Sphingosine kinase-1 is a hypoxia-regulated gene that stimulates migration of human endothelial cells

Sphingosine kinases (SK) catalyze the production of sphingosine-1-phosphate which in turn regulates cell responses such as proliferation and migration. Here, we show that exposure of the human endothelial cell line EA.hy 926 to hypoxia stimulates a increased SK-1, but not SK-2, mRNA, protein expression, and activity. This effect was due to stimulated SK-1 promoter activity which contains two putative hypoxia-inducible factor-responsive-elements (HRE). By deletion of one of the two HREs, hypoxia-induced promoter activation was abrogated. Furthermore, hypoxia upregulated the expression of HIF-1alpha and HIF-2alpha, and both contributed to SK-1 gene transcription as shown by selective depletion of HIF-1alpha or HIF-2alpha by siRNA. The hypoxia-stimulated SK-1 upregulation was functionally coupled to increased migration since the selective depletion of SK-1, but not of SK-2, by siRNAs abolished the migratory response. In summary, these data show that hypoxia upregulates SK-1 activity and results in an accelerated migratory capacity of endothelial cells. SK-1 may thus serve as an attractive therapeutic target to treat diseases associated with increased endothelial migration and angiogenesis such as cancer growth and progression.

The Changing Environment of Audiovisual Media. New Technologies, New Patterns of Consumer/Business Behaviour and Their Implications for Audiovisual Media Regulation

Digital TV offers of 200 channels and 500 video-on-demand films, podcasting, mobile television, a new web blog being created every two seconds - these are some of the factual elements depicting contemporary audiovisual media in the digital environment. The present article looks into some of these technological advances and sketches their implications for the markets of media content, in particular as newly emerging patterns of consumer and business behaviour are concerned. Ultimately, it puts forward the question of whether the existing audiovisual media regulatory models, which are still predominantly analogue-based, have been rendered obsolete by the transformed (and continually transforming) digital environment.

Späte Scheidungen: Fakten, Gründe und Auswirkungen. Ein interdisziplinärer Blick auf Ergebnisse einer Schweizer Studie

Scheidungen im Alter sind eine zunehmende gesellschaftliche Realität, allerdings wurde dieses Phänomen bislang kaum wissenschaftlich untersucht. In diesem Beitrag werden neueste Forschungsergebnisse einer Schweizer Studie vorgestellt, welche zeigen, dass späte Scheidungen ein einschneidendes kritisches Lebensereignis mit multiplen Gründen und mannigfachen negativen Auswirkungen auf persönlicher, familialer und sozialer Ebene ist. Allerdings gibt es grosse individuelle Unterschiede, insbesondere Geschlechterunterschiede, hinsichtlich der Gründe und auch bezüglich der psychosozialen Adaptation. Das Ausleuchten der Forschungsresultate trägt nicht nur zu einem besseren Verständnis des Phänomens bei, sondern liefert auch Grundlagen für die familienrechtliche Praxis.

Sensory innervation of the dorsal longitudinal ligament and the meninges in the lumbar spine of the dog

Although intervertebral disc herniation is a well-known disease in dogs, pain management for this condition has remained a challenge. The goal of the present study is to address the lack of information regarding the innervation of anatomical structures within the canine vertebral canal. Immunolabeling was performed with antibodies against protein gene product 9.5, Tuj-1 (neuron-specific class III β-tubulin), calcitonin gene-related peptide, and neuropeptide Y in combination with the lectin from Lycopersicon esculentum as a marker for blood vessels. Staining was indicative of both sensory and sympathetic fibers. Innervation density was the highest in lateral areas, intermediate in dorsal areas, and the lowest in ventral areas. In the dorsal longitudinal ligament (DLL), the highest innervation density was observed in the lateral regions. Innervation was lower at mid-vertebral levels than at intervertebral levels. The presence of sensory and sympathetic fibers in the canine dura and DLL suggests that pain may originate from both these structures. Due to these regional differences in sensory innervation patterns, trauma to intervertebral DLL and lateral dura is expected to be particularly painful. The results ought to provide a better basis for the assessment of medicinal and surgical procedures.