra of ENA intensities averaged over time for 49 macropixels covering the entire downwind hemisphere. The results confirm previous studies regarding integral intensities and the roll-over around 0.1 keV energy. With the expanded data set, we now find that ENA intensities at 0.2 and 0.1 keV seem to anti-correlate with solar activity. We then derive the product of total plasma pressure and emission thickness of protons in the heliosheath to estimate lower limits on the thickness of the inner heliosheath. The temporally averaged ENA intensities support a rather spherical shape of the termination shock and a heliosheath thickness between 150 and 210 au for most regions of the downwind hemisphere. Around the nominal downwind direction of 76° ecliptic longitude, the heliosheath is at least 280 au thick. There, the neutral hydrogen density seems to be depleted compared to upwind directions by roughly a factor of 2.

The Downwind Hemisphere of the Heliosphere: Eight Years of IBEX -Lo Observations

DOE PAGES

Galli, A.; Wurz, P.; Schwadron, N. A.; ...

2017-12-05

We present a comprehensive study of energetic neutral atoms (ENAs) of 10 eV to 2.5 keV from the downwind hemisphere of the heliosphere. These ENAs are believed to originate mostly from pickup protons and solar wind protons in the inner heliosheath. This study includes all low-energy observations made with the Interstellar Boundary Explorer over the first 8 years. Since the protons around 0.1 keV dominate the plasma pressure in the inner heliosheath in downwind direction, these ENA observations offer the unique opportunity to constrain the plasma properties and dimensions of the heliosheath where no in-situ observations are available. We firstmore » derive energy spectra of ENA intensities averaged over time for 49 macropixels covering the entire downwind hemisphere. The results confirm previous studies regarding integral intensities and the roll-over around 0.1 keV energy. With the expanded dataset we now find that ENA intensities at 0.2 and 0.1 keV seem to anti-correlate with solar activity. We then derive the product of total plasma pressure and emission thickness of protons in the heliosheath to estimate lower limits on the thickness of the inner heliosheath. The temporally averaged ENA intensities support a rather spherical shape of the termination shock and a heliosheath thickness between 150 and 210 au for most regions of the downwind hemisphere. Around the nominal downwind direction of 76° ecliptic longitude, the heliosheath is at least 280 au thick. There, the neutral hydrogen density seems to be depleted compared to upwind directions by roughly a factor of 2.« less

The Downwind Hemisphere of the Heliosphere: Eight Years of IBEX -Lo Observations

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

Galli, A.; Wurz, P.; Schwadron, N. A.

We present a comprehensive study of energetic neutral atoms (ENAs) of 10 eV to 2.5 keV from the downwind hemisphere of the heliosphere. These ENAs are believed to originate mostly from pickup protons and solar wind protons in the inner heliosheath. This study includes all low-energy observations made with the Interstellar Boundary Explorer over the first 8 years. Since the protons around 0.1 keV dominate the plasma pressure in the inner heliosheath in downwind direction, these ENA observations offer the unique opportunity to constrain the plasma properties and dimensions of the heliosheath where no in-situ observations are available. We firstmore » derive energy spectra of ENA intensities averaged over time for 49 macropixels covering the entire downwind hemisphere. The results confirm previous studies regarding integral intensities and the roll-over around 0.1 keV energy. With the expanded dataset we now find that ENA intensities at 0.2 and 0.1 keV seem to anti-correlate with solar activity. We then derive the product of total plasma pressure and emission thickness of protons in the heliosheath to estimate lower limits on the thickness of the inner heliosheath. The temporally averaged ENA intensities support a rather spherical shape of the termination shock and a heliosheath thickness between 150 and 210 au for most regions of the downwind hemisphere. Around the nominal downwind direction of 76° ecliptic longitude, the heliosheath is at least 280 au thick. There, the neutral hydrogen density seems to be depleted compared to upwind directions by roughly a factor of 2.« less

Ca2+ permeability and Na+ conductance in cellular toxicity caused by hyperactive DEG/ENaC channels.

PubMed

Matthewman, Cristina; Miller-Fleming, Tyne W; Miller, David M; Bianchi, Laura

2016-12-01

Hyperactivated DEG/ENaC channels cause neuronal death mediated by intracellular Ca 2+ overload. Mammalian ASIC1a channels and MEC-4(d) neurotoxic channels in Caenorhabditis elegans both conduct Na + and Ca 2+ , raising the possibility that direct Ca 2+ influx through these channels contributes to intracellular Ca 2+ overload. However, we showed that the homologous C. elegans DEG/ENaC channel UNC-8(d) is not Ca 2+ permeable, yet it is neurotoxic, suggesting that Na + influx is sufficient to induce cell death. Interestingly, UNC-8(d) shows small currents due to extracellular Ca 2+ block in the Xenopus oocyte expression system. Thus, MEC-4(d) and UNC-8(d) differ both in current amplitude and Ca 2+ permeability. Given that these two channels show a striking difference in toxicity, we wondered how Na + conductance vs. Ca 2+ permeability contributes to cell death. To address this question, we built an UNC-8/MEC-4 chimeric channel that retains the calcium permeability of MEC-4 and characterized its properties in Xenopus oocytes. Our data support the hypothesis that for Ca 2+ -permeable DEG/ENaC channels, both Ca 2+ permeability and Na + conductance contribute to toxicity. However, for Ca 2+ -impermeable DEG/ENaCs (e.g., UNC-8), our evidence shows that constitutive Na + conductance is sufficient to induce toxicity, and that this effect is enhanced as current amplitude increases. Our work further refines the contribution of different channel properties to cellular toxicity induced by hyperactive DEG/ENaC channels. Copyright © 2016 the American Physiological Society.

Ca2+ permeability and Na+ conductance in cellular toxicity caused by hyperactive DEG/ENaC channels

PubMed Central

Matthewman, Cristina; Miller-Fleming, Tyne W.; Miller, David M.

2016-01-01

Hyperactivated DEG/ENaC channels cause neuronal death mediated by intracellular Ca2+ overload. Mammalian ASIC1a channels and MEC-4(d) neurotoxic channels in Caenorhabditis elegans both conduct Na+ and Ca2+, raising the possibility that direct Ca2+ influx through these channels contributes to intracellular Ca2+ overload. However, we showed that the homologous C. elegans DEG/ENaC channel UNC-8(d) is not Ca2+ permeable, yet it is neurotoxic, suggesting that Na+ influx is sufficient to induce cell death. Interestingly, UNC-8(d) shows small currents due to extracellular Ca2+ block in the Xenopus oocyte expression system. Thus, MEC-4(d) and UNC-8(d) differ both in current amplitude and Ca2+ permeability. Given that these two channels show a striking difference in toxicity, we wondered how Na+ conductance vs. Ca2+ permeability contributes to cell death. To address this question, we built an UNC-8/MEC-4 chimeric channel that retains the calcium permeability of MEC-4 and characterized its properties in Xenopus oocytes. Our data support the hypothesis that for Ca2+-permeable DEG/ENaC channels, both Ca2+ permeability and Na+ conductance contribute to toxicity. However, for Ca2+-impermeable DEG/ENaCs (e.g., UNC-8), our evidence shows that constitutive Na+ conductance is sufficient to induce toxicity, and that this effect is enhanced as current amplitude increases. Our work further refines the contribution of different channel properties to cellular toxicity induced by hyperactive DEG/ENaC channels. PMID:27760755

The nonproton ligand of acid-sensing ion channel 3 activates mollusk-specific FaNaC channels via a mechanism independent of the native FMRFamide peptide.

PubMed

Yang, Xiao-Na; Niu, You-Ya; Liu, Yan; Yang, Yang; Wang, Jin; Cheng, Xiao-Yang; Liang, Hong; Wang, Heng-Shan; Hu, You-Min; Lu, Xiang-Yang; Zhu, Michael X; Xu, Tian-Le; Tian, Yun; Yu, Ye

2017-12-29

The degenerin/epithelial sodium channel (DEG/ENaC) superfamily of ion channels contains subfamilies with diverse functions that are fundamental to many physiological and pathological processes, ranging from synaptic transmission to epileptogenesis. The absence in mammals of some DEG/ENaCs subfamily orthologues such as FMRFamide peptide-activated sodium channels (FaNaCs), which have been identified only in mollusks, indicates that the various subfamilies diverged early in evolution. We recently reported that the nonproton agonist 2-guanidine-4-methylquinazoline (GMQ) activates acid-sensing ion channels (ASICs), a DEG/ENaC subfamily mainly in mammals, in the absence of acidosis. Here, we show that GMQ also could directly activate the mollusk-specific FaNaCs. Differences in ion selectivity and unitary conductance and effects of substitutions at key residues revealed that GMQ and FMRFamide activate FaNaCs via distinct mechanisms. The presence of two activation mechanisms in the FaNaC subfamily diverging early in the evolution of DEG/ENaCs suggested that dual gating is an ancient feature in this superfamily. Notably, the GMQ-gating mode is still preserved in the mammalian ASIC subfamily, whereas FMRFamide-mediated channel gating was lost during evolution. This implied that GMQ activation may be essential for the functions of mammalian DEG/ENaCs. Our findings provide new insights into the evolution of DEG/ENaCs and may facilitate the discovery and characterization of their endogenous agonists. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Ethanol Alters Alveolar Fluid Balance via Nadph Oxidase (NOX) Signaling to Epithelial Sodium Channels (ENaC) in the Lung

PubMed Central

Downs, Charles A.; Kreiner, Lisa H.; Eaton, Amity F.; Johnson, Nicholle M.; Brown, Lou Ann

2013-01-01

Chronic alcohol consumption is associated with increased incidence of ICU-related morbidity and mortality, primarily from acute respiratory distress syndrome (ARDS). However, the mechanisms involved are unknown. One explanation is that alcohol regulates epithelial sodium channels (ENaC) via oxidant signaling to promote a pro- injury environment. We used small rodent models to mimic acute and chronic alcohol consumption and tested the hypothesis that ethanol (EtOH) would affect lung fluid clearance by up-regulating ENaC activity in the lung. Fluorescence labeling of rat lung slices and in vivo mouse lung revealed an increase in ROS production in response to acute EtOH exposure. Using western blots and fluorescein-5-maleimide labeling, we conclude that EtOH exposure modifies cysteines of α-ENaC while data from single channel patch clamp analysis confirm that 0.16% EtOH increased ENaC activity in rat alveolar cells. In vivo lung fluid clearance demonstrated a latent increase in fluid clearance in mice receiving EtOH diet. Ethanol mice given a tracheal instillation of LPS demonstrated early lung fluid clearance compared to caloric control mice and C57Bl/6 mice. Standard biochemical techniques reveal that chronic EtOH consumption resulted in greater protein expression of the catalytic gp91phox subunit and the obligate Rac1 protein. Collectively these data suggest that chronic EtOH consumption may lead to altered regulation of ENaC, contributing to a ‘pro-injury’ environment in the alcohol lung. PMID:23382956

Terrestrial energetic neutral atom emissions and the ground-based geomagnetic indices: First daylong observations by IBEX

NASA Astrophysics Data System (ADS)

Ogasawara, K.; Dayeh, M. A.; Fuselier, S. A.; Goldstein, J.; McComas, D. J.; Valek, P. W.

2017-12-01

We report daylong continuous observations of bright terrestrial energetic neutral atom (ENA) emissions in the energy of 0.5-6.0 keV by Interstellar Boundary Explorer (IBEX). The unique vantage point of IBEX, 48 Earth radii (Re) from the dawn/dusk side, made an unprecedented long duration monitoring of ENAs possible from almost stable locations. This type of observation is difficult with the other ENA imager satellites since they are orbiting closer to the Earth in shorter periods. The studied energy range is unique due to the coverage of the transition from the solar wind plasma to the magnetospheric particles with a single sensor. In addition, the Coulomb decay becomes important for the protons with energy less than 1 keV. In order to minimize contamination from the sub-solar magnetosphere or the cusp emissions, we focused on two events when the auroral electrojet (AE) index exceeded 300 nT in this study. We will also show the ENA images from Two Wide-Angle Imaging Neutral-Atom Spectrometers (TWINS) in support of the IBEX observations. We found a significant correlation between the observed ENA profile and the AE indices, whose correlation coefficients were maximized at >0.75 for >1.4 keV energy. There are systematic differences between two events in terms of AU, AL, and Asy-H correlations: One event has the stronger AU correlation than AL and the Asy-H correlation, suggesting partial ring current contribution. The other has the stronger AL correlation than AU without Asy-H correlation, which suggests substorm related ENA emissions. On the contrary, we could not find a meaningful correlation with Sym-H for these two events. The other important finding is the decay time of these ENA emissions. The observed e-folding decay time, 2 to 4 hours for most of the energy bands, was a little shorter than the conventional ring-current decay time (typically >6 hours) expected from the charge exchange and the field-line curvature effect, suggesting the stronger effect of the Coulomb collision in the energy range investigated in this study. These observations can potentially provide a key to understanding the dependence of geomagnetic indices (e.g., AE and Sym-H) by monitoring and parameterizing the evolution of global ENA emissions from a new perspective.

STEREO Observations of Energetic Neutral Hydrogen Atoms during the 5 December 2006 Solar Flare

NASA Technical Reports Server (NTRS)

Mewaldt, R. A.; Leske, R. A.; Stone, E. C.; Barghouty, A. F.; Labrador, A. W.; Cohen, C. M. S.; Cummings, A. C.; Davis, A. J.; vonRosenvinge, T. T.; Wiedenbeck, M. E.

2009-01-01

We report the discovery of energetic neutral hydrogen atoms emitted during the X9 solar event of December 5, 2006. Beginning 1 hour following the onset of this E79 flare, the Low Energy Telescopes (LETs) on both the STEREO A and B spacecraft observed a sudden burst of 1.6 to 15 MeV protons beginning hours before the onset of the main solar energetic particle (SEP) event at Earth. More than 70% of these particles arrived from a longitude within 10 of the Sun, consistent with the measurement resolution. The derived emission profile at the Sun had onset and peak times remarkably similar to the GOES soft X-ray profile and continued for more than an hour. The observed arrival directions and energy spectrum argue strongly that the particle events less than 5 MeV were due to energetic neutral hydrogen atoms (ENAs). To our knowledge, this is the first reported observation of ENA emission from a solar flare/coronal mass ejection. Possible origins for the production of ENAs in a large solar event are considered. We conclude that the observed ENAs were most likely produced in the high corona and that charge-transfer reactions between accelerated protons and partially-stripped coronal ions are an important source of ENAs in solar events.

Salty Taste Acuity Is Affected by the Joint Action of αENaC A663T Gene Polymorphism and Available Zinc Intake in Young Women

PubMed Central

Noh, Hwayoung; Paik, Hee-Young; Kim, Jihye; Chung, Jayong

2013-01-01

Salty taste perception affects salt intake, of which excess amounts is a major public health concern. Gene polymorphisms in salty taste receptors, zinc status and their interaction may affect salty taste perception. In this study, we examined the relationships among the α-epithelial sodium channel (αENaC) A663T genotype, zinc intake, and salty taste perception including salty taste acuity and preference in healthy young adults. The αENaC A663T genotype was determined by the PCR-restriction fragment length polymorphism in 207 adults. Zinc intake was examined by one 24-h recall and a two-day dietary record. Salty taste acuity and preference were determined by measuring the salty taste recognition threshold and the preferred salinity of beansprout soup, respectively. Men had significantly higher thresholds and preferences for salty taste than women did (p < 0.05). In women, the salty taste threshold was significantly lower in the highest tertile of available zinc intake than in the lowest tertile (12.2 mM and 17.6 mM, respectively, p = 0.02). Interestingly, a significant inverse association between available zinc intake and salty taste threshold was found only in women with αENaC AA homozygotes (β = −0.833, p = 0.02), and no such association was found in T663 allele carriers. The salty taste preference was not associated with the αENaC A663T genotype or available zinc intake in either sex. In conclusion, our data suggest that gene-nutrient interactions between the αENaC A663T genotype and available zinc intake play a role in determining the salty taste acuity in young women. PMID:24317554

Knockout of glial channel ACD-1 exacerbates sensory deficits in a C. elegans mutant by regulating calcium levels of sensory neurons

PubMed Central

Wang, Ying; D'Urso, Giulia

2012-01-01

Degenerin/epithelial Na+ channels (DEG/ENaCs) are voltage-independent Na+ or Na+/Ca2+ channels expressed in many tissues and are needed for a wide range of physiological functions, including sensory perception and transepithelial Na+ transport. In the nervous system, DEG/ENaCs are expressed in both neurons and glia. However, the role of glial vs. neuronal DEG/ENaCs remains unclear. We recently reported the characterization of a novel DEG/ENaC in Caenorhabditis elegans that we named ACD-1. ACD-1 is expressed in glial amphid sheath cells. The glial ACD-1, together with the neuronal DEG/ENaC DEG-1, is necessary for acid avoidance and attraction to lysine. We report presently that knockout of acd-1 in glia exacerbates sensory deficits caused by another mutant: the hypomorphic allele of the cGMP-gated channel subunit tax-2. Furthermore, sensory deficits caused by mutations in Gi protein odr-3 and guanylate cyclase daf-11, which regulate the activity of TAX-2/TAX-4 channels, are worsened by knockout of acd-1. We also show that sensory neurons of acd-1 tax-2(p694) double mutants fail to undergo changes in intracellular Ca2+ when animals are exposed to low concentrations of attractant. Finally, we show that exogenous expression of TRPV1 in sensory neurons and exposure to capsaicin rescue sensory deficits of acd-1 tax-2(p694) mutants, suggesting that sensory deficits of these mutants are bypassed by increasing neuronal excitability. Our data suggest a role of glial DEG/ENaC channel ACD-1 in supporting neuronal activity. PMID:21994266

Knockout of glial channel ACD-1 exacerbates sensory deficits in a C. elegans mutant by regulating calcium levels of sensory neurons.

PubMed

Wang, Ying; D'Urso, Giulia; Bianchi, Laura

2012-01-01

Degenerin/epithelial Na(+) channels (DEG/ENaCs) are voltage-independent Na(+) or Na(+)/Ca(2+) channels expressed in many tissues and are needed for a wide range of physiological functions, including sensory perception and transepithelial Na(+) transport. In the nervous system, DEG/ENaCs are expressed in both neurons and glia. However, the role of glial vs. neuronal DEG/ENaCs remains unclear. We recently reported the characterization of a novel DEG/ENaC in Caenorhabditis elegans that we named ACD-1. ACD-1 is expressed in glial amphid sheath cells. The glial ACD-1, together with the neuronal DEG/ENaC DEG-1, is necessary for acid avoidance and attraction to lysine. We report presently that knockout of acd-1 in glia exacerbates sensory deficits caused by another mutant: the hypomorphic allele of the cGMP-gated channel subunit tax-2. Furthermore, sensory deficits caused by mutations in G(i) protein odr-3 and guanylate cyclase daf-11, which regulate the activity of TAX-2/TAX-4 channels, are worsened by knockout of acd-1. We also show that sensory neurons of acd-1 tax-2(p694) double mutants fail to undergo changes in intracellular Ca(2+) when animals are exposed to low concentrations of attractant. Finally, we show that exogenous expression of TRPV1 in sensory neurons and exposure to capsaicin rescue sensory deficits of acd-1 tax-2(p694) mutants, suggesting that sensory deficits of these mutants are bypassed by increasing neuronal excitability. Our data suggest a role of glial DEG/ENaC channel ACD-1 in supporting neuronal activity.

The Big Picture: Imaging of the Global Geospace Environment by the TWINS Mission

NASA Astrophysics Data System (ADS)

Goldstein, J.; McComas, D. J.

2018-03-01

Encircling our planet at distances of 2.5 to 8 Earth radii is a dynamic plasma population known as the ring current (RC). During geomagnetic storms, the solar wind's interaction with Earth's magnetic field pumps petaJoules of energy into the RC, energizing and transporting particles. To measure the global geospace response, RC imaging is performed by capturing energetic neutral atoms (ENAs) created by charge exchange between geospace ions and the neutral exosphere. The H exosphere is itself imaged via its geocoronal Lyman-α glow. Two Wide-angle Imaging Neutral-atom Spectrometers (TWINS) is a stereoscopic ENA and Lyman-α imaging mission that has recorded the deep minimum of solar cycle (SC) 23 and the moderate maximum of SC 24, observing geospace conditions ranging from utterly quiet to major storms. This review covers TWINS studies of the geospace response published during 2013 to 2017. Stereo ENA imaging has revealed new dimensionality and structure of RC ions. Continuous coverage by two imagers has allowed monitoring storms from start to finish. Deconvolution of the low-altitude signal has extended ENA analysis and revealed causal connections between the trapped and precipitating ion populations. ENA-based temperature and composition analyses have been refined, validated, and applied to an unprecedented sequence of solar activity changes in SC 23 and SC 24. Geocoronal imaging has revealed a surprising amount of time variability and structure in the neutral H exosphere, driven by both Sun and solar wind. Global models have been measurably improved. Routine availability of simultaneous in situ measurements has fostered huge leaps forward in the areas of ENA validation and cross-scale studies.

The alpha subunit of the epithelial sodium channel in the mouse: developmental regulation of its expression.

PubMed

Dagenais, A; Kothary, R; Berthiaume, Y

1997-09-01

Sodium reabsorption by the amiloride-sensitive sodium channel of epithelial cells plays a crucial role in the management of ionic composition and fluid volume in the body. In the respiratory system, sodium transport is involved in the clearance of pulmonary edema and of liquid secreted during fetal life at birth. We have cloned a partial cDNA of the alpha subunit of the mouse amiloride-sensitive sodium channel (alpha mENaC). In the region of comparison, the mouse alpha subunit shows 92% identity at the DNA level and 95% identity at the amino acid level with the rat sequence. The kidneys, lungs, and distal colon are major sites of expression of a 3.5-kb alpha mENaC mRNA. During mouse development, alpha mENaC transcripts appear late during gestation (d 17.5) and are expressed continuously thereafter. In the distal colon, a short 1.2-kb mRNA deleted of the 5' part of the transcript is detected during gestation and is replaced gradually by the mature 3.5-kb transcript after birth. Alpha mENaC and alpha1 Na+-K+-ATPase mRNAs have an expression profile that is modulated similarly during development for a given tissue. The expression of alpha mENaC transcripts increases transiently in the lungs at birth (2.5-fold), as for alpha1 Na+-K+-ATPase mRNAs (1.5-fold), suggesting that the expression of several components of the sodium transport system is modulated in the lungs at that time. In the kidney, there is no significant increase of alpha mENaC and alpha1 Na+-K+-ATPase mRNAs in newborns.

The Downwind Hemisphere of the Heliosphere as Observed with IBEX-Lo from 2009 to 2015

NASA Astrophysics Data System (ADS)

Wurz, P.; Galli, A.; Schwadron, N.; Kucharek, H.; Moebius, E.; Bzowski, M.; Sokol, J. M.; Kubiak, M. A.; Funsten, H. O.; Fuselier, S. A.; McComas, D. J.

2017-12-01

The topic of this study is the vast region towards the tail of the heliosphere. To this end, we comprehensively analyzed energetic neutral hydrogen atoms (ENAs) of energies 10 eV to 2.5 keV from the downwind hemisphere of the heliosheath measured during the first 7 years of the IBEX (Interstellar Boundary Explorer) mission. Neutralized ions from the heliosheath (the region of slow solar wind plasma between termination shock and heliopause) can be remotely observed as ENAs down to 10 eV with the IBEX-Lo sensor onboard IBEX. This sensor covers those energies of the ion spectrum that dominate the total plasma pressure in the downwind region. So far, this region of the heliosphere has never been explored in-situ. Converting observations obtained near Earth orbit at these low energies to the original ion distributions in the heliocentric rest frame at 100 AU is very challenging, making the assessment of uncertainties and implicit assumptions crucial. From the maps of observed ENAs from the heliosheath and their uncertainties we derive observational constraints on heliospheric models for the downwind hemisphere. These constraints limit the possible range of 1) the distance of the termination shock, 2) the total plasma pressure across the termination shock, 3) the radial flow velocity of the heliosheath plasma, 4) the extinction length of said plasma, and finally 5) the dimension of the heliosheath in downwind directions. Because these parameters are coupled and because of observational limitations, we also need to characterize the degeneracy, i.e., the fact that different sets of parameters may reproduce the observations.

The Drosophila actin regulator ENABLED regulates cell shape and orientation during gonad morphogenesis.

PubMed

Sano, Hiroko; Kunwar, Prabhat S; Renault, Andrew D; Barbosa, Vitor; Clark, Ivan B N; Ishihara, Shuji; Sugimura, Kaoru; Lehmann, Ruth

2012-01-01

Organs develop distinctive morphologies to fulfill their unique functions. We used Drosophila embryonic gonads as a model to study how two different cell lineages, primordial germ cells (PGCs) and somatic gonadal precursors (SGPs), combine to form one organ. We developed a membrane GFP marker to image SGP behaviors live. These studies show that a combination of SGP cell shape changes and inward movement of anterior and posterior SGPs leads to the compaction of the spherical gonad. This process is disrupted in mutants of the actin regulator, enabled (ena). We show that Ena coordinates these cell shape changes and the inward movement of the SGPs, and Ena affects the intracellular localization of DE-cadherin (DE-cad). Mathematical simulation based on these observations suggests that changes in DE-cad localization can generate the forces needed to compact an elongated structure into a sphere. We propose that Ena regulates force balance in the SGPs by sequestering DE-cad, leading to the morphogenetic movement required for gonad compaction.

Molecular genetics of Liddle's syndrome.

PubMed

Yang, Kun-Qi; Xiao, Yan; Tian, Tao; Gao, Ling-Gen; Zhou, Xian-Liang

2014-09-25

Liddle's syndrome, an autosomal dominant form of monogenic hypertension, is characterized by salt-sensitive hypertension with early penetrance, hypokalemia, metabolic alkalosis, suppression of plasma rennin activity and aldosterone secretion, and a clear-cut response to epithelial sodium channel (ENaC) blockers but not spironolactone therapy. Our understanding of ENaCs and Na(+) transport defects has expanded greatly over the past two decades and provides detailed insight into the molecular basis of Liddle's syndrome. In this review, we offer an overview of recent advances in understanding the molecular genetics of Liddle's syndrome, involving mutation analysis, molecular mechanisms and genetic testing. The ENaC in the distal nephron is composed of α, β and γ subunits that share similar structures. Mutations associated with Liddle's syndrome are positioned in either β or γ subunits and disturb or truncate a conserved proline-rich sequence (i.e., PY motif), leading to constitutive activation of the ENaC. Genetic testing has made it possible to make accurate diagnoses and develop tailored therapies for mutation carriers. Copyright © 2014 Elsevier B.V. All rights reserved.

Energetics of sodium transport in toad urinary bladder.

PubMed Central

Canessa, M; Labarca, P; DiBona, D R; Leaf, A

1978-01-01

The ratio of the rate of transepithelial sodium transport, JNa, across the isolated toad urinary bladder to the simultaneously measured rate of transport-dependent metabolism, JsbCO2, has been measured as a function of the transepithelial electrical voltage, deltapsi. The ratio remains constant with a mean value of 18 to 20 over the range of imposed voltages of 0 to +70 mV. With increasing hyperpolarization of the bladder, JNa decreases and the calculated electromotive force or apparent "ENa" of the sodium pump increases. From thermodynamic and kinetic arguments it is shown that the apparent "ENa" approaches the maximal electrochemical potential gradient, ENa, against which sodium can be transported by this tissue only when JNa approximately 0. At this unique condition F ENa (in which F is the Faraday constant) is the maximal free energy of the chemical reaction driving sodium transport and thus equal to the maximal extramitochondrial phosphorylation potential and the maximal free energy of the mitochondrial respiratory chain within the transporting cells. PMID:100789

From the Outside Looking In - Looking Back at Our Heliosphere in Energetic Neutral Atoms

NASA Astrophysics Data System (ADS)

Demajistre, R.; Brandt, P. C.; Gruntman, M.; McNutt, R. L., Jr.; Opher, M.; Roelof, E. C.; Wood, B. E.

2017-12-01

Energetic Neutral Atoms (ENAs) have been used over the past two decades to image space plasmas in planetary magnetospheres as well as the structure of the heliosheath. Any energetic plasma containing singly charged ions embedded in a cold neutral gas will 'glow' in ENAs, and this glow can be analyzed to infer the properties of the source plasma, giving us insight into processes that are difficult to study with the more traditional sensors that use photons/electromagnetic waves as an information carrier. ENA measurements of the heliosphere have (obviously) all been taken from vantage points in the inner heliosphere. ENAs created in the inner heliosphere from the solar wind and Pick Up Ions (PUIs) generally have large outward velocity, and thus do not reach sensors closer to the sun. Thus, the plasma is only 'visible' in ENAs to an inner heliosphere observer after it reaches the termination shock, where its outward motion is slowed and it is heated. This perspective from the inside looking out is convenient to study the outer boundary of the heliophere, but contains no direct information about the plasma and processes occurring in the inner heliosphere. ENA sensors placed outside the heliosphere, conversely would allow us to remotely sense both the inner and outer heliosphere, allowing us full access to the evolution of the solar wind and PUIs as they travel from the sun outward. Further, such a perspective would allow us to more directly measure the boundaries of the heliosphere with the LISM without the obscuration of the inner heliosheath. In this paper, we present modeled views of ENA images from the outside looking in at energies between 0.5 and 100 keV. It is important to note that while measurements of the outer heliosphere have been made by IBEX, Cassini/INCA, SoHO/HSTOF and the Voyagers, there are still important outstanding questions about the global structure and plasma flow patterns in the heliosphere. We will show here how new observations from the outside looking in can be used to address these questions.

ELISA subtypization of anti-ENA autoantibodies in clinical management of autoimmune diseases in Bosnia and Herzegovina.

PubMed

Subasic, Djemo; Karamehic, Jasenko; Gavrankapetanovic, Faris; Hodzic, Harun; Kasumovic, Mersija; Delic-Sarac, Marina; Prljaca-Zecevic, Lamija

2009-01-01

The basis of autoimmune diseases such as SLE (Systemic Lupus Eritematodes), Sjogren's syndrome, scleroderma, dermatomyositis and polymiositis is the creation of auto-antibodies to the following specific extractable nuclear antigens (ENA):Jo-1, Ssl-70, SS-A, SS-B, Sm and Sm/RNPs. Some of these antigens are in fact enzymes (Jo-1-histidil-tRNA synthetase, Scl-70-topoisomerase) which are inhibited by specific autoantibodies--this leads to disturbance in the metabolism of DNA and protein biosynthesis. During 2009, we analyzed total of 87 serum samples of patients suspected for autoimmune disorder using ANA-IFA and ELISA-ENA-6 methods. After establishing IFA-ANA positivity (83.9%), all serum specimens; ANA positive and negative, were subtypized by ELISA ENA-6 test. Analysis showed the highest incidence of anti-SS-A (56%), and incidence of anti-SS-B (29.8%), anti-Sm/ RNP (11.5%), anti-Jo-1 (2.3%) and anti-Scl-70 (1,1%) auto-antibodies. Also, 78.5% of IFA-ANA negative serum specimens showed high level of positivity (212.50 and 277.0 IU/ml) to SS-A (78.5%) and SS-B (21.4%) antigenes using ELISA-ENA-6 subtypization. Following these results, we conclude that it is necessary to introduce Western blot confirmation testing. After comparing with other clinical findings, we diagnosed the following autoimmune diseases: SLE, Sjogren's syndrome and dermatomiosytis.

Heliosphere Responds to a Large Solar Wind Intensification: Decisive Observations from IBEX

NASA Astrophysics Data System (ADS)

McComas, D. J.; Dayeh, M. A.; Funsten, H. O.; Heerikhuisen, J.; Janzen, P. H.; Reisenfeld, D. B.; Schwadron, N. A.; Szalay, J. R.; Zirnstein, E. J.

2018-03-01

Our heliosphere—the bubble in the local interstellar medium produced by the Sun’s outflowing solar wind—has finally responded to a large increase in solar wind output and pressure in the second half of 2014. NASA’s Interstellar Boundary Explorer (IBEX) mission remotely monitors the outer heliosphere by observing energetic neutral atoms (ENAs) returning from the heliosheath, the region between the termination shock and heliopause. IBEX observed a significant enhancement in higher energy ENAs starting in late 2016. While IBEX observations over the previous decade reflected a general reduction of ENA intensities, indicative of a deflating heliosphere, new observations show that the large (∼50%), persistent increase in the solar wind dynamic pressure has modified the heliosheath, producing enhanced ENA emissions. The combination of these new observations with simulation results indicate that this pressure is re-expanding our heliosphere, with the termination shock and heliopause already driven outward in the locations closest to the Sun. The timing between the IBEX observations, a large transient pressure enhancement seen by Voyager 2, and the simulations indicates that the pressure increase propagated through the heliosheath, reflected off the heliopause, and the enhanced density of the solar wind filled the heliosheath behind it before generating significantly enhanced ENA emissions. The coming years should see significant changes in anomalous cosmic rays, galactic cosmic radiation, and the filtration of interstellar neutral atoms into the inner heliosphere.

The role of lung inflation and sodium transport in airway liquid clearance during lung aeration in newborn rabbits.

PubMed

Siew, Melissa L; Wallace, Megan J; Allison, Beth J; Kitchen, Marcus J; te Pas, Arjan B; Islam, M Sirajul; Lewis, Robert A; Fouras, Andreas; Yagi, Naoto; Uesugi, Kentaro; Hooper, Stuart B

2013-04-01

Recent phase-contrast X-ray imaging studies suggest that inspiration primarily drives lung aeration and airway liquid clearance at birth, which questions the role of adrenaline-induced activation of epithelial sodium channels (ENaCs). We hypothesized that pressures generated by inspiration have a greater role in airway liquid clearance than do ENaCs after birth. Rabbit pups (30 d of gestation) were delivered and sedated, and 0.1 ml of saline (S) or amiloride (Am; an ENaC inhibitor) was instilled into the lungs before mechanical ventilation. Two other groups (30 d of gestation) were treated similarly but were also given adrenaline (S/Ad and Am/Ad) before mechanical ventilation. Amiloride and adrenaline did not affect functional residual capacity (FRC) recruitment (P > 0.05). Amiloride increased the rate of FRC loss between inflations (Am: -5.2 ± 0.6 ml/kg/s), whereas adrenaline reduced the rate of FRC loss (S/Ad: -1.9 ± 0.3 ml/kg/s) as compared with saline-treated controls (S: -3.5 ± -0.6 ml/kg/s; P < 0.05). These data indicate that inspiration is a major determinant of airway liquid clearance and FRC development during positive pressure ventilation. Although ENaC inhibition and adrenaline administration had no detectable effect on FRC development, ENaC may help to prevent liquid from re-entering the airways during expiration.

Delivery of ENaC siRNA to epithelial cells mediated by a targeted nanocomplex: a therapeutic strategy for cystic fibrosis.

PubMed

Manunta, Maria D I; Tagalakis, Aristides D; Attwood, Martin; Aldossary, Ahmad M; Barnes, Josephine L; Munye, Mustafa M; Weng, Alexander; McAnulty, Robin J; Hart, Stephen L

2017-04-06

The inhibition of ENaC may have therapeutic potential in CF airways by reducing sodium hyperabsorption, restoring lung epithelial surface fluid levels, airway hydration and mucociliary function. The challenge has been to deliver siRNA to the lung with sufficient efficacy for a sustained therapeutic effect. We have developed a self-assembling nanocomplex formulation for siRNA delivery to the airways that consists of a liposome (DOTMA/DOPE; L), an epithelial targeting peptide (P) and siRNA (R). LPR formulations were assessed for their ability to silence expression of the transcript of the gene encoding the α-subunit of the sodium channel ENaC in cell lines and primary epithelial cells, in submerged cultures or grown in air-liquid interface conditions. LPRs, containing 50 nM or 100 nM siRNA, showed high levels of silencing, particularly in primary airway epithelial cells. When nebulised these nanocomplexes still retained their biophysical properties and transfection efficiencies. The silencing ability was determined at protein level by confocal microscopy and western blotting. In vivo data demonstrated that these nanoparticles had the ability to silence expression of the α-ENaC subunit gene. In conclusion, these findings show that LPRs can modulate the activity of ENaC and this approach might be promising as co-adjuvant therapy for cystic fibrosis.

In Vitro Investigation of Wear of CAD/CAM Polymeric Materials Against Primary Teeth.

PubMed

Choi, Jae-Won; Song, Eun-Ju; Shin, Jong-Hyun; Jeong, Tae-Sung; Huh, Jung-Bo

2017-12-09

The aim of the study was to evaluate the effects of polymeric computer-aided design/computer-aided manufacturing CAD/CAM materials on antagonistic primary tooth wear. Five CAD/CAM polymeric materials were examined: Vipi Block Monocolor (VBM), Yamahachi polymethylmethacrylate (PMMA) (YAP), Mazic Duro (MZD), Vita Enamic (ENA), and Pekkton (PEK). All of the specimens were tested in a thermomechanical loading machine with the primary canine as the antagonist (50 N, 1.2 × 10⁵ cycles, 1.7 Hz, 5/55 °C). The wear losses of the antagonist tooth and the restorative materials were calculated using reverse modelling software and an electronic scale. VBM and ENA showed significantly higher antagonist tooth wear than PEK ( p < 0.05), but there was no significant difference observed among VBM, YAP, MZD, and ENA ( p > 0.05). PEK showed the largest value in both material volumetric and weight losses. In terms of material volumetric losses, there was no significant difference between all of the groups ( p > 0.05). In terms of material weight losses, PEK was significantly larger than ENA ( p < 0.05), but there was no significant difference between VBM, YAP, MZD, and ENA ( p > 0.05). Volumetric and weight losses of materials showed similar wear behaviour. However, the wear patterns of antagonists and materials were different, especially in PEK.

In Vitro Investigation of Wear of CAD/CAM Polymeric Materials Against Primary Teeth

PubMed Central

Song, Eun-Ju; Shin, Jong-Hyun; Jeong, Tae-Sung; Huh, Jung-Bo

2017-01-01

The aim of the study was to evaluate the effects of polymeric computer-aided design/computer-aided manufacturing CAD/CAM materials on antagonistic primary tooth wear. Five CAD/CAM polymeric materials were examined: Vipi Block Monocolor (VBM), Yamahachi polymethylmethacrylate (PMMA) (YAP), Mazic Duro (MZD), Vita Enamic (ENA), and Pekkton (PEK). All of the specimens were tested in a thermomechanical loading machine with the primary canine as the antagonist (50 N, 1.2 × 105 cycles, 1.7 Hz, 5/55 °C). The wear losses of the antagonist tooth and the restorative materials were calculated using reverse modelling software and an electronic scale. VBM and ENA showed significantly higher antagonist tooth wear than PEK (p < 0.05), but there was no significant difference observed among VBM, YAP, MZD, and ENA (p > 0.05). PEK showed the largest value in both material volumetric and weight losses. In terms of material volumetric losses, there was no significant difference between all of the groups (p > 0.05). In terms of material weight losses, PEK was significantly larger than ENA (p < 0.05), but there was no significant difference between VBM, YAP, MZD, and ENA (p > 0.05). Volumetric and weight losses of materials showed similar wear behaviour. However, the wear patterns of antagonists and materials were different, especially in PEK. PMID:29232849

Assessment of DNA damage in Ardea cinerea and Ciconia ciconia: A 5-year study in Portuguese birds retrieved for rehabilitation.

PubMed

Santos, Cátia S A; Brandão, Ricardo; Monteiro, Marta S; Bastos, Ana C; Soares, Amadeu M V M; Loureiro, Susana

2017-02-01

Over the past decades, the presence of micronucleated blood cells has been used to detect genotoxic effects of xenobiotics in fish, amphibians and birds. This study assessed the frequency of micronuclei (MN) and other nuclear abnormalities in erythrocytes of individuals of Ardea cinerea and Ciconia ciconia retrieved for rehabilitation in order to evaluate the influence of age, temporal and spatial factors on the occurrence of DNA damage in Portuguese wild birds. Blood smears from 65 birds with different life-history backgrounds (e.g. geographic origin, age) were collected between 2007 and 2011 and the frequency of erythrocyte nuclear abnormalities (ENAs) was analysed. Differences in DNA damage between ages were observed to occur in C. ciconia, with chicks displaying significantly higher frequencies of ENAs (both when looking at total ENAs or only MN frequency) than juveniles and adults. Additionally, significant differences in ENAs frequencies were observed between different years and geographic origins, whereas MN frequency alone did not show significant alterations concerning spatial and temporal variations. These results suggest that the assessment of ENAs rather than MN frequency alone may be a useful and valuable tool to complement the evaluation of DNA damage in populations of birds, as prompted by individual life-history traits and environmental factors. Copyright © 2016 Elsevier Inc. All rights reserved.

Hamilton-Jacobi theory in multisymplectic classical field theories

NASA Astrophysics Data System (ADS)

de León, Manuel; Prieto-Martínez, Pedro Daniel; Román-Roy, Narciso; Vilariño, Silvia

2017-09-01

The geometric framework for the Hamilton-Jacobi theory developed in the studies of Cariñena et al. [Int. J. Geom. Methods Mod. Phys. 3(7), 1417-1458 (2006)], Cariñena et al. [Int. J. Geom. Methods Mod. Phys. 13(2), 1650017 (2015)], and de León et al. [Variations, Geometry and Physics (Nova Science Publishers, New York, 2009)] is extended for multisymplectic first-order classical field theories. The Hamilton-Jacobi problem is stated for the Lagrangian and the Hamiltonian formalisms of these theories as a particular case of a more general problem, and the classical Hamilton-Jacobi equation for field theories is recovered from this geometrical setting. Particular and complete solutions to these problems are defined and characterized in several equivalent ways in both formalisms, and the equivalence between them is proved. The use of distributions in jet bundles that represent the solutions to the field equations is the fundamental tool in this formulation. Some examples are analyzed and, in particular, the Hamilton-Jacobi equation for non-autonomous mechanical systems is obtained as a special case of our results.

Potential Role of the Mirror and Ion Bernstein Instabilities on the Pickup Ion Dynamics in the Outer Heliosheath: Linear Theory and Hybrid Simulations

NASA Astrophysics Data System (ADS)

Min, K.; Liu, K.; Gary, S. P.

2017-12-01

The main challenge of the secondary ENA mechanism, a theory put forth to explain the IBEX ENA ribbon, is maintaining the stability of the pickup ion velocity distribution before the pickup ions in the outer heliosheath go through two consecutive charge exchanges. The Alfvén/ion-cyclotron instability, which has its maximum growth at propagation parallel to Bo, the background magnetic field, is believed to be the main agent leading to rapid isotropization of the pickup ions. However, recent studies found that this instability can be suppressed when parallel temperatures of the background plasma and the pickup ion ring distribution are comparable, allowing the pickup ion distribution to remain stable for a long period. This paper demonstrates that a pickup ion ring distribution can also drive the mirror and ion Bernstein instabilities which lead to growing modes at propagation oblique to Bo. For idealized proton-electron plasmas where relatively cool background electron and proton populations are represented by isotropic Maxwellian distributions and tenuous (1%) pickup protons are represented by a Maxwellian-ring distribution (assuming a 90˚ pickup angle), linear Vlasov theory predicts unstable mirror and ion Bernstein modes with growth rates comparable to or exceeding that of the Alfvén-cyclotron instability. According to quasilinear theory, interactions with these obliquely-propagating modes can lead to substantial pitch angle scattering of the ring protons. Two-dimensional hybrid (kinetic ions and massless fluid electrons) simulations are carried out to examine the nonlinear consequences of the mirror and Bernstein instabilities. The preliminary simulation results are presented. The study suggests a scenario that the oblique mirror and ion Bernstein modes can be an active agent of the pickup ion isotropization when the condition is such that the Alfvén-cyclotron instability is suppressed.

Kinetic modeling of auroral ion outflows observed by the VISIONS sounding rocket

NASA Astrophysics Data System (ADS)

Albarran, R. M.; Zettergren, M. D.

2017-12-01

The VISIONS (VISualizing Ion Outflow via Neutral atom imaging during a Substorm) sounding rocket was launched on Feb. 7, 2013 at 8:21 UTC from Poker Flat, Alaska, into an auroral substorm with the objective of identifying the drivers and dynamics of the ion outflow below 1000km. Energetic ion data from the VISIONS polar cap boundary crossing show evidence of an ion "pressure cooker" effect whereby ions energized via transverse heating in the topside ionosphere travel upward and are impeded by a parallel potential structure at higher altitudes. VISIONS was also instrumented with an energetic neutral atom (ENA) detector which measured neutral particles ( 50-100 eV energy) presumably produced by charge-exchange with the energized outflowing ions. Hence, inferences about ion outflow may be made via remotely-sensing measurements of ENAs. This investigation focuses on modeling energetic outflowing ion distributions observed by VISIONS using a kinetic model. This kinetic model traces large numbers of individual particles, using a guiding-center approximation, in order to allow calculation of ion distribution functions and moments. For the present study we include mirror and parallel electric field forces, and a source of ion cyclotron resonance (ICR) wave heating, thought to be central to the transverse energization of ions. The model is initiated with a steady-state ion density altitude profile and Maxwellian velocity distribution characterizing the initial phase-space conditions for multiple particle trajectories. This project serves to advance our understanding of the drivers and particle dynamics in the auroral ionosphere and to improve data analysis methods for future sounding rocket and satellite missions.

Kinetic modeling of auroral ion Outflows observed by the VISIONS sounding rocket

NASA Astrophysics Data System (ADS)

Albarran, R. M.; Zettergren, M. D.; Rowland, D. E.; Klenzing, J.; Clemmons, J. H.

2016-12-01

The VISIONS (VISualizing Ion Outflow via Neutral atom imaging during a Substorm) sounding rocket was launched on Feb. 7, 2013 at 8:21 UTC from Poker Flat, Alaska, into an auroral substorm with the objective of identifying the drivers and dynamics of the ion outflow below 1000km. Energetic ion data from the VISIONS polar cap boundary crossing show evidence of an ion "pressure cooker" effect whereby ions energized via transverse heating in the topside ionosphere travel upward and are impeded by a parallel potential structure at higher altitudes. VISIONS was also instrumented with an energetic neutral atom (ENA) detector which measured neutral particles ( 50-100 eV energy) presumably produced by charge-exchange with the energized outflowing ions. Hence, inferences about ion outflow may be made via remotely-sensing measurements of ENAs. This investigation focuses on modeling energetic outflowing ion distributions observed by VISIONS using a kinetic model. This kinetic model traces large numbers of individual particles, using a guiding-center approximation, in order to allow calculation of ion distribution functions and moments. For the present study we include mirror and parallel electric field forces, and a source of ion cyclotron resonance (ICR) wave heating, thought to be central to the transverse energization of ions. The model is initiated with a steady-state ion density altitude profile and Maxwellian velocity distribution characterizing the initial phase-space conditions for multiple particle trajectories. This project serves to advance our understanding of the drivers and particle dynamics in the auroral ionosphere and to improve data analysis methods for future sounding rocket and satellite missions.

Observations and Interpretations of Energetic Neutral Hydrogen Atoms from the December 5, 2006 Solar Event

NASA Technical Reports Server (NTRS)

Mewaldt, R. A.; Leske, R. A.; Shih, A. Y.; Stone, E. C.; Barghouty, A. f.; Cohen, C. M. S.; Cummings, A. c.; Labrador, A. W.; vonRosenvinge, T. T.

2009-01-01

We discuss recently reported observations of energetic neutral hydrogen atoms (ENAs) from an X9 solar flare/coronal mass ejection event on 5 December 2006, located at E79. The observations were made by the Low Energy Telescopes (LETs) on STEREO A and B. Prior to the arrival of the main solar energetic particle (SEP) event at Earth, both LETs observed a sudden burst of 1.6 to 15 MeV energetic neutral hydrogen atoms produced by either flare or shock-accelerated protons. RHESSI measurements of the 2.2-MeV gamma-ray line provide an estimate of the number of interacting flare-accelerated protons in this event, which leads to an improved estimate of ENA production by flare-accelerated protons. Taking into account ENA losses, we find that the observed ENAs must have been produced in the high corona at heliocentric distances > or equal to 2 solar radii. Although there are no CME images from this event, it is shown that CME-shock-accelerated protons can, in principle, produce a time-history consistent with the observations.

The mineralocorticoid receptor (MR) regulates ENaC but not NCC in mice with random MR deletion.

PubMed

Czogalla, Jan; Vohra, Twinkle; Penton, David; Kirschmann, Moritz; Craigie, Eilidh; Loffing, Johannes

2016-05-01

Aldosterone binds to the mineralocorticoid receptor (MR) and increases renal Na(+) reabsorption via up-regulation of the epithelial Na(+) channel (ENaC) and the Na(+)-K(+)-ATPase in the collecting system (CS) and possibly also via the NaCl cotransporter (NCC) in the distal convoluted tubule (DCT). However, whether aldosterone directly regulates NCC via MR or indirectly through systemic alterations remains controversial. We used mice with deletion of MR in ∼20 % of renal tubule cells (MR/X mice), in which MR-positive (MR(wt)) and -negative (MR(ko)) cells can be studied side-by-side in the same physiological context. Adult MR/X mice showed similar mRNA and protein levels of renal ion transport proteins to control mice. In MR/X mice, no differences in NCC abundance and phosphorylation was seen between MR(wt) and MR(ko) cells and dietary Na(+) restriction up-regulated NCC to similar extent in both groups of cells. In contrast, MR(ko) cells in the CS did not show any detectable alpha-ENaC abundance or apical targeting of ENaC neither on control diet nor in response to dietary Na(+) restriction. Furthermore, Na(+)-K(+)-ATPase expression was unaffected in MR(ko) cells of the DCT, while it was lost in MR(ko) cells of the CS. In conclusion, MR is crucial for ENaC and Na(+)-K(+)-ATPase regulation in the CS, but is dispensable for NCC and Na(+)-K(+)-ATPase regulation in the DCT.

βENaC acts as a mechanosensor in renal vascular smooth muscle cells that contributes to renal myogenic blood flow regulation, protection from renal injury and hypertension.

PubMed

Drummond, Heather A; Stec, David E

2015-06-01

Pressure-induced constriction (also known as the "myogenic response") is an important mechanodependent response in small renal arteries and arterioles. The response is initiated by vascular smooth muscle cell (VSMC) stretch due to an increase in intraluminal pressure and leads to vasoconstriction. The myogenic response has two important roles as a mechanism of local blood flow autoregulation and protection against systemic blood pressure-induced microvascular damage. However, the molecular mechanisms underlying initiation of myogenic response are unresolved. Although several molecules have been considered initiators of the response, our laboratory has focused on the role of degenerin proteins because of their strong evolutionary link to mechanosensing in the nematode. Our laboratory has addressed the hypothesis that certain degenerin proteins act as mechanosensors in VSMCs. This article discusses the importance of a specific degenerin protein, β Epithelial Na + Channel (βENaC), in pressure-induced vasoconstriction, renal blood flow and susceptibility to renal injury. We propose that loss of the renal myogenic constrictor response delays the correction of renal blood flow that occurs with fluctuations in systemic pressure, which allows pressure swings to be transmitted to the microvasculature, thus increasing the susceptibility to renal injury and hypertension. The role of βENaC in myogenic regulation is independent of tubular βENaC and thus represents a non-tubular role for βENaC in renal-cardiovascular homeostasis.

Origin and evolution of Sariñena Lake (central Ebro Basin): A piping-based model

NASA Astrophysics Data System (ADS)

Castañeda, Carmen; Javier Gracia, F.; Rodríguez-Ochoa, Rafael; Zarroca, Mario; Roqué, Carles; Linares, Rogelio; Desir, Gloria

2017-08-01

The origin and nature of the numerous lakes in the central Ebro Basin have been interpreted according to the prevailing arid or semiarid conditions, the easily-eroded materials and the solubility of the gypsum- and/or carbonate-rich Tertiary/Cenozoic substratum, involving important dissolution (karstic) and/or aeolian deflation. However, the origin of Sariñena Lake, the largest in the central Ebro Basin, remains unknown since the typical lake-generating processes in the region are not applicable. This work provides significant clues to the genesis and evolution of Sariñena Lake in a regional context. The combination of geomorphological mapping and high resolution LiDAR data together with sedimentological observations, the characterisation of soils and sediments around the lake, and the application of high-resolution geophysical techniques suggest that piping is the major genetic process driving the evolution of the Sariñena depression and lake. Field evidence demonstrates that piping is, at present, the most important erosive process in the region, generating significant collapse and surface lowering. Sariñena Lake is located within a deep endorheic depression excavated from Na-rich Tertiary materials. This work hypothesises that once an early, fluvially-originated palustrine area had developed, the progressive lowering of the regional water table linked to regional fluvial incision favoured the establishment of a hydrological gradient high enough to trigger piping processes within the claystones and siltstones underlying the original palustrine area. The Quaternary evolution of the Sariñena lacustrine basin was then controlled by successive water table fluctuations, linked to different phases of incision and alluvial deposition in the surrounding fluvial systems. All the evidence supporting a piping-related origin for this lake, together with examples of lakes generated by similar processes in different contexts, is used to propose a new genetic type of lacustrine depression, generated by piping processes under favourable conditions.

Cyp2c44 epoxygenase is essential for preventing the renal sodium absorption during increasing dietary potassium intake.

PubMed

Sun, Peng; Antoun, Joseph; Lin, Dao-Hong; Yue, Peng; Gotlinger, Katherine H; Capdevila, Jorge; Wang, Wen-Hui

2012-02-01

The aim of this study is to test whether the Cyp2c44 epoxygenase-dependent metabolism of arachidonic acid prevents the hypertensive effect of a high K (HK) intake by inhibiting the epithelial sodium channel (ENaC) activity. A HK intake elevated Cyp2c44 mRNA expression and 11,12-epoxyeicosatrienoic acid levels in the cortical collecting duct in Cyp2c44(+/+) mice (wild-type [wt]). However, an HK intake failed to increase 11,12-epoxyeicosatrienoic acid formation in the cortical collecting ducts of Cyp2c44(-/-) mice. Moreover, increasing K intake enhanced arachidonic acid-induced inhibition of ENaC in the wt but not in Cyp2c44(-/-) mice. In contrast, 11,12-epoxyeicosatrienoic acid, a Cyp2c44 metabolite, inhibited ENaC in the wt and Cyp2c44(-/-) mice. The notion that Cyp2c44 is the epoxygenase responsible for mediating the inhibitory effects of arachidonic acid on ENaC is further suggested by the observation that inhibiting Cyp-epoxygenase increased the whole-cell Na currents in principal cells of wt but not in Cyp2c44(-/-) mice. Feeding mice with an HK diet raised the systemic blood pressures of Cyp2c44(-/-) mice but was without an effect on wt mice. Moreover, application of amiloride abolished the HK-induced hypertension in Cyp2c44(-/-) mice. The HK-induced hypertension of Cyp2c44(-/-) mice was accompanied by decreasing 24-hour urinary Na excretion and increasing the plasma Na concentration, and the effects were absent in wt mice. In contrast, disruption of the Cyp2c44 gene did not alter K excretion. We conclude that Cyp2c44 epoxygenase mediates the inhibitory effect of arachidonic acid on ENaC and that Cyp2c44 functions as an HK-inducible antihypertensive enzyme responsible for inhibiting ENaC activity and Na absorption in the aldosterone-sensitive distal nephron.

Editorial: Interstellar Boundary Explorer (IBEX): Direct Sampling of the Interstellar Medium

NASA Astrophysics Data System (ADS)

McComas, D. J.

