Genes involved in systemic and arterial bed dependent atherosclerosis--Tampere Vascular study

Background

Atherosclerosis is a complex disease with hundreds of genes influencing its progression. In addition, the phenotype of the disease varies significantly depending on the arterial bed.

Methodology/Principal Findings

We characterized the genes generally involved in human advanced atherosclerotic (AHA type V–VI) plaques in carotid and femoral arteries as well as aortas from 24 subjects of Tampere Vascular study and compared the results to non-atherosclerotic internal thoracic arteries (n=6) using genome-wide expression array and QRT-PCR. In addition we determined genes that were typical for each arterial plaque studied. To gain a comprehensive insight into the pathologic processes in the plaques we also analyzed pathways and gene sets dysregulated in this disease using gene set enrichment analysis (GSEA). According to the selection criteria used (>3.0 fold change and p-value <0.05), 235 genes were up-regulated and 68 genes down-regulated in the carotid plaques, 242 genes up-regulated and 116 down-regulated in the femoral plaques and 256 genes up-regulated and 49 genes down-regulated in the aortic plaques. Nine genes were found to be specifically induced predominantly in aortic plaques, e.g., lactoferrin, and three genes in femoral plaques, e.g., chondroadherin, whereas no gene was found to be specific for carotid plaques. In pathway analysis, a total of 28 pathways or gene sets were found to be significantly dysregulated in atherosclerotic plaques (false discovery rate [FDR] <0.25).

Conclusions

This study describes comprehensively the gene expression changes that generally prevail in human atherosclerotic plaques. In addition, site specific genes induced only in femoral or aortic plaques were found, reflecting that atherosclerotic process has unique features in different vascular beds.     

Application of the Red List Index as an indicator of habitat change

For the first time ever, the International Union for Conservation of Nature Red List Index for habitat types was calculated for an entire country, Finland. The RLIs were based on species threat assessments from 2000 and 2010 and included habitat definitions for all 10,131 species of 12 organism groups. The RLIs were bootstrapped to track statistically significant changes. The RLI changes of species grouped by habitats were negative for all habitat types except for forests and rural biotopes which showed a stable trend. Trends of beetles and true bugs were positive in rural and forest habitats. Other 16 observed trends of species group and habitat combinations were negative. Several trends observed were in accordance with studies focusing on particular taxa and habitats, and drivers for their change. This study demonstrates the usefulness of the RLI as a tool for observing habitat change based on species threat assessment data.     

Chinese Cretaceous larva exposes a southern Californian living fossil (Insecta,Coleoptera, Eucnemidae)

Palaeoxenus sinensis Chang, Muona & Teräväinen sp. nov. (Coleoptera, Eucnemidae) is described on the basis of a Cretaceous larva found from the Yixian Formation in Huangbanjigou, Liaoning Province, China. The only previously known member of this clade is a southern Californian endemic, Dohrn's elegant eucnemid beetle (Palaeoxenus dohrni), a species that develops in conifers, especially the incense cedar (Calocedrus decurrens). The new find proves that the highly specialized main eucnemid lineages had evolved 123 Mya, before the main radiation of the angiosperms and probably as an adaptation to development in gymnosperms.     

Afforestation does not necessarily reduce nitrous oxide emissions from managed boreal peat soils

