FTO and MC4R gene variants are associated with obesity in polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is the leading cause of anovulatory infertility in women. It is also associated with metabolic disturbances that place women at increased risk for obesity and type 2 diabetes. There is strong evidence for familial clustering of PCOS and a genetic predisposition. However, the gene(s) responsible for the PCOS phenotypes have not been elucidated. This two-phase family-based and case-control genetic study was designed to address the question of whether SNPs identified as susceptibility loci for obesity in genome-wide association studies (GWAS) are also associated with PCOS and elevated BMI. Members of 439 families having at least one offspring with PCOS were genotyped for 15 SNPs previously shown to be associated with obesity. Linkage and association with PCOS was assessed using the transmission/disequilibrium test (TDT). These SNPs were also analyzed in an independent case-control study involving 395 women with PCOS and 176 healthy women with regular menstrual cycles. Only one of these 15 SNPs (rs2815752 in NEGR1) was found to have a nominally significant association with PCOS (χ² = 6.11, P = 0.013), but this association failed to replicate in the case-control study. While not associated with PCOS itself, five SNPs in FTO and two in MC4R were associated with BMI as assessed with a quantitative-TDT analysis, several of which replicated association with BMI in the case-control cohort. These findings demonstrate that certain SNPs associated with obesity contribute to elevated BMI in PCOS, but do not appear to play a major role in PCOS per se. These findings support the notion that PCOS phenotypes are a consequence of an oligogenic/polygenic mechanism.     

Characterisation of acyltransferases from Synechocystis sp. PCC6803

As phylogenetic ancestors of plant chloroplasts cyanobacteria resemble plastids with respect to lipid and fatty acid composition. These membrane lipids show the typical prokaryotic fatty acid pattern in which the sn-2 position is exclusively esterified by C(16) acyl groups. In the course of de novo glycerolipid biosynthesis this prokaryotic fatty acid pattern is established by the sequential acylation of glycerol-3-phosphate with acyl-ACPs by the activity of different acyltransferases. In silico approaches allowed the identification of putative Synechocystis acyltransferases involved in glycerolipid metabolism. Functional expression studies in Escherichia coli showed that sll1848 codes for a lysophosphatidic acid acyltransferase with a high specificity for 16:0-ACP, whereas slr2060 encodes a lysophospholipid acyltransferase, with a broad acyl-ACP specificity but a strong preference for lysophosphatidyglycerol especially its sn-2 acyl isomer as acyl-acceptor. The generation and analysis of the corresponding Synechocystis knockout mutants revealed that lysophosphatidic acid acyltransferase unlike the lysophospholipid acyltransferase is essential for the vital functions of the cells.     

Signaling pathways involved in PDGF-evoked cellular responses in human RPE cells

We examined whether PDGF may directly stimulate the expression of VEGF by retinal pigment epithelial (RPE) cells in vitro, and the involvement of three signal transduction pathways in the regulation of PDGF-evoked cell proliferation, migration, and production of VEGF-A was investigated. PDGF stimulated the gene and protein expression of VEGF-A by RPE cells, and increased cell proliferation and chemotaxis. PDGF activated all signaling pathways investigated, as determined by increased phosphorylation levels of ERK1/2, p38, and Akt proteins. The three signaling pathways were involved in the mediation of PDGF-evoked cell proliferation, while p38 and PI3K mediated cell migration, and PI3K mediated secretion of VEGF-A. In addition to VEGF-A, the cells expressed mRNAs for various members of the VEGF family and for their receptors, including VEGF-B, -C, -D, flt-1, and KDR. The data indicate that PDGF selectively stimulates the expression of VEGF-A in RPE cells. PDGF evokes at least three signal transduction pathways which are differentially involved in various cellular responses.     

