A primary culture system of mouse thick ascending limb cells with preserved function and uromodulin processing

The epithelial cells lining the thick ascending limb (TAL) of the loop of Henle perform essential transport processes and secrete uromodulin, the most abundant protein in normal urine. The lack of differentiated cell culture systems has hampered studies of TAL functions. Here, we report a method to generate differentiated primary cultures of TAL cells, developed from microdissected tubules obtained in mouse kidneys. The TAL tubules cultured on permeable filters formed polarized confluent monolayers in ∼12days. The TAL cells remain differentiated and express functional markers such as uromodulin, NKCC2, and ROMK at the apical membrane. Electrophysiological measurements on primary TAL monolayers showed a lumen-positive transepithelial potential (+9.4 ± 0.8mV/cm2) and transepithelial resistance similar to that recorded in vivo. The transepithelial potential is abolished by apical bumetanide and in primary cultures obtained from ROMK knockout mice. The processing, maturation and apical secretion of uromodulin by primary TAL cells is identical to that observed in vivo. The primary TAL cells respond appropriately to hypoxia, hypertonicity, and stimulation by desmopressin, and they can be transfected. The establishment of this primary culture system will allow the investigation of TAL cells obtained from genetically modified mouse models, providing a critical tool for understanding the role of that segment in health and disease

Exercise inhibits the effects of smoke-induced COPD involving modulation of STAT3

Purpose . Evaluate the participation of STAT3 in the e ff ects of aerobic exercise (AE) in a model of smoke-induced COPD. Methods . C57Bl/6 male mice were divided into control, Exe, COPD, and COPD+Exe groups. Smoke were administered during 90 days. Treadmill aerobic training begun on day 61 until day 90. Pulmonary in fl ammation, systemic in fl ammation, the level of lung emphysema, and the airway remodeling were evaluated. Analysis of integral and phosphorylated expression of STAT3 by airway epithelial cells, peribronchial leukocytes, and parenchymal leukocytes was performed. Results . AE inhibited smoke-induced accumulation of total cells ( p <0 001 ), lymphocytes ( p <0 001 ), and neutrophils ( p <0 001 ) in BAL, as well as BAL levels of IL- 1 β ( p <0 001 ), CXCL1 ( p <0 001 ), IL-17 ( p <0 001 ), and TNF- α ( p <0 05 ), while increased the levels of IL-10 ( p <0 001 ). AE also inhibited smoke-induced increases in total leukocytes ( p <0 001 ), neutrophils ( p <0 05 ), lymphocytes ( p <0 001 ), and monocytes ( p <0 01 ) in blood, as well as serum levels of IL-1 β ( p <0 01 ), CXCL1 ( p <0 01 ), IL-17 ( p <0 05 ), and TNF- α ( p <0 01 ), while increased the levels of IL-10 ( p <0 001 ). AE reduced smoke-induced emphysema ( p <0 001 ) and collagen fi ber accumulation in the airways ( p <0 001 ). AE reduced smoke-induced STAT3 and phospho-STAT3 expression in airway epithelial cells ( p <0 001 ), peribronchial leukocytes ( p <0 001 ), and parenchymal leukocytes ( p <0 001 ). Conclusions .AE reduces smoke-induced COPD phenotype involving STAT3

High efficiency synthesis of HKUST-1 under mild conditions with high BET surface area and CO2 uptake capacity

This study focuses on the development of a hydrothermal method for the rapid synthesis of good quality copper benzene-1,3,5-tricarboxylate (referred to as HKUST-1) with high yield under mild preparation conditions to address the issues associated with reported methods. Different synthesis conditions and activation methods were studied to understand their influence on the properties of HKUST-1. It was found that mixing the precursors at 50 °C for 3 h followed by activation via methanol refluxing led to the formation of a product with the highest BET specific surface area of 1615 m2/g and a high yield of 84.1%. The XRD and SEM data illustrated that the product was highly crystalline. The sample was also tested on its capacity in CO2 adsorption. The results showed strong correlation between surface area of the sample and its CO2 uptake at 1 bar and 27 °C. The HKUST-1 prepared in this study demonstrated a high CO2 uptake capacity of 4.2 mmol/g. It is therefore concluded that this novel and efficient method can be used in the rapid preparation of HKUST-1 with high surface area and CO2 uptake capacity

