Althebräische Siegel [Illustration] : des Chananjahu ben Akbar [und] des Jehoassar ben Obadjaku

Scan von Monochrom-Mikroform

Siegel der Augsburger Juden [Illustration] : Aus dem Jahre 1298

Scan von Monochrom-Mikroform

Ms. Ff. A. I. Goldschmidt - Urkunde der Ernennung Amschel Isaak Goldschmidts zum kaiserlichen Hoffaktor vom 18. September 1792, ausgestellt auf Veranlassung von Kaiser Franz II., mit dessen Siegel versehen und von ihm unterzeichnet

Vorbesitzer: Amschel Isaak Goldschmidt; Bertha Blum; Akzessionsnummer: 3384/23

Anna Löhn-Siegel, Kniestück

Signatur des Originals: S 36/G01477

Regulation of Alix by an autoinhibitory intramolecular interaction

In eukaryotic cells, the ESCRTs (endosomal sorting complexes required for transport) machinery is required for cellular processes such as endosomal sorting, retroviral budding and cytokinesis. The ALG-2 interacting protein Alix is a modular adaptor protein that is critically involved in these ESCRTs-associated cellular processes and consists of an N-terminal Bro1 domain, a middle V domain and C-terminal Pro-rich domain (PRD). In these cellular processes, Alix interacts with the ESCRT-III component CHMP4 at the Bro1 domain, with HIV-1 p6 Gag or EIAV p9Gag at the V domain, and with the ESCRT-I component TSG101 at the Pro-rich domain. Here we demonstrate that the N-terminal Bro1 domain forms an intramolecular interaction with C-terminal PRD within Alix. This Bro1-PRD intramolecular interaction forms a closed conformation of Alix that autoinhibits Alix interaction with all of these partner proteins. Moreover, the binding of Ca2+-activated ALG-2 to the PRD of Alix relieves the autoinhibitory intramolecular interaction, resulting in an open conformation of Alix which is able to interact with all of these partner proteins. The partner proteins bound to Alix in turn maintain Alix in the open conformation after ALG-2 dissociation with Alix. Consistent with the effect of Ca2+-activated ALG-2 on opening/activating Alix in these ESCRTs-associated functions, ALG-2 overexpression accelerates EGF-induced degradation of EGFR in an Alix-dependent manner. These findings discover an intrinsic autoinhibitory mechanism of Alix and a two-step process to activate/open Alix and then keep Alix active/open. This study has solved long-standing issues on the regulations of Alix in ESCRTs-associated functions and the role of ALG-2-Alix interaction, and may serve as the structural basis for further studies about Alix regulations. ^

Inactivation and self -association of CaM kinase: Effects of ATP, substrate binding domains, and isozymic forms

Calcium/calmodulin-dependent protein kinase II (CaM kinase) is a multifunctional Ser/Thr protein kinase, that is highly enriched in brain and is involved in regulating many aspects of neuronal function. We observed that forebrain CaM kinase from crude homogenates, cytosolic fractions and purified preparations inactivates and translocates into the particulate fraction following autophosphorylation. Using purified forebrain CaM kinase as well as recombinant $\alpha$ isozyme, we determined that the formation of particulate enzyme was due to enzyme self-association. The conditions of autophosphorylation determine whether enzyme self-association and/or inactivation will occur. Self-association of CaM kinase is sensitive to pH, ATP concentration, and enzyme autophosphorylation. This process is prevented by saturating concentrations of ATP. However, in limiting ATP, pH is the dominant factor, and enzyme self-association occurs at pH values $\rm{<}7.0.$ Site-specific mutants were produced by substituting Ala for Thr286, Thr253, or Thr305,306 to determine whether these sites of autophosphorylation affect enzyme inactivation and self-association. The only mutation that influenced these processes was Ala286, which removed the protective effect afforded by autophosphorylation in saturating ATP. Enzyme inactivation occurs in the presence and absence of self-association and appears predominantly sensitive to nucleotide concentration, because saturating concentrations of $\rm Mg\sp{2+}/ADP$ or $\rm Mg\sp{2+}/ATP$ prevent this process. These data implicate the ATP binding pocket in both inactivation and self-association. We also observed that select peptide substrates and peptide inhibitors modeled after the autoregulatory domain of CaM kinase prevented these processes. The $\alpha$ and $\beta$ isozymes of CaM kinase were characterized independently, and were observed to exhibit differences in both enzyme inactivation and self-association. The $\beta$ isozyme was less sensitive to inactivation, and was never observed to self-associate. Biophysical characterization, and transmission electron microscopy coupled with image analysis indicated both isozymes were multimeric, however, the $\alpha$ and $\beta$ isozymes appeared structurally different. We hypothesize that the $\alpha$ subunit of CaM kinase plays both a structural and enzymatic role, and the $\beta$ subunit plays an enzymatic role. The ramifications for the functional differences observed for inactivation and self-association are discussed based on potential structural differences and autoregulation of the $\alpha$ and $\beta$ isozymes in both calcium-induced physiological and pathological processes. ^

Exploring the perception and production of weak and strong forms in English

Como profesoras de Fonética y Fonología Inglesa hemos percibido que nuestros alumnos –hispano-hablantes- enfrentan una serie de dificultades en relación con la percepción y producción de las formas débiles de las palabras estructurales. En consecuencia, evaluamos la percepción y producción de las formas débiles y fuertes en nuestros alumnos, a través de una prueba de escucha y otra de habla, una vez que los estudiantes de primer año de la Facultad de Filosofía, Humanidades y Artes, Universidad Nacional de San Juan (UNSJ), habían finalizado el período de entrenamiento en estas formas. Para la recolección de datos utilizamos dos tipos de tests: uno de percepción y otro de producción. En general, los resultados corroboraron nuestra percepción: los alumnos continuaron teniendo mayor dificultad en la percepción y producción de las formas débiles de las palabras estructurales que en la de las formas fuertes, aún después de haber estado expuestos al entrenamiento explícito.

Concentrations of labile dissolved forms of Cu, Zn, Pb, and Cu in waters of the Kara Sea and Ob and Yenisey estuaries

Concentrations of labile dissolved forms of Cu, Zn, Pb, and Cu in waters of the Kara Sea and Ob and Yenisey estuaries measured on board during Cruise 49 of R/V Dmitry Mendeleev.

Isotopic composition of various forms of sulfur in barite crusts from the Red Sea rift

Barite crusts were formed by an intermittent hydrothermal vent with output temperature from 85 to 465°C. Principal sources of supply of sulfate sulfur are sea water, evaporites, and tholeiitic basalts of the Red Sea rift. Sulfides and sulfates were formed in conditions of isotope disequilibrium with respect to sulfur because rate of precipitation of sulfur compounds from hydrothermal solution was high compared with rate of isotope exchange.