Search results for "TYR"

Studies of Jak/STAT3 expression and signalling in psoriasis identifies STAT3-Ser727 phosphorylation as a modulator of transcriptional activity

2013

Jak/Tyk proteins have recently aroused as possible therapeutic targets for the treatment of psoriasis. In psoriasis, these proteins signal through STAT molecules including STAT3, and STAT3 expression and activation has been shown augmented in psoriatic lesions. Here, we characterized the expression of Jak/Tyk proteins in lesional compared with non-lesional psoriatic skin. Jak1, Jak2 mRNA and protein and Tyk2 mRNA appeared to be downregulated, whereas Jak3 mRNA expression was increased. Moreover, STAT3 expression and activation was examined in psoriasis. STAT3 is activated at two phosphorylation sites: Tyr705 and Ser727. Both phosphorylation sites were phosphorylated in lesional psoriatic sk…

LS104, a Novel Kinase Inhibitor, Induces Apoptosis, Synergizes with Cytostatic Drugs and Is Targeting the Receptor Tyrosine Kinase FLT3.

2005

Abstract Fms-like tyrosine kinase 3 (FLT3), a member of the class III tyrosine kinase receptor family, is expressed in up to 90% of acute myeloid leukemia (AML). Activating mutations like internal tandem duplication (ITD) of the juxtamembrane domain and kinase domain point mutations are found in approximately 35% of AML-cases and are considered to represent an attractive therapeutic target. In this study, we report that the novel hydroxystyryl-acrylonitrile compound LS104 induces potent cytotoxic effects in FLT3 ITD-positive leukemic cells. As a cellular model to investigate FLT3-ITD specific effects we used 32D myeloid cells stably transfected with FLT3-ITD and wt-FLT3, respectively. In MT…

A novel molecular mechanism of primary resistance to FLT3-kinase inhibitors in AML

2009

Abstract Currently, FLT3 tyrosine kinase inhibitors (TKIs) are emerging as the most promising drug therapy to overcome the dismal prognosis of acute myelogenous leukemia (AML) patients harboring internal tandem duplications (ITDs) of FLT3. However, up-front drug resistance occurs in approximately 30% of patients, and molecular mechanisms of resistance are poorly understood. Here, we have uncovered a novel mechanism of primary resistance to FLT3 TKIs in AML: an FLT3 receptor harboring a nonjuxtamembrane ITD atypically integrating into the β-2 sheet of the first kinase domain (FLT3_ITD627E) induces dramatic up-regulation of the anti-apoptotic myeloid cell leukemia 1 protein (MCL-1). Using RNA…

Reaktionskinetik der Polymerisationshemmung durch molekularen Sauerstoff

1957

Die Polymerisationshemmung geschieht bei Styrol nach demselben Mechanismus wie er kurzlich fur Methylmethacrylat berichtet wurde1. Wahrend der Inhibierungsperiode findet streng alternierende Copolymerisation zwischen molekularem Sauerstoff und dem monomeren Styrol statt. Die fur die Anlagerung von O2 an das Radikal RM · masgebende Konstante kMO2 ist etwa von der Grosenordnung 106–107, d. h. die Reaktionsfahigkeit des Sauerstoffs in dieser Reaktion entspricht der eines Radikals. Bruttogeschwindigkeit und kinetische Kettenlange wahrend der Inhibierungsperiode werden auf Grund des Reaktionsmechanismus berechnet und experimentell bestatigt. The inhibition mechanism in the polymerization of styr…

The calculation of the number-average degree of polymerization starting from intrinsic viscosity and overall rate

1962

The relation between the intrinsic viscosity [η] and the number-average degree of polymerization Pn is a function of the molecular weight distribution of the polymer. In a polymer in which the termination of polymer radicals occurs partly by combination of two growing chains, this molecular weight distribution depends on number and extent of additional reactions such as chain transfer; i.e., it is variable. Therefore Pn of such polymers cannot be obtained from intrinsic viscosity measurements by means of an equation of the type [η] = KPna. A new method is proposed which allows the evaluation of Pn in these cases, without necessity of osmotic (or related) measurements or fractionation. The v…

