Late Quaternary climate legacies in contemporary plant functional composition

The functional composition of plant communities is commonly thought to be determined by contemporary climate. However, if rates of climate‐driven immigration and/or exclusion of species are slow, then contemporary functional composition may be explained by paleoclimate as well as by contemporary climate. We tested this idea by coupling contemporary maps of plant functional trait composition across North and South America to paleoclimate means and temporal variation in temperature and precipitation from the Last Interglacial (120 ka) to the present. Paleoclimate predictors strongly improved prediction of contemporary functional composition compared to contemporary climate predictors, with a stronger influence of temperature in North America (especially during periods of ice melting) and of precipitation in South America (across all times). Thus, climate from tens of thousands of years ago influences contemporary functional composition via slow assemblage dynamics.     

Metformin overcomes high glucose-induced insulin resistance of podocytes by pleiotropic effects on SIRT1 and AMPK

Podocyte insulin sensitivity is critical for glomerular function, and the loss of appropriate insulin signaling leads to alterations and disorders featuring diabetic nephropathy. Energy-sensing pathways, such as AMP-dependent protein kinase (AMPK) and protein deacetylase SIRT1, have been shown to play an important role in insulin resistance. The absence of a stimulating effect of insulin on glucose uptake into podocytes after exposure to hyperglycemic conditions has been demonstrated to be related to a decreased level and activity of SIRT1 protein, leading to reduced AMPK phosphorylation.The present work was undertaken to investigate metformin's ability to restore the insulin responsiveness of podocytes by regulating SIRT1 and AMPK activities.Primary rat podocytes cultured with standard or high glucose concentrations for 5 days were transfected with siRNAs targeting SIRT1, AMPKα1, or AMPKα2. SIRT1 activity was measured by a fluorometric method. Insulin-stimulated changes in glucose uptake were used to detect insulin resistance. Podocyte permeability was measured by a transmembrane albumin flux assay to examine podocytes functioning.Our results demonstrated that metformin activated SIRT1 and AMPK, prevented hyperglycemia-induced reduction of SIRT1 protein levels, ameliorated glucose uptake into podocytes, and decreased glomerular filtration barrier permeability. Furthermore, metformin activated AMPK in a SIRT1-independent manner, as the increase in AMPK phosphorylation after metformin treatment was not affected by SIRT1 downregulation. Therefore, the potentiating effect of metformin on insulin-resistant podocytes seemed to be dependent on AMPK, as well as SIRT1 activity, establishing multilateral effects of metformin action.     

Superoxide anion radical scavenging property of catecholamines

The direct effect of the four catecholamines (adrenaline, noradrenaline, dopamine and isoproterenol) on superoxide anion radicals () was investigated. The reaction between 18‐crown‐6‐ether and potassium superoxide in dimethylsulfoxide was used as a source of . The reactivity of catecholamines with was examined using chemiluminescence, reduction of nitroblue tetrazolium and electron paramagnetic resonance spin‐trapping techniques. 5,5‐Dimethyl‐1‐pyrroline‐N‐oxide was included as the spin trap. The results showed that the four catecholamines were effective and efficient in inhibiting chemiluminescence accompanying the potassium superoxide/18‐crown‐6‐ether system in a dose‐dependent manner over the range 0.05–2 mm in the following order: adrenaline > noradrenaline > dopamine > isoproterenol, with, IC₅₀ = 0.15 ± 0.02 mm 0.21 ± 0.03 mm , 0.27 ± 0.03 mm and 0.50 ± 0.04 mm , respectively. The catecholamines examined also exhibited a strong scavenging effect towards when evaluated this property by the inhibition of nitroblue tetrazolium reduction (56–73% at 1 m concentration). A very similar capacity of scavenging was monitored in the 5,5‐dimethyl‐1‐pyrroline‐N‐oxide spin‐trapping assay. The results suggest that catecholamines tested may involve a direct effect on scavenging radicals. Copyright © 2013 John Wiley & Sons, Ltd.     

Conformation and Antiherpes Activity of 3′- and 5′-Azido and Amino Analogs of 5-Methoxymethyl-2′-Deoxyuridine

Abstract

The molecular conformations of 3′- and 5′-azido and amino derivatives of 5-methoxymethyl-2′-deoxyuridine, 1, were investigated by nmr. The glycosidic conformation of 5-methoxymethyl-5′-amino-2′,5′-dideoxy-uridine, 5 had a considerable population of the syn form. The 5′-derivatives show a preference for the S conformation of the furanose ring as in 1. In contrast, the 3′-derivatives show preference for the N conformation. For 5-methoxymethyl-3′-amino-2′,3′-dideoxyuridine, 3, the shift towards the N state is pH dependent. The preferred conformation for the exocyclic (C4′,C5′) side chain is g⁺ for all compounds except 5 which has a strong preference for the t rotamer (79%). Compounds 1, 3 and 5 inhibited growth of HSV-1 by 50% at 2, 18 and 70 μg/ml respectively, whereas 2 and 4 were not active up to 256 μg/ml (highest concentration tested). The compounds were not cytotoxic up to 3,000 μM.     