Entwicklungsgeschichtliche Untersuchung der Blattnervatur von Helleborus foetidus

Unter den zahlreichen Wissenschaftlern, die sich mit verschiedenen Nervatursystemen in Blättern auseinandergesetzt haben, weisen Prantl (1883), Goebel (1922) und auch Troll (1939) auf eine Beziehung zwischen dem Nervaturverlauf und der zur Zeit ihrer Anlegung im Blatt vorherrschenden Wachstumsrichtung bzw. Wachstumsverteilung hin. Für diese entwicklungsgeschichtliche Studie diente das Blatt von Helleborus foetidus, dessen Morphogenese durch die Arbeiten von Schrödinger (1914), Troll (1935), Hagemann (1970) und Kürbs (1973) bekannt ist. Das Fiederblatt gehört dem basipetalpedaten Typ an. Das adulte Nervatursystem setzt sich aus einem Grundgerüst zusammen, das im Zusammenhang mit Wachstumsschwerpunkten in der Blattanlage — von Hagemann als Attraktionszentren bezeichnet — angelegt wird und durch Wachstumsrichtungen im Blatt verformt wird. Es wird ständig durch zusätzliche Verbindungen ergänzt, die das Muster verdichten, wo es durch Flächenwachstum gedehnt wird. Die dabei wirksamen Mechanismen werden diskutiert.     

Über die Lokomotion der Kreuzspinne Aranea diadema beim Netzbau (nach Filmanalysen)

Journal of Comparative Physiology A - Die Arbeit gibt eine Analyse verschiedener Lokomotionsweisen der Aranea diadema mit Hilfe von Filmbildern. 1., 2. und 4. Beinpaar sind neben der...     

Applications of thermal infrared imaging for research in aeroecology

The night sky remains a largely unexplored frontier for biologistsstudying the behavior and physiology of free-ranging, nocturnalorganisms. Conventional imaging tools and techniques such asnight-vision scopes, infrared-reflectance cameras, flash cameras,and radar provide insufficient detail for the scale and resolutiondemanded by field researchers. A new tool is needed that iscapable of imaging noninvasively in the dark at high-temporaland spatial resolution. Thermal infrared imaging representsthe most promising such technology that is poised to revolutionizeour ability to observe and document the behavior of free-rangingorganisms in the dark. Herein we present several examples fromour research on free-ranging bats that highlight the power andpotential of thermal infrared imaging for the study of animalbehavior, energetics and censusing of large colonies, amongothers. Using never-before-seen video footage and data, we havebegun to answer questions that have puzzled biologists for decades,as well as to generate new hypotheses and insight. As we beginto appreciate the functional significance of the aerosphereas a dynamic environment that affects organisms at differentspatial and temporal scales, thermal infrared imaging can beat the forefront of the effort to explore this next frontier.     

PCSK9 inhibition fails to alter hepatic LDLR,circulating cholesterol,and atherosclerosis in the absence of ApoE

LDL cholesterol (LDL-C) contributes to coronary heart disease. Proprotein convertase subtilisin/kexin type 9 (PCSK9) increases LDL-C by inhibiting LDL-C clearance. The therapeutic potential for PCSK9 inhibitors is highlighted by the fact that PCSK9 loss-of-function carriers exhibit 15–30% lower circulating LDL-C and a disproportionately lower risk (47–88%) of experiencing a cardiovascular event. Here, we utilized pcsk9^−/− mice and an anti-PCSK9 antibody to study the role of the LDL receptor (LDLR) and ApoE in PCSK9-mediated regulation of plasma cholesterol and atherosclerotic lesion development. We found that circulating cholesterol and atherosclerotic lesions were minimally modified in pcsk9^−/− mice on either an LDLR- or ApoE-deficient background. Acute administration of an anti-PCSK9 antibody did not reduce circulating cholesterol in an ApoE-deficient background, but did reduce circulating cholesterol (−45%) and TGs (−36%) in APOE*3Leiden.cholesteryl ester transfer protein (CETP) mice, which contain mouse ApoE, human mutant APOE3*Leiden, and a functional LDLR. Chronic anti-PCSK9 antibody treatment in APOE*3Leiden.CETP mice resulted in a significant reduction in atherosclerotic lesion area (−91%) and reduced lesion complexity. Taken together, these results indicate that both LDLR and ApoE are required for PCSK9 inhibitor-mediated reductions in atherosclerosis, as both are needed to increase hepatic LDLR expression.     

