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1
Kowalska, M. Anna, Mariusz Z. Ratajczak, Marcin Majka, Jianguo Jin, Satya Kunapuli, Lawrence Brass, and Mortimer Poncz. "Stromal cell–derived factor-1 and macrophage-derived chemokine: 2 chemokines that activate platelets." Blood 96, no. 1 (July 1, 2000): 50–57. http://dx.doi.org/10.1182/blood.v96.1.50.
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Abstract Platelets play roles in both thrombosis and inflammation, and chemokines that are released at sites of inflammation could potentially activate platelets. Among the chemokine receptors expressed on platelets, the CXCR4 is the receptor for chemokine stromal cell-derived factor-1 (SDF-1), and the CCR4 is the receptor for macrophage-derived chemokine (MDC). Of the chemokines tested, SDF-1 and MDC were the only 2 that activated platelets. Both are weak agonists, but they enhanced response to low-dose adenosine 5′-diphosphate (ADP), epinephrine, or serotonin. When SDF-1 and MDC were added together, full and brisk platelet aggregation occurred. Platelet activation by these 2 chemokines appears to involve distinct pathways: SDF-1 inhibited an increase in cyclic adenosine monophosphate (cAMP) following prostaglandin (PG) I2, while MDC had no effect. In contrast, MDC, but not SDF-1, lead to Ca++mobilization by platelets. Further, second-wave aggregation induced by MDC in platelet-rich plasma was inhibited by aspirin, ADP scavenger creatine phosphate/creative phosphokinase (CP/CPK), and ARL-66096, an antagonist of the ADP P2TAC receptor involved in adenylyl cyclase inhibition. But the aggregation was not affected by A3P5PS, an inhibitor of the ADP P2Y receptor. SDF-1–induced aggregation was inhibited by aspirin, but it was only slightly affected by CP/CPK, ARL-66096, or A3P5PS. Finally, the presence of chemokines in platelets was determined. Reverse transcriptase–polymerase chain reaction studies with platelet RNA did not detect the presence of SDF-1 or MDC. In summary, SDF-1 and MDC are platelet agonists that activate distinct intracellular pathways. Their importance in the development of thrombosis at sites of inflammation needs to be further evaluated.
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Kowalska, M. Anna, Mariusz Z. Ratajczak, Marcin Majka, Jianguo Jin, Satya Kunapuli, Lawrence Brass, and Mortimer Poncz. "Stromal cell–derived factor-1 and macrophage-derived chemokine: 2 chemokines that activate platelets." Blood 96, no. 1 (July 1, 2000): 50–57. http://dx.doi.org/10.1182/blood.v96.1.50.013k40_50_57.
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Platelets play roles in both thrombosis and inflammation, and chemokines that are released at sites of inflammation could potentially activate platelets. Among the chemokine receptors expressed on platelets, the CXCR4 is the receptor for chemokine stromal cell-derived factor-1 (SDF-1), and the CCR4 is the receptor for macrophage-derived chemokine (MDC). Of the chemokines tested, SDF-1 and MDC were the only 2 that activated platelets. Both are weak agonists, but they enhanced response to low-dose adenosine 5′-diphosphate (ADP), epinephrine, or serotonin. When SDF-1 and MDC were added together, full and brisk platelet aggregation occurred. Platelet activation by these 2 chemokines appears to involve distinct pathways: SDF-1 inhibited an increase in cyclic adenosine monophosphate (cAMP) following prostaglandin (PG) I2, while MDC had no effect. In contrast, MDC, but not SDF-1, lead to Ca++mobilization by platelets. Further, second-wave aggregation induced by MDC in platelet-rich plasma was inhibited by aspirin, ADP scavenger creatine phosphate/creative phosphokinase (CP/CPK), and ARL-66096, an antagonist of the ADP P2TAC receptor involved in adenylyl cyclase inhibition. But the aggregation was not affected by A3P5PS, an inhibitor of the ADP P2Y receptor. SDF-1–induced aggregation was inhibited by aspirin, but it was only slightly affected by CP/CPK, ARL-66096, or A3P5PS. Finally, the presence of chemokines in platelets was determined. Reverse transcriptase–polymerase chain reaction studies with platelet RNA did not detect the presence of SDF-1 or MDC. In summary, SDF-1 and MDC are platelet agonists that activate distinct intracellular pathways. Their importance in the development of thrombosis at sites of inflammation needs to be further evaluated.
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Chetham, P. M., H. A. Guldemeester, N. Mons, G. H. Brough, J. P. Bridges, W. J. Thompson, and T. Stevens. "Ca(2+)-inhibitable adenylyl cyclase and pulmonary microvascular permeability." American Journal of Physiology-Lung Cellular and Molecular Physiology 273, no. 1 (July 1, 1997): L22—L30. http://dx.doi.org/10.1152/ajplung.1997.273.1.l22.
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Intracellular mechanisms responsible for endothelial cell disruption are unknown, although either elevated cytosolic Ca2+ ([Ca2+]i) or decreased adenosine 3',5'-cyclic monophosphate (cAMP) promotes permeability. Recent identification that Ca(2+)-inhibitable adenylyl cyclase establishes an inverse relationship between [Ca2+]i and cAMP in macrovascular endothelial cells provided a possible mechanism of development of permeability. However, these data utilized an in vitro model; lacking was evidence supporting 1) expression of Ca(2+)-inhibitable adenylyl cyclase in pulmonary microvascular endothelium and 2) Ca2+ inhibition of adenylyl cyclase and cAMP content as a paradigm for inflammatory mediator-induced permeability in the intact circulation. We therefore addressed these issues in microvascular endothelial cells derived from rat lung and in an isolated perfused rat lung preparation. Results demonstrate expression of a Ca(2+)-inhibitable adenylyl cyclase in microvascular endothelial cells. Furthermore, data suggest that Ca2+ inhibition of adenylyl cyclase is necessary for development of microvascular permeability in the intact circulation. We conclude Ca2+ inhibition of cAMP represents a critical step in genesis of microvascular permeability in the intact pulmonary circulation.
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Hu, Ye, Chuhan Lu, Yujing Qin, and Jiaxi Cai. "Comparison of Two Automatic Identification Algorithms for Cyclones Affecting the Changjiang River–Huaihe River Valleys." Atmosphere 10, no. 3 (March 3, 2019): 115. http://dx.doi.org/10.3390/atmos10030115.
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In this study, two commonly used automated methods of detecting cyclones in the lower troposphere were compared with respect to various features of cyclone activity. The first method is based on the neighbor cyclone center point (NCP), while the second method is the cyclone area algorithm (CAA), which relies on the detection of the outermost enclosed contour to identify the horizontal structure of a cyclone. We obtained climatologies of cyclones that affected the Changjiang River–Huaihe River Valleys (CHV) of China (derived from ERA-Interim data for 1979–2015) and compared their structures. We found that the distribution of the track and the cyclogenesis locations of influential cyclones (ICs) showed a consistent spatial pattern between the NCP and CAA. However, there were still notable differences between the statistical features of cyclone activity derived by the NCP and CAA: (1) Only <46% of cyclones shared the same cyclone center between these two schemes. (2) ICs derived from the CAA typically had longer lifetimes and travel distances, with stronger central intensities than those from the NCP. (3) The track of ICs by the CAA with high resolution was consistent with that of ICs by the low-resolution CAA as well as the low-resolution NCP. However, compared to other methods, the high-resolution NCP presented large deviations during the early cyclone stage. The involvement of open systems in the NCP resulted in weaker cyclone intensities and increased uncertainty in cyclone tracking. On the other hand, more cyclones with stronger intensities and longer lifetimes coming from the midlatitudes were detected using the CAA. In addition, the short-lifetime ICs (<18 h) found using the CAA were active (39%) in the CHV, and were typically excluded by the NCP. These ICs had comparable center intensity and showed a good correlation with the occurrence of simultaneous rainfall events.
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Toya, Yoshiyuki, Carsten Schwencke, Jacques Couet, Michael P. Lisanti, and Yoshihiro Ishikawa. "Inhibition of Adenylyl Cyclase by Caveolin Peptides*." Endocrinology 139, no. 4 (April 1, 1998): 2025–31. http://dx.doi.org/10.1210/endo.139.4.5957.
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Abstract Caveolae and their principal component caveolin have been implicated in playing a major role in G protein-mediated transmembrane signaling. We examined whether caveolin interacts with adenylyl cyclase, an effector of G protein signaling, using a 20-mer peptide derived from the N-terminus scaffolding domain of caveolin-1. When tissue adenylyl cyclases were examined, cardiac adenylyl cyclase was inhibited more potently than other tissue adenylyl cyclases. The caveolin-1 peptide inhibited type V, as well as type III adenylyl cyclase, overexpressed in insect cells, whereas the same peptide had no effect on type II. The caveolin-3 scaffolding domain peptide similarly inhibited type V adenylyl cyclase. In contrast, peptides derived from the caveolin-2 scaffolding domain and a caveolin-1 nonscaffolding domain had no effect. Kinetic studies showed that the caveolin-1 peptide decreased the maximal rate (Vmax) value of type V without changing the Michaelis constant (Km) value for the substrate ATP. Studies with various truncations and point mutations of this peptide revealed that a minimum of 16 amino acid residues and intact aromatic residues are important for the inhibitory effect. The potency of inhibition was greater when adenylyl cyclase was in stimulated condition vs. basal condition. Thus, caveolin may be another cellular component that regulates adenylyl cyclase catalytic activity. Our results also suggest that the caveolin peptide may be used as an isoform-selective inhibitor of adenylyl cyclase.
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Pyne, N. J., N. Moughal, P. A. Stevens, D. Tolan, and S. Pyne. "Protein kinase C-dependent cyclic AMP formation in airway smooth muscle: the role of type II adenylate cyclase and the blockade of extracellular-signal-regulated kinase-2 (ERK-2) activation." Biochemical Journal 304, no. 2 (December 1, 1994): 611–16. http://dx.doi.org/10.1042/bj3040611.
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Bradykinin activates adenylate cyclase via a pathway that involves the ‘up-stream’ regulation of phospholipase D (PLD)-catalysed hydrolysis of phosphatidylcholine and activation of protein kinase C (PKC) in airway smooth muscle [Stevens, Pyne, Grady and Pyne (1994) Biochem. J. 297, 233-239]. Coincident signal (Gs alpha and PKC) amplification of the cyclic AMP response can be completely attenuated either by diverting PLD-derived phosphatidate or by inhibiting PKC. In this regard, the coincident signal detector type II adenylate cyclase is expressed as a 110/112 kDa polypeptide in these cells. PKC alpha is not involved in the activation of adenylate cyclase, since a B2-receptor antagonist (NPC567, 10 microM) blocked its bradykinin-stimulated translocation to the membrane and was without effect against both bradykinin-stimulated PLD activity and cyclic AMP formation. Cyclic AMP formation can also be activated by platelet-derived growth factor (PDGF), via a PKC-dependent pathway, although the magnitude of the response is less than that elicited by bradykinin. Nevertheless, these results indicate that multiple receptor types employ PKC to initiate cyclic AMP signals. PDGF (10 ng/ml) elicited the marked sustained activation of extracellular-signal-regulated kinase-2 (ERK-2), whereas bradykinin (1 microM) provoked only modest transient activation of ERK-2. Deoxyadenosine (0.1 mM), a P-site inhibitor of adenylate cyclase, blocked bradykinin-stimulated cyclic AMP formation and converted the activation of ERK-2 into a sustained response. Thus the PKC-stimulated cyclic AMP response can limit the activation of ERK-2 in response to bradykinin. These studies indicate that the integration of distinct signal pathways by adenylate cyclase can determine the kinetics of ERK activation, an enzyme that appears to be important for mitogenic progression.
