Complete Plastome Sequences of Equisetum arvense and Isoetes flaccida: Implications for Phylogeny and Plastid Genome Evolution of Early Land Plant Lineages

Background Despite considerable progress in our understanding of land plant phylogeny, several nodes in the green tree of life remain poorly resolved. Furthermore, the bulk of currently available data come from only a subset of major land plant clades. Here we examine early land plant evolution using complete plastome sequences including two previously unexamined and phylogenetically critical lineages. To better understand the evolution of land plants and their plastomes, we examined aligned nucleotide sequences, indels, gene and nucleotide composition, inversions, and gene order at the boundaries of the inverted repeats. Results We present the plastome sequences of Equisetum arvense, a horsetail, and of Isoetes flaccida, a heterosporous lycophyte. Phylogenetic analysis of aligned nucleotides from 49 plastome genes from 43 taxa supported monophyly for the following clades: embryophytes (land plants), lycophytes, monilophytes (leptosporangiate ferns + Angiopteris evecta + Psilotum nudum + Equisetum arvense), and seed plants. Resolution among the four monilophyte lineages remained moderate, although nucleotide analyses suggested that P. nudum and E. arvense form a clade sister to A. evecta + leptosporangiate ferns. Results from phylogenetic analyses of nucleotides were consistent with the distribution of plastome gene rearrangements and with analysis of sequence gaps resulting from insertions and deletions (indels). We found one new indel and an inversion of a block of genes that unites the monilophytes. Conclusions Monophyly of monilophytes has been disputed on the basis of morphological and fossil evidence. In the context of a broad sampling of land plant data we find several new pieces of evidence for monilophyte monophyly. Results from this study demonstrate resolution among the four monilophytes lineages, albeit with moderate support; we posit a clade consisting of Equisetaceae and Psilotaceae that is sister to the true ferns, including Marattiaceae

Comparison of ESTs from juvenile and adult phases of the giant unicellular green alga Acetabularia acetabulum

BACKGROUND: Acetabularia acetabulum is a giant unicellular green alga whose size and complex life cycle make it an attractive model for understanding morphogenesis and subcellular compartmentalization. The life cycle of this marine unicell is composed of several developmental phases. Juvenile and adult phases are temporally sequential but physiologically and morphologically distinct. To identify genes specific to juvenile and adult phases, we created two subtracted cDNA libraries, one adult-specific and one juvenile-specific, and analyzed 941 randomly chosen ESTs from them. RESULTS: Clustering analysis suggests virtually no overlap between the two libraries. Preliminary expression data also suggests that we were successful at isolating transcripts differentially expressed between the two developmental phases and that many transcripts are specific to one phase or the other. Comparison of our EST sequences against publicly available sequence databases indicates that ESTs from the adult and the juvenile libraries partition into different functional classes. Three conserved sequence elements were common to several of the ESTs and were also found within the genomic sequence of the carbonic anhydrase1 gene from A. acetabulum. To date, these conserved elements are specific to A. acetabulum. CONCLUSIONS: Our data provide strong evidence that adult and juvenile phases in A. acetabulum vary significantly in gene expression. We discuss their possible roles in cell growth and morphogenesis as well as in phase change. We also discuss the potential role of the conserved elements found within the EST sequences in post-transcriptional regulation, particularly mRNA localization and/or stability

Supported tris-triazole ligands for batch and continuous-flow copper-catalyzed huisgen 1,3-dipolar cycloaddition reactions

The lack of supported versions of the tris[(1-benzyl-1H-1,2,3-triazol-4-yl)methyl]amine (TBTA) ligand, suitable for flow-chemistry applications at scale, prompted us to develop a new route for the immobilization of such tris-triazole chelating units on highly cross-linked polystyrene resins. With this aim, the preparation of the known TBTA-type monomer 3 was optimized to develop a high-yield synthetic sequence, devoid of chromatographic purifications at any stage. Then, bead-type (P7) and monolithic (M7) functional resins were obtained by the easy and scalable suspension-or mold-copolymerization of 3 with divinylbenzene. Both types of materials were found to possess a highly porous morphology and specific surface area in the dry state and could be charged with substantial amounts of Cu(I) or Cu(II) salts. After treatment of the latter with a proper reducing agent, the corresponding supported Cu(I) complexes were tested in the copper-catalyzed alkyne-azide cycloaddition reaction (CuAAC). The immobilized catalysts proved active at room temperature and, in batch and with catalyst loadings as low as 0.6 mol%, afforded quantitative conversions within 20 h. Independent of the alkyne structure, extended use of the supported catalyst in flow was also possible. In the reaction of benzylazide and propargyl alcohol, this allowed a total turnover number larger than 400 to be reached