Effects of hyperhomocysteinemia and betaine–homocysteine S-methyltransferase inhibition on hepatocyte metabolites and the proteome

Both cardiovascular disease and liver injury are major public health issues. Hyperhomocysteinemia has been linked to cardiovascular diseases, and defects in methyl group metabolism, often resulting in hyperhomocysteinemia, are among the key molecular events postulated to play a role in liver injury. We employed proteomics and metabolomics analyses of human hepatocytes in primary cell culture to explore the spectrum of proteins and associated metabolites affected by the disruption of methyl group metabolism. We treated the hepatocytes with homocysteine (Hcy, 0.1 mM and 2 mM) to follow the impact of hyperhomocysteinemia, and in parallel, we used a specific inhibitor of betaine–homocysteine S-methyltransferase (BHMT) to extend our understanding of the physiological functions of the enzyme. The major effect of BHMT inhibition was a 50% decrease in S-adenosylmethionine levels. The treatments with Hcy resulted in multiple changes in the metabolite levels depending on the treatment modality. The BHMT inhibition and 0.1 mM Hcy treatment induced only moderate changes in the hepatocyte proteome and secretome, while the changes induced by the 2 mM Hcy treatment were extensive. Phosphatidylethanolamine carboxykinase and ornithine aminotransferase were up-regulated about two fold indicating an intervention into metabolism. Cellular proliferation was suspended, secretome composition was changed and signs of apoptosis were discernible. We have detected fibrinogen gamma dimers, which might have a role as a potentially new biomarker of early liver injury. Finally, we have demonstrated the failed maturation of apolipoprotein A1, which might be a new mechanism of disruption of cholesterol efflux from tissues.     

Lysozyme Folded In Silico According to the Limited Conformational Sub-space

Abstract

The conformational sub-space oriented on early-stage protein folding is applied to lysozyme folding. The part of the Ramachandran map distinguished on the basis of a geometrical model of the polypeptide chain limited to the mutual orientation of the peptide bond planes is shown to deliver the initial structure of the polypeptide for the energy minimization procedure in the ab initio model of protein folding prediction. Two forms of energy minimization and molecular dynamics simulation procedures were applied to the assumed early-stage protein folding of lysozyme. One of them included the disulphide bond system and the other excluded it. The post-energy-minimization and post-dynamics structures were compared using RMS-D and non-bonding contact maps to estimate the degree of approach to the native, target structure of the protein molecule obtained using the limited conformational sub-space for the early stage of folding.     

Ultradian and Asymmetric Rhythms of Hemispheric Processing Speed

Daily changes in cognitive performance have been documented, both in time of day/effect paradigm studies and in time‐isolation studies. However, in both types of studies, phenomena such as the “post‐lunch dip” have been found that were difficult to explain in terms of theoretical backgrounds. These phenomena may suggest ultradian rhythms in cognitive performance. A number of studies have also shown ultradian and asymmetric rhythms in activity indices of the brain hemispheres. The aim of this study was to test three hypotheses: the first two assumed that there is a significant ultradian frequency in a component of the endogenous rhythm of processing speed, and the third assumed that the ultradian endogenous rhythms of the processing speed (encoding and recognition) of stimuli addressed to the left brain hemisphere differ in period length from those addressed to right hemisphere. During a 24 h constant‐routine experiment, the memory performance of 30 participants was measured eight times (every 2.5–3 h), starting at 06:30 h. Parallel sets of words and pictures were shown to subjects in a random order in either the left or the right visual field on a computer screen. The participants pressed one of two buttons in response to the picture or word, or when answering a question concerning the meaning of a presented stimulus. Cosinor analysis was applied to individual time series data. Two significant ultradian components were found in a majority of the time series. Dominant periods were analyzed using three factor ANOVA. The results showed an asymmetry between both hemispheres in the frequency of ultradian rhythms in encoding speed.     

Daytime Intermittent Bright Light Effects on Processing of Laterally Exposed Stimuli,Mood, and Light Perception

Little is known about intermittent bright light (IBL) exposure during the daytime on oscillations in human performance and mood. The aims of this study were to determine whether the applied regime of IBL can differentially influence the daily oscillations of processing of laterally exposed stimuli, as well as the daily course of alertness and affective state, and the participants' perception of light conditions. A counter‐balanced, within‐subject study design was applied. Performance and mood of 20 student volunteers were measured every 30 min starting at 08:00 h and ending at 20:30 h in IBL and ordinary room light (ORL) conditions. Near to statistical significance, effects of the IBL regime on performance (i.e., main effect on speed of verbal logical task, and interactive effect of light conditions and measurement time on daily oscillations in speed of processing of spatial tasks) and mood (i.e., interactive effect of bright light and measurement time on global vigor assessment) were found. An assessment of IBL conditions as significantly less comfortable and natural and more glaring when compared to ORL conditions draws attention to the importance of participants' perception of the light, which may affect the application of bright light in real life situations.