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Singh, Rajkumar Kamaljit, Khoisnam Nanaoba Singh, Mamata Maisnam, Jayaprasad P., and Saroj Maity. "Antarctic Sea Ice Extent from ISRO’s SCATSAT-1 Using PCA and An Unsupervised Classification." Proceedings 2, no. 7 (March 22, 2018): 340. http://dx.doi.org/10.3390/ecrs-2-05153.
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Indian Space Research Organisation’s SCATSAT-1 is a continuity mission for Oceansat-2 Scatterometer. The sensor works in a Ku-band (13.515 GHz) similar to the one flown on-board Oceansat-2. It provides backscattering coefficient over the globe and wind vector data products over the oceans that are useful for weather forecasting, cyclone detection, and tracking services. Besides backscattering coefficient (sigma nought), two other important parameters, namely, Gamma nought (obtained from backscattering coefficient) and Brightness temperature (obtained from scatterometer noise measurement) are given as the Level-4 data products archived at the ISRO’s Meteorological & Oceanographic Satellite Data Archival Centre. We used these three parameters both in horizontal and vertical polarizations for the Antarctic region (South Polar) to perform, first, a principal component analysis. Then, we used the first three principal components explaining the largest variability in the data set to perform an unsupervised ISODATA clustering classification to estimate the regions of sea ice around Antarctica. The derived sea ice extent through this method is compared with other popular sea ice extent products available elsewhere.
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Foerster, Annette M., and Michael M. Bell. "Thermodynamic Retrieval in Rapidly Rotating Vortices from Multiple-Doppler Radar Data." Journal of Atmospheric and Oceanic Technology 34, no. 11 (November 2017): 2353–74. http://dx.doi.org/10.1175/jtech-d-17-0073.1.
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AbstractThermodynamic retrievals can derive pressure and temperature information from kinematic measurements in regions where no in situ observations are available. This study presents a new retrieval technique called SAMURAI-TR (Spline Analysis at Mesoscale Utilizing Radar and Aircraft Instrumentation–Thermodynamic Retrieval) that derives three-dimensional fields of pressure and density potential temperature from multiple-Doppler radar data using a variational approach. SAMURAI-TR advances existing methods by 1) allowing for a horizontal variation in the reference-state definition and 2) representing the retrieved quantities of pressure and temperature as three-dimensional functions consisting of a series of finite-element cubic B-splines. The first advancement enables the retrieval to explicitly account for the large radial gradient of the mean thermodynamic state in tropical cyclones and other rapidly rotating vortices. The second advancement allows for specification of the three-dimensional pressure and temperature gradients as pseudo-observations from Doppler-derived winds, effectively linking the vertical levels without the use of the thermodynamic equation or a microphysical closure. The retrieval uses only the horizontal and vertical momentum equations, their derivatives, and low-pass filters. The accuracy and sensitivity of the retrieval are assessed using a WRF simulation of a tropical cyclone. SAMURAI-TR has good accuracy compared to prior techniques and retrieves pressure to within 0.25 hPa and temperature to within 0.7 K RMSE. The application of the method to real data is demonstrated using multiple-Doppler data from Hurricane Rita (2005).
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Berger, Howard, Rolf Langland, Christopher S. Velden, Carolyn A. Reynolds, and Patricia M. Pauley. "Impact of Enhanced Satellite-Derived Atmospheric Motion Vector Observations on Numerical Tropical Cyclone Track Forecasts in the Western North Pacific during TPARC/TCS-08." Journal of Applied Meteorology and Climatology 50, no. 11 (November 2011): 2309–18. http://dx.doi.org/10.1175/jamc-d-11-019.1.
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AbstractEnhanced atmospheric motion vectors (AMVs) produced from the geostationary Multifunctional Transport Satellite (MTSAT) are assimilated into the U.S. Navy Operational Global Atmospheric Prediction System (NOGAPS) to evaluate the impact of these observations on tropical cyclone track forecasts during the simultaneous western North Pacific Ocean Observing System Research and Predictability Experiment (THORPEX) Pacific Asian Regional Campaign (TPARC) and the Tropical Cyclone Structure—2008 (TCS-08) field experiments. Four-dimensional data assimilation is employed to take advantage of experimental high-resolution (space and time) AMVs produced for the field campaigns by the Cooperative Institute for Meteorological Satellite Studies. Two enhanced AMV datasets are considered: 1) extended periods produced at hourly intervals over a large western North Pacific domain using routinely available MTSAT imagery and 2) limited periods over a smaller storm-centered domain produced using special MTSAT rapid-scan imagery. Most of the locally impacted forecast cases involve Typhoons Sinlaku and Hagupit, although other storms are also examined. On average, the continuous assimilation of the hourly AMVs reduces the NOGAPS tropical cyclone track forecast errors—in particular, for forecasts longer than 72 h. It is shown that the AMVs can improve the environmental flow analyses that may be influencing the tropical cyclone tracks. Adding rapid-scan AMV observations further reduces the NOGAPS forecast errors. In addition to their benefit in traditional data assimilation, the enhanced AMVs show promise as a potential resource for advanced objective data-targeting methods.
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Velden, Christopher, William E. Lewis, Wayne Bresky, David Stettner, Jaime Daniels, and Steven Wanzong. "Assimilation of High-Resolution Satellite-Derived Atmospheric Motion Vectors: Impact on HWRF Forecasts of Tropical Cyclone Track and Intensity." Monthly Weather Review 145, no. 3 (March 2017): 1107–25. http://dx.doi.org/10.1175/mwr-d-16-0229.1.
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It is well known that global numerical model analyses and forecasts benefit from the routine assimilation of atmospheric motion vectors (AMVs) derived from meteorological satellites. Recent studies have also shown that the assimilation of enhanced (spatial and temporal) AMVs can benefit research-mode regional model forecasts of tropical cyclone track and intensity. In this study, the impact of direct assimilation of enhanced (higher resolution) AMV datasets in the NCEP operational Hurricane Weather Research and Forecasting Model (HWRF) system is investigated. Forecasts of Atlantic tropical cyclone track and intensity are examined for impact by inclusion of enhanced AMVs via direct data assimilation. Experiments are conducted for AMVs derived using two methodologies (“HERITAGE” and “GOES-R”), and also for varying levels of quality control in order to assess and inform the optimization of the AMV assimilation process. Results are presented for three selected Atlantic tropical cyclone events and compared to Control forecasts without the enhanced AMVs as well as the corresponding operational HWRF forecasts. The findings indicate that the direct assimilation of high-resolution AMVs has an overall modest positive impact on HWRF forecasts, but the impact magnitudes are dependent on the 1) availability of rapid scan imagery used to produce the AMVs, 2) AMV derivation approach, 3) level of quality control employed in the assimilation, and 4) vortex initialization procedure (including the degree to which unbalanced states are allowed to enter the model analyses).
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Naud, Catherine M., James F. Booth, Matthew Lebsock, and Mircea Grecu. "Observational Constraint for Precipitation in Extratropical Cyclones: Sensitivity to Data Sources." Journal of Applied Meteorology and Climatology 57, no. 4 (April 2018): 991–1009. http://dx.doi.org/10.1175/jamc-d-17-0289.1.
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AbstractUsing cyclone-centered compositing and a database of extratropical-cyclone locations, the distribution of precipitation frequency and rate in oceanic extratropical cyclones is analyzed using satellite-derived datasets. The distribution of precipitation rates retrieved using two new datasets, the Global Precipitation Measurement radar–microwave radiometer combined product (GPM-CMB) and the Integrated Multisatellite Retrievals for GPM product (IMERG), is compared with CloudSat, and the differences are discussed. For reference, the composites of AMSR-E, GPCP, and two reanalyses are also examined. Cyclone-centered precipitation rates are found to be the largest with the IMERG and CloudSat datasets and lowest with GPM-CMB. A series of tests is conducted to determine the roles of swath width, swath location, sampling frequency, season, and epoch. In all cases, these effects are less than ~0.14 mm h−1 at 50-km resolution. Larger differences in the composites are related to retrieval biases, such as ground-clutter contamination in GPM-CMB and radar saturation in CloudSat. Overall the IMERG product reports precipitation more often, with larger precipitation rates at the center of the cyclones, in conditions of high precipitable water (PW). The CloudSat product tends to report more precipitation in conditions of dry or moderate PW. The GPM-CMB product tends to systematically report lower precipitation rates than the other two datasets. This intercomparison provides 1) modelers with an observational uncertainty and range (0.21–0.36 mm h−1 near the cyclone centers) when using composites of precipitation for model evaluation and 2) retrieval-algorithm developers with a categorical analysis of the sensitivity of the products to PW.
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Conaty, A. L., J. C. Jusem, L. Takacs, D. Keyser, and R. Atlas. "The Structure and Evolution of Extratropical Cyclones, Fronts, Jet Streams, and the Tropopause in the GEOS General Circulation Model." Bulletin of the American Meteorological Society 82, no. 9 (September 1, 2001): 1853–68. http://dx.doi.org/10.1175/1520-0477-82.9.1853.
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The realism of extratropical cyclones, fronts, jet streams, and the tropopause in the Goddard Earth Observing System (GEOS) general circulation model (GCM), implemented in assimilation and simulation modes, is evaluated from climatological and case-study perspectives using the GEOS-1 reanalysis climatology and applicable conceptual models as benchmarks for comparison. The latitude-longitude grid spacing of the datasets derived from the GEOS GCM ranges from 2° × 2.5° to 0.5° × 0.5°. Frontal systems in the higher-resolution datasets are characterized by horizontal potential temperature gradients that are narrower in scale and larger in magnitude than their lower-resolution counterparts, and various structural features in the Shapiro–Keyser cyclone model are replicated with reasonable fidelity at 1° × 1° resolution. The remainder of the evaluation focuses on a 3-month Northern Hemisphere winter simulation of the GEOS GCM at 1° × 1° resolution. The simulation realistically reproduces various large-scale circulation features related to the North Pacific and Atlantic jet streams when compared with the GEOS-1 reanalysis climatology, and conforms closely to a conceptualization of the zonally averaged troposphere and stratosphere proposed originally by Napier Shaw and revised by Hoskins. An extratropical cyclone that developed over the North Atlantic Ocean in the simulation features surface and tropopause evolutions corresponding to the Norwegian cyclone model and to the LC2 life cycle proposed by Thorncroft et al., respectively. These evolutions are related to the position of the developing cyclone with respect to upper-level jets identified in the time-mean and instantaneous flow fields. This article concludes with the enumeration of several research opportunities that may be addressed through the use of state-of-the-art GCMs possessing sufficient resolution to represent mesoscale phenomena and processes explicitly.
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Konor, Celal S., and David A. Randall. "Impacts of the horizontal and vertical grids on the numerical solutions of the dynamical equations – Part 1: Nonhydrostatic inertia–gravity modes." Geoscientific Model Development 11, no. 5 (May 8, 2018): 1753–84. http://dx.doi.org/10.5194/gmd-11-1753-2018.
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Abstract. We have used a normal-mode analysis to investigate the impacts of the horizontal and vertical discretizations on the numerical solutions of the nonhydrostatic anelastic inertia–gravity modes on a midlatitude f plane. The dispersion equations are derived from the linearized anelastic equations that are discretized on the Z, C, D, CD, (DC), A, E and B horizontal grids, and on the L and CP vertical grids. The effects of both horizontal grid spacing and vertical wavenumber are analyzed, and the role of nonhydrostatic effects is discussed. We also compare the results of the normal-mode analyses with numerical solutions obtained by running linearized numerical models based on the various horizontal grids. The sources and behaviors of the computational modes in the numerical simulations are also examined. Our normal-mode analyses with the Z, C, D, A, E and B grids generally confirm the conclusions of previous shallow-water studies for the cyclone-resolving scales (with low horizontal wavenumbers). We conclude that, aided by nonhydrostatic effects, the Z and C grids become overall more accurate for cloud-resolving resolutions (with high horizontal wavenumbers) than for the cyclone-resolving scales. A companion paper, Part 2, discusses the impacts of the discretization on the Rossby modes on a midlatitude β plane.