2012-02-01

This special supplement issue of the Astrophysical Journal comprises six coordinated papers that provide the first detailed analyses of the direct sampling of interstellar neutral atoms by the Interstellar Boundary Explorer (IBEX). Interstellar atoms are the detritus of older stars—their stellar winds, novae, and supernovae—spread across the galaxy, which fill the vast interstellar space between the stars. The very local interstellar medium around the Sun is filled with both ionized and neutral atoms with approximately equal numbers, and occasional ionization, charge exchange, and recombination makes them a single interacting material over large distances. IBEX (McComas et al. 2009a) is a NASA Small Explorer mission with the sole, focused science objective to discover the global interaction between the solar wind and the interstellar medium; this objective has primarily been achieved by taking the first global energetic neutral atom (ENA) images, which provide detailed ENA fluxes and energy spectra over all look directions in space. IBEX was launched 2008 October 19 and subsequently maneuvered into a high-altitude, highly elliptical (~15,000 × 300,000 km), roughly week-long orbit. The payload comprises two very high sensitivity, single-pixel ENA cameras: IBEX-Hi (Funsten et al. 2009a), which measures ENAs from ~300 eV to 6 keV, and IBEX-Lo (Fuselier et al. 2009a), which measures ENAs from ~10 eV to 2 keV. The initial IBEX ENA results were published together in a special issue of Science magazine (McComas et al. 2009b; Funsten et al. 2009b; Fuselier et al. 2009b; Schwadron et al. 2009). Since then there have been numerous additional studies of the IBEX ENA observations of the heliosphere, as well as ENAs from the Moon and Earth's magnetosphere (see recent review by McComas et al. 2011 and references therein). Prior to IBEX, the only interstellar neutral atoms to be directly sampled were He, observed by the Ulysses spacecraft a decade ago (Witte et al. 1996; Witte 2004). The first paper published on IBEX observations of interstellar neutral atoms (Möbius et al. 2009) used observations from the spring of 2009, shortly after IBEX achieved its first long-term orbit; that study showed that IBEX is able to directly observe interstellar H and O in addition to He, but provided only limited analysis of these measurements. IBEX has now completed a second full annual season of neutral observations in 2010, which together with the independent 2009 observations provide data adequate to carry out the first round of detailed, quantitative analyses of the IBEX interstellar neutral observations. In this special supplement issue, the IBEX Science Team presents a coordinated series of six articles that focus on various synergistic aspects of these observations, their analyses, and their implications. A critical foundational paper in this volume, Hlond et al. (2012), analyzes the angular pointing knowledge of IBEX observations and demonstrates that the arrival direction knowledge of neutral atoms can be determined to ~0.1° in both spin angle and elevation. This is no mean feat for a Small Explorer mission designed to measure ENAs in 7° × 7° pixels, and largely at much higher energies than the direct interstellar neutrals. In addition, these authors demonstrate that the in-space (post-launch) bore sight of the IBEX-Lo instrument can achieve this accuracy with either the spacecraft's on board attitude control system or an independent Star Sensor that was designed and built directly into the IBEX-Lo instrument. Lee et al. (2012) derive the analytical solution for the hyperbolic trajectories of individual neutral atoms by using Liouville's theorem, including solar gravity and radiation pressure, photoionization and charge exchange, to produce interstellar neutral atom phase-space distributions. These distributions are then transformed into the IBEX reference frame and integrated over the IBEX-Lo instrumental acceptance to provide an analytic solution for the predicted fluid moments of the interstellar neutral atom distributions. This analytic solution for the interstellar neutral parameters provides the basis for a companion paper by Möbius et al. (2012), who analyze the IBEX He (and Ne+O) measurements using the Lee et al. analytic solutions. This approach allows for physical insights into the dominant physical processes, while in another related paper Bzowski et al. (2012) describe a detailed forward model of the interstellar helium from the edge of the heliosphere all the way through the IBEX instrument geometry. Together, these papers show that the prior values for the interstellar flow speed and direction from Ulysses are inconsistent with our new IBEX observations. Möbius et al. (2012) compare the He and O+Ne flow distributions for both 2009 and 2010 and find interstellar flow parameters of ecliptic longitude at ∞ = 79.0° + 3.0°/-3.5°, ecliptic latitude at ∞ = -4.9° ± 0.2°, ISM speed at ∞ = 23.5 + 3.0/-2.0 km s-1, and neutral He temperature = 5000-8200 K. They also find a combined O+Ne temperature of 5300-9000 K, consistent with an isothermal medium for He, O, and Ne. Bzowski et al. (2012) develop and extensively test a detailed forward model simulation of the interstellar He propagation, losses, and measurement in the IBEX-Lo instrument. These simulations start particles at 150 AU and include more detailed physics than the analytic solutions; they therefore complement the analytic method by allowing detailed mapping of the multi-dimensional space of possible solutions. These authors show that the IBEX results are not in statistical agreement with the Ulysses values and provide new best-fit values of ecliptic longitude 79.2°, ecliptic latitude of -5.1°, speed of ~22.8 km s-1, and He temperature is 6200 K. The values obtained with both complementary methods agree with each other and are in agreement with the flow vector of the local interstellar cloud obtained from studies of interstellar absorption (Redfield & Linsky 2008). Bzowski et al. also show evidence for a previously unknown and unanticipated secondary population of helium. Together, the Möbius et al. (2012) and Bzowski et al. (2012) results provide a new interstellar flow direction and a significantly lower velocity of the incoming gas and therefore significantly lower dynamic pressure on the heliosphere, which translates into a heliospheric interaction that is even less dominated by the external dynamic pressure and clearly lies squarely in the middle ground of astrospheres dominated by the external magnetic and dynamic pressures (McComas et al. 2009b). On another topic, Bochsler et al. (2012) report the first direct measurements of interstellar Ne and estimate the interstellar Ne/O abundance ratio, showing a gas-phase Ne/O ratio for the LISM of 0.27 ± 0.10. This value agrees with results obtained from pickup ion observations (Gloeckler & Geiss 2004; Gloeckler & Fisk 2007) and is significantly larger than the solar abundance ratio, indicating that the LISM is different than the Sun's formation region and/or that a substantial portion of the O in the LISM is tied up (and thus "hidden") in grains and/or ices. Finally, Saul et al. (2012) provide the first detailed analysis of the new interstellar H measurements from IBEX. These authors confirm that the arrival direction of interstellar H is offset from that of He. They further show a variation in the strength of the radiation pressure and thus a change in the apparent arrival direction of H penetrating to 1 AU between the first two years of IBEX observations; these results are consistent with solar cycle variations in the radiation pressure, which works opposite to the Sun's gravitational force to effect the penetration of H into the inner heliosphere. Together, these six studies provide the first detailed analyses of the multi-component local interstellar medium—a medium that both effects us by bounding and interacting with our heliosphere, and a medium that gives us a first direct glimpse of non-solar material from the rest of the galaxy.

Expression and function of Anoctamin 1/TMEM16A calcium-activated chloride channels in airways of in vivo mouse models for cystic fibrosis research.

PubMed

Hahn, Anne; Salomon, Johanna J; Leitz, Dominik; Feigenbutz, Dennis; Korsch, Lisa; Lisewski, Ina; Schrimpf, Katrin; Millar-Büchner, Pamela; Mall, Marcus A; Frings, Stephan; Möhrlen, Frank

2018-06-02

Physiological processes of vital importance are often safeguarded by compensatory systems that substitute for primary processes in case these are damaged by gene mutation. Ca 2+ -dependent Cl - secretion in airway epithelial cells may provide such a compensatory mechanism for impaired Cl - secretion via cystic fibrosis transmembrane conductance regulator (CFTR) channels in cystic fibrosis (CF). Anoctamin 1 (ANO1) Ca 2+ -gated Cl - channels are known to contribute to calcium-dependent Cl - secretion in tracheal and bronchial epithelia. In the present study, two mouse models of CF were examined to assess a potential protective function of Ca 2+ -dependent Cl - secretion, a CFTR deletion model (cftr -/- ), and a CF pathology model that overexpresses the epithelial Na + channel β-subunit (βENaC), which is encoded by the Scnn1b gene, specifically in airway epithelia (Scnn1b-Tg). The expression levels of ANO1 were examined by mRNA and protein content, and the channel protein distribution between ciliated and non-ciliated epithelial cells was analyzed. Moreover, Ussing chamber experiments were conducted to compare Ca 2+ -dependent Cl - secretion between wild-type animals and the two mouse models. Our results demonstrate that CFTR and ANO1 channels were co-expressed with ENaC in non-ciliated cells of mouse tracheal and bronchial epithelia. Ciliated cells did not express these proteins. Despite co-localization of CFTR and ANO1 in the same cell type, cells in cftr -/- mice displayed no altered expression of ANO1. Similarly, ANO1 expression was unaffected by βENaC overexpression in the Scnn1b-Tg line. These results suggest that the CF-related environment in the two mouse models did not induce ANO1 overexpression as a compensatory system.

Effect of ENaC Modulators on Rat Neural Responses to NaCl

PubMed Central

Mummalaneni, Shobha; Qian, Jie; Phan, Tam-Hao T.; Rhyu, Mee-Ra; Heck, Gerard L.; DeSimone, John A.; Lyall, Vijay

2014-01-01

The effects of small molecule ENaC activators N,N,N-trimethyl-2-((4-methyl-2-((4-methyl-1H-indol-3-yl)thio)pentanoyl)oxy)ethanaminium iodide (Compound 1) and N-(2-hydroxyethyl)-4-methyl-2-((4-methyl-1H-indol-3-yl)thio)pentanamide (Compound 2), were tested on the benzamil (Bz)-sensitive NaCl chorda tympani (CT) taste nerve response under open-circuit conditions and under ±60 mV applied lingual voltage-clamp, and compared with the effects of known physiological activators (8-CPT-cAMP, BAPTA-AM, and alkaline pH), and an inhibitor (ionomycin+Ca2+) of ENaC. The NaCl CT response was enhanced at −60 mV and suppressed at +60 mV. In every case the CT response (r) versus voltage (V) curve was linear. All ENaC activators increased the open-circuit response (ro) and the voltage sensitivity (κ, negative of the slope of the r versus V curve) and ionomycin+Ca2+ decreased ro and κ to zero. Compound 1 and Compound 2 expressed a sigmoidal-saturating function of concentration (0.25–1 mM) with a half-maximal response concentration (k) of 0.49 and 1.05 mM, respectively. Following treatment with 1 mM Compound 1, 8-CPT-cAMP, BAPTA-AM and pH 10.3, the Bz-sensitive NaCl CT response to 100 mM NaCl was enhanced and was equivalent to the Bz-sensitive CT response to 300 mM NaCl. Plots of κ versus ro in the absence and presence of the activators or the inhibitor were linear, suggesting that changes in the affinity of Na+ for ENaC under different conditions are fully compensated by changes in the apical membrane potential difference, and that the observed changes in the Bz-sensitive NaCl CT response arise exclusively from changes in the maximum CT response (rm). The results further suggest that the agonists enhance and ionomycin+Ca2+ decreases ENaC function by increasing or decreasing the rate of release of Na+ from its ENaC binding site to the receptor cell cytosol, respectively. Irrespective of agonist type, the Bz-sensitive NaCl CT response demonstrated a maximum response enhancement limit of about 75% over control value. PMID:24839965

Calculating clear-sky radiative heating rates using the Fu-Liou RTM with inputs from observed and reanalyzed profiles

NASA Astrophysics Data System (ADS)

Dolinar, E. K.; Dong, X.; Xi, B.

2015-12-01

One-dimensional radiative transfer models (RTM) are a common tool used for calculating atmospheric heating rates and radiative fluxes. In the forward sense, RTMs use known (or observed) quantities of the atmospheric state and surface characteristics to determine the appropriate surface and top-of-atmosphere (TOA) radiative fluxes. The NASA CERES science team uses the modified Fu-Liou RTM to calculate atmospheric heating rates and surface and TOA fluxes using the CERES observed TOA shortwave (SW) and longwave (LW) fluxes as constraints to derive global surface and TOA radiation budgets using a reanalyzed atmospheric state (e.g. temperature and various greenhouse gases) from the newly developed MERRA-2. However, closure studies have shown that using the reanalyzed state as input to the RTM introduces some disparity between the RTM calculated fluxes and surface observed ones. The purpose of this study is to generate a database of observed atmospheric state profiles, from satellite and ground-based sources, at several permanent Atmospheric Radiation Measurement (ARM) Program sites, including the Southern Great Plains (SGP), Northern Slope of Alaska (NSA) and Tropical Western Pacific Nauru (TWP-C2), and Eastern North Atlantic (ENA) permanent facilities. Since clouds are a major modulator of radiative transfer within the Earth's atmosphere, we will focus on the clear-sky conditions in this study, which will set up the baseline for our cloudy studies in the future. Clear-sky flux profiles are calculated using the Edition 4 NASA LaRC modified Fu-Liou RTM. The aforementioned atmospheric profiles generated in-house are used as input into the RTM, as well as from reanalyses. The calculated surface and TOA fluxes are compared with ARM surface measured and CERES satellite observed SW and LW fluxes, respectively. Clear-sky cases are identified by the ARM radar-lidar observations, as well as satellite observations, at the select ARM sites.

Caveolin-1 siRNA increases the pulmonary microvascular and alveolar epithelial permeability in rats.

PubMed

Gao, Chengjin; Li, Rongrong; Huan, Jingning; Li, Wei

2011-01-01

Increased pulmonary microvascular and epithelial permeability are important contributors to pulmonary edema in acute lung injury. In this study, we used small interfering RNA (siRNA) to knock down caveolin-1 expression in rat lungs and to confirm the important role of caveolin-1 in regulating pulmonary edema. After pulmonary injection of siRNA against caveolin-1 messenger RNA incorporated in liposomes with three concentrations of 0.4, 0.8, and 1.2 mg/kg, the gene silencing rate and the effects of caveolin-1 siRNA on aquaporin (AQP)-1, AQP-5, and epithelial sodium channel (ENaC) were detected. For pulmonary permeability analysis, Evans blue fluorimetry, ratios of albumin concentrations between blood and bronchoalveolar lavage, and wet/dry weight ratios were measured. The impacts of caveolin-1 suppression on interendothelial junctions were evaluated by the performance of electron microscopy and the analysis of vascular endothelial (VE)-cadherin Western blot. Alveolar wall thickness analysis and chest fluoroscopy were performed to determine the pulmonary edema degree. After 72 hours of injection, the gene silencing rate of caveolin-1 siRNA is about 87%. AQP-1, AQP-5, ENaC-α, ENaC-β, ENaC-γ, and VE-cadherin protein levels were decreased by 63%, 66%, 80%, 90%, 89%, and 50%, respectively. Caveolin-1 siRNA also resulted in increasing microvascular and epithelial permeability and pulmonary edema. These data suggest that caveolin-1 plays an important part in regulating the pulmonary permeability by modifying AQP-1, AQP-5, ENaC, and VE-cadherin.

Urinary Proteolytic Activation of Renal Epithelial Na+ Channels in Chronic Heart Failure.

PubMed

Zheng, Hong; Liu, Xuefei; Sharma, Neeru M; Li, Yulong; Pliquett, Rainer U; Patel, Kaushik P

2016-01-01

One of the key mechanisms involved in renal Na(+) retention in chronic heart failure (CHF) is activation of epithelial Na(+) channels (ENaC) in collecting tubules. Proteolytic cleavage has an important role in activating ENaC. We hypothesized that enhanced levels of proteases in renal tubular fluid activate ENaC, resulting in renal Na(+) retention in rats with CHF. CHF was produced by left coronary artery ligation in rats. By immunoblotting, we found that several urinary serine proteases were significantly increased in CHF rats compared with sham rats (fold increases: furin 6.7, prostasin 23.6, plasminogen 2.06, and plasmin 3.57 versus sham). Similar increases were observed in urinary samples from patients with CHF. Whole-cell patch clamp was conducted in cultured renal collecting duct M-1 cells to record Na(+) currents. Protease-rich urine (from rats and patients with CHF) significantly increased the Na(+) inward current in M-1 cells. Two weeks of protease inhibitor treatment significantly abrogated the enhanced diuretic and natriuretic responses to ENaC inhibitor benzamil in rats with CHF. Increased podocyte lesions were observed in the kidneys of rats with CHF by transmission electron microscopy. Consistent with these results, podocyte damage markers desmin and podocin expressions were also increased in rats with CHF (increased ≈2-folds). These findings suggest that podocyte damage may lead to increased proteases in the tubular fluid, which in turn contributes to the enhanced renal ENaC activity, providing a novel mechanistic insight for Na(+) retention commonly observed in CHF. © 2015 American Heart Association, Inc.

Urinary proteolytic activation of renal epithelial Na+ channels in chronic heart failure

PubMed Central

Zheng, Hong; Liu, Xuefei; Sharma, Neeru M.; Li, Yulong; Pliquett, Rainer U; Patel, Kaushik P.

2015-01-01

One of the key mechanisms involved in renal Na+ retention in chronic heart failure (CHF) is activation of epithelial Na+ channels (ENaC) in collecting tubules. Proteolytic cleavage has an important role in activating ENaC. We hypothesized that enhanced levels of proteases in renal tubular fluid activate ENaC resulting in renal Na+ retention in rats with CHF. CHF was produced by left coronary artery ligation in rats. By immunoblotting, we found that several urinary serine proteases were significantly increased in CHF rats compared to sham rats (fold increases: furin 6.7, prostasin 23.6, plasminogen 2.06 and plasmin 3.57 vs. sham). Similar increases were observed in urinary samples from patients with CHF. Whole-cell patch-clamp was conducted in cultured renal collecting duct M-1 cells to record Na+ currents. Protease-rich urine (from rats and patients with CHF) significantly increased the Na+ inward current in M-1 cells. Two weeks of protease inhibitor treatment significantly abrogated the enhanced diuretic and natriuretic responses to ENaC inhibitor benzamil in rats with CHF. Increased podocyte lesions were observed in the kidneys of rats with CHF by transmission electron microscopy. Consistent with these results, podocyte damage markers desmin and podocin expressions were also increased in rats with CHF (increased ~2 folds). These findings suggest that podocyte damage may lead to increased proteases in the tubular fluid which in turn contributes to the enhanced renal ENaC activity, providing a novel mechanistic insight for Na+ retention commonly observed in CHF. PMID:26628676

Detection of autoimmunity in early primary Epstein-Barr virus infection by Western blot analysis.

PubMed

Mascia, M T; Sandri, G; Guerzoni, C; Roncaglia, R; Mantovani, G; Ferri, C

2008-01-01

The Epstein-Barr virus (EBV) represents a potentially important factor in the pathogenesis of certain autoimmune disorders such as systemic lupus erythematosus (SLE), and Sjögren's syndrome, probably through a molecular mimicry mechanism. Several studies have focused on the relationship between previous EBV infection and clinically overt connective tissue diseases (CTDs), while the aim of this study was to investigate the immunological alterations during the early phase of primary acute EBV infection by means of ENA Western blotting (WB) analysis. This technique is able to detect a wide spectrum of anti-ENA autoantibodies, potentially directed against diverse epitopes of the same antigen. Sera from 54 subjects (F/M=24/30, mean age 17+/-6 SD years) with primary acute EBV infection were analysed using indirect immunofluorescence (IF) on Hep-2 cells for ANA, and both ELISA and WB for ENA. Only 8 ANA+ and no ENA+ were found by means of IF and ELISA techniques, respectively; however, one or more ENA autoantibodies were detected in 24/54 (44%) sera using WB. The autoantibodies were no longer present at the second evaluation. Subjects with immunological alterations had not developed any significant clinical manifestations at a 5-year follow-up. This study demonstrated the appearance of autoantibody production in a high proportion of individuals with primary acute EBV infection; interestingly, the observed serological subsets are quite similar to clinical SLE clusters. Moreover, the absence of immunological disorders during the follow-up reinforces the role of multiple genetic and/or environmental co-factors in the pathogenesis of CTDs.

Morphophysiological dormancy in seeds of three eastern North American Sanicula species (Apiaceae subf

Treesearch

Tracy S. Hawkins; Carol C. Baskin; Jerry M Baskin

2010-01-01

Dormancy breaking and germination requirements were determined for seeds of the eastern North American (eNA) species Sanicula canadensis, Sanicula gregaria and Sanicula trifoliata, and the data compared to those available for the European–Asian (EurA) congener Sanicula europaea. Seeds of the three eNA species had underdeveloped embryos that were physiologically dormant...

Sexy DEG/ENaC channels involved in gustatory detection of fruit fly pheromones.

PubMed

Pikielny, Claudio W

2012-11-06

Hydrocarbon pheromones on the cuticle of Drosophila melanogaster modulate the complex courtship behavior of males. Recently, three members of the degenerin/epithelial Na+ channel (DEG/ENaC) family of sodium channel subunits, Ppk25, Ppk23, and Ppk29 (also known as Nope), have been shown to function in gustatory perception of courtship-modulating contact pheromones. All three proteins are required for the activation of male courtship by female pheromones. Specific interactions between two of them have been demonstrated in cultured cells, suggesting that, in a subset of cells where they are coexpressed, these three subunits function within a common heterotrimeric DEG/ENaC channel. Such a DEG/ENaC channel may be gated by pheromones, either directly or indirectly, or alternatively may control the excitability of pheromone-sensing cells. In addition, these studies identify taste neurons that respond specifically to courtship-modulating pheromones and mediate their effects on male behavior. Two types of pheromone-sensing taste neurons, F and M cells, have been defined on the basis of their specific response to either female or male pheromones. These reports set the stage for the dissection of the molecular and cellular mechanisms that mediate gustatory detection of contact pheromones.

Observation and Interpretation of Energetic Neutral Hydrogen Atoms from the December 5, 2006 Solar Flare

NASA Technical Reports Server (NTRS)

Barghouty, A. F.; Mewaldt, R. A.; Leske, R. A.; Shih, A. Y.; Stone, E. C.; Cohen, C. M. S.; Cummings, A. C.; Labrador, A. W.; vonRosenvinge, T. T.; Wiedenbeck, M. E.

2009-01-01

We discuss observations of energetic neutral hydrogen atoms (ENAs) from a solar flare/coronal mass ejection event reported by Mewaldt et al. (2009). The observations were made during the 5 December 2006 X9 solar flare, located at E79, by the Low Energy Telescopes (LETs) on STEREO A and B. Prior to the arrival of the main solar energetic particle (SEP) event at Earth, both LETs observed a sudden burst of 1.6 to 15 MeV particles arriving from the Sun. The derived solar emission profile, arrival directions, and energy spectrum all show that the <5 MeV particles were due to energetic neutral hydrogen atoms produced by either flare or shock-accelerated protons. RHESSI measurements of the 2.2-MeV gamma-ray line provide an estimate of the number of interacting flare-accelerated protons in this event, which leads to an improved estimate of ENA production by flare-accelerated protons. CME-driven shock acceleration is also considered. Taking into account ENA losses, we conclude that the observed ENAs must have been produced in the high corona at heliocentric distances .2 solar radii.

The Origin of Low Altitude ENA Emissions from Storms in 2000-2005 as Observed by IMAGE/MENA

NASA Astrophysics Data System (ADS)

Perez, J. D.; Sheehan, M. M.; Jahn, J.; Mackler, D.; Pollock, C. J.

2013-12-01

Low Altitude Emissions (LAEs) are prevalent features of Energetic Neutral Atom (ENA) images of the inner magnetosphere. It is believed that they are created by precipitating ions that reach altitudes near 500 km and then charge exchange with oxygen atoms, subsequently escaping to be observed by satellite borne ENA imagers. In this study, LAEs from the MENA instrument onboard the IMAGE satellite are studied in order to learn about the origin of the precipitating ions. Using the Tsyganenko 05 magnetic field model, the bright pixels capturing the LAEs are mapped to the equator. The LAEs are believed to originate from ions near their mirroring point, i.e., with pitch angles near 90o. Therefore the angle between the line-of-sight and the magnetic field at the point of origin is used to further constrain possible magnetospheric regions that are the origin of the ENAs. By observing the time dependence of the strength and location of the LAEs during geomagnetic storms in the years 2000-2005, the dynamics of the emptying and filling of the loss cone by injected particles is observed. Thus, information regarding the coupling between the inner magnetosphere and the ionosphere is obtained.

Field Aligned Currents Derived From Pressure Profiles Obtained From TWINS ENA Images for Geomagnetic Storms That Occurred On 01 June 2013 and 17 March 2015.

NASA Astrophysics Data System (ADS)

Wood, K.; Perez, J. D.; Goldstein, J.; McComas, D. J.; Valek, P. W.

2016-12-01

Field aligned currents (FACs) that flow from the Earth's magnetosphere into the ionosphere are an important coupling mechanism in the interaction of the solar wind with the Earth's magnetosphere and ionosphere. Assuming pressure balance and charge conservation yields an expression for the FACs in terms of plasma pressure gradients and pressure anisotropy. The Two Wide-angle Imaging Neutral Atom Spectrometers (TWINS) mission, the first stereoscopic ENA magnetospheric imager, provides global images of the inner magnetosphere from which ion pressure distributions and pressure anisotropies are obtained. Following the formulations in Vasyliunas (1970), Vasyliunas (1984), and Heinemann (1990), and using results from TWINS observations, we calculate the distributions of field aligned currents for geomagnetic storms on 1 June 2013 and 17 March 2015, in which extended ionospheric precipitation was observed. As previous work has assumed isotropic pressure distributions, we perform calculations both assuming pressure isotropy, and using the pressure anisotropy observed by TWINS, and compare the results from the two storms. References: 1. Vasyliunas, V. M. (1970). Mathematical Models of Magnetospheric Convection and its Coupling to the Ionosphere. Particles and Fields in the Magnetosphere Astrophysics and Space Science Library, 60-71. doi:10.1007/978-94-010-3284-1_6 2. Vasyliunas, V. M. (1984). Fundamentals of current description. Magnetospheric Currents Geophysical Monograph Series, 63-66. doi:10.1029/gm028p0063 3. Heinemann, M. (1990). Representations of currents and magnetic fields in anisotropic magnetohydrostatic plasma. J. Geophys. Res. Journal of Geophysical Research, 95(A6), 7789. doi:10.1029/ja095ia06p07789

Water vapor isotopic measurements from the Atmospheric Radiation Measurement site on Graciosa Island, Azores

NASA Astrophysics Data System (ADS)

Delp, J. M.; Galewsky, J.

2017-12-01

Stable isotopic measurements of water vapor can potentially constrain the processes that govern the formation of low-clouds and how their distribution may change as the climate warms. Using off-axis integrated cavity output spectroscopy, in-situ water vapor isotopic measurements will be collected for a period of one year (beginning August 2017) at the US Department of Energy (DOE) Atmospheric Radiation Measurement (ARM) site in the Eastern North Atlantic (ENA) located on Graciosa Island, Azores. The Azores location within the ENA is a prime setting for studying low-cloud processes. After correcting for humidity-dependent biases and normalizing the measurements to the VSMOW-SLAP scale, the measurements from the first several months of the water vapor isotopic analyzer's deployment will be compared to complementary datasets from the suite of instruments at the DOE site, including twice-daily soundings, aerosol instrumentation, and cloud radars, with the purpose of determining links between local stratocumulus and precipitation processes and their impact on the stable isotopic composition of atmospheric water vapor. The results of this study will potentially provide a new approach for linking field observations with climate models and may help better constrain the uncertainties associated with low-cloud feedbacks.

A New Model for the Heliosphere’s “IBEX Ribbon”

NASA Astrophysics Data System (ADS)

Giacalone, J.; Jokipii, J. R.

2015-10-01

We present a model for the narrow, ribbon-like enhancement in the emission of ∼keV energetic neutral atoms (ENA) coming from the outer heliosphere, coinciding roughly with the plane of the very local interstellar magnetic field (LISMF). We show that the pre-existing turbulent LISMF has sufficient amplitude in magnitude fluctuations to efficiently trap ions with initial pitch-angles near 90°, primarily by magnetic mirroring, leading to a narrow region of enhanced pickup-proton intensity. The pickup protons interact with cold interstellar hydrogen to produce ENAs seen at 1 AU. The computed width of the resulting ribbon of emission is consistent with observations. We also present results from a numerical model that are also generally consistent with the observations. Our interpretation relies only on the pre-existing turbulent interstellar magnetic field to trap the pickup protons. This leads to a broader local pitch-angle distribution compared to that of a ring. Our numerical model also predicts that the ribbon is double-peaked with a central depression. This is a further consequence of the (primarily) magnetic mirroring of pickup ions with pitch-angles close to 90° in the pre-existing, turbulent interstellar magnetic field.

A NEW MODEL FOR THE HELIOSPHERE’S “IBEX RIBBON”

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

Giacalone, J.; Jokipii, J. R.

We present a model for the narrow, ribbon-like enhancement in the emission of ∼keV energetic neutral atoms (ENA) coming from the outer heliosphere, coinciding roughly with the plane of the very local interstellar magnetic field (LISMF). We show that the pre-existing turbulent LISMF has sufficient amplitude in magnitude fluctuations to efficiently trap ions with initial pitch-angles near 90°, primarily by magnetic mirroring, leading to a narrow region of enhanced pickup-proton intensity. The pickup protons interact with cold interstellar hydrogen to produce ENAs seen at 1 AU. The computed width of the resulting ribbon of emission is consistent with observations. Wemore » also present results from a numerical model that are also generally consistent with the observations. Our interpretation relies only on the pre-existing turbulent interstellar magnetic field to trap the pickup protons. This leads to a broader local pitch-angle distribution compared to that of a ring. Our numerical model also predicts that the ribbon is double-peaked with a central depression. This is a further consequence of the (primarily) magnetic mirroring of pickup ions with pitch-angles close to 90° in the pre-existing, turbulent interstellar magnetic field.« less

Regulation of Sodium Transport in the Inner Ear

PubMed Central

Kim, Sung Huhn; Marcus, Daniel C.

2011-01-01

Na+ concentrations in endolymph must be controlled to maintain hair cell function since the transduction channels of hair cells are cation-permeable, but not K+-selective. Flooding or fluctuations of the hair cell cytosol with Na+ would be expected to lead to cellular dysfunction, hearing loss and vertigo. This review briefly describes cellular mechanisms known to be responsible for Na+homeostasis in each compartment of the inner ear, including the cochlea, saccule, semicircular canals and endolymphatic sac. The influx of Na+into endolymph of each of the organs is likely via passive diffusion, but these pathways have not yet been identified or characterized. Na+ absorption is controlled by gate -keeper channels in the apical (endolymphatic) membrane of the transporting cells. Highly Na+-selective epithelial sodium channels (ENaC) control absorption by Reissner’s membrane, saccular extramacular epithelium, semicircular canal duct epithelium and endolymphatic sac. ENaC activity is controlled by a number of signal pathways, but most notably by genomic regulation of channel numbers in the membrane via glucocorticoid signaling. Nonselective cation channels in the apical membrane of outer sulcus epithelial cells and vestibular transitional cells mediate Na+ and parasensory K+ absorption. The K+-mediated transduction current in hair cells is also accompanied by a Na+ flux since the transduction channels are nonselective cation channels. Cation absorption by all of these cells is regulated by extracellular ATP via apical nonselective cation channels (P2X receptors). The heterogeneous population of epithelial cells in the endolymphatic sac is thought to have multiple absorptive pathways for Na+ with regulatory pathways that include glucocorticoids and purinergic agonists. PMID:21620939

Activation of the Endogenous Renin-Angiotensin-Aldosterone System or Aldosterone Administration Increases Urinary Exosomal Sodium Channel Excretion.

PubMed

Qi, Ying; Wang, Xiaojing; Rose, Kristie L; MacDonald, W Hayes; Zhang, Bing; Schey, Kevin L; Luther, James M

2016-02-01

Urinary exosomes secreted by multiple cell types in the kidney may participate in intercellular signaling and provide an enriched source of kidney-specific proteins for biomarker discovery. Factors that alter the exosomal protein content remain unknown. To determine whether endogenous and exogenous hormones modify urinary exosomal protein content, we analyzed samples from 14 mildly hypertensive patients in a crossover study during a high-sodium (HS, 160 mmol/d) diet and low-sodium (LS, 20 mmol/d) diet to activate the endogenous renin-angiotensin-aldosterone system. We further analyzed selected exosomal protein content in a separate cohort of healthy persons receiving intravenous aldosterone (0.7 μg/kg per hour for 10 hours) versus vehicle infusion. The LS diet increased plasma renin activity and aldosterone concentration, whereas aldosterone infusion increased only aldosterone concentration. Protein analysis of paired urine exosome samples by liquid chromatography-tandem mass spectrometry-based multidimensional protein identification technology detected 2775 unique proteins, of which 316 exhibited significantly altered abundance during LS diet. Sodium chloride cotransporter (NCC) and α- and γ-epithelial sodium channel (ENaC) subunits from the discovery set were verified using targeted multiple reaction monitoring mass spectrometry quantified with isotope-labeled peptide standards. Dietary sodium restriction or acute aldosterone infusion similarly increased urine exosomal γENaC[112-122] peptide concentrations nearly 20-fold, which correlated with plasma aldosterone concentration and urinary Na/K ratio. Urine exosomal NCC and αENaC concentrations were relatively unchanged during these interventions. We conclude that urinary exosome content is altered by renin-angiotensin-aldosterone system activation. Urinary measurement of exosomal γENaC[112-122] concentration may provide a useful biomarker of ENaC activation in future clinical studies. Copyright © 2016 by the American Society of Nephrology.

Activation of the Endogenous Renin-Angiotensin-Aldosterone System or Aldosterone Administration Increases Urinary Exosomal Sodium Channel Excretion

PubMed Central

Qi, Ying; Wang, Xiaojing; Rose, Kristie L.; MacDonald, W. Hayes; Zhang, Bing; Schey, Kevin L.

2016-01-01

Urinary exosomes secreted by multiple cell types in the kidney may participate in intercellular signaling and provide an enriched source of kidney-specific proteins for biomarker discovery. Factors that alter the exosomal protein content remain unknown. To determine whether endogenous and exogenous hormones modify urinary exosomal protein content, we analyzed samples from 14 mildly hypertensive patients in a crossover study during a high-sodium (HS, 160 mmol/d) diet and low-sodium (LS, 20 mmol/d) diet to activate the endogenous renin-angiotensin-aldosterone system. We further analyzed selected exosomal protein content in a separate cohort of healthy persons receiving intravenous aldosterone (0.7 μg/kg per hour for 10 hours) versus vehicle infusion. The LS diet increased plasma renin activity and aldosterone concentration, whereas aldosterone infusion increased only aldosterone concentration. Protein analysis of paired urine exosome samples by liquid chromatography-tandem mass spectrometry–based multidimensional protein identification technology detected 2775 unique proteins, of which 316 exhibited significantly altered abundance during LS diet. Sodium chloride cotransporter (NCC) and α- and γ-epithelial sodium channel (ENaC) subunits from the discovery set were verified using targeted multiple reaction monitoring mass spectrometry quantified with isotope-labeled peptide standards. Dietary sodium restriction or acute aldosterone infusion similarly increased urine exosomal γENaC[112–122] peptide concentrations nearly 20-fold, which correlated with plasma aldosterone concentration and urinary Na/K ratio. Urine exosomal NCC and αENaC concentrations were relatively unchanged during these interventions. We conclude that urinary exosome content is altered by renin-angiotensin-aldosterone system activation. Urinary measurement of exosomal γENaC[112–122] concentration may provide a useful biomarker of ENaC activation in future clinical studies. PMID:26113616

Collecting duct prorenin receptor knockout reduces renal function, increases sodium excretion, and mitigates renal responses in ANG II-induced hypertensive mice.

PubMed

Prieto, Minolfa C; Reverte, Virginia; Mamenko, Mykola; Kuczeriszka, Marta; Veiras, Luciana C; Rosales, Carla B; McLellan, Matthew; Gentile, Oliver; Jensen, V Behrana; Ichihara, Atsuhiro; McDonough, Alicia A; Pochynyuk, Oleh M; Gonzalez, Alexis A

2017-12-01

Augmented intratubular angiotensin (ANG) II is a key determinant of enhanced distal Na + reabsorption via activation of epithelial Na + channels (ENaC) and other transporters, which leads to the development of high blood pressure (BP). In ANG II-induced hypertension, there is increased expression of the prorenin receptor (PRR) in the collecting duct (CD), which has been implicated in the stimulation of the sodium transporters and resultant hypertension. The impact of PRR deletion along the nephron on BP regulation and Na + handling remains controversial. In the present study, we investigate the role of PRR in the regulation of renal function and BP by using a mouse model with specific deletion of PRR in the CD ( CD PRR-KO). At basal conditions, CD PRR-KO mice had decreased renal function and lower systolic BP associated with higher fractional Na + excretion and lower ANG II levels in urine. After 14 days of ANG II infusion (400 ng·kg -1 ·min -1 ), the increases in systolic BP and diastolic BP were mitigated in CD PRR-KO mice. CD PRR-KO mice had lower abundance of cleaved αENaC and γENaC, as well as lower ANG II and renin content in urine compared with wild-type mice. In isolated CD from CD PRR-KO mice, patch-clamp studies demonstrated that ANG II-dependent stimulation of ENaC activity was reduced because of fewer active channels and lower open probability. These data indicate that CD PRR contributes to renal function and BP responses during chronic ANG II infusion by enhancing renin activity, increasing ANG II, and activating ENaC in the distal nephron segments. Copyright © 2017 the American Physiological Society.

Mineralocorticoid effects in the late gestation ovine fetal lung

PubMed Central

McCartney, Jarret; Richards, Elaine M.; Wood, Charles E.; Keller‐Wood, Maureen

2014-01-01

Abstract This study was designed to determine the effects of corticosteroids at MR in the late‐gestation fetal lung. Since both the mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR) are expressed at relatively high levels in the fetal lung, endogenous corticosteroids may act at MR as well as GR in the preterm fetal lung. The GR agonist, betamethasone, the MR agonist, aldosterone, or both were infused intravenously for 48 h in ovine fetuses of approximately 130 days gestation. Effects on airway pressures during stepwise inflation of the in situ lung, expression of ENaC alpha (SCNN1A), ENaC beta (SCNN1B), and Na,K ATPase (ATP1A1), and elastin and collagen content were determined after the infusions. We found that aldosterone significantly reduced the airway pressure measured during the initial step in inflation of the lung, although aldosterone had no overall effect on lung compliance, nor did aldosterone induce expression of ENaCα, ENaCβ or Na,K ATPaseα1. Betamethasone significantly increased expression of the epithelial sodium channel (ENaC) subunit mRNAs, and collagen and elastin content in the lungs, although this dose of betamethasone also had no effect on lung compliance. There was no synergy between effects of the MR and GR agonists. Transcriptomic analysis suggested that although aldosterone did not alter genes in pathways related to epithelial sodium transport, aldosterone did alter genes in pathways involved in cell proliferation in the lungs. The results are consistent with corticosteroid‐induced fluid reabsorption at birth through GR rather than MR, but suggest that MR facilitates lung maturation, and may contribute to inflation with the first breaths via mechanisms distinct from known aldosterone effects in other epithelia. PMID:25347852

Altered regulation of renal sodium transporters in salt-sensitive hypertensive rats induced by uninephrectomy.

PubMed

Jung, Ji Yong; Lee, Jay Wook; Kim, Sejoong; Jung, Eun Sook; Jang, Hye Ryoun; Han, Jin Suk; Joo, Kwon Wook

2009-12-01

Uninephrectomy (uNx) in young rats causes salt-sensitive hypertension (SSH). Alterations of sodium handling in residual nephrons may play a role in the pathogenesis. Therefore, we evaluated the adaptive alterations of renal sodium transporters according to salt intake in uNx-SSH rats. uNx or sham operations were performed in male Sprague-Dawley rats, and normal-salt diet was fed for 4 weeks. Four experimental groups were used: sham-operated rats raised on a high-salt diet for 2 weeks (CHH) or on a low-salt diet for 1 week after 1 week's high-salt diet (CHL) and uNx rats fed on the same diet (NHH, NHL) as the sham-operated rats were fed. Expression of major renal sodium transporters were determined by semiquantitative immunoblotting. Systolic blood pressure was increased in NHH and NHL groups, compared with CHH and CHL, respectively. Protein abundances of Na(+)/K(+)/2Cl(-) cotransporter (NKCC2) and Na(+)/Cl(-) cotransporter (NCC) in the CHH group were lower than the CHL group. Expression of epithelial sodium channel (ENaC)-γ increased in the CHH group. In contrast, expressions of NKCC2 and NCC in the NHH group didn't show any significant alterations, compared to the NHL group. Expressions of ENaC-α and ENaC-β in the NHH group were higher than the CHH group. Adaptive alterations of NKCC2 and NCC to changes of salt intake were different in the uNx group, and changes in ENaC-α and ENaC-β were also different. These altered regulations of sodium transporters may be involved in the pathogenesis of SSH in the uNx rat model.

Severe hyperkalemia is rescued by low-potassium diet in renal βENaC-deficient mice.

PubMed

Boscardin, Emilie; Perrier, Romain; Sergi, Chloé; Maillard, Marc; Loffing, Johannes; Loffing-Cueni, Dominique; Koesters, Robert; Rossier, Bernard Claude; Hummler, Edith

2017-10-01

In adulthood, an induced nephron-specific deficiency of αENaC (Scnn1a) resulted in pseudohypoaldosteronism type 1 (PHA-1) with sodium loss, hyperkalemia, and metabolic acidosis that is rescued through high-sodium/low-potassium (HNa + /LK + ) diet. In the present study, we addressed whether renal βENaC expression is required for sodium and potassium balance or can be compensated by remaining (α and γ) ENaC subunits using adult nephron-specific knockout (Scnn1b Pax8/LC1 ) mice. Upon induction, these mice present a severe PHA-1 phenotype with weight loss, hyperkalemia, and dehydration, but unlike the Scnn1a Pax8/LC1 mice without persistent salt wasting. This is followed by a marked downregulation of STE20/SPS1-related proline-alanine-rich protein kinase (SPAK) and Na + /Cl - co-transporter (NCC) protein expression and activity. Most of the experimental Scnn1b Pax8/LC1 mice survived with a HNa + /LK + diet that partly normalized NCC phosphorylation, but not total NCC expression. Since salt loss was minor, we applied a standard-sodium/LK + diet that efficiently rescued these mice resulting in normokalemia and normalization of NCC phosphorylation, but not total NCC expression. A further switch to LNa + /standard-K + diet induced again a severe PHA-1-like phenotype, but with only transient salt wasting indicating that low-K + intake is critical to decrease hyperkalemia in a NCC-dependent manner. In conclusion, while the βENaC subunit plays only a minor role in sodium balance, severe hyperkalemia results in downregulation of NCC expression and activity. Our data demonstrate the importance to primarily correct the hyperkalemia with a low-potassium diet that normalizes NCC activity.

2001 Bhuj, India, earthquake engineering seismoscope recordings and Eastern North America ground-motion attenuation relations

USGS Publications Warehouse

Cramer, C.H.; Kumar, A.

2003-01-01

Engineering seismoscope data collected at distances less than 300 km for the M 7.7 Bhuj, India, mainshock are compatible with ground-motion attenuation in eastern North America (ENA). The mainshock ground-motion data have been corrected to a common geological site condition using the factors of Joyner and Boore (2000) and a classification scheme of Quaternary or Tertiary sediments or rock. We then compare these data to ENA ground-motion attenuation relations. Despite uncertainties in recording method, geological site corrections, common tectonic setting, and the amount of regional seismic attenuation, the corrected Bhuj dataset agrees with the collective predictions by ENA ground-motion attenuation relations within a factor of 2. This level of agreement is within the dataset uncertainties and the normal variance for recorded earthquake ground motions.

Modified Mercalli Intensities (MMI) for some earthquakes in eastern North America (ENA) and empirical MMI site corrections for towns in ENA

USGS Publications Warehouse

Bakun, W.H.; Johnston, A.C.; Hopper, M.G.

2002-01-01

Modified Mercalli Intensity (MMI) assignments for earthquakes in eastern North America (ENA) were used by Bakun et al. (submitted) to develop a model for eastern North America for estimating the location and moment magnitude M of earthquakes from MMI observations. MMI assignments for most of the earthquakes considered by Bakun et al. (submitted) are published. MMI assignments for 6 other earthquakes used by Bakun et al. (submitted) are listed in this report: November 18, 1755 near Cape Ann, Massachusetts; January 5, 1843 near Marked Tree, Arkansas; October 31, 1895 in southern Illinois; November 18, 1929 on the Grand Banks, Newfoundland; September 26, 1990 in southeast Missouri; and May 4, 1991 near Risco, Missouri. MMI empirical site corrections developed and used by Bakun et al. (submitted) are also listed in this report.

Pro Atrial Natriuretic Peptide (1-30) and 6-keto PGF1α Activity Affects Na(+) Homeostasis in Non-modulating Hypertension.

PubMed

Sanchez, Ramiro A; Gilbert, Bernardo H; Masnatta, Lucas; Giannone, Carlos; Pesiney, Carlina; Ramirez, Agustin J

2015-01-01

Non-modulating hypertension (NMHT) is a high renin subtype of salt sensitive hypertension, which fails to achieve renal vasodilatation and a correct Na(+) handling during sodium load. We investigate, in MHT and NMHT, the role of ANP, the renin-angiotensin system and PgI2, in the renal sodium handling mechanisms. After 10 days of low (20mmol.L) or after 72hs of high (250mmol.L) sodium intake, 13 NMHT (34±5y; 9 male) and 13 MHT (32±4y; 10male) were studied. Pro-ANP (1-30) PgI2, PRA and total exchangeable Na(+)24 (ENa(+)) were measured. Under low sodium intake, PRA (4.2±0.5ng.ml.h; p<0.05) and Pro-ANP (78.6±2pg/ml, p<0.05) were higher than in NMHT under (3.1±0.4ng.ml.h and 69.8±3 pg/ml). After 72h of high Na(+) intake, Pro-ANP (1-30) increased significantly only in MHT (82.1±3pg/ml, p<0.05). PgI2, under low sodium intake (1.83±0.2pg/24h), increased in MHT after 72h under high sodium (2.58±0.5pg/ 24h, p<0.02). Under low sodium diet, PgI2 (2.16±0.11pg/24h) was as higher in NMHT, as in MHT. After 72h under high Na+ intake, it failed to show any change (2.61±0.36 pg/24h; p=ns). A significant correlation between variations in ENa(+) and mean blood pressure (r=0.50, p<0.01), variations in Pro-ANP (1-30) values and ENa(+) in MHT (r=0.95; p<0.001) while a negative correlation between ENa(+) variations and ENa(+) (r=0.81, p<0.05) was observed in NMHT. ENa(+) variations were only significantly related to variations in FF in MHT. Thus, in NMHT, there is an unbalanced relationship between vasonstrictor and vasodilator mediators. From these, as an extrarenal homeostatic mediator, ANP seems to play an important role to compensate the altered renal sodium handling.

Juvenile primary extranasopharyngeal angiofibroma, presenting as cheek swelling

PubMed Central

Nandhini, J; Ramasamy, S; Kaul, Ronak Nazir; Austin, Ravi David

2018-01-01

Angiofibroma is a locally advancing immensely vascular tumor that essentially arises from the nasopharynx. The clinical characteristics of extranasopharyngeal angiofibroma (ENA) do not accord to that of nasopharyngeal angiofibroma and can present a diagnostic confront. We describe a case of primary juvenile ENA in a 19-year-old patient who presented with a rapidly enlarging mass of the cheek region. The case is unusual because of its anatomic location. The diagnostic and management particulars are sketched. PMID:29491611

Gravity Force Transduced by the MEC-4/MEC-10 DEG/ENaC Channel Modulates DAF-16/FoxO Activity in Caenorhabditis elegans

PubMed Central

Kim, Nahui; Dempsey, Catherine M.; Kuan, Chih-Jen; Zoval, Jim V.; O'Rourke, Eyleen; Ruvkun, Gary; Madou, Marc J.; Sze, Ji Y.

2007-01-01

The gravity response is an array of behavioral and physiological plasticity elicited by changes in ambient mechanical force and is an evolutionarily ancient adaptive mechanism. We show in Caenorhabditis elegans that the force of hypergravity is translated into biological signaling via a genetic pathway involving three factors: the degenerin/epithelial Na+ channel (DEG/ENaC) class of mechanosensory channels of touch receptor neurons, the neurotransmitter serotonin, and the FoxO transcription factor DAF-16 known to regulate development, energy metabolism, stress responses, and aging. After worms were exposed to hypergravity for 3 hr, their muscular and neuronal functions were preserved, but they exhibited DAF-16∷GFP nuclear accumulation in cells throughout the body and accumulated excess fat. Mutations in MEC-4/MEC-10 DEG/ENaC or its partners MEC-6, MEC-7, and MEC-9 blocked DAF-16∷GFP nuclear accumulation induced by hypergravity but did not affect DAF-16 response to other stresses. We show that exogenous serotonin and the antidepressant fluoxetine can attenuate DAF-16∷GFP nuclear accumulation in WT animals exposed to hypergravity. These results reveal a novel physiological role of the mechanosensory channel, showing that the perception of mechanical stress controls FoxO signaling pathways and that inactivation of DEG/ENaC may decouple mechanical loading and physiological responses. PMID:17720915

The interstellar boundary explorer (IBEX): Update at the end of phase B

NASA Astrophysics Data System (ADS)

McComas, D. J.; Allegrini, F.; Bartolone, L.; Bochsler, P.; Bzowski, M.; Collier, M.; Fahr, H.; Fichtner, H.; Frisch, P.; Funsten, H.; Fuselier, Steve; Gloeckler, G.; Gruntman, M.; Izmodenov, V.; Knappenberger, P.; Lee, M.; Livi, S.; Mitchell, D.; Möbius, E.; Moore, T.; Pope, S.; Reisenfeld, D.; Roelof, E.; Runge, H.; Scherrer, J.; Schwadron, N.; Tyler, R.; Wieser, M.; Witte, M.; Wurz, P.; Zank, G.

2006-09-01

The Interstellar Boundary Explorer (IBEX) mission will make the first global observations of the heliosphere's interaction with the interstellar medium. IBEX achieves these breakthrough observations by traveling outside of the Earth's magnetosphere in a highly elliptical orbit and taking global Energetic Neutral Atoms (ENA) images over energies from ~10 eV to 6 keV. IBEX's high-apogee (~50 RE) orbit enables heliospheric ENA measurements by providing viewing from far above the Earth's relatively bright magnetospheric ENA emissions. This high energy orbit is achieved from a Pegasus XL launch vehicle by adding the propulsion from an IBEX-supplied solid rocket motor and the spacecraft's hydrazine propulsion system. IBEX carries two very large-aperture, single-pixel ENA cameras that view perpendicular to the spacecraft's Sun-pointed spin axis. Each six months, the continuous spinning of the spacecraft and periodic re-pointing to maintain the sun-pointing spin axis naturally lead to global, all-sky images. Over the course of our NASA Phase B program, the IBEX team optimized the designs of all subsystems. In this paper we summarize several significant advances in both IBEX sensors, our expected signal to noise (and background), and our groundbreaking approach to achieve a very high-altitude orbit from a Pegasus launch vehicle for the first time. IBEX is in full scale development and on track for launch in June of 2008.

Airway Surface Dehydration Aggravates Cigarette Smoke-Induced Hallmarks of COPD in Mice.

PubMed

Seys, Leen J M; Verhamme, Fien M; Dupont, Lisa L; Desauter, Elke; Duerr, Julia; Seyhan Agircan, Ayca; Conickx, Griet; Joos, Guy F; Brusselle, Guy G; Mall, Marcus A; Bracke, Ken R

2015-01-01

Airway surface dehydration, caused by an imbalance between secretion and absorption of ions and fluid across the epithelium and/or increased epithelial mucin secretion, impairs mucociliary clearance. Recent evidence suggests that this mechanism may be implicated in chronic obstructive pulmonary disease (COPD). However, the role of airway surface dehydration in the pathogenesis of cigarette smoke (CS)-induced COPD remains unknown. We aimed to investigate in vivo the effect of airway surface dehydration on several CS-induced hallmarks of COPD in mice with airway-specific overexpression of the β-subunit of the epithelial Na⁺ channel (βENaC). βENaC-Tg mice and wild-type (WT) littermates were exposed to air or CS for 4 or 8 weeks. Pathological hallmarks of COPD, including goblet cell metaplasia, mucin expression, pulmonary inflammation, lymphoid follicles, emphysema and airway wall remodelling were determined and lung function was measured. Airway surface dehydration in βENaC-Tg mice aggravated CS-induced airway inflammation, mucin expression and destruction of alveolar walls and accelerated the formation of pulmonary lymphoid follicles. Moreover, lung function measurements demonstrated an increased compliance and total lung capacity and a lower resistance and hysteresis in βENaC-Tg mice, compared to WT mice. CS exposure further altered lung function measurements. We conclude that airway surface dehydration is a risk factor that aggravates CS-induced hallmarks of COPD.

Increased apical Na+ permeability in cystic fibrosis is supported by a quantitative model of epithelial ion transport

PubMed Central

O’Donoghue, Donal L; Dua, Vivek; Moss, Guy W J; Vergani, Paola

2013-01-01

Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which encodes an anion channel. In the human lung CFTR loss causes abnormal ion transport across airway epithelial cells. As a result CF individuals produce thick mucus, suffer persistent bacterial infections and have a much reduced life expectancy. Trans-epithelial potential difference (Vt) measurements are routinely carried out on nasal epithelia of CF patients in the clinic. CF epithelia exhibit a hyperpolarised basal Vt and a larger Vt change in response to amiloride (a blocker of the epithelial Na+ channel, ENaC). Are these altered bioelectric properties solely a result of electrical coupling between the ENaC and CFTR currents, or are they due to an increased ENaC permeability associated with CFTR loss? To examine these issues we have developed a quantitative mathematical model of human nasal epithelial ion transport. We find that while the loss of CFTR permeability hyperpolarises Vt and also increases amiloride-sensitive Vt, these effects are too small to account for the magnitude of change observed in CF epithelia. Instead, a parallel increase in ENaC permeability is required to adequately fit observed experimental data. Our study provides quantitative predictions for the complex relationships between ionic permeabilities and nasal Vt, giving insights into the physiology of CF disease that have important implications for CF therapy. PMID:23732645

Cross-talk between insulin and IGF-1 receptors in the cortical collecting duct principal cells: implication for ENaC-mediated Na+ reabsorption

PubMed Central

Ilatovskaya, Daria V.; Levchenko, Vladislav; Brands, Michael W.; Pavlov, Tengis S.

2015-01-01

Insulin and IGF-1 are recognized as powerful regulators of the epithelial Na+ channel (ENaC) in the aldosterone-sensitive distal nephron. As previously described, these hormones both acutely increase ENaC activity in freshly isolated split open tubules and cultured principal cortical collecting duct cells. The present study was aimed at differentiating the effects of insulin and IGF-1 on Na+ transport in immortalized mpkCCDcl4 cells and defining their interrelations. We have shown that both insulin and IGF-1 applied basolaterally, but not apically, enhanced transepithelial Na+ transport in the mpkCCDcl4 cell line with EC50 values of 8.8 and 14.5 nM, respectively. Insulin treatment evoked phosphorylation of both insulin and IGF-1 receptors, whereas the effects of IGF-1 were more profound on its own receptor rather than the insulin receptor. AG-1024 and PPP, inhibitors of IGF-1 and insulin receptor tyrosine kinase activity, diminished insulin- and IGF-1-stimulated Na+ transport in mpkCCDcl4 cells. The effects of insulin and IGF-1 on ENaC-mediated currents were found to be additive, with insulin likely stimulating both IGF-1 and insulin receptors. We hypothesize that insulin activates IGF-1 receptors in addition to its own receptors, making the effects of these hormones interconnected. PMID:25651558

Large-eddy simulations of mechanical and thermal processes within boundary layer of the Graciosa Island

NASA Astrophysics Data System (ADS)

Sever, G.; Collis, S. M.; Ghate, V. P.

2017-12-01

Three-dimensional numerical experiments are performed to explore the mechanical and thermal impacts of Graciosa Island on the sampling of oceanic airflow and cloud evolution. Ideal and real configurations of flow and terrain are planned using high-resolution, large-eddy resolving (e.g., Δ < 100 meter) simulations. Ideal configurations include model initializations with ideal dry and moist temperature and wind profiles to capture flow features over an island-like topography. Real configurations will use observations from different climatological background states over the Eastern Northern Atlantic, Atmospheric Radiation Measurement (ENA-ARM) site on Graciosa Island. Initial small-domain large-eddy simulations (LES) of dry airflow produce cold-pool formation upstream of an ideal two-kilometer island, with von Kármán like vortices propagation downstream. Although the peak height of Graciosa is less than half kilometer, the Azores island chain has a mountain over 2 km, which may be leading to more complex flow patterns when simulations are extended to a larger domain. Preliminary idealized low-resolution moist simulations indicate that the cloud field is impacted due to the presence of the island. Longer simulations that are performed to capture diurnal evolution of island boundary layer show distinct land/sea breeze formations under quiescent flow conditions. Further numerical experiments are planned to extend moist simulations to include realistic atmospheric profiles and observations of surface fluxes coupled with radiative effects. This work is intended to produce a useful simulation framework coupled with instruments to guide airborne and ground sampling strategies during the ACE-ENA field campaign which is aimed to better characterize marine boundary layer clouds.