Detection of VHE gamma-ray emission from the distant blazar 1ES 1101-232 with HESS and broadband characterisation

Context. The blazar 1ES 1101-232 was observed with the High Energy Stereoscopic System (HESS) of Atmospheric Cherenkov Telescopes (ACT) in 2004 and 2005, for a live time of 43 h. VHE (E > 10¹¹ eV) γ-rays were detected for the first time from this object. Aims. VHE observations of blazars are used to investigate the inner parts of the blazar jets, and also to study the extragalactic background light (EBL) in the near-infrared band. Methods. Observations in 2005 were conducted in a multiwavelength campaign, together with the RXTE satellite and optical observations. In 2004, simultaneous observations with XMM-Newton were obtained. Results. 1ES 1101-232 was detected with HESS with an excess of 649 photons, at a significance of 10σ. The measured VHE γ-ray flux amounts to dN/dE = (5.63 ± 0.89) × 10⁻¹³(E/TeV)⁻(²•⁹⁴±⁰•²⁰) cm⁻² s⁻¹ TeV−1, above a spectral energy threshold of 225 GeV. No significant variation of the VHE γ-ray flux on any time scale was found. 1ES 1101-232 exhibits a very hard spectrum, and at a redshift of z = 0.186, is the blazar with the highest confirmed redshift detected in VHE γ-rays so far. Conclusions. The data allow the construction of truly simultaneous spectral energy distributions of the source, from the optical to the VHE band. Using an EBL model with νFν = 14 nWm⁻² sr⁻¹ at 1.5 μm as presented in Aharonian et al. (2006a) suggests an intrinsic VHE power output peak of the source at above 3 TeV.F. Aharonian ... G. Rowell ... et al

Discovery of two candidate pulsar wind nebulae in very-high-energy gamma rays

Context. We present the discovery of two very-high-energy γ-ray sources in an ongoing systematic search for emission above 100 GeV from pulsar wind nebulae in survey data from the HESS telescope array. Aims. Imaging Atmospheric Cherenkov Telescopes are ideal tools for searching for extended emission from pulsar wind nebulae in the very-high-energy regime. HESS, with its large field of view of 5° and high sensitivity, gives new prospects for the search for these objects. Methods. An ongoing systematic search for very-high-energy emission from energetic pulsars over the region of the Galactic plane between -60° < l < 30°, -2° < b < 2° is performed. For the resulting candidates, the standard HESS analysis was applied and a search for multiwavelength counterparts was performed. Results. We present the discovery of two new candidate γ-ray pulsar wind nebulae, HESS J1718-385 and HESS J1809-193. Conclusions. HESS has proven to be a suitable instrument for pulsar wind nebula searches. © ESO 2007.F. Aharonian... G. Rowell... et al

First detection of a VHE gamma-ray spectral maximum from a cosmic source: HESS discovery of the Vela X nebula

The Vela supernova remnant (SNR) is a complex region containing a number of sources of non-thermal radiation. The inner section of this SNR, within 2 degrees of the pulsar PSR B0833-45, has been observed by the HESS γ-ray atmospheric Cherenkov detector in 2004 and 2005. A strong signal is seen from an extended region to the south of the pulsar, within an integration region of radius 0.8° around the position (α = 08h35 m00s, δ = -45°36′ J2000.0). The excess coincides with a region of hard X-ray emission seen by the ROSAT and ASCA satellites. The observed energy spectrum of the source between 550 GeV and 65 TeV is well fit by a power law function with photon index Γ = 1.45 ± 0.09stat ± 0.2sys and an exponential cutoff at an energy of 13.8 ± 2.3stat ± 4.1 sys TeV. The integral flux above 1 TeV is (1.28 ± 0.17 stat ± 0.38sys) × 10-11 cm -2 s-1. This result is the first clear measurement of a peak in the spectral energy distribution from a VHE γ-ray source, likely related to inverse Compton emission. A fit of an Inverse Compton model to the HESS spectral energy distribution gives a total energy in non-thermal electrons of ∼2 × 1045 erg between 5 TeV and 100 TeV, assuming a distance of 290 parsec to the pulsar. The best fit electron power law index is 2.0, with a spectral break at 67 TeV. © ESO 2006.F. A. Aharonian...G. P. Rowell...et al

