Data on plasma levels of apolipoprotein E, correlations with lipids and lipoproteins stratified by <i>APOE</i> genotype, and risk of ischemic heart disease

Data on correlations of plasma apoE with levels of lipids and lipoproteins stratified by APOE genotypes as well as data exploring the association between plasma levels of apoE and risk of ischemic heart disease (IHD) are wanted.The present data on 91,695 individuals from the general population provides correlations between plasma levels of apoE and lipids and lipoproteins for the three APOE genotypes ε33, ε44 and ε22, representing each of the three apoE isoforms. Further, data on extreme groups of plasma apoE (highest 5%) versus lower levels of apoE at enrollment explores risk of IHD and myocardial infarction (MI) and is given as hazard ratios. In addition, IHD and MI as a function of apoE/high-density lipoprotein (HDL) cholesterol ratio, as well as data on lipids, lipoproteins and apolipoproteins are given as hazard ratios. Data is stratified by gender and presented for the Copenhagen General Population Study and the Copenhagen City Heart Study combined

The contributions of flower strips to wild bee conservation in agricultural landscapes can be predicted using pollinator habitat suitability models

1. Sowing flower strips along field edges is a widely adopted method for conserving pollinating insects in agricultural landscapes. To maximize the effect of flower strips given limited resources, we need spatially explicit tools that can prioritize their placement, and for identifying plant species to include in seed mixtures. 2. We sampled bees and plant species as well as their interactions in a semicontrolled field experiment with roadside/field edge pairs with/without a sown flower strip at 31 sites in Norway and used a regional spatial model of solitary bee species richness to test if the effect of flower strips on bee species richness was predictable from the modelled solitary bee species richness. 3. We found that sites with flower strips were more bee species rich compared to sites without flower strips and that this effect was greatest in areas that the regional solitary bee species richness model had identified to be particularly important for bees. Spatial models revealed that even within small landscapes there were pronounced differences between field edges in the predicted effect of sowing flower strips. 4. Of the plant species that attracted the most bee species, the majority mainly attracted bumblebees and only few species also attracted solitary bees. Considering both the taxonomic diversity of bees and the species richness of bees attracted by plants we suggest that seed mixes containing Hieracium spp. such as Hieracium umbellatum, Pilosella officinarum, Taraxacum spp., Trifolium repens, Lotus corniculatus, Stellaria graminea and Achillea millefolium would provide resources for diverse bee communities in our region 5. Spatial prediction models of bee diversity can be used to identify locations where flower strips are likely to have the largest effect and can thereby provide managers with an important tool for prioritizing how funding for agri-environmental schemes such as flower strips should be allocated. Such flower strips should contain plant species that are attractive to both solitary and bumblebees, and do not need to be particularly plant species rich as long as the selected plants complement each other. agri-environmental schemes, bees, flower strips, networks, pollinators, restoration, spatialpublishedVersio

Neutral processes related to regional bee commonness and dispersal distances are important predictors of plant–pollinator networks along gradients of climate and landscape conditions

Understanding how niche-based and neutral processes contribute to the spatial varia-tion in plant–pollinator interactions is central to designing effective pollination con-servation schemes. Such schemes are needed to reverse declines of wild bees and other pollinating insects, and to promote pollination services to wild and cultivated plants. We used data on wild bee interactions with plants belonging to the four tribes Loteae, Trifolieae, Anthemideae and either spring- or summer-flowering Cichorieae, sampled systematically along a 682 km latitudinal gradient to build models that allowed us to 1) predict occurrences of pairwise bee–flower interactions across 115 sampling locations, and 2) estimate the contribution of variables hypothesized to be related to niche-based assembly structuring processes (viz. annual mean temperature, landscape diversity, bee sociality, bee phenology and flower preferences of bees) and neutral processes (viz. regional commonness and dispersal distance to conspecifics). While neutral processes were important predictors of plant–pollinator distributions, niche-based processes were reflected in the contrasting distributions of solitary bee and bumble bees along the temperature gradient, and in the influence of bee flower preferences on the distri-bution of bee species across plant types. In particular, bee flower preferences separated bees into three main groups, albeit with some overlap: visitors to spring-flowering Cichorieae; visitors to Anthemideae and summer-flowering Cichorieae; and visitors to Trifolieae and Loteae. Our findings suggest that both neutral and niche-based pro-cesses are significant contributors to the spatial distribution of plant–pollinator inter-actions so that conservation actions in our region should be directed towards areas: Page 2 of 11near high concentrations of known occurrences of regionally rare bees; in mild climatic conditions; and that are surrounded by heterogenous landscapes. Given the observed niche-based differences, the proportion of functionally distinct plants in flower-mixes could be chosen to target bee species, or guilds, of conservation concern. Keywords: ecological networks, machine learning, plant–pollinator interactions, spatial, wild beesNeutral processes related to regional bee commonness and dispersal distances are important predictors of plant–pollinator networks along gradients of climate and landscape conditionspublishedVersionpublishedVersio