Differential display cloning of a novel rat cDNA (RNB6) that shows high expression in the neonatal brain revealed a member of Ena/VASP family.

PubMed

Ohta, S; Mineta, T; Kimoto, M; Tabuchi, K

1997-08-18

We have used the differential display method to identify genes that control the neural cell development in CNS. Screening of the differential display bands that showed higher expression at neonate than at adult age enabled us to identify a novel rat cDNA (RNB6) coding for a protein of 393 amino acid residues. Database search revealed this gene as a rat homologue of the murine EVL, a member of Ena/VASP protein family that is implicated to be involved in the control of cell motility through actin filament assembly by their GP5 motifs. Although the precise characterization of EVL was not reported, our Northern blot and immunoblot analyses demonstrated that RNB6 expression in the brain gradually increases during embryonic development, reaches maximum at postnatal day 1 and decreases thereafter. Studies of tissue distribution revealed the expression of RNB6 not only in the brain but also in the spleen, thymus and testis. Histochemical analyses showed that RNB6 protein is mainly expressed in neurons and may be expressed in neural fibers. Our analyses suggest that RNB6 is critically involved in the development of CNS probably through the control of neural cell motility and/or including neuronal fiber extension.

Electrochemical noise measurements of sustained microbially influenced pitting corrosion in a laboratory flow loop system

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

Lin, Y.; Frank, J.R.; St. Martin, E.J.

Because of the chaotic nature of the corrosion process and the complexity of the electrochemical noise signals that are generated, there is no generally accepted method of measuring and interpreting these signals that allows the consistent detection and identification of sustained localized pitting (SLP) as compared to general corrosion. The authors have reexamined electrochemical noise analysis (ENA) of localized corrosion using different hardware, signal collection, and signal processing designs than those used in conventional ENA techniques. The new data acquisition system was designed to identify and monitor the progress of SLP by analyzing the power spectral density (PSD) of themore » trend of the corrosion current noise level (CNL) and potential noise level (PNL). Each CNL and PNL data point was calculated from the root-mean-square value of the ac components of current and potential fluctuation signals, which were measured simultaneously during a short time period. The PSD analysis results consistently demonstrated that the trends of PNL and CNL contain information that can be used to differentiate between SLP and general corrosion mechanisms. The degree of linear slope in the low-frequency portion of the PSD analysis was correlated with the SLP process. Laboratory metal coupons as well as commercial corrosion probes were tested to ensure the reproducibility and consistency of the results. The on-line monitoring capability of this new ENA method was evaluated in a bench-scale flow-loop system, which simulated microbially influenced corrosion (MIC) activity. The conditions in the test flow-loop system were controlled by the addition of microbes and different substrates to favor accelerated corrosion. The ENA results demonstrated that this in-situ corrosion monitoring system could effectively identify SLP corrosion associated with MIC, compared to a more uniform general corrosion mechanism. A reduction in SLP activity could be clearly detected by the ENA monitoring system when a corrosion inhibitor was added into one of the test loops during the corrosion testing.« less

Electrochemical noise measurements of sustained microbially influenced pitting corrosion in a laboratory flow loop system.

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

Lin, Y. J.

Because of the chaotic nature of the corrosion process and the complexity of the electrochemical noise signals that are generated, there is no generally accepted method of measuring and interpreting these signals that allows the consistent detection and identification of sustained localized pitting (SLP) as compared to general corrosion. We have reexamined electrochemical noise analysis (ENA) of localized corrosion using different hardware, signal collection, and signal processing designs than those used in conventional ENA techniques. The new data acquisition system was designed to identify and monitor the progress of SLP by analyzing the power spectral density (PSD) of the trendmore » of the corrosion current noise level (CNL) and potential noise level (PNL). Each CNL and PNL data point was calculated from the root-mean- square value of the ac components of current and potential fluctuation signals, which were measured simultaneously during a short time period. The PSD analysis results consistently demonstrated that the trends of PNL and CNL contain information that can be used to differentiate between SLP and general corrosion mechanisms. The degree of linear slope in the low-frequency portion of the PSD analysis was correlated with the SLP process. Laboratory metal coupons as well as commercial corrosion probes were tested to ensure the reproducibility and consistency of the results. The on-line monitoring capability of this new ENA method was evaluated in a bench-scale flow-loop system, which simulated microbially influenced corrosion (MIC) activity. The conditions in the test flow-loop system were controlled by the addition of microbes and different substrates to favor accelerated corrosion. The ENA results demonstrated that this in-situ corrosion monitoring system could effectively identify SLP corrosion associated with MIC, compared to a more uniform general corrosion mechanism. A reduction in SLP activity could be clearly detected by the ENA monitoring system when a corrosion inhibitor was added into one of the test loops during the corrosion testing.« less

Genetic variation in CYP4A11 and blood pressure response to mineralocorticoid receptor antagonism or ENaC inhibition: an exploratory pilot study in African Americans.

PubMed

Laffer, Cheryl L; Elijovich, Fernando; Eckert, George J; Tu, Wanzhu; Pratt, J Howard; Brown, Nancy J

2014-07-01

An rs3890011 variant of CYP4A11, which is in linkage disequilibrium with the loss-of-function variant rs1126742, is associated with hypertension in humans. In mice, Cyp4a deficiency results in salt-sensitive hypertension through activation of ENaC. We tested the hypothesis that the rs3890011 variant is associated with blood pressure response to drugs acting via the ENaC pathway. African Americans with volume-dependent, resistant hypertension were randomized to treatment with placebo, spironolactone, amiloride, or combination. Blood pressure responses were analyzed by CYP4A11 genotypes. Rs3890011 (GG:GC:CC = 20:35:28) and rs1126742 (TT:TC:CC = 45:31:7) were in linkage disequilibrium (D' = 1, r = 0.561). Expected small number of rs1126742 CC homozygotes precluded analysis of the effect of this genotype on treatment responses. Spironolactone reduced blood pressure in rs3890011 GG and GC individuals, but not in CC homozygotes (P = .002), whereas amiloride reduced blood pressure similarly in all rs3890011 genotypes. The antihypertensive effects of spironolactone and amiloride were comparable in GG and GC participants, but only amiloride reduced pressure in CC homozygotes (-6.3 ± 7.3/-3.2 ± 4.0 vs. +6.8 ± 7.9/+4.8 ± 8.6 mm Hg, P < .01/<.05). The aldosterone response to spironolactone was also blunted in the CC genotype. In individuals homozygous for the CYP4A11 rs3890011 C allele, blood pressure is resistant to mineralocorticoid receptor antagonism, but sensitive to ENaC inhibition, consistent with ENaC activation. Studies in a larger population are needed to replicate these findings. Copyright © 2014 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

IBEX Observations and Simulations of the Ribbon: Implications for the Very Local Interstellar Medium

NASA Astrophysics Data System (ADS)

Zirnstein, E.

2017-12-01

The crossing of the Voyager 1 spacecraft into the very local interstellar medium (VLISM) in 2012 August opened a new chapter in humankind's exploration of space. Voyager 1 has been measuring interstellar plasma properties outside the heliosphere, including the galactic cosmic ray flux, (indirectly) the compressed interstellar plasma, as well as the compressed interstellar magnetic field draped around the heliosphere. Interstellar Boundary Explorer (IBEX) neutral atom observations complement the only in situ observations of the VLISM made by Voyager 1. IBEX is an Earth-orbiting spacecraft equipped with two single-pixel cameras that detect neutral atoms produced by the interaction of the solar wind (SW) with the VLISM, as well as neutral atoms flowing into the heliosphere from the VLISM itself. After its launch in 2009, IBEX discovered the unexpected existence of the "ribbon," a nearly circular arc across the sky of enhanced hydrogen ENA fluxes observed at keV energies. The ribbon fluxes originate from look directions perpendicular to the local interstellar magnetic field draped around the heliosphere, and can be used to derive the VLISM magnetic field magnitude and direction far from the heliopause. Thus, IBEX observations of the ribbon complement Voyager 1 in situ observations of the VLISM magnetic field, and provide insight into what Voyager 2 will observe after it crosses the heliopause. This talk will review key IBEX observations of the VLISM environment related to the ribbon and the VLISM magnetic field observed by Voyager 1, and their implications for the VLISM environment.

Specific roles for DEG/ENaC and TRP channels in touch and thermosensation in C. elegans nociceptors

PubMed Central

Chatzigeorgiou, Marios; Yoo, Sungjae; Watson, Joseph D.; Lee, Wei-Hsiang; Spencer, W. Clay; Kindt, Katie S.; Hwang, Sun Wook; Miller, David M.; Treinin, Millet; Driscoll, Monica; Schafer, William R.

2010-01-01

Summary Polymodal nociceptors detect noxious stimuli including harsh touch, toxic chemicals, and extremes of heat and cold. The molecular mechanisms by which nociceptors are able to sense multiple qualitatively distinct stimuli are not well-understood. We show here that the C. elegans PVD neurons are mulitidendritic nociceptors that respond to harsh touch as well as cold temperatures. The harsh touch modality specifically requires the DEG/ENaC proteins MEC-10 and DEGT-1, which represent putative components of a harsh touch mechanotransduction complex. By contrast, responses to cold require the TRPA-1 channel and are MEC-10- and DEGT-1-independent. Heterologous expression of C. elegans TRPA-1 can confer cold responsiveness to other C. elegans neurons or to mammalian cells, indicating that TRPA-1 is itself a cold sensor. These results show that C. elegans nociceptors respond to thermal and mechanical stimuli using distinct sets of molecules, and identify DEG/ENaC channels as potential receptors for mechanical pain. PMID:20512132

Assessment of epithelial sodium channel variants in nonwhite cystic fibrosis patients with non-diagnostic CFTR genotypes.

PubMed

Brennan, Marie-Luise; Pique, Lynn M; Schrijver, Iris

2016-01-01

Several lines of evidence suggest a role for the epithelial sodium channel (ENaC) in cystic fibrosis (CF). The purpose of our study was to assess the contribution of genetic variants in the ENaC subunits (α, β, γ) in nonwhite CF patients in whom CFTR molecular testing has been non-diagnostic. Samples were obtained from patients who were nonwhite and whose molecular CFTR testing did not identify two mutations. Sequencing of the SCNN1A, B, and G genes was performed and variants assessed for pathogenicity and association with CF using databases, protein and splice site mutation analysis software, and literature review. We identified four nonsynonymous amino acid variants in SCNN1A, three in SCNN1B and one in SCNN1G. There was no convincing evidence of pathogenicity. Whereas all have been reported in the dbSNP database, only p.Ala334Thr, p.Val573Ile, and p.Thr663Ala in SCNN1A, p.Gly442Val in SCNN1B and p.Gly183Ser in SCNN1G were previously reported in ENaC genetic studies of CF or CF-like patients. Synonymous substitutions were also observed but novel synonymous variants were not detected. There is no conclusive association of ENaC genetic variants with CF in nonwhite CF patients. Copyright © 2015 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Charging of Interstellar Dust Grains in the out-of-equilibrium Heliosheath Plasma traced by IBEX ENAs

NASA Astrophysics Data System (ADS)

Frisch, P. C.; Ogasawara, K.; Livadiotis, G.; Slavin, J. D.; McComas, D. J.; Funsten, H. O.; Schwadron, N.; Heerikhuisen, J.

2017-12-01

Dusty bow waves are common around stars and anticipated around the heliosphere due to the deficit of low-mass interstellar dust grains in the inner heliosphere. Interstellar grains entering the heliosphere must first cross barriers of non-Maxwellian plasma in the heliosheath regions where collisional charging of grains is highly effective. IBEX measures 0.1-6 keV ENAs in the heliosheath plasma, providing an in situ sample of the heliosheath plasma thermodynamics that can be used for grain-charging calculations. Plasma in three-quarters of the sky can be described with a stationary state kappa-distribution, giving predictions for kappa, kappa-distribution temperature, and plasma density [1]. This thermodynamic description allows a more realistic evaluation of the dominant heliosheath electron and ion currents, and hence also grain gyroradii and exclusion from the heliosphere. At the highest temperatures ion collisional currents dominate grain charging; at lower temperatures collisional electron currents are more important together with the photoelectric ejection of electrons. An absence of data on the thermodynamical state of heliosheath electrons has led to the assumption of similar thermodynamic parameters for the electron and ion populations. The balance between electron, proton and photoionization currents on the grains then yield the equilibrium grain charges. Grain gyroradii calculated based on these charging currents differentiate between interstellar grains able to penetrate the heliosphere, versus those that are excluded, and allow predictions of properties of the dusty bow wave likely to be present around the heliosphere. The smallest grains are excluded and grains at the high latitude edges of the described regions tend to have systematically lower grain potentials. Grain charging calculations utilize the modeling of [2]. [1] Livadiotis et al., ApJ 734, 1 (2011). [2] Weingartner Draine, ApJSS 263 (2001)

Kuang's Semi-Classical Formalism for Calculating Electron Capture Cross Sections: A Space- Physics Application

NASA Technical Reports Server (NTRS)

Barghouty, A. F.

2014-01-01

Accurate estimates of electroncapture cross sections at energies relevant to the modeling of the transport, acceleration, and interaction of energetic neutral atoms (ENA) in space (approximately few MeV per nucleon) and especially for multi-electron ions must rely on detailed, but computationally expensive, quantum-mechanical description of the collision process. Kuang's semi-classical approach is an elegant and efficient way to arrive at these estimates. Motivated by ENA modeling efforts for apace applications, we shall briefly present this approach along with sample applications and report on current progress.

TRIO (Triplet Ionospheric Observatory) Mission

NASA Astrophysics Data System (ADS)

Lee, D.; Seon, J.; Jin, H.; Kim, K.; Lee, J.; Jang, M.; Pak, S.; Kim, K.; Lin, R. P.; Parks, G. K.; Halekas, J. S.; Larson, D. E.; Eastwood, J. P.; Roelof, E. C.; Horbury, T. S.

2009-12-01

Triplets of identical cubesats will be built to carry out the following scientific objectives: i) multi-observations of ionospheric ENA (Energetic Neutral Atom) imaging, ii) ionospheric signature of suprathermal electrons and ions associated with auroral acceleration as well as electron microbursts, and iii) complementary measurements of magnetic fields for particle data. Each satellite, a cubesat for ion, neutral, electron, and magnetic fields (CINEMA), is equipped with a suprathermal electron, ion, neutral (STEIN) instrument and a 3-axis magnetometer of magnetoresistive sensors. TRIO is developed by three institutes: i) two CINEMA by Kyung Hee University (KHU) under the WCU program, ii) one CINEMA by UC Berkeley under the NSF support, and iii) three magnetometers by Imperial College, respectively. Multi-spacecraft observations in the STEIN instruments will provide i) stereo ENA imaging with a wide angle in local times, which are sensitive to the evolution of ring current phase space distributions, ii) suprathermal electron measurements with narrow spacings, which reveal the differential signature of accelerated electrons driven by Alfven waves and/or double layer formation in the ionosphere between the acceleration region and the aurora, and iii) suprathermal ion precipitation when the storm-time ring current appears. In addition, multi-spacecraft magnetic field measurements in low earth orbits will allow the tracking of the phase fronts of ULF waves, FTEs, and quasi-periodic reconnection events between ground-based magnetometer data and upstream satellite data.

Heliospheric Observations of Energetic Particles

NASA Technical Reports Server (NTRS)

Summerlin, Errol J.

2011-01-01

Heliospheric observations of energetic particles have shown that, on long time averages, a consistent v^-5 power-law index arises even in the absence of transient events. This implies an ubiquitous acceleration process present in the solar wind that is required to generate these power-law tails and maintain them against adiabatic losses and coulomb-collisions which will cool and thermalize the plasma respectively. Though the details of this acceleration process are being debated within the community, most agree that the energy required for these tails comes from fluctuations in the magnetic field which are damped as the energy is transferred to particles. Given this source for the tail, is it then reasonable to assume that the turbulent LISM should give rise to such a power-law tail as well? IBEX observations clearly show a power-law tail of index approximately -5 in energetic neutral atoms. The simplest explanation for the origins of these ENAs are that they are energetic ions which have charge-exchanged with a neutral atom. However, this would imply that energetic ions possess a v^-5 power-law distribution at keV energies at the source of these ENAs. If the source is presumed to be the LISM, it provides additional options for explaining the, so called, IBEX ribbon. This presentation will discuss some of these options as well as potential mechanisms for the generation of a power-law spectrum in the LISM.

Voyager in-situ and Cassini Remote Measurements Suggest a Bubble-like Shape for the Global Heliosphere

NASA Astrophysics Data System (ADS)

Dialynas, K.; Krimigis, S. M.; Mitchell, D. G.; Decker, R. B.; Roelof, E. C.

2017-12-01

The Low Energy Charged Particle (LECP) in situ measurements from Voyager 1 and Voyager 2 (V1, V2) have revealed the reservoir of ions and electrons that constitute the heliosheath after crossing the termination shock 35 deg north and 32 deg south of the ecliptic plane at 94 and 84 astronomical units (1 AU=1.5x108 km), respectively. In August 2012, at 121.6 AU, V1 crossed the heliopause to enter the interstellar space, while V2 remains in the heliosheath since 2007. The advent of Energetic Neutral Atom (ENA, produced through charge exchange between ions and neutral particles flowing through the heliosphere) imaging, has revealed the global nature of the heliosheath at both high (5.2-55 keV, Cassini/Ion and Neutral Camera-INCA, from 10 AU) and low (<6 keV, Interstellar Boundary Explorer-IBEX, from 1 AU) energies. The presence of the two Voyagers measuring ions locally in the heliosheath contemporaneously with INCA global imaging through ENA in overlapping energy bands provides a powerful tool for examining the spatial, temporal, and spectral evolution of the source hot plasma ions. Here we report 5.2-55 keV ENA global images of the heliosphere from Cassini/INCA and compare them with V1,2/LECP 28-53 keV ions measured within the heliosheath over a 13-year period (2003-2016). The similarity between the time profiles of ENA and ions establish that the heliosheath ions are the source of ENA. These measurements also demonstrate that the heliosphere responds promptly, within 2-3 years, to outward propagating solar wind changes (manifested in solar sunspot numbers and solar wind energy input) in both the upstream (nose) and downstream (tail) hemispheres. These results, taken together with the V1 measurement of a 0.5 nT interstellar magnetic field and the enhanced ratio between particle pressure and magnetic pressure in the heliosheath, constrain the shape of the global heliosphere: by contrast to the magnetosphere-like heliotail (that past modeling broadly assumed for more than 55 years), a more symmetric, diamagnetic bubble-like heliosphere, with few substantial tail-like features is revealed.

Ten Years of ENA Imaging from Cassini

NASA Astrophysics Data System (ADS)

Brandt, Pontus; Mitchell, Donald; Westlake, Joseph; Carbary, James; Paranicas, Christopher; Mauk, Barry; Krimigis, Stamatios

2014-05-01

In this presentation we will provide a detailed review of the science highlights of the ENA observations obtained by The Ion Neutral Camera (INCA) on board Cassini. Since the launch of Cassini, INCA has unveiled an invisible world of hot plasma and neutral gas of the two biggest objects of our solar system: the giant magnetosphere of Jupiter and Saturn. Although more than ten years ago, INCA captured the first ENA images of the Jovian system revealing magnetospheric dynamics and an asymmetric Europa neutral gas torus. Approaching Saturn, INCA observed variability of Saturn's magnetospheric activity in response to changes in solar wind dynamic pressure, which was contrary to expectations and current theories. In orbit around Saturn, INCA continued the surprises including the first imaging and global characterization of Titan's exosphere extended out to its gravitational Hill sphere; recurring injections correlating with periodic Saturn Kilometric Radiation (SKR) bursts and magnetic field perturbations; and the discovery of energetic ionospheric outflow. Perhaps most significant, and the focal point of this presentation, is INCA's contribution to the understanding of global magnetospheric particle acceleration and transport, where the combination between ENA imaging and in-situ measurements have demonstrated that transport and acceleration of plasma is likely to occur in a two-step process. First, large-scale injections in the post-midnight sector accelerate and transport plasma in to about 12 RS up to energies of several hundreds of keV. Second, centrifugal interchange acts on the plasma inside of this region and provides further heating and transport in to about 6RS. We discuss this finding in the context of the two fundamental types of injections (or ENA intensifications) that INCA has revealed during its ten years of imaging. The first type is large-scale injections appearing beyond 12 RS in the post-midnight sector that have in many cases had an inward component of propagation. The second type is apparently local injections inside of about 12 RS and as far in as 6RS in the pre-midnight sector with a recurrence period around 11h that, interestingly, appear to precede the larges-scale injections.

Mantle source heterogeneity of the Early Jurassic basalt of eastern North America

NASA Astrophysics Data System (ADS)

Gregory Shellnutt, J.; Dostal, Jaroslav; Yeh, Meng-Wan

2018-04-01

One of the defining characteristics of the basaltic rocks from the Early Jurassic Eastern North America (ENA) sub-province of the Central Atlantic Magmatic Province (CAMP) is the systematic compositional variation from South to North. Moreover, the tectono-thermal regime of the CAMP is debated as it demonstrates geological and structural characteristics (size, radial dyke pattern) that are commonly associated with mantle plume-derived mafic continental large igneous provinces but is considered to be unrelated to a plume. Mantle potential temperature ( T P) estimates of the northern-most CAMP flood basalts (North Mountain basalt, Fundy Basin) indicate that they were likely produced under a thermal regime ( T P ≈ 1450 °C) that is closer to ambient mantle ( T P ≈ 1400 °C) conditions and are indistinguishable from other regions of the ENA sub-province ( T Psouth = 1320-1490 °C, T Pnorth = 1390-1480 °C). The regional mantle potential temperatures are consistent along the 3000-km-long ENA sub-province suggesting that the CAMP was unlikely to be generated by a mantle plume. Furthermore, the mantle potential temperature calculation using the rocks from the Northern Appalachians favors an Fe-rich mantle (FeOt = 8.6 wt %) source, whereas the rocks from the South Appalachians favor a less Fe-rich (FeOt = 8.3 wt %) source. The results indicate that the spatial-compositional variation of the ENA basaltic rocks is likely related to differing amounts of melting of mantle sources that reflect the uniqueness of their regional accreted terranes (Carolinia and West Avalonia) and their post-accretion, pre-rift structural histories.

The Interstellar Boundary Explorer (IBEX) - Time to Launch!

NASA Astrophysics Data System (ADS)

McComas, David

The Interstellar Boundary Explorer (IBEX) mission is scheduled to launch in mid-July 2008, right around the time of this COSPAR meeting. IBEX will make the first global observations of the heliosphere's interaction with the interstellar medium. IBEX achieves these breakthrough observations by traveling outside of the Earth's magnetosphere in a highly elliptical orbit and taking global Energetic Neutral Atoms (ENA) images with two very large aperture single pixel ENA cameras. IBEX-Lo makes measurements in 8 contiguous energy pass bands covering from ˜10 eV to 2 keV; IBEX-Hi similarly covers from ˜300 eV to 6 keV in 6 contiguous pass bands. IBEX's high-apogee (˜50RE ) orbit enables heliospheric ENA measurements by providing viewing from far outside the earth's relatively bright magnetospheric ENA emissions. The IBEX cameras view perpendicular to the spacecraft's sun-pointed spin axis. Each six months, the spacecraft spin and progression of the sun-pointing spin axis as the Earth moves around the Sun lead naturally to global, all-sky images. IBEX is the first mission to achieve a high altitude from a standard Pegasus launch vehicle. We accomplish this by adding the propulsion from an IBEX-supplied solid rocket motor and the spacecraft's hydrazine propulsion system. Additional information on IBEX is available at www.ibex.swri.edu. This talk, on behalf of the IBEX science and engineering teams, will summarize the IBEX science and mission and will provide an up-to-the-minute update on the status of the mission, including any new information on the launch and commissioning status.

Feedforward activation of endothelial ENaC by high sodium

PubMed Central

Korte, Stefanie; Sträter, Alexandra S.; Drüppel, Verena; Oberleithner, Hans; Jeggle, Pia; Grossmann, Claudia; Fobker, Manfred; Nofer, Jerzy-Roch; Brand, Eva; Kusche-Vihrog, Kristina

2014-01-01

Kidney epithelial sodium channels (ENaCs) are known to be inactivated by high sodium concentrations (feedback inhibition). Recently, the endothelial sodium channel (EnNaC) was identified to control the nanomechanical properties of the endothelium. EnNaC-dependent endothelial stiffening reduces the release of nitric oxide, the hallmark of endothelial dysfunction. To study the regulatory impact of sodium on EnNaC, endothelial cells (EA.hy926 and ex vivo mouse endothelium) were incubated in aldosterone-free solutions containing either low (130 mM) or high (150 mM) sodium concentrations. By applying atomic force microscopy-based nanoindentation, an unexpected positive correlation between increasing sodium concentrations and cortical endothelial stiffness was observed, which can be attributed to functional EnNaC. In particular, an acute rise in sodium concentration (+20 mM) was sufficient to increase EnNaC membrane abundance by 90% and stiffening of the endothelial cortex by 18%. Despite the absence of exogenous aldosterone, these effects were prevented by the aldosterone synthase inhibitor FAD286 (100 nM) or the mineralocorticoid receptor (MR)-antagonist spironolactone (100 nM), indicating endogenous aldosterone synthesis and MR-dependent signaling. Interestingly, in the presence of high-sodium concentrations, FAD286 increased the transcription of the MR by 69%. Taken together, a novel feedforward activation of EnNaC by sodium is proposed that contrasts ENaC feedback inhibition in kidney.—Korte, S., Sträter, A. S., Drüppel, V., Oberleithner, H., Jeggle, P., Grossmann, C., Fobker, M., Nofer, J.-R., Brand, E., Kusche-Vihrog, K. Feedforward activation of endothelial ENaC by high sodium. PMID:24868010

A MicroRNA Cluster miR-23-24-27 Is Upregulated by Aldosterone in the Distal Kidney Nephron Where it Alters Sodium Transport.

PubMed

Liu, Xiaoning; Edinger, Robert S; Klemens, Christine A; Phua, Yu L; Bodnar, Andrew J; LaFramboise, William A; Ho, Jacqueline; Butterworth, Michael B

2017-06-01

The epithelial sodium channel (ENaC) is expressed in the epithelial cells of the distal convoluted tubules, connecting tubules, and cortical collecting duct (CCD) in the kidney nephron. Under the regulation of the steroid hormone aldosterone, ENaC is a major determinant of sodium (Na + ) and water balance. The ability of aldosterone to regulate microRNAs (miRs) in the kidney has recently been realized, but the role of miRs in Na + regulation has not been well established. Here we demonstrate that expression of a miR cluster mmu-miR-23-24-27, is upregulated in the CCD by aldosterone stimulation both in vitro and in vivo. Increasing the expression of these miRs increased Na + transport in the absence of aldosterone stimulation. Potential miR targets were evaluated and miR-27a/b was verified to bind to the 3'-untranslated region of intersectin-2, a multi-domain protein expressed in the distal kidney nephron and involved in the regulation of membrane trafficking. Expression of Itsn2 mRNA and protein was decreased after aldosterone stimulation. Depletion of Itsn2 expression, mimicking aldosterone regulation, increased ENaC-mediated Na + transport, while Itsn2 overexpression reduced ENaC's function. These findings reinforce a role for miRs in aldosterone regulation of Na + transport, and implicate miR-27 in aldosterone's action via a novel target. J. Cell. Physiol. 232: 1306-1317, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Hypotonic Shock Modulates Na+ Current via a Cl- and Ca2+/Calmodulin Dependent Mechanism in Alveolar Epithelial Cells

PubMed Central

Tatur, Sabina; Brochiero, Emmanuelle; Grygorczyk, Ryszard; Berthiaume, Yves

2013-01-01

Alveolar epithelial cells are involved in Na+ absorption via the epithelial Na+ channel (ENaC), an important process for maintaining an appropriate volume of liquid lining the respiratory epithelium and for lung oedema clearance. Here, we investigated how a 20% hypotonic shock modulates the ionic current in these cells. Polarized alveolar epithelial cells isolated from rat lungs were cultured on permeant filters and their electrophysiological properties recorded. A 20% bilateral hypotonic shock induced an immediate, but transient 52% rise in total transepithelial current and a 67% increase in the amiloride-sensitive current mediated by ENaC. Amiloride pre-treatment decreased the current rise after hypotonic shock, showing that ENaC current is involved in this response. Since Cl- transport is modulated by hypotonic shock, its contribution to the basal and hypotonic-induced transepithelial current was also assessed. Apical NPPB, a broad Cl- channel inhibitor and basolateral DIOA a potassium chloride co-transporter (KCC) inhibitor reduced the total and ENaC currents, showing that transcellular Cl- transport plays a major role in that process. During hypotonic shock, a basolateral Cl- influx, partly inhibited by NPPB is essential for the hypotonic-induced current rise. Hypotonic shock promoted apical ATP secretion and increased intracellular Ca2+. While apyrase, an ATP scavenger, did not inhibit the hypotonic shock current response, W7 a calmodulin antagonist completely prevented the hypotonic current rise. These results indicate that a basolateral Cl- influx as well as Ca2+/calmodulin, but not ATP, are involved in the acute transepithelial current rise elicited by hypotonic shock. PMID:24019969

Redox regulation of epithelial sodium channels examined in alveolar type 1 and 2 cells patch-clamped in lung slice tissue.

PubMed

Helms, My N; Jain, Lucky; Self, Julie L; Eaton, Douglas C

2008-08-15

The alveolar surface of the lung is lined by alveolar type 1 (AT1) and type 2 (AT2) cells. Using single channel patch clamp analysis in lung slice preparations, we are able to uniquely study AT1 and AT2 cells separately from intact lung. We report for the first time the Na+ transport properties of type 2 cells accessed in live lung tissue (as we have done in type 1 cells). Type 2 cells in lung tissue slices express both highly selective cation and nonselective cation channels with average conductances of 8.8 +/- 3.2 and 22.5 +/- 6.3 picosiemens, respectively. Anion channels with 10-picosiemen conductance are also present in the apical membrane of type 2 cells. Our lung slice studies importantly verify the use of cultured cell model systems commonly used in lung epithelial sodium channel (ENaC) studies. Furthermore, we identify novel functional differences between the cells that make up the alveolar epithelium. One important difference is that exposure to the nitric oxide (NO) donor, PAPA-NONOate (1.5 microm), significantly decreases average ENaC NPo in type 2 cells (from 1.38 +/- 0.26 to 0.82 +/- 0.16; p < 0.05 and n = 18) but failed to alter ENaC activity in alveolar type 1 cells. Elevating endogenous superoxide (O2.) levels with Ethiolat, a superoxide dismutase inhibitor, prevented NO inhibition of ENaC activity in type 2 cells, supporting the novel hypothesis that O2. and NO signaling plays an important role in maintaining lung fluid balance.

Sodium channel γENaC mediates IL-17 synergized high salt induced inflammatory stress in breast cancer cells

PubMed Central

Amara, Suneetha; Ivy, Michael T; Myles, Elbert L; Tiriveedhi, Venkataswarup

2015-01-01

Chronic inflammation is known to play a critical role in the development of cancer. Recent evidence suggests that high salt in the tissue microenvironment induces chronic inflammatory milieu. In this report, using three breast cancer-related cell lines, we determined the molecular basis of the potential synergistic inflammatory effect of sodium chloride (NaCl) with interleukin-17 (IL-17). Combined treatment of high NaCl (0.15 M) with sub-effective IL-17 (0.1 nM) induced enhanced growth in breast cancer cells along with activation of reactive nitrogen and oxygen (RNS/ROS) species known to promote cancer. Similar effect was not observed with equi-molar mannitol. This enhanced of ROS/RNS activity correlates with upregulation of γENaC an inflammatiory sodium channel. The similar culture conditions have also induced expression of pro-inflammatory cytokines such as IL-6, TNFα etc. Taken together, these data suggest that high NaCl in the cellular microenvironment induces a γENaC mediated chronic inflammatory response with a potential pro-carcinogenic effect. PMID:26723502

Early cystic fibrosis lung disease: Role of airway surface dehydration and lessons from preventive rehydration therapies in mice.

PubMed

Mall, Marcus A; Graeber, Simon Y; Stahl, Mirjam; Zhou-Suckow, Zhe

2014-07-01

Cystic fibrosis (CF) lung disease starts in the first months of life and remains one of the most common fatal hereditary diseases. Early therapeutic interventions may provide an opportunity to prevent irreversible lung damage and improve outcome. Airway surface dehydration is a key disease mechanism in CF, however, its role in the in vivo pathogenesis and as therapeutic target in early lung disease remains poorly understood. Mice with airway-specific overexpression of the epithelial Na(+) channel (βENaC-Tg) recapitulate airway surface dehydration and phenocopy CF lung disease. Recent studies in neonatal βENaC-Tg mice demonstrated that airway surface dehydration produces early mucus plugging in the absence of mucus hypersecretion, which triggers airway inflammation, promotes bacterial infection and causes early mortality. Preventive rehydration therapy with hypertonic saline or amiloride effectively reduced mucus plugging and mortality in neonatal βENaC-Tg mice. These results support clinical testing of preventive/early rehydration strategies in infants and young children with CF. Copyright © 2014 Elsevier Ltd. All rights reserved.

Method of enhancing cyclotron beam intensity

DOEpatents

Hudson, Ed D.; Mallory, Merrit L.

1977-01-01

When an easily ionized support gas such as xenon is added to the cold cathode in sources of the Oak Ridge Isochronous Cyclotron, large beam enhancements are produced. For example, .sup.20 Ne.sup.7+ is increased from 0.05 enA to 27 enA, and .sup.16 O.sup.5+ intensities in excess of 35 e.mu.A have been extracted for periods up to 30 minutes. Approximately 0.15 cc/min of the easily ionized support gas is supplied to the ion source through a separate gas feed line and the primary gas flow is reduced by about 30%.

Rapid strain improvement through optimized evolution in the cytostat.

PubMed

Gilbert, Alan; Sangurdekar, Dipen P; Srienc, Friedrich

2009-06-15

Acetate is present in lignocellulosic hydrolysates at growth inhibiting concentrations. Industrial processes based on such feedstock require strains that are tolerant of this and other inhibitors present. We investigated the effect of acetate on Saccharomyces cerevisiae and show that elevated acetate concentrations result in a decreased specific growth rate, an accumulation of cells in the G1 phase of the cell cycle, and an increased cell size. With the cytostat cultivation technology under previously derived optimal operating conditions, several acetate resistant mutants were enriched and isolated in the shortest possible time. In each case, the isolation time was less than 5 days. The independently isolated mutant strains have increased specific growth rates under conditions of high acetate concentrations, high ethanol concentrations, and high temperature. In the presence of high acetate concentrations, the isolated mutants produce ethanol at higher rates and titers than the parental strain and a commercial ethanol producing strain that has been analyzed for comparison. Whole genome microarray analysis revealed gene amplifications in each mutant. In one case, the LPP1 gene, coding for lipid phosphate phosphatase, was amplified. Two mutants contained amplified ENA1, ENA2, and ENA5 genes, which code for P-type ATPase sodium pumps. LPP1 was overexpressed on a plasmid, and the growth data at elevated acetate concentrations suggest that LPP1 likely contributes to the phenotype of acetate tolerance. A diploid cross of the two mutants with the amplified ENA genes grew faster than either individual haploid parent strain when 20 g/L acetate was supplemented to the medium, which suggests that these genes contribute to acetate tolerance in a gene dosage dependent manner. 2009 Wiley Periodicals, Inc.

Optimizing nasal potential difference analysis for CFTR modulator development: assessment of ivacaftor in CF subjects with the G551D-CFTR mutation.

PubMed

Rowe, Steven M; Liu, Bo; Hill, Aubrey; Hathorne, Heather; Cohen, Morty; Beamer, John R; Accurso, Frank J; Dong, Qunming; Ordoñez, Claudia L; Stone, Anne J; Olson, Eric R; Clancy, John P

2013-01-01

Nasal potential difference (NPD) is used as a biomarker of the cystic fibrosis transmembrane conductance regulator (CFTR) and epithelial sodium channel (ENaC) activity. We evaluated methods to detect changes in chloride and sodium transport by NPD based on a secondary analysis of a Phase II CFTR-modulator study. Thirty-nine subjects with CF who also had the G551D-CFTR mutation were randomized to receive ivacaftor (Kalydeco™; also known as VX-770) in four doses or placebo twice daily for at least 14 days. All data were analyzed by a single investigator who was blinded to treatment assignment. We compared three analysis methods to determine the best approach to quantify changes in chloride and sodium transport: (1) the average of both nostrils; (2) the most-polarized nostril at each visit; and (3) the most-polarized nostril at screening carried forward. Parameters of ion transport included the PD change with zero chloride plus isoproterenol (CFTR activity), the basal PD, Ringer's PD, and change in PD with amiloride (measurements of ENaC activity), and the delta NPD (measuring CFTR and ENaC activity). The average and most-polarized nostril at each visit were most sensitive to changes in chloride and sodium transport, whereas the most-polarized nostril at screening carried forward was less discriminatory. Based on our findings, NPD studies should assess both nostrils rather than a single nostril. We also found that changes in CFTR activity were more readily detected than changes in ENaC activity, and that rigorous standardization was associated with relatively good within-subject reproducibility in placebo-treated subjects (± 2.8 mV). Therefore, we have confirmed an assay of reasonable reproducibility for detecting chloride-transport improvements in response to CFTR modulation.

Occurrence of mycotoxins in refrigerated pizza dough and risk assessment of exposure for the Spanish population.

PubMed

Quiles, Juan Manuel; Saladino, Federica; Mañes, Jordi; Fernández-Franzón, Mónica; Meca, Giuseppe

2016-08-01

Mycotoxins are toxic metabolites produced by filamentous fungi, as Aspergillus, Penicillium and Fusarium. The first objective of this research was to study the presence of mycotoxins in 60 samples of refrigerated pizza dough, by extraction with methanol and determination by liquid chromatography associated with tandem mass spectrometry (LC-MS/MS). Then, the estimated dietary intakes (EDIs) of these mycotoxins, among the Spanish population, was calculated and the health risk assessment was performed, comparing the EDIs data with the tolerable daily intake values (TDIs). The mycotoxins detected in the analyzed samples were aflatoxin B1 (AFB1), aflatoxin B2 (AFB2), aflatoxin G1 (AFG1), zearalenone (ZEA), enniatin A (ENA), enniatin A1 (ENA1), enniatin (ENB), enniatin B1 (ENB1) and BEA (beauvericin) with average concentration of the positive samples of 4.09 μg/kg, 0.50 μg/kg, 0.79 μg/kg, 77.78 μg/kg, 14.96 μg/kg, 4.54 μg/kg, 3.37 μg/kg, 1.69 μg/kg and 22.39 μg/kg, respectively. The presence of ZEA, ENA1, ENB and ENB1 was detected in 100% of the samples, AFB2 in 32%, AFB1 in 23%, ENA in 8% and BEA in 3%. Twelve percent of the samples contaminated with AFB1 and 12% of the doughs contaminated with ZEA exceeded the EU legislated maximum limits. The dietary intakes were estimated considering three different age groups of population, and the EDIs calculated for the mycotoxins detected in the samples were all below the established TDI. Copyright © 2016 Elsevier Ltd. All rights reserved.

Drought timing and local climate determine the sensitivity of eastern temperate forests to drought.

PubMed

D'Orangeville, Loïc; Maxwell, Justin; Kneeshaw, Daniel; Pederson, Neil; Duchesne, Louis; Logan, Travis; Houle, Daniel; Arseneault, Dominique; Beier, Colin M; Bishop, Daniel A; Druckenbrod, Daniel; Fraver, Shawn; Girard, François; Halman, Joshua; Hansen, Chris; Hart, Justin L; Hartmann, Henrik; Kaye, Margot; Leblanc, David; Manzoni, Stefano; Ouimet, Rock; Rayback, Shelly; Rollinson, Christine R; Phillips, Richard P

2018-06-01

Projected changes in temperature and drought regime are likely to reduce carbon (C) storage in forests, thereby amplifying rates of climate change. While such reductions are often presumed to be greatest in semi-arid forests that experience widespread tree mortality, the consequences of drought may also be important in temperate mesic forests of Eastern North America (ENA) if tree growth is significantly curtailed by drought. Investigations of the environmental conditions that determine drought sensitivity are critically needed to accurately predict ecosystem feedbacks to climate change. We matched site factors with the growth responses to drought of 10,753 trees across mesic forests of ENA, representing 24 species and 346 stands, to determine the broad-scale drivers of drought sensitivity for the dominant trees in ENA. Here we show that two factors-the timing of drought, and the atmospheric demand for water (i.e., local potential evapotranspiration; PET)-are stronger drivers of drought sensitivity than soil and stand characteristics. Drought-induced reductions in tree growth were greatest when the droughts occurred during early-season peaks in radial growth, especially for trees growing in the warmest, driest regions (i.e., highest PET). Further, mean species trait values (rooting depth and ψ 50 ) were poor predictors of drought sensitivity, as intraspecific variation in sensitivity was equal to or greater than interspecific variation in 17 of 24 species. From a general circulation model ensemble, we find that future increases in early-season PET may exacerbate these effects, and potentially offset gains in C uptake and storage in ENA owing to other global change factors. © 2018 John Wiley & Sons Ltd.

K+ channel openers restore verapamil-inhibited lung fluid resolution and transepithelial ion transport

PubMed Central

2010-01-01

Background Lung epithelial Na+ channels (ENaC) are regulated by cell Ca2+ signal, which may contribute to calcium antagonist-induced noncardiogenic lung edema. Although K+ channel modulators regulate ENaC activity in normal lungs, the therapeutical relevance and the underlying mechanisms have not been completely explored. We hypothesized that K+ channel openers may restore calcium channel blocker-inhibited alveolar fluid clearance (AFC) by up-regulating both apical and basolateral ion transport. Methods Verapamil-induced depression of heterologously expressed human αβγ ENaC in Xenopus oocytes, apical and basolateral ion transport in monolayers of human lung epithelial cells (H441), and in vivo alveolar fluid clearance were measured, respectively, using the two-electrode voltage clamp, Ussing chamber, and BSA protein assays. Ca2+ signal in H441 cells was analyzed using Fluo 4AM. Results The rate of in vivo AFC was reduced significantly (40.6 ± 6.3% of control, P < 0.05, n = 12) in mice intratracheally administrated verapamil. KCa3.1 (1-EBIO) and KATP (minoxidil) channel openers significantly recovered AFC. In addition to short-circuit current (Isc) in intact H441 monolayers, both apical and basolateral Isc levels were reduced by verapamil in permeabilized monolayers. Moreover, verapamil significantly altered Ca2+ signal evoked by ionomycin in H441 cells. Depletion of cytosolic Ca2+ in αβγ ENaC-expressing oocytes completely abolished verapamil-induced inhibition. Intriguingly, KV (pyrithione-Na), K Ca3.1 (1-EBIO), and KATP (minoxidil) channel openers almost completely restored the verapamil-induced decrease in Isc levels by diversely up-regulating apical and basolateral Na+ and K+ transport pathways. Conclusions Our observations demonstrate that K+ channel openers are capable of rescuing reduced vectorial Na+ transport across lung epithelial cells with impaired Ca2+ signal. PMID:20507598

Measurement of Antinuclear Antibodies: Assessment of Different Test Systems

PubMed Central

Kern, P.; Kron, M.; Hiesche, K.

2000-01-01

The performance of rat liver and HEp-2 in the detection of antinuclear antibodies (ANA) was studied by two independent sites and compared against an ANA enzyme immunoassay (EIA) screen and EIA systems for the measurement of antibodies to double-stranded DNA (dsDNA) and ENA. Sixty-two sera from patients with connective tissue disease (CTD) and 398 from controls suffering from other disorders were included. The level of agreement was, for HEp-2 and rat liver (within one site), 82.0% (ANA positive/ANA negative) and 51.0% (ANA pattern); and for HEp2- and HEp-2 (between sites), 71.8 and 86.5%. On sera with the ANA homogeneous pattern, the measurement of anti-ENA EIA added little to the detection rate with anti-dsDNA EIA alone. On ANA speckled sera, the EIA reactivity depended on the reaction of the mitotic cells: while sera with positive mitoses reacted similarly to ANA homogeneous sera, in those with negative mitoses the measurement of anti-ENA added about 10% to the detection rate achieved with anti-dsDNA alone. The measurement of anti-Scl-70 and anti-Jo-1 did not markedly improve the positive rate with classical ENA (anti-SSA, -SSB, -Sm, and -RNP) alone, raising doubts about the cost efficiency of including these measurements in unselected sera. The ANA EIA identified patients with CTD at a rate similar to that for rat liver and HEp-2. However, up to 98% of the sera found to be negative by ANA EIA but positive by use of rat liver and HEp-2 were from controls. Thus, the ANA EIA may possible be used as an alternative screen, particularly in laboratories with a high frequency of sera from patients not suffering from CTD. PMID:10618281

Potassium Supplementation Prevents Sodium Chloride Cotransporter Stimulation during Angiotensin II Hypertension

PubMed Central

Veiras, Luciana C.; Han, Jiyang; Ralph, Donna L.; McDonough, Alicia A.

2016-01-01

Ang II hypertension increases distal tubule Na-Cl cotransporter (NCC) abundance and phosphorylation (NCCp), as well as epithelial Na+ channel (ENaC) abundance and activating cleavage. Acutely raising plasma [K+] by infusion or ingestion provokes a rapid decrease in NCCp that drives a compensatory kaliuresis. The first aim tested whether acutely raising plasma [K+] with a single 3 hr 2% potassium meal would lower NCCp in Sprague Dawley rats after 14 days of AngII (400 ng/kg/min). The potassium-rich meal neither decreased NCCp nor increased K+ excretion. AngII infused rats exhibited lower plasma [K+] versus controls (3.6 ± 0.2 vs. 4.5 ± 0.1 mmol/L, p < 0.05) suggesting that Ang II mediated ENaC activation provokes K+ depletion. The second aim tested whether doubling dietary potassium intake from 1% (A1K) to 2% (A2K) would prevent K+ depletion during AngII infusion and, thus, prevent NCC accumulation. A2K fed rats exhibited normal plasma [K+] and 2-fold higher K+ excretion and plasma [aldosterone] versus A1K. In A1K rats, NCC, NCCpS71, and NCCpT53 abundance increased 1.5- to 3-fold versus controls (p< 0.05). The rise in NCC and NCCp abundance was prevented in the A2K rats, yet blood pressure did not significantly decrease. ENaC subunit abundance and cleavage increased 1.5- to 3-fold in both A1K and A2K; ROMK abundance was unaffected by Ang II or dietary K+. In summary, the accumulation and phosphorylation of NCC seen during chronic AngII infusion hypertension is likely secondary to potassium deficiency driven by ENaC stimulation. PMID:27600183

Nedd4-2 Modulates Renal Na+-Cl− Cotransporter via the Aldosterone-SGK1-Nedd4-2 Pathway

PubMed Central

Arroyo, Juan Pablo; Lagnaz, Dagmara; Ronzaud, Caroline; Vázquez, Norma; Ko, Benjamin S.; Moddes, Lauren; Ruffieux-Daidié, Dorothée; Hausel, Pierrette; Koesters, Robert; Yang, Baoli; Stokes, John B.; Hoover, Robert S.

2011-01-01

Regulation of renal Na+ transport is essential for controlling blood pressure, as well as Na+ and K+ homeostasis. Aldosterone stimulates Na+ reabsorption by the Na+-Cl− cotransporter (NCC) in the distal convoluted tubule (DCT) and by the epithelial Na+ channel (ENaC) in the late DCT, connecting tubule, and collecting duct. Aldosterone increases ENaC expression by inhibiting the channel's ubiquitylation and degradation; aldosterone promotes serum-glucocorticoid-regulated kinase SGK1-mediated phosphorylation of the ubiquitin-protein ligase Nedd4-2 on serine 328, which prevents the Nedd4-2/ENaC interaction. It is important to note that aldosterone increases NCC protein expression by an unknown post-translational mechanism. Here, we present evidence that Nedd4-2 coimmunoprecipitated with NCC and stimulated NCC ubiquitylation at the surface of transfected HEK293 cells. In Xenopus laevis oocytes, coexpression of NCC with wild-type Nedd4-2, but not its catalytically inactive mutant, strongly decreased NCC activity and surface expression. SGK1 prevented this inhibition in a kinase-dependent manner. Furthermore, deficiency of Nedd4-2 in the renal tubules of mice and in cultured mDCT15 cells upregulated NCC. In contrast to ENaC, Nedd4-2-mediated inhibition of NCC did not require the PY-like motif of NCC. Moreover, the mutation of Nedd4-2 at either serine 328 or 222 did not affect SGK1 action, and mutation at both sites enhanced Nedd4-2 activity and abolished SGK1-dependent inhibition. Taken together, these results suggest that aldosterone modulates NCC protein expression via a pathway involving SGK1 and Nedd4-2 and provides an explanation for the well-known aldosterone-induced increase in NCC protein expression. PMID:21852580

Hydronephrosis is associated with elevated plasmin in urine in pediatric patients and rats and changes in NCC and γ-ENaC abundance in rat kidney.

PubMed

Zachar, Rikke; Al-Mashhadi, Ammar; Dimke, Henrik; Svenningsen, Per; Jensen, Boye L; Carlström, Mattias

2018-05-16

Obstruction of urine flow at the level of the pelvo-ureteric junction (UPJO) and subsequent development of hydronephrosis is one of the most common congenital renal malformations. UPJO is associated with development of salt-sensitive hypertension, which is set by the obstructed kidney, and with a stimulated renin-angiotensin-aldosterone system (RAAS) in rodent models. This study aimed at investigating the hypothesis that i) in pediatric patients with UPJO the RAAS is activated prior to surgical relief of the obstruction; ii) in rats with UPJO the RAAS activation is reflected by increased abundance of renal aldosterone-stimulated Na+ transporters; and iii) the injured UPJO kidney allows aberrant filtration of plasminogen leading to proteolytic activation of the epithelial sodium channel gamma subunit (γ-ENaC). Hydronephrosis due to UPJO in pediatric patients and rats was associated with increased urinary plasminogen/creatinine ratio. In pediatric patients, plasma renin, angiotensin II, urine and plasma aldosterone and urine soluble pro-renin receptor did not differ significantly before and after surgery, or compared with controls. Increased plasmin/plasminogen ratio was seen in UPJO rats. Intact γ-ENaC abundance was not changed in UPJO kidney while low-molecular cleavage product abundance increased. The Na-Cl cotransporter (NCC) displayed significantly lower abundance in the UPJO kidney compared to the non-obstructed contralateral kidney. The Na-K-ATPase alpha-subunit was unaltered. Treatment with an angiotensin-converting enzyme inhibitor (8 days, captopril) significantly lowered blood pressure in UPJO rats. It is concluded that the RAAS contributes to hypertension following partial obstruction of urine flow at the pelvo-ureteric junction with potential contribution from proteolytic activation of ENaC.

CFTR/ENaC dependent regulation of membrane potential during human sperm capacitation is initiated by bicarbonate uptake through NBC.

PubMed

Puga Molina, Lis C; Pinto, Nicolas A; Torres, Nicolás I; Gonzalez-Cota, Ana L; Luque, Guillermina M; Balestrini, Paula A; Romarowski, Ana; Krapf, Dario; Santi, Celia M; Trevino, Claudia L; Darszon, Alberto; Buffone, Mariano G

2018-05-09

To fertilize an egg, sperm must reside in the female reproductive tract to undergo several maturational changes that are collectively referred to as capacitation. From a molecular point of view, the HCO3--dependent activation of the atypical soluble adenylyl cyclase (ADCY10) is one of the first events that occurs during capacitation and leads to the subsequent cAMP-dependent activation of protein kinase A (PKA). Capacitation is also accompanied by hyperpolarization of the sperm plasma membrane. We previously reported that PKA activation is necessary for CFTR (Cystic Fibrosis Transmembrane Conductance Regulator Channel) activity and for the modulation of membrane potential (Em). However, the main HCO3- transporters involved in the initial transport and the PKA-dependent Em changes are not well known nor characterized. Here, we analyzed how the activity of CFTR regulates Em during capacitation and examined its relationship with an electrogenic Na+/HCO3- cotransporter (NBC) and epithelial Na+ channels (ENaCs). We observed that inhibition of both CFTR and NBC decreased HCO3- influx, resulting in lower PKA activity, and that events downstream the cAMP-activation of PKA are essential for the regulation of Em. Addition of a permeable cAMP analog partially rescued the inhibitory effects caused by these inhibitors. HCO3-  also produced a rapid membrane hyperpolarization mediated by ENaC channels, which contribute to the regulation of Em during capacitation. Altogether, we demonstrate for the first time, that NBC cotransporters and ENaC channels are essential in the CFTR-dependent activation of the cAMP/PKA signaling pathway and Em regulation during human sperm capacitation. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

Retinal vasculopathy is reduced by dietary salt restriction: involvement of Glia, ENaCα, and the renin-angiotensin-aldosterone system.

PubMed

Deliyanti, Devy; Armani, Roksana; Casely, David; Figgett, William A; Agrotis, Alex; Wilkinson-Berka, Jennifer L

2014-09-01

Neovascularization and vaso-obliteration are vision-threatening events that develop by interactions between retinal vascular and glial cells. A high-salt diet is causal in cardiovascular and renal disease, which is linked to modulation of the renin-angiotensin-aldosterone system. However, it is not known whether dietary salt influences retinal vasculopathy and if the renin-angiotensin-aldosterone system is involved. We examined whether a low-salt (LS) diet influenced vascular and glial cell injury and the renin-angiotensin-aldosterone system in ischemic retinopathy. Pregnant Sprague Dawley rats were fed LS (0.03% NaCl) or normal salt (0.3% NaCl) diets, and ischemic retinopathy was induced in the offspring. An LS diet reduced retinal neovascularization and vaso-obliteration, the mRNA and protein levels of the angiogenic factors, vascular endothelial growth factor, and erythropoietin. Microglia, which influence vascular remodeling in ischemic retinopathy, were reduced by LS as was tumor necrosis factor-α. Macroglial Müller cells maintain the integrity of the blood-retinal barrier, and in ischemic retinopathy, LS reduced their gliosis and also vascular leakage. In retina, LS reduced mineralocorticoid receptor, angiotensin type 1 receptor, and renin mRNA levels, whereas, as expected, plasma levels of aldosterone and renin were increased. The aldosterone/mineralocorticoid receptor-sensitive epithelial sodium channel alpha (ENaCα), which is expressed in Müller cells, was increased in ischemic retinopathy and reduced by LS. In cultured Müller cells, high salt increased ENaCα, which was prevented by mineralocorticoid receptor and angiotensin type 1 receptor blockade. Conversely, LS reduced ENaCα, angiotensin type 1 receptor, and mineralocorticoid receptor expression. An LS diet reduced retinal vasculopathy, by modulating glial cell function and the retinal renin-angiotensin-aldosterone system. © 2014 American Heart Association, Inc.

