Impact of climate change on alpine vegetation of mountain summits in Norway

Climate change is affecting the composition and functioning of ecosystems across the globe. Mountain ecosystems are particularly sensitive to climate warming since their biota is generally limited by low temperatures. Cryptogams such as lichens and bryophytes are important for the biodiversity and functioning of these ecosystems, but have not often been incorporated in vegetation resurvey studies. Hence, we lack a good understanding of how vascular plants, lichens and bryophytes respond interactively to climate warming in alpine communities. Here we quantified long-term changes in species richness, cover, composition and thermophilization (i.e. the increasing dominance of warm-adapted species) of vascular plants, lichens and bryophytes on four summits at Dovrefjell, Norway. These summits are situated along an elevational gradient from the low alpine to high alpine zone and were surveyed for all species in 2001, 2008 and 2015. During the 15-year period, a decline in lichen richness and increase in bryophyte richness was detected, whereas no change in vascular plant richness was found. Dwarf-shrub abundance progressively increased at the expense of lichens, and thermophilization was most pronounced for vascular plants, but occurred only on the lowest summits and northern aspects. Lichens showed less thermophilization and, for the bryophytes, no significant thermophilization was found. Although recent climate change may have primarily caused the observed changes in vegetation, combined effects with non-climatic factors (e.g. grazing and trampling) are likely important as well. At a larger scale, alpine vegetation shifts could have a profound impact on biosphere functioning with feedbacks to the global climate.     

Red wine decreases asymmetric dimethylarginine via SIRT1 induction in human endothelial cells

To investigate the effect of three red wines (RWs) from different growing areas and made from different grapes on asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, in young and senescent human endothelial cells (ECs). All RWs decreased ADMA levels, but 2-fold concentration of German RW was necessary to reach the same effect on ADMA compared to Italian RW and French RW without affecting the cell viability and morphology. The ADMA-lowering effect of RW was increased in senescent compared to young cells, accompanied by enhanced activity of the metabolizing enzyme: dimethylarginine dimethylaminohydrolase (DDAH) II, whereas the same amount in the upregulated protein expression of DDAH II and the downregulated protein expression of the synthesizing enzyme: protein arginine methyltransferase 1 was revealed. These effects were associated with decreased 8-iso-prostaglandin F_2α and peroxynitrite formation, enhanced protein expression of NAD⁺-dependent class III histone deacetylase sirtuin (SIRT) 1, and downregulated protein expression of histone senescence factor p53. Blockade of SIRT1 activity abolished the effect of red wine on ADMA. These data are the first demonstration that RW by activating SIRT1 impairs synthesis and increases metabolism of ADMA. This effect of RW is accentuated in senescent cells probably due to enhanced DDAH activity.     

Structure of the Mature Streptococcal Cysteine Protease Exotoxin mSpeB in Its Active Dimeric Form

Invasive infections of Streptococcus pyogenes are dependent on the cysteine protease streptococcal pyrogenic exotoxin B. Previous structures of the enzyme have not disclosed the proper active-site configuration. Here, the crystal structure of the mature enzyme is presented to 1.55 Å, disclosing a homodimer. A serine from one subunit inserts into the active site of the other to donate to the oxyanion hole and coordinates the ligand proximal to the active-site cysteine. Dimerization is unique to the mature form and is clearly a prerequisite for catalysis. The present structure supports a tripartite switch system that is triggered upon dimerization and substrate binding: (1) liberation of the active-site histidine from an inactive configuration, (2) relocation of residues blocking the substrate binding pockets and (3) repositioning of two active-site tryptophans to settle in the active configuration. Based on the present structure, the active site of clan CA cysteine proteases is expanded and a detailed mechanism of the deacylation mechanism is proposed. The results may have applications for the development of protease inhibitors specific to bacterial cysteine proteases.     

Alterations of cholesterol precursor levels in Alzheimer's disease

Cerebral and extracerebral cholesterol metabolism are altered in Alzheimer's disease (AD) as indicated by reduced plasma levels of the cholesterol elimination products 24S-hydroxycholesterol, which is of cerebral origin, and of 27-hydroxycholesterol, which is formed extracerebrally. However, it has to be evaluated, if changes of cholesterol metabolism in the whole body or in the CNS are exclusively due to the altered elimination of cholesterol or are also due to altered de novo synthesis in AD. We investigated CSF and plasma levels of cholesterol and of its precursors lanosterol, lathosterol and desmosterol in AD patients and non-demented controls. We found CSF levels of cholesterol (p = 0.011), absolute levels of all investigated cholesterol precursors (each p < 0.001) and ratios of cholesterol precursors/cholesterol (each < 0.01) to be lower in AD patients as compared to controls. In plasma, the absolute levels of lanosterol (p = 0.026) and lathosterol (p < 0.001) and the ratio of lathosterol/cholesterol (p = 0.002) but none of the other investigated parameters were reduced in AD patients (p > 0.1). Furthermore, ratios of desmosterol/lathosterol in CSF (p = 0.023) and plasma (p = 0.009) were higher in AD patients as compared to controls. Our data support the hypothesis that cholesterol metabolism is altered in AD and further suggest that especially cholesterol de novo synthesis within the CNS of AD patients might be reduced. These findings raise doubt on a beneficial effect of cholesterol lowering treatment in manifest AD.