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Heymsfield, Gerald M., Lin Tian, Andrew J. Heymsfield, Lihua Li, and Stephen Guimond. "Characteristics of Deep Tropical and Subtropical Convection from Nadir-Viewing High-Altitude Airborne Doppler Radar." Journal of the Atmospheric Sciences 67, no. 2 (February 1, 2010): 285–308. http://dx.doi.org/10.1175/2009jas3132.1.
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Abstract This paper presents observations of deep convection characteristics in the tropics and subtropics that have been classified into four categories: tropical cyclone, oceanic, land, and sea breeze. Vertical velocities in the convection were derived from Doppler radar measurements collected during several NASA field experiments from the nadir-viewing high-altitude ER-2 Doppler radar (EDOP). Emphasis is placed on the vertical structure of the convection from the surface to cloud top (sometimes reaching 18-km altitude). This unique look at convection is not possible from other approaches such as ground-based or lower-altitude airborne scanning radars. The vertical motions from the radar measurements are derived using new relationships between radar reflectivity and hydrometeor fall speed. Various convective properties, such as the peak updraft and downdraft velocities and their corresponding altitude, heights of reflectivity levels, and widths of reflectivity cores, are estimated. The most significant findings are the following: 1) strong updrafts that mostly exceed 15 m s−1, with a few exceeding 30 m s−1, are found in all the deep convection cases, whether over land or ocean; 2) peak updrafts were almost always above the 10-km level and, in the case of tropical cyclones, were closer to the 12-km level; and 3) land-based and sea-breeze convection had higher reflectivities and wider convective cores than oceanic and tropical cyclone convection. In addition, the high-resolution EDOP data were used to examine the connection between reflectivity and vertical velocity, for which only weak linear relationships were found. The results are discussed in terms of dynamical and microphysical implications for numerical models and future remote sensors.
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Noel, James, and David Changnon. "A Pilot Study Examining U.S. Winter Cyclone Frequency Patterns Associated with Three ENSO Parameters." Journal of Climate 11, no. 8 (August 1, 1998): 2152–59. http://dx.doi.org/10.1175/1520-0442-11.8.2152.
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Abstract Teleconnections were used to link three El Niño–Southern Oscillation (ENSO) parameters to winter (December–February) cyclone frequencies over the United States during the 1949–96 period. Since each ENSO event is not exactly the same, small subsets of ENSO events were examined in addition to the more common composite ENSO event. Mean winter cyclone frequencies, derived by counting cyclones passing through 30, 5° latitude equal-area circles located in a grid from 70° to 120°W and 30° to 50°N were determined for classes of El Niños and La Niñas based on 1) the intensity of the equatorial Pacific sea surface temperature anomaly, 2) the intensity of the Tahiti–Darwin sea level pressure anomaly, and 3) the location of the 28°C isotherm. The average cyclone count for each class of El Niño and La Niña was compared to the average count for winters when no ENSO event occurred. Expected differences in cyclone frequency patterns when comparing an average of all El Niño winters to all La Niña winters were found; however, large pattern differences were also determined when comparing winters with strong El Niños to moderate–weak El Niños and similarly for La Niñas. Significant differences in number of cyclones were found in 8 of 30 circles located in the Pacific Northwest, the Great Lakes, New England, and the Southeast. The differences found in the cyclone frequency patterns for El Niños and La Niñas of different intensities and locations indicated that using a composite of all El Niños or La Niñas may provide misleading information while examination of each of these parameters independently may assist in the preparation of long-range climate predictions.
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Nelson, T. Connor, Lee Harrison, and Kristen L. Corbosiero. "Examination of the Expendable Digital Dropsonde–Derived Vertical Velocities from the Tropical Cyclone Intensity (TCI) Experiment." Monthly Weather Review 147, no. 7 (June 11, 2019): 2367–86. http://dx.doi.org/10.1175/mwr-d-18-0414.1.
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Abstract The newly developed expendable digital dropsonde (XDD) allows for high spatial and temporal resolution data collection in tropical cyclones (TCs). In 2015, a total of 725 XDDs were launched into Hurricanes Marty (27–28 September), Joaquin (2–5 October), and Patricia (20–23 October) as part of the Tropical Cyclone Intensity (TCI) experiment. These dropsondes were launched from a NASA WB-57 at altitudes above 18 km, capturing the full depth of the TCs to the tropopause. This study documents the vertical velocity distributions observed in TCI using the XDDs and examines the distributions altitudinally, radially, and azimuthally. The strongest mean or median XDD-derived vertical velocities observed during TCI occurred in the upper levels and within the cores of the three TCs. There was little azimuthal signal in the vertical velocity distribution, likely due to sampling asymmetries and noise in the data. Downdrafts were strongest in Joaquin, while updrafts were strongest in Patricia, especially within the eyewall on 23 October. Patricia also had an impressive low-level (<2 km) updraft that exceeded 10 m s−1 associated with a shallow, overturning, radial circulation in the secondary eyewall.
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Hodyss, Daniel, and Eric Hendricks. "The Resonant Excitation of Baroclinic Waves by the Divergent Circulation of Recurving Tropical Cyclones." Journal of the Atmospheric Sciences 67, no. 11 (November 1, 2010): 3600–3616. http://dx.doi.org/10.1175/2010jas3459.1.
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Abstract This paper explores the hypothesis that a tropical cyclone (TC) may produce baroclinic waves through the divergent circulation that arises from its low-level inflow and upper-level outflow. The model setting is a quasigeostrophic (QG) two-layer fluid in which the effect of the tropical cyclone is parameterized through a source term on the QG potential vorticity equation. Equations predicting the spectral subset of baroclinic waves that are excited through linear resonance are derived. The near-TC pattern of the baroclinic waves in the streamfunction field typically takes the form of a ridge–trough couplet whose phase with respect to the TC varies with the speed and direction of the TCs motion vector. The predictions from the linearized theory are verified in two ways: 1) fully nonlinear simulations are shown and 2) comparison is made to the observed upper-level ridge–trough couplets produced by recurving TCs in the Navy’s Operational Global Prediction System (NOGAPS). The implications of this work for the predictability of downstream impacts from recurving TCs are briefly described.
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PYNE, Susan, and Nigel J. PYNE. "The differential regulation of cyclic AMP by sphingomyelin-derived lipids and the modulation of sphingolipid-stimulated extracellular signal regulated kinase-2 in airway smooth muscle." Biochemical Journal 315, no. 3 (May 1, 1996): 917–23. http://dx.doi.org/10.1042/bj3150917.
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We report that sphingosine and short-chain ceramides activate adenylate cyclase and stimulate intracellular cyclic AMP formation in airway-smooth-muscle (ASM) cells. In each case, there is a conditional requirement for GTP-Gsα. Sphingosine utilizes a protein kinase C-dependent pathway to elicit activation of adenylate cyclase, whereas for short-chain ceramides the mechanism remains unidentified. In contrast, sphingosine phosphate inhibits Gs-stimulated cyclic AMP formation via a Gi-dependent mechanism. Therefore, the potential interconversion of sphingosine and sphingosine phosphate is a switch that can elicit reciprocal changes in cyclic AMP levels. This may have a significant impact upon the regulation of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal specific kinase (JNK) by sphingolipids and may help to explain how growth factors that utilize these second messengers evoke pleiotropic responses such as proliferation and cell survival. In this context, short-chain ceramides are poor stimulators of ERKs in ASM cells, and sphingosine is inactive, whereas both sphingolipids are powerful activators of the JNK module. Activated JNK catalyses N-terminal phosphorylation of c-Jun, a kinase cascade that programmes growth arrest. Therefore, in blocking ceramide-stimulated ERK-2 activity, cyclic AMP may allow the ceramide-dependent activation of JNK to programme cells to opt out of the cell cycle. In contrast, sphingosine phosphate activates ERK-2, potentiates growth-factor-stimulated DNA synthesis and fails to activate JNK, indicating that its sequential formation from ceramide and sphingosine may commit cells to DNA synthesis. ERK-2 can be activated by both cyclic AMP-sensitive c-Raf-1 kinase-dependent and cyclic AMP-insensitive c-Raf-1 kinase-independent pathways in ASM cells. In this context, sphingosine phosphate activates ERK-2 exclusively via c-Raf-1 kinase. Sphingosine phosphate-stimulated ERK-2 activity is also abolished by pertussis toxin, indicating that c-Raf-1 kinase is activated via a Gi-dependent mechanism.
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Miller, BA, K. Foster, JD Robishaw, CF Whitfield, L. Bell, and JY Cheung. "Role of pertussis toxin-sensitive guanosine triphosphate-binding proteins in the response of erythroblasts to erythropoietin." Blood 77, no. 3 (February 1, 1991): 486–92. http://dx.doi.org/10.1182/blood.v77.3.486.486.
Full textAbstract:
Abstract Human progenitor-derived erythroblasts have been recently shown to respond to erythropoietin (Epo) with an increase in intracellular free calcium concentration [Cac]. To explore the role of guanosine triphosphate (GTP)-binding proteins in mediating the rise in [Cac], single day 10 erythroid burst forming unit (BFU-E)-derived erythroblasts loaded with Fura-2 were pretreated with pertussis toxin (PT), stimulated with Epo, and [Cac] measured over 18 minutes with fluorescence microscopy coupled to digital video imaging. The [Cac] increase in day 10 erythroblasts stimulated with Epo was blocked by pretreatment with PT in a dose-dependent manner but not by heat- inactivated PT. These observations provided strong evidence that a PT- sensitive GTP-binding protein is involved. To further characterize the GTP-binding protein, day 10 erythroblast membrane preparations were solubilized, electrophoresed, and immunoblotted with antibodies specific for the known PT-sensitive G-protein subunits: the three subtypes of Gia (1,2, and 3) and Goa, Gia1 or Gia3 and Gia2 were identified but no Goa was found. To examine the influence of Epo on adenylate cyclase activity, day 10 erythroblasts were initially treated with Epo, isolated membrane preparations made, and cyclic adenosine monophosphate (cAMP) production by adenylate cyclase in membrane preparations in the presence of theophylline measured. Epo did not inhibit but significantly stimulated adenylate cyclase activity. However, the mechanism of increase of [Cac] appears to be independent of adenylate cyclase stimulation because treatment of erythroblasts with the cell-permeant dibutyryl cAMP failed to increase [Cac]. In summary, pertussis toxin blocks the increase in [Cac] in erythroblasts after Epo stimulation suggesting that this response is mediated through a pertussis toxin-sensitive GTP-binding protein. Candidate PT-sensitive GTP-binding proteins identified on day 10 erythroblasts were Gia 1, 2, or 3, but not Goa.
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Miller, BA, K. Foster, JD Robishaw, CF Whitfield, L. Bell, and JY Cheung. "Role of pertussis toxin-sensitive guanosine triphosphate-binding proteins in the response of erythroblasts to erythropoietin." Blood 77, no. 3 (February 1, 1991): 486–92. http://dx.doi.org/10.1182/blood.v77.3.486.bloodjournal773486.