The central mechanism underlying hypertension: a review of the roles of sodium ions, epithelial sodium channels, the renin–angiotensin–aldosterone system, oxidative stress and endogenous digitalis in the brain

PubMed Central

Takahashi, Hakuo; Yoshika, Masamichi; Komiyama, Yutaka; Nishimura, Masato

2011-01-01

The central nervous system has a key role in regulating the circulatory system by modulating the sympathetic and parasympathetic nervous systems, pituitary hormone release, and the baroreceptor reflex. Digoxin- and ouabain-like immunoreactive materials were found >20 years ago in the hypothalamic nuclei. These factors appeared to localize to the paraventricular and supraoptic nuclei and the nerve fibers at the circumventricular organs and supposed to affect electrolyte balance and blood pressure. The turnover rate of these materials increases with increasing sodium intake. As intracerebroventricular injection of ouabain increases blood pressure via sympathetic activation, an endogenous digitalis-like factor (EDLF) was thought to regulate cardiovascular system-related functions in the brain, particularly after sodium loading. Experiments conducted mainly in rats revealed that the mechanism of action of ouabain in the brain involves sodium ions, epithelial sodium channels (ENaCs) and the renin–angiotensin–aldosterone system (RAAS), all of which are affected by sodium loading. Rats fed a high-sodium diet develop elevated sodium levels in their cerebrospinal fluid, which activates ENaCs. Activated ENaCs and/or increased intracellular sodium in neurons activate the RAAS; this releases EDLF in the brain, activating the sympathetic nervous system. The RAAS promotes oxidative stress in the brain, further activating the RAAS and augmenting sympathetic outflow. Angiotensin II and aldosterone of peripheral origin act in the brain to activate this cascade, increasing sympathetic outflow and leading to hypertension. Thus, the brain Na+–ENaC–RAAS–EDLF axis activates sympathetic outflow and has a crucial role in essential and secondary hypertension. This report provides an overview of the central mechanism underlying hypertension and discusses the use of antihypertensive agents. PMID:21814209

Nadph oxidase regulates alveolar epithelial sodium channel activity and lung fluid balance in vivo via O2− signaling

PubMed Central

Goodson, Preston; Kumar, Amrita; Jain, Lucky; Kundu, Kousik; Murthy, Niren; Koval, Michael

2012-01-01

To define roles for reactive oxygen species (ROS) and epithelial sodium channel (ENaC) in maintaining lung fluid balance in vivo, we used two novel whole animal imaging approaches. Live X-ray fluoroscopy enabled quantification of air space fluid content of C57BL/6J mouse lungs challenged by intratracheal (IT) instillation of saline; results were confirmed by using conventional lung wet-to-dry weight ratios and Evans blue as measures of pulmonary edema. Visualization and quantification of ROS produced in lungs was performed in mice that had been administered a redox-sensitive dye, hydro-Cy7, by IT instillation. We found that inhibition of NADPH oxidase with a Rac-1 inhibitor, NSC23766, resulted in alveolar flooding, which correlated with a decrease in lung ROS production in vivo. Consistent with a role for Nox2 in alveolar fluid balance, Nox2−/− mice showed increased retention of air space fluid compared with wild-type controls. Interestingly, fluoroscopic analysis of C57BL/6J lungs IT instilled with LPS showed an acute stimulation of lung fluid clearance and ROS production in vivo that was abrogated by the ROS scavenger tetramethylpiperidine-N-oxyl (TEMPO). Acute application of LPS increased the activity of 20 pS nonselective ENaC channels in rat type 1 cells; the average number of channel and single-channel open probability (NPo) increased from 0.14 ± 0.04 to 0.62 ± 0.23. Application of TEMPO to the same cell-attached recording caused an immediate significant decrease in ENaC NPo to 0.04 ± 0.03. These data demonstrate that, in vivo, ROS has the capacity to stimulate lung fluid clearance by increasing ENaC activity. PMID:22160304

Nadph oxidase regulates alveolar epithelial sodium channel activity and lung fluid balance in vivo via O⁻₂ signaling.

PubMed

Goodson, Preston; Kumar, Amrita; Jain, Lucky; Kundu, Kousik; Murthy, Niren; Koval, Michael; Helms, My N

2012-02-15

To define roles for reactive oxygen species (ROS) and epithelial sodium channel (ENaC) in maintaining lung fluid balance in vivo, we used two novel whole animal imaging approaches. Live X-ray fluoroscopy enabled quantification of air space fluid content of C57BL/6J mouse lungs challenged by intratracheal (IT) instillation of saline; results were confirmed by using conventional lung wet-to-dry weight ratios and Evans blue as measures of pulmonary edema. Visualization and quantification of ROS produced in lungs was performed in mice that had been administered a redox-sensitive dye, hydro-Cy7, by IT instillation. We found that inhibition of NADPH oxidase with a Rac-1 inhibitor, NSC23766, resulted in alveolar flooding, which correlated with a decrease in lung ROS production in vivo. Consistent with a role for Nox2 in alveolar fluid balance, Nox2(-/-) mice showed increased retention of air space fluid compared with wild-type controls. Interestingly, fluoroscopic analysis of C57BL/6J lungs IT instilled with LPS showed an acute stimulation of lung fluid clearance and ROS production in vivo that was abrogated by the ROS scavenger tetramethylpiperidine-N-oxyl (TEMPO). Acute application of LPS increased the activity of 20 pS nonselective ENaC channels in rat type 1 cells; the average number of channel and single-channel open probability (NPo) increased from 0.14 ± 0.04 to 0.62 ± 0.23. Application of TEMPO to the same cell-attached recording caused an immediate significant decrease in ENaC NPo to 0.04 ± 0.03. These data demonstrate that, in vivo, ROS has the capacity to stimulate lung fluid clearance by increasing ENaC activity.

INTRARENAL GHRELIN RECEPTOR INHIBITION AMELIORATES ANGIOTENSIN II-DEPENDENT HYPERTENSION IN RATS.

PubMed

Kemp, Brandon A; Howell, Nancy L; Padia, Shetal H

2018-06-20

The intrarenal ghrelin receptor (GR) is localized to collecting duct (CD) cells where it increases αENaC-dependent sodium reabsorption in rodents. We hypothesized that chronic GR inhibition with intrarenal GR siRNA lowers blood pressure (BP) in Angiotensin II-dependent hypertension via reductions in αENaC-dependent sodium reabsorption. Uninephrectomized Sprague-Dawley rats (N=121) received subcutaneous osmotic pumps for chronic systemic delivery of Angiotensin II or vehicle (5% dextrose in water). Rats also received intrarenal infusion of vehicle, GR siRNA, or scrambled (SCR) siRNA. In rats receiving intrarenal vehicle or intrarenal SCR siRNA, systemic Angiotensin II infusion increased sodium retention and BP on day 1, and BP remained elevated throughout the 5-day study. These rats also demonstrated increased CD GR expression after 5 days of infusion. However, intrarenal GR siRNA infusion prevented Angiotensin II-mediated sodium retention on day 1, induced a continuously negative cumulative sodium balance compared with Angiotensin II alone, and reduced BP chronically. Glomerular filtration rate and renal blood flow remained unchanged in GR siRNA-infused rats. Systemic Angiotensin II infusion also increased serum aldosterone levels, CD αENaC and pSGK1 expression in rats with intrarenal SCR siRNA; however these effects were not observed in the presence of intrarenal GR siRNA, despite exposure to the same systemic Angiotensin II. These data demonstrate that chronic inhibition of intrarenal GR activity significantly reduces αENaC -dependent sodium retention, resulting in a negative cumulative sodium balance, thereby ameliorating Angiotensin II-induced hypertension in rats. Renal GRs represent a novel therapeutic target for the treatment of hypertension and other sodium-retaining states.

Improved Background Removal in Sounding Rocket Neutral Atom Imaging Data

NASA Astrophysics Data System (ADS)

Smith, M. R.; Rowland, D. E.

2017-12-01

The VISIONS sounding rocket, launched into a substorm on Feb 7, 2013 from Poker Flat, Alaska had a novel miniaturized energetic neutral atom (ENA) imager onboard. We present further analysis of the ENA data from this rocket flight, including improved removal of ultraviolet and electron contamination. In particular, the relative error source contributions due to geocoronal, auroral, and airglow UV, as well as energetic electrons from 10 eV to 3 keV were assessed. The resulting data provide a more clear understanding of the spatial and temporal variations of the ion populations that are energized to tens or hundreds of eV.

IMPACT OF PLANETARY GRAVITATION ON HIGH-PRECISION NEUTRAL ATOM MEASUREMENTS

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

Kucharek, H.; Möbius, E.; Lee, M. A.

2015-10-15

Measurements of energetic neutral atoms (ENAs) have been extremely successful in providing very important information on the physical processes inside and outside of our heliosphere. For instance, recent Interstellar Boundary Explorer (IBEX) observations have provided new insights into the local interstellar environment and improved measurements of the interstellar He temperature, velocity, and direction of the interstellar flow vector. Since particle collisions are rare, and radiation pressure is negligible for these neutrals, gravitational forces mainly determine the trajectories of neutral He atoms. Depending on the distance of an ENA to the source of a gravitational field and its relative speed andmore » direction, this can result in significant deflection and acceleration. In this paper, we investigate the impact of the gravitational effects of Earth, the Moon, and Jupiter on ENA measurements performed in Earth’s orbit. The results show that current analysis of the interstellar neutral parameters by IBEX is not significantly affected by planetary gravitational effects. We further studied the possibility of whether or not the Helium focusing cone of the Sun and Jupiter could be measured by IBEX and whether or not these cones could be used as an independent measure of the temperature of interstellar Helium.« less

A Cytosolic Amphiphilic α-Helix Controls the Activity of the Bile Acid-sensitive Ion Channel (BASIC)*

PubMed Central

Schmidt, Axel; Löhrer, Daniel; Alsop, Richard J.; Lenzig, Pia; Oslender-Bujotzek, Adrienne; Wirtz, Monika; Rheinstädter, Maikel C.; Gründer, Stefan; Wiemuth, Dominik

2016-01-01

The bile acid-sensitive ion channel (BASIC) is a member of the degenerin/epithelial Na+ channel (Deg/ENaC) family of ion channels. It is mainly found in bile duct epithelial cells, the intestinal tract, and the cerebellum and is activated by alterations of its membrane environment. Bile acids, one class of putative physiological activators, exert their effect by changing membrane properties, leading to an opening of the channel. The physiological function of BASIC, however, is unknown. Deg/ENaC channels are characterized by a trimeric subunit composition. Each subunit is composed of two transmembrane segments, which are linked by a large extracellular domain. The termini of the channels protrude into the cytosol. Many Deg/ENaC channels contain regulatory domains and sequence motifs within their cytosolic domains. In this study, we show that BASIC contains an amphiphilic α-helical structure within its N-terminal domain. This α-helix binds to the cytosolic face of the plasma membrane and stabilizes a closed state. Truncation of this domain renders the channel hyperactive. Collectively, we identify a cytoplasmic domain, unique to BASIC, that controls channel activity via membrane interaction. PMID:27679529

The possible role of Mena protein and its splicing-derived variants in embryogenesis, carcinogenesis, and tumor invasion: a systematic review of the literature.

PubMed

Gurzu, Simona; Ciortea, Diana; Ember, Istvan; Jung, Ioan

2013-01-01

The Ena/VASP (enabled/vasodilator stimulated phosphoprotein) family includes the binding actin proteins such as mammalian Ena (Mena), VASP, and Ena-VASP-like. It is known that the perturbation of actin cycle could determine alteration in the mobility of cells and in consequence of organogenesis. Few recent studies have revealed that Mena protein could play a role in breast or pancreatic carcinogenesis. Based on our researches, we observed that the intensity of Mena expression increased from premalignant to malignant lesions in some organs such as large bowel, stomach, cervix, and salivary glands. These findings prove that Mena could be a marker of premalignant epithelial lesions. In premalignant lesions, it could be helpful to define more accurately the risk for malignant transformation. In malignant tumors, correlation of expression of its splice variants could indicate metastatic behavior. In conclusion, we consider that it is necessary to analyze the expression of Mena splice variants in a higher number of cases, in different epithelial lesions, and also in experimental studies to define its exact role in carcinogenesis and also its possible prognostic and predictive values.

A Cytosolic Amphiphilic α-Helix Controls the Activity of the Bile Acid-sensitive Ion Channel (BASIC).

PubMed

Schmidt, Axel; Löhrer, Daniel; Alsop, Richard J; Lenzig, Pia; Oslender-Bujotzek, Adrienne; Wirtz, Monika; Rheinstädter, Maikel C; Gründer, Stefan; Wiemuth, Dominik

2016-11-18

The bile acid-sensitive ion channel (BASIC) is a member of the degenerin/epithelial Na + channel (Deg/ENaC) family of ion channels. It is mainly found in bile duct epithelial cells, the intestinal tract, and the cerebellum and is activated by alterations of its membrane environment. Bile acids, one class of putative physiological activators, exert their effect by changing membrane properties, leading to an opening of the channel. The physiological function of BASIC, however, is unknown. Deg/ENaC channels are characterized by a trimeric subunit composition. Each subunit is composed of two transmembrane segments, which are linked by a large extracellular domain. The termini of the channels protrude into the cytosol. Many Deg/ENaC channels contain regulatory domains and sequence motifs within their cytosolic domains. In this study, we show that BASIC contains an amphiphilic α-helical structure within its N-terminal domain. This α-helix binds to the cytosolic face of the plasma membrane and stabilizes a closed state. Truncation of this domain renders the channel hyperactive. Collectively, we identify a cytoplasmic domain, unique to BASIC, that controls channel activity via membrane interaction. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Biotransformation, genotoxic, and histopathological effects of environmental contaminants in European eel (Anguilla anguilla L.).

PubMed

Pacheco, Mário; Santos, Maria Ana

2002-11-01

A prolonged toxicity study was carried out in young European eel (Anguilla anguilla L.) to evaluate the effects of environmental contaminants, namely, two individual standard compounds, benzo[a]pyrene (BaP) and dehydroabietic acid (DHAA), and a complex mixture, bleached kraft pulp mill effluent (BKPME). Fish were exposed to BaP (0.22, 0.45, and 0.9 microM) and BKPME (3.12%, 6.25%, and 12.5% (v/v)) for 3, 7, and 30 days and to DHAA (0.07, 0.15, and 0.30 microM) for 3, 7, 30, 90, and 180 days. The biomarkers include biotransformation and genotoxicity indicators, such as total ethoxyresorufin O-deethylase (EROD) activity and frequency of erythrocytic nuclear abnormalities (ENAs), respectively. Hematological dynamics was assessed as frequency of immature erythrocytes (IEs). Histopathological examinations were carried out for the highest concentrations and for 30 days and longer exposures. Total EROD increases significantly only after 180 days of DHAA exposure. However, significant ENA induction was generally observed during exposure to all contaminants tested. Nevertheless, some of the ENA results suggest an altered genotoxic response, which may arise either from short-term exposures to the highest contaminant levels or long-term exposures to the lowest contaminant levels. IE frequency decreased significantly after 30 days of exposure to 0.45 microM BaP and 180 days of exposure to the entire DHAA concentration range. Increased density of pigmented macrophage aggregates in 30-day BaP- and BKPME-exposed fish as well as in 90- and 180-day DHAA-exposed fish confirmed histopathological liver alterations. Bile accumulation in hepatocytes after BaP treatment, cytoplasmic vacuolization and cell atrophy following DHAA exposure, as well as liver loss of parenchymal cells in BKPME-exposed fish, were also detected. Dispersed necrosis and focal inflammation were observed in the livers of all treated groups. Fish exposed to DHAA and BKPME showed skin and gill disruption as well as kidney Malpighian corpuscle alterations. All 30-day-treated groups revealed intense spleen hemosiderosis, indicating increased erythrophagia. This splenic effect may be strongly correlated with the observed disappearance of ENAs. Neoplastic lesions were not found. A multibiomarker strategy, which includes EROD, ENA, and IE assays as well as histopathological studies, contributed to a better understanding of the global toxic process.

The Role of Epithelial Sodium Channel ENaC and the Apical Cl-/HCO3- Exchanger Pendrin in Compensatory Salt Reabsorption in the Setting of Na-Cl Cotransporter (NCC) Inactivation.

PubMed

Patel-Chamberlin, Mina; Varasteh Kia, Mujan; Xu, Jie; Barone, Sharon; Zahedi, Kamyar; Soleimani, Manoocher

2016-01-01

The absence of NCC does not cause significant salt wasting in NCC deficient mice under basal conditions. We hypothesized that ENaC and pendrin play important roles in compensatory salt absorption in the setting of NCC inactivation, and their inhibition and/or downregulation can cause significant salt wasting in NCC KO mice. WT and NCC KO mice were treated with a daily injection of either amiloride, an inhibitor of ENaC, or acetazolamide (ACTZ), a blocker of salt and bicarbonate reabsorption in the proximal tubule and an inhibitor of carbonic anhydrases in proximal tubule and intercalated cells, or a combination of acetazolamide plus amiloride for defined durations. Animals were subjected to daily balance studies. At the end of treatment, kidneys were harvested and examined. Blood samples were collected for electrolytes and acid base analysis. Amiloride injection significantly increased the urine output (UO) in NCC KO mice (from 1.3 ml/day before to 2.5 ml/day after amiloride, p<0.03, n = 4) but caused only a slight change in UO in WT mice (p>0.05). The increase in UO in NCC KO mice was associated with a significant increase in sodium excretion (from 0.25 mmol/24 hrs at baseline to 0.35 mmol/24 hrs after amiloride injection, p<0.05, n = 4). Daily treatment with ACTZ for 6 days resulted in >80% reduction of kidney pendrin expression in both WT and NCC KO mice. However, ACTZ treatment noticeably increased urine output and salt excretion only in NCC KO mice (with urine output increasing from a baseline of 1.1 ml/day to 2.3 ml/day and sodium excretion increasing from 0.22 mmole/day before to 0.31 mmole/day after ACTZ) in NCC KO mice; both parameters were significantly higher than in WT mice. Western blot analysis demonstrated significant enhancement in ENaC expression in medulla and cortex of NCC KO and WT mice in response to ACTZ injection for 6 days, and treatment with amiloride in ACTZ-pretreated mice caused a robust increase in salt excretion in both NCC KO and WT mice. Pendrin KO mice did not display a significant increase in urine output or salt excretion after treatment with amiloride or ACTZ. 1. ENaC plays an important role in salt reabsorption in NCC KO mice. 2. NCC contributes to compensatory salt reabsorption in the setting of carbonic anhydrase inhibition, which is associated with increased delivery of salt from the proximal tubule and the down regulation of pendrin. 3. ENaC is upregulated by ACTZ treatment and its inhibition by amiloride causes significant diuresis in NCC KO and WT mice. Despite being considered mild agents individually, we propose that the combination of acetazolamide and amiloride in the setting of NCC inhibition (i.e., hydrochlorothiazide) will be a powerful diuretic regimen.

Distribution Functions of Sizes and Fluxes Determined from Supra-Arcade Downflows

NASA Technical Reports Server (NTRS)

McKenzie, D.; Savage, S.

2011-01-01

The frequency distributions of sizes and fluxes of supra-arcade downflows (SADs) provide information about the process of their creation. For example, a fractal creation process may be expected to yield a power-law distribution of sizes and/or fluxes. We examine 120 cross-sectional areas and magnetic flux estimates found by Savage & McKenzie for SADs, and find that (1) the areas are consistent with a log-normal distribution and (2) the fluxes are consistent with both a log-normal and an exponential distribution. Neither set of measurements is compatible with a power-law distribution nor a normal distribution. As a demonstration of the applicability of these findings to improved understanding of reconnection, we consider a simple SAD growth scenario with minimal assumptions, capable of producing a log-normal distribution.

Near-Local Interstellar Medium (LISM): What we know from the Voyagers and ENA and what an Interstellar Probe (ISP) can do

NASA Astrophysics Data System (ADS)

Krimigis, S. M.

2017-12-01

In situ measurements by the two Voyagers over the past 13 years have revealed the presence of the long-predicted termination shock (TS) and heliopause (HP), albeit not where theory had placed them. Further, the advent of energetic neutral atom (ENA) imaging by Cassini/INCA since 2003 and IBEX since 2009 have provided images of the global heliosphere that have challenged our long-held views of its shape and the processes that are dominant in its formation (Krimigis et al, and McComas et al, 2009; Dialynas et al, 2017). In addition, continuing measurements from Voyager 1 beyond the HP, now at 140 AU (1 AU=1.5x108 km, the Sun-Earth distance), have shown that the influence of the Sun extends well beyond the HP (at 122 AU). This influence is manifested through the occasional appearance of anisotropies in the galactic cosmic rays (GCR) where none were predicted, that last as long as a year and are accompanied by electron plasma oscillations in the vicinity of the spacecraft. Thus, an ISP mission with a fast ( 15 AU per year compared to Voyager's 3.6) trajectory would traverse a dynamic region near and beyond the TS and HP, and enable imaging the shape of the heliosphere from beyond its boundaries through ENA. In situ measurements should include the ISM magnetic field (ISMF), plasma density and distribution function, plasma waves, and neutral atom density and composition, as a minimum. All of these measurements would be new information with modern instrumentation that would place the very limited Voyager measurements into the proper context. References: Krimigis, S. M., D. G. Mitchell, E. C. Roelof, K. C. Hsieh and D. J. McComas, Imaging the Interaction of the Heliosphere with the Interstellar Medium from Saturn with Cassini, Science, 326, 5955, p. 971, doi: 10.1126/science.1181079, 2009 McComas, D. J., et al, Global Observations of the Interstellar Interaction from the Interstellar Boundary Explorer (IBEX), Science, 326, 5955, pp. 959, doi: 10.1126/science.1180906, 2009. Dialynas, K., S. M. Krimigis, D. G. Mitchell, R. B. Decker, and E. C. Roelof, Voyager and Cassini measurements suggest a "bubble-like" shape of the global heliosphere, Nature Astronomy, 1, 0115 (2017) | DOI: 10.1038/s41550-017-0115

Combinatorial effects of quercetin and sex-steroids on fluid and electrolytes’ (Na+, Cl-, HCO3-) secretory mechanisms in the uterus of ovariectomised female Sprague-Dawley rats

PubMed Central

Shahzad, Huma; Giribabu, Nelli; Karim, Kamarulzaman; Kassim, Normadiah M.; Muniandy, Sekaran

2017-01-01

Dysregulation of uterine fluid environment could impair successful reproduction and this could be due to the effect of environmental estrogens. Therefore, in this study, effect of quercetin, an environmental estrogen on uterine fluid and electrolytes concentrations were investigated under sex-steroid influence. Ovariectomised adult female Sprague-Dawley rats were given 10, 50 or 100mg/kg/day quercetin subcutaneously with 17-β estradiol (E) for seven days or three days E, then three days E plus progesterone (P) (E+P) treatment. Uterine fluid secretion rate, Na+, Cl- and HCO3- concentrations were determined by in-vivo perfusion. Following sacrifice, uteri were harvested and levels of the proteins of interest were identified by Western blotting and Realtime PCR. Distribution of these proteins in the uterus was observed by immunofluorescence. Levels of uterine cAMP were measured by enzyme-linked immunoassay (EIA). Administration of quercetin at increasing doses increased uterine fluid secretion rate, Na+, Cl- and HCO3- concentrations, but to the levels lesser than that of E. In concordant, levels of CFTR, SLC4A4, ENaC (α, β and γ), Na+/K+-ATPase, GPα/β, AC and cAMP in the uterus increased following increased in the doses of quercetin. Co-administration of quercetin with E caused uterine fluid secretion rate, Na+, Cl- and HCO3- concentrations to decrease. In concordant, uterine CFTR, SLC26A6, SLC4A4, ENaC (α, β and γ), Na+/K+-ATPase, GPα/β, AC and cAMP decreased. Greatest effects were observed following co-administration of 10mg/kg/day quercetin with E. Co-administration of quercetin with E+P caused uterine fluid Na+ and HCO3- concentrations to increase but no changes in fluid secretion rate and Cl- concentration were observed. Co-administration of high dose quercetin (100 mg/kg/day) with E+P caused uterine CFTR, SLC26A6, AC, GPα/β and ENaC (α, β and γ) to increase. Quercetin-induced changes in the uterine fluid secretion rate and electrolytes concentrations could potentially affect the uterine reproductive functions under female sex-steroid influence. PMID:28253299

Energetic Neutral Atom (ENA) Movies and Other Cool Data from Cassini's Magnetosphere Imaging Instrument (MIMI)

NASA Astrophysics Data System (ADS)

Kusterer, M. B.; Mitchell, D. G.; Krimigis, S. M.; Vandegriff, J. D.

2014-12-01

Having been at Saturn for over a decade, the MIMI instrument on Cassini has created a rich dataset containing many details about Saturn's magnetosphere. In particular, the images of energetic neutral atoms (ENAs) taken by the Ion and Neutral Camera (INCA) offer a global perspective on Saturn's plasma environment. The MIMI team is now regularly making movies (in MP4 format) consisting of consecutive ENA images. The movies correct for spacecraft attitude changes by projecting the images (whose viewing angles can substantially vary from one image to the next) into a fixed inertial frame that makes it easy to view spatial features evolving in time. These movies are now being delivered to the PDS and are also available at the MIMI team web site. Several other higher order products are now also available, including 20-day energy-time spectrograms for the Charge-Energy-Mass Spectrometer (CHEMS) sensor, and daily energy-time spectrograms for the Low Energy Magnetospheric Measurements system (LEMMS) sensor. All spectrograms are available as plots or digital data in ASCII format. For all MIMI sensors, a Data User Guide is also available. This paper presents details and examples covering the specifics of MIMI higher order data products. URL: http://cassini-mimi.jhuapl.edu/

Zonal asymmetric evolution of aerosol optical depth in the subtropics of northern hemisphere in boreal spring and its association with the thermal forcing of Tibetan Plateau

NASA Astrophysics Data System (ADS)

Liu, B.; Jin, Q.; He, J.

2017-12-01

More than 70% population living in the subtropics of the northern hemisphere are exposed to the serious air pollution. In the present, the zonal asymmetric evolution of the 550-nm aerosol optical depth (AOD) over this region has been observed between the East Asian (EA) and the East North American (ENA) continent from boreal winter to summer. The peak of AOD emerges in April over the EA and decreases evidently till June, meanwhile the AOD is still increasing over the ENA, although the low-level southerly is prevailing over the two areas. The diagnosis suggests that such zonal asymmetry is ascribed to the distinct feedback between general circulation and atmospheric heat source (AHS) in situ. The condensation heating becomes dominant in the AHS over the East Asia in April, along with the low-level southerly and the upper-tropospheric northerly, implicating the formation of summertime circulation pattern. Afterwards, the deep convection and the ventilation with strong ascending is generated to reduce the AOD over the EA. Whereas the similar configuration between circulation and AHS takes place over the ENA in June. Furthermore, the possible reason for the different evolution of atmospheric heating source between East Asia and East North America has been discussed.

Coregulated Expression of the Na+/Phosphate Pho89 Transporter and Ena1 Na+-ATPase Allows Their Functional Coupling under High-pH Stress

PubMed Central

Serra-Cardona, Albert; Petrezsélyová, Silvia; Canadell, David; Ramos, José

2014-01-01

The yeast Saccharomyces cerevisiae has two main high-affinity inorganic phosphate (Pi) transporters, Pho84 and Pho89, that are functionally relevant at acidic/neutral pH and alkaline pH, respectively. Upon Pi starvation, PHO84 and PHO89 are induced by the activation of the PHO regulon by the binding of the Pho4 transcription factor to specific promoter sequences. We show that PHO89 and PHO84 are induced by alkalinization of the medium with different kinetics and that the network controlling Pho89 expression in response to alkaline pH differs from that of other members of the PHO regulon. In addition to Pho4, the PHO89 promoter is regulated by the transcriptional activator Crz1 through the calcium-activated phosphatase calcineurin, and it is under the control of several repressors (Mig2, Nrg1, and Nrg2) coordinately regulated by the Snf1 protein kinase and the Rim101 transcription factor. This network mimics the one regulating expression of the Na+-ATPase gene ENA1, encoding a major determinant for Na+ detoxification. Our data highlight a scenario in which the activities of Pho89 and Ena1 are functionally coordinated to sustain growth in an alkaline environment. PMID:25266663

Global differences between moderate and large storms

NASA Astrophysics Data System (ADS)

Valek, P. W.; Buzulukova, N.; Fok, M. C. H.; Goldstein, J.; Keesee, A. M.; McComas, D. J.; Perez, J. D.

2015-12-01

The current solar maximum has been relatively quiet compared to previous solar cycles. Whereas numerous moderate storms (Dst < -50 nT) have occurred, there have been only a small number of large (Dst < - 100 nT) and extreme (Dst < -200 nT) storms. Throughout this sequence of storms, the Two Wide-angle Imaging Neutral-atom Spectrometers (TWINS) mission has since 2008 observed the inner magnetosphere. TWINS consists of two ENA cameras flown aboard two separate spacecraft in Molniya orbits. TWINS images the ENA emissions from the inner magnetosphere across a broad range of energies (1 to 100 keV for H, 16 to 256 keV for O). This allows TWINS to observe the evolution in space and time of the trapped and precipitating particles most relevant for storm time dynamics on very high time scales (i.e., minutes). Here we will present the differences seen between moderate storms and the two large storms of 17 March 2015 (Dst < -223, St. Patrick's day storm) and 22 June 2015 (Dst < -195 nT). We will present composition-separated ENA observations of the inner magnetosphere covering the both the medium (1 to 30 keV) and high (30 to > 100 keV) energy ranges, and describe how the inner magnetosphere evolves during storm time.

Temperature Influences Chorda Tympani Nerve Responses to Sweet, Salty, Sour, Umami, and Bitter Stimuli in Mice.

PubMed

Lu, Bo; Breza, Joseph M; Contreras, Robert J

2016-08-06

Temperature profoundly affects the perceived intensity of taste, yet we know little of the extent of temperature's effect on taste in the peripheral nervous system. Accordingly, we investigated the influence of temperature from 23 °C to 43 °C in 4 °C intervals on the integrated responses of the chorda tympani (CT) nerve to a large series of chemical stimuli representing sweet, salty, sour, bitter, and umami tastes in C57BL/J6 mice. We also measured neural responses to NaCl, Na-gluconate, Na-acetate, Na-sulfate, and MSG with and without 5 µM benzamil, an epithelial sodium channel (ENaC) antagonist, to assess the influence of temperature on ENaC-dependent and ENaC-independent response components. Our results showed that for most stimuli (0.5M sucrose, glucose, fructose, and maltose; 0.02M saccharin and sucralose; 0.5M NaCl, Na-gluconate, Na-acetate, Na-sulfate, KCl, K-gluconate, K-acetate, and K-sulfate; 0.05M citric acid, acetic acid, and HCl; 0.1M MSG and 0.05M quinine hydrochloride: QHCl), CT response magnitudes were maximal between 35 °C and 39 °C and progressively smaller at cooler or warmer temperatures. In contrast, the weakest responses to NH 4 Cl, (NH 4 ) 2 SO4, and K-sulfate were at the lowest temperature, with response magnitude increasing monotonically with increasing temperature, while the largest responses to acetic acid were at the lowest temperature, with response magnitude decreasing with increasing temperature. The response to sweet and umami stimuli across temperatures were similar reflecting the involvement of TRPM5 activity, in contrast to bitter stimuli, which were weakly affected by temperature. Temperature-modulated responses to salts and acids most likely operate through mechanisms independent of ENaC and TRPM5. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Binding of antibodies to the extractable nuclear antigens SS-A/Ro and SS-B/La is induced on the surface of human keratinocytes by ultraviolet light (UVL): Implications for the pathogenesis of photosensitive cutaneous lupus

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

Furukawa, F.; Kashihara-Sawami, M.; Lyons, M.B.

1990-01-01

Autoantibodies to the non-histone nucleoprotein antigens SS-A/Ro, SS-B/La, and RNP are highly associated with photosensitive cutaneous lupus erythematosus (LE). In order to better understand the potential mechanisms of ultraviolet (UV) light on photosensitivity in patients with cutaneous LE, we designed immunopathologic in vitro and in vivo experiments to evaluate the effects of UV on the binding of such autoantibodies to the surface of human keratinocytes, one major target of immunologic damage in photosensitive LE. Short-term 2% paraformaldehyde fixation of suspensions of cultured human keratinocytes previously incubated with monospecific antiserum probes enabled the detection of ENA expression on the cell surfacemore » by flow-cytometry analysis. UVB light (280-320 nm) induced the binding of monospecific antibody probes for SS-A/Ro and SS-B/La on keratinocytes in a dose-dependent pattern with maximal induction observed at the dose of 200 mJ/cm2 UVB. Binding of SS-A/Ro, SS-B/La, and RNP antibody was augmented strongly, but binding of anti-Sm was very weak. In contrast, UVA (320-400 nm) light had no effect on the induction of binding of these antibody probes. Identical results were seen by standard immunofluorescence techniques. Hydroxyurea-treated keratinocytes showed similar induction of those antigens by UVB irradiation, which suggested that ENA expression on cultured keratinocytes by UVB were cell-cycle independent. Tunicamycin, an inhibitor of glycosylation of proteins, reduced UVB light effect on the SS-A/Ro and SS-B/La antigen's expression. These in vitro FACS analyses revealed that ENA augmentation on the keratinocyte cell surface was dose dependent, UVB dependent, glycosylation dependent, and cell-cycle independent. In vivo ENA augmentation on the keratinocyte surface was examined in suction blister epidermal roofs.« less

Temperature Influences Chorda Tympani Nerve Responses to Sweet, Salty, Sour, Umami, and Bitter Stimuli in Mice

PubMed Central

Lu, Bo; Breza, Joseph M.

2016-01-01

Temperature profoundly affects the perceived intensity of taste, yet we know little of the extent of temperature’s effect on taste in the peripheral nervous system. Accordingly, we investigated the influence of temperature from 23 °C to 43 °C in 4 °C intervals on the integrated responses of the chorda tympani (CT) nerve to a large series of chemical stimuli representing sweet, salty, sour, bitter, and umami tastes in C57BL/J6 mice. We also measured neural responses to NaCl, Na-gluconate, Na-acetate, Na-sulfate, and MSG with and without 5 µM benzamil, an epithelial sodium channel (ENaC) antagonist, to assess the influence of temperature on ENaC-dependent and ENaC-independent response components. Our results showed that for most stimuli (0.5M sucrose, glucose, fructose, and maltose; 0.02M saccharin and sucralose; 0.5M NaCl, Na-gluconate, Na-acetate, Na-sulfate, KCl, K-gluconate, K-acetate, and K-sulfate; 0.05M citric acid, acetic acid, and HCl; 0.1M MSG and 0.05M quinine hydrochloride: QHCl), CT response magnitudes were maximal between 35 °C and 39 °C and progressively smaller at cooler or warmer temperatures. In contrast, the weakest responses to NH4Cl, (NH4)2SO4, and K-sulfate were at the lowest temperature, with response magnitude increasing monotonically with increasing temperature, while the largest responses to acetic acid were at the lowest temperature, with response magnitude decreasing with increasing temperature. The response to sweet and umami stimuli across temperatures were similar reflecting the involvement of TRPM5 activity, in contrast to bitter stimuli, which were weakly affected by temperature. Temperature-modulated responses to salts and acids most likely operate through mechanisms independent of ENaC and TRPM5. PMID:27497433

The Role of Epithelial Sodium Channel ENaC and the Apical Cl-/HCO3- Exchanger Pendrin in Compensatory Salt Reabsorption in the Setting of Na-Cl Cotransporter (NCC) Inactivation

PubMed Central

Patel-Chamberlin, Mina; Varasteh Kia, Mujan; Xu, Jie; Barone, Sharon; Zahedi, Kamyar; Soleimani, Manoocher

2016-01-01

Background The absence of NCC does not cause significant salt wasting in NCC deficient mice under basal conditions. We hypothesized that ENaC and pendrin play important roles in compensatory salt absorption in the setting of NCC inactivation, and their inhibition and/or downregulation can cause significant salt wasting in NCC KO mice. Methods WT and NCC KO mice were treated with a daily injection of either amiloride, an inhibitor of ENaC, or acetazolamide (ACTZ), a blocker of salt and bicarbonate reabsorption in the proximal tubule and an inhibitor of carbonic anhydrases in proximal tubule and intercalated cells, or a combination of acetazolamide plus amiloride for defined durations. Animals were subjected to daily balance studies. At the end of treatment, kidneys were harvested and examined. Blood samples were collected for electrolytes and acid base analysis. Results Amiloride injection significantly increased the urine output (UO) in NCC KO mice (from 1.3 ml/day before to 2.5 ml/day after amiloride, p<0.03, n = 4) but caused only a slight change in UO in WT mice (p>0.05). The increase in UO in NCC KO mice was associated with a significant increase in sodium excretion (from 0.25 mmol/24 hrs at baseline to 0.35 mmol/24 hrs after amiloride injection, p<0.05, n = 4). Daily treatment with ACTZ for 6 days resulted in >80% reduction of kidney pendrin expression in both WT and NCC KO mice. However, ACTZ treatment noticeably increased urine output and salt excretion only in NCC KO mice (with urine output increasing from a baseline of 1.1 ml/day to 2.3 ml/day and sodium excretion increasing from 0.22 mmole/day before to 0.31 mmole/day after ACTZ) in NCC KO mice; both parameters were significantly higher than in WT mice. Western blot analysis demonstrated significant enhancement in ENaC expression in medulla and cortex of NCC KO and WT mice in response to ACTZ injection for 6 days, and treatment with amiloride in ACTZ-pretreated mice caused a robust increase in salt excretion in both NCC KO and WT mice. Pendrin KO mice did not display a significant increase in urine output or salt excretion after treatment with amiloride or ACTZ. Conclusion 1. ENaC plays an important role in salt reabsorption in NCC KO mice. 2. NCC contributes to compensatory salt reabsorption in the setting of carbonic anhydrase inhibition, which is associated with increased delivery of salt from the proximal tubule and the down regulation of pendrin. 3. ENaC is upregulated by ACTZ treatment and its inhibition by amiloride causes significant diuresis in NCC KO and WT mice. Despite being considered mild agents individually, we propose that the combination of acetazolamide and amiloride in the setting of NCC inhibition (i.e., hydrochlorothiazide) will be a powerful diuretic regimen. PMID:26963391

Statistical models for RNA-seq data derived from a two-condition 48-replicate experiment.

PubMed

Gierliński, Marek; Cole, Christian; Schofield, Pietà; Schurch, Nicholas J; Sherstnev, Alexander; Singh, Vijender; Wrobel, Nicola; Gharbi, Karim; Simpson, Gordon; Owen-Hughes, Tom; Blaxter, Mark; Barton, Geoffrey J

2015-11-15

High-throughput RNA sequencing (RNA-seq) is now the standard method to determine differential gene expression. Identifying differentially expressed genes crucially depends on estimates of read-count variability. These estimates are typically based on statistical models such as the negative binomial distribution, which is employed by the tools edgeR, DESeq and cuffdiff. Until now, the validity of these models has usually been tested on either low-replicate RNA-seq data or simulations. A 48-replicate RNA-seq experiment in yeast was performed and data tested against theoretical models. The observed gene read counts were consistent with both log-normal and negative binomial distributions, while the mean-variance relation followed the line of constant dispersion parameter of ∼0.01. The high-replicate data also allowed for strict quality control and screening of 'bad' replicates, which can drastically affect the gene read-count distribution. RNA-seq data have been submitted to ENA archive with project ID PRJEB5348. g.j.barton@dundee.ac.uk. © The Author 2015. Published by Oxford University Press.

Statistical models for RNA-seq data derived from a two-condition 48-replicate experiment

PubMed Central

Cole, Christian; Schofield, Pietà; Schurch, Nicholas J.; Sherstnev, Alexander; Singh, Vijender; Wrobel, Nicola; Gharbi, Karim; Simpson, Gordon; Owen-Hughes, Tom; Blaxter, Mark; Barton, Geoffrey J.

2015-01-01

Motivation: High-throughput RNA sequencing (RNA-seq) is now the standard method to determine differential gene expression. Identifying differentially expressed genes crucially depends on estimates of read-count variability. These estimates are typically based on statistical models such as the negative binomial distribution, which is employed by the tools edgeR, DESeq and cuffdiff. Until now, the validity of these models has usually been tested on either low-replicate RNA-seq data or simulations. Results: A 48-replicate RNA-seq experiment in yeast was performed and data tested against theoretical models. The observed gene read counts were consistent with both log-normal and negative binomial distributions, while the mean-variance relation followed the line of constant dispersion parameter of ∼0.01. The high-replicate data also allowed for strict quality control and screening of ‘bad’ replicates, which can drastically affect the gene read-count distribution. Availability and implementation: RNA-seq data have been submitted to ENA archive with project ID PRJEB5348. Contact: g.j.barton@dundee.ac.uk PMID:26206307

Living with a leaky skin: upregulation of ion transport proteins during sloughing.

PubMed

Wu, Nicholas C; Cramp, Rebecca L; Franklin, Craig E

2017-06-01

Amphibian skin is a multifunctional organ providing protection from the external environment and facilitating the physiological exchange of gases, water and salts with the environment. In order to maintain these functions, the outer layer of skin is regularly replaced in a process called sloughing. During sloughing, the outermost layer of the skin is removed in its entirety, which has the potential to interfere with skin permeability and ion transport, disrupting homeostasis. In this study, we measured, in vivo , the effects of sloughing on the cutaneous efflux of ions in toads Rhinella marina kept in freshwater conditions. We also measured transepithelial potential, cutaneous resistance, active ion transport and the distribution, abundance and gene expression of the key ion transport proteins sodium-potassium ATPase (NKA) and epithelial sodium channel (ENaC) during sloughing. We hypothesised that the increase in transepithelial efflux of ions during sloughing is a consequence of increased permeability and/or a reduction in the abundance or expression of cutaneous ion transport proteins, resulting in disruption of internal ion homeostasis. There was a significant increase in sodium and chloride efflux during sloughing in R. marina However, although in vitro skin resistance decreased after sloughing, active sodium transport increased commensurate with an increase in NKA and ENaC protein abundance in the skin. These changes in skin function associated with sloughing did not affect the maintenance of internal electrolyte homeostasis. These results suggest that during sloughing, amphibians actively maintain internal homeostasis by increasing cutaneous rates of ion uptake. © 2017. Published by The Company of Biologists Ltd.

Energetic neutral atom emissions from Titan interaction with Saturn's magnetosphere.

PubMed

Mitchell, D G; Brandt, P C; Roelof, E C; Dandouras, J; Krimigis, S M; Mauk, B H

2005-05-13

The Cassini Magnetospheric Imaging Instrument (MIMI) observed the interaction of Saturn's largest moon, Titan, with Saturn's magnetosphere during two close flybys of Titan on 26 October and 13 December 2004. The MIMI Ion and Neutral Camera (INCA) continuously imaged the energetic neutral atoms (ENAs) generated by charge exchange reactions between the energetic, singly ionized trapped magnetospheric ions and the outer atmosphere, or exosphere, of Titan. The images reveal a halo of variable ENA emission about Titan's nearly collisionless outer atmosphere that fades at larger distances as the exospheric density decays exponentially. The altitude of the emissions varies, and they are not symmetrical about the moon, reflecting the complexity of the interactions between Titan's upper atmosphere and Saturn's space environment.

Characterization of extreme air-sea turbulent fluxes

NASA Astrophysics Data System (ADS)

Gulev, Sergey; Belyaev, Konstantin

2017-04-01

Extreme ocean-atmosphere turbulent fluxes play a critical role in the convective processes in the mid and subpolar latitudes and may also affect a variety of atmospheric processes, such as generation and re-intensification of extreme cyclones in the areas of the mid latitude storm tracks. From the ocean dynamics perspective, specifically for quantifying extreme vertical mixing, characterization of the extreme fluxes requires, besides estimation of the extreme events, also consideration of the relative extremeness of surface fluxes and their timing, e.g. the duration of periods of high surface fluxes. In order to comprehensively characterize extreme turbulent fluxes at sea surface we propose a formalism based upon probability density distributions of surface turbulent fluxes and flux-related variables. Individual absolute flux extremes were derived using Modified Fisher-Tippett (MFT) distribution of turbulent fluxes. Then, we extend this distribution to the fractional distribution, characterizing the fraction of time-integrated turbulent heat flux provided by the fluxes exceeding a given percentile. Finally, we consider the time durations during which fluxes of a given intensity provide extreme accumulations of heat loss from the surface. For estimation of these characteristics of surface fluxes we use fluxes recomputed from the state variables available from modern era reanalyses (ERA-Interim, MERRA and CFSR) for the period from 1979 onwards. Applications of the formalism to the VOS (Voluntary Observing Ship) - based surface fluxes are also considered. We discuss application of the new metrics of mesoscale and synoptic variability of surface fluxes to the dynamics of mixed layer depth in the North Atlantic.

Renal intercalated cells and blood pressure regulation.

PubMed

Wall, Susan M

2017-12-01

Type B and non-A, non-B intercalated cells are found within the connecting tubule and the cortical collecting duct. Of these cell types, type B intercalated cells are known to mediate Cl - absorption and HCO 3 - secretion largely through pendrin-dependent Cl - /HCO 3 - exchange. This exchange is stimulated by angiotensin II administration and is also stimulated in models of metabolic alkalosis, for instance after aldosterone or NaHCO 3 administration. In some rodent models, pendrin-mediated HCO 3 - secretion modulates acid-base balance. However, the role of pendrin in blood pressure regulation is likely of more physiological or clinical significance. Pendrin regulates blood pressure not only by mediating aldosterone-sensitive Cl - absorption, but also by modulating the aldosterone response for epithelial Na + channel (ENaC)-mediated Na + absorption. Pendrin regulates ENaC through changes in open channel of probability, channel surface density, and channels subunit total protein abundance. Thus, aldosterone stimulates ENaC activity through both direct and indirect effects, the latter occurring through its stimulation of pendrin expression and function. Therefore, pendrin contributes to the aldosterone pressor response. Pendrin may also modulate blood pressure in part through its action in the adrenal medulla, where it modulates the release of catecholamines, or through an indirect effect on vascular contractile force. This review describes how aldosterone and angiotensin II-induced signaling regulate pendrin and the contributory role of pendrin in distal nephron function and blood pressure.

Characterization and Remediation of Contaminated Sites:Modeling, Measurement and Assessment

NASA Astrophysics Data System (ADS)

Basu, N. B.; Rao, P. C.; Poyer, I. C.; Christ, J. A.; Zhang, C. Y.; Jawitz, J. W.; Werth, C. J.; Annable, M. D.; Hatfield, K.

2008-05-01

The complexity of natural systems makes it impossible to estimate parameters at the required level of spatial and temporal detail. Thus, it becomes necessary to transition from spatially distributed parameters to spatially integrated parameters that are capable of adequately capturing the system dynamics, without always accounting for local process behavior. Contaminant flux across the source control plane is proposed as an integrated metric that captures source behavior and links it to plume dynamics. Contaminant fluxes were measured using an innovative technology, the passive flux meter at field sites contaminated with dense non-aqueous phase liquids or DNAPLs in the US and Australia. Flux distributions were observed to be positively or negatively correlated with the conductivity distribution, depending on the source characteristics of the site. The impact of partial source depletion on the mean contaminant flux and flux architecture was investigated in three-dimensional complex heterogeneous settings using the multiphase transport code UTCHEM and the reactive transport code ISCO3D. Source mass depletion reduced the mean contaminant flux approximately linearly, while the contaminant flux standard deviation reduced proportionally with the mean (i.e., coefficient of variation of flux distribution is constant with time). Similar analysis was performed using data from field sites, and the results confirmed the numerical simulations. The linearity of the mass depletion-flux reduction relationship indicates the ability to design remediation systems that deplete mass to achieve target reduction in source strength. Stability of the flux distribution indicates the ability to characterize the distributions in time once the initial distribution is known. Lagrangian techniques were used to predict contaminant flux behavior during source depletion in terms of the statistics of the hydrodynamic and DNAPL distribution. The advantage of the Lagrangian techniques lies in their small computation time and their inclusion of spatially integrated parameters that can be measured in the field using tracer tests. Analytical models that couple source depletion to plume transport were used for optimization of source and plume treatment. These models are being used for the development of decision and management tools (for DNAPL sites) that consider uncertainty assessments as an integral part of the decision-making process for contaminated site remediation.

Measurement and simulation of thermal neutron flux distribution in the RTP core

NASA Astrophysics Data System (ADS)

Rabir, Mohamad Hairie B.; Jalal Bayar, Abi Muttaqin B.; Hamzah, Na'im Syauqi B.; Mustafa, Muhammad Khairul Ariff B.; Karim, Julia Bt. Abdul; Zin, Muhammad Rawi B. Mohamed; Ismail, Yahya B.; Hussain, Mohd Huzair B.; Mat Husin, Mat Zin B.; Dan, Roslan B. Md; Ismail, Ahmad Razali B.; Husain, Nurfazila Bt.; Jalil Khan, Zareen Khan B. Abdul; Yakin, Shaiful Rizaide B. Mohd; Saad, Mohamad Fauzi B.; Masood, Zarina Bt.

2018-01-01

The in-core thermal neutron flux distribution was determined using measurement and simulation methods for the Malaysian’s PUSPATI TRIGA Reactor (RTP). In this work, online thermal neutron flux measurement using Self Powered Neutron Detector (SPND) has been performed to verify and validate the computational methods for neutron flux calculation in RTP calculations. The experimental results were used as a validation to the calculations performed with Monte Carlo code MCNP. The detail in-core neutron flux distributions were estimated using MCNP mesh tally method. The neutron flux mapping obtained revealed the heterogeneous configuration of the core. Based on the measurement and simulation, the thermal flux profile peaked at the centre of the core and gradually decreased towards the outer side of the core. The results show a good agreement (relatively) between calculation and measurement where both show the same radial thermal flux profile inside the core: MCNP model over estimation with maximum discrepancy around 20% higher compared to SPND measurement. As our model also predicts well the neutron flux distribution in the core it can be used for the characterization of the full core, that is neutron flux and spectra calculation, dose rate calculations, reaction rate calculations, etc.

ON THE GEOMETRY OF THE IBEX RIBBON

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

Sylla, Adama; Fichtner, Horst

2015-10-01

The Energetic Neutral Atom (ENA) full-sky maps obtained with the Interstellar Boundary Explorer (IBEX) show an unexpected bright narrow band of increased intensity. This so-called ENA ribbon results from charge exchange of interstellar neutral atoms with protons in the outer heliosphere or beyond. Among other hypotheses it has been argued that this ribbon may be related to a neutral density enhancement, or H-wave, in the local interstellar medium. Here we quantitatively demonstrate, on the basis of an analytical model of the principal large-scale heliospheric structure, that this scenario for the ribbon formation leads to results that are fully consistent withmore » the observed location of the ribbon in the full-sky maps at all energies detected with high-energy sensor IBEX-Hi.« less

Stepwise inference of likely dynamic flux distributions from metabolic time series data.

PubMed

Faraji, Mojdeh; Voit, Eberhard O

2017-07-15

Most metabolic pathways contain more reactions than metabolites and therefore have a wide stoichiometric matrix that corresponds to infinitely many possible flux distributions that are perfectly compatible with the dynamics of the metabolites in a given dataset. This under-determinedness poses a challenge for the quantitative characterization of flux distributions from time series data and thus for the design of adequate, predictive models. Here we propose a method that reduces the degrees of freedom in a stepwise manner and leads to a dynamic flux distribution that is, in a statistical sense, likely to be close to the true distribution. We applied the proposed method to the lignin biosynthesis pathway in switchgrass. The system consists of 16 metabolites and 23 enzymatic reactions. It has seven degrees of freedom and therefore admits a large space of dynamic flux distributions that all fit a set of metabolic time series data equally well. The proposed method reduces this space in a systematic and biologically reasonable manner and converges to a likely dynamic flux distribution in just a few iterations. The estimated solution and the true flux distribution, which is known in this case, show excellent agreement and thereby lend support to the method. The computational model was implemented in MATLAB (version R2014a, The MathWorks, Natick, MA). The source code is available at https://github.gatech.edu/VoitLab/Stepwise-Inference-of-Likely-Dynamic-Flux-Distributions and www.bst.bme.gatech.edu/research.php . mojdeh@gatech.edu or eberhard.voit@bme.gatech.edu. Supplementary data are available at Bioinformatics online. © The Author (2017). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

High time resolution characteristics of intermediate ion distributions upstream of the earth's bow shock

NASA Technical Reports Server (NTRS)

Potter, D. W.

1985-01-01

High time resolution particle data upstream of the bow shock during time intervals that have been identified as having intermediate ion distributions often show high amplitude oscillations in the ion fluxes of energy 2 and 6 keV. These ion oscillations, observed with the particle instruments of the University of California, Berkeley, on the ISEE 1 and 2 spacecraft, are at the same frequency (about 0.04 Hz) as the magnetic field oscillations. Typically, the 6-keV ion flux increases then the 2-keV flux increases followed by a decrease in the 2-keV flux and then the 6-keV flux decreases. This process repeats many times. Although there is no entirely satisfactory explanation, the presence of these ion flux oscillations suggests that distributions often are misidentified as intermediate ion distributions.

Magnetosphere dynamics during the 14 November 2012 storm inferred from TWINS, AMPERE, Van Allen Probes, and BATS-R-US-CRCM

NASA Astrophysics Data System (ADS)

Buzulukova, Natalia; Goldstein, Jerry; Fok, Mei-Ching; Glocer, Alex; Valek, Phil; McComas, David; Korth, Haje; Anderson, Brian

2018-01-01

During the 14 November 2012 geomagnetic storm, the Van Allen Probes spacecraft observed a number of sharp decreases (dropouts) in particle fluxes for ions and electrons of different energies. In this paper, we investigate the global magnetosphere dynamics and magnetosphere-ionosphere (M-I) coupling during the dropout events using multipoint measurements by Van Allen Probes, TWINS, and AMPERE together with the output of the two-way coupled global BATS-R-US-CRCM model. We find different behavior for two pairs of dropouts. For one pair, the same pattern was repeated: (1) weak nightside Region 1 and 2 Birkeland currents before and during the dropout; (2) intensification of Region 2 currents after the dropout; and (3) a particle injection detected by TWINS after the dropout. The model predicted similar behavior of Birkeland currents. TWINS low-altitude emissions demonstrated high variability during these intervals, indicating high geomagnetic activity in the near-Earth tail region. For the second pair of dropouts, the structure of both Birkeland currents and ENA emissions was relatively stable. The model also showed quasi-stationary behavior of Birkeland currents and simulated ENA emissions with gradual ring current buildup. We confirm that the first pair of dropouts was caused by large-scale motions of the OCB (open-closed boundary) during substorm activity. We show the new result that this OCB motion was associated with global changes in Birkeland (M-I coupling) currents and strong modulation of low-altitude ion precipitation. The second pair of dropouts is the result of smaller OCB disturbances not related to magnetospheric substorms. The local observations of the first pair of dropouts result from a global magnetospheric reconfiguration, which is manifested by ion injections and enhanced ion precipitation detected by TWINS and changes in the structure of Birkeland currents detected by AMPERE. This study demonstrates that multipoint measurements along with the global model results enable the reconstruction of a more complete system-level picture of the dropout events and provides insight into M-I coupling aspects that have not previously been investigated.

