Aurelian’s Monetary Reform: Between Debasement and Public Trust

Die Münzverschlechterung im 3. Jahrhundert n.Chr. wird traditionell als die Hauptursache für den Zusammenbruch des überkommenen römischen Währungssystems angesehen. Der Artikel hebt die Bedeutung des Vertrauens der Bevölkerung in die Währung für deren Stabilität hervor und untersucht die Wechselwirkung zwischen Vertrauen der Bevölkerung und Münzverschlechterung. Wesentlich für das Verständnis dieses Zusammenhangs ist die von Aurelian angeordnete Währungsreform von 274 mit ihren weitreichenden Konsequenzen für den Münzwert. Anhand eines Wirtschaftsmodells erklärt die Autorin, warum Aurelians Währungsreform entscheidend den Rückgang des allgemeinen Vertrauens auslöste und schließlich zum Ende der bestehenden Währungsordnung führte.Coin debasement in the third-century CE is traditionally seen as a main cause for the collapse of Rome’s long-lasting monetary system. The article stresses the significance of public trust in the currency for the stability of the Roman monetary order and investigates the relation between public trust and coin debasement. Essential for understanding this relation is Aurelian’s monetary reform of 274, with its grave consequences on coin value. The article offers an economic model which explains why Aurelian’s monetary reform was the coordinating event that triggered the decline in public trust, eventually leading to the end of the existing monetary order.La dépréciation monétaire du IIIe s. p.C. est généralement perçue comme la cause principale de l’écroulement du système monétaire de Rome. L’article souligne l’importance, pour la stabilité de l’ordre monétaire romain, de la confiance publique envers le système monétaire, et examine la relation entre la confiance publique et la dépréciation de la monnaie. La réforme monétaire d’Aurélien de 274, avec ses graves conséquences sur la valeur du numéraire, est essentielle pour comprendre cette relation. L’article présente un modèle économique qui explique pourquoi la réforme monétaire d’Aurélien fut l’événement de coordination qui déclencha la baisse de la confiance publique, menant finalement à la fin de l’ordre monétaire en place

Mortality rates in Israel from causes amenable to health care, regional and international comparison

BACKGROUND: Mortality from causes amenable to health care is a valuable indicator of quality of the health care system, which can be used to assess inter-regional differences and trends over time. This study investigates these mortality rates in Israel over time, and compares inter-regional and international rates in recent years. RESULTS: Age-adjusted amenable mortality rates have been decreasing steadily in Israel, by 31% for males and 28% for females between 1998–2000 and 2007–2009. Amenable mortality was lower in the center of the country than in the Northern, Southern, and Haifa districts. The proportion of mortality from circulatory diseases was highest in the North and Haifa districts and from cancer in the Tel-Aviv and Central districts. A higher proportion of infectious diseases was seen in the Southern district. In comparison with amenable mortality rates in 20 European countries, Israel ranked 8(th) lowest for males and 12(th) lowest for females, in 2008. The rate was lower than in Britain, Ireland, and Portugal; lower than in Germany, Spain, Austria, and Finland for males; and higher than France, Netherlands, Sweden, Norway, and Italy. But Israel ranked higher in the decrease in amenable mortality rates between 2001 and 2007 for females than males in a 19 country comparison. Genitourinary diseases were a larger component in Israel than other countries and circulatory diseases were smaller. CONCLUSION: The indicator of amenable mortality shows improvement in health outcomes over the years, but continuing improvement is needed in health care and education, in particular in the periphery of Israel and for females

Rasosomes originate from the Golgi to dispense Ras signals

Ras proteins undergo an incompletely understood trafficking process in the cell. Rasosomes are protein nanoparticles of 80–100 nm diameter that carry lipidated Ras isoforms (H-Ras and N-Ras) as well as their effectors through the cytoplasm and near the plasma membrane (PM). In this study, we identified the subcellular origin of rasosomes and how they spread Ras proteins through the cell. We found no dependency of rasosome formation on galectins, or on the GDP-/GTP-bound state of Ras. We found that significantly more rasosomes are associated with forms of Ras that are localized to the Golgi, namely N-Ras or the singly palmitoylated H-Ras mutant (C181S). To explore the possibility that rasosome originate from the Golgi, we used photoactivatable (PA)-GFP-H-Ras mutants and showed that rasosomes bud from the Golgi in a two-step mechanism. Newly released rasosomes first move in an energy-dependent directed fashion and then convert to randomly diffusing rasosomes. Dual fluorescence time-lapse imaging revealed the appearance of dually labeled rasosomes, indicating a dynamic exchange of cytoplasmic and PM-associated Ras with rasosome-associated Ras. Finally, higher levels of rasosomes correlate with higher levels of ERK phosphorylation, a key marker of Ras downstream signaling. We suggest that H-Ras and N-Ras proteins exchange with rasosomes that can function as carriers of palmitoylated Ras and its signals