Full textAbstract:
Human progenitor-derived erythroblasts have been recently shown to respond to erythropoietin (Epo) with an increase in intracellular free calcium concentration [Cac]. To explore the role of guanosine triphosphate (GTP)-binding proteins in mediating the rise in [Cac], single day 10 erythroid burst forming unit (BFU-E)-derived erythroblasts loaded with Fura-2 were pretreated with pertussis toxin (PT), stimulated with Epo, and [Cac] measured over 18 minutes with fluorescence microscopy coupled to digital video imaging. The [Cac] increase in day 10 erythroblasts stimulated with Epo was blocked by pretreatment with PT in a dose-dependent manner but not by heat- inactivated PT. These observations provided strong evidence that a PT- sensitive GTP-binding protein is involved. To further characterize the GTP-binding protein, day 10 erythroblast membrane preparations were solubilized, electrophoresed, and immunoblotted with antibodies specific for the known PT-sensitive G-protein subunits: the three subtypes of Gia (1,2, and 3) and Goa, Gia1 or Gia3 and Gia2 were identified but no Goa was found. To examine the influence of Epo on adenylate cyclase activity, day 10 erythroblasts were initially treated with Epo, isolated membrane preparations made, and cyclic adenosine monophosphate (cAMP) production by adenylate cyclase in membrane preparations in the presence of theophylline measured. Epo did not inhibit but significantly stimulated adenylate cyclase activity. However, the mechanism of increase of [Cac] appears to be independent of adenylate cyclase stimulation because treatment of erythroblasts with the cell-permeant dibutyryl cAMP failed to increase [Cac]. In summary, pertussis toxin blocks the increase in [Cac] in erythroblasts after Epo stimulation suggesting that this response is mediated through a pertussis toxin-sensitive GTP-binding protein. Candidate PT-sensitive GTP-binding proteins identified on day 10 erythroblasts were Gia 1, 2, or 3, but not Goa.
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Davis, J. B., and P. Stroobant. "Platelet-derived growth factors and fibroblast growth factors are mitogens for rat Schwann cells." Journal of Cell Biology 110, no. 4 (April 1, 1990): 1353–60. http://dx.doi.org/10.1083/jcb.110.4.1353.
Full textAbstract:
Rat sciatic nerve Schwann cells in culture respond to a limited range of mitogens, including glial growth factor, transforming growth factors beta-1 and beta-2 (TGF-beta 1, TGF-beta 2), some cell membrane-associated factors, and to agents such as cholera toxin and forskolin which raise intracellular levels of cAMP. These responses require the presence of FCS, which exhibits little or no mitogenic activity in the absence of other factors. However, we recently found that forskolin greatly potentiates the mitogenic signal from TGFs-beta 1 and beta 2, raising the possibility that cAMP might couple other factors to mitogenesis. We have therefore screened a range of candidate mitogens using DNA synthesis assays. Other than TGFs-beta and glial growth factor, none of the factors tested were mitogenic in the presence of 10% serum alone. With the addition of forskolin, however, porcine PDGF, human PDGF, acidic and basic FGF were potent mitogens for rat Schwann cells, stimulating DNA synthesis and increasing cell number. Cholera toxin and dibutyrylcyclicAMP, but not 1,9-dideoxyforskolin, can substitute for forskolin indicating that the mitogenic effect is mediated via adenylyl cyclase activation. Porcine PDGF gave half-maximal stimulation at 15 pM, and human PGDF an equivalent response at 1 nM. Basic FGF was half maximal at 5 pM, acidic FGF at 1 nM. The recognition of PDGFs and FGFs as mitogens for Schwann cells has many implications for the study of Schwann cell proliferation in the development and regeneration of nerves, and in Schwann cell tumorigenesis.
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Gonuguntla, Hemalatha, Khudoyberdi Abdivaitov, Mahalingam Bose, and Muzaffar Rakhmataliev. "A comparison of Sentinel-1 and Sentinel-2 in assessing flooded area and built-up land use: A case study of selected coastal districts in Andra Pradesh, India." InterCarto. InterGIS 26, no. 2 (2020): 421–35. http://dx.doi.org/10.35595/2414-9179-2020-2-26-421-435.
Full textAbstract:
In tropical climatic conditions, floods occur during heavy rainfall. Floods during this thick cloud cover partially stops the optical imagery to pass through the atmosphere and record the surface reflectance. Another kind of satellite imagery that is available is microwave remote sensing data that can pass through the clouds. However, the exploration of this microwave remote sensing began recently for earth observation applications. So, the algorithms and methods available for exploiting advantages from microwave data is still under research. The current part of the work is to explore the methods available to differentiate between the microwave data (Sentinel-1) and Optical imagery (Sentinel-2) in flooded and built-up area estimation. The ultimate aim is to conclude with most suitable datasets and fast computing methods in estimating the built-up area and flooded area during the emergency disaster time. Two case studies taken up for the study are August 2019 East Godavari floods and October 2019 Titli cyclone. So, the adopted method to estimate the flooded areas and built-up areas from the Sentinel-1A and Sentinel-2B was RGB clustering (Red, Green and Blue clustering) using the derived RGB colour combinations in snap 7.0 software. The datasets were classified into built-up, flooded area and vegetation areas using Random Forest supervised classification, a machine learning technique Validation of estimated built-up and flooded areas estimated from Sentinel-1A and Sentinel-2B was done using the random pixel distribution technique. Since the de-centralisation of estimated flooded areas and built-up area helps in fast distribution of the response forces to the affected area, estimation of built-up and flooded area was also taken up for the sub-districts of East Godavari district, India. Finally, the study estimates the damaged built-up and vegetation due to August 2019 East Godavari floods from Sentinel-1A and Sentinel-2B. Flooded area due to ‘Titli’ cyclone 2018 was estimated in East Godavari, Visakhapatnam and Vijianagaram districts of Andhra Pradesh state.
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Beasley, Debbie. "COX-2 and cytosolic PLA2mediate IL-1β-induced cAMP production in human vascular smooth muscle cells." American Journal of Physiology-Heart and Circulatory Physiology 276, no. 4 (April 1, 1999): H1369—H1378. http://dx.doi.org/10.1152/ajpheart.1999.276.4.h1369.
Full textAbstract:
Interleukin (IL)-1 is a potent vasodilator that causes prolonged induction of prostacyclin (PGI2) and cAMP synthesis in human vascular smooth muscle cells (HVSMC). The present study investigated IL-1 induction of PG synthetic enzymes in HVSMC and tested their respective roles in PGI2 and cAMP production. Cyclooxygenase (COX)-1 mRNA was not detectable in either control or IL-1-treated HVSMC, as assessed by RT-PCR. In contrast, COX-2 mRNA was detectable in control HVSMC, increased markedly (16-fold) after 1 h of IL-1 exposure, and increased further (52-fold) after 24 h. COX-2 protein levels, assessed by Western analysis, were increased concomitantly. HVSMC contained mRNA encoding both the secreted and cytosolic forms of phospholipase A2(sPLA2 and cPLA2, respectively). IL-1 stimulation did not affect sPLA2mRNA levels, but cPLA2 mRNA levels increased at 8 h, after the initial induction of PG synthesis. HVSMC constitutively expressed PGI2synthase mRNA, and its levels were not affected by IL-1. A selective COX-2 inhibitor, NS-398, reversed IL-1-induced PGI2 and cAMP production, supporting a role of COX-2 in mediating increased PG synthesis. IL-1-induced cAMP was also reversed by a selective cPLA2 inhibitor, AACOCF3, but not by thioetheramide phosphorylcholine, which inhibits sPLA2 preferentially over cPLA2, supporting a requirement for cPLA2-derived arachidonic acid in IL-1-induced PG synthesis. The delayed induction of cPLA2 mRNA was also attenuated by NS-398, suggesting that it was secondary to the initial COX-2-induced PG synthesis. Together, the results support the hypothesis that IL-1 induces intracellular PG synthesis in HVSMC via rapid upregulation of COX-2, which utilizes cPLA2-derived arachidonic acid to generate PG metabolites that regulate adenylate cyclase.
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Agarwal, Neeraj, Stephane Oudard, Josep M. Piulats, Michael Thomas Schweizer, Aude Flechon, Teresa Alonso Gordoa, Karim Nacerddine, Andrew Lithio, Erica L. Johnston, and Matthew Raymond Smith. "CYCLONE 1: A phase 2 study of abemaciclib in patients with metastatic castration-resistant prostate cancer (mCRPC) previously treated with a novel hormonal agent and taxane-based chemotherapy." Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021): TPS5086. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.tps5086.
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TPS5086 Background: In cancer cells, the cyclin-dependent kinases 4 and 6 (CDK4 & 6)/retinoblastoma protein (Rb) pathway is commonly altered, resulting in uncontrolled cell cycle entry and proliferation. CDK4 & 6 inhibitors represent a major advance in the management of hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced or metastatic breast cancer (ABC or MBC, respectively). Abemaciclib is an oral selective inhibitor of CDK4 & 6 administered on a continuous dosing schedule, approved in combination with endocrine therapy for HR+, HER2- ABC or MBC. In addition, abemaciclib is also approved by the FDA as monotherapy for HR+, HER2- ABC or MBC following endocrine therapy and prior chemotherapy in the metastatic setting. Similar to the estrogen receptor signaling pathway in breast cancer cells, there is evidence that the androgen receptor axis activates CDK4 & 6 to sustain prostate cancer cell proliferation and survival. Preclinical studies in prostate cancer cell lines and xenograft models showed that abemaciclib exhibits single agent activity by inducing cell cycle arrest and tumor growth inhibition. Clinical activity of abemaciclib in combination with abiraterone and prednisone is investigated in a randomized phase 2 study in the first-line mCRPC setting (CYCLONE 2, NCT03706365). Despite recent advances, management of heavily pretreated mCRPC remains a major clinical challenge. Herein, we hypothesize that mCRPC patients whose disease progressed after novel hormonal agents (NHA) and taxane therapies may derive therapeutic benefit from single agent abemaciclib. Methods: CYCLONE 1 is a phase 2, single-arm, multicenter study to assess the safety and efficacy of abemaciclib monotherapy in 40 patients with mCRPC progressing after ≥1 NHA and 2 taxane regimens. Patients will be enrolled at time of prostate specific antigen (PSA) or radiographic progression per PCWG3 criteria and have at least 1 measurable lesion per RECIST 1.1. Metastatic tumor tissue (fresh biopsy or archival material <12 weeks) is required at baseline for biomarker analysis. Patients will receive abemaciclib 200 mg twice daily until unacceptable adverse events or disease progression. The primary objective is investigator-assessed objective response rate (ORR). Key secondary objectives include safety, radiographic progression-free survival, overall survival, PSA response rate, time to PSA progression, time to symptomatic progression, Ki-67 expression, patient-reported outcomes, and pharmacokinetics. Assuming an ORR of 15%, the study has over 73% power to observe a response rate of at least 12.5%. Accrual began in January 2021. Clinical trial information: NCT04408924.
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Chang, Edmund K. M. "Effects of Secular Changes in Frequency of Observations and Observational Errors on Monthly Mean MSLP Summary Statistics Derived from ICOADS." Journal of Climate 18, no. 17 (September 1, 2005): 3623–33. http://dx.doi.org/10.1175/jcli3491.1.
Full textAbstract:
Abstract A Monte Carlo technique has been employed to assess how sextile mean sea level pressure (MSLP) statistics derived from ship observations can be affected by changes in the frequency of observations. The results show that when the number of observations is small (less than 20 per month), the estimates of the first sextile as well as the intersextile range, which is considered to be a resistant estimate of the standard deviation, can contain large biases. The results also suggest that, while changes in the frequency of observations do not have strong impacts on the standard way of estimating the standard deviation, such statistics are strongly affected by secular trends in observational error statistics. The results are applied to examine the increasing trend in cool season (December–March) Pacific cyclone activity during the second half of the twentieth century. The results show that the trends in sextile statistics derived from the NCEP–NCAR reanalysis data are only consistent with those derived from the International Comprehensive Ocean–Atmosphere Data Set (ICOADS) summary statistics if biases due to changes in the frequency of observation are not taken into account. When such biases are accounted for, the trends derived from the observations are significantly smaller than those derived from the reanalysis data. As for the increasing trend in MSLP variance, the trends derived from the ICOADS statistics are smaller than those derived from the reanalysis regardless of whether corrections are made to account for the secular trend in MSLP error statistics. In either case, the corrections that have to be applied have the same order of magnitude as the observed trends. The two main conclusions are that 1) climate statistics can be strongly affected by changes in frequency of observations as well as changes in observational error statistics and 2) the trends in North Pacific winter cyclone activity, as derived from NCEP–NCAR reanalysis data, appear to be significantly larger than similar trends computed from ICOADS sextile and variance statistics, when biases due to changes in frequency of observations and observational error statistics have been taken into account.