Fifteen new risk loci for coronary artery disease highlight arterial-wall-specific mechanisms

Coronary artery disease (CAD) is a leading cause of morbidity and mortality worldwide. Although 58 genomic regions have been associated with CAD thus far, most of the heritability is unexplained, indicating that additional susceptibility loci await identification. An efficient discovery strategy may be larger-scale evaluation of promising associations suggested by genome-wide association studies (GWAS). Hence, we genotyped 56,309 participants using a targeted gene array derived from earlier GWAS results and performed meta-analysis of results with 194,427 participants previously genotyped, totaling 88,192 CAD cases and 162,544 controls. We identified 25 new SNP-CAD associations (P &lt; 5 × 10(-8), in fixed-effects meta-analysis) from 15 genomic regions, including SNPs in or near genes involved in cellular adhesion, leukocyte migration and atherosclerosis (PECAM1, rs1867624), coagulation and inflammation (PROCR, rs867186 (p.Ser219Gly)) and vascular smooth muscle cell differentiation (LMOD1, rs2820315). Correlation of these regions with cell-type-specific gene expression and plasma protein levels sheds light on potential disease mechanisms

In situ aromatase expression in primary tumor is associated with estrogen receptor expression but is not predictive of response to endocrine therapy in advanced breast cancer

<p>Abstract</p> <p>Background</p> <p>New, third-generation aromatase inhibitors (AIs) have proven comparable or superior to the anti-estrogen tamoxifen for treatment of estrogen receptor (ER) and/or progesterone receptor (PR) positive breast cancer. AIs suppress total body and intratumoral estrogen levels. It is unclear whether <it>in situ </it>carcinoma cell aromatization is the primary source of estrogen production for tumor growth and whether the aromatase expression is predictive of response to endocrine therapy. Due to methodological difficulties in the determination of the aromatase protein, COX-2, an enzyme involved in the synthesis of aromatase, has been suggested as a surrogate marker for aromatase expression.</p> <p>Methods</p> <p>Primary tumor material was retrospectively collected from 88 patients who participated in a randomized clinical trial comparing the AI letrozole to the anti-estrogen tamoxifen for first-line treatment of advanced breast cancer. Semi-quantitative immunohistochemical (IHC) analysis was performed for ER, PR, COX-2 and aromatase using Tissue Microarrays (TMAs). Aromatase was also analyzed using whole sections (WS). Kappa analysis was applied to compare association of protein expression levels. Univariate Wilcoxon analysis and the Cox-analysis were performed to evaluate time to progression (TTP) in relation to marker expression.</p> <p>Results</p> <p>Aromatase expression was associated with ER, but not with PR or COX-2 expression in carcinoma cells. Measurements of aromatase in WS were not comparable to results from TMAs. Expression of COX-2 and aromatase did not predict response to endocrine therapy. Aromatase in combination with high PR expression may select letrozole treated patients with a longer TTP.</p> <p>Conclusion</p> <p>TMAs are not suitable for IHC analysis of <it>in situ </it>aromatase expression and we did not find COX-2 expression in carcinoma cells to be a surrogate marker for aromatase. <it>In situ </it>aromatase expression in tumor cells is associated with ER expression and may thus point towards good prognosis. Aromatase expression in cancer cells is not predictive of response to endocrine therapy, indicating that <it>in situ </it>estrogen synthesis may not be the major source of intratumoral estrogen. However, aromatase expression in combination with high PR expression may select letrozole treated patients with longer TTP.</p> <p>Trial registration</p> <p>Sub-study of trial P025 for advanced breast cancer.</p