Magnetosphere dynamics during the 14 November 2012 storm inferred from TWINS, AMPERE, Van Allen Probes, and BATS-R-US–CRCM

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

Buzulukova, Natalia; Goldstein, Jerry; Fok, Mei-Ching

During the 14 November 2012 geomagnetic storm, the Van Allen Probes spacecraft observed a number of sharp decreases ("dropouts") in particle fluxes for ions and electrons of different energies. In this paper, we investigate the global magnetosphere dynamics and magnetosphere–ionosphere (M–I) coupling during the dropout events using multipoint measurements by Van Allen Probes, TWINS, and AMPERE together with the output of the two-way coupled global BATS-R-US–CRCM model. We find different behavior for two pairs of dropouts. For one pair, the same pattern was repeated: (1) weak nightside Region 1 and 2 Birkeland currents before and during the dropout; (2) intensificationmore » of Region 2 currents after the dropout; and (3) a particle injection detected by TWINS after the dropout. The model predicted similar behavior of Birkeland currents. TWINS low-altitude emissions demonstrated high variability during these intervals, indicating high geomagnetic activity in the near-Earth tail region. For the second pair of dropouts, the structure of both Birkeland currents and ENA emissions was relatively stable. The model also showed quasi-stationary behavior of Birkeland currents and simulated ENA emissions with gradual ring current buildup. We confirm that the first pair of dropouts was caused by large-scale motions of the OCB (open–closed boundary) during substorm activity. We show the new result that this OCB motion was associated with global changes in Birkeland (M–I coupling) currents and strong modulation of low-altitude ion precipitation. The second pair of dropouts is the result of smaller OCB disturbances not related to magnetospheric substorms. The local observations of the first pair of dropouts result from a global magnetospheric reconfiguration, which is manifested by ion injections and enhanced ion precipitation detected by TWINS and changes in the structure of Birkeland currents detected by AMPERE. This study demonstrates that multipoint measurements along with the global model results enable the reconstruction of a more complete system-level picture of the dropout events and provides insight into M–I coupling aspects that have not previously been investigated.« less

Magnetosphere Dynamics During the 14 November 2012 Storm Inferred from TWINS, AMPERE, Van Allen Probes, and BATS-R-US-CRCM

NASA Technical Reports Server (NTRS)

Buzulukova, Natalia; Goldstein, Jerry; Fok, Mei-Ching; Glocer, Alex; Valek, Phil; McComas, David; Korth, Haje; Anderson, Brian

2018-01-01

During the 14 November 2012 geomagnetic storm, the Van Allen Probes spacecraft observed a number of sharp decreases ('dropouts') in particle fluxes for ions and electrons of different energies. In this paper, we investigate the global magnetosphere dynamics and magnetosphere- ionosphere (M-I) coupling during the dropout events using multipoint measurements by Van Allen Probes, TWINS, and AMPERE together with the output of the two-way coupled global BATS-R-US-CRCM model. We find different behavior for two pairs of dropouts. For one pair, the same pattern was repeated: (1) weak nightside Region 1 and 2 Birkeland currents before and during the dropout; (2) intensification of Region 2 currents after the dropout; and (3) a particle injection detected by TWINS after the dropout. The model predicted similar behavior of Birkeland currents. TWINS low-altitude emissions demonstrated high variability during these intervals, indicating high geomagnetic activity in the near-Earth tail region. For the second pair of dropouts, the structure of both Birkeland currents and ENA emissions was relatively stable. The model also showed quasi-stationary behavior of Birkeland currents and simulated ENA emissions with gradual ring current buildup. We confirm that the first pair of dropouts was caused by large-scale motions of the OCB (open-closed boundary) during substorm activity. We show the new result that this OCB motion was associated with global changes in Birkeland (M-I coupling) currents and strong modulation of low-altitude ion precipitation. The second pair of dropouts is the result of smaller OCB disturbances not related to magnetospheric substorms. The local observations of the first pair of dropouts result from a global magnetospheric reconfiguration, which is manifested by ion injections and enhanced ion precipitation detected by TWINS and changes in the structure of Birkeland currents detected by AMPERE. This study demonstrates that multipoint measurements along with the global model results enable the reconstruction of a more complete system-level picture of the dropout events and provides insight into M-I coupling aspects that have not previously been investigated.

Magnetosphere dynamics during the 14 November 2012 storm inferred from TWINS, AMPERE, Van Allen Probes, and BATS-R-US–CRCM

DOE PAGES

Buzulukova, Natalia; Goldstein, Jerry; Fok, Mei-Ching; ...

2018-01-25

During the 14 November 2012 geomagnetic storm, the Van Allen Probes spacecraft observed a number of sharp decreases ("dropouts") in particle fluxes for ions and electrons of different energies. In this paper, we investigate the global magnetosphere dynamics and magnetosphere–ionosphere (M–I) coupling during the dropout events using multipoint measurements by Van Allen Probes, TWINS, and AMPERE together with the output of the two-way coupled global BATS-R-US–CRCM model. We find different behavior for two pairs of dropouts. For one pair, the same pattern was repeated: (1) weak nightside Region 1 and 2 Birkeland currents before and during the dropout; (2) intensificationmore » of Region 2 currents after the dropout; and (3) a particle injection detected by TWINS after the dropout. The model predicted similar behavior of Birkeland currents. TWINS low-altitude emissions demonstrated high variability during these intervals, indicating high geomagnetic activity in the near-Earth tail region. For the second pair of dropouts, the structure of both Birkeland currents and ENA emissions was relatively stable. The model also showed quasi-stationary behavior of Birkeland currents and simulated ENA emissions with gradual ring current buildup. We confirm that the first pair of dropouts was caused by large-scale motions of the OCB (open–closed boundary) during substorm activity. We show the new result that this OCB motion was associated with global changes in Birkeland (M–I coupling) currents and strong modulation of low-altitude ion precipitation. The second pair of dropouts is the result of smaller OCB disturbances not related to magnetospheric substorms. The local observations of the first pair of dropouts result from a global magnetospheric reconfiguration, which is manifested by ion injections and enhanced ion precipitation detected by TWINS and changes in the structure of Birkeland currents detected by AMPERE. This study demonstrates that multipoint measurements along with the global model results enable the reconstruction of a more complete system-level picture of the dropout events and provides insight into M–I coupling aspects that have not previously been investigated.« less

Enthalpy Distributions of Arc Jet Flow Based on Measured Laser Induced Fluorescence, Heat Flux and Stagnation Pressure Distributions

NASA Technical Reports Server (NTRS)

Suess, Leonard E.; Milhoan, James D.; Oelke, Lance; Godfrey, Dennis; Larin, Maksim Y.; Scott, Carl D.; Grinstead, Jay H.; DelPapa, Steven

2011-01-01

The centerline total enthalpy of arc jet flow is determined using laser induced fluorescence of oxygen and nitrogen atoms. Each component of the energy, kinetic, thermal, and chemical can be determined from LIF measurements. Additionally, enthalpy distributions are inferred from heat flux and pressure probe distribution measurements using an engineering formula. Average enthalpies are determined by integration over the radius of the jet flow, assuming constant mass flux and a mass flux distribution estimated from computational fluid dynamics calculations at similar arc jet conditions. The trends show favorable agreement, but there is an uncertainty that relates to the multiple individual measurements and assumptions inherent in LIF measurements.

Using a spatially-distributed hydrologic biogeochemistry model with nitrogen transport to study the spatial variation of carbon stocks and fluxes in a Critical Zone Observatory

NASA Astrophysics Data System (ADS)

Shi, Y.; Eissenstat, D. M.; He, Y.; Davis, K. J.

2017-12-01

Most current biogeochemical models are 1-D and represent one point in space. Therefore, they cannot resolve topographically driven land surface heterogeneity (e.g., lateral water flow, soil moisture, soil temperature, solar radiation) or the spatial pattern of nutrient availability. A spatially distributed forest biogeochemical model with nitrogen transport, Flux-PIHM-BGC, has been developed by coupling a 1-D mechanistic biogeochemical model Biome-BGC (BBGC) with a spatially distributed land surface hydrologic model, Flux-PIHM, and adding an advection dominated nitrogen transport module. Flux-PIHM is a coupled physically based model, which incorporates a land-surface scheme into the Penn State Integrated Hydrologic Model (PIHM). The land surface scheme is adapted from the Noah land surface model, and is augmented by adding a topographic solar radiation module. Flux-PIHM is able to represent the link between groundwater and the surface energy balance, as well as land surface heterogeneities caused by topography. In the coupled Flux-PIHM-BGC model, each Flux-PIHM model grid couples a 1-D BBGC model, while nitrogen is transported among model grids via surface and subsurface water flow. In each grid, Flux-PIHM provides BBGC with soil moisture, soil temperature, and solar radiation, while BBGC provides Flux-PIHM with spatially-distributed leaf area index. The coupled Flux-PIHM-BGC model has been implemented at the Susquehanna/Shale Hills Critical Zone Observatory. The model-predicted aboveground vegetation carbon and soil carbon distributions generally agree with the macro patterns observed within the watershed. The importance of abiotic variables (including soil moisture, soil temperature, solar radiation, and soil mineral nitrogen) in predicting aboveground carbon distribution is calculated using a random forest. The result suggests that the spatial pattern of aboveground carbon is controlled by the distribution of soil mineral nitrogen. A Flux-PIHM-BGC simulation without the nitrogen transport module is also executed. The model without nitrogen transport fails in predicting the spatial patterns of vegetation carbon, which indicates the importance of having a nitrogen transport module in spatially distributed ecohydrologic modeling.

Neural precursor cell-expressed developmentally down-regulated protein 4-2 (Nedd4-2) regulation by 14-3-3 protein binding at canonical serum and glucocorticoid kinase 1 (SGK1) phosphorylation sites.

PubMed

Chandran, Sindhu; Li, Hui; Dong, Wuxing; Krasinska, Karolina; Adams, Chris; Alexandrova, Ludmila; Chien, Allis; Hallows, Kenneth R; Bhalla, Vivek

2011-10-28

Regulation of epithelial Na(+) channel (ENaC)-mediated transport in the distal nephron is a critical determinant of blood pressure in humans. Aldosterone via serum and glucocorticoid kinase 1 (SGK1) stimulates ENaC by phosphorylation of the E3 ubiquitin ligase Nedd4-2, which induces interaction with 14-3-3 proteins. However, the mechanisms of SGK1- and 14-3-3-mediated regulation of Nedd4-2 are unclear. There are three canonical SGK1 target sites on Nedd4-2 that overlap phosphorylation-dependent 14-3-3 interaction motifs. Two of these are termed "minor," and one is termed "major," based on weak or strong binding to 14-3-3 proteins, respectively. By mass spectrometry, we found that aldosterone significantly stimulates phosphorylation of a minor, relative to the major, 14-3-3 binding site on Nedd4-2. Phosphorylation-deficient minor site Nedd4-2 mutants bound less 14-3-3 than did wild-type (WT) Nedd4-2, and minor site Nedd4-2 mutations were sufficient to inhibit SGK1 stimulation of ENaC cell surface expression. As measured by pulse-chase and cycloheximide chase assays, a major binding site Nedd4-2 mutant had a shorter cellular half-life than WT Nedd4-2, but this property was not dependent on binding to 14-3-3. Additionally, a dimerization-deficient 14-3-3ε mutant failed to bind Nedd4-2. We conclude that whereas phosphorylation at the Nedd4-2 major site is important for interaction with 14-3-3 dimers, minor site phosphorylation by SGK1 may be the relevant molecular switch that stabilizes Nedd4-2 interaction with 14-3-3 and thus promotes ENaC cell surface expression. We also propose that major site phosphorylation promotes cellular Nedd4-2 protein stability, which potentially represents a novel form of regulation for turnover of E3 ubiquitin ligases.

Redox Regulation of Epithelial Sodium Channels Examined in Alveolar Type 1 and 2 Cells Patch-clamped in Lung Slice Tissue*

PubMed Central

Helms, My N.; Jain, Lucky; Self, Julie L.; Eaton, Douglas C.

2008-01-01

The alveolar surface of the lung is lined by alveolar type 1 (AT1) and type 2 (AT2) cells. Using single channel patch clamp analysis in lung slice preparations, we are able to uniquely study AT1 and AT2 cells separately from intact lung. We report for the first time the Na+ transport properties of type 2 cells accessed in live lung tissue (as we have done in type 1 cells). Type 2 cells in lung tissue slices express both highly selective cation and nonselective cation channels with average conductances of 8.8 ± 3.2 and 22.5 ± 6.3 picosiemens, respectively. Anion channels with 10-picosiemen conductance are also present in the apical membrane of type 2 cells. Our lung slice studies importantly verify the use of cultured cell model systems commonly used in lung epithelial sodium channel (ENaC) studies. Furthermore, we identify novel functional differences between the cells that make up the alveolar epithelium. One important difference is that exposure to the nitric oxide (NO) donor, PAPA-NONOate (1.5 μm), significantly decreases average ENaC NPo in type 2 cells (from 1.38 ± 0.26 to 0.82 ± 0.16; p < 0.05 and n = 18) but failed to alter ENaC activity in alveolar type 1 cells. Elevating endogenous superoxide (\\documentclass[10pt]{article} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{pmc} \\usepackage[Euler]{upgreek} \\pagestyle{empty} \\oddsidemargin -1.0in \\begin{document} \\begin{equation*}{\\mathrm{O}}_{2}^{\\overline{.}}\\end{equation*}\\end{document}) levels with Ethiolat, a superoxide dismutase inhibitor, prevented NO inhibition of ENaC activity in type 2 cells, supporting the novel hypothesis that \\documentclass[10pt]{article} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{pmc} \\usepackage[Euler]{upgreek} \\pagestyle{empty} \\oddsidemargin -1.0in \\begin{document} \\begin{equation*}{\\mathrm{O}}_{2}^{\\overline{.}}\\end{equation*}\\end{document} and NO signaling plays an important role in maintaining lung fluid balance. PMID:18541535

Enhanced Resolution Maps of Energetic Neutral Atoms from IBEX

NASA Astrophysics Data System (ADS)

Teodoro, L. A.; Elphic, R. C.; Janzen, P.; Reisenfeld, D.; Wilson, J. T.

2017-12-01

The discovery by the Interstellar Boundary Explorer (IBEX) of a "Ribbon" in the measurements of Energetic Neutral Particles (ENA) was a major surprise that lead to the re-thinking of the Physics underpinning the heliosphere-intergalactic medium boundary dynamics. Several physical models have been proposed and tested in their ability to mimic the IBEX observations. Some of the ENA IBEX's include the following features: 1) The presence of fine structure within the ribbon suggests that the physical properties of it exhibit small-scale spacial structure and possibly rapid small-scale variations. 2) The ribbon is a fairly narrow feature at low energies and broadens with increasing energy;The IBEX detectors were designed to maximize count rate by incorporating wide angular and broad energy acceptance. Thus far, the existing mapping software used by the IBEX Science Operation Center has not been design with the "Ribbon" ( 20o wide) in mind: the current generation of maps are binned in 6o longitude pixels by 6o latitude pixels (so the pixels are all of the same size in angle and are quite "blocky"). Furthermore, the instrumental point spread function has not been deconvolved, making any potential narrow features broader than they are. An improvement in the spatial resolution of the IBEX maps would foster a better understanding of the Ribbon and its substructure, and thus reply to some of the basic and profound questions related to its origin, the nature of the outer boundaries of the our solar system and the surrounding interstellar Galactic medium.Here we report on the application of the Bayesian image reconstruction algorithm "Speedy Pixons" to the ENA data with the aim to sharpen the ENA IBEX maps. A preliminary application allow us to conclude that: The peaks in the count rate do appear to be more enhanced in the reconstruction; The reconstruction is clearly denoised; The "Ribbon" is better defined in the reconstruction. We are currently studying the implications of our preliminary results in the current generation of models. Potentially, our results can also be used in the design and planning of future missions whose aim is to produce higher resolution maps of the interstellar medium (e.g. IMAP).

Why the New Madrid earthquakes are M 7–8 and the Charleston earthquake is ∼M 7

USGS Publications Warehouse

Cramer, Chris H.; Boyd, Oliver

2014-01-01

Estimates of magnitudes of large historical earthquakes are an essential input to and can seriously affect seismic‐hazard estimates. The earthquake‐intensity observations, modified Mercalli intensities (MMI), and assigned magnitudes Mof the 1811–1812 New Madrid events have been reinterpreted several times in the last decade and have been a source of controversy in making seismic‐hazard estimates in the central United States. Observations support the concept that the larger the earthquake, the greater the maximum‐felt distance. For the same crustal attenuation and local soil conditions, magnitude should be the main influence on intensity values at large distances. We apply this concept by comparing the mean MMI at distances of 600–1200 km for each of the four largest New Madrid 1811–1812 earthquakes, the 1886 Charleston, South Carolina, earthquake, the 1929 M 7.2 Grand Banks earthquake, and the 2001M 7.6 Bhuj, India, earthquake. We fit the intensity observations using the form MMI=A+C×dist−0.8×log(dist) to better define intensity attenuation in eastern North America (ENA). The intensity attenuation in cratonic India differs from ENA and is corrected to ENA using both the above estimate and published intensity relations. We evaluate source, marine geophysical, Q, and stress‐drop information, as well as a 1929 Milne–Shaw record at Chicago to confirm that the 1929 Grand Banks earthquake occurred in ENA crust. Our direct comparison of mean intensities beyond 600 km suggests M 7.5, 7.3, 7.7, and 6.9 for the three New Madrid 1811–1812 mainshocks and the largest aftershock and M 7.0 for the 1886 Charleston, South Carolina, earthquake, with an estimated uncertainty of 0.3 units at the 95% confidence level (based on a Monte Carlo analysis). Our mean New Madrid and Charleston mainshock magnitudes are similar to those of Bakun and Hopper (2004) and are much higher than those of Hough and Page (2011) for New Madrid.

The 2011 Mineral, VA M5.8 Earthquake Ground Motions and Stress Drop: An Important Contribution to the NGA East Ground Motion Database

NASA Astrophysics Data System (ADS)

Cramer, C. H.; Kutliroff, J.; Dangkua, D.

2011-12-01

The M5.8 Mineral, Virginia earthquake of August 23, 2011 is the largest instrumentally recorded earthquake in eastern North America since the 1988 M5.9 Saguenay, Canada earthquake. Historically, a similar magnitude earthquake occurred on May 31, 1897 at 18:58 UCT in western Virginia west of Roanoke. Paleoseismic evidence for larger magnitude earthquakes has also been found in the central Virginia region. The Next Generation Attenuation (NGA) East project to develop new ground motion prediction equations for stable continental regions (SCRs), including eastern North America (ENA), is ongoing at the Pacific Earthquake Engineering Research Center funded by the U.S. Nuclear Regulatory Commission, the U.S. Geological Survey, the Electric Power Research Institute, and the U.S. Department of Energy. The available recordings from the M5.8 Virginia are being added to the NGA East ground motion database. Close in (less than 100 km) strong motion recordings are particularly interesting for both ground motion and stress drop estimates as most close-in broadband seismometers clipped on the mainshock. A preliminary estimate for earthquake corner frequency for the M5.8 Virginia earthquake of ~0.7 Hz has been obtained from a strong motion record 57 km from the mainshock epicenter. For a M5.8 earthquake this suggests a Brune stress drop of ~300 bars for the Virginia event. Very preliminary comparisons using accelerometer data suggest the ground motions from the M5.8 Virginia earthquake agree well with current ENA ground motion prediction equations (GMPEs) at short periods (PGA, 0.2 s) and are below the GMPEs at longer periods (1.0 s), which is the same relationship seen from other recent M5 ENA earthquakes. We will present observed versus GMPE ground motion comparisons for all the ground motion observations and stress drop estimates from strong motion recordings at distances less than 100 km. A review of the completed NGA East ENA ground motion database will also be provided.

A linked land-sea modeling framework to inform ridge-to-reef management in high oceanic islands.

PubMed

Delevaux, Jade M S; Whittier, Robert; Stamoulis, Kostantinos A; Bremer, Leah L; Jupiter, Stacy; Friedlander, Alan M; Poti, Matthew; Guannel, Greg; Kurashima, Natalie; Winter, Kawika B; Toonen, Robert; Conklin, Eric; Wiggins, Chad; Knudby, Anders; Goodell, Whitney; Burnett, Kimberly; Yee, Susan; Htun, Hla; Oleson, Kirsten L L; Wiegner, Tracy; Ticktin, Tamara

2018-01-01

Declining natural resources have led to a cultural renaissance across the Pacific that seeks to revive customary ridge-to-reef management approaches to protect freshwater and restore abundant coral reef fisheries. Effective ridge-to-reef management requires improved understanding of land-sea linkages and decision-support tools to simultaneously evaluate the effects of terrestrial and marine drivers on coral reefs, mediated by anthropogenic activities. Although a few applications have linked the effects of land cover to coral reefs, these are too coarse in resolution to inform watershed-scale management for Pacific Islands. To address this gap, we developed a novel linked land-sea modeling framework based on local data, which coupled groundwater and coral reef models at fine spatial resolution, to determine the effects of terrestrial drivers (groundwater and nutrients), mediated by human activities (land cover/use), and marine drivers (waves, geography, and habitat) on coral reefs. We applied this framework in two 'ridge-to-reef' systems (Hā'ena and Ka'ūpūlehu) subject to different natural disturbance regimes, located in the Hawaiian Archipelago. Our results indicated that coral reefs in Ka'ūpūlehu are coral-dominated with many grazers and scrapers due to low rainfall and wave power. While coral reefs in Hā'ena are dominated by crustose coralline algae with many grazers and less scrapers due to high rainfall and wave power. In general, Ka'ūpūlehu is more vulnerable to land-based nutrients and coral bleaching than Hā'ena due to high coral cover and limited dilution and mixing from low rainfall and wave power. However, the shallow and wave sheltered back-reef areas of Hā'ena, which support high coral cover and act as nursery habitat for fishes, are also vulnerable to land-based nutrients and coral bleaching. Anthropogenic sources of nutrients located upstream from these vulnerable areas are relevant locations for nutrient mitigation, such as cesspool upgrades. In this study, we located coral reefs vulnerable to land-based nutrients and linked them to priority areas to manage sources of human-derived nutrients, thereby demonstrating how this framework can inform place-based ridge-to-reef management.

Effects of orally administered enalapril on blood pressure and hemodynamic response to vasopressors during isoflurane anesthesia in healthy dogs.

PubMed

Coleman, Amanda E; Shepard, Molly K; Schmiedt, Chad W; Hofmeister, Erik H; Brown, Scott A

2016-09-01

To examine whether preanesthetic administration of enalapril, compared with placebo, results in a greater decline in blood pressure (BP) or decreased responsiveness of BP to isotonic fluids or vasopressors in healthy dogs during isoflurane anesthesia. Randomized, experimental, placebo-controlled, blinded, crossover study. Twelve healthy, female, purpose-bred beagles. Dogs underwent the following week-long treatment protocols, each preceded by a 1 week washout period: oral placebo twice daily (PLA); oral enalapril, 0.5 mg kg(-1) twice daily, with the 15th dose withheld on the day of anesthesia (ENA-W), and oral enalapril, 0.5 mg kg(-1) twice daily, with the 15th dose administered 90 minutes prior to anesthetic induction (ENA). On day 8 of each treatment period, dogs were anesthetized in random order utilizing a standard protocol. Following stabilization at an end-tidal isoflurane concentration (Fe'Iso) of 1.3%, invasively measured systolic (SAP), diastolic (DAP) and mean (MAP) arterial blood pressure were continuously recorded via telemetry. Hypotension (SAP < 85 mmHg) was treated with the following sequential interventions: lactated Ringer's solution (LRS) bolus (10 mL kg(-1) ); repeated LRS bolus; dopamine (7 μg kg(-1)  min(-1) ); and dopamine (10 μg kg(-1)  min(-1) ) first without and then with vasopressin (1 mU kg(-1)  hour(-1) ). Compared with the PLA but not the ENA-W group, the ENA group had significantly lower average SAP, DAP and MAP at an Fe'Iso of 1.3%, spent more minutes in hypotension, and required a greater number of interventions to correct moderate-to-severe mean arterial hypotension. In healthy dogs, enalapril administered 90 minutes prior to isoflurane anesthesia increases the degree of intra-anesthetic hypotension and the number of interventions required to correct moderate-to-severe hypotension. Dogs receiving angiotensin-converting enzyme inhibitors on the day of anesthesia may exhibit clinically significant intra-anesthetic hypotension. © 2016 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

Spectral unfolding of fast neutron energy distributions

NASA Astrophysics Data System (ADS)

Mosby, Michelle; Jackman, Kevin; Engle, Jonathan

2015-10-01

The characterization of the energy distribution of a neutron flux is difficult in experiments with constrained geometry where techniques such as time of flight cannot be used to resolve the distribution. The measurement of neutron fluxes in reactors, which often present similar challenges, has been accomplished using radioactivation foils as an indirect probe. Spectral unfolding codes use statistical methods to adjust MCNP predictions of neutron energy distributions using quantified radioactive residuals produced in these foils. We have applied a modification of this established neutron flux characterization technique to experimentally characterize the neutron flux in the critical assemblies at the Nevada National Security Site (NNSS) and the spallation neutron flux at the Isotope Production Facility (IPF) at Los Alamos National Laboratory (LANL). Results of the unfolding procedure are presented and compared with a priori MCNP predictions, and the implications for measurements using the neutron fluxes at these facilities are discussed.

Multi-year Estimates of Methane Fluxes in Alaska from an Atmospheric Inverse Model

NASA Astrophysics Data System (ADS)

Miller, S. M.; Commane, R.; Chang, R. Y. W.; Miller, C. E.; Michalak, A. M.; Dinardo, S. J.; Dlugokencky, E. J.; Hartery, S.; Karion, A.; Lindaas, J.; Sweeney, C.; Wofsy, S. C.

2015-12-01

We estimate methane fluxes across Alaska over a multi-year period using observations from a three-year aircraft campaign, the Carbon Arctic Reservoirs Vulnerability Experiment (CARVE). Existing estimates of methane from Alaska and other Arctic regions disagree in both magnitude and distribution, and before the CARVE campaign, atmospheric observations in the region were sparse. We combine these observations with an atmospheric particle trajectory model and a geostatistical inversion to estimate surface fluxes at the model grid scale. We first use this framework to estimate the spatial distribution of methane fluxes across the state. We find the largest fluxes in the south-east and North Slope regions of Alaska. This distribution is consistent with several estimates of wetland extent but contrasts with the distribution in most existing flux models. These flux models concentrate methane in warmer or more southerly regions of Alaska compared to the estimate presented here. This result suggests a discrepancy in how existing bottom-up models translate wetland area into methane fluxes across the state. We next use the inversion framework to explore inter-annual variability in regional-scale methane fluxes for 2012-2014. We examine the extent to which this variability correlates with weather or other environmental conditions. These results indicate the possible sensitivity of wetland fluxes to near-term variability in climate.

Estimating Collisionally-Induced Escape Rates of Light Neutrals from Early Mars

NASA Astrophysics Data System (ADS)

Gacesa, M.; Zahnle, K. J.

2016-12-01

Collisions of atmospheric gases with hot oxygen atoms constitute an important non-thermal mechanism of escape of light atomic and molecular species at Mars. In this study, we present revised theoretical estimates of non-thermal escape rates of neutral O, H, He, and H2 based on recent atmospheric density profiles obtained from the NASA Mars Atmosphere and Volatile Evolution (MAVEN) mission and related theoretical models. As primary sources of hot oxygen, we consider dissociative recombination of O2+ and CO2+ molecular ions. We also consider hot oxygen atoms energized in primary and secondary collisions with energetic neutral atoms (ENAs) produced in charge-exchange of solar wind H+ and He+ ions with atmospheric gases1,2. Scattering of hot oxygen and atmospheric species of interest is modeled using fully-quantum reactive scattering formalism3. This approach allows us to construct distributions of vibrationally and rotationally excited states and predict the products' emission spectra. In addition, we estimate formation rates of excited, translationally hot hydroxyl molecules in the upper atmosphere of Mars. The escape rates are calculated from the kinetic energy distributions of the reaction products using an enhanced 1D model of the atmosphere for a range of orbital and solar parameters. Finally, by considering different scenarios, we estimate the influence of these escape mechanisms on the evolution of Mars's atmosphere throughout previous epochs and their impact on the atmospheric D/H ratio. M.G.'s research was supported by an appointment to the NASA Postdoctoral Program at the NASA Ames Research Center, administered by Universities Space Research Association under contract with NASA. 1N. Lewkow and V. Kharchenko, "Precipitation of Energetic Neutral Atoms and Escape Fluxes induced from the Mars Atmosphere", Astroph. J., 790, 98 (2014) 2M. Gacesa, N. Lewkow, and V. Kharchenko, "Non-thermal production and escape of OH from the upper atmosphere of Mars", arXiv:1607.03602 (2016) 3M. Gacesa and V. Kharchenko, "Non-thermal escape of molecular hydrogen from Mars", Geophys. Res. Lett., 39, L10203 (2012).

Using isotopes to quantify evaporation and non-stationary transit times distributions in lake water budgets

NASA Astrophysics Data System (ADS)

Smith, A. A.; Tetzlaff, D.; Soulsby, C.

2017-12-01

Evaporative fluxes from northern lakes are essential components of catchment water balances, providing large supplies of water to the atmosphere, and affecting downstream water availability. However, measurement of lake evaporation is difficult in many catchments due to remoteness and inaccessibility. Evaporative flux may also influence mean transit times of lakes and catchments, identified through water- and tracer mass-balance. We combined stable water isotopes (δ2H and δ18O), transit, and residence time distributions in a non-stationary transit time model to estimate the evaporative flux from two lakes in the Scottish Highlands. The lakes were in close proximity to each other ( 2km), shallow (mean depth, 1.5 m) with one large (0.88km2) and one small (0.4km2). Model calibration used measurements of precipitation, air temperature, water level, and isotopic stream compositions of lake inflow and outflows. Evaporation flux was identified using lake fractionation of δ2H and δ18O. Mixing patterns of the lakes and their respective outlet isotopic compositions were accounted for by comparing three probability distributions for discharge and evaporation. We found that the evaporation flux was strongly influenced by these discharge and evaporation distributions. Decreased mixing within the lake resulted in greater evaporation fluxes. One of the three distributions yielded similar mean daily evaporation and uncertainty for both lakes (max 5mm/day), while evaporation using the other two distributions was inconsistent between the lakes. Importantly, our approach also estimated distributions of evaporation age, which were significantly different between the lakes, reflecting a combination of inflow stream magnitude and the mixing regimes. The mean evaporation flux age of the large lake was 160 days, and 14 days for the small lake. Our integrated approach of stable isotopes, time variant transit time distributions has shown to be a useful tool for quantifying evaporative fluxes and closing the water balance, while simultaneously providing useful transit times of fluxes for lake dominated catchments.

Systematic review and meta-analysis of nasal potential difference in hypoxia-induced lung injury.

PubMed

Su, Zhenlei; Zhu, Lili; Wu, Jing; Zhao, Runzhen; Ji, Hong-Long

2016-08-04

Nasal potential difference (NPD), a well-established in vivo clinical test for cystic fibrosis, reflects transepithelial cation and anion transport in the respiratory epithelium. To analyze whether NPD can be applied to diagnose hypoxic lung injury, we searched PubMed, EMBASE, Scopus, Web of Science, Ovid MEDLINE, and Google Scholar, and analyzed data retrieved from eleven unbiased studies for high altitude pulmonary edema (HAPE) and respiratory distress syndrome (RDS) using the software RevMan and R. There was a significant reduction in overall basal (WMD -5.27 mV, 95% CI: -6.03 to -4.52, P < 0.00001, I(2) = 42%), amiloride-sensitive (ENaC) (-2.87 mV, 95% CI: -4.02 to -1.72, P < 0.00001, I(2) = 51%), and -resistant fractions (-3.91 mV, 95% CI: -7.64 to -0.18, P = 0.04, I(2) = 95%) in lung injury patients. Further analysis of HAPE and RDS separately corroborated these observations. Moreover, SpO2 correlated with ENaC-associated NPD positively in patients only, but apparently related to CFTR-contributed NPD level inversely. These correlations were confirmed by the opposite associations between NPD values and altitude, which had a negative regression with SpO2 level. Basal NPD was significantly associated with amiloride-resistant but not ENaC fraction. Our analyses demonstrate that acute lung injury associated with systemic hypoxia is characterized by dysfunctional NPD.

Antiinflammatory and Antimicrobial Effects of Thiocyanate in a Cystic Fibrosis Mouse Model

PubMed Central

Chandler, Joshua D.; Min, Elysia; Huang, Jie; McElroy, Cameron S.; Dickerhof, Nina; Mocatta, Tessa; Fletcher, Ashley A.; Evans, Christopher M.; Liang, Liping; Patel, Manisha; Kettle, Anthony J.; Nichols, David P.

2015-01-01

Thiocyanate (SCN) is used by the innate immune system, but less is known about its impact on inflammation and oxidative stress. Granulocytes oxidize SCN to evolve the bactericidal hypothiocyanous acid, which we previously demonstrated is metabolized by mammalian, but not bacterial, thioredoxin reductase (TrxR). There is also evidence that SCN is dysregulated in cystic fibrosis (CF), a disease marked by chronic infection and airway inflammation. To investigate antiinflammatory effects of SCN, we administered nebulized SCN or saline to β epithelial sodium channel (βENaC) mice, a phenotypic CF model. SCN significantly decreased airway neutrophil infiltrate and restored the redox ratio of glutathione in lung tissue and airway epithelial lining fluid to levels comparable to wild type. Furthermore, in Pseudomonas aeruginosa–infected βENaC and wild-type mice, SCN decreased inflammation, proinflammatory cytokines, and bacterial load. SCN also decreased airway neutrophil chemokine keratinocyte chemoattractant (also known as C-X-C motif chemokine ligand 1) and glutathione sulfonamide, a biomarker of granulocyte oxidative activity, in uninfected βENaC mice. Lung tissue TrxR activity and expression increased in inflamed lung tissue, providing in vivo evidence for the link between hypothiocyanous acid metabolism by TrxR and the promotion of selective biocide of pathogens. SCN treatment both suppressed inflammation and improved host defense, suggesting that nebulized SCN may have important therapeutic utility in diseases of both chronic airway inflammation and persistent bacterial infection, such as CF. PMID:25490247

Whole-exome sequencing reveals an inherited R566X mutation of the epithelial sodium channel β-subunit in a case of early-onset phenotype of Liddle syndrome.

PubMed

Polfus, Linda M; Boerwinkle, Eric; Gibbs, Richard A; Metcalf, Ginger; Muzny, Donna; Veeraraghavan, Narayanan; Grove, Megan; Shete, Sanjay; Wallace, Stephanie; Milewicz, Dianna; Hanchard, Neil; Lupski, James R; Hashmi, Syed Shahrukh; Gupta-Malhotra, Monesha

2016-11-01

To comprehensively evaluate a European-American child with severe hypertension, whole-exome sequencing (WES) was performed on the child and parents, which identified causal variation of the proband's early-onset disease. The proband's hypertension was resistant to treatment, requiring a multiple drug regimen including amiloride, spironolactone, and hydrochlorothiazide. We suspected a monogenic form of hypertension because of the persistent hypokalemia with low plasma levels of renin and aldosterone. To address this, we focused on rare functional variants and indels, and performed gene-based tests incorporating linkage scores and allele frequency and filtered on deleterious functional mutations. Drawing upon clinical presentation, 27 genes were selected evidenced to cause monogenic hypertension and matched to the gene-based results. This resulted in the identification of a stop-gain mutation in an epithelial sodium channel (ENaC), SCNN1B , an established Liddle syndrome gene, shared by the child and her father. Interestingly, the father also harbored a missense mutation (p.Trp552Arg) in the α-subunit of the ENaC trimer, SCNN1A , possibly pointing to pseudohypoaldosteronism type I. This case is unique in that we present the early-onset disease and treatment response caused by a canonical stop-gain mutation (p.Arg566*) as well as ENaC digenic hits in the father, emphasizing the utility of WES informing precision medicine.

Renal intercalated cells and blood pressure regulation

PubMed Central

Wall, Susan M.

2017-01-01

Type B and non-A, non-B intercalated cells are found within the connecting tubule and the cortical collecting duct. Of these cell types, type B intercalated cells are known to mediate Cl− absorption and HCO3− secretion largely through pendrin-dependent Cl−/HCO3− exchange. This exchange is stimulated by angiotensin II administration and is also stimulated in models of metabolic alkalosis, for instance after aldosterone or NaHCO3 administration. In some rodent models, pendrin-mediated HCO3− secretion modulates acid-base balance. However, the role of pendrin in blood pressure regulation is likely of more physiological or clinical significance. Pendrin regulates blood pressure not only by mediating aldosterone-sensitive Cl− absorption, but also by modulating the aldosterone response for epithelial Na+ channel (ENaC)-mediated Na+ absorption. Pendrin regulates ENaC through changes in open channel of probability, channel surface density, and channels subunit total protein abundance. Thus, aldosterone stimulates ENaC activity through both direct and indirect effects, the latter occurring through its stimulation of pendrin expression and function. Therefore, pendrin contributes to the aldosterone pressor response. Pendrin may also modulate blood pressure in part through its action in the adrenal medulla, where it modulates the release of catecholamines, or through an indirect effect on vascular contractile force. This review describes how aldosterone and angiotensin II-induced signaling regulate pendrin and the contributory role of pendrin in distal nephron function and blood pressure. PMID:29285423

A scaling theory for number-flux distributions generated during steady-state coagulation and settling and application to particles in Lake Zurich, Switzerland.

PubMed

Boehm, Alexandria B

2002-10-15

In this study, we extend the established scaling theory for cluster size distributions generated during unsteady coagulation to number-flux distributions that arise during steady-state coagulation and settling in an unmixed water mass. The scaling theory predicts self-similar number-flux distributions and power-law decay of total number flux with depth. The shape of the number-flux distributions and the power-law exponent describing the decay of the total number flux are shown to depend on the homogeneity and small i/j limit of the coagulation kernel and the exponent kappa, which describes the variation in settling velocity with cluster volume. Particle field measurements from Lake Zurich, collected by U. Weilenmann and co-workers (Limnol. Oceanogr.34, 1 (1989)), are used to illustrate how the scaling predictions can be applied to a natural system. This effort indicates that within the mid-depth region of Lake Zurich, clusters of the same size preferentially interact and large clusters react with one another more quickly than small ones, indicative of clusters coagulating in a reaction-limited regime.

Are There Different Populations of Flux Ropes in the Solar Wind?

NASA Astrophysics Data System (ADS)

Janvier, M.; Démoulin, P.; Dasso, S.

2014-07-01

Flux ropes are twisted magnetic structures that can be detected by in-situ measurements in the solar wind. However, different properties of detected flux ropes suggest different types of flux-rope populations. As such, are there different populations of flux ropes? The answer is positive and is the result of the analysis of four lists of flux ropes, including magnetic clouds (MCs), observed at 1 AU. The in-situ data for the four lists were fitted with the same cylindrical force-free field model, which provides an estimate of the local flux-rope parameters such as its radius and orientation. Since the flux-rope distributions have a broad dynamic range, we went beyond a simple histogram analysis by developing a partition technique that uniformly distributes the statistical fluctuations across the radius range. By doing so, we found that small flux ropes with radius R<0.1 AU have a steep power-law distribution in contrast to the larger flux ropes (identified as MCs), which have a Gaussian-like distribution. Next, from four CME catalogs, we estimated the expected flux-rope frequency per year at 1 AU. We found that the predicted numbers are similar to the frequencies of MCs observed in-situ. However, we also found that small flux ropes are at least ten times too abundant to correspond to CMEs, even to narrow ones. Investigating the different possible scenarios for the origin of these small flux ropes, we conclude that these twisted structures can be formed by blowout jets in the low corona or in coronal streamers.

Surface flux density distribution characteristics of bulk high- Tc superconductor in external magnetic field

NASA Astrophysics Data System (ADS)

Torii, S.; Yuasa, K.

2004-10-01

Various magnetic levitation systems using oxide superconductors are developed as strong pinning forces are obtained in melt-processed bulk. However, the trapped flux of superconductor is moved by flux creep and fluctuating magnetic field. Therefore, to examine the internal condition of superconductor, the authors measure the dynamic surface flux density distribution of YBCO bulk. Flux density measurement system has a structure with the air-core coil and the Hall sensors. Ten Hall sensors are arranged in series. The YBCO bulk, which has 25 mm diameter and 13 mm thickness, is field cooled by liquid nitrogen. After that, magnetic field is changed by the air-core coil. This paper describes about the measured results of flux density distribution of YBCO bulk in the various frequencies of air-core coils currents.

The heliolongitudinal distribution of solar flares associated with solar proton events.

PubMed

Smart, D F; Shea, M A

1996-01-01

We find that the heliolongitudinal distribution of solar flares associated with earth-observed solar proton events is a function of the particle measurement energy. For solar proton events containing fluxes with energies exceeding 1 GeV, we find a Gaussian distribution about the probable root of the Archimedean spiral favorable propagation path leading from the earth to the sun. This distribution is modified as the detection threshold is lowered. For > 100 MeV solar proton events with fluxes > or = 10 protons (cm2-sec-ster)-1 we find the distribution becomes wider with a secondary peak near the solar central meridian. When the threshold is lowered to 10 MeV the distribution further evolves. For > 10 MeV solar proton events having a flux threshold at 10 protons (cm2-sec-ster)-1 the distribution can be considered to be a composite of two Gaussians. One distribution is centered about the probable root of the Archimedean spiral favorable propagation path leading from the earth to the sun, and the other is centered about the solar central meridian. For large flux solar proton events, those with flux threshold of 1000 (cm2-sec-ster)-1 at energies > 10 MeV, we find the distribution is rather flat for about 40 degrees either side of central meridian.

Biocatalyst Enhancement

EPA Science Inventory

The increasing availability of enzyme collections has assisted attempts by pharmaceutical producers to adopt green chemistry approaches to manufacturing. A joint effort between an enzyme producer and a pharmaceutical manufacturer has been enhanced over the past three years by ena...

Gas Flux and Density Surrounding a Cylindrical Aperture in the Free Molecular Flow Regime

NASA Technical Reports Server (NTRS)

Soulas, George C.

2011-01-01

The equations for rigorously calculating the particle flux and density surrounding a cylindrical aperture in the free molecular flow regime are developed and presented. The fundamental equations for particle flux and density from a reservoir and a diffusely reflecting surface will initially be developed. Assumptions will include a Maxwell-Boltzmann speed distribution, equal particle and wall temperatures, and a linear flux distribution along the cylindrical aperture walls. With this information, the equations for axial flux and density surrounding a cylindrical aperture will be developed. The cylindrical aperture will be divided into multiple volumes and regions to rigorously determine the surrounding axial flux and density, and appropriate limits of integration will be determined. The results of these equations will then be evaluated. The linear wall flux distribution assumption will be assessed. The axial flux and density surrounding a cylindrical aperture with a thickness-to-radius ratio of 1.25 will be presented. Finally, the equations determined in this study will be verified using multiple methods.

A random wave model for the Aharonov-Bohm effect

NASA Astrophysics Data System (ADS)

Houston, Alexander J. H.; Gradhand, Martin; Dennis, Mark R.

2017-05-01

We study an ensemble of random waves subject to the Aharonov-Bohm effect. The introduction of a point with a magnetic flux of arbitrary strength into a random wave ensemble gives a family of wavefunctions whose distribution of vortices (complex zeros) is responsible for the topological phase associated with the Aharonov-Bohm effect. Analytical expressions are found for the vortex number and topological charge densities as functions of distance from the flux point. Comparison is made with the distribution of vortices in the isotropic random wave model. The results indicate that as the flux approaches half-integer values, a vortex with the same sign as the fractional part of the flux is attracted to the flux point, merging with it in the limit of half-integer flux. We construct a statistical model of the neighbourhood of the flux point to study how this vortex-flux merger occurs in more detail. Other features of the Aharonov-Bohm vortex distribution are also explored.

The effect of heating on mineral composition and grain size distribution of flux calcined porcelanites from the Gafsa-Metlaoui basin, southwestern Tunisia

NASA Astrophysics Data System (ADS)

Saidi, Raja; Tlili, Ali; Jamoussi, Fakher

2016-12-01

The porcelanite rock of Ypresian phosphatic series of the Gafsa-Metlaoui basin (south-western Tunisia), is composed mainly of opal CT, and presents a variable percentage of carbonates and fibrous clays. This rock is treated with flux calcination at different temperatures in order to prepare a specific filter aid for cleaning melting sulfur which can be used for the production of sulfuric acid. This work presents the effect of heating on the mineralogy and grain size distribution of carbonate-rich porcelanite (Tm1) and clay-rich porcelanite (Gh) compared to flux calcined silica-rich porcelanite (CHM3) and diatomaceous filtration aids. The porcelanite samples used in this work come from three localities of the Gafsa-Metlaoui basin: Kef El Ghis (Gh), Tamarza (Tm1) and Mides (CHM3). Flux calcination at 1000 °C provokes a mineralogical transformation on carbonate-rich porcelanite samples. The opal CT transforms to opal C and becomes neater and more stable. The Thermal treatment of porcelanite (Tm1) incites also the apparition of new peaks of wollastonite. However, the structural change of opal CT to opal C by heat treatment is blocked for flux calcination of clay-rich porcelanite. The opal CT of fluxing clay-rich porcelanite becomes more ordered without significant change to opal C. The difference between fluxing carbonate-rich porcelanite (Tm1) and fluxing clay-rich porcelanite (Gh) appears also with granulometric distribution histogram of the tow heated samples. All raw samples have unimodal granulometric distribution (1-100 μm). After calcination with alkaline flux at 1000 °C fluxing carbonate-rich porcelanite displays bimodal granulometric distribution and a new mode appears systematically, between 0.1 μm and 1 μm. This occurs for fluxing silica-riche porcelanite and diatomaceous filtration aids as well and corresponds to the opal C formed after heat treatment. Whereas fluxing clay-rich porcelanite present trimodal granulometric distribution and a third mode appears (100-300 μm), which due to silica glass phase. Since, the granulometric rearrangement of porcelanite during thermal treatment may due to mineralogical transformation of opal CT to opal C and crystal grow.

Influence of Oxygen on Cu Distribution Behavior Between Molten Iron and FeS-Based Flux

NASA Astrophysics Data System (ADS)

Kang, Youngjo; Shin, Kil-Sun; Morita, Kazuki

2018-06-01

Cu distribution behavior between molten iron and a sulfide flux was investigated under different oxygen contents in the sulfide flux to clarify the effect of oxygen content in FeS-based flux on Cu removal. The activity coefficient of CuS0.5 could be experimentally estimated according to the oxygen content. Based on the present result, the possibility of Cu removal by sulfide flux containing a certain amount of oxide was discussed.

Understanding the role of pore size homogeneity in the water transport through graphene layers.

PubMed

Su, Jiaye; Zhao, Yunzhen; Fang, Chang

2018-06-01

Graphene is a versatile 2D material and attracts an increasing amount of attention from a broad scientific community, including novel nanofluidic devices. In this work, we use molecular dynamics simulations to study the pressure driven water transport through graphene layers, focusing on the pore size homogeneity, realized by the arrangement of two pore sizes. For a given layer number, we find that water flux exhibits an excellent linear behavior with pressure, in agreement with the prediction of the Hagen-Poiseuille equation. Interestingly, the flux for concentrated pore size distribution is around two times larger than that of a uniform distribution. More surprisingly, under a given pressure, the water flux changes in an opposite way for these two distributions, where the flux ratio almost increases linearly with the layer number. For the largest layer number, more distributions suggest the same conclusion that higher water flux can be attained for more concentrated pore size distributions. Similar differences for the water translocation time and occupancy are also identified. The major reason for these results should clearly be due to the hydrogen bond and density profile distributions. Our results are helpful to delineate the exquisite role of pore size homogeneity, and should have great implications for the design of high flux nanofluidic devices and inversely the detection of pore structures.

Understanding the role of pore size homogeneity in the water transport through graphene layers

NASA Astrophysics Data System (ADS)

Su, Jiaye; Zhao, Yunzhen; Fang, Chang

2018-06-01

Graphene is a versatile 2D material and attracts an increasing amount of attention from a broad scientific community, including novel nanofluidic devices. In this work, we use molecular dynamics simulations to study the pressure driven water transport through graphene layers, focusing on the pore size homogeneity, realized by the arrangement of two pore sizes. For a given layer number, we find that water flux exhibits an excellent linear behavior with pressure, in agreement with the prediction of the Hagen–Poiseuille equation. Interestingly, the flux for concentrated pore size distribution is around two times larger than that of a uniform distribution. More surprisingly, under a given pressure, the water flux changes in an opposite way for these two distributions, where the flux ratio almost increases linearly with the layer number. For the largest layer number, more distributions suggest the same conclusion that higher water flux can be attained for more concentrated pore size distributions. Similar differences for the water translocation time and occupancy are also identified. The major reason for these results should clearly be due to the hydrogen bond and density profile distributions. Our results are helpful to delineate the exquisite role of pore size homogeneity, and should have great implications for the design of high flux nanofluidic devices and inversely the detection of pore structures.

Method and system using power modulation and velocity modulation producing sputtered thin films with sub-angstrom thickness uniformity or custom thickness gradients

DOEpatents

Montcalm, Claude [Livermore, CA; Folta, James Allen [Livermore, CA; Walton, Christopher Charles [Berkeley, CA

2003-12-23

A method and system for determining a source flux modulation recipe for achieving a selected thickness profile of a film to be deposited (e.g., with highly uniform or highly accurate custom graded thickness) over a flat or curved substrate (such as concave or convex optics) by exposing the substrate to a vapor deposition source operated with time-varying flux distribution as a function of time. Preferably, the source is operated with time-varying power applied thereto during each sweep of the substrate to achieve the time-varying flux distribution as a function of time. Preferably, the method includes the steps of measuring the source flux distribution (using a test piece held stationary while exposed to the source with the source operated at each of a number of different applied power levels), calculating a set of predicted film thickness profiles, each film thickness profile assuming the measured flux distribution and a different one of a set of source flux modulation recipes, and determining from the predicted film thickness profiles a source flux modulation recipe which is adequate to achieve a predetermined thickness profile. Aspects of the invention include a computer-implemented method employing a graphical user interface to facilitate convenient selection of an optimal or nearly optimal source flux modulation recipe to achieve a desired thickness profile on a substrate. The method enables precise modulation of the deposition flux to which a substrate is exposed to provide a desired coating thickness distribution.

DistributedFBA.jl: High-level, high-performance flux balance analysis in Julia

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

Heirendt, Laurent; Thiele, Ines; Fleming, Ronan M. T.

Flux balance analysis and its variants are widely used methods for predicting steady-state reaction rates in biochemical reaction networks. The exploration of high dimensional networks with such methods is currently hampered by software performance limitations. DistributedFBA.jl is a high-level, high-performance, open-source implementation of flux balance analysis in Julia. It is tailored to solve multiple flux balance analyses on a subset or all the reactions of large and huge-scale networks, on any number of threads or nodes. DistributedFBA.jl is a high-level, high-performance, open-source implementation of flux balance analysis in Julia. It is tailored to solve multiple flux balance analyses on amore » subset or all the reactions of large and huge-scale networks, on any number of threads or nodes.« less

DistributedFBA.jl: High-level, high-performance flux balance analysis in Julia

DOE PAGES

Heirendt, Laurent; Thiele, Ines; Fleming, Ronan M. T.

2017-01-16

Flux balance analysis and its variants are widely used methods for predicting steady-state reaction rates in biochemical reaction networks. The exploration of high dimensional networks with such methods is currently hampered by software performance limitations. DistributedFBA.jl is a high-level, high-performance, open-source implementation of flux balance analysis in Julia. It is tailored to solve multiple flux balance analyses on a subset or all the reactions of large and huge-scale networks, on any number of threads or nodes. DistributedFBA.jl is a high-level, high-performance, open-source implementation of flux balance analysis in Julia. It is tailored to solve multiple flux balance analyses on amore » subset or all the reactions of large and huge-scale networks, on any number of threads or nodes.« less

Plasmaspheric Erosion via Plasmasphere Coupling to Ring Current Plasmas: EUV Observations and Modeling

NASA Technical Reports Server (NTRS)

Adrian, M. L.; Gallagher, D. L.; Khazanov, G. V.; Chsang, S. W.; Liemohn, M. W.; Perez, J. D.; Green, J. L.; Sandel, B. R.; Mitchell, D. G.; Mende, S. B.;

Global Anisotropies in TeV Cosmic Rays Related to the Sun's Local Galactic Environment from IBEX

NASA Technical Reports Server (NTRS)

Schwadron, N. A.; Adams, F. C.; Christian, E. R.; Desiati, P.; Frisch, P.; Funsten, H. O.; Jokipii, J. R.; McComas, D. J.; Moebius, E.; Zank, G. P.

2014-01-01

Observations with the Interstellar Boundary Explorer (IBEX) have shown enhanced energetic neutral atom (ENA) emission from a narrow, circular ribbon likely centered on the direction of the local interstellar medium (LISM) magnetic field. Here, we show that recent determinations of the local interstellar velocity, based on interstellar atom measurements with IBEX, are consistent with the interstellar modulation of high-energy (tera-electron volts, TeV) cosmic rays and diffusive propagation from supernova sources revealed in global anisotropy maps of ground-based high-energy cosmic-ray observatories (Milagro, Asg, and IceCube). Establishing a consistent local interstellar magnetic field direction using IBEX ENAs at hundreds to thousands of eV and galactic cosmic rays at tens of TeV has wide-ranging implications for the structure of our heliosphere and its interactions with the LISM, which is particularly important at the time when the Voyager spacecraft are leaving our heliosphere.

Verification of key odorants in rose oil by gas chromatography-olfactometry/aroma extract dilution analysis, odour activity value and aroma recombination.

PubMed

Xiao, Zuobing; Li, Jing; Niu, Yunwei; Liu, Qiang; Liu, Junhua

2017-10-01

Rose oil is much too expensive but very popular. It's well known that the flower oil's aroma profile hasn't been intensively investigated. In order to verify the aroma profile of rose oil, the synthetic blend of odorants was prepared and then compared with the original rose oil using electronic nose analysis (ENA) combined with quantitative descriptive analysis (QDA). The odorants from rose oils were screened out by Gas Chromatography-Olfactometry/aroma extract dilution analysis (GC-O/AEDA) combined with odour activity value (OAV). Both ENA and QDA indicated the recombination model derived from OAV and GC-O/AEDA closely resembled the original rose oil. The experiment results show that rose oxide, linalool, α-pinene, β-pinene, nonanal, heptanal citronellal, phenyl ethyl alcohol, benzyl alcohol, eugenol, methyl eugenol, β-citronellol, hexyl acetate, β-ionone, nerol, etc. are very important constituent to rose oil aroma profile.

Global, Energy-Dependent Ring Current Response During Two Large Storms

NASA Astrophysics Data System (ADS)

Goldstein, J.; Angelopoulos, V.; Burch, J. L.; De Pascuale, S.; Fuselier, S. A.; Genestreti, K. J.; Kurth, W. S.; LLera, K.; McComas, D. J.; Reeves, G. D.; Spence, H. E.; Valek, P. W.

2015-12-01

Two recent large (~200 nT) geomagnetic storms occurred during 17--18 March 2015 and 22--23 June 2015. The global, energy-dependent ring current response to these two extreme events is investigated using both global imaging and multi-point in situ observations. Energetic neutral atom (ENA) imaging by the Two Wide-angle Imaging Neutral-atom Spectrometers (TWINS) mission provides a global view of ring current ions. Local measurements are provided by two multi-spacecraft missions. The two Van Allen Probes measure in situ plasma (including ion composition) and fields at ring current and plasmaspheric L values. The recently launched Magnetospheric Multiscale (MMS) comprises four spacecraft that have just begun to measure particles (including ion composition) and fields at outer magnetospheric L-values. We analyze the timing and energetics of the stormtime evolution of ring current ions, both trapped and precipitating, using TWINS ENA images and in situ data by the Van Allen Probes and MMS.

Global anisotropies in TeV cosmic rays related to the Sun's local galactic environment from IBEX.

PubMed

Schwadron, N A; Adams, F C; Christian, E R; Desiati, P; Frisch, P; Funsten, H O; Jokipii, J R; McComas, D J; Moebius, E; Zank, G P

2014-02-28

Observations with the Interstellar Boundary Explorer (IBEX) have shown enhanced energetic neutral atom (ENA) emission from a narrow, circular ribbon likely centered on the direction of the local interstellar medium (LISM) magnetic field. Here, we show that recent determinations of the local interstellar velocity, based on interstellar atom measurements with IBEX, are consistent with the interstellar modulation of high-energy (tera-electron volts, TeV) cosmic rays and diffusive propagation from supernova sources revealed in global anisotropy maps of ground-based high-energy cosmic-ray observatories (Milagro, Asγ, and IceCube). Establishing a consistent local interstellar magnetic field direction using IBEX ENAs at hundreds to thousands of eV and galactic cosmic rays at tens of TeV has wide-ranging implications for the structure of our heliosphere and its interactions with the LISM, which is particularly important at the time when the Voyager spacecraft are leaving our heliosphere.

Magnetopause modeling - Flux transfer events and magnetosheath quasi-trapped distributions

NASA Technical Reports Server (NTRS)

Speiser, T. W.; Williams, D. J.

1982-01-01

Three-dimensional distribution functions for energetic ions are studied numerically in the magnetosphere, through the magnetopause, and in the magnetosheath using a simple one-dimensional quasi-static model and ISEE 1 magnetopause crossing data for November 10, 1977. Quasi-trapped populations in the magnetosheath observed near flux transfer events (FTEs) are investigated, and it is shown that the population in the sheath appears to sandwich the FTE distributions. These quasi-trapped distributions are due to slow, large pitch angle, outward moving particles left behind by the outward rush of the ions more field-aligned at the time the flux was opened. It is found that sheath convective flows can map along the connected flux tube without drastically changing the distribution function, and results suggest that localized tangential fields above the upper limit may exist.