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Ferguson, Craig R., Shubhi Agrawal, Mark C. Beauharnois, Geng Xia, D. Alex Burrows, and Lance F. Bosart. "Assimilation of Satellite-Derived Soil Moisture for Improved Forecasts of the Great Plains Low-Level Jet." Monthly Weather Review 148, no. 11 (November 2020): 4607–27. http://dx.doi.org/10.1175/mwr-d-20-0185.1.
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AbstractIn the context of forecasting societally impactful Great Plains low-level jets (GPLLJs), the potential added value of satellite soil moisture (SM) data assimilation (DA) is high. GPLLJs are both sensitive to regional soil moisture gradients and frequent drivers of severe weather, including mesoscale convective systems. An untested hypothesis is that SM DA is more effective in forecasts of weakly synoptically forced, or uncoupled GPLLJs, than in forecasts of cyclone-induced coupled GPLLJs. Using the NASA Unified Weather Research and Forecasting (NU-WRF) Model, 75 GPLLJs are simulated at 9-km resolution both with and without NASA Soil Moisture Active Passive SM DA. Differences in modeled SM, surface sensible (SH) and latent heat (LH) fluxes, 2-m temperature (T2), 2-m humidity (Q2), PBL height (PBLH), and 850-hPa wind speed (W850) are quantified for individual jets and jet-type event subsets over the south-central Great Plains, as well as separately for each GPLLJ sector (entrance, core, and exit). At the GPLLJ core, DA-related changes of up to 5.4 kg m−2 in SM can result in T2, Q2, LH, SH, PBLH, and W850 differences of 0.68°C, 0.71 g kg−2, 59.9 W m−2, 52.4 W m−2, 240 m, and 4 m s−1, respectively. W850 differences focus along the jet axis and tend to increase from south to north. Jet-type differences are most evident at the GPLLJ exit where DA increases and decreases W850 in uncoupled and coupled GPLLJs, respectively. Data assimilation marginally reduces negative wind speed bias for all jets, but the correction is greater for uncoupled GPLLJs, as hypothesized.
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Tanaka, Hiroyuki, Takanori Maruta, Masahiro Tamoi, Yukinori Yabuta, Kazuya Yoshimura, Takahiro Ishikawa, and Shigeru Shigeoka. "Transcriptional control of vitamin C defective 2 and tocopherol cyclase genes by light and plastid-derived signals: The partial involvement of GENOMES UNCOUPLED 1." Plant Science 231 (February 2015): 20–29. http://dx.doi.org/10.1016/j.plantsci.2014.11.007.
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Wang, Yaping, Xiaopeng Cui, Xiaofan Li, Wenlong Zhang, and Yongjie Huang. "Kinetic Energy Budget during the Genesis Period of Tropical Cyclone Durian (2001) in the South China Sea." Monthly Weather Review 144, no. 8 (July 22, 2016): 2831–54. http://dx.doi.org/10.1175/mwr-d-15-0042.1.
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Abstract A set of kinetic energy (KE) budget equations associated with four horizontal flow components was derived to study the KE characteristics during the genesis of Tropical Cyclone (TC) Durian (2001) in the South China Sea using numerical simulation data. The genesis process was divided into three stages: the monsoon trough stage (stage 1), the midlevel mesoscale convective vortex (MCV) stage (stage 2), and the establishment stage of the TC vortex (stage 3). Analysis showed that the KE of the symmetric rotational flow (SRF) was the largest and kept increasing, especially in stages 2 and 3, representing the symmetrization process during TC genesis. The KE of the SRF was mainly converted from the KE of the symmetric divergent flow (SDF), largely transformed from the available potential energy (APE). It was found that vortical hot towers (VHTs) emerged abundantly, aggregated, and merged within the MCV region in stages 1 and 2. From the energy budget perspective, massive moist-convection-produced latent heat was concentrated and accumulated within the MCV region, especially in stage 2, and further warmed the atmosphere, benefiting the accumulation of APE and the transformation from APE to KE. As a result, the midlevel circulation (or MCV) grew strong rapidly. In stage 3, the intensity and number of VHTs both decreased. However, affected by increasing lower-level inward radial wind, latent heat released by the organized convection, instead of disorganized VHTs in the first two stages, continuously contributed to the strengthening of the surface TC circulation as well as the warm core.
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Rodan, S. B., G. Wesolowski, J. Ianacone, M. A. Thiede, and G. A. Rodan. "Production of parathyroid hormone-like peptide in a human osteosarcoma cell line: stimulation by phorbol esters and epidermal growth factor." Journal of Endocrinology 122, no. 1 (July 1989): 219—NP. http://dx.doi.org/10.1677/joe.0.1220219.
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ABSTRACT A clonal cell line (Saos-2/B-10) derived from human osteosarcoma Saos-2 cells had the same osteoblastic characteristics as the mother line, but lacked sensitivity to parathyroid hormone (PTH) at early passages. At later passages (> 70) the cells became very sensitive to PTH (0·1 nmol/l). The absence of PTH-stimulatable adenylate cyclase correlated with the secretion of an adenylate cyclase-stimulatory activity which had the properties of the recently characterized PTH-like peptide (PTH-LP). This activity was inhibited by the PTH antagonist [8norleucyl, 18norleucyl, 34tyrosinyl]bovine PTH-(3–34)amide and could be neutralized by an antiserum raised against the synthetic PTH-LP-(1–34). Hybridization with a human PTH-LP cDNA showed that these cells produce two PTH-LP mRNAs of approximately 1·5 and 1·8 kb. The production of PTH-LP was stimulated by 12-O-tetradecanoylphorbol-13-acetate (TPA; 150 nmol/l) and epidermal growth factor (EGF; 10 ng/ml). The increased accumulation of PTH-LP in conditioned media in response to TPA was seen after 1 h and levelled off at 6 h. In contrast, EGF stimulation was lower at 3 and 6 h but continued for 24 h. Both agents increased PTH-LP mRNA levels in Saos-2/B-10 cells. A TPA analogue which does not stimulate protein kinase C had no effect on PTH-LP production. Cycloheximide blocked the stimulatory effect of both TPA and EGF and the TPA effect was blocked by actinomycin D, suggesting transcriptional control. The regulation of PTH-LP by these agents may offer clues regarding the association of this protein with malignancy. Journal of Endocrinology (1989) 122, 219–227
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Mitrescu, Cristian, Steven Miller, Jeffrey Hawkins, Tristan L’Ecuyer, Joseph Turk, Philip Partain, and Graeme Stephens. "Near-Real-Time Applications of CloudSat Data." Journal of Applied Meteorology and Climatology 47, no. 7 (July 1, 2008): 1982–94. http://dx.doi.org/10.1175/2007jamc1794.1.
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Abstract Within 2 months of its launch in April 2006 as part of the Earth Observing System A-Train satellite constellation, the National Aeronautics and Space Administration Earth System Science Pathfinder (ESSP) CloudSat mission began making significant contributions toward broadening the understanding of detailed cloud vertical structures around the earth. Realizing the potential benefit of CloudSat to both the research objectives and operational requirements of the U.S. Navy, the Naval Research Laboratory coordinated early on with the CloudSat Data Processing Center to receive and process first-look 94-GHz Cloud Profiling Radar datasets in near–real time (4–8 h latency), thereby making the observations more relevant to the operational community. Applications leveraging these unique data, described herein, include 1) analysis/validation of cloud structure and properties derived from conventional passive radiometers, 2) tropical cyclone vertical structure analysis, 3) support of research field programs, 4) validation of numerical weather prediction model cloud fields, and 5) quantitative precipitation estimation in light rainfall regimes.
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Beasley, D., and M. McGuiggin. "Interleukin 1 activates soluble guanylate cyclase in human vascular smooth muscle cells through a novel nitric oxide-independent pathway." Journal of Experimental Medicine 179, no. 1 (January 1, 1994): 71–80. http://dx.doi.org/10.1084/jem.179.1.71.
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Recent demonstration of cytokine-inducible production of nitric oxide (NO) in vascular smooth muscle cells (VSMC) from rat aorta has implicated VSMC-derived NO as a key mediator of hypotension in septic shock. Our studies to determine whether an inducible NO pathway exists in human VSMC have revealed a novel cytokine-inducible, NO-independent pathway of guanylate cyclase activation in VSMC from human saphenous vein (HSVSMC). Interleukin 1 (IL-1), tumor necrosis factor (TNF), interferon gamma (IFN-gamma) and Escherichia coli lipopolysaccharide (LPS) increased cGMP at 24 h, whereas IL-2 and IL-6 were ineffective. The effect of IL-1 on cyclic guanosine 3',5'-monophosphate (cGMP) was delayed, occurring after 6 h of exposure, and was maximal after 10 h. Methylene blue and LY83583 reversed the IL-1-induced increase in cGMP, suggesting that it was mediated by activation of soluble guanylate cyclase. However, IL-1-induced cGMP in HSVSMC was not inhibited by extracellular hemoglobin. Also, the effect of IL-1 on cGMP was not reversed by nitro- or methyl-substituted L-arginine analogs, aminoguanidine, or diphenyleneiodonium, all of which inhibit IL-1-induced NO synthase in rat aortic VSMC (RAVSMC). IL-1-induced cGMP in HSVSMC was also independent of tetrahydrobiopterin and extracellular L-arginine, as it was not affected by 2,4-diamino-6-hydroxyprytimidine, an inhibitor of tetrahydrobiopterin biosynthesis, and was similar in L-arginine-free and L-arginine-containing media. Analysis of NO synthase mRNA with the use of polymerase chain reaction indicates that levels of mRNA for inducible NO synthase are several orders of magnitude lower in IL-1-treated human HSVSMC than in IL-1-treated RAVSMC. IL-1-induced cGMP was also NO independent in human umbilical artery VSMC, and NO dependent in rat vena cava VSMC. Together these results indicate that IL-1 activates a novel NO-independent pathway of soluble guanylate cyclase activation in human VSMC.
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Ramsay, Hamish A., Savin S. Chand, and Suzana J. Camargo. "A Statistical Assessment of Southern Hemisphere Tropical Cyclone Tracks in Climate Models." Journal of Climate 31, no. 24 (December 2018): 10081–104. http://dx.doi.org/10.1175/jcli-d-18-0377.1.
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Reliable projections of future changes in tropical cyclone (TC) characteristics are highly dependent on the ability of global climate models (GCMs) to simulate the observed characteristics of TCs (i.e., their frequency, genesis locations, movement, and intensity). Here, we investigate the performance of a suite of GCMs from the U.S. CLIVAR Working Group on Hurricanes in simulating observed climatological features of TCs in the Southern Hemisphere. A subset of these GCMs is also explored under three idealized warming scenarios. Two types of simulated TC tracks are evaluated on the basis of a commonly applied cluster analysis: 1) explicitly simulated tracks, and 2) downscaled tracks, derived from a statistical–dynamical technique that depends on the models’ large-scale environmental fields. Climatological TC properties such as genesis locations, annual frequency, lifetime maximum intensity (LMI), and seasonality are evaluated for both track types. Future changes to annual frequency, LMI, and the latitude of LMI are evaluated using the downscaled tracks where large sample sizes allow for statistically robust results. An ensemble approach is used to assess future changes of explicit tracks owing to their small number of realizations. We show that the downscaled tracks generally outperform the explicit tracks in relation to many of the climatological features of Southern Hemisphere TCs, despite a few notable biases. Future changes to the frequency and intensity of TCs in the downscaled simulations are found to be highly dependent on the warming scenario and model, with the most robust result being an increase in the LMI under a uniform 2°C surface warming.