Pristine peatlands have generally low nitrous oxide (N₂O) emissions but drainage and management practices enhance the microbial processes and associated N₂O emissions. It is assumed that leaving peat soils from intensive management, such as agriculture, will decrease their N₂O emissions. In this paper we report how the annual N₂O emission rates will change when agricultural peat soil is either left abandoned or afforested and also N₂O emissions from afforested peat extraction sites. In addition, we evaluated a biogeochemical model (DNDC) with a view to explaining GHG emissions from peat soils under different land uses. The abandoned agricultural peat soils had lower mean annual N₂O emissions (5.5?±?5.4?kg?N?ha^?1) than the peat soils in active agricultural use in Finland. Surprisingly, N₂O emissions from afforested organic agricultural soils (12.8?±?9.4?kg?N?ha^?1) were similar to those from organic agricultural soils in active use. These emissions were much higher than those from the forests on nutrient rich peat soils. Abandoned and afforested peat extraction sites emitted more N₂O, (2.4?±?2.1?kg?N?ha^?1), than the areas under active peat extraction (0.7?±?0.5?kg?N?ha^?1). Emissions outside the growing season contributed significantly, 40% on an average, to the annual emissions. The DNDC model overestimated N₂O emission rates during the growing season and indicated no emissions during winter. The differences in the N₂O emission rates were not associated with the age of the land use change, vegetation characteristics, peat depth or peat bulk density. The highest N₂O emissions occurred when the soil C:N ratio was below 20 with a significant variability within the measured C:N range (13–27). Low soil pH, high nitrate availability and water table depth (50–70?cm) were also associated with high N₂O emissions. Mineral soil has been added to most of the soils studied here to improve the fertility and this may have an impact on the N₂O emissions. We infer from the multi-site dataset presented in this paper that afforestation is not necessarily an efficient way to reduce N₂O emissions from drained boreal organic fields.     

Carbon fluxes from a tropical peat swamp forest floor

A tropical ombrotrophic peatland ecosystem is one of the largest terrestrial carbon stores. Flux rates of carbon dioxide (CO₂) and methane (CH₄) were studied at various peat water table depths in a mixed‐type peat swamp forest floor in Central Kalimantan, Indonesia. Temporary gas fluxes on microtopographically differing hummock and hollow peat surfaces were combined with peat water table data to produce annual cumulative flux estimates. Hummocks formed mainly from living and dead tree roots and decaying debris maintained a relatively steady CO₂ emission rate regardless of the water table position in peat. In nearly vegetation‐free hollows, CO₂ emission rates were progressively smaller as the water table rose towards the peat surface. Methane emissions from the peat surface remained small and were detected only in water‐saturated peat. By applying long‐term peat water table data, annual gas emissions from the peat swamp forest floor were estimated to be 3493±316 g CO₂ m^?2 and less than 1.36±0.57 g CH₄ m^?2. On the basis of the carbon emitted, CO₂ is clearly a more important greenhouse gas than CH₄. CO₂ emissions from peat are the highest during the dry season, when the oxic peat layer is at its thickest because of water table lowering.     

Dual signalling by different octopamine receptors converges on adenylate cyclase in Sf9 cells.

The Sf9 insect cell line, derived from Spodoptera frugiperda, was used to study the regulation of adenylate cyclase (AC) activity by octopamine receptors. The cyclic AMP (cAMP) production was stimulated in a concentration-dependent manner by octopamine. Octopamine also elicited a rise in cytosolic Ca(2+). The Ca(2+) elevation was independent of the cAMP elevation whereas the cAMP elevation was partially inhibited by removal of Ca(2+). The antagonistic effects of a series of compounds were tested on both responses. Phentolamine inhibited both responses with similar potency. Two of the tested compounds, MK-912 and RS 79948, were over 1000-fold more potent in blocking the Ca(2+) response. Ionomycin, a Ca(2+) ionophore, or activation of the heterologously expressed muscarinic M(3) receptors in the cells did not alone stimulate cAMP production. However, a Ca(2+) elevation potentiated cAMP production in the presence of a primary stimulant such as forskolin or activated G(s) proteins. This type of regulation of AC is different from previously identified Ca(2+)-sensitive AC isoforms. For comparison the Ca(2+)/calmodulin-activated type I AC was expressed and demonstrated to be stimulated directly by an increase in Ca(2+). Together the results demonstrate that octopamine can synergistically regulate the AC activity via two different receptors in Sf9 cells.     

Ethanol Specifically Inhibits NMDA Receptors with Affinity for Ifenprodil in the Low Micromolar Range in Cultured Cerebellar Granule Cells

Abstract: The effect of ethanol on the intracellular Ca²⁺ concentration response to NMDA in rat cerebellar granule cells grown in low or high KCI concentrations has been studied using image analysis. The cells grown in low KCI displayed high sensitivity for glycine. The subtype-selective antagonist ifenprodil inhibited the response with high (in the low micromolar range) and low (in the high micromolar range) potency. Ethanol affected the high-potency component in these cultures. In cells grown in high KCI the glycine sensitivity was lower, and a low potency for ifenprodil (high micromolar) dominated. These cells were not significantly sensitive to ethanol. The results indicate that the component displaying potency for ifenprodil in the low micromolar range with properties of the NR2B subunit is the target for ethanol action on the NMDA receptor.     

