978 resultados para 4 diamino 1


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Availability of voltage-gated calcium channels (Cav) at the plasma membrane is paramount to maintaining the calcium homeostasis of the cell. It is proposed that the ubiquitylation/de-ubiquitylation balance regulates the density of ion channels at the cell surface. Voltage-gated calcium channels Cav1.2 have been found to be ubiquitylated under basal conditions both in vitro and in vivo. In a previous study, we have shown that Cav1.2 channels are ubiquitylated by neuronal precursor cell-expressed developmentally downregulated 4 (Nedd4-1) ubiquitin ligases, but the identity of the counterpart de-ubiquitylating enzyme remained to be elucidated. Regarding sodium and potassium channels, it has been reported that the action of the related isoform Nedd4-2 is counteracted by the ubiquitin-specific protease (USP) 2-45. In this study, we show that USP 2-45 also de-ubiquitylates Cav channels. We co-expressed USPs and Cav1.2 channels together with the accessory subunits β2 and α2δ-1, in tsA-201 and HEK-293 mammalian cell lines. Using whole-cell current recordings and surface biotinylation assays, we show that USP2-45 specifically decreases both the amplitude of Cav currents and the amount of Cav1.2 subunits inserted at the plasma membrane. Importantly, co-expression of the α2δ-1 accessory subunit is necessary to support the effect of USP2-45. We further show that USP2-45 promotes the de-ubiquitylation of both Cav1.2 and α2δ-1 subunits. Remarkably, α2δ-1, but not Cav1.2 nor β2, co-precipitated with USP2-45. These results suggest that USP2-45 binding to α2δ-1 promotes the de-ubiquitylation of both Cav1.2 and α2δ-1 subunits, in order to regulate the expression of Cav1.2 channels at the plasma membrane.

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Besetzung: Coro S, Coro A, Coro T, Coro B, Vl 1 2, Va, Trp 1 2, Timp, Org

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New coordination polymers [M(Pht)(4-MeIm)2(H2O)]n (M=Co (1), Cu (2); Pht2−=dianion of o-phthalic acid; 4-MeIm=4-methylimidazole) have been synthesized and characterized by IR spectroscopy, X-ray crystallography, thermogravimetric analysis and magnetic measurements. The crystal structures of 1 and 2 are isostructural and consist of [M(4-MeIm)2(H2O)] building units linked in infinite 1D helical chains by 1,6-bridging phthalate ions which also act as chelating ligands through two O atoms from one carboxylate group in the case of 1. In complex 1, each Co(II) atom adopts a distorted octahedral N2O4 geometry being coordinated by two N atoms from two 4-MeIm, three O atoms of two phthalate residues and one O atom of a water molecule, whereas the square-pyramidal N2O3 coordination of the Cu(II) atom in 2 includes two N atoms of N-containing ligands, two O atoms of two carboxylate groups from different Pht, and a water molecule. An additional strong O–H⋯O hydrogen bond between a carboxylate group of the phthalate ligand and a coordinated water molecule join the 1D helical chains to form a 2D network in both compounds. The thermal dependences of the magnetic susceptibilities of the polymeric helical Co(II) chain compound 1 were simulated within the temperature range 20–300 K as a single ion case, whereas for the Cu(II) compound 2, the simulations between 25 and 300 K, were made for a linear chain using the Bonner–Fisher approximation. Modelling the experimental data of compound 1 with MAGPACK resulted in: g=2.6, |D|=62 cm−1. Calculations using the Bonner–Fisher approximation gave the following result for compound 2: g=2.18, J=–0.4 cm−1.