Very high energy gamma rays from the composite SNR G 0.9+0.1

Very high energy (>100 GeV) gamma-ray emission has been detected for the first time from the composite supernova remnant G 0.9+0.1 using the HESS instrument. The source is detected with a significance of ≈13σ, and a photon flux above 200 GeV of (5.7 ± 0.7 stat ± 1.2 sys) × 10 -12 cm -2 s -1, making it one of the weakest sources ever detected at TeV energies. The photon spectrum is compatible with a power law (dN/dE ∝ E Γ) with photon index Γ = 2.40 ± 0.11 stat ± 0.20 sys. The gamma-ray emission appears to originate in the plerionic core of the remnant, rather than the shell, and can be plausibly explained as inverse Compton scattering of relativistic electrons. © ESO 2005.F. Aharonian...G. Rowell...et al

Discovery of extended VHE gamma-ray emission from the asymmetric pulsar wind nebula in MSH 15-52 with H.E.S.S.

The Supernova Remnant MSH 15-52 has been observed in very high energy (VHE) γ-rays using the HESS 4-telescope array located in Namibia. A γ-ray signal is detected at the 25 sigma level during an exposure of 22.1 h live time. The image reveals an elliptically shaped emission region around the pulsar PSR B1509-58, with semi-major axis ∼ 6′ in the NW-SE direction and semi-minor axis ∼ 2′. This morphology coincides with the diffuse pulsar wind nebula as observed at X-ray energies by ROSAT. The overall energy spectrum from 280 GeV up to 40TeV can be fitted by a power law with photon index Γ = 2.27 ±0.03stat ±0.20syst. The detected emission can be plausibly explained by inverse Compton scattering of accelerated relativistic electrons with soft photons. © ESO 2005.F. A. Aharonian ... G. P. Rowell ... et al

Discovery of the binary pulsar PSRB1259-63 in very-high-energy gamma rays around periastron with HESS

We report the discovery of very-high-energy (VHE) γ-ray emission of the binary system PSR B1259-63/SS 2883 of a radio pulsar orbiting a massive, luminous Be star in a highly eccentric orbit. The observations around the 2004 periastron passage of the pulsar were performed with the four 13m Cherenkov telescopes of the HESS experiment, recently installed in Namibia and in full operation since December 2003. Between February and June 2004, a γ-ray signal from the binary system was detected with a total significance above 13σ. The flux was found to vary significantly on timescales of days which makes PSR B1259-63 the first variable galactic source of VHE γ-rays observed so far. Strong emission signals were observed in pre- and post-periastron phases with a flux minimum around periastron, followed by a gradual flux decrease in the months after. The measured time-averaged energy spectrum above a mean threshold energy of 380 GeV can be fitted by a simple power law F 0(E/1 TeV) -Γ with a photon index Γ = 2.7 ± 0.2 stat ± 0.2 sys and flux normalisation F 0 = (1.3 ± 0.l stat ± 0.3 sys) × 10 -12 TeV -1 cm -2 s -1. This detection of VHE γ-rays provides unambiguous evidence for particle acceleration to multi-TeV energies in the binary system. In combination with coeval observations of the X-ray synchrotron emission by the RXTE and INTEGRAL instruments, and assuming the VHE γ-ray emission to be produced by the inverse Compton mechanism, the magnetic field strength can be directly estimated to be of the order of 1 G. © ESO 2005.F. Aharonian,... G. Rowell,..., and S. J. Wagner [et al

New constraints on the mid-IR EBL from the HESS discovery of VHE gamma-rays from 1ES 0229+200