An analytical method based on multipole moment expansion to calculate the flux distribution in Gammacell-220

NASA Astrophysics Data System (ADS)

Rezaeian, P.; Ataenia, V.; Shafiei, S.

2017-12-01

In this paper, the flux of photons inside the irradiation cell of the Gammacell-220 is calculated using an analytical method based on multipole moment expansion. The flux of the photons inside the irradiation cell is introduced as the function of monopole, dipoles and quadruples in the Cartesian coordinate system. For the source distribution of the Gammacell-220, the values of the multipole moments are specified by direct integrating. To confirm the validation of the presented methods, the flux distribution inside the irradiation cell was determined utilizing MCNP simulations as well as experimental measurements. To measure the flux inside the irradiation cell, Amber dosimeters were employed. The calculated values of the flux were in agreement with the values obtained by simulations and measurements, especially in the central zones of the irradiation cell. In order to show that the present method is a good approximation to determine the flux in the irradiation cell, the values of the multipole moments were obtained by fitting the simulation and experimental data using Levenberg-Marquardt algorithm. The present method leads to reasonable results for the all source distribution even without any symmetry which makes it a powerful tool for the source load planning.

LOCAL INTERSTELLAR MAGNETIC FIELD DETERMINED FROM THE INTERSTELLAR BOUNDARY EXPLORER RIBBON

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

Zirnstein, E. J.; Livadiotis, G.; McComas, D. J.

2016-02-10

The solar wind emanating from the Sun interacts with the local interstellar medium (LISM), forming the heliosphere. Hydrogen energetic neutral atoms (ENAs) produced by the solar-interstellar interaction carry important information about plasma properties from the boundaries of the heliosphere, and are currently being measured by NASA's Interstellar Boundary Explorer (IBEX). IBEX observations show the existence of a “ribbon” of intense ENA emission projecting a circle on the celestial sphere that is centered near the local interstellar magnetic field (ISMF) vector. Here we show that the source of the IBEX ribbon as a function of ENA energy outside the heliosphere, uniquelymore » coupled to the draping of the ISMF around the heliopause, can be used to precisely determine the magnitude (2.93 ± 0.08 μG) and direction (227.°28 ± 0.°69, 34.°62 ± 0.°45 in ecliptic longitude and latitude) of the pristine ISMF far (∼1000 AU) from the Sun. We find that the ISMF vector is offset from the ribbon center by ∼8.°3 toward the direction of motion of the heliosphere through the LISM, and their vectors form a plane that is consistent with the direction of deflected interstellar neutral hydrogen, thought to be controlled by the ISMF. Our results yield draped ISMF properties close to that observed by Voyager 1, the only spacecraft to directly measure the ISMF close to the heliosphere, and give predictions of the pristine ISMF that Voyager 1 has yet to sample.« less

Local interstellar magnetic field determined from the interstellar boundary explorer ribbon

DOE PAGES

Zirnstein, E. J.; Heerikhuisen, J.; Funsten, H. O.; ...

2016-02-08

The solar wind emanating from the Sun interacts with the local interstellar medium (LISM), forming the heliosphere. Hydrogen energetic neutral atoms (ENAs) produced by the solar-interstellar interaction carry important information about plasma properties from the boundaries of the heliosphere, and are currently being measured by NASA's Interstellar Boundary Explorer (IBEX). IBEX observations show the existence of a “ribbon” of intense ENA emission projecting a circle on the celestial sphere that is centered near the local interstellar magnetic field (ISMF) vector. Here we show that the source of the IBEX ribbon as a function of ENA energy outside the heliosphere, uniquelymore » coupled to the draping of the ISMF around the heliopause, can be used to precisely determine the magnitude (2.93 ± 0.08 μG) and direction (227.°28 ± 0.°69, 34.°62 ± 0.°45 in ecliptic longitude and latitude) of the pristine ISMF far (~1000 AU) from the Sun. We find that the ISMF vector is offset from the ribbon center by ~8.°3 toward the direction of motion of the heliosphere through the LISM, and their vectors form a plane that is consistent with the direction of deflected interstellar neutral hydrogen, thought to be controlled by the ISMF. Lastly, our results yield draped ISMF properties close to that observed by Voyager 1, the only spacecraft to directly measure the ISMF close to the heliosphere, and give predictions of the pristine ISMF that Voyager 1 has yet to sample.« less

Elevated antinuclear antibodies and altered anti-Epstein-Barr virus immune responses.

PubMed

Cuomo, Laura; Cirone, Mara; Di Gregorio, Ana Oliva; Vitillo, Marina; Cattivelli, Marina; Magliocca, Vittoria; Maiorano, Silvana; Meledandri, Marcello; Scagnolari, Carolina; La Rocca, Sebastiano; Trivedi, Pankaj

2015-01-02

It has been shown that Epstein-Barr virus (EBV) is able to alter the immune response towards self-antigens and may enhance risk of autoimmune diseases such as systemic lupus erythematosus (SLE) in genetically predisposed individuals. In this study, we evaluated the specific antibody immune response against EBV in patients with anti-nuclear autoantibodies (ANA) in comparison with ANA-negative healthy controls. For this purpose, 92 patients with an high anti-ANA reactivity with or without concomitant extractable nuclear antigen (ENA) or double stranded DNA (dsDNA) positivity were selected and compared with 146 healthy donors. We found that anti-EBV-VCA and EA IgG concentrations were significantly higher in ANA-positive patients in comparison to the controls (VCA P<0.0001 and EA P<0,03) as well as in those ANA-positive patients that showed a concomitant ENA positivity (P=0.0002). Interestingly, elevated anti-EBNA-1 IgG was found in a group of patients who had anti SSA/Ro antibodies. Anti-VCA IgM Abs were more frequently found in those patients with a very high titer of ANA (P=0.06); moreover detection of anti-VCA IgM/IgG in absence of anti-EBNA-1 IgG was more frequent in the patient than in the control group. Both these conditions correlate with a recent EBV infection or reactivation. The data suggest that EBV, particularly during acute infection or in its reactivation phase, could be involved in the ANA and ENA autoantibody formation. Copyright © 2014 Elsevier B.V. All rights reserved.

Nonantibiotic macrolides prevent human neutrophil elastase-induced mucus stasis and airway surface liquid volume depletion.

PubMed

Tarran, Robert; Sabater, Juan R; Clarke, Tainya C; Tan, Chong D; Davies, Catrin M; Liu, Jia; Yeung, Arthur; Garland, Alaina L; Stutts, M Jackson; Abraham, William M; Phillips, Gary; Baker, William R; Wright, Clifford D; Wilbert, Sibylle

2013-06-01

Mucus clearance is an important component of the lung's innate defense system. A failure of this system brought on by mucus dehydration is common to both cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD). Mucus clearance rates are regulated by the volume of airway surface liquid (ASL) and by ciliary beat frequency (CBF). Chronic treatment with macrolide antibiotics is known to be beneficial to both CF and COPD patients. However, chronic macrolide usage may induce bacterial resistance. We have developed a novel macrolide, 2'-desoxy-9-(S)-erythromycylamine (GS-459755), that has significantly diminished antibiotic activity against Staphylococcus aureus, Streptococcus pneumonia, Moraxella catarrhalis, and Haemophilus influenzae. Since neutrophilia frequently occurs in chronic lung disease and human neutrophil elastase (HNE) induces mucus stasis by activating the epithelial sodium channel (ENaC), we tested the ability of GS-459755 to protect against HNE-induced mucus stasis. GS-459755 had no effect on HNE activity. However, GS-459755 pretreatment protected against HNE-induced ASL volume depletion in human bronchial epithelial cells (HBECs). The effect of GS-459755 on ASL volume was dose dependent (IC₅₀ ~3.9 μM) and comparable to the antibacterial macrolide azithromycin (IC₅₀ ~2.4 μM). Macrolides had no significant effect on CBF or on transepithelial water permeability. However, the amiloride-sensitive transepithelial voltage, a marker of ENaC activity, was diminished by macrolide pretreatment. We conclude that GS-459755 may limit HNE-induced activation of ENaC and may be useful for the treatment of mucus dehydration in CF and COPD without inducing bacterial resistance.

A Correction for IUE UV Flux Distributions from Comparisons with CALSPEC

NASA Astrophysics Data System (ADS)

Bohlin, Ralph C.; Bianchi, Luciana

2018-04-01

A collection of spectral energy distributions (SEDs) is available in the Hubble Space Telescope (HST) CALSPEC database that is based on calculated model atmospheres for pure hydrogen white dwarfs (WDs). A much larger set (∼100,000) of UV SEDs covering the range (1150–3350 Å) with somewhat lower quality are available in the IUE database. IUE low-dispersion flux distributions are compared with CALSPEC to provide a correction that places IUE fluxes on the CALSPEC scale. While IUE observations are repeatable to only 4%–10% in regions of good sensitivity, the average flux corrections have a precision of 2%–3%. Our re-calibration places the IUE flux scale on the current UV reference standard and is relevant for any project based on IUE archival data, including our planned comparison of GALEX to the corrected IUE fluxes. IUE SEDs may be used to plan observations and cross-calibrate data from future missions, so the IUE flux calibration must be consistent with HST instrumental calibrations to the best possible precision.

Sensitivity Analysis of Flux Determination in Heart by H2 18O -provided Labeling Using a Dynamic Isotopologue Model of Energy Transfer Pathways

PubMed Central

Schryer, David W.; Peterson, Pearu; Illaste, Ardo; Vendelin, Marko

2012-01-01

To characterize intracellular energy transfer in the heart, two organ-level methods have frequently been employed: inversion and saturation transfer, and dynamic labeling. Creatine kinase (CK) fluxes obtained by following oxygen labeling have been considerably smaller than the fluxes determined by saturation transfer. It has been proposed that dynamic labeling determines net flux through CK shuttle, whereas saturation transfer measures total unidirectional flux. However, to our knowledge, no sensitivity analysis of flux determination by oxygen labeling has been performed, limiting our ability to compare flux distributions predicted by different methods. Here we analyze oxygen labeling in a physiological heart phosphotransfer network with active CK and adenylate kinase (AdK) shuttles and establish which fluxes determine the labeling state. A mathematical model consisting of a system of ordinary differential equations was composed describing enrichment in each phosphoryl group and inorganic phosphate. By varying flux distributions in the model and calculating the labeling, we analyzed labeling sensitivity to different fluxes in the heart. We observed that the labeling state is predominantly sensitive to total unidirectional CK and AdK fluxes and not to net fluxes. We conclude that measuring dynamic incorporation of into the high-energy phosphotransfer network in heart does not permit unambiguous determination of energetic fluxes with a higher magnitude than the ATP synthase rate when the bidirectionality of fluxes is taken into account. Our analysis suggests that the flux distributions obtained using dynamic labeling, after removing the net flux assumption, are comparable with those from inversion and saturation transfer. PMID:23236266

Photoelectron escape fluxes over the equatorial and midlatitude regions

NASA Technical Reports Server (NTRS)

Narasingarao, B. C.; Singh, R. N.; Maier, E. J.

1972-01-01

Satellite measurements of photoelectron escape flux around noontime made by Explorer 31 in 600-800 km altitude range are reported for the equatorial and midlatitude regions. The pitch angle distributions and the spectral distributions are derived from the data. Analyzed data show that the flux for equatorial regions is lower by a factor 2 to 3 in comparison to that of midlatitude regions. Theoretical calculations are also made to compare with observed escape fluxes.

Determination of meteor flux distribution over the celestial sphere

NASA Technical Reports Server (NTRS)

Andreev, V. V.; Belkovich, O. I.; Filimonova, T. K.; Sidorov, V. V.

1992-01-01

A new method of determination of meteor flux density distribution over the celestial sphere is discussed. The flux density was derived from observations by radar together with measurements of angles of arrival of radio waves reflected from meteor trails. The role of small meteor showers over the sporadic background is shown.

Steady-state distributions of probability fluxes on complex networks

NASA Astrophysics Data System (ADS)

Chełminiak, Przemysław; Kurzyński, Michał

2017-02-01

We consider a simple model of the Markovian stochastic dynamics on complex networks to examine the statistical properties of the probability fluxes. The additional transition, called hereafter a gate, powered by the external constant force breaks a detailed balance in the network. We argue, using a theoretical approach and numerical simulations, that the stationary distributions of the probability fluxes emergent under such conditions converge to the Gaussian distribution. By virtue of the stationary fluctuation theorem, its standard deviation depends directly on the square root of the mean flux. In turn, the nonlinear relation between the mean flux and the external force, which provides the key result of the present study, allows us to calculate the two parameters that entirely characterize the Gaussian distribution of the probability fluxes both close to as well as far from the equilibrium state. Also, the other effects that modify these parameters, such as the addition of shortcuts to the tree-like network, the extension and configuration of the gate and a change in the network size studied by means of computer simulations are widely discussed in terms of the rigorous theoretical predictions.

Size Distributions of Solar Flares and Solar Energetic Particle Events

NASA Technical Reports Server (NTRS)

Cliver, E. W.; Ling, A. G.; Belov, A.; Yashiro, S.

2012-01-01

We suggest that the flatter size distribution of solar energetic proton (SEP) events relative to that of flare soft X-ray (SXR) events is primarily due to the fact that SEP flares are an energetic subset of all flares. Flares associated with gradual SEP events are characteristically accompanied by fast (much > 1000 km/s) coronal mass ejections (CMEs) that drive coronal/interplanetary shock waves. For the 1996-2005 interval, the slopes (alpha values) of power-law size distributions of the peak 1-8 Angs fluxes of SXR flares associated with (a) >10 MeV SEP events (with peak fluxes much > 1 pr/sq cm/s/sr) and (b) fast CMEs were approx 1.3-1.4 compared to approx 1.2 for the peak proton fluxes of >10 MeV SEP events and approx 2 for the peak 1-8 Angs fluxes of all SXR flares. The difference of approx 0.15 between the slopes of the distributions of SEP events and SEP SXR flares is consistent with the observed variation of SEP event peak flux with SXR peak flux.

A linked land-sea modeling framework to inform ridge-to-reef management in high oceanic islands

PubMed Central

Whittier, Robert; Stamoulis, Kostantinos A.; Bremer, Leah L.; Jupiter, Stacy; Friedlander, Alan M.; Poti, Matthew; Guannel, Greg; Kurashima, Natalie; Winter, Kawika B.; Toonen, Robert; Conklin, Eric; Wiggins, Chad; Knudby, Anders; Goodell, Whitney; Burnett, Kimberly; Yee, Susan; Htun, Hla; Oleson, Kirsten L. L.; Wiegner, Tracy; Ticktin, Tamara

2018-01-01

Declining natural resources have led to a cultural renaissance across the Pacific that seeks to revive customary ridge-to-reef management approaches to protect freshwater and restore abundant coral reef fisheries. Effective ridge-to-reef management requires improved understanding of land-sea linkages and decision-support tools to simultaneously evaluate the effects of terrestrial and marine drivers on coral reefs, mediated by anthropogenic activities. Although a few applications have linked the effects of land cover to coral reefs, these are too coarse in resolution to inform watershed-scale management for Pacific Islands. To address this gap, we developed a novel linked land-sea modeling framework based on local data, which coupled groundwater and coral reef models at fine spatial resolution, to determine the effects of terrestrial drivers (groundwater and nutrients), mediated by human activities (land cover/use), and marine drivers (waves, geography, and habitat) on coral reefs. We applied this framework in two ‘ridge-to-reef’ systems (Hā‘ena and Ka‘ūpūlehu) subject to different natural disturbance regimes, located in the Hawaiian Archipelago. Our results indicated that coral reefs in Ka‘ūpūlehu are coral-dominated with many grazers and scrapers due to low rainfall and wave power. While coral reefs in Hā‘ena are dominated by crustose coralline algae with many grazers and less scrapers due to high rainfall and wave power. In general, Ka‘ūpūlehu is more vulnerable to land-based nutrients and coral bleaching than Hā‘ena due to high coral cover and limited dilution and mixing from low rainfall and wave power. However, the shallow and wave sheltered back-reef areas of Hā‘ena, which support high coral cover and act as nursery habitat for fishes, are also vulnerable to land-based nutrients and coral bleaching. Anthropogenic sources of nutrients located upstream from these vulnerable areas are relevant locations for nutrient mitigation, such as cesspool upgrades. In this study, we located coral reefs vulnerable to land-based nutrients and linked them to priority areas to manage sources of human-derived nutrients, thereby demonstrating how this framework can inform place-based ridge-to-reef management. PMID:29538392

The effect of NO-donors on chloride efflux, intracellular Ca(2+) concentration and mRNA expression of CFTR and ENaC in cystic fibrosis airway epithelial cells.

PubMed

Oliynyk, Igor; Hussain, Rashida; Amin, Ahmad; Johannesson, Marie; Roomans, Godfried M

2013-06-01

Since previous studies showed that the endogenous bronchodilator, S-nitrosglutathione (GSNO), caused a marked increase in CFTR-mediated chloride (Cl(-)) efflux and improved the trafficking of CFTR to the plasma membrane, and that also the nitric oxide (NO)-donor GEA3162 had a similar, but smaller, effect on Cl(-) efflux, it was investigated whether the NO-donor properties of GSNO were relevant for its effect on Cl(-) efflux from airway epithelial cells. Hence, the effect of a number of other NO-donors, sodium nitroprusside (SNP), S-nitroso-N-acetyl-DL-penicillamine (SNAP), diethylenetriamine/nitric oxide adduct (DETA-NO), and diethylenetriamine/nitric oxide adduct (DEA-NONOate) on Cl(-) efflux from CFBE (∆F508/∆F508-CFTR) airway epithelial cells was tested. Cl(-) efflux was determined using the fluorescent N-(ethoxycarbonylmethyl)-6-methoxyquinoliniu bromide (MQAE)-technique. Possible changes in the intracellular Ca(2+) concentration were tested by the fluorescent fluo-4 method in a confocal microscope system. Like previously with GSNO, after 4 h incubation with the NO-donor, an increased Cl(-) efflux was found (in the order SNAP>DETA-NO>SNP). The effect of DEA-NONOate on Cl(-) efflux was not significant, and the compound may have (unspecific) deleterious effects on the cells. Again, as with GSNO, after a short (5 min) incubation, SNP had no significant effect on Cl(-) efflux. None of the NO-donors that had a significant effect on Cl(-) efflux caused significant changes in the intracellular Ca(2+) concentration. After 4 h preincubation, SNP caused a significant increase in the mRNA expression of CFTR. SNAP and DEA-NONOate decreased the mRNA expression of all ENaC subunits significantly. DETA-NO caused a significant decrease only in α-ENaC expression. After a short preincubation, none of the NO-donors had a significant effect, neither on the expression of CFTR, nor on that of the ENaC subunits in the presence and absence of L-cysteine. It can be concluded that the effect of GSNO on Cl(-) efflux is, at least in part, due to its properties as an NO-donor, and the effect is likely to be mediated by CFTR, not by Ca(2+)-activated Cl(-) channels. Copyright © 2013. Published by Elsevier Inc.

Evaporation Flux Distribution of Drops on a Hydrophilic or Hydrophobic Flat Surface by Molecular Simulations.

PubMed

Xie, Chiyu; Liu, Guangzhi; Wang, Moran

2016-08-16

The evaporation flux distribution of sessile drops is investigated by molecular dynamic simulations. Three evaporating modes are classified, including the diffusion dominant mode, the substrate heating mode, and the environment heating mode. Both hydrophilic and hydrophobic drop-substrate interactions are considered. To count the evaporation flux distribution, which is position dependent, we proposed an azimuthal-angle-based division method under the assumption of spherical crown shape of drops. The modeling results show that the edge evaporation, i.e., near the contact line, is enhanced for hydrophilic drops in all the three modes. The surface diffusion of liquid molecular absorbed on solid substrate for hydrophilic cases plays an important role as well as the space diffusion on the enhanced evaporation rate at the edge. For hydrophobic drops, the edge evaporation flux is higher for the substrate heating mode, but lower than elsewhere of the drop for the diffusion dominant mode; however, a nearly uniform distribution is found for the environment heating mode. The evidence shows that the temperature distribution inside drops plays a key role in the position-dependent evaporation flux.

Development of a Rotary Wing Unmanned Aerial Vehicle (UAV) Simulation Model

DTIC Science & Technology

2014-03-01

Features Language URL Autopilot: DIY UAV - 2 DOF proportional controller - Kalman filtering C http://autopilot.sour ceforge.net Paperazzi - 3 DOF...proprtional controller - Basic navigation OCaml http://paparazzi.ena c.fr JSBSim - Basic control system blockset - Sample autopilot

The role of nitrogen ions in the ring current dynamics

NASA Astrophysics Data System (ADS)

Ilie, R.; Liemohn, M. W.; Dandouras, I. S.

2017-12-01

Changes in the ion composition throughout the Earth's magnetosphere can have profound implications on plasma structures and dynamics, since it can modify the temperature and the magnetic field configuration, altering the convection patterns inside the magnetosphere. The ratio of hydrogen to oxygen ions has been shown to be highly dependent of geomagnetic activity, with the O+ content increasing with increasing activity. This suggests that ions of ionospheric origin can become the dominant species in the inner magnetosphere during disturbed times. Therefore, numerous studies have focused on the transport and energization of O+ through the ionosphere-magnetosphere system; however, relatively few have considered the contribution of N+, in addition to that of O+ to the near-Earth plasma dynamics, even though past observations have established that N+ is a significant ion species in the ionosphere and its presence in the magnetosphere is significant. Ring current observations from the Active Magnetospheric Particle Tracer Explorer (AMPTE) spacecraft show that high energy N+ fluxes are comparable to those of O+ during disturbed times, confirming the substantial presence of N+ions in the inner magnetosphere. In spite of only 12% mass difference, N+ and O+ have different ionization potentials, scale heights and charge exchange cross sections. The latter, together with the geocoronal density distribution, plays a key role in the formation of Energetic Neutral Atoms (ENAs), which in turn control the energy budget of the inner magnetosphere and the decay of the ring current. Numerical simulations using the Hot Electron and Ion Drift Integrator (HEIDI) model suggest that the contribution of N+ to the ring current dynamics is significant, as the presence of N+, in addition to that of O+, alters the development and the decay rate of the ring current. These findings suggest that differentiating the N+ transport from that of O+ in the near-Earth environment has a profound impact on global magnetosphere dynamics, as plasma composition affects both the local and the global properties of the plasma.

Magnetic flux in modeled magnetic clouds at 1 AU and some specific comparisons to associated photospheric flux

NASA Technical Reports Server (NTRS)

Lepping, R. P.; Szabo, A.; DeForest, C. E.; Thompson, B. J.

1997-01-01

In order to better understand the solar origins of magnetic clouds, statistical distributions of the estimated axial magnetic flux of 30 magnetic clouds at 1 AU, separated according to their occurrence during the solar cycle, were obtained and a comparison was made of the magnetic flux of a magnetic cloud to the aggregate flux of apparently associated photospheric magnetic flux tubes, for some specific cases. The 30 magnetic clouds comprise 12 cases from WIND, and the remainder from IMP-8, earlier IMPs, the International Sun-Earth Explorer (ISEE) 3 and HELIOS. The total magnetic flux along the cloud axis was estimated using a constant alpha, cylindrical, force-free flux rope model to determine cloud diameter and axial magentic field strength. The distribution of magentic fluxes for the 30 clouds is shown to be in the form of a skewed Gaussian.

Flux concentrations on solar dynamic components due to mispointing

NASA Technical Reports Server (NTRS)

Rylicki, Daniel S.

1992-01-01

Mispointing of the solar dynamic (SD) concentrator designed for use on Space Station Freedom (SSF) causes the optical axis of the concentrator to be nonparallel to the incoming rays from the Sun. This causes solar flux not to be focused into the aperture hole of the receiver and may position the flux on other SSF components. A Rocketdyne analysis has determined the thermal impact of off-axis radiation due to mispointing on elements of the SD module and photovoltaic (PV) arrays. The conclusion was that flux distributions on some of the radiator components, the two-axis gimbal rings, the truss, and the PV arrays could present problems. The OFFSET computer code was used at Lewis Research Center to further investigate these flux distributions incident on components. The Lewis study included distributions for a greater range of mispoint angles than the Rocketdyne study.

Gravity wave momentum flux estimation from CRISTA satellite data

NASA Astrophysics Data System (ADS)

Ern, M.; Preusse, P.; Alexander, M. J.; Offermann, D.

2003-04-01

Temperature altitude profiles measured by the CRISTA satellite were analyzed for gravity waves (GWs). Amplitudes, vertical and horizontal wavelengths of GWs are retrieved by applying a combination of maximum entropy method (MEM) and harmonic analysis (HA) to the temperature height profiles and subsequently comparing the so retrieved GW phases of adjacent altitude profiles. From these results global maps of the absolute value of the vertical flux of horizontal momentum have been estimated. Significant differences between distributions of the temperature variance and distributions of the momentum flux exist. For example, global maps of the momentum flux show a pronounced northward shift of the equatorial maximum whereas temperature variance maps of the tropics/subtropics are nearly symmetric with respect to the equator. This indicates the importance of the influence of horizontal and vertical wavelength distribution on global structures of the momentum flux.

TORT/MCNP coupling method for the calculation of neutron flux around a core of BWR.

PubMed

Kurosawa, Masahiko

2005-01-01

For the analysis of BWR neutronics performance, accurate data are required for neutron flux distribution over the In-Reactor Pressure Vessel equipments taking into account the detailed geometrical arrangement. The TORT code can calculate neutron flux around a core of BWR in a three-dimensional geometry model, but has difficulties in fine geometrical modelling and lacks huge computer resource. On the other hand, the MCNP code enables the calculation of the neutron flux with a detailed geometry model, but requires very long sampling time to give enough number of particles. Therefore, a TORT/MCNP coupling method has been developed to eliminate the two problems mentioned above in each code. In this method, the TORT code calculates angular flux distribution on the core surface and the MCNP code calculates neutron spectrum at the points of interest using the flux distribution. The coupling method will be used as the DOT-DOMINO-MORSE code system. This TORT/MCNP coupling method was applied to calculate the neutron flux at points where induced radioactivity data were measured for 54Mn and 60Co and the radioactivity calculations based on the neutron flux obtained from the above method were compared with the measured data.

[Expression profiles and clinical implication of plasma chemokines in patients with Stanford type A aortic dissection].

PubMed

Fan, F D; Xu, Z J; Zhou, Q; Wang, D J

2017-04-24

Objective: To explore the plasma chemokines expressions and related clinical implication in patients with Stanford type A aortic dissection (AD). Methods: We retrospectively analyzed the data of 65 patients with Stanford type A aortic dissection, hypertensive patients and 11 healthy subjects admitted in our department from October 2013 to December 2014, they were divided into four groups: NH-CON group (11 healthy subjects), H-AD group (29 AD patients with hypertension), NH-AD group (21 AD patients without hypertension), and H-CON group (14 hypertension patients). Four plasma samples from AD patients and 4 plasma samples from healthy subjects were collected randomly with random numbers table, and the levels of different chemokines were examined by protein array analysis. Then, plasma levels of chemokines including macrophage inflammatory protein 1β(MIP-1β), epithelial neutrophil activating peptide 78(ENA-78), interleukin 16(IL-16), interferon inducible protein 10(IP-10) and FMS-like tyrosine kinase 3(Flt-3) ligand were analyzed by luminex. Pearson analysis was used to determine the correlations between the chemokines and serum C reactive protein (CRP) levels. Results: Plasma levels of MIP-1β(34.0(29.3, 47.2) ng/L vs. 51.0(28.2, 80.7) ng/L, P <0.05) and ENA-78(110.5(59.1, 161.4) ng/L vs. 475.7(299.3, 837.3) ng/L, P <0.05) were significantly lower in H-AD group, while plasma IL-16 level was significantly higher in H-AD group(54.7(16.3, 187.8) ng/L vs. 17.5(11.9, 20.8) ng/L, P <0.05) than in H-CON group. Plasma levels of MIP-1β(48.3(26.4, 62.1) ng/L, P <0.05) were significantly lower in H-AD patients than in NH-AD patients. Plasma level of ENA-78 was significantly lower in NH-AD group than in NH-CON group (95.0(58.0, 155.0) ng/L vs. 257.7(85.2, 397.8) ng/L, P <0.05). The levels of IP-10 and Flt-3 ligand were similar among the 4 groups (all P >0.05). Pearson analysis showed that there were no correlation between MIP-1β( r (2)=0.01, P >0.05), ENA-78( r (2)=0.02, P >0.05), IL-16( r (2)=0.02, P >0.05), IP-10( r (2)=0.00, P >0.05), Flt-3 ligand( r (2)=0.02, P >0.05) and CRP levels in patients with Stanford type A aortic dissection. Conclusions: Lower plasma levels of MIP-1β and ENA-78 and higher plasma levels of IL-16 may associate with the occurrence and development of type A aortic dissection, but their concentrations are not correlated with serum CRP levels. There is no significant change on plasma levels of IP-10 and Flt-3 in the Stanford type A aortic dissection patients.

The Ability of Atmospheric Data to Reduce Disagreements in Wetland Methane Flux Estimates over North America

NASA Astrophysics Data System (ADS)

Miller, S. M.; Andrews, A. E.; Benmergui, J. S.; Commane, R.; Dlugokencky, E. J.; Janssens-Maenhout, G.; Melton, J. R.; Michalak, A. M.; Sweeney, C.; Worthy, D. E. J.

2015-12-01

Existing estimates of methane fluxes from wetlands differ in both magnitude and distribution across North America. We discuss seven different bottom-up methane estimates in the context of atmospheric methane data collected across the US and Canada. In the first component of this study, we explore whether the observation network can even detect a methane pattern from wetlands. We find that the observation network can identify a methane pattern from Canadian wetlands but not reliably from US wetlands. Over Canada, the network can even identify spatial patterns at multi-provence scales. Over the US, by contrast, anthropogenic emissions and modeling errors obscure atmospheric patterns from wetland fluxes. In the second component of the study, we then use these observations to reconcile disagreements in the magnitude, seasonal cycle, and spatial distribution of existing estimates. Most existing estimates predict fluxes that are too large with a seasonal cycle that is too narrow. A model known as LPJ-Bern has a spatial distribution most consistent with atmospheric observations. By contrast, a spatially-constant model outperforms the distribution of most existing flux estimates across Canada. The results presented here provide several pathways to reduce disagreements among existing wetland flux estimates across North America.

Enantiomer Specific Measurements of Current-Use Pesticides in Aquatic Systems.

EPA Science Inventory

Research has shown that current-use pesticides can enter urban and agricultural watersheds and adversely affect aquatic organisms. A potential cause may be higher concentrations of the more toxic pesticide enantiomer present in the pesticide mixture. The presence of pesticide ena...

On contemporary sedimentation at the titanic survey area

NASA Astrophysics Data System (ADS)

Lukashin, V. N.

2009-12-01

The basic parameters of the sedimentation environment are considered: the Western Boundary Deep Current that transports sedimentary material and distributes it on the survey area; the nepheloid layer, its features, and the distribution of the concentrations and particulate standing crop in it; the distribution of the horizontal and vertical fluxes of the sedimentary material; and the bottom sediments and their absolute masses. The comparison of the vertical fluxes of the particulate matter and the absolute masses of the sediments showed that the contemporary fluxes of sedimentary material to the bottom provided the distribution of the absolute masses of the sediments in the survey area during the Holocene.

An automated model-based aim point distribution system for solar towers

NASA Astrophysics Data System (ADS)

Schwarzbözl, Peter; Rong, Amadeus; Macke, Ansgar; Säck, Jan-Peter; Ulmer, Steffen

2016-05-01

Distribution of heliostat aim points is a major task during central receiver operation, as the flux distribution produced by the heliostats varies continuously with time. Known methods for aim point distribution are mostly based on simple aim point patterns and focus on control strategies to meet local temperature and flux limits of the receiver. Lowering the peak flux on the receiver to avoid hot spots and maximizing thermal output are obviously competing targets that call for a comprehensive optimization process. This paper presents a model-based method for online aim point optimization that includes the current heliostat field mirror quality derived through an automated deflectometric measurement process.

[Characteristics of water and heat fluxes and its footprint climatology on farmland in low hilly region of red soil].

PubMed

Li, Yang; Jing, Yuan Shu; Qin, Ben Ben

2017-01-01

The analysis of the characteristics and footprint climatology of farmland water and heat fluxes has great significance to strengthen regional climate resource management and improve the hydrothermal resource utilization in the region of red soil. Based on quality controlled data from large aperture scintillometer and automatic meteorological station in hilly region of red soil, this paper analyzed in detail the characteristics of farmland water and heat fluxes at different temporal scales and the corresponding source area distribution of flux measurement in the non-rainy season and crop growth period in hilly region of red soil. The results showed that the diurnal variation of water and heat fluxes showed a unimodal trend, but compared with the sunny day, the diurnal variation curves fluctuated more complicatedly on cloudy day. In the whole, either ten-day periods or month scale, the water and heat fluxes were greater in August than in September, while the net radiation flux was more distributed to latent heat exchange. The proportion of net radiation to latent heat flux decreased in September compared to August, but the sensible heat flux was vice versa. With combined effects of weather conditions (particularly wind), stability, and surface condition, the source areas of flux measurement at different temporal scales showed different distribution characteristics. Combined with the underlying surface crops, the source areas at different temporal scales also had different contribution sources.

Measurement of air and VOC vapor fluxes during gas-driven soil remediation: bench-scale experiments.

PubMed

Kim, Heonki; Kim, Taeyun; Shin, Seungyeop; Annable, Michael D

2012-09-04

In this laboratory study, an experimental method was developed for the quantitative analyses of gas fluxes in soil during advective air flow. One-dimensional column and two- and three-dimensional flow chamber models were used in this study. For the air flux measurement, n-octane vapor was used as a tracer, and it was introduced in the air flow entering the physical models. The tracer (n-octane) in the gas effluent from the models was captured for a finite period of time using a pack of activated carbon, which then was analyzed for the mass of n-octane. The air flux was calculated based on the mass of n-octane captured by the activated carbon and the inflow concentration. The measured air fluxes are in good agreement with the actual values for one- and two-dimensional model experiments. Using both the two- and three-dimensional models, the distribution of the air flux at the soil surface was measured. The distribution of the air flux was found to be affected by the depth of the saturated zone. The flux and flux distribution of a volatile contaminant (perchloroethene) was also measured by using the two-dimensional model. Quantitative information of both air and contaminant flux may be very beneficial for analyzing the performance of gas-driven subsurface remediation processes including soil vapor extraction and air sparging.

Including metabolite concentrations into flux balance analysis: thermodynamic realizability as a constraint on flux distributions in metabolic networks

PubMed Central

Hoppe, Andreas; Hoffmann, Sabrina; Holzhütter, Hermann-Georg

2007-01-01

Background In recent years, constrained optimization – usually referred to as flux balance analysis (FBA) – has become a widely applied method for the computation of stationary fluxes in large-scale metabolic networks. The striking advantage of FBA as compared to kinetic modeling is that it basically requires only knowledge of the stoichiometry of the network. On the other hand, results of FBA are to a large degree hypothetical because the method relies on plausible but hardly provable optimality principles that are thought to govern metabolic flux distributions. Results To augment the reliability of FBA-based flux calculations we propose an additional side constraint which assures thermodynamic realizability, i.e. that the flux directions are consistent with the corresponding changes of Gibb's free energies. The latter depend on metabolite levels for which plausible ranges can be inferred from experimental data. Computationally, our method results in the solution of a mixed integer linear optimization problem with quadratic scoring function. An optimal flux distribution together with a metabolite profile is determined which assures thermodynamic realizability with minimal deviations of metabolite levels from their expected values. We applied our novel approach to two exemplary metabolic networks of different complexity, the metabolic core network of erythrocytes (30 reactions) and the metabolic network iJR904 of Escherichia coli (931 reactions). Our calculations show that increasing network complexity entails increasing sensitivity of predicted flux distributions to variations of standard Gibb's free energy changes and metabolite concentration ranges. We demonstrate the usefulness of our method for assessing critical concentrations of external metabolites preventing attainment of a metabolic steady state. Conclusion Our method incorporates the thermodynamic link between flux directions and metabolite concentrations into a practical computational algorithm. The weakness of conventional FBA to rely on intuitive assumptions about the reversibility of biochemical reactions is overcome. This enables the computation of reliable flux distributions even under extreme conditions of the network (e.g. enzyme inhibition, depletion of substrates or accumulation of end products) where metabolite concentrations may be drastically altered. PMID:17543097

Scoring of predicted GRK2 phosphorylation sites in Nedd4-2.

PubMed

Arthur, Jonathan W; Sanchez-Perez, Angeles; Cook, David I

2006-09-15

Epithelial Na(+) channels (ENaC) mediate the transport of sodium (Na) across epithelia in the kidney, gut and lungs and are required for blood pressure regulation. They are inhibited by ubiquitin protein ligases, such as Nedd4-2. These ligases bind to proline-rich motifs (PY motifs) present in the C-termini of ENaC subunits. Loss of this inhibition leads to hypertension. We have previously reported that ENaC channels are maintained in the active state by the G protein coupled receptor kinase, GRK2. The enzyme has been implicated in the development of essential hypertension [R. D. Feldman (2002) Mol. Pharmacol., 61, 707-709]. Additional findings in our lab pointed towards a possible role for GRK2 in the phosphorylation and inactivation of Nedd4-2. We have predicted GRK2 phosphorylation sites on Nedd4-2 by combining sequence analysis, homology modeling and surface accessibility calculations. A total of 24 potential phosphorylation sites were predicted by sequence analysis. Of these, 16 could be modeled using homology modeling and 6 of these were found to have sufficient surface exposure to be accessible to the GRK2 enzyme responsible for the phosphorylation of Nedd4-2. The method provides an ordered list of the most probable GRK2 phosphorylation sites on Nedd4-2 providing invaluable guidance to future experimental studies aimed at mutating certain Nedd4-2 residues in order to prevent phosphorylation by GRK2. The method developed could be applied in a wide variety of biological applications involving the binding of one molecule to a protein. The relative effectiveness of the technique is determined mainly by the quality of the homology model built for the protein of interest. jarthur@med.usyd.edu.au

Altered ion transport by thyroid epithelia from CFTR−/− pigs suggests mechanisms for hypothyroidism in Cystic Fibrosis

PubMed Central

Li, Hui; Ganta, Suhasini; Fong, Peying

2010-01-01

Subclinical hypothyroidism has been linked to Cystic Fibrosis (CF), and the cystic fibrosis transmembrane conductance regulator (CFTR) shown to be expressed in the thyroid. The thyroid epithelium secretes Cl− and absorbs Na+ in response to cAMP. Chloride secretion may provide a counter-ion for the SLC26A4 (Pendrin)-mediated I− secretion which is required for the first step of thyroid hormonogenesis, thyroglobulin iodination. In contrast, few models exist to explain a role for Na+ absorption. Whether CFTR mediates the secretory Cl− current in thyroid epithelium has not been directly addressed. We used thyroids from a novel pig CFTR−/− model, generated primary pig thyroid epithelial cell cultures (pThECs), analyzed these cultures for preservation of thyroid-specific transcripts and proteins, and monitored 1) the Cl− secretory response to the cAMP agonist, isoproterenol and 2) the amiloride-sensitive Na+ current. Baseline short-circuit current (Isc) did not differ between CFTR+/+ and CFTR−/− cultures. Serosal isoproterenol increased Isc in CFTR+/+, but not CFTR−/−, monolayers. Compared to CFTR+/+ thyroid cultures, amiloride-sensitive Na+ absorption measured in CFTR−/− pThECs represented a greater fraction of the resting Isc. However, levels of transcripts encoding ENaC subunits did not differ between CFTR+/+ and CFTR−/− pThECs. Immunoblot analysis verified ENaC subunit protein expression, but quantification indicated no difference in expression levels. Our studies definitively demonstrate that CFTR mediates cAMP-stimulated Cl− secretion in a well-differentiated thyroid culture model, and that knockout of CFTR promotes increased Na+ absorption by a mechanism other than increased ENaC expression. These findings suggest several models for the mechanism of CF-associated hypothyroidism. PMID:20729267

Radiodine therapy of the autonomous thyroid nodule in patients with or without visible extranodular activity

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

Clerc, J.; Dagousset, F.; Izembart, M.

1995-02-01

Patients with an autonomously functioning throid nodule (ATN) may present with various clinical, biochemical and scintigraphic features. To optimize 1 dose planning and treatment timing in these patients, relationships between dosimetric data and clinical follow-up events must be established. The authors retrospectively reviewed the records of 88 patients who received 1 (intended dose of 80 Gy) for an ATN, of whom 39 had evidence of extranodular activity (ENA) and 76 presented with overt thyrotoxicosis. In all of the patients, dosage calculation was monitored to estimate precisely both beta and gamma absorbed doses received by the ATN and the nodule-free lobe.more » The mean duration of follow-up was 75 mo (max 180) and always included biochemical thyroid tests. Finally, they compared the dosimetric profiles of four dosage schemes which had been normalized by simulation to ensure that the same absorbed dose threshold value was always delivered to the ATN. About 75% of the patients were cured at 6 mo for a mean 305 MBq administered. The absorbed doses delivered to the nodule-free lobe to the ATN, mainly in the form of beta irradiation. Life-table estimates for hypothyroidism and death were 9.6% and 22% at 75 mo, respectively. Hypothyroidism mainly developed in patients with nonsuppressed TSH levels but regardless of ENA, which often accounted for multifocal disease. The authors suggest that fixed doses bordering on 370 MBq are advisable in younger individuals and in patients with mild thyrotoxocosis, while 555 MBq-740 MBq can be administered in other patients and that ENA indicates multifocal autonomy in patients with toxic ATN and is a further indication for radioiodine treatment which should be begun as soon as possible to avoid the development of cardiac complications. 27 refs., 5 tabs.« less

The Importance of Non-Thermal Pressures in the Heliosheath: Towards New Methods of Analysis

NASA Astrophysics Data System (ADS)

Roelof, E. C.; Gruntman, M.; Krimigis, S. M.; Mitchell, D. G.; McComas, D. J.; Funsten, H. O.

2009-12-01

The in-situ plasma measurements when Voyager 2 crossed the termination shock into the heliosheath revealed that only ~20% of the downstream pressure resided in the thermal ion population at energies << 1 keV. The LECP ion measurements > 30 keV at both VGRs 1 and 2 implied a partial pressure ΔP~0.02pPa that accounted for another ~15% of the total pressure. Adding in the missing 70% of the non-thermal pressure, the total non-thermal pressure at the VGRs must be P~0.12pPa. Consensus estimates of the local interstellar magnetic field (ISMF) are near B~0.25nT which gives a hydrostatic magnetic pressure B2/2μ0~0.25pPa. Cassini/INCA all-sky images of 5-44keV ENAs from the heliosheath [Krimigis et al., this session] show that neither VGR1 nor VGR2 is in the direction of maximum ENA emission. Consequently, it is possible that the pressure of non-thermal protons in the heliosheath is comparable to the hydrostatic pressure of the interstellar magnetic field (ISMF) that confines the heliosheath. An immediate corollary is that we will not understand the physics of the heliosheath until we find ways of quantitatively describing the dynamics of pressures produced by non-thermal ion populations. Present MHD theories and simulations simply do not capture these essential dynamical processes. We point out that the magnetospheric communities studying the dynamics of non-thermal ion injections (with plasma beta>1) at Earth and Saturn revealed by ENA imaging have been making significant progress in a quite similar problem. We offer some possible approaches for the quantitative analysis of the heliosheath, based on the magnetospheric experience.

CINEMA (Cubesat for Ion, Neutral, Electron, MAgnetic fields)

NASA Astrophysics Data System (ADS)

Lin, R. P.; Parks, G. K.; Halekas, J. S.; Larson, D. E.; Eastwood, J. P.; Wang, L.; Sample, J. G.; Horbury, T. S.; Roelof, E. C.; Lee, D.; Seon, J.; Hines, J.; Vo, H.; Tindall, C.; Ho, J.; Lee, J.; Kim, K.

2009-12-01

The NSF-funded CINEMA mission will provide cutting-edge magnetospheric science and critical space weather measurements, including high sensitivity mapping and high cadence movies of ring current, >4 keV Energetic Neutral Atom (ENA), as well as in situ measurements of suprathermal electrons (>~2 keV) and ions (>~ 4 keV) in the auroral and ring current precipitation regions, all with ~1 keV FWHM resolution and uniform response up to ~100 keV. A Suprathermal Electron, Ion, Neutral (STEIN) instrument adds an electrostatic deflection system to the STEREO STE (SupraThermal Electron) 4-pixel silicon semiconductor sensor to separate ions from electrons and from ENAs up to ~20 keV. In addition, inboard and outboard (on an extendable 1m boom) magnetoresistive sensor magnetometers will provide high cadence 3-axis magnetic field measurements. A new attitude control system (ACS) uses torque coils, a solar aspect sensor and the magnetometers to de-tumble the 3u CINEMA spacecraft, then spin it up to ~1 rpm with the spin axis perpendicular to the ecliptic, so STEIN can sweep across most of the sky every minute. Ideally, CINEMA will be placed into a high inclination low earth orbit that crosses the auroral zone and cusp. An S-band transmitter will be used to provide > ~8 kbps orbit-average data downlink to the ~11m diameter antenna of the Berkeley Ground Station. Two more identical CINEMA spacecraft will be built by Kyung Hee University (KHU) in Korea under their World Class University (WCU) program, to provide stereo ENA imaging and multi-point in situ measurements. Furthermore, CINEMA’s development of miniature particle and magnetic field sensors, and cubesat-size spinning spacecraft will be important for future nanosatellite space missions.

Induction of micronuclei and nuclear abnormalities in tadpoles of the common toad (Rhinella arenarum) treated with the herbicides Liberty® and glufosinate-ammonium.

PubMed

Lajmanovich, Rafael C; Cabagna-Zenklusen, Mariana C; Attademo, Andrés M; Junges, Celina M; Peltzer, Paola M; Bassó, Agustín; Lorenzatti, Eduardo

2014-07-15

The assessment of micronucleated erythrocytes (ME) in blood represents a widely used method for the detection of chromosomal damage by chemical agents, such as herbicides that may occur as water contaminants. We investigated the changes in some circulating blood-cell parameters of tadpoles of the common toad (Rhinella arenarum) that were exposed during 48 or 96 h to three sub-lethal concentrations (3.75, 7.5, and 15 mg/L) of a commercial formulation of a glufosinate-ammonium (GLA)-based herbicide (Liberty(®), LY(®)) as well as to the corresponding active ingredient GLA. The frequency of ME and other erythrocyte nuclear abnormalities (ENA, i.e., lobed nuclei, binucleates or segmented nuclei, kidney-shaped nuclei, notched nuclei, and picnotic nuclei) were evaluated and compared with positive (cyclophosphamide, CP, 40 mg/L) and negative (de-chlorinated tap water) controls. The results indicate that the exposure of R. arenarum tadpoles to LY(®) induces a concentration-dependent increase in ME frequency. The ENA frequency at 48 h was also significantly higher than that in the negative control group for all the chemicals assayed (CP, LY(®) and GLA) whereas at 96 h, increases in ENA over the negative control group were found only for CP and GLA (7.5 mg/L). Our study demonstrates that the commercial formulation of a GLA-based herbicide induces micronucleus formation in R. arenarum tadpoles, in contrast to the active ingredient. According to these results, the inert ingredients of the commercial formulation played an important role in the production of genotoxic damage in erythrocytes of amphibian tadpoles. Copyright © 2014 Elsevier B.V. All rights reserved.

Impaired natriuretic response to high-NaCl diet plus aldosterone infusion in mice overexpressing human CD39, an ectonucleotidase (NTPDase1).

PubMed

Zhang, Yue; Robson, Simon C; Morris, Kaiya L; Heiney, Kristina M; Dwyer, Karen M; Kishore, Bellamkonda K; Ecelbarger, Carolyn M

2015-06-15

Extracellular nucleotides acting through P2 receptors facilitate natriuresis. To define how purinergic mechanisms are involved in sodium homeostasis, we used transgenic (TG) mice that globally overexpress human CD39 (hCD39, NTPDase1), an ectonucleotidase that hydrolyzes extracellular ATP/ADP to AMP, resulting in an altered extracellular purine profile. On a high-sodium diet (HSD, 3.5% Na(+)), urine volume and serum sodium were significantly higher in TG mice but sodium excretion was unaltered. Furthermore, TG mice showed an attenuated fall in urine aldosterone with HSD. Western blot analysis revealed significantly lower densities (∼40%) of the β-subunit of the epithelial sodium channel (ENaC) in medulla, and the major band (85-kDa) of γ-ENaC in TG mice cortex. To evaluate aldosterone-independent differences, in a second experiment, aldosterone was clamped by osmotic minipump at 20 μg/day, and mice were fed either an HSD or a low-sodium diet (LSD, 0.03% Na(+)). Here, no differences in urine volume or osmolality, or serum aldosterone were found, but TG mice showed a modest, yet significant impairment in late natriuresis (days 3 and 4). Several major sodium transporters or channel subunits were differentially expressed between the genotypes. HSD caused a downregulation of Na-Cl cotransporter (NCC) in both genotypes; and had higher cortical levels of NCC, Na-K-ATPase (α-1 subunit), and α- and γ-ENaC. The Na-K-2Cl cotransporter (NKCC2) was downregulated by HSD in wild-type mice, but it increased in TG mice. In summary, our data support the concept that extracellular nucleotides facilitate natriuresis; they also reveal an aldosterone-independent downregulation of major renal sodium transporters and channel subunits by purinergic signaling.

Simultaneous Determination of Acetylsalicylic Acid, Hydrochlorothiazide, Enalapril, and Atorvastatin in a Polypill-Based Quaternary Mixture by TLC.

PubMed

Maślanka, Anna; Stolarczyk, Mariusz; Apola, Anna; Kwiecień, Anna; Hubicka, Urszula; Opoka, Włodzimierz

2018-05-01

A new chromatographic-densitometric method has been developed for the qualitative and quantitative determination of the active ingredients in a simulated mixture corresponding to the PolyIran polypill, composed of acetylsalicylic acid, hydrochlorothiazide (HCT), enalapril (ENA), and atorvastatin (ATR), whose efficacy in the treatment and prevention of cardiovascular disease has been documented in clinical trials. Chromatographic separation was performed using TLC silica gel 60 plates with fluorescent indicator F254 as the stationary phase and a mixture of n-hexane-ethyl acetate-methanol-water-acetic acid (8.4 + 8 + 3 + 0.4 + 0.2, v/v/v/v/v) as the mobile phase. Densitometric measurements were carried out at λ = 210 nm when determining ENA and at λ = 265 nm in the case of the other drugs. Peaks of examined substances were well separated in the recorded chromatograms, enabling the evaluation of the results in terms of both qualitative and quantitative analysis. The method was specific for the analyzed components and was characterized by high sensitivity. The LOD was between 0.043 and 0.331 μg/spot, and LOQ was between 0.100 and 0.942 μg/spot. Recovery was in the range of 97.02-101.34%. The linearity range was broad and ranged from 0.600 to 6.000 μg/spot for acetylsalicylic acid, from 0.058 to 1.102 μg/spot for HCT, from 0.505 to 6.560 μg/spot for ENA, and from 0.100 to 1.000 μg/spot for ATR. The method was characterized by good precision, with RSD values that ranged from 0.10 to 2.26%.

Thirst Increases Chorda Tympani Responses to Sodium Chloride.

PubMed

Mast, Thomas G; Breza, Joseph M; Contreras, Robert J

2017-10-01

In nature, water is present as a low-salt solution, thus we hypothesized that thirst would increase taste responses to low-salt solutions. We investigated the effect of thirst on the 2 different salt detection mechanisms present in the rat chorda tympani (CT) nerve. The first mechanism is dependent upon the epithelial sodium channel (ENaC), is blocked by benzamil, and is specific to the cation sodium. The second mechanism, while undefined, is independent of ENaC, and detects multiple cations. We expected thirst to increase benzamil-sensitive sodium responses due to mechanistically increasing the benzamil-sensitive ENaC. We recorded CT whole-nerve electrophysiological responses to lingual application of NaCl, KCl (30, 75, 150, 300, 500, and 600 mM), and imitation rainwater in both control and 24-h water-restricted male rats. NaCl solutions were presented in artificial saliva before and after lingual application of 5µM benzamil. Water restriction significantly increased the integrated CT responses to NaCl but not to KCl or imitation rainwater. Consistent with our hypothesis, only the benzamil-sensitive, and not the benzamil-insensitive, CT sodium response significantly increased. Additionally, CT responses to salt were recorded following induction of either osmotic or volemic thirst. Both thirsts significantly enhanced the integrated CT responses to NaCl and KCl, but not imitation rainwater. Interestingly, osmotic and volemic thirsts increased CT responses by increasing both the benzamil-sensitive and benzamil-insensitive CT sodium responses. We propose that thirst increases the sensitivity of the CT nerve to sodium. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Mechanisms of renal control of potassium homeostasis in complete aldosterone deficiency.

PubMed

Todkar, Abhijeet; Picard, Nicolas; Loffing-Cueni, Dominique; Sorensen, Mads V; Mihailova, Marija; Nesterov, Viatcheslav; Makhanova, Natalia; Korbmacher, Christoph; Wagner, Carsten A; Loffing, Johannes

2015-02-01

Aldosterone-independent mechanisms may contribute to K(+) homeostasis. We studied aldosterone synthase knockout (AS(-/-)) mice to define renal control mechanisms of K(+) homeostasis in complete aldosterone deficiency. AS(-/-) mice were normokalemic and tolerated a physiologic dietary K(+) load (2% K(+), 2 days) without signs of illness, except some degree of polyuria. With supraphysiologic K(+) intake (5% K(+)), AS(-/-) mice decompensated and became hyperkalemic. High-K(+) diets induced upregulation of the renal outer medullary K(+) channel in AS(-/-) mice, whereas upregulation of the epithelial sodium channel (ENaC) sufficient to increase the electrochemical driving force for K(+) excretion was detected only with a 2% K(+) diet. Phosphorylation of the thiazide-sensitive NaCl cotransporter was consistently lower in AS(-/-) mice than in AS(+/+) mice and was downregulated in mice of both genotypes in response to increased K(+) intake. Inhibition of the angiotensin II type 1 receptor reduced renal creatinine clearance and apical ENaC localization, and caused severe hyperkalemia in AS(-/-) mice. In contrast with the kidney, the distal colon of AS(-/-) mice did not respond to dietary K(+) loading, as indicated by Ussing-type chamber experiments. Thus, renal adaptation to a physiologic, but not supraphysiologic, K(+) load can be achieved in aldosterone deficiency by aldosterone-independent activation of the renal outer medullary K(+) channel and ENaC, to which angiotensin II may contribute. Enhanced urinary flow and reduced activity of the thiazide-sensitive NaCl cotransporter may support renal adaptation by activation of flow-dependent K(+) secretion and increased intratubular availability of Na(+) that can be reabsorbed in exchange for K(+) secreted. Copyright © 2015 by the American Society of Nephrology.

