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.

Uptake and transport of high-density lipoprotein (HDL) and HDL-associated alpha-tocopherol by an in vitro blood-brain barrier model.

Abstract: The present study aimed to investigate pathways that contribute to uptake and transcytosis of high-density lipoproteins (HDLs) and HDL-associated α-tocopherol (αTocH) across an in vitro model of the blood–brain barrier (BBB). In primary porcine brain capillary endothelial cells HDL-associated αTocH was taken up in 10-fold excess of HDL holoparticles, indicating efficient selective uptake, a pathway mediated by scavenger receptor class B, type I (SR-BI). SR-BI was present in caveolae of brain capillary endothelial cells and expressed almost exclusively at the apical membrane. Disruption of caveolae with methyl-β-cyclodextrin (CDX) resulted in (mis)sorting of SR-BI to the basolateral membrane. Immunohistochemistry of porcine brain cryosections revealed SR-BI expression on brain capillary endothelial cells and presumably astrocytic endfeet. HDL-associated [14C]αTocH taken up by brain capillary endothelial cells was recovered in sucrose gradient fractions containing the majority of cellular caveolin-1, the major caveolae-associated protein. During mass transfer studies using αTocH-enriched HDL, approximately 50% of cellular αTocH was recovered with the bulk of cellular caveolin-1 and SR-BI. Efflux experiments revealed that a substantial amount of cell-associated [14C]αTocH could be mobilized into the culture medium. In addition, apical-to-basolateral transport of HDL holoparticles and HDL-associated αTocH was saturable. Results from the present study suggest that part of cerebral apolipoprotein A-I and αTocH originates from plasma HDL transcytosed across the BBB and that caveolae-located SR-BI facilitates selective uptake of HDL-associated αTocH at the BBB.

The Oligo-/Miocene Qom Formation (Iran): evidence for an early Burdigalian restriction of the Tethyan Seaway and closure of its Iranian gateways

Abstract: In the central Iranian Esfahan-Sirjan and Qom basins sedimentation of the Oligo-/Miocene Qom Formation took place on extensive mixed carbonate–siliciclastic ramps. During this time, both basins were positioned at the Eurasian margin of the Tethyan Seaway, which connected the western and eastern regions of the Tethys Ocean at least until the late Burdigalian. During the so-called Terminal Tethyan Event the Tethyan Seaway was then closed due to the collision of the African/Arabian and Iranian/Eurasian plates. Facies analysis of the sedimentary record of both basins indicates paleoenvironments ranging from terrestrial to open marine settings, including mangrove, restricted inner shelf lagoon, seagrass meadow, reefal, and deeper offshore environments. Recognition of eight depositional sequences and elaboration of an integrated biostratigraphic framework (calcareous nannoplankton, planktic and larger benthic foraminifers, gastropods, and pectinids) allow us to construct a basin-spanning stratigraphy. The assignment of the recognized sea-level lowstands to the Ru 3 to Bur 3 lowstands of the global sea-level curve enables a comparison with time-equivalent sections from the Zagros Basin, which was part of the African/Arabian Plate on the opposing southern margin of the Tethyan Seaway. The so calibrated sections display restrictions of the Tethyan Seaway and interruption of the south Iranian gateways between the Qom Basin and the Proto-Indopacific in relation to ongoing plate collision during the early Burdigalian.

The seasonal distribution of campylobacter infection in nine European countries and New Zealand.

Abstract: In all temperate countries campylobacter infection in humans follows a striking seasonal pattern, but little attention has been given to exploring the epidemiological explanations. In order to better characterize the seasonal patterns, data from nine European countries and New Zealand have been examined. Several European countries with weekly data available showed remarkably consistent seasonal patterns from year to year, with peaks in week 22 in Wales, week 26 in Scotland, week 32 in Denmark, week 30 in Finland and week 33 in Sweden. In Europe, the seasonal peak was most prominent in Finland and least prominent in Scotland and Austria. In New Zealand the seasonality was less consistent since the peak was more prolonged. Possible explanations for the seasonal peaks are discussed. Research into the causes of campylobacter seasonality should help considerably in elucidating the sources of human infection.