Aims.To investigate the very high energy (VHE: >100 GeV) γ-ray emission from the high-frequency peaked BL Lac 1ES 0229+200. Methods: Observations of 1ES 0229+200 at energies above 580 GeV were performed with the High Energy Stereoscopic System (HESS) in 2005 and 2006. Results: 1ES 0229+200 is discovered by HESS to be an emitter of VHE photons. A signal is detected at the 6.6σ level in the HESS observations (41.8 h live time). The integral flux above 580 GeV is (9.4±1.5_stat±1.9_syst) × 10-13 cm-2 s-1, corresponding to ~1.8% of the flux observed from the Crab Nebula. The data show no evidence for significant variability on any time scale. The observed spectrum is characterized by a hard power law (Γ = 2.50±0.19_stat±0.10_syst) from 500 GeV to ~15 TeV. Conclusions: The high-energy range and hardness of the observed spectrum, coupled with the object's relatively large redshift (z = 0.1396), enable the strongest constraints so far on the density of the Extragalactic Background Light (EBL) in the mid-infrared band. Assuming that the emitted spectrum is not harder than Γ_int ≈ 1.5, the HESS data support an EBL spectrum ∝λ-1 and density close to the lower limit from source counts measured by Spitzer, confirming the previous indications from the HEGRA data of 1ES 1426+428 (z=0.129). Irrespective of the EBL models used, the intrinsic spectrum of 1ES 0229+200 is hard, thus locating the high-energy peak of its spectral energy distribution above a few TeV.Aharonian, F.; Akhperjanian, A. G.; Barres de Almeida, U.; Bazer-Bachi, A. R.; Behera, B.; Beilicke, M.; Benbow, W.; Bernlöhr, K.; Boisson, C.; Bolz, O.; Borrel, V.; Braun, I.; Brion, E.; Brown, A. M.; Bühler, R.; Bulik, T.; Büsching, I.; Boutelier, T.; Carrigan, S.; Chadwick, P. M.; Chounet, L.-M.; Clapson, A. C.; Coignet, G.; Cornils, R.; Costamante, L.; Dalton, M.; Degrange, B.; Dickinson, H. J.; Djannati-Ataï, A.; Domainko, W.; O'C. Drury, L.; Dubois, F.; Dubus, G.; Dyks, J.; Egberts, K.; Emmanoulopoulos, D.; Espigat, P.; Farnier, C.; Feinstein, F.; Fiasson, A.; Förster, A.; Fontaine, G.; Funk, Seb.; Füßling, M.; Gallant, Y. A.; Giebels, B.; Glicenstein, J. F.; Glück, B.; Goret, P.; Hadjichristidis, C.; Hauser, D.; Hauser, M.; Heinzelmann, G.; Henri, G.; Hermann, G.; Hinton, J. A.; Hoffmann, A.; Hofmann, W.; Holleran, M.; Hoppe, S.; Horns, D.; Jacholkowska, A.; de Jager, O. C.; Jung, I.; Katarzyński, K.; Kendziorra, E.; Kerschhaggl, M.; Khélifi, B.; Keogh, D.; Komin, Nu.; Kosack, K.; Lamanna, G.; Latham, I. J.; Lemière, A.; Lemoine-Goumard, M.; Lenain, J.-P.; Lohse, T.; Martin, J. M.; Martineau-Huynh, O.; Marcowith, A.; Masterson, C.; Maurin, D.; Maurin, G.; McComb, T. J. L.; Moderski, R.; Moulin, E.; de Naurois, M.; Nedbal, D.; Nolan, S. J.; Ohm, S.; Olive, J.-P.; de Oña Wilhelmi, E.; Orford, K. J.; Osborne, J. L.; Ostrowski, M.; Panter, M.; Pedaletti, G.; Pelletier, G.; Petrucci, P.-O.; Pita, S.; Pühlhofer, G.; Punch, M.; Ranchon, S.; Raubenheimer, B. C.; Raue, M.; Rayner, S. M.; Renaud, M.; Ripken, J.; Rob, L.; Rolland, L.; Rosier-Lees, S.; Rowell, G.; Rudak, B.; Ruppel, J.; Sahakian, V.; Santangelo, A.; Schlickeiser, R.; Schöck, F.; Schröder, R.; Schwanke, U.; Schwarzburg, S.; Schwemmer, S.; Shalchi, A.; Sol, H.; Spangler, D.; Stawarz, Ł.; Steenkamp, R.; Stegmann, C.; Superina, G.; Tam, P. H.; Tavernet, J.-P.; Terrier, R.; van Eldik, C.; Vasileiadis, G.; Venter, C.; Vialle, J. P.; Vincent, P.; Vivier, M.; Völk, H. J.; Volpe, F.; Wagner, S. J.; Ward, M.; Zdziarski, A. A.; Zech,