Acute Geometric Changes of the Mitral Annulus after Coronary Occlusion: A Real-Time 3D Echocardiographic Study

We performed real-time 3D echocardiography in sixteen sheep to compare acute geometric changes in the mitral annulus after left anterior descending coronary artery (LAD, n=8) ligation and those after left circumflex coronary artery (LCX, n=8) ligation. The mitral regurgitation (MR) was quantified by regurgitant volume (RV) using the proximal isovelocity surface area method. The mitral annulus was reconstructed through the hinge points of the annulus traced on 9 rotational apical planes (angle increment=20°). Mitral annular area (MAA) and the ratio of antero-posterior (AP) to commissure-commissure (CC) dimension of the annulus were calculated. Non-planar angle (NPA) representing non-planarity of the annulus was measured. After LCX occlusion, there were significant increases of the MAA during both early and late systole (p<0.01) with significant MR (RV: 30±14 mL), while there was neither a significant increase of MAA, nor a significant MR (RV: 4±5 mL) after LAD occlusion. AP/CC ratio (p<0.01) and NPA (p<0.01) also significantly increased after LCX occlusion during both early and late systole. The mitral annulus was significantly enlarged in the antero-posterior direction with significant decrease of non-planarity compared to LAD occlusion immediately after LCX occlusion

A perspective on Hypericum perforatum Genetic transformation

Hypericum perforatum (St John's wort) is a reservoir of diverse classes of biologically active and high value secondary metabolites, which captured the interest of both researchers and the pharmaceutical industry alike. Several studies and clinical trials have shown that H. perforatum extracts possess an astounding array of pharmacological properties. These properties include antidepressant, anti-inflammatory, antiviral, anti-cancer, and antibacterial activities; and are largely attributed to the naphtodianthrones and xanthones found in the genus. Hence, improving their production via genetic manipulation is an important strategy. In spite of the presence of contemporary genome editing tools, genetic improvement of this genus remains challenging without robust transformation methods in place. In the recent past, we found that H. perforatum remains recalcitrant to Agrobacterium tumefaciens mediated transformation partly due to the induction of plant defense responses coming into play. However, H. perforatum transformation is possible via a non-biological method, biolistic bombardment. Some research groups have observed the induction of hairy roots in H. perforatum after Agrobacterium rhizogenes co-cultivation. In this review, we aim at updating the available methods for regeneration and transformation of H. perforatum. In addition, we also propose a brief perspective on certain novel strategies to improve transformation efficiency in order to meet the demands of the pharmaceutical industry via metabolic engineering.GF and PS are financed from the BIOTALENT project (GA621321) funded by the European Union Seventh Framework Programme (FP7) ERA Chairs Pilot Call and co-financed by funds allocated for education through project no W26/7.PR/2015 [GA 3413/7.PR/2015/2] for the years 2015-2019. This work was partially supported by Fundacao para a Ciencia e a Tecnologia (FCT) project (PTDC/AGR-GPL/119211/2010). WEE acknowledges the financial support provided by the FCT (SFRH/BD/52561/2014), under the Doctoral Programme "Agricultural Production Chains-from fork to farm" (PD/00122/2012).info:eu-repo/semantics/publishedVersio

Nanocomposite electrospun nanofiber membranes for environmental remediation

Rapid worldwide industrialization and population growth is going to lead to an extensive environmental pollution. Therefore, so many people are currently suffering from the water shortage induced by the respective pollution, as well as poor air quality and a huge fund is wasted in the world each year due to the relevant problems. Environmental remediation necessitates implementation of novel materials and technologies, which are cost and energy efficient. Nanomaterials, with their unique chemical and physical properties, are an optimum solution. Accordingly, there is a strong motivation in seeking nano-based approaches for alleviation of environmental problems in an energy efficient, thereby, inexpensive manner. Thanks to a high porosity and surface area presenting an extraordinary permeability (thereby an energy efficiency) and selectivity, respectively, nanofibrous membranes are a desirable candidate. Their functionality and applicability is even promoted when adopting a nanocomposite strategy. In this case, specific nanofillers, such as metal oxides, carbon nanotubes, precious metals, and smart biological agents, are incorporated either during electrospinning or in the post-processing. Moreover, to meet operational requirements, e.g., to enhance mechanical stability, decrease of pressure drop, etc., nanofibrous membranes are backed by a microfibrous non-woven forming a hybrid membrane. The novel generation of nanocomposite/hybrid nanofibrous membranes can perform extraordinarily well in environmental remediation and control. This reality justifies authoring of this review paper

Ror2 Enhances Polarity and Directional Migration of Primordial Germ Cells

The trafficking of primordial germ cells (PGCs) across multiple embryonic structures to the nascent gonads ensures the transmission of genetic information to the next generation through the gametes, yet our understanding of the mechanisms underlying PGC migration remains incomplete. Here we identify a role for the receptor tyrosine kinase-like protein Ror2 in PGC development. In a Ror2 mouse mutant we isolated in a genetic screen, PGC migration and survival are dysregulated, resulting in a diminished number of PGCs in the embryonic gonad. A similar phenotype in Wnt5a mutants suggests that Wnt5a acts as a ligand to Ror2 in PGCs, although we do not find evidence that WNT5A functions as a PGC chemoattractant. We show that cultured PGCs undergo polarization, elongation, and reorientation in response to the chemotactic factor SCF (secreted KitL), whereas Ror2 PGCs are deficient in these SCF-induced responses. In the embryo, migratory PGCs exhibit a similar elongated geometry, whereas their counterparts in Ror2 mutants are round. The protein distribution of ROR2 within PGCs is asymmetric, both in vitro and in vivo; however, this asymmetry is lost in Ror2 mutants. Together these results indicate that Ror2 acts autonomously to permit the polarized response of PGCs to KitL. We propose a model by which Wnt5a potentiates PGC chemotaxis toward secreted KitL by redistribution of Ror2 within the cell

Epigenetic Mechanisms Regulate Stem Cell Expressed Genes Pou5f1 and Gfra1 in a Male Germ Cell Line

Male fertility is declining and an underlying cause may be due to environment-epigenetic interactions in developing sperm, yet nothing is known of how the epigenome controls gene expression in sperm development. Histone methylation and acetylation are dynamically regulated in spermatogenesis and are sensitive to the environment. Our objectives were to determine how histone H3 methylation and acetylation contribute to the regulation of key genes in spermatogenesis. A germ cell line, GC-1, was exposed to either the control, or the chromatin modifying drugs tranylcypromine (T), an inhibitor of the histone H3 demethylase KDM1 (lysine specific demethylase 1), or trichostatin (TSA), an inhibitor of histone deacetylases, (HDAC). Quantitative PCR (qPCR) was used to identify genes that were sensitive to treatment. As a control for specificity the Myod1 (myogenic differentiation 1) gene was analyzed. Chromatin immunoprecipitation (ChIP) followed by qPCR was used to measure histone H3 methylation and acetylation at the promoters of target genes and the control, Myod1. Remarkably, the chromatin modifying treatment specifically induced the expression of spermatogonia expressed genes Pou5f1 and Gfra1. ChIP-qPCR revealed that induction of gene expression was associated with a gain in gene activating histone H3 methylation and acetylation in Pou5f1 and Gfra1 promoters, whereas CpG DNA methylation was not affected. Our data implicate a critical role for histone H3 methylation and acetylation in the regulation of genes expressed by spermatogonia – here, predominantly mediated by HDAC-containing protein complexes