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Buckingham, Ty J., and David M. Schultz. "Synoptic-Scale Environments and Precipitation Morphologies of Tornado Outbreaks from Quasi-Linear Convective Systems in the United Kingdom." Weather and Forecasting 35, no. 5 (July 31, 2020): 1733–59. http://dx.doi.org/10.1175/waf-d-20-0021.1.
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Abstract Nine tornado outbreaks (days with three or more tornadoes) have occurred in the United Kingdom from quasi-linear convective systems (QLCSs) in the 16 years between 2004 and 2019. Of the nine outbreaks, eight can be classified into two synoptic categories: type 1 and type 2. Synoptic categories are derived from the location of the parent extratropical cyclone and the orientation of the surface front associated with the QLCS. Environmental differences between the categories are assessed using ERA5 reanalysis data. Type 1 events are characterized by a confluent 500-hPa trough from the west, meridional cold front, strong cross-frontal wind veer (about 90°), cross-frontal temperature decrease of 2°–4°C, prefrontal 2-m dewpoint temperatures of 12°–14°C, a prefrontal low-level jet, and prefrontal 0–1- and 0–3-km bulk shears of 15 and 25 m s−1, respectively. In contrast, type 2 events are characterized by a diffluent 500-hPa trough from the northwest, zonal front, weaker cross-frontal wind veer (≤45°), much smaller cross-frontal temperature decrease, lower prefrontal 2-m dewpoint temperatures of 6°–10°C, and weaker prefrontal 0–1- and 0–3-km bulk shears of 10 and 15 m s−1, respectively. Analysis of the Met Office radar reflectivity mosaics revealed that narrow cold-frontal rainbands developed in all type 1 events and subsequently displayed precipitation core-and-gap structures. Conversely, type 2 events did not develop narrow cold-frontal rainbands, although precipitation cores developed sporadically within the wide cold-frontal rainband. Type 1 events produced tornadoes 2–4 h after core-and-gap development, whereas type 2 events produced tornadoes within 1 h of forming cores and gaps. All events produced tornadoes during a relatively short time period (1–3 h).
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Hong, Sungwook, Hwa-Jeong Seo, and Young-Joo Kwon. "A Unique Satellite-Based Sea Surface Wind Speed Algorithm and Its Application in Tropical Cyclone Intensity Analysis." Journal of Atmospheric and Oceanic Technology 33, no. 7 (July 2016): 1363–75. http://dx.doi.org/10.1175/jtech-d-15-0128.1.
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AbstractThis study proposes a sea surface wind speed retrieval algorithm (the Hong wind speed algorithm) for use in rainy and rain-free conditions. It uses a combination of satellite-observed microwave brightness temperatures, sea surface temperatures, and horizontally polarized surface reflectivities from the fast Radiative Transfer for TOVS (RTTOV), and surface and atmospheric profiles from the European Centre for Medium-Range Weather Forecasts (ECMWF). Regression relationships between satellite-observed brightness temperature and satellite-simulated brightness temperatures, satellite-simulated brightness temperatures, rough surface reflectivities, and between sea surface roughness and sea surface wind speed are derived from the Advanced Microwave Scanning Radiometer 2 (AMSR-2). Validation results of sea surface wind speed between the proposed algorithm and the Tropical Atmosphere Ocean (TAO) data show that the estimated bias and RMSE for AMSR-2 6.925- and 10.65-GHz bands are 0.09 and 1.13 m s−1, and −0.52 and 1.21 m s−1, respectively. Typhoon intensities such as the current intensity (CI) number, maximum wind speed, and minimum pressure level based on the proposed technique (the Hong technique) are compared with best-track data from the Japan Meteorological Agency (JMA), the Joint Typhoon Warning Center (JTWC), and the Cooperative Institute for Mesoscale Meteorological Studies (CIMSS) for 13 typhoons that occurred in the northeastern Pacific Ocean throughout 2012. Although the results show good agreement for low- and medium-range typhoon intensities, the discrepancy increases with typhoon intensity. Consequently, this study provides a useful retrieval algorithm for estimating sea surface wind speed, even during rainy conditions, and for analyzing characteristics of tropical cyclones.
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Cosker, François, Francisco J. B. Lima, Saad Lahlou, and Pedro J. C. Magalhães. "Cytoprotective effect of 1-nitro-2-phenylethane in mice pancreatic acinar cells subjected to taurocholate: Putative role of guanylyl cyclase-derived 8-nitro-cyclic-GMP." Biochemical Pharmacology 91, no. 2 (September 2014): 191–201. http://dx.doi.org/10.1016/j.bcp.2014.07.030.
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Bielli, Soline, Christelle Barthe, Olivier Bousquet, Pierre Tulet, and Joris Pianezze. "The Effect of Atmosphere-Ocean Coupling on the Structure and Intensity of Tropical Cyclone Bejisa in the Southwest Indian Ocean." Atmosphere 12, no. 6 (May 27, 2021): 688. http://dx.doi.org/10.3390/atmos12060688.
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A set of numerical simulations is relied upon to evaluate the impact of air-sea interactions on the behaviour of tropical cyclone (TC) Bejisa (2014), using various configurations of the coupled ocean-atmosphere numerical system Meso-NH-NEMO. Uncoupled (SST constant) as well as 1D (use of a 1D ocean mixed layer) and 3D (full 3D ocean) coupled experiments are conducted to evaluate the impact of the oceanic response and dynamic processes, with emphasis on the simulated structure and intensity of TC Bejisa. Although the three experiments are shown to properly capture the track of the tropical cyclone, the intensity and the spatial distribution of the sea surface cooling show strong differences from one coupled experiment to another. In the 1D experiment, sea surface cooling (∼1 °C) is reduced by a factor 2 with respect to observations and appears restricted to the depth of the ocean mixed layer. Cooling is maximized along the right-hand side of the TC track, in apparent disagreement with satellite-derived sea surface temperature observations. In the 3D experiment, surface cooling of up to 2.5 °C is simulated along the left hand side of the TC track, which shows more consistency with observations both in terms of intensity and spatial structure. In-depth cooling is also shown to extend to a much deeper depth, with a secondary maximum of nearly 1.5 °C simulated near 250 m. With respect to the uncoupled experiment, heat fluxes are reduced from about 20% in both 1D and 3D coupling configurations. The tropical cyclone intensity in terms of occurrence of 10-m TC wind is globally reduced in both cases by about 10%. 3D-coupling tends to asymmetrize winds aloft with little impact on intensity but rather a modification of the secondary circulation, resulting in a slight change in structure.
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Mohazzab-H., Kamal M., Ritu Agarwal, and Michael S. Wolin. "Influence of glutathione peroxidase on coronary artery responses to alterations in Po 2 and H2O2." American Journal of Physiology-Heart and Circulatory Physiology 276, no. 1 (January 1, 1999): H235—H241. http://dx.doi.org/10.1152/ajpheart.1999.276.1.h235.
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Our previous work suggests that relaxation of endothelium-removed bovine coronary arteries (BCA) to posthypoxic reoxygenation is mediated by NADH oxidase-dependent superoxide anion-derived H2O2 and cGMP. The purpose of this study was to investigate if altering BCA GSH peroxidase activity by enhancing its activity with a GSH peroxidase-mimetic (0.1 mM Ebselen) or by inhibiting its activity with an inhibitor of GSH peroxidase [10 mM mercaptosuccinic acid (MS)] causes a selective modulation of responses to exogenously (1 μM–1 mM H2O2) and endogenously generated (reoxygenation and 1–10 mM lactate) H2O2. Ebselen inhibited and MS enhanced all of the responses that are thought to be mediated by H2O2, without having significant effects on relaxation to hypoxia or a nitric oxide donor [1 nM–10 μM S-nitroso- N-acetylpenicillamine (SNAP)]. Thus enhancement of BCA GSH peroxidase activity with Ebselen inhibits relaxation to reoxygenation, lactate, and H2O2, whereas inhibition of GSH peroxidase with MS causes potentiation of responses thought to be mediated by H2O2 in BCA. Inactivation of catalase by pretreatment of BCA with 3-amino-1,2,4-triazole (50 mM, 30 min) inhibited relaxation to H2O2 and the potentiation by MS. Whereas the actions of these probes are not consistent with a role for oxidation of GSH in the relaxation to H2O2, their effects are potentially a result of modulating the metabolism of H2O2 by endogenous catalase, which is thought to mediate the stimulation of the cytosolic or soluble form of guanylate cyclase.
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Zamora, Ruben, Louis Alarcon, Yoram Vodovotz, Binnie Betten, Peter K. M. Kim, Kevin F. Gibson, and Timothy R. Billiar. "Nitric Oxide Suppresses the Expression of Bcl-2 Binding Protein BNIP3 in Hepatocytes." Journal of Biological Chemistry 276, no. 50 (October 9, 2001): 46887–95. http://dx.doi.org/10.1074/jbc.m101865200.
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Nitric oxide (NO) is not only an important signaling molecule, but it also regulates the expression of a number of genes in the liver. We have previously shown that apoptosis in hepatocytes exposed to tumor necrosis factor-α and actinomycin D is prevented by NO derived from the inducible nitric-oxide synthase (iNOS), by mechanisms that are both dependent on and independent of modulation of cyclic guanosine monophosphate (cGMP) subsequent to activation of soluble guanylyl cyclase (sGC). We hypothesize that one mechanism by which NO exerts these effects is by regulating the expression of genes involved in apoptosis. We used differential display-polymerase chain reaction to isolate NO-regulated genes in hepatocytes fromiNOSknockout mice (to eliminate endogenous inducible NO production). Using this analysis, we identified a NO-suppressed gene fragment homologous with the pro-apoptotic Bcl-2 binding protein BNIP3. Northern analysis confirmed the NO-dependent suppression ofBNIP3in cultured cells. Similarly, the NO donorS-nitroso-N-acetyl-dl-penicillamine (1–1000 μm) down-regulated the expression ofBNIP3in bothiNOSknockout and wild-type hepatocytes. This effect of NO was reversed by the sGC inhibitor 1H-(1,2,4)-oxadiazole[4,3-a]quinoxalon-1-one (ODQ),suggesting the involvement of the sGC/cGMP pathway in the modulation of BNIP3 by NO. We propose that suppression of BNIP3 expression is one sGC/cGMP-dependent mechanism by which NO might affect the process of hepatocyte apoptosis.
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Jiang, Haiyan, Cheng Tao, and Yongxian Pei. "Estimation of Tropical Cyclone Intensity in the North Atlantic and Northeastern Pacific Basins Using TRMM Satellite Passive Microwave Observations." Journal of Applied Meteorology and Climatology 58, no. 2 (February 2019): 185–97. http://dx.doi.org/10.1175/jamc-d-18-0094.1.
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AbstractA statistical passive microwave intensity estimation (PMW-IE) algorithm for estimating the intensity of tropical cyclones (TCs) in the North Atlantic and northeastern and central Pacific basins is developed and tested. The algorithm is derived from Tropical Rainfall Measuring Mission (TRMM) Microwave Imager (TMI) 85-GHz brightness temperatures and near-surface rain-rate retrievals to provide objective estimates of current maximum sustained surface winds (Vmax) and 6-h future Vmax of TCs. The full record of TRMM data (1998–2013) including 2326 TMI overpasses of 503 TCs is separated into dependent samples (1998–2010) for model development and independent samples (2011–13) for model verification. The best track intensities are used as dependent variables in a stepwise multiple-regression approach. Separately for each basin, three regression models are derived using selected 1) 85-GHz-only variables, 2) rain-rate-only variables, and 3) combined 85-GHz and rain variables. The algorithms are evaluated using independent samples and those with contemporaneous aircraft-reconnaissance measurements. Rain-only and combined models perform better than the 85-GHz-only model. Lower errors are found for estimating the 6-h future Vmax than estimating the current Vmax using all three models. This suggests that it is optimal to use passive-microwave-retrieved rain variables observed a few hours earlier to estimate TC intensity. The MAE (RMSE) of 6-h future Vmax is 9 (12) kt (1 kt ≈ 0.51 m s−1) when testing the combined models with ATL and EPA independent samples. Aircraft-reconnaissance-based independent samples yields a MAE of 9.6 kt and RMSE of 12.6 kt for estimating 6-h future Vmax.
