Pannexin1 is part of the pore forming unit of the P2X7 receptor death complex

AbstractThe purinergic receptor P2X7 is part of a complex signaling mechanism participating in a variety of physiological and pathological processes. Depending on the activation scheme, P2X7 receptors in vivo are non-selective cation channels or form large pores that can mediate apoptotic cell death. Expression of P2X7R in Xenopus oocytes results exclusively in formation of a non-selective cation channel. However, here we show that co-expression of P2X7R with pannexin1 in oocytes leads to the complex response seen in many mammalian cells, including cell death with prolonged ATP application. While the cation channel activity is resistant to carbenoxolone treatment, this gap junction and hemichannel blocking drug suppressed the currents induced by ATP in pannexin1/P2X7R co-expressing cells. Thus, pannexin1 appears to be the molecular substrate for the permeabilization pore (or death receptor channel) recruited into the P2X7R signaling complex

UNILAC Upgrades for Coulomb Barrier Energy Experiments

The GSI linear accelerator UNILAC provides heavy ion beams at Coulomb barrier energies for search and study of super heavy elements. Typical cross-sections of 55 fb require beam doses of 1.4·10¹⁹ according to a beam time of 117 days. Several upgrades will reduce the beam time to only 16 days. A second injection branch with a 28GHz-MS-ECRIS anticipates a factor of 10 in particle intensity. By a new cw rfq-structure all accelerator tanks are suitable for a duty cycle of at least 50% instead of 25% presently. Due to this, thermal power increase of 19 rf-amplifiers eased by higher ion charge states of the ECRIS is necessary. Finally the UNILAC timing system controlling 50Hz pulse-to-pulse operation of up to six beams differing in ion species and energy has to be modified considering beam diagnostics electronics and pulsable magnets. The front end comprising ECRIS, rfq- and IH-structure is cw suitable and will serve as injector for a new future sc-cw-linac

Механический метод очистки сточных вод

В статье рассматриваются основные методы очистки сточных вод. Описан механический метод очистки и представлены его особенности. Приведен процесс очистки вод данным методом. The article deals with the basic methods of wastewater treatment. Described mechanical method of cleaning and presents its features. An process water treatment by this method

Straight injection of an intense uranium beam into the GSI High Current RFQ

A dedicated high current uranium ion source and LEBT will be built at the GSI High Current Injector (HSI), to fulfil the intensity requirements for FAIR (Facility forAntiproton and Ion Research at Darmstadt). This new injection line will be integrated into the existingcomplex which already comprises two branches. The new LEBT is designed as a straight injection linewithout dipole magnet, i.e. without dispersive charge stateseparation. All uranium charge states, coming from theion source, are transported to the heavy ion high current GSI-HSI-RFQ. Only the design charge state U4+ is accelerated to the final RFQ energy. The new LEBT design is based on beam emittance and current measurements behind the existing ion source. Beam dynamics simulations have been performed with thecodes TRACE-3D (envelopes), DYNAMION,BEAMPATH and TRACK (multiparticle). The recentlayout of the LEBT, as well as the results of beam dynamics studies are presented

Mechanical behavior and collagen structure of degenerative mitral valve leaflets and a finite element model of primary mitral regurgitation

Degenerative mitral valve disease is the main cause of primary mitral regurgitation with two phenotypes: fibroelastic deficiency (FED) often with localized myxomatous degeneration and diffuse myxomatous degeneration or Barlow’s disease. Myxomatous degeneration disrupts the microstructure of the mitral valve leaflets, particularly the collagen fibers, which affects the mechanical behavior of the leaflets. The present study uses biaxial mechanical tests and second harmonic generation microscopy to examine the mechanical behavior of Barlow and FED tissue. Three tissue samples were harvested from a FED patient and one sample is from a Barlow patient. Then we use an appropriate constitutive model by excluding the collagen fibers under compression. Finally, we built an FE model based on the echocardiography of patients diagnosed with FED and Barlow and the characterized material model and collagen fiber orientation. The Barlow sample and the FED sample from the most affected segment showed different mechanical behavior and collagen structure compared to the other two FED samples. The FE model showed very good agreement with echocardiography with 2.02 ± 1.8 mm and 1.05 ± 0.79 mm point-to-mesh distance errors for Barlow and FED patients, respectively. It has also been shown that the exclusion of collagen fibers under compression provides versatility for the material model; it behaves stiff in the belly region, preventing excessive bulging, while it behaves very softly in the commissures to facilitate folding.publishedVersio

SCAM analysis of Panx1 suggests a peculiar pore structure

Vertebrates express two families of gap junction proteins: the well-characterized connexins and the pannexins. In contrast to connexins, pannexins do not appear to form gap junction channels but instead function as unpaired membrane channels. Pannexins have no sequence homology to connexins but are distantly related to the invertebrate gap junction proteins, innexins. Despite the sequence diversity, pannexins and connexins form channels with similar permeability properties and exhibit similar membrane topology, with two extracellular loops, four transmembrane (TM) segments, and cytoplasmic localization of amino and carboxy termini. To test whether the similarities extend to the pore structure of the channels, pannexin 1 (Panx1) was subjected to analysis with the substituted cysteine accessibility method (SCAM). The thiol reagents maleimidobutyryl-biocytin and 2-trimethylammonioethyl-methanethiosulfonate reacted with several cysteines positioned in the external portion of the first TM segment (TM1) and the first extracellular loop. These data suggest that portions of TM1 and the first extracellular loop line the outer part of the pore of Panx1 channels. In this aspect, the pore structures of Panx1 and connexin channels are similar. However, although the inner part of the pore is lined by amino-terminal amino acids in connexin channels, thiol modification was detected in carboxyterminal amino acids in Panx1 channels by SCAM analysis. Thus, it appears that the inner portion of the pores of Panx1 and connexin channels may be distinct