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Institution

University of Graz

EducationGraz, Steiermark, Austria
About: University of Graz is a education organization based out in Graz, Steiermark, Austria. It is known for research contribution in the topics: Population & Quantum chromodynamics. 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.


Papers
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Journal ArticleDOI
TL;DR: High performance liquid chromatography indicated that NKA-LI consisted of several cross-reacting substances, presumably other peptides of the tachykinin family, which was the most potent one to contract tracheal smooth muscle of guinea pigs in vitro.
Abstract: Recent evidence suggests that activation of airway C-fibers, besides causing afferent transmission, also causes release of transmitters from peripheral endings, probably via local axon reflexes, resulting in effects on vascular and bronchial smooth muscle, i.e., vasodilatation, increase in vascular permeability, and bronchoconstriction. In the present study, the release of tachykinins was investigated in the perfused guinea pig lung by various ways of neuronal activation. Substance-P-like immunoreactivity (SP-LI) and neurokinin-A-like immunoreactivity (NKA-LI) was determined by radioimmunoassay in the perfusates. A significantly increased outflow of both SP-LI and NKA-LI was observed during perfusion of the lung with high potassium concentration (60 mM), the C-fiber activator capsaicin (1 µM), bradykinin (1 µM), histamine (100 µM), or the nicotinic agonist dimethylphenyl piperazinium (DMPP) (32 µM). Release of both SP-LI and NKA-LI could also be achieved by electrical stimulation of vagal nerves. The perc...

406 citations

Journal ArticleDOI
TL;DR: It is hypothesized that clearing cellular damage by autophagy is a common denominator of many lifespan-extending manipulations.
Abstract: Organismal lifespan can be extended by genetic manipulation of cellular processes such as histone acetylation, the insulin/IGF-1 (insulin-like growth factor 1) pathway or the p53 system. Longevity-promoting regimens, including caloric restriction and inhibition of TOR with rapamycin, resveratrol or the natural polyamine spermidine, have been associated with autophagy (a cytoprotective self-digestive process) and in some cases were reported to require autophagy for their effects. We summarize recent developments that outline these links and hypothesize that clearing cellular damage by autophagy is a common denominator of many lifespan-extending manipulations.

404 citations

Journal ArticleDOI
TL;DR: In this paper, the authors present a compilation of data for 144 distinct mutations that alter the coding sequence of the BMPR2 gene identified in 210 independent pulmonary arterial hypertension (PAH) subjects.
Abstract: Pulmonary arterial hypertension (PAH) is clinically characterized by a sustained elevation in mean pulmonary artery pressure leading to significant morbidity and mortality. The disorder is typically sporadic, and in such cases the term idiopathic PAH (IPAH) is used. However, cases that occur within families (familial PAH (FPAH)) display similar clinical and histopathological features, suggesting a common etiology. Heterozygous mutations of a type II member of the TGF-beta cell signaling superfamily known as BMPR2 on chromosome 2q33 have been identified in many kindreds with FPAH, yet display both reduced penetrance and sex bias. This report presents the compilation of data for 144 distinct mutations that alter the coding sequence of the BMPR2 gene identified in 210 independent PAH subjects. This large data set characterizes the extent of sequence variation and reveals that the majority (71%) of mutations in FPAH and IPAH comprise nonsense, frameshift, and splice-site defects, and gene rearrangements. These predict premature termination of the transcript with likely loss through the process of nonsense-mediated decay (NMD). A total of 44 missense mutations were identified that substitute amino acid residues at highly conserved sites within recognized functional domains of the mature receptor. We assess this category of mutations in the context of their heterogeneous effects on cell signaling when assayed by in vitro cell-based systems. Disease-causing mutation hot-spots within BMPR2 are summarized. Taken together, these observations are likely to aid in the development of targeted mutation detection strategies relevant for patient management. Finally, we examine the age- and sex-dependent reduced penetrance of BMPR2 mutations by reviewing bmpr2 animal models and the requirement for additional genetic and/or environmental modifiers of disease. In conclusion, these data provide compelling genetic evidence that haploinsufficiency is the predominant molecular mechanism underlying disease predisposition, and support the concept of a critical threshold of signaling activity below which disease may be precipitated.

404 citations

Journal ArticleDOI
TL;DR: Distinct plasma ceramide ratios are significant predictors of CV death both in patients with stable CAD and ACS, over and above currently used lipid markers.
Abstract: All authors:Reijo Laaksonen, Kim Ekroos, Marko Sysi-Aho, Mika Hilvo, Terhi Vihervaara, Dimple Kauhanen, Matti Suoniemi, Reini Hurme, Winfried Marz, Hubert Scharnagl, Tatjana Stojakovic, Efthymia Vlachopoulou, Marja-Liisa Lokki, Markku S. Nieminen, Roland Klingenberg, Christian M. Matter, Thorsten Hornemann, Peter Juni, Nicolas Rodondi, Lorenz Raber, Stephan Windecker, Baris Gencer, Eva Ringdal Pedersen, Grethe S. Tell, Ottar Nygard, Francois Mach, Juha Sinisalo, Thomas F. Lusche

402 citations

Journal ArticleDOI
TL;DR: Stable peptide inhibitors are designed that specifically disrupt proinflammatory CCL5-CXCL4 interactions, thereby attenuating monocyte recruitment and reducing atherosclerosis without the aforementioned side effects.
Abstract: Atherosclerosis is characterized by chronic inflammation of the arterial wall due to chemokine-driven mononuclear cell recruitment. Activated platelets can synergize with chemokines to exacerbate atherogenesis; for example, by deposition of the chemokines platelet factor-4 (PF4, also known as CXCL4) and RANTES (CCL5), triggering monocyte arrest on inflamed endothelium. Homo-oligomerization is required for the recruitment functions of CCL5, and chemokine heteromerization has more recently emerged as an additional regulatory mechanism, as evidenced by a mutual modulation of CXCL8 and CXCL4 activities and by enhanced monocyte arrest resulting from CCL5-CXCL4 interactions. The CCL5 antagonist Met-RANTES reduces diet-induced atherosclerosis; however, CCL5 antagonism may not be therapeutically feasible, as suggested by studies using Ccl5-deficient mice which imply that direct CCL5 blockade would severely compromise systemic immune responses, delay macrophage-mediated viral clearance and impair normal T cell functions. Here we determined structural features of CCL5-CXCL4 heteromers and designed stable peptide inhibitors that specifically disrupt proinflammatory CCL5-CXCL4 interactions, thereby attenuating monocyte recruitment and reducing atherosclerosis without the aforementioned side effects. These results establish the in vivo relevance of chemokine heteromers and show the potential of targeting heteromer formation to achieve therapeutic effects.

402 citations


Authors

Showing all 18136 results

NameH-indexPapersCitations
David Haussler172488224960
Russel J. Reiter1691646121010
Frederik Barkhof1541449104982
Philip Scheltens1401175107312
Christopher D.M. Fletcher13867482484
Jennifer S. Haas12884071315
Jelena Krstic12683973457
Michael A. Kamm12463753606
Frances H. Arnold11951049651
Gert Pfurtscheller11750762873
Georg Kresse111430244729
Manfred T. Reetz11095942941
Alois Fürstner10845943085
David N. Herndon108122754888
David J. Williams107206062440
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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
2023174
2022422
20211,775
20201,759
20191,649
20181,541