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Jin, N., C. S. Packer, and R. A. Rhoades. "Pulmonary arterial hypoxic contraction: signal transduction." American Journal of Physiology-Lung Cellular and Molecular Physiology 263, no. 1 (July 1, 1992): L73—L78. http://dx.doi.org/10.1152/ajplung.1992.263.1.l73.
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The response of isolated rat pulmonary arteries to acute hypoxia has previously been reported to be biphasic, consisting of an initial rapid contraction of short duration, followed by partial relaxation (phase 1) and then a second slowly developed but sustained contraction (phase 2). The purpose of this study was to determine the following: 1) whether products from the endothelium might be required, 2) whether extra- and/or intracellular calcium or protein kinase C might be second messengers in mediating the pulmonary arterial hypoxic contraction, and 3) whether or not guanosine 3',5'-cyclic monophosphate (cGMP), endothelium-derived relaxing factor (EDRF), prostaglandin I2 (PGI2) or A2 adenosine receptor activation is involved in phase 1 relaxation. Neither Ca(2+)-free media nor verapamil (a Ca2+ channel blocker) altered the phase 1 contraction, but the phase 2 contraction was abolished by either of these treatments. Ryanodine (a sarcoplasmic reticulum Ca2+ depleter) had no effect on phase 1 contraction. H-7 (a PKC inhibitor) inhibited the phase 2 contraction, whereas it had no effect on phase 1 contraction. Removal of the endothelium abolished phase 1 contraction in either Ca(2+)-free media or normal Ca2+ media but did not alter phase 2 contraction or phase 1 relaxation. Neither methylene blue (guanylate cyclase inhibitor), N omega-nitro-L-arginine, (EDRF blocker), acetylsalicylic acid (cyclooxygenase inhibitor), xanthine amino congener (adenosine receptor blocker), nor glybenclamide blocked the phase 1 relaxation.(ABSTRACT TRUNCATED AT 250 WORDS)
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Sawada, Masahiro, Zaizhong Ma, Avichal Mehra, Vijay Tallapragada, Ryo Oyama, and Kazuki Shimoji. "Impacts of Assimilating High-Resolution Atmospheric Motion Vectors Derived from Himawari-8 on Tropical Cyclone Forecast in HWRF." Monthly Weather Review 147, no. 10 (September 30, 2019): 3721–40. http://dx.doi.org/10.1175/mwr-d-18-0261.1.
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Abstract The impact of the assimilation of high spatial and temporal resolution atmospheric motion vectors (AMVs) on tropical cyclone (TC) forecasts has been investigated. The high-resolution AMVs are derived from the full disk scan of the new generation geostationary satellite Himawari-8. Forecast experiments for three TCs in 2016 in a western North Pacific basin are performed using the National Centers for Environmental Prediction (NCEP) operational Hurricane Weather Research and Forecasting Model (HWRF). Two different ensemble–variational hybrid data assimilation configurations (using background error covariance created by global ensemble forecast and HWRF ensemble forecast), based on the Gridpoint Statistical Interpolation (GSI), are used for the sensitivity experiments. The results show that the inclusion of high-resolution Himawari-8 AMVs (H8AMV) can benefit the track forecast skill, especially for long-range lead times. The diagnosis of optimal steering flow indicates that the improved track forecast seems to be attributed to the improvement of initial steering flow surrounding the TC. However, the assimilation of H8AMV increases the negative intensity bias and error, especially for short-range forecast lead times. The investigation of the structural change from the assimilation of H8AMV revealed that the following two factors are likely related to this degradation: 1) an increase of inertial stability outside the radius of maximum wind (RMW), which weakens the boundary layer inflow; and 2) a drying around and outside the RMW. Assimilating H8AMV using background error covariance created from HWRF ensemble forecast contributes to a significant reduction in negative intensity bias and error, and there is a significant benefit to TC size forecast.
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Reinhart, Brad, Henry Fuelberg, Richard Blakeslee, Douglas Mach, Andrew Heymsfield, Aaron Bansemer, Stephen L. Durden, Simone Tanelli, Gerald Heymsfield, and Bjorn Lambrigtsen. "Understanding the Relationships between Lightning, Cloud Microphysics, and Airborne Radar-Derived Storm Structure during Hurricane Karl (2010)." Monthly Weather Review 142, no. 2 (January 24, 2014): 590–605. http://dx.doi.org/10.1175/mwr-d-13-00008.1.
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Abstract This study explores relationships between lightning, cloud microphysics, and tropical cyclone (TC) storm structure in Hurricane Karl (16 September 2010) using data collected by the NASA DC-8 and Global Hawk (GH) aircraft during NASA’s Genesis and Rapid Intensification Processes (GRIP) experiment. The research capitalizes on the unique opportunity provided by GRIP to synthesize multiple datasets from two aircraft and analyze the microphysical and kinematic properties of an electrified TC. Five coordinated flight legs through Karl by the DC-8 and GH are investigated, focusing on the inner-core region (within 50 km of the storm center) where the lightning was concentrated and the aircraft were well coordinated. GRIP datasets are used to compare properties of electrified and nonelectrified inner-core regions that are related to the noninductive charging mechanism, which is widely accepted to explain the observed electric fields within thunderstorms. Three common characteristics of Karl’s electrified regions are identified: 1) strong updrafts of 10–20 m s−1, 2) deep mixed-phase layers indicated by reflectivities >30 dBZ extending several kilometers above the freezing level, and 3) microphysical environments consisting of graupel, very small ice particles, and the inferred presence of supercooled water. These characteristics describe an environment favorable for in situ noninductive charging and, hence, TC electrification. The electrified regions in Karl’s inner core are attributable to a microphysical environment that was conducive to electrification because of occasional, strong convective updrafts in the eyewall.
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Dwinell, Michael B., Hiroyuki Ogawa, Kim E. Barrett, and Martin F. Kagnoff. "SDF-1/CXCL12 regulates cAMP production and ion transport in intestinal epithelial cells via CXCR4." American Journal of Physiology-Gastrointestinal and Liver Physiology 286, no. 5 (May 2004): G844—G850. http://dx.doi.org/10.1152/ajpgi.00112.2003.
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Human colonic epithelial cells express CXCR4, the sole cognate receptor for the chemokine stromal cell-derived factor (SDF)-1/CXC chemokine ligand (CXCL) 12. The aim of this study was to define the mechanism and functional consequences of signaling intestinal epithelial cells through the CXCR4 chemokine receptor. CXCR4, but not SDF-1/CXCL12, was constitutively expressed by T84, HT-29, HT-29/-18C1, and Caco-2 human colon epithelial cell lines. Studies using T84 cells showed that CXCR4 was G protein-coupled in intestinal epithelial cells. Moreover, stimulation of T84 cells with SDF-1/CXCL12 inhibited cAMP production in response to the adenylyl cyclase activator forskolin, and this inhibition was abrogated by either anti-CXCR4 antibody or receptor desensitization. Studies with pertussis toxin suggested that SDF-1/CXCL12 activated negative regulation of cAMP production through Giα subunits coupled to CXCR4. Consistent with the inhibition of forskolin-stimulated cAMP production, SDF-1/CXCL12 also inhibited forskolin-induced ion transport in voltage-clamped polarized T84 cells. Taken together, these data indicate that epithelial CXCR4 can transduce functional signals in human intestinal epithelial cells that modulate important cAMP-mediated cellular functions.
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Lu, Lu, Xuemin Rao, Rigang Cong, Chenxi Zhang, Zhimei Wang, Jinyi Xu, Genzoh Tanabe, Osamu Muraoka, Xiaoming Wu, and Weijia Xie. "Design, Synthesis and Biological Evaluation of Nitrate Derivatives of Sauropunol A and B as Potent Vasodilatory Agents." Molecules 24, no. 3 (February 6, 2019): 583. http://dx.doi.org/10.3390/molecules24030583.
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A group of nitrate derivatives of naturally occurring sauropunol A and B were designed and synthesized. Nitric oxide (NO) releasing capacity and vasodilatory capacity studies were performed to explore the structure-activity relationship of resulted nitrates. Biological evaluation of these compounds revealed that most of the synthesized mononitrate derivatives demonstrated superior releasing capacity than isosorbide mononitrate (ISMN), and 2MNS-6 even demonstrated stronger NO releasing capacity than isosorbide dinitrate (ISDN). Two dinitrates, DNS-1 and DNS-2, showed higher NO releasing capacity than ISDN. Evaluation of inhibitory activities to the contractions in mesenteric artery rings revealed that 2MNS-8 and DNS-2 showed stronger vasorelaxation activities than ISDN. High level of NO and soluble guanylyl cyclase (sGC) may be essential for the potent vasodilatory effect of DNS-2. The vasodilatory effects of DNS-2 may result from cellular signal transduction of NO-sGC-cGMP. DNS-2 was found to be the most potent sauropunol-derived nitrate vasodilatory agent for further pharmaceutical investigation against cardiovascular diseases.
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Yanda, Murali K., Qiangni Liu, and Liudmila Cebotaru. "An inhibitor of histone deacetylase 6 activity, ACY-1215, reduces cAMP and cyst growth in polycystic kidney disease." American Journal of Physiology-Renal Physiology 313, no. 4 (October 1, 2017): F997—F1004. http://dx.doi.org/10.1152/ajprenal.00186.2017.
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Adult-onset autosomal-dominant polycystic kidney disease (ADPKD) is caused by mutations in either the PKD1 or PKD2 gene, leading to malfunction of their gene products, polycystin 1 or 2. Histone deacetylase 6 (HDAC6) expression and activity are increased in PKD1 mutant renal epithelial cells. Here we studied the effect of ACY-1215, a specific HDAC6 inhibitor, on cyst growth in ADPKD. Treatment with ACY-1215 slowed cyst growth in a mouse model of ADPKD that forms massive cysts within 3 wk after knockout of polycystin 1 function. It also prevented cyst formation in MDCK.2 cells, an in vitro model of cystogenesis, and in an ADPKD cell line derived from the proximal tubules from a pkd1−/−.mouse (PN cells). In PN cells ACY-1215 also reduced the size of already established cysts. We found that ACY-1215 lowered cAMP levels and protein expression of adenylyl cyclase 6. Our results suggest that HDAC6 could potentially serve as a therapeutic target in ADPKD.
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Lee, Fang Chun, Wen Hua Lin, and John R. C. Hsu. "STORM BEACH BUFFER REQUIREMENT FOR STORM WAVES FROM A TROPICAL CYCLONE." Coastal Engineering Proceedings 1, no. 32 (January 29, 2011): 46. http://dx.doi.org/10.9753/icce.v32.sediment.46.
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Storm beach buffer, being different from the coastal set back currently in place in many countries in the world, is the provision of a sufficient beach width to safe guard against the onslaught of a fierce storm. The extent of this requirement is tentatively assessed using the SBEACH module in the CEDAS package. The inputs for the SBEACH module include berm width, medium sand grain diameter, beach slope, design water level and wave conditions; while the outputs consist of a range of characteristic parameters for the change in beach profile, especially berm erosion and bar formation resulting from a storm of different return periods. After having systematically performed a series of numerical studies, we may conclude that: (1) Berm erosion increases and bar becomes further offshore as the storm return period increases on a beach with identical sand grain size (i.e., non-dimensional fall velocity), or as sand grain dimension reduces; (2) Higher storm waves result in a larger bar to form quicker and cause wave breaking on the bar crest which could reduce the wave energy and limit the extent of the subsequent berm erosion; (3) Empirical equations can be derived to calculate the storm beach buffer width; and (4) A larger buffer is required for a beach with smaller sand grain, in order to effectively absorb the storm wave energy. The results presented in this paper can be used to assist in a beach nourishment project for shore protection and the design of a recreational beach.