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BACKGROUND  Reducing the fraction of transmissions during recent human immunodeficiency virus (HIV) infection is essential for the population-level success of "treatment as prevention". METHODS  A phylogenetic tree was constructed with 19 604 Swiss sequences and 90 994 non-Swiss background sequences. Swiss transmission pairs were identified using 104 combinations of genetic distance (1%-2.5%) and bootstrap (50%-100%) thresholds, to examine the effect of those criteria. Monophyletic pairs were classified as recent or chronic transmission based on the time interval between estimated seroconversion dates. Logistic regression with adjustment for clinical and demographic characteristics was used to identify risk factors associated with transmission during recent or chronic infection. FINDINGS  Seroconversion dates were estimated for 4079 patients on the phylogeny, and comprised between 71 (distance, 1%; bootstrap, 100%) to 378 transmission pairs (distance, 2.5%; bootstrap, 50%). We found that 43.7% (range, 41%-56%) of the transmissions occurred during the first year of infection. Stricter phylogenetic definition of transmission pairs was associated with higher recent-phase transmission fraction. Chronic-phase viral load area under the curve (adjusted odds ratio, 3; 95% confidence interval, 1.64-5.48) and time to antiretroviral therapy (ART) start (adjusted odds ratio 1.4/y; 1.11-1.77) were associated with chronic-phase transmission as opposed to recent transmission. Importantly, at least 14% of the chronic-phase transmission events occurred after the transmitter had interrupted ART. CONCLUSIONS  We demonstrate a high fraction of transmission during recent HIV infection but also chronic transmissions after interruption of ART in Switzerland. Both represent key issues for treatment as prevention and underline the importance of early diagnosis and of early and continuous treatment.

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4-Aryl-1,1,1-trifluorobut-3-en-2-ones ArCH[double bond, length as m-dash]CHCOCF3 (CF3-enones) react with arenes in excess of Brønsted superacids (TfOH, FSO3H) to give, stereoselectively, trans-1,3-diaryl-1-trifluoromethyl indanes in 35-85% yields. The reaction intermediates, the O-protonated ArCH[double bond, length as m-dash]CHC(OH(+))CF3 and the O,C-diprotonated ArHC(+)CH2C(OH(+))CF3 species, have been studied by means of (1)H, (13)C, (19)F NMR, and DFT calculations. Both types of the cations may participate in the reaction, depending on their electrophilicity and electron-donating properties of the arenes. The formation of CF3-indanes is a result of cascade reaction of protonated CF3-enones to form chemo-, regio- and stereoselectively three new C-C bonds. The obtained trans-1,3-diaryl-1-trifluoromethyl indanes were investigated as potential ligands for cannabinoid receptors CB1 and CB2 types. The most potent compound showed sub-micromolar affinity for both receptor subtypes with a 6-fold selectivity toward the CB2 receptor with no appreciable cytotoxicity toward SHSY5Y cells.

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[Carl Oestreich]

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"The International Institute of Social Research. Its History, Program and Needs" (1943?), als Typoskript vervielfältigt, 18 Blatt, mit 6 Photographien und einem Anhang: Rezensionen von "Autorität und Familie" und "Abstracts" von Aufsätzen aus der Zeitschrift für Sozialforschung, Photokopien, 12 Blatt; "Über Geschichte, Organisation und Tätigkeiten des Instituts für Sozialforschung. Aus einem Bericht" (1943), Teilstück, Typoskript mit handschriftlichen Korrekturen, 10 Blatt; "Annual Report on the Activities of the Social Studies Association, Inc." (6.5.1944), Typoskript, 6 Blatt; "Ten Years on Morningside Hights. A Report on the Institute's History 1934 to 1944 (Dezember 1944): 1. Report, a) als Typoskript vervielfältigt, 36 Blatt, b) Typoskript, 48 Blatt, c) Entwurf des Teils "Philosophical Studies", Typoskript, 4 Blatt; 2. "Letters Regarding Ten Years Report", 1 Blatt; 3. Liste der Empfänger des Reports. 1 Blatt; 4. Max Horkheimer: 1 Brief an Nicholas Murray Butler, New York, 17.4.1945 , 1 Blatt; 5. Briefentwürfe zur Versendung des Reports, 2 Blatt; Theodore Abel: "Evaluation of the Institute's Work" (1944?): 1. Würdigung, Typoskript, englisch, 4 Blatt; 2. Theodore Abel: 1 Brief mit Unterschrift an Leo Löwenthal, New York, 6.3.1946; 3. Abschrift von 1. und 2., Typoskript, 5 Blatt; Über Organisation und Tätigkeiten des Instituts für Sozialforschung (Mai 1945), Typoskript, 3 Blatt;

