SIRT2 deficiency modulates macrophage polarization and susceptibility to experimental colitis

BACKGROUND SIRT2 belongs to a highly conserved family of NAD+-dependent deacylases, consisting of seven members (SIRT1-SIRT7), which vary in subcellular localizations and have substrates ranging from histones to transcription factors and enzymes. Recently SIRT2 was revealed to play an important role in inflammation, directly binding, deacetylating, and inhibiting the p65 subunit of NF-κB. METHODS A Sirt2 deficient mouse line (Sirt2-/-) was generated by deleting exons 5-7, encoding part of the SIRT2 deacetylase domain, by homologous recombination. Age- and sex-matched Sirt2-/- and Sirt2+/+ littermate mice were subjected to dextran sulfate sodium (DSS)-induced colitis and analyzed for colitis susceptibility. RESULTS Sirt2-/- mice displayed more severe clinical and histological manifestations after DSS colitis compared to wild type littermates. Notably, under basal condition, Sirt2 deficiency does not affect the basal phenotype and intestinal morphology Sirt2 deficiency, however, affects macrophage polarization, creating a pro-inflammatory milieu in the immune cells compartment. CONCLUSION These data confirm a protective role for SIRT2 against the development of inflammatory processes, pointing out a potential role for this sirtuin as a suppressor of colitis. In fact, SIRT2 deletion promotes inflammatory responses by increasing NF-κB acetylation and by reducing the M2-associated anti-inflammatory pathway. Finally, we speculate that the activation of SIRT2 may be a potential approach for the treatment of inflammatory bowel disease.

Moral Opinion Polarization and the Erosion of Trust

Since Puntam's seminal work on declining levels of social capital, the question of how social trust is formed has reached unprecedented heights of critical enquiry. While most of the current research concentrates on ethnic diversity and income inequality as the main influences driving down generalized trust, we focus on opinion polarization as another potential impact factor on trust. In more detail, we investigate the extent to which polarization over morally charged issues such as homsexuality, abortion and euthanasia affects individuals' likelihood to trust others. We hypothesize that moral issues have a natural tendency to divide societies' opinions into opposing poles and, thus, to challenge social cohesion in modern civil societies. Based on hierarchical analyses of the fifth wave of the World Values Survey (WVS) — comprising a sample of 39 countries — our results reveal that individuals living in countries characterized by more opinion polarization tend to have less trust in other people.

The 2015 National Elections in Switzerland: Renewed Polarization and Shift to the Right

The 2015 election to the Swiss Parliament marks a return to an already observed trend that was only interrupted in 2011: a shift to the right and an increase in polarization. The vote share of the nationalist-conservative Swiss People's Party (SVP) has now reached a historical height of 29.4% (+2.8). This note discusses why cantons matter in the Swiss national elections, and to what degree elections have become nationalized. Institutionally, the 26 cantons serve as electoral districts. This leads to a highly disproportional electoral system and has magnified the minor vote shifts to a slightly more pronounced shift in seats, with the right now holding a tiny majority of 101 of 200 seats in the first chamber. The two winners, the SVP and the Liberals, also had most campaign funds at their disposal. They were able to guide an extensive nationwide campaign in which they advocated their core issues instead of candidates. Other parties only advertised at the cantonal level.