The TWEAK/Fn14/CD163 axis - Implications for metabolic disease

TWEAK (tumor necrosis factor-like weak inducer of apoptosis) is a member of the TNF superfamily that controls a multitude of cellular events including proliferation, migration, differentiation, apoptosis, angiogenesis, and inflammation. TWEAK control of these events is via an expanding list of intracellular signalling pathways which include NF-κB, ERK/MAPK, Notch, EGFR and AP-1. Two receptors have been identified for TWEAK – Fn14, which targets the membrane bound form of TWEAK, and CD163, which scavenges the soluble form of TWEAK. TWEAK appears to elicit specific events based on the receptor to which it binds, tissue type in which it is expressed, specific extrinsic conditions, and the presence of other cytokines. TWEAK signalling is protective in healthy tissues, but in chronic inflammatory states become detrimental to the tissue. Consistent data show a role for the TWEAK/FN14/CD163 axis in metabolic disease, chronic autoimmune diseases, and acute ischaemic stroke. Low circulating concentrations of soluble TWEAK are predictive of poor cardiovascular outcomes in those with and without diabetes. This review details the current understanding of the TWEAK/Fn14/CD163 axis as one of the chief regulators of immune signalling and its cell-specific role in metabolic disease development and progression

Middle Pleistocene fauna and palaeoenvironment in the south of Eastern Europe: A case study of the Medzhybizh 1 locality (MIS 11, Ukraine)

The Middle Pleistocene was a period of dynamic changes in Europe. During MIS 11, a number of modern mammal taxa appeared and environmental conditions remained warm and favourable for a relatively long time. The Medzhybizh 1 locality of Ukraine dated to this very period comprises alluvial deposits with rich animal remains, which allow not only to reconstruct the fauna composition, but also to highlight the environmental conditions that dominated at this locality. A revision of the fauna of Medzhybizh 1 locality based on remains of all vertebrate groups revealed a taxonomically diverse fish community (16 species of 11 genera) dominated by cyprinids common for lacustrine or riverine assemblages. Amphibians are represented by 11 species, while the number of reptile and bird remains are less significant. Mammals are the most represented group at the locality, including small mammals (30 species), carnivorans (2 species), and ungulates (5 taxa), the latter dominated by C. elaphus. The taxonomic composition of terrestrial groups indicates temperate climate with boreal-type forests and meadows similar to cold steppe, as well as low wet areas and riparian habitats inhabited by amphibians, reptiles, insectivores, beavers, and various voles. The fish assemblage indicates a partially overgrown but well-aerated water body (lake or slow-flowing river) with sandy-silty bottom. Lithic artefacts found at the Medzhybizh 1 locality contribute to a better understanding of relationships between ancient hominins and faunas during the Middle Pleistocene of Eastern Europe.Archaeological field works at Medzhybizh were supported by the NASU state research projects 0105U001383 (2005–2009), 0109U008921 (2010–2014) and partly funded by the State Fund of Fundamental Research of Ukraine grant 0118U001457 (F77/50–2018). This research was also supported by the grant 0201/2048/18 ‘Life and death of extinct rhino (Stephanorhinus sp.) from Western Poland: a multi-proxy palaeoenvironmental approach’ financed from the funds of the National Science Centre, Poland. JvdM received support from the Spanish Ministerio de Ciencia, Inovación y Universidades (current grant numbers PGC2018-093925-B-C31 and PGC2018-095489-B-I00).Peer reviewe

Isoenzyme pattern of glutamate dehydrogenase as a reflection of nitrogen metabolism in Lupinus albus

Glutamate dehydrogenase (L-glutamate: NAD dehydrogenase, EC 1.4. 1.2; GDH) activity and electrophoretic separation pattern of the enzyme were studied. The enzyme was extracted from embryos of Lupinus albus decotyledonized and cultured for 24, 48 and 72 hours in media containing various combinations of saccharose, ammonium chloride, nitrate as well as amino acids: glutamate, aspartate, glutamine and asparagine. The absence of sugar in the medium resulted in an increase of specific activity of GDH, measured by the rate of NADH + H+ oxidation, and induced formation of new isoenzymes of NAD+ - dependent GDH. Most significant increase in GDH specific activity and most evident appearance of new isoenzymes in the embryos were noted when sugar was substituted in the medium by any of the mentioned amino acids. Induction of new isoenzymes could also be seen when ammonium salts were pre-sent in the medium. GHD isoenzymatic patterns were obtained in various trophic conditions. It is suggested that the GDH isoenzyme patterns may serve as a nitrogen metabolism index of a tissue from which the enzyme has been extracted