Muscle-specific overexpression of lipoprotein lipase causes a severe myopathy characterized by proliferation of mitochondria and peroxisomes in transgenic mice.

Abstract: In extrahepatic tissues lipoprotein lipase (LPL) hydrolyzes triglycerides thereby generating FFA for tissue uptake and metabolism. To study the effects of increased FFA uptake in muscle tissue, transgenic mouse lines were generated with a human LPL minigene driven by the promoter of the muscle creatine kinase gene. In these mice human LPL was expressed in skeletal muscle and cardiac muscle, but not in other tissues. In proportion to the level of LPL overexpression, decreased plasma triglyceride levels, elevated FFA uptake by muscle tissue, weight loss, and premature death were observed in three independent transgenic mouse lines. The animals developed a severe myopathy characterized by muscle fiber degeneration, fiber atrophy, glycogen storage, and extensive proliferation of mitochondria and peroxisomes. This degree of proliferation suggests that FFA play an important role in the biogenesis of these organelles. Our experiments indicate that LPL is rate limiting for the supply of muscle tissue with triglyceride-derived FFA. Improper regulation of muscle LPL can lead to major pathological changes and may be important in the pathogenesis of some human myopathies. Muscle-specific LPL transgenic mouse lines will serve as a useful animal model for the investigation of myopathies and the biogenesis of mitochondria and peroxisomes.

Cytochrome P450 mono-oxygenase-regulated signalling of Ca2+ entry in human and bovine endothelial cells.

Abstract: 1. We tested the hypothesis that agonist-stimulated Ca2+ entry, and thus formation of endothelium-derived nitric oxide (EDNO) in vascular endothelial cells, is related to activation of microsomal P450 mono-oxygenase (P450 MO) and the biosynthesis of 5,6-epoxyeicosatrienoic acid (5,6-EET). 2. Several P450 inhibitors diminished the sustained [Ca2+]i plateau response to agonist or intracellular Ca2+ store depletion with ATPase inhibitors by 31-69% (fura-2 technique). Mn2+ influx stimulated by agonists or ATPase inhibitors was prevented by P450 inhibitors. 3. Histamine- or ATPase inhibitor-stimulated formation of EDNO was strongly attenuated (50-83%) by P450 inhibitors, without any effect on EDNO formation by the Ca2+ ionophore A23187, indicating that decreased EDNO synthesis is due specifically to the inhibition of Ca2+ entry by these compounds. 4. Induction of P450 MO by beta-naphthoflavone potentiated agonist-induced Ca2+ and Mn2+ influx by 60 and 53%, respectively. Intracellular Ca2+ release remained unchanged. 5. The P450 MO product, 5,6-EET (< 156 nmol l-1), activated Ca2+/Mn2+ entry without any depletion of intracellular Ca2+ stores. The 5,6-EET-stimulated Ca2+/Mn2+ entry was not affected by P450 inhibitors. 6. As with the bradykinin-stimulated Ca2+ entry pathway, the 5,6-EET-activated Ca2+ entry pathway was permeable to Mn2+ and Ba2+, sensitive to Ni2+, La3+ and membrane depolarization, and insensitive to the removal of extracellular Na+ or the organic Ca2+ antagonist, nitrendipine. 7. In the presence of 5,6-EET, stimulation with bradykinin only transiently increased [Ca2+]i. Vice versa, 5,6-EET failed to increase [Ca2+]i further in bradykinin-stimulated cells. The sustained [Ca2+]i plateau phase induced by a co-stimulation with bradykinin and 5,6-EET was identical to that observed with bradykinin or 5,6-EET alone. 8. These results demonstrate that Ca2+ entry induced by the P450 MO product, 5,6-EET, is indistinguishable to that observed by stimulation with bradykinin. 9. All data support our hypothesis that depletion of endothelial Ca2+ stores activates microsomal P450 MO which in turn synthesizes 5,6-EET. We propose that the arachidonic acid metabolite 5,6-EET or one of its metabolites is a second messenger for activation of endothelial Ca2+ entry.