A new insight into solid-state conformation of macrolide antibiotics

Quantitative analysis of the molecular conformations of the 14-membered macrolide antibiotics erythromycin A and B, clarithromycin, and roxithromycin in the solid state was performed. While the erythronolide macrocycle adopts a very similar folded-out conformation in all the macrolides studied, the proximity of the monosaccharide moieties, L-cladinose and D-desosamine, to each other is demonstrated to be the distinctive feature of their molecular conformations, based on atom-atom interaction energy analysis. More surprisingly, the common features in the relative orientation of the monosaccharide moieties (in terms of non-bonded atom-atom interactions) were revealed between the 14- and 15-membered (azithromycin) macrolide antibiotics. Herein we report on the details of the spatial arrangement of the monosaccharide moieties in these structurally related drug molecules and their influence on the biopharmaceutical properties of erythromycin derivatives.     

Structural MRI in Frontotemporal Dementia: Comparisons between Hippocampal Volumetry,Tensor-Based Morphometry and Voxel-Based Morphometry

Background

MRI is an important clinical tool for diagnosing dementia-like diseases such as Frontemporal Dementia (FTD). However there is a need to develop more accurate and standardized MRI analysis methods.

Objective

To compare FTD with Alzheimer’s Disease (AD) and Mild Cognitive Impairment (MCI) with three automatic MRI analysis methods - Hippocampal Volumetry (HV), Tensor-based Morphometry (TBM) and Voxel-based Morphometry (VBM), in specific regions of interest in order to determine the highest classification accuracy.

Methods

Thirty-seven patients with FTD, 46 patients with AD, 26 control subjects, 16 patients with progressive MCI (PMCI) and 48 patients with stable MCI (SMCI) were examined with HV, TBM for shape change, and VBM for gray matter density. We calculated the Correct Classification Rate (CCR), sensitivity (SS) and specificity (SP) between the study groups.

Results

We found unequivocal results differentiating controls from FTD with HV (hippocampus left side) (CCR = 0.83; SS = 0.84; SP = 0.80), with TBM (hippocampus and amygdala (CCR = 0.80/SS = 0.71/SP = 0.94), and with VBM (all the regions studied, especially in lateral ventricle frontal horn, central part and occipital horn) (CCR = 0.87/SS = 0.81/SP = 0.96). VBM achieved the highest accuracy in differentiating AD and FTD (CCR = 0.72/SS = 0.67/SP = 0.76), particularly in lateral ventricle (frontal horn, central part and occipital horn) (CCR = 0.73), whereas TBM in superior frontal gyrus also achieved a high accuracy (CCR = 0.71/SS = 0.68/SP = 0.73). TBM resulted in low accuracy (CCR = 0.62) in the differentiation of AD from FTD using all regions of interest, with similar results for HV (CCR = 0.55).

Conclusion

Hippocampal atrophy is present not only in AD but also in FTD. Of the methods used, VBM achieved the highest accuracy in its ability to differentiate between FTD and AD.     

High-performance liquid chromatographic analysis of phlorotannins from the brown alga Fucus vesiculosus

Separating individual compounds by HPLC represents an effective method for the detection and quantification of phenolic compounds and has been widely utilised. However, phlorotannins are commonly quantified using colorimetric methods, as the total amount of the whole compound group. In the present paper the separation of a set of individual soluble phlorotannins from the phenolic crude extract of Fucus vesiculosus was achieved by HPLC with UV photodiode array detection. Different gradient programs for reversed- and normal-phase HPLC methods were developed and tested. Normal-phase (NP) conditions with a silica stationary phase and a mobile phase with a linear gradient of increasing polarity were found to separate 16 individual components of the phenolic extract. The suitability of the NP-HPLC method for mass spectrometric application was preliminarily tested. Sample preparation was found to be a critical step in the analysis owing to the rapid oxidation of phlorotannins; ascorbic acid was used as an antioxidant.