A genome for gnetophytes and early evolution of seed plants

Genome sequencing, assembly and annotation were conducted by the Novogene Bioinformatics Institute, Beijing, China; mutual contracts were No. NHT140016 and NVT140016004. This work was supported by funding from the Scientific Project of Shenzhen Urban Administration (201519) and a Major Technical Research Project of the Innovation of Science and Technology Commission of Shenzhen (JSGG20140515164852417). Additional funding was provided in particular by the Scientific Research Program of Sino-Africa Joint Research Center (SAJL201607). We thank X.Q. Wang, G.W. Hu, Z.D. Chen and Y.H. Guo for comments on gnetophyte phylogenetic relationships and ecological issues; H. Wu and X.P. Ning for discussion of related organ development; K.K. Wan and S. Sun for additional help on the analysis of repeats. We also thank X.Y. for support of funding coordination. Y.V.d.P. acknowledges the Multidisciplinary Research Partnership ‘Bioinformatics: from nucleotides to networks’ Project (no. 01MR0310W) of Ghent University, and funding from the European Union Seventh Framework Programme (FP7/2007-2013) under European Research Council Advanced Grant Agreement 322739-DOUBLEUP

Association of Carotid Plaque Lp-PLA2 with Macrophages and Chlamydia pneumoniae Infection among Patients at Risk for Stroke

BACKGROUND: We previously showed that the burden of Chlamydia pneumoniae in carotid plaques was significantly associated with plaque interleukin (IL)-6, and serum IL-6 and C-reactive protein (CRP), suggesting that infected plaques contribute to systemic inflammatory markers in patients with stroke risk. Since lipoprotein-associated phospholipase A2 (Lp-PLA(2)) mediates inflammation in atherosclerosis, we hypothesized that serum Lp-PLA(2) mass and activity levels and plaque Lp-PLA(2) may be influenced by plaque C. pneumoniae infection. METHODOLOGY/PRINCIPAL FINDINGS: Forty-two patients underwent elective carotid endarterectomy. Tissue obtained at surgery was stained by immunohistochemistry for Lp-PLA(2) grade, macrophages, IL-6, C. pneumoniae and CD4+ and CD8+ cells. Serum Lp-PLA(2) activity and mass were measured using the colorimetric activity method (CAM) and ELISA, respectively. Serum homocysteine levels were measured by HPLC. Eleven (26.2%) patients were symptomatic with transient ischemic attacks. There was no correlation between patient risk factors (smoking, coronary artery disease, elevated cholesterol, diabetes, obesity, hypertension and family history of genetic disorders) for atherosclerosis and serum levels or plaque grade for Lp-PLA(2). Plaque Lp-PLA(2) correlated with serum homocysteine levels (p = 0.013), plaque macrophages (p<0.01), and plaque C. pneumoniae (p<0.001), which predominantly infected macrophages, co-localizing with Lp-PLA(2). CONCLUSIONS: The significant association of plaque Lp-PLA(2) with plaque macrophages and C. pneumoniae suggests an interactive role in accelerating inflammation in atherosclerosis. A possible mechanism for C. pneumoniae in the atherogenic process may involve infection of macrophages that induce Lp-PLA(2) production leading to upregulation of inflammatory mediators in plaque tissue. Additional in vitro and in vivo research will be needed to advance our understanding of specific C. pneumoniae and Lp-PLA(2) interactions in atherosclerosis

Therapeutic Dosing of Acenocoumarol: Proposal of a Population Specific Pharmacogenetic Dosing Algorithm and Its Validation in North Indians

Objectives: To develop a population specific pharmacogenetic acenocoumarol dosing algorithm for north Indian patients and show its efficiency in dosage prediction. Methods: Multiple and linear stepwise regression analyses were used to include age, sex, height, weight, body surface area, smoking status, VKORC1-1639 G.A, CYP4F2 1347 G.A, CYP2C9*2,*3 and GGCX 12970 C.G polymorphisms as variables to generate dosing algorithms. The new dosing models were compared with already reported algorithms and also with the clinical data for various performance measures. Odds ratios for association of genotypes with drug sensitive and resistant groups were calculated. Results: The pharmacogenetic dosing algorithm generated by multiple regression analysis explains 41.4 % (p-value,0.001) of dosage variation. Validation of the new algorithm showed its predictive ability to be better than the already established algorithms based on similar variables. Its validity in our population is reflected by increased sensitivity, specificity, accuracy and decreased rates of over- and under- estimation in comparison to clinical data. The VKORC1-1639 G.A polymorphism was found to be strongly associated with acenocoumarol sensitivity according to recessive model. Conclusions: We have proposed an efficient north India specific pharmacogenetic acenocoumarol dosing algorithm whic

Association of Chromosome 9p21 with Subsequent Coronary Heart Disease events:A GENIUS-CHD study of individual participant data

BACKGROUND:Genetic variation at chromosome 9p21 is a recognized risk factor for coronary heart disease (CHD). However, its effect on disease progression and subsequent events is unclear, raising questions about its value for stratification of residual risk. METHODS:A variant at chromosome 9p21 (rs1333049) was tested for association with subsequent events during follow-up in 103,357 Europeans with established CHD at baseline from the GENIUS-CHD Consortium (73.1% male, mean age 62.9 years). The primary outcome, subsequent CHD death or myocardial infarction (CHD death/MI), occurred in 13,040 of the 93,115 participants with available outcome data. Effect estimates were compared to case/control risk obtained from CARDIoGRAMPlusC4D including 47,222 CHD cases and 122,264 controls free of CHD. RESULTS:Meta-analyses revealed no significant association between chromosome 9p21 and the primary outcome of CHD death/MI among those with established CHD at baseline (GENIUS-CHD OR 1.02; 95% CI 0.99-1.05). This contrasted with a strong association in CARDIoGRAMPlusC4D OR 1.20; 95% CI 1.18-1.22; p for interaction Conclusions: In contrast to studies comparing individuals with CHD to disease free controls, we found no clear association between genetic variation at chromosome 9p21 and risk of subsequent acute CHD events when all individuals had CHD at baseline. However, the association with subsequent revascularization may support the postulated mechanism of chromosome 9p21 for promoting atheroma development

Surviving in isolation: genetic variation, bottlenecks and reproductive strategies in the Canarian endemic Limonium macrophyllum (Plumbaginaceae)

Oceanic archipelagos are typically rich in endemic taxa, because they offer ideal conditions for diversification and speciation in isolation. One of the most remarkable evolutionary radiations on the Canary Islands comprises the 16 species included in Limonium subsection Nobiles, all of which are subject to diverse threats, and legally protected. Since many of them are single-island endemics limited to one or a few populations, there exists a risk that a loss of genetic variation might limit their longterm survival. In this study, we used eight newly developed microsatellite markers to characterize the levels of genetic variation and inbreeding in L. macrophyllum, a species endemic to the North-east of Tenerife that belongs to Limonium subsection Nobiles. We detected generally low levels of genetic variation over all populations (HT = 0.363), and substantial differentiation among populations (FST = 0.188;RST = 0.186) coupled with a negligible degree of inbreeding (F = 0.042). Obligate outcrossing may have maintained L. macrophyllum relatively unaffected by inbreeding despite the species’ limited dispersal ability and the genetic bottlenecks likely caused by a prolonged history of grazing. Although several factors still constitute a risk for the conservation of L. macrophyllum, the lack of inbreeding and the recent positive demographic trends observed in the populations of this species are factors that favour its future persistence