J Cell Biochem

Elevated cellular oxidative stress and oxidative DNA damage are key contributors to impaired cardiac function in diabetes. During chronic inflammation, reactive oxygen species (ROS)-induced lipid peroxidation results in the formation of reactive aldehydes, foremost of which is 4-hydroxy-2-nonenal (4HNE). 4HNE forms covalent adducts with proteins, negatively impacting cellular protein function. During conditions of elevated oxidative stress, oxidative DNA damage such as modification by 8-hydroxydeoxyguanosine (8OHdG) is repaired by 8-oxoguanine glycosylase-1 (OGG-1). Based on these facts, we hypothesized that 4HNE forms adducts with OGG-1 inhibiting its activity, and thus, increases the levels of 8OHG in diabetic heart tissues. To test our hypothesis, we evaluated OGG-1 activity, 8OHG and 4HNE in the hearts of leptin receptor deficient db/db mice, a type-2 diabetic model. We also treated the recombinant OGG-1 with 4HNE to measure direct adduction. We found decreased OGG-1 activity (P\u2009>\u2009.05), increased 8OHG (P\u2009>\u2009.05) and increased 4HNE adducts (P\u2009>\u2009.05) along with low aldehyde dehydrogenase-2 activity (P\u2009>\u2009.05). The increased colocalization of OGG-1 and 4HNE in cardiomyocytes suggest 4HNE adduction on OGG-1. Furthermore, colocalization of 8OHG and OGG-1 with mitochondrial markers TOM 20 and aconitase, respectively, indicated significant levels of oxidatively-induced mtDNA damage and implicated a role for mitochondrial OGG-1 function. In vitro exposure of recombinant OGG-1 (rOGG-1) with increasing concentrations of 4HNE resulted in a concentration-dependent decrease in OGG-1 activity. Mass spectral analysis of trypsin digests of 4HNE-treated rOGG-1 identified 4HNE adducts on C28, C75, C163, H179, H237, C241, K249, H270, and H282. In silico molecular modeling of 4HNE-K249 OGG-1 and 4HNE-H270 OGG-1 mechanistically supported 4HNE-mediated enzymatic inhibition of OGG-1. In conclusion, these data support the hypothesis that inhibition of OGG-1 by direct modification by 4HNE contributes to decreased OGG-1 activity and increased 8OHG-modified DNA that are present in the diabetic heart.1R56 HL131891-01A1/HL/NHLBI NIH HHSUnited States/A10249/Henry Ford Health System/S10 OD010700/OD/NIH HHSUnited States/R01 HL139877/HL/NHLBI NIH HHSUnited States/F32 AA018613/AA/NIAAA NIH HHSUnited States/1R01HL139877-01A1/HL/NHLBI NIH HHSUnited States/R37AA009300-22/National Institute of Alcohol Abuse and Alcoholism/P30 DK020572/DK/NIDDK NIH HHSUnited States/P30 ES020957/ES/NIEHS NIH HHSUnited States/R56 HL131891/HL/NHLBI NIH HHSUnited States/P30 CA 022453/National Institute of Health/S10 OD010700/CD/ODCDC CDC HHSUnited States/R37 AA009300/AA/NIAAA NIH HHSUnited States/P30 CA022453/CA/NCI NIH HHSUnited States/2022-01-06T00:00:00Z32628320PMC793501710762vault:3667

From education for democratic citizenship to the global citizenship education: On the necessity for a paradigm shift

Ovaj članak analizira i komparira dva glavna koncepta u oblasti građanskog obrazovanja: obrazovanje za demokratsko građanstvo (ODG), koncept koji je prevalentan u evropskom diskursu, i obrazovanje za globalno građanstvo (OGG), koje je dominantno u međunarodnim organizacijama poput UNESCO-a. Ova dva koncepta i njihov sadržaj su predstavljeni i podvrgnuti analizi, a potreba za promenom paradigme ka OGG je ilustrovana nekim od globalnih tendencija i ozbiljnih izazova globalnog društva. Istaknuta je odgovornost za uključivanje OGG-a u evropski koncept građanskog obrazovanja i naglašeni su izazovi sa kojima se OGG suočava u okviru politike i implementacije globalnog programa rada - Ciljeva Održivog Razvoja (naročito COR 4) i programa Obrazovanje 2030.The article analyses and compares two main concepts in the field of civic education: education for democratic citizenship (EDC), prevailing in European discourse, and global citizenship education (GCE), dominant in international organisations like UNESCO. The concepts and their content are presented and analysed, and the need for the shift to the GCE is illustrated by some global tendencies and serious challenges of the global world. The responsibility to include GCE into the European concept of civic education is pointed out, as well as the challenges GCE is facing within the policy and implementation of the global agenda, SDG 4 and Education 2030

Geological indicators for impact: The anomalous case of the Vredefort structure, South Africa

The Vredefort Dome is located within and almost central to the Witwatersrand basin in its presently known extent. It exposes a central Archean granite core which is surrounded by a collar of supracrustal rocks. These collar rocks outline a strong polygonal geometry. The Archean core is comprised of two concentric zones, the Outer Granite Gneiss (OGG), and the core central Inlandsee Leucogranofels (ILG). The rocks of the inner core display granulite facies metamorphism, while the OGG is in amphibolite facies. The inner core is believed from recent drill hole information to be underlain by mafic and ultramafic gneisses, the extent of which cannot be assessed at present. A fairly broad zone of charnockites separates the OGG and ILG domains. This zone is characterized by a high concentration of pseudotachylite and ductile shearing. Whereas a number of other domical structures are located within or surrounding the Witwatersrand basin, the Vredefort structure is anomalous, in that it has: a partly polygonal geometry; extensive alkali intrusives in the northwestern sector; granophyre dykes (ring-dykes peripheral to the contact collar-basement and NW-SE or NE-SW trending dykes within the Archean basement); contact metamorphism of the collar supracrustal rocks; the overturning of collar supracrustals in the northern sectors; deformation phenomena widely regarded as representing shock metamorphism (pseudotachylite, (sub)planar microdeformation features in quartz, shatter cones and occurrences of high-P quartz polymorphs); a positive 30 mgal gravity anomaly; and high amplitude magnetic anomalies. Recent geophysical, structural and petrological evidence pertinent for the identification of the processes that led to the formation of the Vredefort structure are summarized