Pathophysiologic risk stratification of chronic heart failure: coexisting left atrial and right ventricular damage and the role of pulmonary circulation

Abstract Funding Acknowledgements Type of funding sources: None. Background in heart failure with reduced ejection fraction (HFrEF) the chronic increase of filling pressures progressively involves left atrium (LA), pulmonary circulation (PC) and right ventricle (RV), leading to worse outcome. Purpose we investigated the prognostic impact of either isolate LA impairment, RV dysfunction combined with pulmonary hypertension, or both, in HFrEF, using basic and advanced echocardiography. Methods 106 outpatients with HFrEF were enrolled. Exclusion criteria were primary lung disease, non-sinus rhythm, previous cardiac surgery, poor acoustic window. Clinical examination and basic echocardiography were performed. Speckle tracking analysis was used to measure peak atrial longitudinal strain (PALS) and a new marker of interaction between RV and PC: absolute free wall RV longitudinal strain(fwRVLS)/systolic pulmonary artery pressure(sPAP). Patients were followed for all-cause or cardiovascular death and heart failure (HF) hospitalization. Results of 84 eligible patients [mean age: 60.1 ± 11.5; 82% male, mean left ventricular ejection fraction (LV EF) 28 ± 5%], 48 reached the combined endpoint. Population was divided into 3 groups: Group 1 [PALS≥15 and fwRVLS/sPAP ≤ 0.5]; Group 2 [PALS ≤ 15 and fwRVLS/sPAP ≤ 0.5 or PALS≥15 and fwRVLS/sPAP≥0.5]; Group 3 [PALS ≤ 15 and fwRVLS/sPAP≥0.5]. Mean follow-up was 3.5 ± 0.3years. The increasing severity groups were associated with higher LA volume index (LAVI), New York Heart Association (NYHA) class, mitral regurgitation (MR) and tricuspid regurgitation (TR) grades, lower LV EF, LV global longitudinal strain (GLS), PALS, tricuspid annular plane systolic excursion (TAPSE), sPAP, fwRVLS and global RVLS(p < 0.0001). Reduced PALS and fwRVLS/sPAP were independent predictors of NYHA > 2 at univariate and multivariate analysis adjusted for age, sex, LV EF, and of any events with adjusted Cox models (Table 1). Kaplan-Meier curves showed a clear divergence between the groups for the prediction of the combined endpoint (Fig.1), cardiovascular death and HF hospitalization. Conclusions the combination of LA and RV damage could represent the transition point to end-stage HF, with considerably worse prognosis. Its assessment with PALS and fwRVLS/sPAP could help risk stratification of HFrEF patients in order to provide early treatment. Table 1 Unadjusted hazard ratio [95% CI] Adjusted for GLS hazard ratio [95% CI] Adjusted for GLS, LAVi, TR, RVFAC hazard ratio [95% CI] Group 3 vs 1 10.61 [4.16-27.06], p < 0.0001 10.24 [3.49-30.02], p < 0.0001 9.54 [2.95-30.92], p = 0.0002 Group 3 vs 2 3.90 [1.92-7.93], p = 0.0002 3.82 [1.74-8.36], p = 0.0008 3.78 [1.66-8.61], p = 0.002 Group 2 vs 1 2.72 [1.03-7.20], p = 0.04 2.69 [0.99-7.25], p = 0.05 2.53 [0.84-7.58], p = 0.1 CI, confidence interval; EF, ejection fraction; GLS, global longitudinal strain;LAVI, left atrial volume index; MR, mitral regurgitation, TR, tricuspid regurgitation Abstract Figure. Fig.

Chloroplast Genome Sequence of the Moss Torula ruralis: Gene Content, Polymorphism, and Structural Arrangement Relative to Other Green Plant Chloroplast Genomes

Background Tortula ruralis, a widely distributed species in the moss family Pottiaceae, is increasingly used as a model organism for the study of desiccation tolerance and mechanisms of cellular repair. In this paper, we present the chloroplast genome sequence of T. ruralis, only the second published chloroplast genome for a moss, and the first for a vegetatively desiccation-tolerant plant. Results The Tortula chloroplast genome is ~123,500 bp, and differs in a number of ways from that of Physcomitrella patens, the first published moss chloroplast genome. For example, Tortula lacks the ~71 kb inversion found in the large single copy region of the Physcomitrella genome and other members of the Funariales. Also, the Tortula chloroplast genome lacks petN, a gene found in all known land plant plastid genomes. In addition, an unusual case of nucleotide polymorphism was discovered. Conclusions Although the chloroplast genome of Tortula ruralis differs from that of the only other sequenced moss, Physcomitrella patens, we have yet to determine the biological significance of the differences. The polymorphisms we have uncovered in the sequencing of the genome offer a rare possibility (for mosses) of the generation of DNA markers for fine-level phylogenetic studies, or to investigate individual variation within population