Dickkopf-1 Overexpression in vitro Nominates Candidate Blood Biomarkers Relating to Alzheimer's Disease Pathology

Previous studies suggest that Dickkopf-1 (DKK1), an inhibitor of Wnt signaling, plays a role in amyloid-induced toxicity and hence Alzheimer's disease (AD). However, the effect of DKK1 expression on protein expression, and whether such proteins are altered in disease, is unknown. We aim to test whether DKK1 induced protein signature obtained in vitro were associated with markers of AD pathology as used in the amyloid/tau/neurodegeneration (ATN) framework as well as with clinical outcomes. We first overexpressed DKK1 in HEK293A cells and quantified 1,128 proteins in cell lysates using aptamer capture arrays (SomaScan) to obtain a protein signature induced by DKK1. We then used the same assay to measure the DKK1-signature proteins in human plasma in two large cohorts, EMIF (n = 785) and ANM (n = 677). We identified a 100-protein signature induced by DKK1 in vitro. Subsets of proteins, along with age and apolipoprotein E ɛ 4 genotype distinguished amyloid pathology (A + T-N-, A+T+N-, A+T-N+, and A+T+N+) from no AD pathology (A-T-N-) with an area under the curve of 0.72, 0.81, 0.88, and 0.85, respectively. Furthermore, we found that some signature proteins (e.g., Complement C3 and albumin) were associated with cognitive score and AD diagnosis in both cohorts. Our results add further evidence for a role of DKK regulation of Wnt signaling in AD and suggest that DKK1 induced signature proteins obtained in vitro could reflect theATNframework as well as predict disease severity and progression in vivo

Genome-wide association study identifies Sjögren’s risk loci with functional implications in immune and glandular cells

Sjögren’s disease is a complex autoimmune disease with twelve established susceptibility loci. This genome-wide association study (GWAS) identifies ten novel genome-wide significant (GWS) regions in Sjögren’s cases of European ancestry: CD247, NAB1, PTTG1-MIR146A, PRDM1-ATG5, TNFAIP3, XKR6, MAPT-CRHR1, RPTOR-CHMP6-BAIAP6, TYK2, SYNGR1. Polygenic risk scores yield predictability (AUROC = 0.71) and relative risk of 12.08. Interrogation of bioinformatics databases refine the associations, define local regulatory networks of GWS SNPs from the 95% credible set, and expand the implicated gene list to >40. Many GWS SNPs are eQTLs for genes within topologically associated domains in immune cells and/or eQTLs in the main target tissue, salivary glands.Research reported in this publication was supported by the National Institutes of Health (NIH): R01AR073855 (C.J.L.), R01AR065953 (C.J.L.), R01AR074310 (A.D.F.), P50AR060804 (K.L.S.), R01AR050782 (K.L.S), R01DE018209 (K.L.S.), R33AR076803 (I.A.), R21AR079089 (I.A.); NIDCR Sjögren’s Syndrome Clinic and Salivary Disorders Unit were supported by NIDCR Division of Intramural Research at the National Institutes of Health funds - Z01-DE000704 (B.W.); Birmingham NIHR Biomedical Research Centre (S.J.B.); Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy – EXC 2155 – Projektnummer 390874280 (T.W.); Research Council of Norway (Oslo, Norway) – Grant 240421 (TR.R.), 316120 (M.W-H.); Western Norway Regional Health Authority (Helse Vest) – 911807, 912043 (R.O.); Swedish Research Council for Medicine and Health (L.R., G.N., M.W-H.); Swedish Rheumatism Association (L.R., G.N., M.W-H.); King Gustav V’s 80-year Foundation (G.N.); Swedish Society of Medicine (L.R., G.N., M.W-H.); Swedish Cancer Society (E.B.); Sjögren’s Syndrome Foundation (K.L.S.); Phileona Foundation (K.L.S.). The Stockholm County Council (M.W-H.); The Swedish Twin Registry is managed through the Swedish Research Council - Grant 2017-000641. The French ASSESS (Atteinte Systémique et Evolution des patients atteints de Syndrome de Sjögren primitive) was sponsored by Assistance Publique-Hôpitaux de Paris (Ministry of Health, PHRC 2006 P060228) and the French society of Rheumatology (X.M.).publishedVersio