University of Graz

About: University of Graz is a education organization based out in Graz, Steiermark, Austria. It is known for research contribution in the topics: Population & Context (language use). The organization has 17934 authors who have published 37489 publications receiving 1110980 citations. The organization is also known as: Carolo Franciscea Graecensis & Karl Franzens Universität.

The Liebeskind-Srogl C-C cross-coupling reaction.

Abstract: Although a plethora of highly selective and reliable methods for the construction of C-C bonds are known to organic chemists, there is growing interest in the development of new protocols that offer different or orthogonal reactivity to that of existing methods. In 2000, Liebeskind and Srogl described a mechanistically unprecedented transition-metal-catalyzed cross-coupling of thioesters with boronic acids to produce ketones under neutral conditions. This desulfitative cross-coupling process is catalytic in palladium(0), stoichiometric in copper(I), and applicable to a range of organosulfur derivatives and nucleophilic organometallic reagents. In this Minireview, we highlight recent applications of this intriguing cross-coupling reaction in modern organic synthesis, with an emphasis on cases in which traditional methods for C-C bond formation have failed.

Functions of c-Jun in Liver and Heart Development

Abstract: The proto-oncogene c-jun encodes a component of the transcription factor AP-1 (activating protein 1)1, which has been implicated in the regulation of diverse cellular functions, such as proliferation, differentiation, transformation, and apoptosis. AP-1 is a dimer consisting of different subunits, e.g., proteins of the Jun (c-Jun, JunB, and JunD) and Fos (c-Fos, FosB, Fra1, and Fra2) family as well as CREB/ATF, and Maf proteins. The different AP-1 components are expressed in a development- and tissue-specific manner, implying that AP-1 composed of different subunits may exert different functions in different cell types. Although AP-1 was found to regulate a few genes, such as human metallothionein IIA (Lee et al., 1987), collagenase (Angel et al., 1987), stromelysin (Kerr et al., 1988), and keratin 18 (Oshima et al., 1990), the biological function of the different AP-1 complexes during development is still elusive. The characterization of the role of AP-1 is further impeded by the fact that there are, in addition to the variability in subunit composition, numerous possible interactions between AP-1 and other transcription factors, such as glucocorticoid hormone receptors (Jonat et al., 1990), estrogen receptors (Gaub et al., 1990), retinoic acid and vitamin D3 receptors (Schule et al., 1990), and MyoD (Bengal et al., 1992) yielding a network of transcriptional regulation. First clues on tissue-specific functions of AP-1 components came from gene knockout experiments. In c-fos knockout mice the development of bone is impaired because of a block in osteoclast differentiation (Grigoriadis et al., 1994). Moreover, lymphoid cells, germ cells, and neuronal tissues are affected in the absence of c-Fos (Johnson et al., 1992; Wang et al., 1992). In contrast to the inactivation of c-fos, targeted disruption of c-jun and junB is lethal (Hilberg et al., 1993; Johnson et al., 1993; Schorpp-Kistner et al., 1999). Lethality of c-jun−/− fetuses has been suggested to be due to defective liver development. The livers of some E12.5 animals appeared hypoplastic with rounded, dissociated hepatoblasts showing features of apoptosis and necrosis. Moreover, increased numbers of erythropoietic cells were noted in these livers (Hilberg et al., 1993). A defect in hepatogenesis in c-Jun knockout mice was further indicated by the observation that c-jun−/− embryonic stem (ES) cells failed to contribute to the liver but not to other tissues of adult chimeric mice (Hilberg et al., 1993). These observations, together with the fact that no morphological alterations were found in organs other than the liver, led to the conclusion that the absence of c-Jun might preferentially affect the development of the liver (Hilberg et al., 1993). In the mouse, liver development starts at around E9.5 when epithelial cells of the foregut endoderm proliferate and invade the mesenchyme of the septum transversum thus forming the embryonic liver. At around E11 hematopoietic stem and progenitor cells derived from the yolk sac and aorta-gonad-mesonephros region colonize the liver, and the liver becomes the major hematopoietic organ during further fetal development (Dzierzak and Medvinsky, 1995). To allow establishment and maintenance of hematopoiesis, liver cells have to provide the proper