Role of plastidial acyl-acyl carrier protein: Glycerol 3-phosphate acyltransferase and acyl-acyl carrier protein hydrolase in channelling the acyl flux through the prokaryotic and eukaryotic pathway

Monoclonal antibodies raised against extracts of the rachis abscission zone of Sambucus nigra L. were selected for high reactivity towards abscission-zone proteins. One antibody (YZ1/2.23) has been shown to cross-react, by both indirect and competition enzyme-linked immunosorbent assay and by Western blotting, with a number of plant enzymes including horseradish peroxidase, rice -glucosidase, almond -glucosidase and the lectins from Phaseolus vulgaris and Erythrina cristagalli.The major N-linked oligosaccharide isolated from horseradish peroxidase has the sequence Man 3(Man6)(Xyl2)Man4GlcNAc4(Fuc3) GlcNAc. This oligosaccharide was found to be a potent inhibitor of the binding of YZ1/2.23 to the intact glycoprotein. The common determinant is therefore contained within this structure.Abbreviations ELISA enzyme-linked immunosorbent assay - Fuc fucose - GlcNAc N-acetylglucosamine - HRP horseradish peroxidase - Ig immunoglobulin - Man mannose - SDS-PAGE Sodium dodecyl sulphate-polyacrylamide gel electrophoresis - Xyl xylose     

Newly found selenium-containing proteins in the tissues of the rat

The Se-containing proteins in 27 tissues of the rat were investigated by in vivo labeling with⁷⁵Se-selenite, separation of the tissue homogenate proteins by SDS-polyacrylamide gel electrophoresis, and determination of the labeled proteins by autoradiography. By using Se-depleted rats and a⁷⁵Se-tracer with a high specific activity, Se compounds present at only very low concentrations could be detected. Besides the 13 Se-containing proteins previously described, for which apparent molecular masses of 12, 15, 18, 20, 22, 25, 28, 34, 56, 60, 65, 70, and 75 kD have been found here, a further 15⁷⁵Se-labeled bands, with apparent molecular masses of 8, 10, 15.5, 16.5, 24, 32, 34.5, 38, 40, 41, 44, 45, 46.5, 53 and 116 kD could be distinguished. Two-dimensional separation of the kidney homogenate proteins showed that some of the Se-containing bands could be resolved into several labeled spots. Most of the newly found compounds were present in various tissues, but with some the enrichment in certain tissues suggested specific sites of action.     

Structural features and selective expression of three Ly-5+ cell-surface molecules

Conventional Ly-5 alloantisera precipitate cell-surface molecules of three sizes: 200K, 205K, and 220K. In SDS-PAGE, the rat monoclonal antibody 74/8 precipitates the same three molecules from both Ly-5.1 and Ly-5.2 cells. Cleveland mapping of the three molecules, precipitated by reaction of conventional Ly-5 alloantisera or 74/8 monoclonal antibody with lysates of ¹²⁵I-labeled cells, disclosed no differences among the three molecular forms, but markedly distinguished all three Ly-5.1 molecules from all three Ly-5.2 molecules. Each of the three molecular forms can be expressed independently of the other two by cloned culture lines of Ly-5⁺ cells of different hematopoietic lineage. All of the seven cloned lines tested expressed only one form. However, two of the seven uncloned culture lines tested, plasmacytoma MOPC-70A and the X.1 putative macrophage line which originated from an SJL tumor, yielded both 200K and 205K forms.American Cancer Society Research Professor of Cell Surface Immunogenetics