Towards a green new deal : lessons after a lost decade

In his essay, the author presents a stock-taking of the debate on Green Deals. The starting point of this personal assessment is a brief outline of the content and impact of a study in which the author and colleagues published a first outline of a "Green New Deal for Europe" as a political response to the 2008 financial crisis. 2008 had been a critical juncture for mainstream economics: however, from the perspective of policy-learning, the period after has been a lost decade. The European Green Deal as presented by the European Commission in 2019 can be perceived as a historic milestone and confirmation of a regime change in mainstream economic policy in which ecological considerations gain in importance. Yet, the Deal suffers from major deficits. In sum, the European Green Deal could be interpreted as an insufficient attempt to take advantage of the rapidly closing windows of opportunity for a peaceful transition towards sustainability. On the eve of a planetary crisis, the governance of economic transitions towards sustainability needs to be improved and accelerated. Reflecting on the 2009 study A Green New Deal for Europe, this essay attempts to draw a few lessons and frugal heuristics for the policy-design of Green Deals

Retardation of atherosclerosis in immunocompetent apolipoprotein (apo) E-deficient mice followingliver-directed administration of a [E1-, E3-,polymerase-] adenovirus vector containing the elongation factor-1a promoter driving expression of human apoE cDNA

Although gene transfer of human apolipoprotein E (apoE), a 34-kDa circulating glycoprotein, to the liver of apoEdeficient(apoE-/-) mice using recombinant adenoviral vectors (rAd) is antiatherogenic, its full therapeutic potentialhas yet to be realized. First generation vectors led to immune clearance of transduced hepatocytes, while animproved vector with adenovirus regions E1, E3 and DNA polymerase deleted also had transient effects due tocellular shutdown of the cytomegalovirus (CMV) promoter. Here, we have studied an alternative promoter from thecellular elongation factor 1a (EF-1a) gene, injecting 6-8 week old apoE-/- mice intravenously with 2x1010 virusparticles (vp) of the [E1-, E3-, polymerase-] rAd vector Ad-EF1·-apoE. Plasma apoE levels were low (18-55 ng/ml)and failed to reduce plasma cholesterol or normalize the adverse lipoprotein profile. By contrast, thehyperlipidaemic phenotype of apoE-/- mice treated with Ad-CMV-apoE (2x1010 vp) was transiently normalized.Nevertheless, at termination (265 days) the aortic lesion areas in animals given Ad-EF1·-apoE were significantlyreduced by 15% (P<0.05) compared to untreated animals, a decrease approaching that in Ad-CMV-apoE-treatedmice (23%; P<0.02). Importantly, the attenuation of apoE transgene expression noted with the CMV promoter wasabsent with the EF-1a promoter, which gave relatively sustained, albeit low, levels of plasma apoE throughout thestudy period

Kollaps oder Rückkehr zur Politik?

Die Rio+10-Konferenz nächstes Jahr in Johannesburg wirft ihre Schatten vor­aus. Nicht nur in Deutschland und anderen Ländern werden die diesbezüglichen Aktivitäten verstärkt, auch die Europäische Union plant, Ende Juni eine Nach­haltigkeitsstrategie zu beschließen. Im Mittelpunkt der Diskussion steht die Frage, wie der laufende Prozess zur Integration der Umweltpolitik in andere Politikbereiche mit der sozialen und ökonomischen Dimension der Nachhaltig­keit verknüpft werden kann bzw. sollte