Dominant ethnicity: from minority to majority

This article argues that the world is in the midst of a long-term transition from dominant minority to dominant majority ethnicity. Whereas minority domination was common in premodern societies, modernity (with its accent on democracy and popular sovereignty) has engendered a shift to dominant majority ethnicity. The article begins with conceptual clarifications. The second section provides a broad overview of the general patterns of ethnic dominance that derive from the logic of modern nationalism and democratisation. The third section discusses remnants of dominant minorities in the modern era and suggests that their survival hinges on peculiar historical and social circumstances coupled with resistance to democratisation. The fourth section shifts the focus to dominant majorities in the modern era and their relationship to national identities. The article ends with a discussion of the fortunes of dominant ethnicity in the West

FTS and 2-DG induce pancreatic cancer cell death and tumor shrinkage in mice

The Ras inhibitor S-trans-trans farnesylthiosalicylic acid (FTS) inhibits active Ras, which controls cell proliferation, differentiation, survival, and metabolism. FTS also inhibits HIF1α expression in cancer cells, leading to an energy crisis. The synthetic glucose analog 2-deoxy-D-glucose (2-DG), which inhibits glycolysis, is selectively directed to tumor cells that exhibit increased glucose consumption. The 2-DG enters tumor cells, where it competes with glucose for glycolytic enzymes. In cancer models, as well as in human phase 1 trials, 2-DG inhibits tumor growth without toxicity. We postulated that under normoxic conditions, tumor cells treated with FTS would be more sensitive than normal cells to 2-DG. We show here that combined treatment with FTS and 2-DG inhibited cancer cell proliferation additively, yet induced apoptotic cell death synergistically both in vitro and in vivo. The induced apoptosis was inferred from QVD-OPH inhibition, an increase in cleaved caspase 3, and loss of survivin. FTS and 2-DG when combined, but not separately, also induced an increase in fibrosis of the tumor tissue, chronic inflammation, and tumor shrinkage. Overall, these results suggest a possible new treatment of pancreatic tumors by the combined administration of FTS and 2-DG, which together induce pancreatic tumor cell death and tumor shrinkage under non-toxic conditions

The Ras Antagonist, Farnesylthiosalicylic Acid (FTS), Decreases Fibrosis and Improves Muscle Strength in dy2J/dy2J Mouse Model of Muscular Dystrophy

The Ras superfamily of guanosine-triphosphate (GTP)-binding proteins regulates a diverse spectrum of intracellular processes involved in inflammation and fibrosis. Farnesythiosalicylic acid (FTS) is a unique and potent Ras inhibitor which decreased inflammation and fibrosis in experimentally induced liver cirrhosis and ameliorated inflammatory processes in systemic lupus erythematosus, neuritis and nephritis animal models. FTS effect on Ras expression and activity, muscle strength and fibrosis was evaluated in the dy2J/dy2J mouse model of merosin deficient congenital muscular dystrophy. The dy2J/dy2J mice had significantly increased RAS expression and activity compared with the wild type mice. FTS treatment significantly decreased RAS expression and activity. In addition, phosphorylation of ERK, a Ras downstream protein, was significantly decreased following FTS treatment in the dy2J/dy2J mice. Clinically, FTS treated mice showed significant improvement in hind limb muscle strength measured by electronic grip strength meter. Significant reduction of fibrosis was demonstrated in the treated group by quantitative Sirius Red staining and lower muscle collagen content. FTS effect was associated with significantly inhibition of both MMP-2 and MMP-9 activities. We conclude that active RAS inhibition by FTS was associated with attenuated fibrosis and improved muscle strength in the dy2J/dy2J mouse model of congenital muscular dystrophy

H-Ras Nanocluster Stability Regulates the Magnitude of MAPK Signal Output

H-Ras is a binary switch that is activated by multiple co-factors and triggers several key cellular pathways one of which is MAPK. The specificity and magnitude of downstream activation is achieved by the spatio-temporal organization of the active H-Ras in the plasma membrane. Upon activation, the GTP bound H-Ras binds to Galectin-1 (Gal-1) and becomes transiently immobilized in short-lived nanoclusters on the plasma membrane from which the signal is propagated to Raf. In the current study we show that stabilizing the H-Ras-Gal-1 interaction, using bimolecular fluorescence complementation (BiFC), leads to prolonged immobilization of H-Ras.GTP in the plasma membrane which was measured by fluorescence recovery after photobleaching (FRAP), and increased signal out-put to the MAPK module. EM measurements of Raf recruitment to the H-Ras.GTP nanoclusters demonstrated that the enhanced signaling observed in the BiFC stabilized H-Ras.GTP nanocluster was attributed to increased H-Ras immobilization rather than to an increase in Raf recruitment. Taken together these data demonstrate that the magnitude of the signal output from a GTP-bound H-Ras nanocluster is proportional to its stability