Genetic Drivers of Epigenetic and Transcriptional Variation in Human Immune Cells

Characterizing the multifaceted contribution of genetic and epigenetic factors to disease phenotypes is a major challenge in human genetics and medicine. We carried out high-resolution genetic, epigenetic, and transcriptomic profiling in three major human immune cell types (CD14$^{+}$ monocytes, CD16$^{+}$ neutrophils, and naive CD4$^{+}$ T cells) from up to 197 individuals. We assess, quantitatively, the relative contribution of $\textit{cis}$-genetic and epigenetic factors to transcription and evaluate their impact as potential sources of confounding in epigenome-wide association studies. Further, we characterize highly coordinated genetic effects on gene expression, methylation, and histone variation through quantitative trait locus (QTL) mapping and allele-specific (AS) analyses. Finally, we demonstrate colocalization of molecular trait QTLs at 345 unique immune disease loci. This expansive, high-resolution atlas of multi-omics changes yields insights into cell-type-specific correlation between diverse genomic inputs, more generalizable correlations between these inputs, and defines molecular events that may underpin complex disease risk.This work was predominantly funded by the EU FP7 High Impact Project BLUEPRINT (HEALTH-F5-2011-282510) and the Canadian Institutes of Health Research (CIHR EP1-120608). The research leading to these results has received funding from the European Union's Seventh Framework Programme (FP7/2007-2013) under grant agreement no 282510 (BLUEPRINT), the European Molecular Biology Laboratory, the Max Planck society, the Spanish Ministry of Economy and Competitiveness, ‘Centro de Excelencia Severo Ochoa 2013-2017’, SEV-2012-0208 and Spanish National Bioinformatics Institute (INB-ISCIII) PT13/0001/0021 co-funded by FEDER "“Una Manera de hacer Europa”. D.G. is supported by a “la Caixa”-Severo Ochoa pre-doctoral fellowship, M.F. was supported by the BHF Cambridge Centre of Excellence [RE/13/6/30180], K.D. is funded as a HSST trainee by NHS Health Education England, S.E. is supported by a fellowship from La Caixa, V.P. is supported by a FEBS long-term fellowship and N.S.'s research is supported by the Wellcome Trust (Grant Codes WT098051 and WT091310), the EU FP7 (EPIGENESYS Grant Code 257082 and BLUEPRINT Grant Code HEALTH-F5-2011-282510) and the NIHR BRC. The Blood and Transplant Unit (BTRU) in Donor Health and Genomics is part of and funded by the National Institute for Health Research (NIHR) and is a partnership between the University of Cambridge and NHS Blood and Transplant (NHSBT) in collaboration with the University of Oxford and the Wellcome Trust Sanger Institute. The T-cell data was produced by the McGill Epigenomics Mapping Centre (EMC McGill). It is funded under the Canadian Epigenetics, Environment, and Health Research Consortium (CEEHRC) by the Canadian Institutes of Health Research and by Genome Quebec (CIHR EP1-120608), with additional support from Genome Canada and FRSQ. T.P. holds a Canada Research Chair

Cerium Oxide Nanoparticles Protect Cardiac Progenitor Cells from Oxidative Stress

Cardiac progenitor cells (CPCs) are a promising autologous source of cells for cardiac regenerative medicine. However, CPC culture in vitro requires the presence of microenvironmental conditions (a complex array of bioactive substance concentration, mechanostructural factors, and physicochemical factors) closely mimicking the natural cell surrounding in vivo, including the capability to uphold reactive oxygen species (ROS) within physiological levels in vitro. Cerium oxide nanoparticles (nanoceria) are redox-active and could represent a potent tool to control the oxidative stress in isolated CPCs. Here, we report that 24 h exposure to 5, 10, and 50 !g/mL of nanoceria did not a!ect cell growth and function in cardiac progenitor cells, while being able to protect CPCs from H2O2-induced cytotoxicity for at least 7 days, indicating that nanoceria in an e!ective antioxidant. Therefore, these "ndings con"rm the great potential of nanoceria for controlling ROS-induced cell damage