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Linder, Jürgen U. "Structure–function relationships in Escherichia coli adenylate cyclase." Biochemical Journal 415, no. 3 (October 15, 2008): 449–54. http://dx.doi.org/10.1042/bj20080350.
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Class I adenylate cyclases are found in γ- and δ-proteobacteria. They play central roles in processes such as catabolite repression in Escherichia coli or development of full virulence in pathogens such as Yersinia enterocolitica and Vibrio vulnificus. The catalytic domain (residues 2–446) of the adenylate cyclase of E. coli was overexpressed and purified. It displayed a Vmax of 665 nmol of cAMP·mg−1·min−1 and a Km of 270 μM. Titration of the metal cofactor Mg2+ against the substrate ATP showed a requirement for free metal ions in addition to the MgATP complex, suggesting a two-metal-ion mechanism as is known for class II and class III adenylate cyclases. Twelve residues which are essential for catalysis were identified by mutagenesis of a total of 20 polar residues conserved in all class I adenylate cyclases. Five essential residues (Ser103, Ser113, Asp114, Asp116 and Trp118) were part of a region which is found in all members of the large DNA polymerase β-like nucleotidyltransferase superfamily. Alignment of the E. coli adenylate cyclase with the crystal structure of a distant member of the superfamily, archaeal tRNA CCA-adding enzyme, suggested that Asp114 and Asp116 are the metal-cofactor-ion-binding residues. The S103A mutant had a 17-fold higher Km than wild-type, demonstrating its important role in substrate binding. In comparison with the tRNA CCA-adding enzyme, Ser103 of the E. coli adenylate cyclase apparently binds the γ-phosphate group of ATP. Consistent with this function, the S103A mutation caused a marked reduction of discrimination between ATP- and ADP- or AMP-derived inhibitors.
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Roth, Nora, Christoph Faul, Christiane Dorn, Wichard Vogel, Wolfgang A. Bethge, Lothar Kanz, Hans-Georg Rammensee, and Sebastian P. Haen. "Development of New Autoimmunity Against T Cell Antigens Derived From Retinal Proteins After Allogeneic Hematopoietic Cell Transplantation." Blood 120, no. 21 (November 16, 2012): 3060. http://dx.doi.org/10.1182/blood.v120.21.3060.3060.
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Abstract Abstract 3060 Introduction: Graft versus host disease (GvHD) is mainly mediated by T cells recognizing major (MHC) and minor (miHAG) histocompatibility antigens (human leukocyte antigens and MHC-restricted epitopes, respectively). The clinical appearance of a GvHD affecting the central nervous system (CNS) and the retina as part of the CNS is rare and evidence is limited to single case reports. Some publications describe the development of new autoimmunity after hematopoietic cell transplantation (HCT) manifested as hemolytic anemia (AIHA), immune thrombocytopenia (ITP) or myasthenia gravis. Of note, new autoinflammatory diseases affecting the retina have not been reported. In this study we investigated the GvHD of the retina and examined the development of new autoimmune T cell responses against epitopes derived from proteins exclusively expressed in the retina. Patients and Methods: We analyzed T cells from 8 women and 12 men with a median age of 55 years (range 29 – 69 years) that had underwent HCT. Underlying diseases were acute lymphoblastic leukemia (n = 1), acute myeloid leukemia, (n = 6), chronic myeloid leukemia (n = 1), myelodysplastic syndrome (n = 3), myeloproliferative syndromes (primary myelofibrosis, n = 2; essential thrombocytemia with secondary myelofibrosis, n = 2; polycythemia vera with secondary myelofibrosis, n = 1), B-cell non-Hodgkin lymphoma (gray zone lymphoma, n = 1; follicular lymphoma, n = 1; peripheral T cell lymphoma, n = 1) and Hodgkin's lymphoma (n = 1). Potential T cell epitopes from four unique highly polymorphic retinal proteins (membrane-bound retinal guanylate cyclase 1 protein (retGC), the guanylate cyclase activating proteins 1 and 2 (GCAP1 and GCAP2) and the retinoid binding protein 3 (RBP3)) were identified using 2 approaches. First, genomic DNA derived from both donor and recipient coding for these proteins was sequenced by Sanger sequencing in search of single nucleotide polymorphisms (SNP). Second, alternate peptide expression based on known SNP was predicted using internet based databases (EpiToolKit). The predicted epitopes were synthesized and used in T cell assays. Peripheral blood mononuclear cells (PBMCs) from patients after hematopoietic regeneration (neutrophils > 500/μl) were stimulated with SNP peptide pairs (peptides pairs differing in one amino acid) and analyzed by IFNg-ELISPOT and flow cytometry. Results: In 5 out of 20 patients (25%), strong T cell responses against peptides derived from retGC as well as from GCAP1 and GCAP2 were observed which were not detectable before HCT and not reflected by a difference in the DNA sequence between donor and recipient. Two patients of the cohort presented with visual loss which was due to cone dystrophy (n = 1) and retrobulbar optic neuritis (n = 1). In the patient with cone dystrophy, we observed circulating antigen specific T cells against peptides derived from retGC. The patient with retrobulbar optic neuritis did not have antigen specific T cell responses. In 2 clinically silent patients, we found IFNg producing CD4+ T cells that recognized a predicted GCAP1-derived self-peptide. One patient also had a strong T cell response against a GCAP2-derived self-peptide. The T cells specifically recognized the peptide represented in the autologous DNA sequence; no reactivity was seen after stimulation with the SNP peptide. Furthermore, the T cell reactions persisted over time and were still detectable one year after HCT. In another patient, T cell responses against the pair of GCAP2 peptides were detected. Here, the reactivity against one peptide could not be discriminated due to limited availability of patient T cells. One further patient displayed T cell responses against GCAP and retGC peptides, which were directed against both self- and SNP peptides. As controls we stimulated T cells from 5 HLA-matched healthy individuals with all respective peptides and observed no T cell reaction. Conclusions: 25% of the patients revealed strong T cell responses against retinal autoantigens after HCT. T cell responses detected late after HCT as observed in 3 patients might indicate a chronic antigen exposure. Clinical manifestations were cone dystrophy (here, antigen-specific T cells against cone protein-derived peptides could be detected) and retrobulbar optic neuritis. To our knowledge, this is the first report on antigen-specificity of neoautoinflammatory cells after allogeneic HCT. Disclosures: No relevant conflicts of interest to declare.
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Iwamoto, J., M. Yoshinaga, S. P. Yang, E. Krasney, and J. Krasney. "Methylene blue inhibits hypoxic cerebral vasodilation in awake sheep." Journal of Applied Physiology 73, no. 6 (December 1, 1992): 2226–32. http://dx.doi.org/10.1152/jappl.1992.73.6.2226.
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Cerebral vasodilation in hypoxia may involve endothelium-derived relaxing factor-nitric oxide. Methylene blue (MB), an in vitro inhibitor of soluble guanylate cyclase, was injected intravenously into six adult ewes instrumented chronically with left ventricular, aortic, and sagittal sinus catheters. In normoxia, MB (0.5 mg/kg) did not alter cerebral blood flow (CBF, measured with 15-microns radiolabeled microspheres), cerebral O2 uptake, mean arterial pressure (MAP), heart rate, cerebral lactate release, or cerebral O2 extraction fraction (OEF). After 1 h of normobaric poikilocapnic hypoxia (arterial PO2 40 Torr, arterial O2 saturation 50%), CBF increased from 51 +/- 5.8 to 142 +/- 18.8 ml.min-1 x 100 g-1, cerebral O2 uptake from 3.5 +/- 0.25 to 4.7 +/- 0.41 ml.min-1 x 100 g-1, cerebral lactate release from 2 +/- 10 to 100 +/- 50 mumol.min- x 100 g-1, and heart rate from 107 +/- 5 to 155 +/- 9 beats/min (P < 0.01). MAP and OEF were unchanged from 91 +/- 3 mmHg and 48 +/- 4%, respectively. In hypoxia, 30 min after MB (0.5 mg/kg), CBF declined to 79.3 +/- 11.7 ml.min-1 x 100 g-1 (P < 0.01), brain O2 uptake (4.3 +/- 0.9 ml.min-1 x 100 g-1) and heart rate (133 +/- 9 beats/min) remained elevated, cerebral lactate release became negative (-155 +/- 60 mumol.min-1 x 100 g-1, P < 0.01), OEF increased to 57 +/- 3% (P < 0.01), and MAP (93 +/- 5 mmHg) was unchanged. The sheep became behaviorally depressed, probably because of global cerebral ischemia. These results may be related to interference with a guanylate cyclase-dependent mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)
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Cappello, Sandra, Tommaso Angelone, Bruno Tota, Pasquale Pagliaro, Claudia Penna, Raffaella Rastaldo, Angelo Corti, Gianni Losano, and Maria Carmela Cerra. "Human recombinant chromogranin A-derived vasostatin-1 mimics preconditioning via an adenosine/nitric oxide signaling mechanism." American Journal of Physiology-Heart and Circulatory Physiology 293, no. 1 (July 2007): H719—H727. http://dx.doi.org/10.1152/ajpheart.01352.2006.
Full textAbstract:
The acidic protein chromogranin A (CgA) is the precursor of several regulatory peptides generated by specific proteolytic processes. Human recombinant CgA NH2-terminal fragment STA-CgA1-78 (hrSTA-CgA1-78), containing vasostatin-1 (CgA1-76) domain, exerts a negative inotropic effect and counteracts the β-adrenergic positive inotropic effect on the rat heart. We hypothesized an involvement of nitric oxide (NO)-dependent pathway in both cardiodepression and cardioprotection by hrSTA-CgA1-78. We also hypothesized an involvement of adenosine A1 receptor and protein kinase C (PKC) in cardioprotection by hrSTA-CgA1-78. Therefore, we evaluated whether 1) the cardioinhibition mediated by hrSTA-CgA1-78 involves the Gi/o proteins/NO-dependent signal transduction cascade, 2) hrSTA-CgA1-78 induces ischemic preconditioning-like protective effects on the myocardium, and 3) inhibition of NO synthase (NOS), adenosine A1 receptor, or PKC affects hrSTA-CgA1-78 protection. Using the isolated rat heart, we found that the reduction of left ventricular pressure (LVP), rate-pressure product, and maximal values of the first derivative of LVP elicited by hrSTA-CgA1-78 at 33 nM is abolished by blocking Gi/o proteins with pertussis toxin, scavenging NO with hemoglobin, and blocking NOS activity with NG-monomethyl-l-arginine or N5-(iminoethyl)-l-ornithine, soluble guanylate cyclase with 1 H-[1,2,4]oxadiazole-[4,4-a]quinoxalin-1-one, and protein kinase (PKG) with KT5823. Data suggest the involvement of the Gi/o proteins/NO-cGMP-PKG pathway in the hrSTA-CgA1-78-dependent cardioinhibition. When given before 30 min of ischemia, hrSTA-CgA1-78 significantly reduced the size of the infarct from 64 ± 4 to 32 ± 3% of the left ventricular mass. This protective effect was abolished by either NOS inhibition or PKC blockade and was attenuated, but not suppressed, by the blockade of A1 receptors. These results suggest that hrSTA-CgA1-78 activity triggers two different pathways: one of these pathways is mediated by A1 receptors, and the other is mediated by NO release. As with repeated brief preconditioning ischemia, hrSTA-CgA1-78 may be considered a stimulus strong enough to trigger both pathways, which may converge on PKC.