scholarly journals Impact of Extrinsic and Intrinsic Hypoxia on Catecholamine Biosynthesis in Absence or Presence of Hif2α in Pheochromocytoma Cells

Cancers ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 594 ◽  
Author(s):  
Nicole Bechmann ◽  
Isabel Poser ◽  
Verena Seifert ◽  
Christian Greunke ◽  
Martin Ullrich ◽  
...  

Pheochromocytomas and paragangliomas (PPGLs) with activated pseudohypoxic pathways are associated with an immature catecholamine phenotype and carry a higher risk for metastasis. For improved understanding of the underlying mechanisms we investigated the impact of hypoxia and pseudohypoxia on catecholamine biosynthesis in pheochromocytoma cells naturally lacking Hif2α (MPC and MTT) or expressing both Hif1α and Hif2α (PC12). Cultivation under extrinsic hypoxia or in spheroid culture (intrinsic hypoxia) increased cellular dopamine and norepinephrine contents in all cell lines. To distinguish further between Hif1α- and Hif2α-driven effects we expressed Hif2α in MTT and MPC-mCherry cells (naturally lacking Hif2α). Presence of Hif2α resulted in similarly increased cellular dopamine and norepinephrine under hypoxia as in the control cells. Furthermore, hypoxia resulted in enhanced phosphorylation of tyrosine hydroxylase (TH). A specific knockdown of Hif1α in PC12 diminished these effects. Pseudohypoxic conditions, simulated by expression of Hif2α under normoxia resulted in increased TH phosphorylation, further stimulated by extrinsic hypoxia. Correlations with PPGL tissue data led us to conclude that catecholamine biosynthesis under hypoxia is mainly mediated through increased phosphorylation of TH, regulated as a short-term response (24–48 h) by HIF1α. Continuous activation of hypoxia-related genes under pseudohypoxia leads to a HIF2α-mediated phosphorylation of TH (permanent status).

2016 ◽  
Vol 106 (09) ◽  
pp. 631-636
Author(s):  
H. Prinzhorn ◽  
M. Zenker ◽  
R. Sporrer ◽  
P. Prof. Nyhuis

Die hohe Störfanfälligkeit bei der Montage großskaliger Produkte verlangt eine kurzfristige Auswahl von Maßnahmen zur Reaktion auf Störungen, um Auswirkungen wie Lieferterminverspätungen oder Auslastungsverluste zu reduzieren. Die Nutzung von Flexibilitätspotenzialen eines Produktionssystems stellt einen Ansatz dar, um diese Herausforderung zu bewältigen. Dieser Fachbeitrag zeigt auf, welche Flexibilitätspotenziale in diesem speziellen Umfeld zur Verfügung stehen und genutzt werden können.   Assembling large-scale products involves frequent process interruptions why in order to reduce the impact of interruptions, a short-term response is necessary to reduce delivery delays and idle times of resources. An approach for challenge this represents the flexibility of a production system. Regarding the environment of large-scale product assembly, it has to be shown which potentials of flexibility are able to use in a short-term manner.


1993 ◽  
Vol 7 ◽  
pp. 17-37 ◽  
Author(s):  
Patrick Clawson

This article looks at some major goals that have been set for sanctions and evaluates how effective sanctions have been at reaching those goals. It also examines the costs of sanctions, i.e., the impact on civilians and on international support for sanctions. Clawson concludes that sanctions are useful only as a short-term response in situations in which the world community is prepared to use force in the likely event that the target regime does not change its behavior. If there is not will to use force to back the sanctions, then the sanctions are morally dubious: they impose suffering and may cause deaths without offering a reasonable prospect of accomplishing good.


Author(s):  
Florian Arendt

A test was done to see if reading a newspaper which consistently overrepresents foreigners as criminals strengthens the automatic association between foreign country and criminal in memory (i.e., implicit cultivation). Further, an investigation was done to find out if reading articles from the same newspaper produces a short-term effect on the same measure and if (1) emotionalization of the newspaper texts, (2) emotional reactions of the reader (indicated by arousal), and (3) attributed text credibility moderate the short-term treatment effect. Eighty-five participants were assigned to one of three experimental conditions. Participants in the control group received short factual crime texts, where the nationality of the offender was not mentioned. Participants in the factual treatment group received the same texts, but the foreign nationality was mentioned. Participants in the emotionalized treatment group received emotionalized articles (i.e., texts which are high in vividness and frequency) covering the same crimes, with the foreign nationality mentioned. Supporting empirical evidence for implicit cultivation and a short-term effect was found. However, only emotionalized articles produced a short-term effect on the strength of the automatic association, indicating that newspaper texts must have a minimum of stimulus intensity to overcome an effect threshold. There were no moderating effects of arousal or credibility pertaining to the impact on the implicit measure. However, credibility moderated the short-term effect on a first-order judgment (i.e., estimated frequency of foreigners of all criminals). This indicates that a newspaper’s effect on the strength of automatic associations is relatively independent from processes of propositional reasoning.


Author(s):  
Irina A. Prushkovskaya ◽  
Ira B. Tsoy

The study of diatoms in the sediments of the Amur Bay (Sea of Japan), formed over the last 2000 years, showed that the sharp short-term drops in the concentration of diatoms coincide with the minima of bromine content, which can be explained by the influence of typhoons or other catastrophic events leading to floods and used later in paleoreconstructions.


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