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"Über Kants Kritik der Urteilskraft als Bindeglied zwischen theoretischer und praktischer Philosophie", Habilitationsschrift, Typoskript, gebunden, 109 Blatt (GS 2, S. 74-146); Zur Habilitation, "Referat Habilitationsschrift", Typoskript, 2 Blatt (GS 11, S. 76-79); Zur Habilitation, "Lebenslauf", Typoskript, 4 Blatt; "Über Husserls erkenntnistheoretische Fundierung der Wesensschau", Habilitations- Probevortrag, vom 27.02.1925, Manuskript, 1 Heft, 18 Blatt, davon 4 leer, 1 zusätzliches Blatt (GS 11, S. 80-99); Kollegheft zu einer Vorlesung von K. Goldstein über Gehirnpsychologie" eigenhändige Notizen, 1 Heft, 19 Blatt, davon 1 leer; Über Kant, Vorlesungsskript einer Begleitveranstaltung zu einer Vorlesung von Hans Cornelius, enthält auch Notizen zu einer Vorlesung über die Anfänge der bürgerlichen Philosophie, Manuskript, 1 Heft, 11 Blatt, Datierung unklar;

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During CO2 storage operations in mature oilfields or saline aquifers it is desirable to trace the movement of injected CO2 for verification and safety purposes. We demonstrate the successful use of carbon isotope abundance ratios for tracing the movement of CO2 injected at the Cardium CO2 Storage Monitoring project in Alberta between 2005 and 2007. Injected CO2 had a d13C value of -4.6±1.1 per mil that was more than 10 per mil higher than the carbon isotope ratios of casing gas CO2 prior to CO2 injection with average d13C values ranging from -15.9 to -23.5 per mil. After commencement of CO2 injection, d13C values of casing gas CO2 increased in all observation wells towards those of the injected CO2 consistent with a two-source end-member mixing model. At four wells located in a NE-SW trend with respect to the injection wells, breakthrough of injected CO2 was registered chemically (>50 mol % CO2) and isotopically 1-6 months after commencement of CO2 injection resulting in cumulative CO2 fluxes exceeding 100000 m**3 during the observation period. At four other wells, casing gas CO2 contents remained below 5 mol % resulting in low cumulative CO2 fluxes (<2000 m**3) throughout the entire observation period, but carbon isotope ratios indicated contributions between <30 and 80% of injected CO2. Therefore, we conclude that monitoring the movement of CO2 in the injection reservoir with geochemical and isotopic techniques is an effective approach to determine plume expansion and to identify potential preferential flow paths provided that the isotopic composition of injected CO2 is constant and distinct from that of baseline CO2.

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We analyze 2006-2009 data from four continuous Global Positioning System (GPS) receivers located between 5 and 150 km from the glacier Jakobshavn Isbrae, West Greenland. The GPS stations were established on bedrock to determine the vertical crustal motion due to the unloading of ice from Jakobshavn Isbrae. All stations experienced uplift, but the uplift rate at Kangia North, only 5 km from the glacier front, was about 10 mm/yr larger than the rate at Ilulissat, located only ~45 km further away. This suggests that most of the uplift is due to the unloading of the Earth's surface as Jakobshavn thins and loses mass. Our estimate of Jakobshavn's contribution to uplift rates at Kangia North and Ilulissat are 14.6 ± 1.7 mm/yr and 4.9 ± 1.1 mm/yr, respectively. The observed rates are consistent with a glacier thinning model based on repeat altimeter surveys from NASA's Airborne Topographic Mapper (ATM), which shows that Jakobshavn lost mass at an average rate of 22 ± 2 km**3/yr between 2006 and 2009. At Kangia North and Ilulissat, the predicted uplift rates computed using thinning estimates from the ATM laser altimetry are 12.1 ± 0.9 mm/yr and 3.2 ± 0.3 mm/yr, respectively. The observed rates are slightly larger than the predicted rates. The fact that the GPS uplift rates are much larger closer to Jakobshavn than further away, and are consistent with rates inferred using the ATM-based glacier thinning model, shows that GPS measurements of crustal motion are a potentially useful method for assessing ice-mass change models.