Politisk styring i markedsorienterte kommuner

2006

Masteroppgave i offentlig politikk og ledelse 2006 - Høgskolen i Agder, Kristiansand Reformer tar sikte på å fornye offentlig sektor. Allerede fra slutten av 1970-tallet og frem til i dag, har offentlig sektor blitt utsatt for reformer. Inn under slike reformer hører virkemidler som konkurranseutsetting. Hovedhensikten i denne oppgaven er å se hvilken effekt konkurranseutsetting får på politisk styring. Det interessante å se er om eventuelle endringer medfører svekket eller styrket politisk styring. Det er utarbeidet to hypoteser: Hypotesene har sitt utgangspunkt fra to teoretiske retninger som mener å kunne si noe om hva som skjer i kommuner som innfører markedstenkning. For å kunne ha en …

O ks. Antonim Korczoku (1891–1941) w 80. rocznicę jego męczeńskiej śmierci (nowe ustalenia)

2022

Z okazji mijającej w ubiegłym roku 80. rocznicy męczeńskiej śmierci ks. Antoniego Korczoka (5 lutego 1941 r.), jaką poniósł za wiarę w obozie koncentracyjnym w Dachau, zarówno w Gliwicach, jak i na terenie diecezji gliwickiej, przeżywano „Rok ks. Antoniego Korczoka”. W czasie organizowanych spotkań, w tym konferencji międzynarodowej (2 października 2021 r.), raz jeszcze przypomniano historię jego świątobliwego życia i okoliczności męczeńskiej śmierci. Przy okazji lokalni historycy ponownie przyjrzeli się osobie przedwojennego proboszcza z Gliwic-Sośnicy, próbując rozwiązać zawiłości związane z historią jego życia. W taki sposób, dzięki przeprowadzonej kwerendzie archiwalnej i na podstawie w…

2015

Polyphenolic compounds affect the color, odor and taste of numerous food products of plant origin. In addition to the visual and gustatory properties, they serve as radical scavengers and have antioxidant effects. Polyphenols, especially resveratrol in red wine, have gained increasing scientific and public interest due to their presumptive beneficial impact on human health. Enzymatic oxidation of phenolic compounds takes place under the influence of polyphenol oxidases (PPO), including tyrosinase and laccase. Several studies have demonstrated the radical scavenger effect of plants, food products and individual polyphenols in vitro, but, apart from resveratrol, such impact has not been prove…

Copper-Containing Oxidases: Occurrence in Soil Microorganisms, Properties, and Applications

2009

Copper is an essential trace element in living systems, where it is used as a cofactor in many enzymatic redox reactions and oxygen transport. The copper-containing oxidases tyrosinase and laccase are widely distributed in soil microorganisms. Recently, progress has been made with respect to structural and catalytic data for the tyrosinase of the soil bacterium Streptomyces. The formation of eumelanins—dark polymers with multiple functionality (e.g., UV protection, immune defense)—is a well-established task of tyrosinases. An abundance of information exists on the structures and biochemical properties of fungal laccases. Many studies have demonstrated a physiological role for them in the de…

Enantioselective Henry addition of methyl 4-nitrobutyrate to aldehydes. Chiral building blocks for 2-pyrrolidinones and other derivatives.

2010

A catalytic highly enantioselective Henry addition of methyl 4-nitrobutyrate to aldehydes using a Cu(II)-amino pyridine complex as catalyst is described. The products resulting from this reaction constitute a new, highly versatile family of chiral building blocks as a result of the presence of three different functional groups on the molecule. These products have been transformed into nonracemic chiral gamma-lactams, 5-hydroxy-5-substituted levulinic acid derivatives, and delta-lactones.