Characterization of Rat Meibomian Gland Ion and Fluid Transport

PubMed Central

Yu, Dongfang; Davis, Richard M.; Aita, Megumi; Burns, Kimberlie A.; Clapp, Phillip W.; Gilmore, Rodney C.; Chua, Michael; O'Neal, Wanda K.; Schlegel, Richard; Randell, Scott H.; C. Boucher, Richard

2016-01-01

Purpose We establish novel primary rat meibomian gland (MG) cell culture systems and explore the ion transport activities of the rat MG. Methods Freshly excised rat MG tissues were characterized as follows: (1) mRNA expression of selected epithelial ion channels/transporters were measured by RT-PCR, (2) localization of epithelial sodium channel (ENaC) mRNAs was performed by in situ hybridization, and (3) protein expression and localization of βENaC, the Na+/K+/Cl− cotransporter (NKCC), and the Na+/K+ ATPase were evaluated by immunofluorescence. Primary isolated rat MG cells were cocultured with 3T3 feeder cells and a Rho-associated kinase (ROCK) inhibitor (Y-27632) for expansion. Passaged rat MG cells were cultured as planar sheets under air-liquid interface (ALI) conditions for gene expression and electrophysiologic studies. Passaged rat MG cells also were cultured in matrigel matrices to form spheroids, which were examined ultrastructurally by transmission electron microscopy (TEM) and functionally using swelling assays. Results Expression of multiple ion channel/transporter genes was detected in rat MG tissues. β-ENaC mRNA and protein were localized more to MG peripheral acinar cells than central acinar cells or ductular epithelial cells. Electrophysiologic studies of rat MG cell planar cultures demonstrated functional sodium, chloride, and potassium channels, and cotransporters activities. Transmission electron microscopic analyses of rat MG spheroids revealed highly differentiated MG cells with abundant lysosomal lamellar bodies. Rat MG spheroids culture-based measurements demonstrated active volume regulation by ion channels. Conclusions This study demonstrates the presence and function of ion channels and volume transport by rat MG. Two novel primary MG cell culture models that may be useful for MG research were established. PMID:27127933

NaCl responsive taste cells in the mouse fungiform taste buds.

PubMed

Yoshida, R; Horio, N; Murata, Y; Yasumatsu, K; Shigemura, N; Ninomiya, Y

2009-03-17

Previous studies have demonstrated that rodents' chorda tympani (CT) nerve fibers responding to NaCl can be classified according to their sensitivities to the epithelial sodium channel (ENaC) blocker amiloride into two groups: amiloride-sensitive (AS) and -insensitive (AI). The AS fibers were shown to respond specifically to NaCl, whereas AI fibers broadly respond to various electrolytes, including NaCl. These data suggest that salt taste transduction in taste cells may be composed of at least two different systems; AS and AI ones. To further address this issue, we investigated the responses to NaCl, KCl and HCl and the amiloride sensitivity of mouse fungiform papilla taste bud cells which are innervated by the CT nerve. Comparable with the CT data, the results indicated that 56 NaCl-responsive cells tested were classified into two groups; 25 cells ( approximately 44%) narrowly responded to NaCl and their NaCl response were inhibited by amiloride (AS cells), whereas the remaining 31 cells ( approximately 56%) responded not only to NaCl, but to KCl and/or HCl and showed no amiloride inhibition of NaCl responses (AI cells). Amiloride applied to the basolateral side of taste cells had no effect on NaCl responses in the AS and AI cells. Single cell reverse transcription-polymerase chain reaction (RT-PCR) experiments indicated that ENaC subunit mRNA was expressed in a subset of AS cells. These findings suggest that the mouse fungiform taste bud is composed of AS and AI cells that can transmit taste information differently to their corresponding types of CT fibers, and apical ENaCs may be involved in the NaCl responses of AS cells.

Rapid elevation of sodium transport through insulin is mediated by AKT in alveolar cells

PubMed Central

Mattes, Charlott; Laube, Mandy; Thome, Ulrich H.

2014-01-01

Abstract Alveolar fluid clearance is driven by vectorial Na+ transport and promotes postnatal lung adaptation. The effect of insulin on alveolar epithelial Na+ transport was studied in isolated alveolar cells from 18–19‐day gestational age rat fetuses. Equivalent short‐circuit currents (ISC) were measured in Ussing chambers and different kinase inhibitors were used to determine the pathway of insulin stimulation. In Western Blot measurements the activation of mediators stimulated by insulin was analyzed. The ISC showed a fast dose‐dependent increase by insulin, which could be attributed to an increased ENaC (epithelial Na+ channel) activity in experiments with permeabilized apical or basolateral membrane. 5‐(N‐Ethyl‐N‐isopropyl)amiloride inhibition of ISC was not affected, however, benzamil‐sensitive ISC was increased in insulin‐stimulated monolayers. The application of LY‐294002 and Akti1/2 both completely blocked the stimulating effect of insulin on ISC. PP242 partly blocked the effect of insulin, whereas Rapamycin evoked no inhibition. Western Blot measurements revealed an increased phosphorylation of AKT after insulin stimulation. SGK1 activity was also increased by insulin as shown by Western Blot of pNDRG1. However, in Ussing chamber measurements, GSK650394, an inhibitor of SGK1 did not prevent the increase in ISC induced by insulin. The application of IGF‐1 mimicked the effect of insulin and increased the ENaC activity. In addition, an increased autophosphorylation of the IGF‐1R/IR was observed after insulin stimulation. We conclude that insulin rapidly increases epithelial Na+ transport by enhancing the activity of endogenous ENaC through activation of PI3K/AKT in alveolar cells. PMID:24760523

Three homologous subunits form a high affinity peptide-gated ion channel in Hydra.

PubMed

Dürrnagel, Stefan; Kuhn, Anne; Tsiairis, Charisios D; Williamson, Michael; Kalbacher, Hubert; Grimmelikhuijzen, Cornelis J P; Holstein, Thomas W; Gründer, Stefan

2010-04-16

Recently, three ion channel subunits of the degenerin (DEG)/epithelial Na(+) channel (ENaC) gene family have been cloned from the freshwater polyp Hydra magnipapillata, the Hydra Na(+) channels (HyNaCs) 2-4. Two of them, HyNaC2 and HyNaC3, co-assemble to form an ion channel that is gated by the neuropeptides Hydra-RFamides I and II. The HyNaC2/3 channel is so far the only cloned ionotropic receptor from cnidarians and, together with the related ionotropic receptor FMRFamide-activated Na(+) channel (FaNaC) from snails, the only known peptide-gated ionotropic receptor. The HyNaC2/3 channel has pore properties, like a low Na(+) selectivity and a low amiloride affinity, that are different from other channels of the DEG/ENaC gene family, suggesting that a component of the native Hydra channel might still be lacking. Here, we report the cloning of a new ion channel subunit from Hydra, HyNaC5. The new subunit is closely related to HyNaC2 and -3 and co-localizes with HyNaC2 and -3 to the base of the tentacles. Coexpression in Xenopus oocytes of HyNaC5 with HyNaC2 and -3 largely increases current amplitude after peptide stimulation and affinity of the channel to Hydra-RFamides I and II. Moreover, the HyNaC2/3/5 channel has altered pore properties and amiloride affinity, more similarly to other DEG/ENaC channels. Collectively, our results suggest that the three homologous subunits HyNaC2, -3, and -5 form a peptide-gated ion channel in Hydra that could contribute to fast synaptic transmission.

Thyroxine-induced cardiac hypertrophy: influence of adrenergic nervous system versus renin-angiotensin system on myocyte remodeling.

PubMed

Hu, L W; Benvenuti, L A; Liberti, E A; Carneiro-Ramos, M S; Barreto-Chaves, M L M

2003-12-01

The present study assessed the possible involvement of the renin-angiotensin system (RAS) and the sympathetic nervous system (SNS) in thyroxine (T4)-induced cardiac hypertrophy. Hemodynamic parameters, heart weight (HW), ratio of HW to body weight (HW/BW), and myocyte width were evaluated in absence of thyroid hormone (hypothyroidism) and after T4 administration. Male Wistar rats were used. Some were subjected to thyroidectomies, whereas hyperthyroidism was induced in others via daily intraperitoneal injection of T4 (25 or 100 microg x 100 g BW(-1) x day(-1)) for 7 days. In some cases, T4 administration was combined with the angiotensin I-converting enzyme inhibitor enalapril (Ena), with the angiotensin type 1 (AT1) receptor blocker losartan (Los) or with the beta-adrenergic blocker propanolol (Prop). Hemodynamics and morphology were then evaluated. Systolic blood pressure (SBP) was not altered by administration of either T4 alone or T4 in combination with the specific inhibitors. However, SBP decreased significantly in hypothyroid rats. An increased heart rate was seen after administration of either T4 alone or T4 in combination with either Los or Ena. Although the higher dose of T4 significantly increased HW, HW/BW increased in both T4-treated groups. Ena and Prop inhibited the increase in HW or HW/BW in hyperthyroid rats. Morphologically, both T4 dose levels significantly increased myocyte width, an occurrence prevented by RAS or SNS blockers. There was a good correlation between changes in HW/BW and myocyte width. These results indicate that T4-induced cardiac hypertrophy is associated with both the SNS and the RAS.

Nonantibiotic macrolides prevent human neutrophil elastase-induced mucus stasis and airway surface liquid volume depletion

PubMed Central

Sabater, Juan R.; Clarke, Tainya C.; Tan, Chong D.; Davies, Catrin M.; Liu, Jia; Yeung, Arthur; Garland, Alaina L.; Stutts, M. Jackson; Abraham, William M.; Phillips, Gary; Baker, William R.; Wright, Clifford D.; Wilbert, Sibylle

2013-01-01

Mucus clearance is an important component of the lung's innate defense system. A failure of this system brought on by mucus dehydration is common to both cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD). Mucus clearance rates are regulated by the volume of airway surface liquid (ASL) and by ciliary beat frequency (CBF). Chronic treatment with macrolide antibiotics is known to be beneficial to both CF and COPD patients. However, chronic macrolide usage may induce bacterial resistance. We have developed a novel macrolide, 2′-desoxy-9-(S)-erythromycylamine (GS-459755), that has significantly diminished antibiotic activity against Staphylococcus aureus, Streptococcus pneumonia, Moraxella catarrhalis, and Haemophilus influenzae. Since neutrophilia frequently occurs in chronic lung disease and human neutrophil elastase (HNE) induces mucus stasis by activating the epithelial sodium channel (ENaC), we tested the ability of GS-459755 to protect against HNE-induced mucus stasis. GS-459755 had no effect on HNE activity. However, GS-459755 pretreatment protected against HNE-induced ASL volume depletion in human bronchial epithelial cells (HBECs). The effect of GS-459755 on ASL volume was dose dependent (IC50 ∼3.9 μM) and comparable to the antibacterial macrolide azithromycin (IC50 ∼2.4 μM). Macrolides had no significant effect on CBF or on transepithelial water permeability. However, the amiloride-sensitive transepithelial voltage, a marker of ENaC activity, was diminished by macrolide pretreatment. We conclude that GS-459755 may limit HNE-induced activation of ENaC and may be useful for the treatment of mucus dehydration in CF and COPD without inducing bacterial resistance. PMID:23542952

β-Liddle mutation of the epithelial sodium channel increases alveolar fluid clearance and reduces the severity of hydrostatic pulmonary oedema in mice

PubMed Central

Randrianarison, Nadia; Escoubet, Brigitte; Ferreira, Chrystophe; Fontayne, Alexandre; Fowler-Jaeger, Nicole; Clerici, Christine; Hummler, Edith; Rossier, Bernard C; Planès, Carole

2007-01-01

Transepithelial sodium transport via alveolar epithelial Na+ channels and Na+,K+-ATPase constitutes the driving force for removal of alveolar oedema fluid. Decreased activity of the amiloride-sensitive epithelial Na+ channel (ENaC) in the apical membrane of alveolar epithelial cells impairs sodium-driven alveolar fluid clearance (AFC) and predisposes to pulmonary oedema. We hypothesized that hyperactivity of ENaC in the distal lung could improve AFC and facilitate the resolution of pulmonary oedema. AFC and lung fluid balance were studied at baseline and under conditions of hydrostatic pulmonary oedema in the β-Liddle (L) mouse strain harbouring a gain-of-function mutation (R566stop) within the Scnn1b gene. As compared with wild-type (+/+), baseline AFC was increased by 2- and 3-fold in heterozygous (+/L) and homozygous mutated (L/L) mice, respectively, mainly due to increased amiloride-sensitive AFC. The β2-agonist terbutaline stimulated AFC in +/+ and +/L mice, but not in L/L mice. Acute volume overload induced by saline infusion (40% of body weight over 2 h) significantly increased extravascular (i.e. interstitial and alveolar) lung water as assessed by the bloodless wet-to-dry lung weight ratio in +/+ and L/L mice, as compared with baseline. However, the increase was significantly larger in +/+ than in L/L groups (P= 0.01). Volume overload also increased the volume of the alveolar epithelial lining fluid in +/+ mice, indicating the presence of alveolar oedema, but not in L/L mice. Cardiac function as evaluated by echocardiography was comparable in both groups. These data show that constitutive ENaC activation improved sodium-driven AFC in the mouse lung, and attenuated the severity of hydrostatic pulmonary oedema. PMID:17430990

Self-equilibration of the radius distribution in self-catalyzed GaAs nanowires

NASA Astrophysics Data System (ADS)

Leshchenko, E. D.; Turchina, M. A.; Dubrovskii, V. G.

2016-08-01

This work addresses the evolution of radius distribution function in self-catalyzed vapor-liquid-solid growth of GaAs nanowires from Ga droplets. Different growth regimes are analyzed depending on the V/III flux ratio. In particular, we find a very unusual selfequilibration regime in which the radius distribution narrows up to a certain stationary radius regardless of the initial size distribution of Ga droplets. This requires that the arsenic vapor flux is larger than the gallium one and that the V/III influx imbalance is compensated by a diffusion flux of gallium adatoms. Approximate analytical solution is compared to the numerical radius distribution obtained by solving the corresponding Fokker-Planck equation by the implicit difference scheme.

Combined point and distributed techniques for multidimensional estimation of spatial groundwater-stream water exchange in a heterogeneous sand bed-stream.

NASA Astrophysics Data System (ADS)

Gaona Garcia, J.; Lewandowski, J.; Bellin, A.

2017-12-01

Groundwater-stream water interactions in rivers determine water balances, but also chemical and biological processes in the streambed at different spatial and temporal scales. Due to the difficult identification and quantification of gaining, neutral and losing conditions, it is necessary to combine techniques with complementary capabilities and scale ranges. We applied this concept to a study site at the River Schlaube, East Brandenburg-Germany, a sand bed stream with intense sediment heterogeneity and complex environmental conditions. In our approach, point techniques such as temperature profiles of the streambed together with vertical hydraulic gradients provide data for the estimation of fluxes between groundwater and surface water with the numerical model 1DTempPro. On behalf of distributed techniques, fiber optic distributed temperature sensing identifies the spatial patterns of neutral, down- and up-welling areas by analysis of the changes in the thermal patterns at the streambed interface under certain flow. The study finally links point and surface temperatures to provide a method for upscaling of fluxes. Point techniques provide point flux estimates with essential depth detail to infer streambed structures while the results hardly represent the spatial distribution of fluxes caused by the heterogeneity of streambed properties. Fiber optics proved capable of providing spatial thermal patterns with enough resolution to observe distinct hyporheic thermal footprints at multiple scales. The relation of thermal footprint patterns and temporal behavior with flux results from point techniques enabled the use of methods for spatial flux estimates. The lack of detailed information of the physical driver's spatial distribution restricts the spatial flux estimation to the application of the T-proxy method, whose highly uncertain results mainly provide coarse spatial flux estimates. The study concludes that the upscaling of groundwater-stream water interactions using thermal measurements with combined point and distributed techniques requires the integration of physical drivers because of the heterogeneity of the flux patterns. Combined experimental and modeling approaches may help to obtain more reliable understanding of groundwater-surface water interactions at multiple scales.

[Spectra and thermal analysis of the arc in activating flux plasma arc welding].

PubMed

Chai, Guo-Ming; Zhu, Yi-Feng

2010-04-01

In activating flux plasma arc welding the welding arc was analyzed by spectra analysis technique, and the welding arc temperature field was measured by the infrared sensing and computer image technique. The distribution models of welding arc heat flow density of activating flux PAW welding were developed. The composition of welding arc affected by activated flux was studied, and the welding arc temperature field was studied. The results show that the spectral lines of argon atom and ionized argon atom of primary ionization are the main spectra lines of the conventional plasma welding arc. The spectra lines of weld metal are inappreciable in the spectra lines of the conventional plasma welding arc. The gas particle is the main in the conventional plasma welding arc. The conventional plasma welding arc is gas welding arc. The spectra lines of argon atom and ionized argon atom of primary ionization are intensified in the activating flux plasma welding arc, and the spectra lines of Ti, Cr and Fe elements are found in the activating flux plasma welding arc. The welding arc temperature distribution in activating flux plasma arc welding is compact, the outline of the welding arc temperature field is narrow, the range of the welding arc temperature distribution is concentrated, the welding arc radial temperature gradient is large, and the welding arc radial temperature gradient shows normal Gauss distribution.

A mobile ferromagnetic shape detection sensor using a Hall sensor array and magnetic imaging.

PubMed

Misron, Norhisam; Shin, Ng Wei; Shafie, Suhaidi; Marhaban, Mohd Hamiruce; Mailah, Nashiren Farzilah

2011-01-01

This paper presents a mobile Hall sensor array system for the shape detection of ferromagnetic materials that are embedded in walls or floors. The operation of the mobile Hall sensor array system is based on the principle of magnetic flux leakage to describe the shape of the ferromagnetic material. Two permanent magnets are used to generate the magnetic flux flow. The distribution of magnetic flux is perturbed as the ferromagnetic material is brought near the permanent magnets and the changes in magnetic flux distribution are detected by the 1-D array of the Hall sensor array setup. The process for magnetic imaging of the magnetic flux distribution is done by a signal processing unit before it displays the real time images using a netbook. A signal processing application software is developed for the 1-D Hall sensor array signal acquisition and processing to construct a 2-D array matrix. The processed 1-D Hall sensor array signals are later used to construct the magnetic image of ferromagnetic material based on the voltage signal and the magnetic flux distribution. The experimental results illustrate how the shape of specimens such as square, round and triangle shapes is determined through magnetic images based on the voltage signal and magnetic flux distribution of the specimen. In addition, the magnetic images of actual ferromagnetic objects are also illustrated to prove the functionality of mobile Hall sensor array system for actual shape detection. The results prove that the mobile Hall sensor array system is able to perform magnetic imaging in identifying various ferromagnetic materials.

A Mobile Ferromagnetic Shape Detection Sensor Using a Hall Sensor Array and Magnetic Imaging

PubMed Central

Misron, Norhisam; Shin, Ng Wei; Shafie, Suhaidi; Marhaban, Mohd Hamiruce; Mailah, Nashiren Farzilah

2011-01-01

This paper presents a Mobile Hall Sensor Array system for the shape detection of ferromagnetic materials that are embedded in walls or floors. The operation of the Mobile Hall Sensor Array system is based on the principle of magnetic flux leakage to describe the shape of the ferromagnetic material. Two permanent magnets are used to generate the magnetic flux flow. The distribution of magnetic flux is perturbed as the ferromagnetic material is brought near the permanent magnets and the changes in magnetic flux distribution are detected by the 1-D array of the Hall sensor array setup. The process for magnetic imaging of the magnetic flux distribution is done by a signal processing unit before it displays the real time images using a netbook. A signal processing application software is developed for the 1-D Hall sensor array signal acquisition and processing to construct a 2-D array matrix. The processed 1-D Hall sensor array signals are later used to construct the magnetic image of ferromagnetic material based on the voltage signal and the magnetic flux distribution. The experimental results illustrate how the shape of specimens such as square, round and triangle shapes is determined through magnetic images based on the voltage signal and magnetic flux distribution of the specimen. In addition, the magnetic images of actual ferromagnetic objects are also illustrated to prove the functionality of Mobile Hall Sensor Array system for actual shape detection. The results prove that the Mobile Hall Sensor Array system is able to perform magnetic imaging in identifying various ferromagnetic materials. PMID:22346653

#2) Enantiomer Specific Measurements of Current-use Pesticides in Aquatic Systems

EPA Science Inventory

Research has shown that current-use pesticides can enter urban and agricultural watersheds and adversely affect aquatic organisms. A potential cause may be higher concentrations of the more toxic pesticide enantiomer present in the pesticide mixture. The presence of pesticide ena...

Enantiomer Specific Measurements of Current-use Pesticides in Aquatic Systems (#2)

EPA Science Inventory

Research has shown that current-use pesticides can enter urban and agricultural watersheds and adversely affect aquatic organisms. A potential cause may be higher concentrations of the more toxic pesticide enantiomer present in the pesticide mixture. The presence of pesticide ena...

Using a spatially-distributed hydrologic biogeochemistry model to study the spatial variation of carbon processes in a Critical Zone Observatory

NASA Astrophysics Data System (ADS)

Shi, Y.; Eissenstat, D. M.; Davis, K. J.; He, Y.

2016-12-01

Forest carbon processes are affected by, among other factors, soil moisture, soil temperature, soil nutrients and solar radiation. Most of the current biogeochemical models are 1-D and represent one point in space. Therefore, they cannot resolve the topographically driven hill-slope land surface heterogeneity or the spatial pattern of nutrient availability. A spatially distributed forest ecosystem model, Flux-PIHM-BGC, has been developed by coupling a 1-D mechanistic biogeochemical model Biome-BGC (BBGC) with a spatially distributed land surface hydrologic model, Flux-PIHM. Flux-PIHM is a coupled physically based model, which incorporates a land-surface scheme into the Penn State Integrated Hydrologic Model (PIHM). The land surface scheme is adapted from the Noah land surface model. Flux-PIHM is able to represent the link between groundwater and the surface energy balance, as well as the land surface heterogeneities caused by topography. In the coupled Flux-PIHM-BGC model, each Flux-PIHM model grid couples a 1-D BBGC model, while soil nitrogen is transported among model grids via subsurface water flow. In each grid, Flux-PIHM provides BBGC with soil moisture, soil temperature, and solar radiation information, while BBGC provides Flux-PIHM with leaf area index. The coupled Flux-PIHM-BGC model has been implemented at the Susquehanna/Shale Hills critical zone observatory (SSHCZO). Model results suggest that the vegetation and soil carbon distribution is primarily constrained by nitorgen availability (affected by nitorgen transport via topographically driven subsurface flow), and also constrained by solar radiation and root zone soil moisture. The predicted vegetation and soil carbon distribution generally agrees with the macro pattern observed within the watershed. The coupled ecosystem-hydrologic model provides an important tool to study the impact of topography on watershed carbon processes, as well as the impact of climate change on water resources.

Genetics of Taste Receptors

PubMed Central

Bachmanov, Alexander A.; Bosak, Natalia P.; Lin, Cailu; Matsumoto, Ichiro; Ohmoto, Makoto; Reed, Danielle R.; Nelson, Theodore M.

2016-01-01

Taste receptors function as one of the interfaces between internal and external milieus. Taste receptors for sweet and umami (T1R [taste receptor, type 1]), bitter (T2R [taste receptor, type 2]), and salty (ENaC [epithelial sodium channel]) have been discovered in the recent years, but transduction mechanisms of sour taste and ENaC-independent salt taste are still poorly understood. In addition to these five main taste qualities, the taste system detects such noncanonical “tastes” as water, fat, and complex carbohydrates, but their reception mechanisms require further research. Variations in taste receptor genes between and within vertebrate species contribute to individual and species differences in taste-related behaviors. These variations are shaped by evolutionary forces and reflect species adaptations to their chemical environments and feeding ecology. Principles of drug discovery can be applied to taste receptors as targets in order to develop novel taste compounds to satisfy demand in better artificial sweeteners, enhancers of sugar and sodium taste, and blockers of bitterness of food ingredients and oral medications. PMID:23886383

Tes, a specific Mena interacting partner, breaks the rules for EVH1 binding.

PubMed

Boëda, Batiste; Briggs, David C; Higgins, Theresa; Garvalov, Boyan K; Fadden, Andrew J; McDonald, Neil Q; Way, Michael

2007-12-28

The intracellular targeting of Ena/VASP family members is achieved via the interaction of their EVH1 domain with FPPPP sequence motifs found in a variety of cytoskeletal proteins, including lamellipodin, vinculin, and zyxin. Here we show that the LIM3 domain of Tes, which lacks the FPPPP motif, binds to the EVH1 domain of Mena, but not to those of VASP or Evl. The structure of the LIM3:EVH1 complex reveals that Tes occludes the FPPPP-binding site and competes with FPPPP-containing proteins for EVH1 binding. Structure-based gain-of-function experiments define the molecular basis for the specificity of the Tes-Mena interaction. Consistent with in vitro observations, the LIM3 domain displaces Mena, but not VASP, from the leading edge and focal adhesions. It also regulates cell migration through a Mena-dependent mechanism. Our observations identify Tes as an atypical EVH1 binding partner and a regulator specific to a single Ena/VASP family member.

Identification of best particle radiation shielded region through Energetic Neutral Atoms mapping

NASA Astrophysics Data System (ADS)

Milillo, A.; De Angelis, E.; Mura, A.; Orsini, S.; Mangano, V.; Massetti, S.; Rispoli, R.; Lazzarotto, F.; Vertolli, N.; Lavagna, M.; Ferrari, F.; Lunghi, P.; Attinà, P.; Parissenti, G.

2017-09-01

The lunar surface is directly exposed either to direct solar wind, or to Earth's magnetospheric plasma due to the Moon's lack of a magnetosphere or a dense atmosphere. This exposure could create inhospitable conditions for a possible human presence on the Moon, so it is crucial to investigate the close-to-surface environment for establishing the best reliable locations for future human bases. Although it lacks a global magnetic field, the Moon possesses magnetic anomalies that create mini-magnetospheres, where the solar wind is partly deflected. The local protection of the surface from the solar wind radiation inside the mini-magnetospheres could make these sites preferred for future lunar colonization. It is crucial a detailed characterization of these sites. In this paper, an investigation based on the detection of Energetic Neutral Atoms (ENA) from the surface for identifying the best particle radiation shielded region is proposed. A high spatial resolution mapping via ENA is a feasible and it is powerful way for reaching this goal.

Channel-transporter complexes: an emerging theme in cell signaling.

PubMed

Abbott, Geoffrey W

2016-11-01

In a recent edition of Biochemical Journal, Mistry et al. described the discovery of a novel protein complex, formed from the epithelial sodium channel (ENaC) and the sodium chloride cotransporter (NCC) [Mistry et al. (2016) Biochem. J. 473, 3237–3252]. The importance of these two proteins in the regulation of salt balance and blood pressure has long been known, as has their overlapping expression in the distal convoluted tubule of the kidney. The new study by Mistry et al. now demonstrates their physical interaction in the kidney and when heterologously co-expressed. Furthermore, the authors demonstrate some degree of functional co-dependence between ENaC and NCC, with pharmacological inhibition of the latter diminishing activity of the former when the two are co-assembled. This novel and potentially important interaction adds to a growing number of recently identified channel-transporter ('chansporter') complexes, which together constitute an emerging theme in cell signaling. © 2016 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

A Mena invasion isoform potentiates EGF-induced carcinoma cell invasion and metastasis.

PubMed

Philippar, Ulrike; Roussos, Evanthia T; Oser, Matthew; Yamaguchi, Hideki; Kim, Hyung-Do; Giampieri, Silvia; Wang, Yarong; Goswami, Sumanta; Wyckoff, Jeffrey B; Lauffenburger, Douglas A; Sahai, Erik; Condeelis, John S; Gertler, Frank B

2008-12-01

The spread of cancer during metastatic disease requires that tumor cells subvert normal regulatory networks governing cell motility to invade surrounding tissues and migrate toward blood and lymphatic vessels. Enabled (Ena)/vasodilator-stimulated phosphoprotein (VASP) proteins regulate cell motility by controlling the geometry of assembling actin networks. Mena, an Ena/VASP protein, is upregulated in the invasive subpopulation of breast cancer cells. In addition, Mena is alternately spliced to produce an invasion isoform, Mena(INV). Here we show that Mena and Mena(INV) promote carcinoma cell motility and invasiveness in vivo and in vitro, and increase lung metastasis. Mena and Mena(INV) potentiate epidermal growth factor (EGF)-induced membrane protrusion and increase the matrix degradation activity of tumor cells. Interestingly, Mena(INV) is significantly more effective than Mena in driving metastases and sensitizing cells to EGF-dependent invasion and protrusion. Upregulation of Mena(INV) could therefore enable tumor cells to invade in response to otherwise benign EGF stimulus levels.

The current impact flux on Mars and its seasonal variation

NASA Astrophysics Data System (ADS)

JeongAhn, Youngmin; Malhotra, Renu

2015-12-01

We calculate the present-day impact flux on Mars and its variation over the martian year, using the current data on the orbital distribution of known Mars-crossing minor planets. We adapt the Öpik-Wetherill formulation for calculating collision probabilities, paying careful attention to the non-uniform distribution of the perihelion longitude and the argument of perihelion owed to secular planetary perturbations. We find that, at the current epoch, the Mars crossers have an axial distribution of the argument of perihelion, and the mean direction of their eccentricity vectors is nearly aligned with Mars' eccentricity vector. These previously neglected angular non-uniformities have the effect of depressing the mean annual impact flux by a factor of about 2 compared to the estimate based on a uniform random distribution of the angular elements of Mars-crossers; the amplitude of the seasonal variation of the impact flux is likewise depressed by a factor of about 4-5. We estimate that the flux of large impactors (of absolute magnitude H < 16) within ±30° of Mars' aphelion is about three times larger than when the planet is near perihelion. Extrapolation of our results to a model population of meter-size Mars-crossers shows that if these small impactors have a uniform distribution of their angular elements, then their aphelion-to-perihelion impact flux ratio would be 11-15, but if they track the orbital distribution of the large impactors, including their non-uniform angular elements, then this ratio would be about 3. Comparison of our results with the current dataset of fresh impact craters on Mars (detected with Mars-orbiting spacecraft) appears to rule out the uniform distribution of angular elements.

IBEX-lo Sky Maps of Secondary Interstellar Neutrals Helium and Oxygen

NASA Astrophysics Data System (ADS)

Kucharek, H.; Isenberg, P. A.; Jeewoo, P.; Kubiak, M. A.; Bzowski, M.

2017-12-01

There are several populations of heliospheric energetic neutral atoms (ENAs) generated at the various heliospheric interfaces, the inner heliosheath, outer heliosheath (OHS), and the termination shock (TS). Depending on where and how these ENAs are generated, they belong to different energy regimes. While interstellar neutral (ISN) particles flow through the heliospheric boundary is mostly unimpeded, a substantial fraction of ISN H and O is filtered through charge exchange with ambient plasma ions before reaching the TS. Secondary ISN atoms are generated by the charge exchange reaction between primary ISN atoms and interstellar ions in the outer heliosheath, forming walls of H and O in front of the heliopause (HP). The flowing interstellar plasma encounters the heliopause as an obstacle, which deflects the flow. Thus, secondary neutrals measured at 1 AU carry information about the deflected interstellar plasma and the shape of the heliopause that causes the deflection. Due to very different magnitudes of charge exchange cross sections, the main source of the secondary He is charge exchange with the OHS He+, while that of the secondary O is the charge exchange between interstellar O+ and the OHS H. Therefore, the oxygen results are drastically different from those of helium. Interstellar O+ ions behave in principle like the He+ particles with an over-density due to the plasma deceleration. The high density decelerated oxygen ions just upwind of the heliopause encounter an over-density in neutral hydrogen, the hydrogen wall, allowing frequent charge exchange that produce slow neutral oxygen atoms forming the oxygen wall. Thus, the distribution in the sky maps of secondary He and O carries information on the shape as well as the structures in front of it. To investigate the secondary component of the interstellar neutral in detail we have distinguish between the two secondary component's. We engaged theory and simulations for the primary and secondary components to determine differences of between measurements and model predicted data.

Cellular distribution and function of ion channels involved in transport processes in rat tracheal epithelium.

PubMed

Hahn, Anne; Faulhaber, Johannes; Srisawang, Lalita; Stortz, Andreas; Salomon, Johanna J; Mall, Marcus A; Frings, Stephan; Möhrlen, Frank

2017-06-01

Transport of water and electrolytes in airway epithelia involves chloride-selective ion channels, which are controlled either by cytosolic Ca 2+ or by cAMP The contributions of the two pathways to chloride transport differ among vertebrate species. Because rats are becoming more important as animal model for cystic fibrosis, we have examined how Ca 2+ - dependent and cAMP- dependent Cl - secretion is organized in the rat tracheal epithelium. We examined the expression of the Ca 2+ -gated Cl - channel anoctamin 1 (ANO1), the cystic fibrosis transmembrane conductance regulator (CFTR) Cl - channel, the epithelial Na + channel ENaC, and the water channel aquaporin 5 (AQP5) in rat tracheal epithelium. The contribution of ANO1 channels to nucleotide-stimulated Cl - secretion was determined using the channel blocker Ani9 in short-circuit current recordings obtained from primary cultures of rat tracheal epithelial cells in Ussing chambers. We found that ANO1, CFTR and AQP5 proteins were expressed in nonciliated cells of the tracheal epithelium, whereas ENaC was expressed in ciliated cells. Among nonciliated cells, ANO1 occurred together with CFTR and Muc5b and, in addition, in a different cell type without CFTR and Muc5b. Bioelectrical studies with the ANO1-blocker Ani9 indicated that ANO1 mediated the secretory response to the nucleotide uridine-5'-triphosphate. Our data demonstrate that, in rat tracheal epithelium, Cl - secretion and Na + absorption are routed through different cell types, and that ANO1 channels form the molecular basis of Ca 2+ -dependent Cl - secretion in this tissue. These characteristic features of Cl - -dependent secretion reveal similarities and distinct differences to secretory processes in human airways. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Cassini/MIMI Science Today and Tomorrow

NASA Astrophysics Data System (ADS)

Mitchell, D. G.

2014-12-01

Between Saturn Orbit Insertion in July 2004 and the present, the Magnetospheric IMaging Instrument (MIMI) on the Cassini spacecraft has measured electrons and ions (energies ~5 keV to over 10 MeV and energetic neutrals (energies ~5 - 200 keV) throughout Saturn's magnetosphere including Saturn's bow shock and magnetopause, plasma sheet, magnetotail, and cis-moon spaces. MIMI observations have included auroral acceleration, magnetotail reconnection, global and local-scale injection events, identifications of charged particle species,, dual and multiple periodicities associated with planetary rotation, and the seasonal variations of many of these phenomena. Most recent MIMI investigations have shown (1) short-period charged-particle oscillations (~1 hour) at high latitude are associated with similar magnetic field, radio, and aurora variations (2) quasi-periodic relativistic electron injection in Saturn's outer magnetosphere, (3) modeling of radiation belt particles to explain their distribution and energy spectrum, and to anticipate the population inside the D-ring, (4) continuing the imaging of energetic neutral atoms (ENAs) from the heliosheath and beyond, (5) characterizing the interaction of Titan with the un-shocked solar wind, (6) deep tail observations supporting the "bowl model" of plasma sheet curvature, (7) asymmetries in the charged particles that are associated with a still-unexplained noon-midnight electric field, (8) local time variations in the energetic particle periodicities, (9) and signatures of satellite-magnetosphere interactions and their implications for both the body and the whole system. During the final sets of orbits of the Cassini Mission at Saturn (dubbed the Grand Finale, which includes the F-ring—periapsis outside the F-ring—and the Proximal Orbits—periapsis between the innermost D-ring and the atmosphere), MIMI will make the first-ever measurements of the innermost radiation belts of Saturn, detailed ENA imaging of charged particle acceleration above the high-latitude polar caps, composition of any energetic plasma between the rings and the ionosphere, and evidence for coupling between the rings, ionosphere, and magnetosphere.

Systems with a constant heat flux with applications to radiative heat transport across nanoscale gaps and layers

NASA Astrophysics Data System (ADS)

Budaev, Bair V.; Bogy, David B.

2018-06-01

We extend the statistical analysis of equilibrium systems to systems with a constant heat flux. This extension leads to natural generalizations of Maxwell-Boltzmann's and Planck's equilibrium energy distributions to energy distributions of systems with a net heat flux. This development provides a long needed foundation for addressing problems of nanoscale heat transport by a systematic method based on a few fundamental principles. As an example, we consider the computation of the radiative heat flux between narrowly spaced half-spaces maintained at different temperatures.

The distribution of ion orbit loss fluxes of ions and energy from the plasma edge across the last closed flux surface into the scrape-off layer

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

Stacey, Weston M.; Schumann, Matthew T.

A more detailed calculation strategy for the evaluation of ion orbit loss of thermalized plasma ions in the edge of tokamaks is presented. In both this and previous papers, the direct loss of particles from internal flux surfaces is calculated from the conservation of canonical angular momentum, energy, and magnetic moment. The previous result that almost all of the ion energy and particle fluxes crossing the last closed flux surface are in the form of ion orbit fluxes is confirmed, and the new result that the distributions of these fluxes crossing the last closed flux surface into the scrape-off layermore » are very strongly peaked about the outboard midplane is demonstrated. Previous results of a preferential loss of counter current particles leading to a co-current intrinsic rotation peaking just inside of the last closed flux surface are confirmed. Various physical details are discussed.« less

Tropical Gravity Wave Momentum Fluxes and Latent Heating Distributions

NASA Technical Reports Server (NTRS)

Geller, Marvin A.; Zhou, Tiehan; Love, Peter T.

2015-01-01

Recent satellite determinations of global distributions of absolute gravity wave (GW) momentum fluxes in the lower stratosphere show maxima over the summer subtropical continents and little evidence of GW momentum fluxes associated with the intertropical convergence zone (ITCZ). This seems to be at odds with parameterizations forGWmomentum fluxes, where the source is a function of latent heating rates, which are largest in the region of the ITCZ in terms of monthly averages. The authors have examined global distributions of atmospheric latent heating, cloud-top-pressure altitudes, and lower-stratosphere absolute GW momentum fluxes and have found that monthly averages of the lower-stratosphere GW momentum fluxes more closely resemble the monthly mean cloud-top altitudes rather than the monthly mean rates of latent heating. These regions of highest cloud-top altitudes occur when rates of latent heating are largest on the time scale of cloud growth. This, plus previously published studies, suggests that convective sources for stratospheric GW momentum fluxes, being a function of the rate of latent heating, will require either a climate model to correctly model this rate of latent heating or some ad hoc adjustments to account for shortcomings in a climate model's land-sea differences in convective latent heating.

Dynamics of low- and high-Z metal ions emitted during nanosecond laser-produced plasmas

NASA Astrophysics Data System (ADS)

Elsied, Ahmed M.; Diwakar, Prasoon K.; Polek, Mathew; Hassanein, Ahmed

2016-11-01

Dynamics of metal ions during laser-produced plasmas was studied. A 1064 nm, Nd: YAG laser pulse was used to ablate pure Al, Fe, Co, Mo, and Sn samples. Ion flux and velocity were measured using Faraday cup ion collector. Time-of-flight measurements showed decreasing ion flux and ion velocity with increasing atomic weight, and heavy metal ion flux profile exhibited multiple peaks that was not observed in lighter metals. Slow peak was found to follow shifted Maxwell Boltzmann distribution, while the fast peak was found to follow Gaussian distribution. Ion flux angular distribution that was carried out on Mo and Al using fixed laser intensity 2.5 × 1010 W/cm2 revealed that the slow ion flux peaks at small angles, that is, close to normal to the target ˜0° independent of target's atomic weight, and fast ion flux for Mo peaks at large angles ˜40° measured from the target normal, while it completely absents for Al. This difference in spatial and temporal distribution reveals that the emission mechanism of the fast and slow ions is different. From the slow ion flux angular distribution, the measured plume expansion ratio (plume forward peaking) was 1.90 and 2.10 for Al and Mo, respectively. Moreover, the effect of incident laser intensity on the ion flux emission as well as the emitted ion velocity were investigated using laser intensities varying from 2.5 × 1010 W/cm2 to 1.0 × 1011 W/cm2. Linear increase of fast ion flux and velocity, and quadratic increase of slow ion flux and velocity were observed. For further understanding of plume dynamics, laser optical emission spectroscopy was used to characterize Sn plasma by measuring the temporal and spatial evolution of plasma electron density Ne and electron temperature Te. At 3.5 mm away from the target, plasma density showed slow decrease with time, however electron temperature was observed to decrease dramatically. The maximum plasma density and temperature occurred at 0.5 mm away from target and were measured to be 8.0 × 1017 cm-3 and 1.3 eV, respectively.

Representation of the Geosynchronous Plasma Environment in Spacecraft Charging Calculations

NASA Technical Reports Server (NTRS)

Davis, V. A.; Mandell, M. J.; Thomsen, M. F.

2006-01-01

Historically, our ability to predict and postdict spacecraft surface charging has been limited by the characterization of the plasma environment. One difficulty lies in the common practice of fitting the plasma data to a Maxwellian or Double Maxwellian distribution function, which may not represent the data well for charging purposes. We use electron and ion flux spectra measured by the Los Alamos National Laboratory (LANL) Magnetospheric Plasma Analyzer (MPA) to examine how the use of different spectral representations of the charged particle environment in computations of spacecraft potentials during magnetospheric substorms affects the accuracy of the results. We calculate the spacecraft potential using both the measured fluxes and several different fits to these fluxes. These measured fluxes have been corrected for the difference between the measured and calculated potential. The potential computed using the measured fluxes and the best available material properties of graphite carbon, with a secondary electron escape fraction of 81%, is within a factor of three of the measured potential for 87% of the data. Potentials calculated using a Kappa function fit to the incident electron flux distribution function and a Maxwellian function fit to the incident ion flux distribution function agree with measured potentials nearly as well as do potentials calculated using the measured fluxes. Alternative spectral representations gave less accurate estimates of potential. The use of all the components of the net flux, along with spacecraft specific average material properties, gives a better estimate of the spacecraft potential than the high energy flux alone.

Comparison between measured and computed magnetic flux density distribution of simulated transformer core joints assembled from grain-oriented and non-oriented electrical steel

NASA Astrophysics Data System (ADS)

Shahrouzi, Hamid; Moses, Anthony J.; Anderson, Philip I.; Li, Guobao; Hu, Zhuochao

2018-04-01

The flux distribution in an overlapped linear joint constructed in the central region of an Epstein Square was studied experimentally and results compared with those obtained using a computational magnetic field solver. High permeability grain-oriented (GO) and low permeability non-oriented (NO) electrical steels were compared at a nominal core flux density of 1.60 T at 50 Hz. It was found that the experimental results only agreed well at flux densities at which the reluctance of different paths of the flux are similar. Also it was revealed that the flux becomes more uniform when the working point of the electrical steel is close to the knee point of the B-H curve of the steel.

Characteristics of Low-latitude Coronal Holes near the Maximum of Solar Cycle 24

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

Hofmeister, Stefan J.; Veronig, Astrid; Reiss, Martin A.

We investigate the statistics of 288 low-latitude coronal holes extracted from SDO /AIA-193 filtergrams over the time range of 2011 January 01–2013 December 31. We analyze the distribution of characteristic coronal hole properties, such as the areas, mean AIA-193 intensities, and mean magnetic field densities, the local distribution of the SDO /AIA-193 intensity and the magnetic field within the coronal holes, and the distribution of magnetic flux tubes in coronal holes. We find that the mean magnetic field density of all coronal holes under study is 3.0 ± 1.6 G, and the percentaged unbalanced magnetic flux is 49 ± 16%.more » The mean magnetic field density, the mean unsigned magnetic field density, and the percentaged unbalanced magnetic flux of coronal holes depend strongly pairwise on each other, with correlation coefficients cc > 0.92. Furthermore, we find that the unbalanced magnetic flux of the coronal holes is predominantly concentrated in magnetic flux tubes: 38% (81%) of the unbalanced magnetic flux of coronal holes arises from only 1% (10%) of the coronal hole area, clustered in magnetic flux tubes with field strengths >50 G (10 G). The average magnetic field density and the unbalanced magnetic flux derived from the magnetic flux tubes correlate with the mean magnetic field density and the unbalanced magnetic flux of the overall coronal hole (cc>0.93). These findings give evidence that the overall magnetic characteristics of coronal holes are governed by the characteristics of the magnetic flux tubes.« less

A model for the flux-r.m.s. correlation in blazar variability or the minijets-in-a-jet statistical model

NASA Astrophysics Data System (ADS)

Biteau, J.; Giebels, B.

2012-12-01

Very high energy gamma-ray variability of blazar emission remains of puzzling origin. Fast flux variations down to the minute time scale, as observed with H.E.S.S. during flares of the blazar PKS 2155-304, suggests that variability originates from the jet, where Doppler boosting can be invoked to relax causal constraints on the size of the emission region. The observation of log-normality in the flux distributions should rule out additive processes, such as those resulting from uncorrelated multiple-zone emission models, and favour an origin of the variability from multiplicative processes not unlike those observed in a broad class of accreting systems. We show, using a simple kinematic model, that Doppler boosting of randomly oriented emitting regions generates flux distributions following a Pareto law, that the linear flux-r.m.s. relation found for a single zone holds for a large number of emitting regions, and that the skewed distribution of the total flux is close to a log-normal, despite arising from an additive process.

Reconstructing metabolic flux vectors from extreme pathways: defining the alpha-spectrum.

PubMed

Wiback, Sharon J; Mahadevan, Radhakrishnan; Palsson, Bernhard Ø

2003-10-07

The move towards genome-scale analysis of cellular functions has necessitated the development of analytical (in silico) methods to understand such large and complex biochemical reaction networks. One such method is extreme pathway analysis that uses stoichiometry and thermodynamic irreversibly to define mathematically unique, systemic metabolic pathways. These extreme pathways form the edges of a high-dimensional convex cone in the flux space that contains all the attainable steady state solutions, or flux distributions, for the metabolic network. By definition, any steady state flux distribution can be described as a nonnegative linear combination of the extreme pathways. To date, much effort has been focused on calculating, defining, and understanding these extreme pathways. However, little work has been performed to determine how these extreme pathways contribute to a given steady state flux distribution. This study represents an initial effort aimed at defining how physiological steady state solutions can be reconstructed from a network's extreme pathways. In general, there is not a unique set of nonnegative weightings on the extreme pathways that produce a given steady state flux distribution but rather a range of possible values. This range can be determined using linear optimization to maximize and minimize the weightings of a particular extreme pathway in the reconstruction, resulting in what we have termed the alpha-spectrum. The alpha-spectrum defines which extreme pathways can and cannot be included in the reconstruction of a given steady state flux distribution and to what extent they individually contribute to the reconstruction. It is shown that accounting for transcriptional regulatory constraints can considerably shrink the alpha-spectrum. The alpha-spectrum is computed and interpreted for two cases; first, optimal states of a skeleton representation of core metabolism that include transcriptional regulation, and second for human red blood cell metabolism under various physiological, non-optimal conditions.

The Multileveled Regulation of the Human Cholinesterase Genes and Their Protein Products

DTIC Science & Technology

1993-09-30

s that are involved in binding and penetration of ligands. In essence , binding affinity consists of ligand penetration in addition to its binding to...J. Cell Biol. 110, 715-719. Rotundo RL, Jasmin BJ, Lee RK, Rossi SG (1992) Compartmentalization of acetylcholinesterase mENA and protein expression

Using a spatially-distributed hydrologic biogeochemistry model with a nitrogen transport module to study the spatial variation of carbon processes in a Critical Zone Observatory

DOE PAGES

Shi, Yuning; Eissenstat, David M.; He, Yuting; ...

2018-05-12

Terrestrial carbon processes are affected by soil moisture, soil temperature, nitrogen availability and solar radiation, among other factors. Most of the current ecosystem biogeochemistry models represent one point in space, and have limited characterization of hydrologic processes. Therefore these models can neither resolve the topographically driven spatial variability of water, energy, and nutrient, nor their effects on carbon processes. A spatially-distributed land surface hydrologic biogeochemistry model, Flux-PIHM-BGC, is developed by coupling the Biome-BGC model with a physically-based land surface hydrologic model, Flux-PIHM. In the coupled system, each Flux-PIHM model grid couples a 1-D Biome-BGC model. In addition, a topographic solarmore » radiation module and an advection-driven nitrogen transport module are added to represent the impact of topography on nutrient transport and solar energy distribution. Because Flux-PIHM is able to simulate lateral groundwater flow and represent the land surface heterogeneities caused by topography, Flux-PIHM-BGC is capable of simulating the complex interaction among water, energy, nutrient, and carbon in time and space. The Flux-PIHM-BGC model is tested at the Susquehanna/Shale Hills Critical Zone Observatory. Model results show that distributions of carbon and nitrogen stocks and fluxes are strongly affected by topography and landscape position, and tree growth is nitrogen limited. The predicted aboveground and soil carbon distributions generally agree with the macro patterns observed. Although the model underestimates the spatial variation, the predicted watershed average values are close to the observations. Lastly, the coupled Flux-PIHM-BGC model provides an important tool to study spatial variations in terrestrial carbon and nitrogen processes and their interactions with environmental factors, and to predict the spatial structure of the responses of ecosystems to climate change.« less

Using a spatially-distributed hydrologic biogeochemistry model with a nitrogen transport module to study the spatial variation of carbon processes in a Critical Zone Observatory

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

Shi, Yuning; Eissenstat, David M.; He, Yuting

Terrestrial carbon processes are affected by soil moisture, soil temperature, nitrogen availability and solar radiation, among other factors. Most of the current ecosystem biogeochemistry models represent one point in space, and have limited characterization of hydrologic processes. Therefore these models can neither resolve the topographically driven spatial variability of water, energy, and nutrient, nor their effects on carbon processes. A spatially-distributed land surface hydrologic biogeochemistry model, Flux-PIHM-BGC, is developed by coupling the Biome-BGC model with a physically-based land surface hydrologic model, Flux-PIHM. In the coupled system, each Flux-PIHM model grid couples a 1-D Biome-BGC model. In addition, a topographic solarmore » radiation module and an advection-driven nitrogen transport module are added to represent the impact of topography on nutrient transport and solar energy distribution. Because Flux-PIHM is able to simulate lateral groundwater flow and represent the land surface heterogeneities caused by topography, Flux-PIHM-BGC is capable of simulating the complex interaction among water, energy, nutrient, and carbon in time and space. The Flux-PIHM-BGC model is tested at the Susquehanna/Shale Hills Critical Zone Observatory. Model results show that distributions of carbon and nitrogen stocks and fluxes are strongly affected by topography and landscape position, and tree growth is nitrogen limited. The predicted aboveground and soil carbon distributions generally agree with the macro patterns observed. Although the model underestimates the spatial variation, the predicted watershed average values are close to the observations. Lastly, the coupled Flux-PIHM-BGC model provides an important tool to study spatial variations in terrestrial carbon and nitrogen processes and their interactions with environmental factors, and to predict the spatial structure of the responses of ecosystems to climate change.« less

Analysis of solar receiver flux distributions for US/Russian solar dynamic system demonstration on the MIR Space Station

NASA Technical Reports Server (NTRS)

Kerslake, Thomas W.; Fincannon, James

1995-01-01

The United States and Russia have agreed to jointly develop a solar dynamic (SD) system for flight demonstration on the Russian MIR space station starting in late 1997. Two important components of this SD system are the solar concentrator and heat receiver provided by Russia and the U.S., respectively. This paper describes optical analysis of the concentrator and solar flux predictions on target receiver surfaces. The optical analysis is performed using the code CIRCE2. These analyses account for finite sun size with limb darkening, concentrator surface slope and position errors, concentrator petal thermal deformation, gaps between petals, and the shading effect of the receiver support struts. The receiver spatial flux distributions are then combined with concentrator shadowing predictions. Geometric shadowing patterns are traced from the concentrator to the target receiver surfaces. These patterns vary with time depending on the chosen MIR flight attitude and orbital mechanics of the MIR spacecraft. The resulting predictions provide spatial and temporal receiver flux distributions for any specified mission profile. The impact these flux distributions have on receiver design and control of the Brayton engine are discussed.

Soil-atmosphere trace gas exchange from tropical oil palm plantations on peat

NASA Astrophysics Data System (ADS)

Arn Teh, Yit; Manning, Frances; Zin Zawawi, Norliyana; Hill, Timothy; Chocholek, Melanie; Khoon Kho, Lip

2015-04-01

Oil palm is the largest agricultural crop in the tropics, accounting for 13 % of all tropical land cover. Due to its large areal extent, oil palm cultivation may have important implications not only for terrestrial stores of C and N, but may also impact regional and global exchanges of material and energy, including fluxes of trace gases and water vapor. In particular, recent expansion of oil palm into tropical peatlands has raised concerns over enhanced soil C emissions from degradation of peat, and elevated N-gas fluxes linked to N fertilizer application. Here we report our preliminary findings on soil carbon dioxide (CO2), methane (CH4) and nitrous oxide (N2O) fluxes from a long-term, multi-scale project investigating the C, N and greenhouse gas (GHG) dynamics of oil palm ecosystems established on peat soils in Sarawak, Malaysian Borneo. Flux chamber measurements indicate that soil CO2, CH4 and N2O fluxes averaged 20.0 ± 16.0 Mg CO2-C ha-1 yr-1, 37.4 ± 29.9 kg CH4-C ha-1 yr-1 and 4.7 ± 4.2 g N2O-N ha-1 yr-1, respectively. Soil CO2 fluxes were on par with other drained tropical peatlands; whereas CH4 fluxes exceeded observations from similar study sites elsewhere. Nitrous oxide fluxes were in a similar range to fluxes from other drained tropical peatlands, but lower than emissions from mineral-soil plantations by up to three orders of magnitude. Fluxes of soil CO2 and N2O were spatially stratified, and contingent upon the distribution of plants, deposited harvest residues, and soil moisture. Soil CO2 fluxes were most heavily influenced by the distribution of palms and their roots. On average, autotrophic (root) respiration accounted for approximately 78 % of total soil CO2 flux, and total soil respiration declined steeply away from palms; e.g. soil CO2 fluxes in the immediate 1 m radius around palms were up to 6 times greater than fluxes in inter-palm spaces due to higher densities of roots. Placement of harvest residues played an important - but secondary - role in modulating soil CO2 fluxes; soil respiration rates doubled in areas where harvest residues were deposited, reflecting an enhanced input of labile organic matter for decomposition. In contrast, N2O fluxes were best-predicted by the distribution of harvest residues, and were only weakly related to plant distributions or soil moisture. For example, N2O fluxes from harvest residue piles were up to twice of the overall plot-average. In contrast, N2O fluxes showed no clear pattern around palms or in inter-palm spaces; this finding is surprising because N fertilizers are applied within the 1 m radius around palms, and we expected to observe enhanced N2O fluxes in areas of greater fertilizer input. This suggests that palms may be a strong competitor for N in these ecosystems, and that fertilizer application may more closely match overall plant demand than in mineral-soil plantations. Overall, the spatial patterning of soil CO2 and N2O fluxes implies that soil biogeochemical processes are predictably distributed in space, potentially making it easier to model and constrain fluxes of these soil-derived GHGs.

The Intensity Distribution for Gamma-Ray Bursts Observed with BATSE

NASA Technical Reports Server (NTRS)

Pendleton, Geoffrey N.; Mallozzi, Robert S.; Paciesas, William S.; Briggs, Michael S.; Preece, Robert D.; Koshut, Tom M.; Horack, John M.; Meegan, Charles A.; Fishman, Gerald J.; Hakkila, Jon;

Seasonal Clear-Sky Flux and Cloud Radiative Effect Anomalies in the Arctic Atmospheric Column Associated with the Arctic Oscillation and Arctic Dipole

NASA Technical Reports Server (NTRS)

Hegyi, Bradley M.; Taylor, Patrick C.

2017-01-01

The impact of the Arctic Oscillation (AO) and Arctic Dipole (AD) on the radiative flux into the Arctic mean atmospheric column is quantified. 3-month-averaged AO and AD indices are regressed with corresponding surface and top-of-atmosphere (TOA) fluxes from the CERES-SFC and CERES-TOA EBAF datasets over the period 2000-2014. An increase in clear-sky fluxes into the Arctic mean atmospheric column during fall is the largest net flux anomaly associated with AO, primarily driven by a positive net longwave flux anomaly (i.e. increase of net flux into the atmospheric column) at the surface. A decrease in the Arctic mean atmospheric column cloud radiative effect during winter and spring is the largest flux anomaly associated with AD, primarily driven by a change in the longwave cloud radiative effect at the surface. These prominent responses to AO and AD are widely distributed across the ice-covered Arctic, suggesting that the physical process or processes that bring about the flux change associated with AO and AD are distributed throughout the Arctic.

