Altered Composition of Liver Proteasome Assemblies Contributes to Enhanced Proteasome Activity in the Exceptionally Long-Lived Naked Mole-Rat

The longest-lived rodent, the naked mole-rat (Bathyergidae; Heterocephalus glaber), maintains robust health for at least 75% of its 32 year lifespan, suggesting that the decline in genomic integrity or protein homeostasis routinely observed during aging, is either attenuated or delayed in this extraordinarily long-lived species. The ubiquitin proteasome system (UPS) plays an integral role in protein homeostasis by degrading oxidatively-damaged and misfolded proteins. In this study, we examined proteasome activity in naked mole-rats and mice in whole liver lysates as well as three subcellular fractions to probe the mechanisms behind the apparently enhanced effectiveness of UPS. We found that when compared with mouse samples, naked mole-rats had significantly higher chymotrypsin-like (ChT-L) activity and a two-fold increase in trypsin-like (T-L) in both whole lysates as well as cytosolic fractions. Native gel electrophoresis of the whole tissue lysates showed that the 20S proteasome was more active in the longer-lived species and that 26S proteasome was both more active and more populous. Western blot analyses revealed that both 19S subunits and immunoproteasome catalytic subunits are present in greater amounts in the naked mole-rat suggesting that the observed higher specific activity may be due to the greater proportion of immunoproteasomes in livers of healthy young adults. It thus appears that proteasomes in this species are primed for the efficient removal of stress-damaged proteins. Further characterization of the naked mole-rat proteasome and its regulation could lead to important insights on how the cells in these animals handle increased stress and protein damage to maintain a longer health in their tissues and ultimately a longer life

The naked truth: a comprehensive clarification and classification of current 'myths' in naked mole-rat biology.

The naked mole-rat (Heterocephalus glaber) has fascinated zoologists for at least half a century. It has also generated considerable biomedical interest not only because of its extraordinary longevity, but also because of unusual protective features (e.g. its tolerance of variable oxygen availability), which may be pertinent to several human disease states, including ischemia/reperfusion injury and neurodegeneration. A recent article entitled 'Surprisingly long survival of premature conclusions about naked mole-rat biology' described 28 'myths' which, those authors claimed, are a 'perpetuation of beautiful, but falsified, hypotheses' and impede our understanding of this enigmatic mammal. Here, we re-examine each of these 'myths' based on evidence published in the scientific literature. Following Braude et al., we argue that these 'myths' fall into four main categories: (i) 'myths' that would be better described as oversimplifications, some of which persist solely in the popular press; (ii) 'myths' that are based on incomplete understanding, where more evidence is clearly needed; (iii) 'myths' where the accumulation of evidence over the years has led to a revision in interpretation, but where there is no significant disagreement among scientists currently working in the field; (iv) 'myths' where there is a genuine difference in opinion among active researchers, based on alternative interpretations of the available evidence. The term 'myth' is particularly inappropriate when applied to competing, evidence-based hypotheses, which form part of the normal evolution of scientific knowledge. Here, we provide a comprehensive critical review of naked mole-rat biology and attempt to clarify some of these misconceptions

Tax law in the Mediterranean Area

This book is the collection of papers delivered during the 2011 edition of the Mediterranean research Meetings, held in Montecatini terme under the aegis of the European Universitary Institute. Despite the fact that the economic systems of the Mediterranean states are so connected to each other, remarkable differences remains for what concerns the application of taxes, the taxpayer's rights, the fundamental principles taxation is based on. After the first volume (Bridging a Sea, Aracne, 2010) Yoseph Edrey and Marco Greggi bring their attention, in particular to the effect of the global crisis on the mediterranean tax systems, and on the way and means to overtake it

Bridging a Sea - Constitutional and Supranational Limitations to Taxing Powers of the States Across the Mediterranean Sea

This book is the first attempt ever made by a group of Mediterranean Tax researchers to get together and discuss on general principles on taxation law concerning their countries, or of some specific aspects of taxation that are of peculiar relevance in their legal framework, and it's the collection of papers presented and discussed during the 2009 edition of the Mediterranean Research Meeting, organized by the European University Institute, Robert Schumann Center for Advanced Studies. The objective of the seminar was to assess, in a comparative approach, the Constitutional and supranational limits to taxation in states around the Mediterranean sea (and in nearby Countries as well): to evaluate and compare the impact of fundamental principles and rights on the taxing power of the Sovereign States. Peculiar attention was given to EU law for European countries, Religious laws for some of the Arab countries and to the Human rights recognized and implemented by the UN. The EU has recently introduced new limits to tax that however are not related to a social dimension but rather to market-economic approach. At the same time, it could be argued that the situation in other Mediterranean countries is different, being less concerned with ability to pay and redistributive issues. Hence, the first goal of the seminar is to study, in a comparative approach, the possible limitations on the state’s taxing power the participants observe today and what others will be developed in the coming future