Potential mechanisms behind blood pressure modulation by melatonin

Melatonin, das in der Zirbeldrüse gebildet wird, ist eine sehr vielseitige Substanz. Melatonin moduliert die innere Uhr, den Appetites, den Schlafs und den Blutdruckes und ist ein starker Radikalfänger. Es wird angenommen, dass die zwei in Säugetieren vorkommenden Melatonin-Rezeptoren MT1 und MT2 auch im Herz-Kreislaufsystem exprimiert sind, allerdings sind die Daten zu Funktion und Ort dieser Rezeptoren strittig. Es gibt viele Hinweise, dass MT1 Vasokonstriktion und MT2 Vasodilatation vermitteln. Da exogenes Melatonin den Blutdruck senkt, sind die Mechanismen, die hinter der blutdruckregulierenden Wirkung durch MT1 und MT2 stehen, von großem Interesse. Im Projekt wurden mehrere Ratten-Aorten mittels RT-PCR und RT-qPCR auf MT1 und MT2 mRNA Expression untersucht. Aus den Ergebnissen kann geschlossen werden, dass MT1 mRNA in der exprimiert ist, wohingegen MT2 mRNA in der Ratten-Aorta gar nicht vorkommt. Die Expression von MT1 mRNA scheint keinem zirkadianen Rhythmus zu folgen, da kein Unterschied in der Expressionsrate zwischen Aorten von zwei 12 h auseinanderliegenden Zeitpunkten festgestellt werden konnte. Im Gegensatz dazu stellten wir eine 4-fache Erhöhung der MT1 mRNA Expressionsrate in Aorten von spontan-hypertensiven Ratten, einem Modell für primäre Hypertonie, fest. Dieser Befund unterstützt die Annahme einer Beteiligung von MT1 an den Blutdruck-modulierenden Eigenschaften von Melatonin. Mit Hilfe der Immunfluoreszenz-Mikroskopie stellten wir fest, dass MT1 Protein hauptsächlich in der Tunica Adventitia der Ratten-Aorta exprimiert ist. Diese Lokalisation und die Abwesenheit von MT2 stehen im Gegensatz zu derzeitigen Hypothesen über den Einfluss der Melatonin-Rezeptoren MT1 und MT2 und bedürfen weiterer Untersuchung.Melatonin is a versatile substance produced in the pineal gland. It influences the body’s internal clock, appetite, sleep, blood pressure and is a potent radical scavenger. The two mammalian G-protein coupled receptors for melatonin, MT1 and MT2, are believed to be expressed in the cardiovascular system; however, the function and location of these receptors in the cardiovascular system remain under debate. Various data suggested that MT1 mediates vasoconstriction, while MT2 mediates vasodilation. Since exogenous melatonin lowers blood pressure, the mechanisms involved in blood pressure regulation via MT1 and MT2 are of great interest. We investigated various rat aortas with RT-PCR and RT-qPCR for expression of MT1 and MT2 mRNA. It can be concluded that MT1 mRNA is indeed present in the rat aorta, whereas MT2 mRNA is not expressed at all. MT1 mRNA expression exhibits no circadian variations, since we observed no difference between aortas from 12 h away time points. Moreover, we discovered that MT1 mRNA expression is about 4-fold increased in spontaneously hypertensive rats, a model for essential hypertension. This finding supports a function of MT1 in the blood pressure modulating capabilities of melatonin. By use of immunofluorescence microscopy, we learned that MT1 protein is mainly expressed in the tunica adventitia of the rat aorta. This localization of MT1 and the absence of MT2, however, are in conflict with the current hypothesis on the influence of the melatonin GPCRs on blood pressure regulation by melatonin and ask for further investigation

Wissenschaft ohne Ethos : Wissensproduktion als gesellschaftliches Interesse

Angesichts der drängenden Herausforderungen unserer Zeit erwarten große Teile der Öffentlichkeit und Politik eine engagierte Wissenschaft, die sich aktiv an der Lösung ökologischer, ökonomischer und sozialer Probleme beteiligt. Diese Erwartungshaltung hat dazu beigetragen, Diskussionen über eine "third mission" der Wissenschaft aufzuwerfen. Damit verbunden sind Fragen zu gesellschaftlichem Engagement und Distanz zur Politik in Forschung und Lehre, mit denen sich bereits der amerikanische Wissenschaftssoziologe Robert K. Merton in den 30er Jahren des vergangenen Jahrhunderts beschäftigte und die ihn dazu bewogen, ein Ethos der Wissenschaft zu postulieren. (...) Vor dem Hintergrund der Traumatisierung der Wissenschaft durch den Nationalsozialismus und seine dramatischen Folgen stellt sich heute nach wie vor die Frage, ob - und wenn ja wie - Forschung und Lehre gegen politische Intervention und Pervertierung immunisiert werden können. Gibt es überhaupt so etwas wie "reine Wissenschaft" und wie lässt sich diese abgrenzen? Brauchen wir ein Wissenschaftsethos oder gibt es dazu Alternativen? Im Folgenden versuchen wir uns diesen Fragen zu nähern. Wir sind weder Wissenschaftssoziologen noch Wissenschaftshistoriker und werden deshalb nur sehr kursorisch auf die entsprechenden Forschungen verweisen. Wir nähern uns den Fragen zum einen aus der Perspektive der angewandten Nachhaltigkeitsforschung und zum anderen mit einem wissenschaftsphilosophischen und erkenntnistheoretischen Hintergrund. Unsere Kritik an Mertons Ansatz hat daher sowohl einen explizit praktischen als auch philosophischen Zugang

Determining the role of the calcium sensing receptor in vascular smooth muscle cells via targeted gene deletion