Measurement of limiter particle fluxes and carbon erosion in the helical scrape-off layer of startup plasmas at W7-X

NASA Astrophysics Data System (ADS)

Winters, V.; Biedermann, C.; Brezinsek, S.; Effenberg, F.; Frerichs, H.; Harris, J.; Schmitz, O.; Stephey, L.; Unterberg, E.; Wurden, G.; W7-X Team

2016-10-01

Measurement of the 2D recycling flux and calculations of the carbon erosion from the limiter in startup plasmas of W7-X provides a first insight into neutral particle release and impurity inflow into the helical scrape-off layer. H-alpha, C-II (514.5nm) and C-III (465.1nm) line emissions were collected with filter-scopes and a visible camera aimed at limiter 3 of W7-X. Local plasma parameters are considered to estimate physical and chemical sputtering contributions. The analytical model for chemical sputtering by Roth is used to convert the measured particle flux into a chemically eroded C flux. The particle flux as well as the extracted C erosion pattern deviates from the measured heat flux distribution and also from the predicted particle flux distribution from EMC3-EIRENE. Candidates to resolve this discrepancy are measurement uncertainties and physics related (e.g. asymmetry in the last closed flux surface position). Post-mortem analysis of the limiter will be taken into account and compared to these in-situ measurements to gather first detailed insight on the net C erosion distribution and the impurity sourcing into the helical scrape-off layer. This work was funded by DE-SC0014210, DE-AC5206NA25396, DE-AC05-00OR22725 and by EUROfusion under Grant No 633053.

SMALL-SCALE AND GLOBAL DYNAMOS AND THE AREA AND FLUX DISTRIBUTIONS OF ACTIVE REGIONS, SUNSPOT GROUPS, AND SUNSPOTS: A MULTI-DATABASE STUDY

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

Muñoz-Jaramillo, Andrés; Windmueller, John C.; Amouzou, Ernest C.

2015-02-10

In this work, we take advantage of 11 different sunspot group, sunspot, and active region databases to characterize the area and flux distributions of photospheric magnetic structures. We find that, when taken separately, different databases are better fitted by different distributions (as has been reported previously in the literature). However, we find that all our databases can be reconciled by the simple application of a proportionality constant, and that, in reality, different databases are sampling different parts of a composite distribution. This composite distribution is made up by linear combination of Weibull and log-normal distributions—where a pure Weibull (log-normal) characterizesmore » the distribution of structures with fluxes below (above) 10{sup 21}Mx (10{sup 22}Mx). Additionally, we demonstrate that the Weibull distribution shows the expected linear behavior of a power-law distribution (when extended to smaller fluxes), making our results compatible with the results of Parnell et al. We propose that this is evidence of two separate mechanisms giving rise to visible structures on the photosphere: one directly connected to the global component of the dynamo (and the generation of bipolar active regions), and the other with the small-scale component of the dynamo (and the fragmentation of magnetic structures due to their interaction with turbulent convection)« less

Method and system using power modulation for maskless vapor deposition of spatially graded thin film and multilayer coatings with atomic-level precision and accuracy

DOEpatents

Montcalm, Claude [Livermore, CA; Folta, James Allen [Livermore, CA; Tan, Swie-In [San Jose, CA; Reiss, Ira [New City, NY

2002-07-30

A method and system for producing a film (preferably a thin film with highly uniform or highly accurate custom graded thickness) on a flat or graded substrate (such as concave or convex optics), by sweeping the substrate across a vapor deposition source operated with time-varying flux distribution. In preferred embodiments, the source is operated with time-varying power applied thereto during each sweep of the substrate to achieve the time-varying flux distribution as a function of time. A user selects a source flux modulation recipe for achieving a predetermined desired thickness profile of the deposited film. The method relies on precise modulation of the deposition flux to which a substrate is exposed to provide a desired coating thickness distribution.

Validation of absolute axial neutron flux distribution calculations with MCNP with 197Au(n,γ)198Au reaction rate distribution measurements at the JSI TRIGA Mark II reactor.

PubMed

Radulović, Vladimir; Štancar, Žiga; Snoj, Luka; Trkov, Andrej

2014-02-01

The calculation of axial neutron flux distributions with the MCNP code at the JSI TRIGA Mark II reactor has been validated with experimental measurements of the (197)Au(n,γ)(198)Au reaction rate. The calculated absolute reaction rate values, scaled according to the reactor power and corrected for the flux redistribution effect, are in good agreement with the experimental results. The effect of different cross-section libraries on the calculations has been investigated and shown to be minor. Copyright © 2013 Elsevier Ltd. All rights reserved.

Influence of the late winter bloom on migrant zooplankton metabolism and its implications on export fluxes

NASA Astrophysics Data System (ADS)

Putzeys, S.; Yebra, L.; Almeida, C.; Bécognée, P.; Hernández-León, S.

2011-12-01

Studies on carbon active fluxes due to diel migrants are scarce and critical for carbon flux models and biogeochemical estimates. We studied the temporal variability and vertical distribution of biomass, indices of feeding and respiration of the zooplanktonic community north off the Canary Islands during the end of the late winter bloom, in order to assess vertical carbon fluxes in this area. Biomass distribution during the day presented two dense layers of organisms at 0-200 m and around 500 m, whereas at night, most of the biomass concentrated in the epipelagic layer. The gut pigment flux (0.05-0.18 mgC·m - 2 ·d - 1 ) represented 0.22% of the estimated passive export flux (POC flux) while potential ingestion represented 3.91% of the POC (1.24-3.40 mgC·m - 2 ·d - 1 ). The active respiratory flux (0.50-1.36 mgC·m - 2 ·d - 1 ) was only 1.57% of the POC flux. The total carbon flux mediated by diel migrants (respiration plus potential ingestion) ranged between 3.37 and 9.22% of the POC flux; which is three-fold higher than calculating ingestion fluxes from gut pigments. Our results suggest that the fluxes by diel migrants play a small role in the downward flux of carbon in the open ocean during the post-bloom period.

Extreme air-sea surface turbulent fluxes in mid latitudes - estimation, origins and mechanisms

NASA Astrophysics Data System (ADS)

Gulev, Sergey; Natalia, Tilinina

2014-05-01

Extreme turbulent heat fluxes in the North Atlantic and North Pacific mid latitudes were estimated from the modern era and first generation reanalyses (NCEP-DOE, ERA-Interim, MERRA NCEP-CFSR, JRA-25) for the period from 1979 onwards. We used direct surface turbulent flux output as well as reanalysis state variables from which fluxes have been computed using COARE-3 bulk algorithm. For estimation of extreme flux values we analyzed surface flux probability density distribution which was approximated by Modified Fisher-Tippett distribution. In all reanalyses extreme turbulent heat fluxes amount to 1500-2000 W/m2 (for the 99th percentile) and can exceed 2000 W/m2 for higher percentiles in the western boundary current extension (WBCE) regions. Different reanalyses show significantly different shape of MFT distribution, implying considerable differences in the estimates of extreme fluxes. The highest extreme turbulent latent heat fluxes are diagnosed in NCEP-DOE, ERA-Interim and NCEP-CFSR reanalyses with the smallest being in MERRA. These differences may not necessarily reflect the differences in mean values. Analysis shows that differences in statistical properties of the state variables are the major source of differences in the shape of PDF of fluxes and in the estimates of extreme fluxes while the contribution of computational schemes used in different reanalyses is minor. The strongest differences in the characteristics of probability distributions of surface fluxes and extreme surface flux values between different reanalyses are found in the WBCE extension regions and high latitudes. In the next instance we analyzed the mechanisms responsible for forming surface turbulent fluxes and their potential role in changes of midlatitudinal heat balance. Midlatitudinal cyclones were considered as the major mechanism responsible for extreme turbulent fluxes which are typically occur during the cold air outbreaks in the rear parts of cyclones when atmospheric conditions provide locally high winds and air-sea temperature gradients. For this purpose we linked characteristics of cyclone activity over the midlatitudinal oceans with the extreme surface turbulent heat fluxes. Cyclone tracks and parameters of cyclone life cycle (deepening rates, propagation velocities, life time and clustering) were derived from the same reanalyses using state of the art numerical tracking algorithm. The main questions addressed in this study are (i) through which mechanisms extreme surface fluxes are associated with cyclone activity? and (ii) which types of cyclones are responsible for forming extreme turbulent fluxes? Our analysis shows that extreme surface fluxes are typically associated not with cyclones themselves but rather with cyclone-anticyclone interaction zones. This implies that North Atlantic and North Pacific series of intense cyclones do not result in the anomalous surface fluxes. Alternatively, extreme fluxes are most frequently associated with blocking situations, particularly with the intensification of the Siberian and North American Anticyclones providing cold-air outbreaks over WBC regions.

Scaling-up of CO2 fluxes to assess carbon sequestration in rangelands of Central Asia

Treesearch

Bruce K. Wylie; Tagir G. Gilmanov; Douglas A. Johnson; Nicanor Z. Saliendra; Larry L. Tieszen; Ruth Anne F. Doyle; Emilio A. Laca

2006-01-01

Flux towers provide temporal quantification of local carbon dynamics at specific sites. The number and distribution of flux towers, however, are generally inadequate to quantify carbon fluxes across a landscape or ecoregion. Thus, scaling up of flux tower measurements through use of algorithms developed from remote sensing and GIS data is needed for spatial...

The impact of land-surface wetness heterogeneity on mesoscale heat fluxes

NASA Technical Reports Server (NTRS)

Chen, Fei; Avissar, Roni

1994-01-01

Vertical heat fluxes associated with mesoscale circulations generated by land-surface wetness discontinuities are often stronger than turbulent fluxes, especially in the upper part of the atmospheric planetary boundary layer. As a result, they contribute significantly to the subgrid-scale fluxes in large-scale atmospheric models. Yet they are not considered in these models. To provide some insights into the possible parameterization of these fluxes in large-scale models, a state-of-the-art mesoscale numerical model was used to investigate the relationships between mesoscale heat fluxes and atmospheric and land-surface characteristics that play a key role in the generation of mesoscale circulations. The distribution of land-surface wetness, the wavenumber and the wavelength of the land-surface discontinuities, and the large-scale wind speed have a significant impact on the mesoscale heat fluxes. Empirical functions were derived to characterize the relationships between mesoscale heat fluxes and the spatial distribution of land-surface wetness. The strongest mesoscale heat fluxes were obtained for a wavelength of forcing corresponding approximately to the local Rossby deformation radius. The mesoscale heat fluxes are weakened by large-scale background winds but remain significant even with moderate winds.

An Equivalent cross-section Framework for improving computational efficiency in Distributed Hydrologic Modelling

NASA Astrophysics Data System (ADS)

Khan, Urooj; Tuteja, Narendra; Ajami, Hoori; Sharma, Ashish

2014-05-01

While the potential uses and benefits of distributed catchment simulation models is undeniable, their practical usage is often hindered by the computational resources they demand. To reduce the computational time/effort in distributed hydrological modelling, a new approach of modelling over an equivalent cross-section is investigated where topographical and physiographic properties of first-order sub-basins are aggregated to constitute modelling elements. To formulate an equivalent cross-section, a homogenization test is conducted to assess the loss in accuracy when averaging topographic and physiographic variables, i.e. length, slope, soil depth and soil type. The homogenization test indicates that the accuracy lost in weighting the soil type is greatest, therefore it needs to be weighted in a systematic manner to formulate equivalent cross-sections. If the soil type remains the same within the sub-basin, a single equivalent cross-section is formulated for the entire sub-basin. If the soil type follows a specific pattern, i.e. different soil types near the centre of the river, middle of hillslope and ridge line, three equivalent cross-sections (left bank, right bank and head water) are required. If the soil types are complex and do not follow any specific pattern, multiple equivalent cross-sections are required based on the number of soil types. The equivalent cross-sections are formulated for a series of first order sub-basins by implementing different weighting methods of topographic and physiographic variables of landforms within the entire or part of a hillslope. The formulated equivalent cross-sections are then simulated using a 2-dimensional, Richards' equation based distributed hydrological model. The simulated fluxes are multiplied by the weighted area of each equivalent cross-section to calculate the total fluxes from the sub-basins. The simulated fluxes include horizontal flow, transpiration, soil evaporation, deep drainage and soil moisture. To assess the accuracy of equivalent cross-section approach, the sub-basins are also divided into equally spaced multiple hillslope cross-sections. These cross-sections are simulated in a fully distributed settings using the 2-dimensional, Richards' equation based distributed hydrological model. The simulated fluxes are multiplied by the contributing area of each cross-section to get total fluxes from each sub-basin referred as reference fluxes. The equivalent cross-section approach is investigated for seven first order sub-basins of the McLaughlin catchment of the Snowy River, NSW, Australia, and evaluated in Wagga-Wagga experimental catchment. Our results show that the simulated fluxes using an equivalent cross-section approach are very close to the reference fluxes whereas computational time is reduced of the order of ~4 to ~22 times in comparison to the fully distributed settings. The transpiration and soil evaporation are the dominant fluxes and constitute ~85% of actual rainfall. Overall, the accuracy achieved in dominant fluxes is higher than the other fluxes. The simulated soil moistures from equivalent cross-section approach are compared with the in-situ soil moisture observations in the Wagga-Wagga experimental catchment in NSW, and results found to be consistent. Our results illustrate that the equivalent cross-section approach reduces the computational time significantly while maintaining the same order of accuracy in predicting the hydrological fluxes. As a result, this approach provides a great potential for implementation of distributed hydrological models at regional scales.

Inverse modeling of Asian (222)Rn flux using surface air (222)Rn concentration.

PubMed

Hirao, Shigekazu; Yamazawa, Hiromi; Moriizumi, Jun

2010-11-01

When used with an atmospheric transport model, the (222)Rn flux distribution estimated in our previous study using soil transport theory caused underestimation of atmospheric (222)Rn concentrations as compared with measurements in East Asia. In this study, we applied a Bayesian synthesis inverse method to produce revised estimates of the annual (222)Rn flux density in Asia by using atmospheric (222)Rn concentrations measured at seven sites in East Asia. The Bayesian synthesis inverse method requires a prior estimate of the flux distribution and its uncertainties. The atmospheric transport model MM5/HIRAT and our previous estimate of the (222)Rn flux distribution as the prior value were used to generate new flux estimates for the eastern half of the Eurasian continent dividing into 10 regions. The (222)Rn flux densities estimated using the Bayesian inversion technique were generally higher than the prior flux densities. The area-weighted average (222)Rn flux density for Asia was estimated to be 33.0 mBq m(-2) s(-1), which is substantially higher than the prior value (16.7 mBq m(-2) s(-1)). The estimated (222)Rn flux densities decrease with increasing latitude as follows: Southeast Asia (36.7 mBq m(-2) s(-1)); East Asia (28.6 mBq m(-2) s(-1)) including China, Korean Peninsula and Japan; and Siberia (14.1 mBq m(-2) s(-1)). Increase of the newly estimated fluxes in Southeast Asia, China, Japan, and the southern part of Eastern Siberia from the prior ones contributed most significantly to improved agreement of the model-calculated concentrations with the atmospheric measurements. The sensitivity analysis of prior flux errors and effects of locally exhaled (222)Rn showed that the estimated fluxes in Northern and Central China, Korea, Japan, and the southern part of Eastern Siberia were robust, but that in Central Asia had a large uncertainty.

Glucose metabolic flux distribution of Lactobacillus amylophilus during lactic acid production using kitchen waste saccharified solution.

PubMed

Liu, Jianguo; Wang, Qunhui; Zou, Hui; Liu, Yingying; Wang, Juan; Gan, Kemin; Xiang, Juan

2013-11-01

The (13) C isotope tracer method was used to investigate the glucose metabolic flux distribution and regulation in Lactobacillus amylophilus to improve lactic acid production using kitchen waste saccharified solution (KWSS). The results demonstrate that L. amylophilus is a homofermentative bacterium. In synthetic medium, 60.6% of the glucose entered the Embden-Meyerhof-Parnas (EMP) to produce lactic acid, whereas 36.4% of the glucose entered the pentose phosphate metabolic pathway (HMP). After solid-liquid separation of the KWSS, the addition of Fe(3+) during fermentation enhanced the NADPH production efficiency and increased the NADH content. The flux to the EMP was also effectively increased. Compared with the control (60.6% flux to EMP without Fe(3+) addition), the flux to the EMP with the addition of Fe(3+) (74.3%) increased by 23.8%. In the subsequent pyruvate metabolism, Fe(3+) also increased lactate dehydrogenase activity, and inhibited alcohol dehydrogenase, pyruvate dehydrogenase and pyruvate carboxylase, thereby increasing the lactic acid production to 9.03 g l(-1) , an increase of 8% compared with the control. All other organic acid by-products were lower than in the control. However, the addition of Zn(2+) showed an opposite effect, decreasing the lactic acid production. In conclusion it is feasible and effective means using GC-MS, isotope experiment and MATLAB software to integrate research the metabolic flux distribution of lactic acid bacteria, and the results provide the theoretical foundation for similar metabolic flux distribution. © 2013 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.

Magnetic flux amplification by Lenz lenses.

PubMed

Schoenmaker, J; Pirota, K R; Teixeira, J C

2013-08-01

Tailoring magnetic flux distribution is highly desirable in a wide range of applications such as magnetic sensors and biomedicine. In this paper we study the manipulation of induced currents in passive devices in order to engineer the distribution of magnetic flux intensity in a given region. We propose two different approaches, one based on especially designed wire loops (Lenz law) and the other based on solid conductive pieces (eddy currents). The gain of such devices is mainly determined by geometry giving perspective of high amplification. We consistently modeled, simulated, and executed the proposed devices. Doubled magnetic flux intensity is demonstrated experimentally for a moderate aspect ratio.

Magnetic flux amplification by Lenz lenses

NASA Astrophysics Data System (ADS)

Schoenmaker, J.; Pirota, K. R.; Teixeira, J. C.

2013-08-01

Tailoring magnetic flux distribution is highly desirable in a wide range of applications such as magnetic sensors and biomedicine. In this paper we study the manipulation of induced currents in passive devices in order to engineer the distribution of magnetic flux intensity in a given region. We propose two different approaches, one based on especially designed wire loops (Lenz law) and the other based on solid conductive pieces (eddy currents). The gain of such devices is mainly determined by geometry giving perspective of high amplification. We consistently modeled, simulated, and executed the proposed devices. Doubled magnetic flux intensity is demonstrated experimentally for a moderate aspect ratio.

Magnetic field distribution in superconducting composites as revealed by ESR-probe and magnetization

NASA Astrophysics Data System (ADS)

Davidov, D.; Bontemps, N.; Golosovsky, M.; Waysand, G.

1998-03-01

The distribution of a static magnetic field in superconductor-insulator composites consisting of BSCCO (YBCO) powder in paraffin wax is studied by ESR bulk probing and magnetization. The average field and field variance in the non-superconducting host are measured as function of temperature and volume fraction of superconductor. We develop a model of the field distribution in dilute magnetic and superconducting composites that relates the field inhomogeneity to magnetization and particle shape. We find that this model satisfactorily describes field distribution in our superconducting composites in the regime of strong flux pinning, i.e. below irreversibility line. We find deviations from the model above the irreversibility line and attribute this to flux motion. We show that the field distribution in superconducting composites is determined not only by magnetization and particle shape, but is strongly affected by the flux profile within the superconducting particles.

Estimation of in-canopy flux distributions of reactive nitrogen and sulfur within a mixed hardwood forest in southern Appalachia

EPA Science Inventory

Estimating the source/sink distribution and vertical fluxes of air pollutants within and above forested canopies is critical for understanding biological, physical, and chemical processes influencing the soil-vegetation-atmosphere exchange. The vertical source-sink profiles of re...

In-situ measurement of concentrated solar flux and distribution at the aperture of a central solar receiver

NASA Astrophysics Data System (ADS)

Ferriere, Alain; Volut, Mikael; Perez, Antoine; Volut, Yann

2016-05-01

A flux mapping system has been designed, implemented and experimented at the top of the Themis solar tower in France. This system features a moving bar associated to a CCD video camera and a flux gauge mounted onto the bar used as reference measurement for calibration purpose. Images and flux signal are acquired separately. The paper describes the equipment and focus on the data processing to issue the distribution of flux density and concentration at the aperture of the solar receiver. Finally, the solar power entering into the receiver is estimated by integration of flux density. The processing is largely automated in the form of a dedicated software with fast execution. A special attention is paid to the accuracy of the results, to the robustness of the algorithm and to the velocity of the processing.

Evidence for ion heat flux in the light ion polar wind

NASA Technical Reports Server (NTRS)

Biddle, A. P.; Moore, T. E.; Chappell, C. R.

1985-01-01

Cold flowing hydrogen and helium ions have been observed using the retarding ion mass spectrometer on board the Dynamics Explorer 1 spacecraft in the dayside magnetosphere at subauroral latitudes. The ions show a marked flux asymmetry with respect to the relative wind direction. The observed data are fitted by a model of drifting Maxwellian distributions perturbed by a first order-Spritzer-Haerm heat flux distribution function. It is shown that both ion species are supersonic just equatorward of the auroral zone at L = 14, and the shape of asymmetry and direction of the asymmetry are consistent with the presence of an upward heat flux. At L = 6, both species evolve smoothly into warmer subsonic upward flows with downward heat fluxes. In the case of subsonic flows the downward heat flux implies a significant heat source at higher altitudes. Spin curves of the spectrometer count rate versus the spin phase angle are provided.

Theory and Performance of AIMS for Active Interrogation

NASA Astrophysics Data System (ADS)

Walters, William J.; Royston, Katherine E. K.; Haghighat, Alireza

2014-06-01

A hybrid Monte Carlo and deterministic methodology has been developed for application to active interrogation systems. The methodology consists of four steps: i) determination of neutron flux distribution due to neutron source transport and subcritical multiplication; ii) generation of gamma source distribution from (n, γ) interactions; iii) determination of gamma current at a detector window; iv) detection of gammas by the detector. This paper discusses the theory and results of the first three steps for the case of a cargo container with a sphere of HEU in third-density water. In the first step, a response-function formulation has been developed to calculate the subcritical multiplication and neutron flux distribution. Response coefficients are pre-calculated using the MCNP5 Monte Carlo code. The second step uses the calculated neutron flux distribution and Bugle-96 (n, γ) cross sections to find the resulting gamma source distribution. Finally, in the third step the gamma source distribution is coupled with a pre-calculated adjoint function to determine the gamma flux at a detector window. A code, AIMS (Active Interrogation for Monitoring Special-Nuclear-materials), has been written to output the gamma current for an source-detector assembly scanning across the cargo using the pre-calculated values and takes significantly less time than a reference MCNP5 calculation.

Ecological network analysis on global virtual water trade.

PubMed

Yang, Zhifeng; Mao, Xufeng; Zhao, Xu; Chen, Bin

2012-02-07

Global water interdependencies are likely to increase with growing virtual water trade. To address the issues of the indirect effects of water trade through the global economic circulation, we use ecological network analysis (ENA) to shed insight into the complicated system interactions. A global model of virtual water flow among agriculture and livestock production trade in 1995-1999 is also built as the basis for network analysis. Control analysis is used to identify the quantitative control or dependency relations. The utility analysis provides more indicators for describing the mutual relationship between two regions/countries by imitating the interactions in the ecosystem and distinguishes the beneficiary and the contributor of virtual water trade system. Results show control and utility relations can well depict the mutual relation in trade system, and direct observable relations differ from integral ones with indirect interactions considered. This paper offers a new way to depict the interrelations between trade components and can serve as a meaningful start as we continue to use ENA in providing more valuable implications for freshwater study on a global scale.

Assessment of trophic transfer of benzo(a)pyrene genotoxicity from the post-larval pink shrimp F. brasiliensis to the juvenile Florida pompano T. carolinus.

PubMed

Rocha, Arthur José da Silva; Santos, Thaís Cruz Alves; Gomes, Vicente; Bícego, Márcia Caruso; Barbosa, Ana Cecília Rizzatti de Albergaria; Passos, Maria José de Arruda Campos Rocha; Hasue, Fabio Matsu; Van Ngan, Phan

2012-11-01

In the present study, the polycyclic aromatic hydrocarbon (PAH) genotoxicity was investigated in a one-step predator-prey relationship with the trophic-related marine species. Florida pompanos were fed for 5 and 10 days with pink shrimp post larvae previously exposed to benzo(a)pyrene (BaP) concentrations. Parent BaP body burden was measured in samples of Farfantepenaeus brasiliensis. BaP metabolites were determined in bile samples of Trachinotus carolinus and DNA damage was assessed through the comet and erythrocyte nuclear abnormalities (ENAs) assays in fish erythrocytes. BaP body burden increased significantly with the PAH concentration in pink shrimp PLs as well as the fish bile BaP metabolites. Both, comet and ENAs assays indicated significant increase on erythrocyte DNA damage of Florida pompanos fed with BaP-exposed pink shrimp on both feeding periods. The trophic route of BaP genotoxicity is discussed as well as the PAH biotransformation as the inducing mechanism for the DNA damages observed. Copyright © 2012 Elsevier B.V. All rights reserved.

Addressing the impact of mercury estuarine contamination in the European eel (Anguilla anguilla L., 1758) - An early diagnosis in glass eel stage based on erythrocytic nuclear morphology.

PubMed

Castro, D; Mieiro, C L; Coelho, J P; Guilherme, S; Marques, A; Santos, M A; Duarte, A C; Pereira, E; Pacheco, M

2018-02-01

The decline of the European eel (Anguilla anguilla L., 1758) population throughout Europe has been partially attributed to pollution. As glass eel estuarine migration may represent a considerable threat, the impact of mercury (Hg) contamination at this stage was evaluated through an in situ experiment (7days). Total Hg (tHg) bioaccumulation was evaluated concomitantly with erythrocytic nuclear morphology alterations: erythrocytic nuclear abnormalities assay (ENA), frequency of immature erythrocytes (IE) and the erythrocytic maturity index (EMI). The ENA results suggested a genotoxic pressure at the most contaminated sites, in line with the tHg increase. The EMI data, together with IE frequency, showed that fish exposed to high levels of Hg exhibited alterations of haematological dynamics, translated into an erythropoiesis increment. Despite the presence of these compensatory mechanisms, the present findings suggest a harmful impact of Hg on genome integrity at this early development stage, potentially affecting eels' condition and ultimately the population sustainability. Copyright © 2017. Published by Elsevier Ltd.

Ecological network analysis for economic systems: growth and development and implications for sustainable development.

PubMed

Huang, Jiali; Ulanowicz, Robert E

2014-01-01

The quantification of growth and development is an important issue in economics, because these phenomena are closely related to sustainability. We address growth and development from a network perspective in which economic systems are represented as flow networks and analyzed using ecological network analysis (ENA). The Beijing economic system is used as a case study and 11 input-output (I-O) tables for 1985-2010 are converted into currency networks. ENA is used to calculate system-level indices to quantify the growth and development of Beijing. The contributions of each direct flow toward growth and development in 2010 are calculated and their implications for sustainable development are discussed. The results show that during 1985-2010, growth was the main attribute of the Beijing economic system. Although the system grew exponentially, its development fluctuated within only a small range. The results suggest that system ascendency should be increased in order to favor more sustainable development. Ascendency can be augmented in two ways: (1) strengthen those pathways with positive contributions to increasing ascendency and (2) weaken those with negative effects.

Association of Piebaldism, multiple café-au-lait macules, and intertriginous freckling: clinical evidence of a common pathway between KIT and sprouty-related, ena/vasodilator-stimulated phosphoprotein homology-1 domain containing protein 1 (SPRED1).

PubMed

Chiu, Yvonne E; Dugan, Stefanie; Basel, Donald; Siegel, Dawn H

2013-01-01

Piebaldism is a rare genodermatosis caused by KIT mutations. We report the case of a 5-year-old boy who had the white forelock and leukoderma of piebaldism, but the presence of many café-au-lait macules and axillary and inguinal freckling complicated the diagnosis. Patients with similar cutaneous findings have been previously reported, and their disorder has been attributed to an overlap of piebaldism and neurofibromatosis type 1. Legius syndrome is a recently described syndrome caused by Sprouty-related, Ena/vasodilator-stimulated phosphoprotein homology-1 domain containing protein 1 (SPRED1) mutations that also has multiple café-au-lait macules and intertriginous freckling. Based on our current understanding of KIT and SPRED1 protein interactions, we propose that café-au-lait macules and freckling may be seen in some patients with piebaldism and does not necessarily represent coexistence of neurofibromatosis type 1. © 2012 Wiley Periodicals, Inc.

Viral to metazoan marine plankton nucleotide sequences from the Tara Oceans expedition

PubMed Central

Alberti, Adriana; Poulain, Julie; Engelen, Stefan; Labadie, Karine; Romac, Sarah; Ferrera, Isabel; Albini, Guillaume; Aury, Jean-Marc; Belser, Caroline; Bertrand, Alexis; Cruaud, Corinne; Da Silva, Corinne; Dossat, Carole; Gavory, Frédérick; Gas, Shahinaz; Guy, Julie; Haquelle, Maud; Jacoby, E'krame; Jaillon, Olivier; Lemainque, Arnaud; Pelletier, Eric; Samson, Gaëlle; Wessner, Mark; Bazire, Pascal; Beluche, Odette; Bertrand, Laurie; Besnard-Gonnet, Marielle; Bordelais, Isabelle; Boutard, Magali; Dubois, Maria; Dumont, Corinne; Ettedgui, Evelyne; Fernandez, Patricia; Garcia, Espérance; Aiach, Nathalie Giordanenco; Guerin, Thomas; Hamon, Chadia; Brun, Elodie; Lebled, Sandrine; Lenoble, Patricia; Louesse, Claudine; Mahieu, Eric; Mairey, Barbara; Martins, Nathalie; Megret, Catherine; Milani, Claire; Muanga, Jacqueline; Orvain, Céline; Payen, Emilie; Perroud, Peggy; Petit, Emmanuelle; Robert, Dominique; Ronsin, Murielle; Vacherie, Benoit; Acinas, Silvia G.; Royo-Llonch, Marta; Cornejo-Castillo, Francisco M.; Logares, Ramiro; Fernández-Gómez, Beatriz; Bowler, Chris; Cochrane, Guy; Amid, Clara; Hoopen, Petra Ten; De Vargas, Colomban; Grimsley, Nigel; Desgranges, Elodie; Kandels-Lewis, Stefanie; Ogata, Hiroyuki; Poulton, Nicole; Sieracki, Michael E.; Stepanauskas, Ramunas; Sullivan, Matthew B.; Brum, Jennifer R.; Duhaime, Melissa B.; Poulos, Bonnie T.; Hurwitz, Bonnie L.; Acinas, Silvia G.; Bork, Peer; Boss, Emmanuel; Bowler, Chris; De Vargas, Colomban; Follows, Michael; Gorsky, Gabriel; Grimsley, Nigel; Hingamp, Pascal; Iudicone, Daniele; Jaillon, Olivier; Kandels-Lewis, Stefanie; Karp-Boss, Lee; Karsenti, Eric; Not, Fabrice; Ogata, Hiroyuki; Pesant, Stéphane; Raes, Jeroen; Sardet, Christian; Sieracki, Michael E.; Speich, Sabrina; Stemmann, Lars; Sullivan, Matthew B.; Sunagawa, Shinichi; Wincker, Patrick; Pesant, Stéphane; Karsenti, Eric; Wincker, Patrick

2017-01-01

A unique collection of oceanic samples was gathered by the Tara Oceans expeditions (2009–2013), targeting plankton organisms ranging from viruses to metazoans, and providing rich environmental context measurements. Thanks to recent advances in the field of genomics, extensive sequencing has been performed for a deep genomic analysis of this huge collection of samples. A strategy based on different approaches, such as metabarcoding, metagenomics, single-cell genomics and metatranscriptomics, has been chosen for analysis of size-fractionated plankton communities. Here, we provide detailed procedures applied for genomic data generation, from nucleic acids extraction to sequence production, and we describe registries of genomics datasets available at the European Nucleotide Archive (ENA, www.ebi.ac.uk/ena). The association of these metadata to the experimental procedures applied for their generation will help the scientific community to access these data and facilitate their analysis. This paper complements other efforts to provide a full description of experiments and open science resources generated from the Tara Oceans project, further extending their value for the study of the world’s planktonic ecosystems. PMID:28763055

Ecological Network Analysis for Economic Systems: Growth and Development and Implications for Sustainable Development

PubMed Central

Huang, Jiali; Ulanowicz, Robert E.

2014-01-01

The quantification of growth and development is an important issue in economics, because these phenomena are closely related to sustainability. We address growth and development from a network perspective in which economic systems are represented as flow networks and analyzed using ecological network analysis (ENA). The Beijing economic system is used as a case study and 11 input–output (I-O) tables for 1985–2010 are converted into currency networks. ENA is used to calculate system-level indices to quantify the growth and development of Beijing. The contributions of each direct flow toward growth and development in 2010 are calculated and their implications for sustainable development are discussed. The results show that during 1985–2010, growth was the main attribute of the Beijing economic system. Although the system grew exponentially, its development fluctuated within only a small range. The results suggest that system ascendency should be increased in order to favor more sustainable development. Ascendency can be augmented in two ways: (1) strengthen those pathways with positive contributions to increasing ascendency and (2) weaken those with negative effects. PMID:24979465

Genetic ablation of zyxin causes Mena/VASP mislocalization, increased motility, and deficits in actin remodeling

PubMed Central

Hoffman, Laura M.; Jensen, Christopher C.; Kloeker, Susanne; Wang, C.-L. Albert; Yoshigi, Masaaki; Beckerle, Mary C.

2006-01-01

Focal adhesions are specialized regions of the cell surface where integrin receptors and associated proteins link the extracellular matrix to the actin cytoskeleton. To define the cellular role of the focal adhesion protein zyxin, we characterized the phenotype of fibroblasts in which the zyxin gene was deleted by homologous recombination. Zyxin-null fibroblasts display enhanced integrin-dependent adhesion and are more migratory than wild-type fibroblasts, displaying reduced dependence on extracellular matrix cues. We identified differences in the profiles of 75- and 80-kD tyrosine-phosphorylated proteins in the zyxin-null cells. Tandem array mass spectrometry identified both modified proteins as isoforms of the actomyosin regulator caldesmon, a protein known to influence contractility, stress fiber formation, and motility. Zyxin-null fibroblasts also show deficits in actin stress fiber remodeling and exhibit changes in the molecular composition of focal adhesions, most notably by severely reduced accumulation of Ena/VASP proteins. We postulate that zyxin cooperates with Ena/VASP proteins and caldesmon to influence integrin-dependent cell motility and actin stress fiber remodeling. PMID:16505170

Viral to metazoan marine plankton nucleotide sequences from the Tara Oceans expedition.

PubMed

Alberti, Adriana; Poulain, Julie; Engelen, Stefan; Labadie, Karine; Romac, Sarah; Ferrera, Isabel; Albini, Guillaume; Aury, Jean-Marc; Belser, Caroline; Bertrand, Alexis; Cruaud, Corinne; Da Silva, Corinne; Dossat, Carole; Gavory, Frédérick; Gas, Shahinaz; Guy, Julie; Haquelle, Maud; Jacoby, E'krame; Jaillon, Olivier; Lemainque, Arnaud; Pelletier, Eric; Samson, Gaëlle; Wessner, Mark; Acinas, Silvia G; Royo-Llonch, Marta; Cornejo-Castillo, Francisco M; Logares, Ramiro; Fernández-Gómez, Beatriz; Bowler, Chris; Cochrane, Guy; Amid, Clara; Hoopen, Petra Ten; De Vargas, Colomban; Grimsley, Nigel; Desgranges, Elodie; Kandels-Lewis, Stefanie; Ogata, Hiroyuki; Poulton, Nicole; Sieracki, Michael E; Stepanauskas, Ramunas; Sullivan, Matthew B; Brum, Jennifer R; Duhaime, Melissa B; Poulos, Bonnie T; Hurwitz, Bonnie L; Pesant, Stéphane; Karsenti, Eric; Wincker, Patrick

2017-08-01

A unique collection of oceanic samples was gathered by the Tara Oceans expeditions (2009-2013), targeting plankton organisms ranging from viruses to metazoans, and providing rich environmental context measurements. Thanks to recent advances in the field of genomics, extensive sequencing has been performed for a deep genomic analysis of this huge collection of samples. A strategy based on different approaches, such as metabarcoding, metagenomics, single-cell genomics and metatranscriptomics, has been chosen for analysis of size-fractionated plankton communities. Here, we provide detailed procedures applied for genomic data generation, from nucleic acids extraction to sequence production, and we describe registries of genomics datasets available at the European Nucleotide Archive (ENA, www.ebi.ac.uk/ena). The association of these metadata to the experimental procedures applied for their generation will help the scientific community to access these data and facilitate their analysis. This paper complements other efforts to provide a full description of experiments and open science resources generated from the Tara Oceans project, further extending their value for the study of the world's planktonic ecosystems.

High-flux source of low-energy neutral beams using reflection of ions from metals

NASA Technical Reports Server (NTRS)

Cuthbertson, John W.; Motley, Robert W.; Langer, William D.

1992-01-01

Reflection of low-energy ions from surfaces can be applied as a method of producing high-flux beams of low-energy neutral particles, and is an important effect in several areas of plasma technology, such as in the edge region of fusion devices. We have developed a beam source based on acceleration and reflection of ions from a magnetically confined coaxial RF plasma source. The beam provides a large enough flux to allow the energy distribution of the reflected neutrals to be measured despite the inefficiency of detection, by means of an electrostatic cylindrical mirror analyzer coupled with a quadrupole mass spectrometer. Energy distributions have been measured for oxygen, nitrogen, and inert gas ions incident with from 15 to 70 eV reflected from amorphous metal surfaces of several compositions. For ions of lighter atomic mass than the reflecting metal, reflected beams have peaked energy distributions; beams with the peak at 4-32 eV have been measured. The energy and mass dependences of the energy distributions as well as measurements of absolute flux, and angular distribution and divergence are reported. Applications of the neutral beams produced are described.

DETECTION OF FLUX EMERGENCE, SPLITTING, MERGING, AND CANCELLATION OF NETWORK FIELD. I. SPLITTING AND MERGING

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

Iida, Y.; Yokoyama, T.; Hagenaar, H. J.

2012-06-20

Frequencies of magnetic patch processes on the supergranule boundary, namely, flux emergence, splitting, merging, and cancellation, are investigated through automatic detection. We use a set of line-of-sight magnetograms taken by the Solar Optical Telescope (SOT) on board the Hinode satellite. We found 1636 positive patches and 1637 negative patches in the data set, whose time duration is 3.5 hr and field of view is 112'' Multiplication-Sign 112''. The total numbers of magnetic processes are as follows: 493 positive and 482 negative splittings, 536 positive and 535 negative mergings, 86 cancellations, and 3 emergences. The total numbers of emergence and cancellationmore » are significantly smaller than those of splitting and merging. Further, the frequency dependence of the merging and splitting processes on the flux content are investigated. Merging has a weak dependence on the flux content with a power-law index of only 0.28. The timescale for splitting is found to be independent of the parent flux content before splitting, which corresponds to {approx}33 minutes. It is also found that patches split into any flux contents with the same probability. This splitting has a power-law distribution of the flux content with an index of -2 as a time-independent solution. These results support that the frequency distribution of the flux content in the analyzed flux range is rapidly maintained by merging and splitting, namely, surface processes. We suggest a model for frequency distributions of cancellation and emergence based on this idea.« less

Modelling the Surface Distribution of Magnetic Activity on Sun-Like Stars

NASA Astrophysics Data System (ADS)

Isik, Emre

2018-04-01

With the advent of high-precision space-borne stellar photometry and prospects for direct imaging, it is timely and essential to improve our understanding of stellar magnetic activity in rotational time scales. We present models for 'younger suns' with rotation and flux emergence rates between 1 and 16 times the solar rate. The models provide latitudinal distributions and tilt angles of bipolar magnetic regions, using flux tube rise simulations. Using these emergence patterns, we model the subsequent surface flux transport, to predict surface distributions of star-spots. Based on these models, we present preliminary results from our further modelling of the observed azimuthal magnetic fields, which strengthen for more rapidly rotating Sun-like stars.

Thermally Driven One-Fluid Electron-Proton Solar Wind: Eight-Moment Approximation

NASA Astrophysics Data System (ADS)

Olsen, Espen Lyngdal; Leer, Egil

1996-05-01

In an effort to improve the "classical" solar wind model, we study an eight-moment approximation hydrodynamic solar wind model, in which the full conservation equation for the heat conductive flux is solved together with the conservation equations for mass, momentum, and energy. We consider two different cases: In one model the energy flux needed to drive the solar wind is supplied as heat flux from a hot coronal base, where both the density and temperature are specified. In the other model, the corona is heated. In that model, the coronal base density and temperature are also specified, but the temperature increases outward from the coronal base due to a specified energy flux that is dissipated in the corona. The eight-moment approximation solutions are compared with the results from a "classical" solar wind model in which the collision-dominated gas expression for the heat conductive flux is used. It is shown that the "classical" expression for the heat conductive flux is generally not valid in the solar wind. In collisionless regions of the flow, the eight-moment approximation gives a larger thermalization of the heat conductive flux than the models using the collision-dominated gas approximation for the heat flux, but the heat flux is still larger than the "saturation heat flux." This leads to a breakdown of the electron distribution function, which turns negative in the collisionless region of the flow. By increasing the interaction between the electrons, the heat flux is reduced, and a reasonable shape is obtained on the distribution function. By solving the full set of equations consistent with the eight-moment distribution function for the electrons, we are thus able to draw inferences about the validity of the eight-moment description of the solar wind as well as the validity of the very commonly used collision-dominated gas approximation for the heat conductive flux in the solar wind.

Stereo ENA Imaging of the Ring Current and Multi-point Measurements of Suprathermal Particles and Magnetic Fields by TRIO-CINEMA

NASA Astrophysics Data System (ADS)

Lin, R. P.; Sample, J. G.; Immel, T. J.; Lee, D.; Horbury, T. S.; Jin, H.; SEON, J.; Wang, L.; Roelof, E. C.; Lee, E.; Parks, G. K.; Vo, H.

2012-12-01

The TRIO (Triplet Ionospheric Observatory) - CINEMA (Cubesat for Ions, Neutrals, Electrons, & Magnetic fields) mission consists of three identical 3-u cubesats to provide high sensitivity, high cadence, stereo measurements of Energetic Neutral Atoms (ENAs) from the Earth's ring current with ~1 keV FWHM energy resolution from ~4 to ~200 keV, as well as multi-point in situ measurements of magnetic fields and suprathermal electrons (~2 -200 keV) and ions (~ 4 -200 keV) in the auroral and ring current precipitation regions in low Earth orbit (LEO). A new Suprathermal Electron, Ion, Neutral (STEIN) instrument, using a 32-pixel silicon semiconductor detector with an electrostatic deflection system to separate ENAs from ions and from electrons below 30 keV, will sweep over most of the sky every 15 s as the spacecraft spins at 4 rpm. In addition, inboard and outboard (on an extendable 1m boom) miniature magnetoresistive sensor magnetometers will provide high cadence 3-axis magnetic field measurements. An S-band transmitter will be used to provide ~8 kbps orbit-average data downlink to the ~11m diameter antenna of the Berkeley Ground Station.The first CINEMA (funded by NSF) is scheduled for launch on August 14, 2012 into a 65 deg. inclination LEO. Two more identical CINEMAs are being developed by Kyung Hee University (KHU) in Korea under the World Class University (WCU) program, for launch in November 2012 into a Sun-synchronous LEO to form TRIO-CINEMA. A fourth CINEMA is being developed for a 2013 launch into LEO. This LEO constellation of nanosatellites will provide unique measurements highly complementary to NASA's RBSP and THEMIS missions. Furthermore, CINEMA's development of miniature particle and magnetic field sensors, and cubesat-size spinning spacecraft may be important for future constellation space missions. Initial results from the first CINEMA will be presented if available.

Overview of Results from the Cassini Magnetospheric Imaging Instrument (MIMI) During the First Year of Operations

NASA Technical Reports Server (NTRS)

Krimigis, S. M.; Mitchell, D. G.; Hamilton, D. C.; Krupp, N.; Livi, S.; Roelof, E. C.; Dandouras, J.; Mauk, B. H.; Brandt, J. P.; Paranicas, C.

2005-01-01

The MIMI investigation comprises three sensors covering the indicated energy ranges: the Ion and Neutral Camera (INCA) -- 7 keV/nuc 3 Mev) and protons (1.6 < E < 160 Mev) from the back end of the dual field-of-view telescope. The Saturn observation sequences began in January, 2004 and culminated in Saturn Orbit Insertion on July 1, 2004. The MIMI sensors observed substantial activity in interplanetary space for several months prior to SOI, including several interplanetary shocks associated with corotating interaction regions, numerous increases most likely originating from particle streams in the vicinity of the Saturnian bow shock and energetic neutral atoms (ENA) emanating from Saturn s magnetosphere. Results following SOI revealed: a dynamical magnetosphere with a day-night asymmetry and an 11-hour periodicity; several water-product ions (O+, OH+, H2O+), but little N+; inferred quantities of neutral gas sufficient to cause major losses in the trapped ions and electrons in the middle and inner magnetosphere; a Titan exosphere that is a copious source of ENA; INCA imaging through ENA has also revealed a previously unknown radiation belt residing inward of the D-ring that is most likely the result of double charge-exchange between the main radiation belt and the upper layers of Saturn s exosphere. Finally, there is ample evidence for the presence of substorm-like injections of plasma that subsequently corotates for a number of days before dissipating on the night-side magnetotail. The observations will be presented and discussed in the context of current theoretical models.

Energetic neutral atom and interstellar flow observations with IBEX: Implications for the global heliosphere

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

Schwadron, N. A., E-mail: nschwadron@unh.edu; Southwest Research Institute, San Antonio, TX, 78238; McComas, D. J.

2016-03-25

Since launch in Oct. 2008, IBEX, with its two energetic neutral atom (ENA) cameras, has provided humankind with the first-ever global images of the complex boundary separating the heliosphere from the local interstellar medium (LISM). IBEX’s energy-resolved all-sky maps, collected every six months, are yielding remarkable new insights into the heliospheres structure as it is shaped by the combined forces of the local interstellar flow, the local interstellar magnetic field (LISMF), and the evolving solar wind. IBEX has also acquired the first images of ENAs backscattered from the surface of the moon as well as global images of the magnetosphericmore » response to solar wind disturbances. IBEX thus addresses all three Heliophysics science objectives set forth in the 2014 Science Plan for NASAs Science Mission Directorate (SMD) as well as the goals in the recent Solar and Space Physics Decadal Survey (NRC 2012). In addition, with the information it provides on the properties of the LISM and the LISMF, IBEX represents a unique bridge between heliophysics and astrophysics, and fills in critical knowledge for understanding the habitability of exoplanetary systems and the future habitability of Earth and the solar system. Because of the few-year time lag due to solar wind and ENA transport, IBEX observed the solar wind/ LISM interaction characteristic of declining phase/solar minimum conditions. In the continuing mission, IBEX captures the response of the interstellar boundaries to the changing structure of the solar wind in its transition toward the “mini” solar maximum and possibly the decline into the next solar minimum. The continuing IBEX mission affords never-to-be-repeated opportunities to coordinate global imaging of the heliospheric boundary with in-situ measurements by the Voyagers as they pass beyond the heliopause and start to directly sample the LISM.« less

The Near-Earth Meteoroid Flux, Speed Distribution, and Uncertainty

NASA Technical Reports Server (NTRS)

Moorhead, Althea; Cooke, William J.; Brown, Peter G.; Campbell-Brown, Margaret; Moser, Danielle E.

2016-01-01

Meteoroids are known to pose a threat to spacecraft; they can puncture components, disturb spacecraft attitude, and possibly create secondary electrical effects. Accurate environment models are therefore critical for mitigating meteoroid-related risks. While there are several meteoroid environment models available for assessing spacecraft risk, the uncertainties associated with these models are not well understood. Because meteoroid properties are derived from indirect observations such as meteors and impact craters, the uncertainty in the meteoroid flux is potentially quite large. We combine existing meteoroid flux measurements with new radar and optical meteor data to improve our characterization of the meteoroid flux onto the Earth and its velocity distribution. We use data extracted from the NASA all-sky network, the Canadian Automated Meteor Observatory, and the Canadian Meteor Orbit Radar. We improve our characterization of the observed meteoroid speed distribution by incorporating modern descriptions of the ionization efficiency (e.g., Thomas et al., 2016). We also present estimates of the uncertainties associated with our meteoroid flux distribution. Finally, we discuss the implications for spacecraft. Our model is constrained by the cratering rate on the space-facing surface of LDEF, and thus the risk posed to spacecraft by meteoroid-induced physical damage is the least uncertain component of our model. Other sources of risk, however, may vary. For instance, a lower average meteoroid speed would require a higher meteoroid mass flux in order to match the LDEF crater counts, leading to higher predicted rates of attitude disturbances.

Flux tubes in the SU(3) vacuum

NASA Astrophysics Data System (ADS)

Cardaci, M. S.; Cea, P.; Cosmai, L.; Falcone, R.; Papa, A.

We analyze the distribution of the chromoelectric field generated by a static quark-antiquark pair in the SU(3) vacuum. We find that the transverse profile of the flux tube resembles the dual version of the Abrikosov vortex field distribution and give an estimate of the London penetration length in the confined vacuum.

Point and Compact Hα Sources in the Interior of M33

NASA Astrophysics Data System (ADS)

Moody, J. Ward; Hintz, Eric G.; Joner, Michael D.; Roming, Peter W. A.; Hintz, Maureen L.

2017-12-01

A variety of interesting objects such as Wolf-Rayet stars, tight OB associations, planetary nebulae, X-ray binaries, etc., can be discovered as point or compact sources in Hα surveys. How these objects distribute through a galaxy sheds light on the galaxy star formation rate and history, mass distribution, and dynamics. The nearby galaxy M33 is an excellent place to study the distribution of Hα-bright point sources in a flocculant spiral galaxy. We have reprocessed an archived WIYN continuum-subtracted Hα image of the inner 6.‧5 × 6.‧5 of M33 and, employing both eye and machine searches, have tabulated sources with a flux greater than approximately 10-15 erg cm-2s-1. We have effectively recovered previously mapped H II regions and have identified 152 unresolved point sources and 122 marginally resolved compact sources, of which 39 have not been previously identified in any archive. An additional 99 Hα sources were found to have sufficient archival flux values to generate a Spectral Energy Distribution. Using the SED, flux values, Hα flux value, and compactness, we classified 67 of these sources.

Exact analytic flux distributions for two-dimensional solar concentrators.

PubMed

Fraidenraich, Naum; Henrique de Oliveira Pedrosa Filho, Manoel; Vilela, Olga C; Gordon, Jeffrey M

2013-07-01

A new approach for representing and evaluating the flux density distribution on the absorbers of two-dimensional imaging solar concentrators is presented. The formalism accommodates any realistic solar radiance and concentrator optical error distribution. The solutions obviate the need for raytracing, and are physically transparent. Examples illustrating the method's versatility are presented for parabolic trough mirrors with both planar and tubular absorbers, Fresnel reflectors with tubular absorbers, and V-trough mirrors with planar absorbers.

Effect of boundary heat flux on columnar formation in binary alloys: A phase-field study

NASA Astrophysics Data System (ADS)

Du, Lifei; Zhang, Peng; Yang, Shaomei; Chen, Jie; Du, Huiling

2018-02-01

A non-isothermal phase-field model was employed to simulate the columnar formation during rapid solidification in binary Ni-Cu alloy. Heat flux at different boundaries was applied to investigate the temperature gradient effect on the morphology, concentration and temperature distributions during directional solidifications. With the heat flux input/extraction from boundaries, coupling with latent heat release and initial temperature gradient, temperature distributions are significantly changed, leading to solute diffusion changes during the phase-transition. Thus, irregular columnar structures are formed during the directional solidification, and the concentration distribution in solid columnar arms could also be changed due to the different growing speeds and temperature distributions at the solid-liquid interfaces. Therefore, applying specific heat conditions at the solidifying boundaries could be an efficient way to control the microstructure during solidifications.

Empirical effective temperatures and bolometric corrections for early-type stars

NASA Technical Reports Server (NTRS)

Code, A. D.; Bless, R. C.; Davis, J.; Brown, R. H.

1976-01-01

An empirical effective temperature for a star can be found by measuring its apparent angular diameter and absolute flux distribution. The angular diameters of 32 bright stars in the spectral range O5f to F8 have recently been measured with the stellar interferometer at Narrabri Observatory, and their absolute flux distributions have been found by combining observations of ultraviolet flux from the Orbiting Astronomical Observatory (OAO-2) with ground-based photometry. In this paper, these data have been combined to derive empirical effective temperatures and bolometric corrections for these 32 stars.

Resistivity analysis of epitaxially grown, doped semiconductors using energy dependent secondary ion mass spectroscopy

NASA Astrophysics Data System (ADS)

Burnham, Shawn D.; Thomas, Edward W.; Doolittle, W. Alan

2006-12-01

A characterization technique is discussed that allows quantitative optimization of doping in epitaxially grown semiconductors. This technique uses relative changes in the host atom secondary ion (HASI) energy distribution from secondary ion mass spectroscopy (SIMS) to indicate relative changes in conductivity of the material. Since SIMS is a destructive process due to sputtering through a film, a depth profile of the energy distribution of sputtered HASIs in a matrix will contain information on the conductivity of the layers of the film as a function of depth. This process is demonstrated with Mg-doped GaN, with the Mg flux slowly increased through the film. Three distinct regions of conductivity were observed: one with Mg concentration high enough to cause compensation and thus high resistivity, a second with moderate Mg concentration and low resistivity, and a third with little to no Mg doping, causing high resistivity due to the lack of free carriers. During SIMS analysis of the first region, the energy distributions of sputtered Ga HASIs were fairly uniform and unchanging for a Mg flux above the saturation, or compensation, limit. For the second region, the Ga HASI energy distributions shifted and went through a region of inconsistent energy distributions for Mg flux slightly below the critical flux for saturation, or compensation. Finally, for the third region, the Ga HASI energy distributions then settled back into another fairly unchanging, uniform pattern. These three distinct regions were analyzed further through growth of Mg-doped step profiles and bulk growth of material at representative Mg fluxes. The materials grown at the two unchanging, uniform regions of the energy distributions yielded highly resistive material due to too high of Mg concentration and low to no Mg concentration, respectively. However, material grown in the transient energy distribution region with Mg concentration between that of the two highly resistive regions yielded low resistivity (0.59Ωcm) and highly p-type (1.2×1018cm-3 holes) Mg-doped GaN.

Quantifying trace element and isotope fluxes at the ocean-sediment boundary: a review.

PubMed

Homoky, William B; Weber, Thomas; Berelson, William M; Conway, Tim M; Henderson, Gideon M; van Hulten, Marco; Jeandel, Catherine; Severmann, Silke; Tagliabue, Alessandro

2016-11-28

Quantifying fluxes of trace elements and their isotopes (TEIs) at the ocean's sediment-water boundary is a pre-eminent challenge to understand their role in the present, past and future ocean. There are multiple processes that drive the uptake and release of TEIs, and properties that determine their rates are unevenly distributed (e.g. sediment composition, redox conditions and (bio)physical dynamics). These factors complicate our efforts to find, measure and extrapolate TEI fluxes across ocean basins. GEOTRACES observations are unveiling the oceanic distributions of many TEIs for the first time. These data evidence the influence of the sediment-water boundary on many TEI cycles, and underline the fact that our knowledge of the source-sink fluxes that sustain oceanic distributions is largely missing. Present flux measurements provide low spatial coverage and only part of the empirical basis needed to predict TEI flux variations. Many of the advances and present challenges facing TEI flux measurements are linked to process studies that collect sediment cores, pore waters, sinking material or seawater in close contact with sediments. However, such sampling has not routinely been viable on GEOTRACES expeditions. In this article, we recommend approaches to address these issues: firstly, with an interrogation of emergent data using isotopic mass-balance and inverse modelling techniques; and secondly, by innovating pursuits of direct TEI flux measurements. We exemplify the value of GEOTRACES data with a new inverse model estimate of benthic Al flux in the North Atlantic Ocean. Furthermore, we review viable flux measurement techniques tailored to the sediment-water boundary. We propose that such activities are aimed at regions that intersect the GEOTRACES Science Plan on the basis of seven criteria that may influence TEI fluxes: sediment provenance, composition, organic carbon supply, redox conditions, sedimentation rate, bathymetry and the benthic nepheloid inventory.This article is part of the themed issue 'Biological and climatic impacts of ocean trace element chemistry'. © 2015 The Authors.