microenvironment for hematopoietic cells comparable to stromal cells in the bone marrow during postnatal life. The next major step in mouse liver development occurs at approximately E14.5 when hepatoblasts start to differentiate into the hepatocytic and bile duct epithelial lineage, which is indicated by the formation of the ductal plate, which later differentiates into the intrahepatic bile ducts (Desmet, 1998). It is as yet unclear at which developmental stage c-Jun becomes essential for the liver, and whether the defect is restricted to the hepatocytic lineage or other cell types of the fetal liver, such as bile duct epithelia, endothelial cells, stellate cells (vitamin A–storing cells), Kupffer cells, and hematopoietic cells. Besides the poorly characterized function in liver development, c-Jun plays a more general role in the regulation of cell proliferation and apoptosis. It has been shown in fibroblasts isolated from E11.5 c-jun−/− and c-jun+/− embryos that the absence or diminished expression of c-Jun resulted in greatly reduced growth rates, and that this proliferation defect could not be compensated by addition of purified mitogens (Johnson et al., 1993; Schreiber et al., 1999). Evidence for a role of c-Jun and c-Jun phosphorylation in apoptosis was obtained in neuronal cells where transient overexpression of c-Jun induced apoptosis, and expression of a dominant negative c-jun mutant inhibited apoptosis in vitro (Estus et al., 1994; Ham et al., 1995; Behrens et al., 1999). In vivo, however, c-Jun was regarded not to be essential for apoptosis since in the developing mouse (E11.5 c-jun−/− fetuses) the physiologically occurring apoptosis appeared unaffected (Roffler-Tarlov et al., 1996). The different phenotypes observed in the various AP-1 knockout mice point to cell type– and developmental-specific roles of AP-1 complexes. The biological basis for the specific roles is not yet understood. To gain more insight into how the absence of a widely expressed transcription factor like c-Jun affects the liver, and to see whether other tissues are affected, we investigated in detail the morphological and functional alterations in c-jun knockout mice as well as the distribution of c-jun−/− cells in chimeric mice at various stages during fetal development and postnatal life. A deregulation of apoptosis was found in a variety of cell types lacking c-jun, such as hepatoblasts, erythroid cells, and fibroblasts. In contrast to previous reports that suggested that c-Jun is essential for cells to undergo apoptosis, we observed markedly increased apoptotic rates in the absence of c-Jun. It is possible that an increased susceptibility of cells to apoptosis was responsible for the morphologic alterations seen in the livers of c-jun−/− mice. Increased apoptotic rates in combination with reduced proliferation rates would result in a disturbance of hepatocyte turnover which could explain the absence of c-jun−/− hepatocytes in livers of adult chimeric mice. Furthermore, a novel function of c-Jun in heart development was identified, since all c-jun−/− fetuses had a malformation of the outflow tract of the heart which could be a contributing factor to the fetal lethality.

Adverse reactions to injectable soft tissue fillers.

Abstract: In recent years, injections with filler agents are often used for wrinkle-treatment and soft tissue augmentation by dermatologists and plastic surgeons. Unfortunately, the ideal filler has not yet been discovered and all of them may induce adverse reactions. Quickly biodegradable or resorbable agents may induce severe complications, but they will normally disappear spontaneously in a few months. Slowly biodegradable or nonresorbable fillers may give rise to severe reactions that show little or no tendency to spontaneous improvement. They may appear several years after the injection, when the patient does not remember which product was injected, and treatment is often insufficient. In this review, we discuss the most commonly used fillers, their most frequent adverse reactions as well as the characteristic histopathologic findings that allow the identification of the injected filler agent. In conclusion, histopathologic study remains as the gold standard technique to identify the responsible filler. Learning objectives After completing this learning activity, participants should be able to recognize the most frequent adverse reactions induced by cosmetic fillers, identify their histopathologic characteristics so that they can be distinguished from each other, and advise their patients with adverse reactions about the different nature of these according to the filler for subsequent successful treatment.