The extracellular-Ca2+ sensing receptor (CaSR) is a G protein-coupled receptor which is essential for Ca2+ homeostasis in the body. The best studied function of the CaSR lies in the parathyroid gland, where hypercalcaemia activates the receptor which in consequence inhibits parathyroid hormone secretion. However, for other tissues like the vasculature the physiological and pathophysiological roles of the CaSR are a lot less well defined. The CaSR is expressed in all layers of blood vessels, the endothelium, the vascular smooth muscle cells (VSMC) and the tunica adventitia. Previous studies have suggested roles for the vascular CaSR in protection against vascular calcification and in blood pressure regulation. In the course of my thesis, I have investigated the specific roles of the vascular CaSR by characterising the phenotype of a transgenic mouse model of targeted CaSR deletion from VSMC (SM22α-Cre x LoxP-CaSR). In characterising this mouse model, I have made three principal discoveries: 1) The VSMC CaSR protects against vascular calcification induced by high Ca2+ and Pi in vitro. No calcification was discovered in mice lacking the VSMC CaSR in vivo, suggesting that this protective effect of the CaSR might only assert itself in pathological disease. 2) The VSMC CaSR contributes to blood pressure regulation. Mice lacking the VSMC CaSR exhibit hypotension which is due to impaired vascular contractility and therefore reduced total peripheral resistance. I propose a role for the VSMC CaSR as auto- / paracrine amplifier of VSMC contraction. Furthermore, knock-out mice exhibit bradycardia and sporadic cardiac remodelling. 3) Mice lacking the VSMC CaSR exhibit profound changes in mineral ion metabolism, together with severe hypercalcaemia, hypercalciuria, hyperphosphaturia and increased 1,25-(OH)2-Vitamin D3 and phosphaturic FGF23 levels, and decreased bone mineral density, consistent with a phenotype resembling primary hyperparathyroidism. The mechanisms behind this influence remain yet to be fully understood

Pitfall of vertebral artery insonation: Bidirectional flow without subclavian artery pathology

SummaryBackgroundA bidirectional flow pattern within the intracranial segment of the vertebral artery (V4–VA) should be indicative of a proximal steno-occlusive disorder of the ipsilateral subclavian artery (SA). Here we present two patients revealing this ultrasound finding without evidence of a specific SA pathology.Methods/case reportsIn case 1 duplex sonography revealed a diameter of the left V2–VA of 3.3mm and 2.7mm on the right side. Normal flow signals were detected in the left V2–VA, a systolic flow deceleration was seen on the right side. Intracranially, a biphasic flow pattern was observed in the right V4–VA. The left V4–VA, the basilar artery and the brachial arteries (BrA) as well as the cuff-test were normal. Conventional angiography ruled out a SA or VA pathology. A bilateral fetal-type posterior cerebral artery (FT-PCA) was seen. CT angiography demonstrated a small diameter of the right intracranial V4–VA close to the basilar confluens.In case 2 VA diameter of the left and right V2–VA was 3.3 and 2.3mm, respectively. Flow signals, similar to case 1 were observed in the non-dominant V2–VA and V4–VA segment. The remaining vessels and the cuff-test were normal. MR angiography demonstrated a FT-PCA and an incomplete posterior inferior cerebellar artery (PICA)-ending VA on the right side.ConclusionsA bidirectional flow in V4–VA can not prove a subclavian steal phenomenon. A normal triphasic flow signal of the brachial artery excludes a relevant proximal obstruction of the SA. Also, diameter measurements of the VA are mandatory.It seems that physiological variants of the vertebrobasilar circulation like a VA hypoplasia, PICA-ending VA or FT-PCA might also cause the above type of VA flow pattern

Overview and Evaluation of a Computational Bone Physiology Modeling Toolchain and Its Application to Testing of Exercise Countermeasures

Prolonged microgravity exposure disrupts natural bone remodeling processes and can lead to a significant loss of bone strength, increasing injury risk during missions and placing astronauts at a greater risk of bone fracture later in life. Resistance-based exercise during missions is used to combat bone loss, but current exercise countermeasures do not completely mitigate the effects of microgravity. To address this concern, we present work to develop a personalizable, site-specific computational modeling toolchain of bone remodeling dynamics to understand and estimate changes in volumetric bone mineral density (BMD) in response to microgravity-induced bone unloading and in-flight exercise. The toolchain is evaluated against data collected from subjects in a 70-day bedrest study and is found to provide insight into the amount of exercise stimulus needed to minimize bone loss, quantitatively predicting post-study volumetric BMD of control subjects who did not perform exercise, and qualitatively predicting the effects of exercise. Results suggest that, with additional data, the toolchain could be improved to aid in developing customized in-flight exercise regimens and predict exercise effectiveness